The distance learning system and method provide distance learning efficiently and effectively. The distance learning system (DLS) includes an education program, and an education center server of an educational platform for database management, data transfers and communications amongst the education system users. The DLS divides the education program into several education levels, and students register and receive an electronic data carrier in the form of CD or DVD disk containing educational material for the subject studied. The DLS establishes an interactive on-line session of electronic workshops and the students, who do not login to the educational platform before the start of the electronic workshops are directed into a “waiting room” and later included in the electronic workshops, preferably prior to the commencement of a next part of the workshops. The “waiting room” for delayed students may be created by parallel, shifted in time running of several similar electronic workshops.

Economic changes and technologic progress of any country results in the necessity to acquire, in accordance with current needs, new abilities, usually obtained by university studies. Traditional education requires students to travel to an education center, often distant from their homes, frequent commuting and organizing of time for participation in daytime, evening or week-end classes, can significantly increase the cost of study for some and limit the time available to study for others. As a result, many segments of the population, desirous to improve their qualifications, particularly those working, raising children, physically handicapped or with limited financial means have little opportunity to follow a traditionally conducted education.
The progress and development of informatics has provided unlimited possibilities of application for distance education, resolving the above problems, and making education available for a considerably larger segment of the population. New computer technologies provide quick access to extensive data sources and databases (Internet), new communication means (e-mail, chat, voice mail, videoconferencing) and work tools, including better and constantly improved software and hardware.
These advantageous properties offered by new technologies have resulted in the very fast development of new remote learning methods and an enormous increase the growth of the number of on-line students. In tracing the requirements for distance education using technology, a number of systems and methods for teaching, utilizing electronic means of data processing, transfer and communication, have been proposed.
U.S. Patent Application No US 2001/051330 A1 by Futakuchi, describes an apparatus and a method for providing remote teaching. The apparatus is comprised of a question database, an answer database and a comment database as well as a control unit, connected via the Internet to the students' personal computers. The system determines, whether the answer to a given question is right and generates an appropriate comment.
U.S. Patent Application No US 2002/0018984 by Ho et al. relates to a method and a system of learning based on questions and answers. After working on the study materials presented by the system, the user introduces a question into the system, which generates and presents an answer. Then the system compares the questions with those previously entered, to determine his level of understanding of the subject and to select appropriate study materials.
U.S. Pat. No. 6,139,330 to Ho et al. describes a computer-aided learning method and system based on tests. The system is provided with a recommendation generator which may have a form of a software, hardware or some combination of both. The generator is configured to assess user's understanding of the subject.
U.S. Patent Application No. US 2001/0039002 to Delehanty, describes a system and a method for implementing and managing training programs over a network of computers. The system comprises computers of the server-client type, while the server contains a user database, an actionable database and reference database. The system and method enable training by means of the Internet and a web browser. When a user follows the training, the system monitors the student's results and enables the web administrator to determine in real time the student's progress and add additional materials of study if a need for supplementary education is perceived. During the training, the administrator may communicate with the user directly.
U.S. Pat. No. 6,164,974 by Carlile et al. relates to a learning system to be used by authors, teachers, students and education administrators. Within this system, a student, while studying a displayed subject matter, may check the degree of their knowledge using tests that are provided and the results of those tests are displayed together with an assessment of the student's knowledge of the subject matter.
U.S. Pat. No. 6,326,632 by Chao et al. relates to a computer-aided learning method, allowing a student to select an appropriate instructor for learning a language and vice versa. After the student's choice of instructor has been made, establishing a connection between them occurs and then automatic management and payment collection for the session.
U.S. Pat. No. 6,341,960 to Frasson et al. describes a method of providing a learner with information, during a session of automatic distance learning using the Internet. The method comprises an automatic selection of learning strategy, determination of a need to use help data, being a separate part of educative information, and their selective presentation. When using a model of an automatic learner, possible difficulties are revealed, then, on this basis, explanations from a local database or the web are provided.
PCT/IT01/00336 (WO 02/09065) by Valenti relates to a computer-implemented didactic method, which is comprised of the following steps: a user connecting to a central management system; downloading from the central management system the program-environment to their computer (if not already available); checking the student's registration in the system (if there is none, it is started); the user obtaining data files containing educational material for subjects to be studied and possible extension programs; creating for each user a personal download area; disconnecting the user from the system; and activation of the data files for realizing a training session.
U.S. Pat. No. 6,336,813 by Siefert and U.S. Pat. No. 6,386,883 by Siefert and U.S. Patent Application No. US 2001/0018178 by Siefert describe a computer-assisted education method, in which individual learning profiles for every student are maintained, including their capabilities, preferred learning style, and progress. Based on the student's profile, the system's administrator selects an appropriate material for each student, during each learning session. Then the administrator assesses if the student has mastered the material. If not, a presentation of the material explained differently follows and in the case of a student continuing to fail to master the material, the administrator establishes a videoconference between the student and a lecturer. Learning programs and education material are contained in master computers, accessible via a communication network. The invention is applicable for known education programs and known management systems.
Computer-based, interactive learning method and system, permitting application of various teaching techniques, adapted to individual abilities and needs of the students is disclosed in PCT/US00/32960 (WO 01/43107) to Koneru et al. The system includes students' computers, teachers' computers and a remote server, containing several databases consisting of exams, tests and vocabulary, detailed student information and their individual learning schedule and teaching profile, as well as information of the teachers, interconnected by a web. For each student is created an individual homepage with a graphic interface, containing among other things questions, tests, exams, study subjects and helpful tools. Electronic mail, fax and voicemail remain at a disposal of the system's users.
UK Patent No. 2 368 710 to Dugdale at al. discloses computer-readable CD-ROM disc media, containing data grouped in sections and at least one URL address for communication with an active server page, which contains a database of external links corresponding to specific keywords within a given section.
U.S. Pat. No. 6,190,178 relates to a remote education method and apparatus. Students connect via the Internet with an education server, which contains an educational program, including individual progress data for each student. The remote education method is comprised of a student selecting required learning procedures in an Internet homepage of the education server, consequently finding data related to the procedure selected and then creating an educational homepage, with the assistance of which the student implements his study. Upon completion of the study, the student answers tests, which are then analyzed by the server and upon analysis of the results a direction for continuing study is indicated.
PCT/US01/42230 (WO 02/25619) by Crilly describes a method of adaptation of educational standards in different states and regions, comprising the steps of providing each class with a computer and DVD disks containing educational aids in the form of video and audio, connecting the computer with a World Wide Web, from which are taken additional educational aids, lesson plans and projects, being relevant to the particular operating location, and presenting the educational material, together with that contained in DVD disk, to the students in a classroom.
U.S. Pat. No. 6,195,528 by Young et al. describe a remote teaching method and system. Each student is provided with a CD-ROM disk, containing an educational material in various formats and a software, with the aid of which, the student's computer may connect with a central computer to download appropriate data, particularly those updated in relation to the data contained in the student's CD-ROM disk.
Interactive method for distance education using a computer network is disclosed in U.S. Pat. No. 6,381,444 to Aggarwal et al. The method comprises the steps of student registration to a chosen virtual class on a main server, downloading from this server of an educational material by an instructor and sending it before starting the lesson to all students of a given class. After start of the lesson, the instructor controls, on the server level, the students' computers where the educational material is presented. The student interface contains windows, where various information is displayed, including the material presented, video pictures, e.g. that of a real classroom, as well as students' questions to the instructor and his answers.
U.S. Pat. No. 6,155,840 by Sallette relates to a system and method for distributed learning by means of computer systems and a communication network such as Internet. The system includes a server with which are connected a presenter, presenting an educational material, and the users' computers, coupled to the server via Internet. The presenter's interface includes a few windows and tools intended to configurate the presentation. Individual windows are provided for a list of information sources for the presentation, like films, homepages or slides, for an information about material presented and about the presenter, a window for communication with students, e.g. by means of chat, as well as two windows for presenting two streams of educational material of which one serves for video-presentation. Users' interfaces include similar windows.
Another method of on-line education in the frame of an open virtual university is disclosed in PCT/US01/40102 (WO 01/61670) to Wheeler. The educational system is created by various universities and schools, sponsors, students and an interconnected intermediary, being for instance a virtual medical school, an Internet provider or a governmental agency. A program of the studies includes lectures on various subjects, which are presented to the students by several institutions by means of the intermediary and the Internet. Sponsors, for instance a pharmaceutical firm or a health organization, cover at least partially the costs of the system's implementation, which reduces the students' education costs. Studies maybe divided in two stages, of which one includes the on-line education and the second stage is conducted on campus upon satisfying completion of the first stage.
Yet another system and method of on-line education is disclosed in PCT/US00/17979 (WO 01/01372) to Alcorn. The system includes a server, connecting students' and instructors' computers via a network. The server contains course files, accessible for registered users in accordance with their authorized access level. Course files include announcement and information files, documents, exercise files and communication files. On-line education comprises the steps of generating by the course instructor of a set of course files, transferring the files to a server for storage, and making access to the files to a group of students being registered for that particular course. During the course, the instructor selects, from a batch of available files, appropriate exercise files or creates such files and adds them to those existing, and transfers these to the students for resolving. Upon resolution of the exercises, the students create answer files, transfer them to the instructor which evaluates them and presents to the students a list of ratings. The instructor has at his disposal several tools, such as those for creating the course, for the presentation of educational material in an appropriate format, a list of Internet links, chat, electronic mail and similar tools, permitting him to conduct the course by various techniques.
UK Patent No. GB 2 334 119 A by Young et al. refers to a teaching method and system, in which are used CD-ROM-s with educational material and software for managing educational material, communicating with another computer to obtain access to other parts of the educational material as well as for downloading material updates and tests.
The systems and methods of remote education, described above most often relate to a fully automated teaching to obtain or improve a knowledge upon a given subject, hence to a fragmentary education. They are adapted to a fast and easy means of gaining knowledge, with the assistance of computers and communication networks, with lack or considerable limitation for the participation of highly qualified persons, e.g. a university lecturer. Although a majority of known remote education systems and methods have several advantages, it is not possible to apply them directly for teaching students in accordance with high level traditional education programs. For this purpose it is necessary to develop a coherent education system including the whole program of the studies, which should be the same as in the case of traditional studies and should ensure a high level of education, with frequent contacts between the students and the lecturers. Thanks to this, it will be possible for the students to gain the same knowledge and qualifications as in traditional studies.


A power circuit which can reduce power consumption. More specifically, a testing apparatus for testing an electronic device which includes: a pattern generation unit for generating a test pattern which is supplied to the electronic device; a power supply circuit for supplying power to the electronic device; and a decision unit for deciding pass/fail of the electronic device based on an output signal output from the electronic device, wherein the power supply circuit has: a voltage source for generating a predetermined input voltage to be applied to the electronic device; a power device for supplying the power to the electronic device based on the input voltage generated by the voltage source; a power supply for supplying drive power of the power device; and a voltage control unit for controlling a drive voltage applied by the power supply to the power device based on the power output from the power device.

1. Field of the Invention
The present invention relates to a testing apparatus for testing of electronic devices, and to a power supply circuit for use in such a testing apparatus or other like apparatus.
2. Description of Related Art
Conventionally, a testing apparatus which performs tests on electronic devices is provided with a power supply circuit for powering the testing apparatus. For example, the power supply circuit has a power device configured to generate a power supply voltage and a power supply current for supply to an electronic device, and a power supply for driving the power device.
For example, the power device has an amplification circuit for amplifying an applied input voltage and producing an output as a power supply voltage, a source-side circuit for supplying a source current to the electronic device according to the input voltage, and a sink-side circuit for drawing a sink current from the electric device according to the input voltage. Each of the source-side circuit and the sink-side circuit has a CMOS disposed between the power supply and the electronic device. A voltage according to the input voltage is supplied to a gate terminal of each of the CMOSs, and whether the power supply current is to be supplied to the electronic device from the power supply or it is drawn to the power supply from the electronic device, is controlled according to the input voltage.
In a conventional power supply circuit, however, the drive voltage, which is applied to the power device from the power supply, is constant. Besides, a differential between the drive voltage and the power supply voltage is supplied to the source-side. For example, when, at this time, the power supply voltage becomes extremely low, this causes application of a voltage of approximately the same level as the drive voltage to the source-side circuit and the sink-side circuit, with the result that the consumption of power in the power device increases.
Accordingly, an object of the present invention is to provide a testing apparatus and a power supply circuit which can solve the problems discussed above. The above and other objects can be achieved by combinations described in the independent claims. The dependent claims define further advantageous and exemplary combinations of the present invention.


There is described an improved semiconductor device of chip-scale package (CSP) comprising posts provided on respective electrode pads of a semiconductor chip, and solder balls which are provided on the respective posts as external terminals after the semiconductor chip has been encapsulated with resin while the posts are held in a projecting manner. The semiconductor device prevents occurrence of cracks, which would otherwise be caused by stress which is induced by a difference in coefficient of linear expansion between the semiconductor chip and the sealing resin and is imposed on the posts. In order to alleviate the stress imposed on the posts, a stress-absorbing layer formed from a metal layer having a low Young's modulus, such as gold (Au) or palladium (Pd), is interposed in the middle of each of the posts.

1. Field of the Invention
In association with miniaturization of and a reduction in the profile of an electronic component using an LSI, demand has recently arisen for miniaturizing an LSI package. A chip-scale package (CSP), which is identical in size with a semiconductor chip, has been developed.
2. Background Art
CSPs are classified into two types; that is, a CSP comprising a semiconductor chip electrically and mechanically connected to a printed board and a film carrier, with solder balls (bumps) being provided on the printed board and the film carrier as external terminals; and a CSP having neither a printed board nor a film carrier and comprising posts provided on respective electrode pads of a semiconductor chip, with solder balls being provided on the respective posts as external terminals after the semiconductor chip has been encapsulated with resin while the posts are held in a projecting manner.
FIG. 3 is a cross-sectional view of a conventional CSP of the latter type, wherein reference numeral 1 designates a semiconductor chip; 2 designates an electrode pad; 3 designates a protective dielectric layer; 4 designates a post as a connecting conductor; 5 designates sealing resin; 6 designates a bump as an external terminal; and 7 designates a coating layer.
The CSP of latter type does not use any printed board or a film carrier for effecting plastic encapsulation or forming external terminals and hence is advantageous over a CSP of the former type.
Because of a difference in coefficient of linear expansion between the semiconductor chip 1 and the sealing resin 5, the conventional CSP of latter type encounters a structural problem of cracks being caused by a stress imposed on the posts 4.


Embodiments of a thermal compression bonding process bond head and a method for producing a thermal compression bonding process bond head are disclosed. In some embodiments, the bond head includes a thermal compression bonding process heater and a cooling block coupled to the heater through an annular structure. The annular structure surrounds a lower portion of the cooling block and couples the cooling block to the heater such that there is no direct mechanical contact between the cooling block and the heater.

Integrated circuit dies may be attached to substrates, circuit boards, or other dies using a process commonly referred to in the art as thermal compression bonding. Solder balls may be attached to various points of the die that are desired to be anchored to the substrate. The die may then be heated to melt the solder balls. The die and substrate may then be compressed such that, when the solder balls cool, the die may be attached to the substrate. A thermal compression bonding (TCB) process bond head may include a heater used during a fabrication process to heat the die, substrate, and solder balls in order to perform the bonding.
FIG. 1 illustrates a typical stack of a memory die 100, a logic die 101, and a substrate 102 that may be bonded using a TCB process. TCB may be used for attaching the memory die 100 to the logic die 101 with through silicon vias at a joint that may commonly be referred to as a logic-to-memory interconnect (LMI) joint 110. TCB may also be used in a first level interconnect (FLI) joint 111 between the logic die 101 and the substrate 102. The LMI joint 110 height may be very small compared to the FLI joint 111 height. For example, the LMI joint 110 height might be around 5 μm while the FLI joint 111 height might be around 50 μm. Thus, the positioning of the memory and logic dies 100, 101 during the TCB process should be very accurate to avoid bonding and joint problems.
One problem that may occur with the present TCB process is that, as the heater temperature increases, the TCB head may expand. Downward expansion of the head may cause the LMI joint height to become even smaller. This may result in solder ball bridging, resulting in shorting together of interconnects, and/or cracks in the dies 100, 101.
There are general needs for better control of joint heights during a thermal compression bonding process.

Reduced expansion thermal compression bonding process bond head


A method, system, computer program product, and related business methods for concisely communicating real-time business information to end users in an enterprise network is described. An integrated business system having at least ERP and CRM functionality is accessed via a browser-based user interface. A plurality of portlet windows are simultaneously displayed within a browser window, each portlet window occupying a relatively small area therein. The portlet windows are selected and arranged according to a customizable user profile for each user, and include reporting portlets displaying up-to-date business results retrieved from the integrated business system. Each reporting portlet further comprises report access links associated with at least one of the business results that, when selected by the user, invoke browser-based displays of up-to-date business data underlying those business results. Preferably, in accordance with a user-customizable alert setting stored in the user profile, regular electronic mail messages are sent to the user communicating up-to-date versions of those business results. Preferably, data labels that identify business items within the browser-based user interface and on the electronic mails are expressed in a business vernacular tuned to each user according to customizable business vernacular settings in their user profiles.

The ability of business users to access crucial business information has been greatly enhanced by the proliferation of IP-based networking together with advances in object oriented Web-based programming and browser technology. Using these advancements, systems have been developed that permit web-based access to business information systems, thereby allowing any user with a browser and an Internet or intranet connection to view, enter, or modify the required business information.
On a roughly similar timeline, substantial efforts have been directed to Enterprise Resource Planning (ERP) systems that integrate the capabilities of several historically separate business computing systems into a common system, with a view toward streamlining business processes and increasing efficiencies on a business-wide level. By way of example, the capabilities or modules of an ERP system can include: accounting, order processing, time and billing, inventory management, employee management/payroll, and employee calendaring and collaboration, as well as reporting and analysis capabilities relating to these functions.
In a related movement, substantial efforts have also been directed to integrated Customer Relationship Management (CRM) systems, with a view toward obtaining a better understanding of customers, enhancing service to existing customers, and acquiring new, profitable customers. By way of example, the capabilities or modules of a CRM system can include: sales force automation (SFA), marketing automation, contact list, call center support, and web-based customer support, as well as reporting and analysis capabilities relating to these functions. With differing levels of overlap with ERP/CRM initiatives and with each other, substantial efforts have also been directed toward development of increasingly integrated partner and vendor management systems, web store/e-commerce systems, Product Lifecycle Management (PLM) systems, and Supply Chain Management (SCM) systems.
As known in the art, both functional advantages and strategic advantages are gained through a the use of an integrated business system comprising ERP, CRM and other business capabilities, particularly where the integrated business system offers a thin-client, browser-based user interface. Functionally, for example, a remote sales person can enter a sales transaction into their browser-based interface reflecting the successful sale of an item, whereupon the integrated business system can not only update accounts receivable, inventory databases, and other ERP-based systems, but can also automatically update commission schedules, strategic customer information databases, and other CRM-based systems. The integrated business system can also send a trigger, for example, for a vendor to send more inventory to replace sold items, and can send a corresponding message to the company warehouse to expect the incoming shipment. Strategically, integrated reporting capabilities of the above systems allow executives and managers to view current information from virtually any location, the information ranging from lists of the top performing sales people and the most lucrative customers to inventory levels and available warehouse space, so that timely changes or adjustments can be made to optimize performance across the enterprise.
Generally speaking, business software industry analysts expect that efforts toward the integration of the above systems will continue, with the goal of allowing clients to optimize the acquisition, dissemination, and use of business knowledge across enterprise functions. From an ERP perspective, AMR Research predicts that "ERP vendors will soon derive most of their revenues from adding customer relationship management (CRM), supply chain management (SCM), and product lifecycle management (PLM) capabilities." CIO.com, "Executive Summaries: Enterprise Resource Planning," CXO Media, Inc. (Aug. 22, 2002). From a CRM perspective, Patricia Seybold Group characterizes a so-called "fourth wave" of CRM development as follows: "Fourth-wave solutions also begin to tie together customer self-service via the Web with customer service through the contact center. Customers can now begin an interaction online and then pick up the phone and have some hope that the call center rep will be able to see their Web interaction and help them complete the transaction. In this fourth wave, most CRM buyers are also scrambling to tightly integrate their CRM systems with their ERP and other back-end operational systems. . . . Every ERP supplier is now also a CRM supplier." Patricia Seybold Group, "An Executive 's Guide to CRM: How to Evaluate CRM Alternatives by Functionality, Architecture, & Analytics" (2002).
However, with respect to individual end users, problems can arise as integrated business systems grow ever more powerful and cross-functional. A first problem relates generally to an "information bottleneck" that can occur directly at the user interface of the system. Even if all of the internal bottlenecks of a business information system have been resolved, with information flowing freely and effortlessly among different system modules and enterprise databases, the increasingly large body of available business information has little utility to end users if they cannot efficiently perceive that business information. A related problem is that of "information overload" that can result from the wide array of information and capabilities offered to end users, especially business executives. In one scenario, executive users may find an integrated business system to be so "intimidating" as to avoid adopting the system altogether. In another scenario, even sophisticated users may avoid adopting or fully using the integrated business system if access to the information is considered to be awkward or unnecessarily time-consuming.
Another problem that arises with the introduction of more powerful, centralized business information systems relates to business nomenclatures. In particular, depending on the particular industry in question, different business functions within an enterprise may have been using different names to refer to the same business item or category. By way of example, sales people might prefer to use the term "quote" while accounting people might prefer to use the term "estimate." This difference may have historically presented no problem where the ERP/accounting systems were distinct from the CRM/SFA systems. However, the new introduction of an integrated ERP/CRM business system might force an enterprise-wide choice between competing terminology sets, leaving at least some of the users with undesired or unfamiliar terminology in the user interface. Geographic differences may also account for different terminology sets within the same business function, e.g., "accounts receivable" and "accounts payable" may be preferred in one location while "debtors" and "creditors" is preferred in another location.
Accordingly, it would be desirable to provide an integrated business information system that facilitates efficient user perception of real-time business information.
It would be further desirable to provide a user interface to an integrated business information system that allows business executives to perceive overviews of key business performance metrics in a single glance.
It would be still further desirable to provide such a user interface that also permits rapid drill-down access to data underlying the overviews of the key business performance metrics.
It would be still further desirable to provide such a user interface that offers other pathways to efficient dissemination and perception of the key business information.
It would be even further desirable to provide an integrated business information system that integrates functional, geographic, demographic, or other nomenclature differences therein while still retaining the original advantages of business system integration.

Concise communication of real-time business information in an enterprise network


Antibodies having modified constant regions so as to permit conjugation of the antibody to a payload such as a therapeutic agent are described. Preferred antibodies include a mutation at light chain position 180 (positional numbering), most preferably the mutation is to a residue selected from C, K, Q, or a non-natural amino acid. Additional mutations may also be combined with a mutation at position 180; including one or more of light chain (LC) S208, LC S171, LC S182, LC A184, LC V191, LC S202, LC S203, LC T206, heavy chain (HC) S160, HC T190, HC S443, HC S447, HC S139, HC S168, HC V170, HC V176, HC T200, HC S445 according to a positional numbering convention.

Antibody-drug conjugates (ADCs) are a class of targeted therapies which combine the specificity of antibodies with the cytotoxicity of cytotoxic therapeutics. ADCs are primarily considered candidates for the treatment of various cancers. ADCs comprise an antibody linked to a therapeutic drug.
One problem with development of ADCs is the conjugation technology used; if drugs are conjugated non-selectively to cysteine or lysine residues in the antibody, then this can result in a heterogeneous mixture of ADCs. This approach leads to suboptimal safety and efficacy properties and makes optimization of the biological, physical and pharmacological properties of an ADC challenging. In particular, heterogeneity can be a problem with respect to the distribution of cytotoxins (that is, site of attachment), and the loading of cytotoxins (that is, number of drug molecules per antibody).
Heterogeneity presents safety concerns since high drug/antibody ratio (DAR) species can have poor binding to their target and increase risks of off-target toxicity. Low drug loading species are less active (DAR 1) or inactive (DAR 0). As the number of drugs per mAb decreases, the pharmacokinetic properties of the ADC improves (Hamblett, Clin. Cancer Res. 2004, 10, 7063-7070). Furthermore, heterogeneity of ADCs leads to challenges associated with consistent manufacturing and analytical testing.
Site-selective conjugation (SSC) would presumably improve ADCs' safety and efficacy, and thus, results in higher ADC quality. Junutula et al Nature Biotech 2008 report that same activity is achieved with half ADC dose in a SSC-ADC compared to control. Thus, ADC homogeneity will improve Therapeutic Index (TI is the ratio between maximum tolerated dose and effective dose. (TI=TD50/ED50)). Furthermore, higher DAR homogeneity would result in:                Simpler product characterization for regulatory filings, better defined product specifications and        Reduced off-target or bystander toxicity        Potentially more controlled pharmacology (fewer species to reckon on)        Potentially reduce dosage requirements (per gram) to achieve similar pharmacological effect        Reduced potential incidence of side-effects (e.g. immunogenicity, toxicity, etc.)        Reduced costs due to higher conjugation yields and reduced dosage (required amount of ADC to be administered)
However, simply making antibodies with modified residues may result in unforeseen effects, such as changes to antibody aggregation propensity, solubility, or efficacy. The present applicants therefore developed a rational screening process to determine which residues may be modified. In selected embodiments, the modification achieves an antibody suitable for conjugation to a payload (such as a drug) to give a DAR of around 2.


An augmentation circuit for use in connection with a self-bootstrap type output buffer having an n-channel pullup transistor is disclosed. The augmentation circuit includes a capacitor formed by a second n-channel transistor, connected as a capacitor, and disposed between first and second capacitor terminals. A non-overlapping signal generator is formed from a pair of NOR gates, and an inverter, to generate a pair of control signals CS1, and CS2 wherein when one of the control signals is active, the other control signal is inactive. Four n-channel transistors are provided in a switching matrix. One pair of the four n-channel transistors responds to control signal CS2 to connect the capacitor formed by the n-channel transistor across and between ground, and the output pad. In this switched configuration, a voltage level on the output pad is effectively impressed upon the capacitor, and is stored thereon. When an input signal to the buffer changes state to a logic high signal, the output of the control signals also change state, wherein the two n-channel transistors previously conducting, are now turned OFF, and the other two of the four n-channel transistors, which are controlled by CS1, are made to conduct. In this second switched configuration, the capacitor is connected across and between the positive power supply V.sub.cc, and a gate terminal of the pullup n-channel power supply. Accordingly, a voltage magnitude equal to V.sub.cc plus the pad voltage level stored on the capacitor is developed by the augmentation circuit and transferred to the gate of the pullup transistor. In another embodiment, a pair of transfer gates are used, which are controlled by a voltage level on the output node, to augment the input signal voltage level (using a stored level of approximately V.sub.cc). In a third low power embodiment, a capacitor (e.g. a p-channel device) is charged to V.sub.cc and is used to provide the required augmentation, as a function of the output node voltage.

1. Field of the Invention
The present invention relates generally to output buffers of the type employed to control the voltage on an output pad of a semiconductor device, and, more particularly, to a circuit for use with a self-bootstrap type n-channel output buffer that augments the self-bootstrapping capability of such buffer when the output pad transitions to a logic one state from an initial state with a non-zero voltage magnitude.
2. Description of the Related Art
A self-bootstrapping buffer, for example, of the type using a pullup n-channel field effect transistor, such as disclosed in my copending application entitled "Ultra Low Power Pumped N-Channel Output Buffer With Self-Bootstrap", employs a gate-to-source capacitance C.sub.gs of the pullup transistor to bootstrap an input data signal in order to provide the needed pumped gate drive signal. In this configuration, a drain terminal of the pullup transistor is tied to V.sub.cc, a source terminal is tied to the pad, and the gate terminal receives the input drive signal. In particular, a potential problem arises when the input data signal is driven high to turn-on the pullup transistor but the output node voltage is not at a logic zero. This situation may occur, for example, when the output of the buffer is tri-stated, and, the output node has been pulled to a logic one by some other device, or, perhaps, when the input data is changing very fast so that the output node does no more than "glitch" towards a logic zero state before being driven back to a logic one state.
When the output node is not near ground potential (i.e., zero volts), then the self-bootstrapping will either not occur, or, alternatively, will not happen to a sufficient degree. For example, if the output node (i.e., a first capacitor terminal of C.sub.gs) is at a logic one, then, when the input data signal transitions from a low to a high state, thus placing a logic high on a second capacitor terminal of C.sub.gs, there is no final voltage developed across C.sub.gs. Accordingly, once the pullup transistor conducts, the boost amount developed on the gate terminal of the pullup transistor, does not rise appreciably above the device operating voltage level V.sub.cc. Under these circumstances, the pullup transistor having no "pumped" gate drive signal on the gate terminal, would be incapable of generating the desired output voltage (V.sub.OH) (for example, V.sub.cc when V.sub.cc =3.3 volts), and current (I.sub.OH) levels for the logic high state.
Accordingly, there is a need to provide a circuit and method for use with a self-bootstrapping output buffer of the type suitable for driving an output pad of the semiconductor device, that reduces or eliminates one or more of the problems as described above, and, in particular, addresses the problem related to the impairment or failure of the self-bootstrapping mechanism which may occur when the output node is not at zero volts when the input data signal begins to change from a logic zero to a logic one.

Bootstrap augmentation circuit and method


A semiconductor storage device having a security function for imposing limitation on data rewriting includes: at least one non-volatile memory cell array block which is capable of receiving concurrent electrical erasure; at least one memory region, each one of said at least one memory region being provided in the at least one memory cell array block, for storing a security release key; at least one non-volatile storage means for storing a security registration lock corresponding to each of the at least one memory cell array block; a determination circuit for generating a security release signal using the security release key and the security registration lock; and a memory cell array data output switching circuit for outputting security released data externally.

1. Field of the Invention
The present invention relates to a semiconductor storage device having non-volatile memory cell array blocks, e.g., as used in semiconductor integrated circuits. In particular, the present invention relates to a semiconductor storage device having a security function for preventing unauthorized tampering with any content stored in a memory.
2. Description of the Related Art
Electrically erasable non-volatile semiconductor storage devices, such as flash memories, are capable of on-system data rewriting. That is, the data and/or codes stored in such a semiconductor storage device can still be updated even after the semiconductor storage device has been incorporated into a system. Therefore, electrically erasable non-volatile semiconductor storage devices, such as flash memories, are widely used as means for storing programs for driving a microcomputer-based system or the like in accordance with a desired procedure. In such cases, information to be utilized for user authentication, checking programs, and the like are also stored in the same storage device. Therefore, an ability to prevent unauthorized rewriting of data (or "tampering") while also permitting easy updating of stored content is desired.
For example, as disclosed in Japanese Laid-Open Publication No. 9-34797, in actual implementations or proposed structures of tamper prevention circuits, a function limitation release key code (i.e., a key code which disengages a function limitation) is externally input to enable authentication of any access made by an authorized user.
FIG. 3 illustrates a semiconductor memory incorporating a conventional data tamper prevention circuit. This conventional circuit (lock circuit) 300 includes: an internal register 30 for storing a key code which has been subjected to a unidirectional hash conversion; a decoder circuit (security communication circuit) 31 for decoding an input code; a conversion circuit 32 including a unidirectional hash function; a function limitation release determination circuit (comparison circuit) 33; a write control circuit; and a gating circuit.
In accordance with the lock circuit 300, in order to provide data protection in the case where a reference value (key code) which is previously stored in the internal register 30 is directly read by an unauthorized party, the reference value is converted by the unidirectional hash conversion circuit 32 so as to be stored in a converted form, rather than in a plaintext form. In order to also protect a function limitation release key code which is externally input to the device, the externally-input function limitation release key is encrypted. The function limitation release key is decoded by the security communication circuit 31 (to become a key code Iv1), and thereafter converted by the unidirectional hash conversion circuit 32 (to become a key code Iv2). This converted value is compared against the reference value stored in the internal register 30 by the comparison circuit 33. If the two values match, a function limitation release signal 34 is issued to release the function limitation. In order to survive "repetitive attacks" (i.e., a fraudulent technique of trying every possible key input pattern until obtaining a match), the security communication circuit 31 is constructed based on a Diffie-Hellman Key Exchange algorithm or the like, so that a different valid key is generated each time.
However, the aforementioned conventional techniques have the following problems.
First, in order to release the function limitation, it is necessary to externally input a function limitation release key. Accordingly, the above-described system requires an external key storage device for storing the function limitation release key. However, since the function limitation release key is retained external to the device, the key must pass through an interfacing section every time access is requested, independent of what sort of encryption technique may be employed in the communication path between the devices, i.e., between the device shown in FIG. 3 and any other device within the system (e.g., the key storage device). This may run the risk of the function limitation release key being intercepted during communication, or being directly read from the external key storage device.
Moreover, complicated circuitry is required for encrypting signals exchanged between devices, and particularly complicated encryption is required. Hence, complicated decoding circuitry within the device is required to provide protection against repetitive attacks.
Furthermore, in order to effectuate a good tamper prevention function, merely replacing a given semiconductor storage device with a semiconductor storage device having a tamper prevention function does not suffice. In addition, the entire system must be redesigned to enable a good tamper prevention function.


The present invention is directed to a method of identifying plant proteins that function as or similar to G protein coupled receptors, or as plant G protein subunits utilizing a bioassay system that incorporates such plant proteins. Further aspects of the present invention provides expression vectors and yeast cells transformed therewith encoding the plant proteins whose identity it is desired to determine, and methods utilizing same.

In animal systems, the actions of many extracellular signals, for example: neurotransmitters, hormones, odorants and light, are mediated by receptors with seven transmembrane domains (G protein-coupled receptors) and heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins). G proteins are comprised of three subunits: a guanyl-nucleotide binding .alpha. subunit; a .beta. subunit; and a .gamma. subunit [for review, see Conklin, B. R and Bourne, H. R. (1993) Cell 73, 631-641]. G proteins cycle between two forms, depending on whether GDP or GTP is bound to the .alpha. subunit. When GDP is bound, the G protein exists as a heterotrimer, the G.alpha..beta..gamma. complex. When GTP is bound, the .alpha. subunit disassociates, leaving a G.beta..gamma. complex. Importantly, when a G.alpha..beta..gamma. complex operatively associates with an activated G protein coupled receptor in a cell membrane, the rate of exchange of GTP for bound GDP is increased and, hence, the rate of disassociation of the bound G.alpha. subunit from the G.beta..gamma. complex increases. The free G.alpha. subunit and G.beta..gamma. complex are capable of transmitting a signal to downstream elements of a variety of signal transduction pathways. This fundamental scheme of events forms the basis for a multiplicity of different cell signaling phenomena. For additional review, see H. G. Dohlman, J. Thomer, M. Caron, and R. J. Lefkowitz, Ann. Rev. Biochem, 60, 653-688 (1991).
In plants, there is evidence that a number of plant signal transduction pathways, including red and blue light signaling (Warpeha et al., 1991; Romero and Lam, 1993; Neuhaus et al, 1993), K+ channel regulation of stomatal opening (Fairley-Grenot and Assmann, 1991; Li and Assmann, 1993; Armstrong and Blatt, 1995), and auxin signal transduction (Zaina et al., 1990) are regulated through G-protein intermediates. More specifically, in certain of these studies, red light-dependent responses in the tomato mutant aureus were measured after microinjection of either the GTP analogue GTP.gamma.S or cholera toxin, either of which cause constitutive activation of a G-protein, and were found to produce the same effects as microinjecting phytochrome and exposing the plant to red light. Injection of inhibitors GDP.beta.S or pertussis toxin were effective in blocking red light-dependent responses.
It has also been suggested that an inhibitory G-protein modulates blue light-dependent K+ channel opening on the basis of electrophysiological studies using GTP.gamma.S, GDP.beta.S and toxins. In separate experiments it was shown that blue light can activate a GTP-binding protein in the plasma membrane of peas. In rice, the binding of GTP.gamma.S to vesicles in vitro is increased by auxin, while binding of GTP.gamma.S decreased binding of auxin. This binding relationship suggests that auxin activation of a G-protein stimulates cell elongation. In addition, there is evidence for G-protein mediation of plant defense responses (Legendre et al., 1992, Vera-Estralla et al., 1994; Beffa et al., 1995).
G.alpha.-like proteins, having molecular weights close to that of the animal G.alpha. subunits and recognized by antibodies against animal G.alpha. subunits, have been detected in a large number of plant species (for reviews see Ma, 1994 and Kaufman, 1994) and three genes encoding G protein-.alpha. subunits have been identified. The first was cloned from Arabidopsis thaliana (Ma et al. 1990) using PCR primers based on sequences known to be conserved between animal G protein .alpha.-subunits. The predicted protein has all of the consensus sequences for guanine nucleotide binding and hydrolysis that are characteristic of GTP-binding proteins and shows 36% identity with rat Gi(1-3) and bovine transducin. Using the Arabidopsis thaliana gene as a probe, genes were identified in both tomato (Ma et al., 1991) and soybean (Kim et al., 1995). The Arabidopsis thaliana tomato and soybean genes share over 80% identity, suggesting that plant G-protein .alpha.-subunits may be highly conserved. Both Arabidopsis thaliana and tomato DNA appear to have single genes based on Southern blot analysis, whereas multiple genes may be present in soybean. Single genes encoding G protein .beta. subunits have also been cloned from maize and Arabidopsis thaliana (Weiss et al., 1994). The predicted protein sequences shares 76% identity with each other and 41% identity with mammalian G protein .beta. subunits.
Although the sequence of the plant G .alpha. subunits have been conserved relative to that of the mammalian G .alpha. subunits, there is no published data that demonstrates that the function of the plant protein is also conserved. Although physiological studies implicate G protein mediated responses in a number of pathways based on sensitivity of the response to cholera or pertussis toxins or the enhancement of the GTP binding to membranes by specific stimuli, this evidence is indirect. Prior to the work as detailed herein, the art has failed to provide direct evidence that these effects occur by the same mechanism by which they occur in other systems. In fact, it has recently been reported by one of the leaders in the field of plant G-protein molecular biology, that it is " . . . unlikely that the plant G .alpha.s are functional homologues of any of the non-plant ones." . . . (ibid. Hong Ma 1994).
Protein-mediated signaling systems are present in organisms as divergent as yeast, plant, and man. The yeast Saccharomyces cerevisiae is utilized as a model eukaryotic organism. Due to the ease with which one can manipulate the genetic constitution of the yeast Saccharomyces cerevisiae, researchers have developed a detailed understanding of many complex biological pathways. It has been demonstrated in numerous systems that the evolutionary conservation of protein structure is such that many heterologous proteins can substitute for their yeast equivalents. For example, mammalian G.alpha. proteins can form heterotrirerlc complexes with yeast G.beta..gamma. proteins [Kang, Y.-S., Kane, J., Kuijan, J., Stadel, J. M., and Tipper, D. J. (1990) Mol. Cell. Biol. 10, 2582-2590]. Screening assays utilizing yeast strains genetically modified to accommodate functional expression of plant G proteins offer significant advantages in research involving the identification of plant proteins that function in intracellular signaling systems, such as G-protein coupled systems.

Method to identify plant proteins that function in G protein coupled systems and compositions therefor


A power system that provides power between an energy storage device, an external charging-source/load, an onboard electrical power generator, and a vehicle drive shaft. The power system has at least one energy storage device electrically connected across a dc bus, at least one filter capacitor leg having at least one filter capacitor electrically connected across the dc bus, at least one power inverter/converter electrically connected across the dc bus, and at least one multiphase motor/generator having stator windings electrically connected at one end to form a neutral point and electrically connected on the other end to one of the power inverter/converters. A charging-sourcing selection socket is electrically connected to the neutral points and the external charging-source/load. At least one electronics controller is electrically connected to the charging-sourcing selection socket and at least one power inverter/converter. The switch legs in each of the inverter/converters selected by the charging-source/load socket collectively function as a single switch leg. The motor/generators function as an inductor.

The use of electric vehicles (EVs) has been promoted in recent years to reduce oil consumption and the emissions of harmful pollutants and carbon dioxide. EVs may include battery powered vehicles, fuel cell powered vehicles, and hybrid electric vehicles (HEVs). Commercially available HEVs employ a battery and an electrical motor that are sized to optimize the energy efficiency of an internal combustion engine and to capture a portion of the kinetic energy for later use through dynamic braking by the motor during deceleration. As such, the batteries can only provide a very limited driving distance (a few miles) in the electrical only mode, in which the engine is not used. On the other hand, plug-in hybrids use a substantially larger battery to enable a driving distance of 20 to 60 miles for normal commuting in the all-electric mode after fully charged. To avoid fuel consumption and air pollutions by operating the engine, the battery is fully charged by a standalone external charger powered by the utility grid and the charging is done preferably overnight to leverage energy costs by taking advantage of off-peak electricity rates. Plug-in hybrids thus offer a greater potential than those hybrid vehicles currently available on the market to reduce oil consumption and the emissions of pollutants and carbon dioxide.
HEVs can have a variety of electrical motor drive systems and use different coupling mechanisms to combine the propulsion forces from an engine and the electrical motor(s) to drive the wheels. An electrical motor drive system may include an energy storage device and one or more drive units. A drive unit typically consists of a power inverter/converter and a motor, in which the inverter/converter either functions as an inverter to convert a dc voltage to an ac voltage suitable to operate the motor, or a converter when the motor is operating in power generation mode. Multiple electrical drive units can be used to provide four-wheel drive capabilities.
As an example, FIG. 1 illustrates a simplified block diagram of a parallel configuration HEV. It employs a single motor drive unit, whose electric motor is connected to the engine shaft through a mechanical transmission and works in parallel with the engine to provide propulsion force to the wheels (not shown in the figure) of the vehicle. The vehicle can be propelled by the engine alone, by the electrical motor alone (all-electric mode), or by both (hybrid mode). The electric motor, controlled by a power inverter/converter and powered by a high voltage (H.V.) battery, can provide the sole driving force in the all-electric mode, where the engine is disconnected from the transmission by the clutch. Or in hybrid mode, the motor handles the variations in the driving force demand to optimize the fuel efficiency of the engine. The motor is also used to start the engine and to charge the H.V. battery when needed during vehicle operations. For charging the battery, the motor functions as a generator driven by the engine or by the vehicle inertia during deceleration and produces an ac voltage, which is converted to dc by the power converter to supply the H.V. dc bus. An electronic controller based on one or more microprocessors is used to control the operations of the engine and electrical motor drive system.
It is desirable to have a large capacity battery being able to store energy enough to power the HEV for a driving distance long enough for a typical daily commuting without using the engine at all, and to be able to charge the battery by plugging into the grid through the charging socket. Traditionally this is accomplished by using a standalone battery charger, typically consisting of an inductor, a rectifier and a dc-to-dc converter to regulate a dc voltage across the dc bus for charging the battery. The standalone charger may be assembled into a single unit installed onboard or off-board the vehicle. Or it may be constructed into two pieces by separating the primary and secondary magnetic cores and windings of a transformer (as disclosed in U.S. Pat. Nos. 5,264,776 and 5,463,303) with one onboard and the other off-board the vehicle. When the two pieces are brought together power can be transferred from the ac source to the battery across the transformer.
An onboard battery charger can also be realized by using the electrical drive inverter and motor in an HEV. In a disclosure (Japanese patent P2000-232737A), a charging device was disclosed, which uses two additional diodes and the electrical motor and inverter to charge the battery from the utility grid. This device, however, cannot operate as a power source to supply external loads.
It is also desirable to make EVs/HEVs to be able to function as mobile electrical power generators for emergency and other uses. While battery-engine hybrids may be suitable for emergency needs, fuel cell powered vehicles may even be suited for regular uses because fuel cells do not generate air-polluting by-products. In a disclosure (US 2004/0062059 A1), an apparatus and method was disclosed to charge a battery in a fuel cell powered inverter-motor drive system or to make the drive system an electrical power source. It employs two switches to selectively couple a three-phase inverter to an electrical motor for operating the motor or to an ac power source through an additional inductor/filter for charging the battery with or without an optional "boosting circuit".
It is now desirable to eliminate or minimize the number of additional components by integrating the battery charging function into the electrical motor drive systems to minimize the cost. The present invention presents hybrid electric vehicle systems and methods for battery charging and/or supplying electrical power to external loads. It is done by utilizing only the already onboard inverter(s) and motor(s) without adding any inductors or switches. Therefore, the present invention can fulfill all the requirements while not incurring any additional cost.

Electric vehicle system for charging and supplying electrical power


A method for treating a subject having a diseased or atrophic state of fibrotic tissue, kidney disease and associated nerve endings, or for promoting tissue regeneration in muscle tissue is accomplished through exposing the tissue with a laser light having a wavelength of about 400 nm to about 700 nm, or more preferably having a wavelength of about 405 nm, about 532 nm, about 635 nm, or a combination thereof. Subsequent to exposure, mesenchymal stem cells can be administered to the subject. After the administration of mesenchymal stem cells, the tissue is further exposed to laser light having a wavelength of about 400 nm to about 700 nm, or a laser light having a single wavelength of about 400 nm to about 700 nm. The mesenchymal cells can be interferon gamma activated.

A. Renal Fibrosis and the Public Health Problem of Kidney Failure
Kidney disease, including both acute and chronic, is the 8th leading cause of death in the United States (US) with over 50,000 deaths in 2010 alone. Chronic Kidney Disease (CKD), affects 23 million adults in the US accounting for 11.5% of the population. Progression to chronic kidney disease is marked by fibrosis of both the tubular epithelium as well as the glomeruli with overexpression of extracellular matrix (ECM) proteins such as collagen. Fibrosis is the formation of excess fibrous connective tissue (such as collagen and glycosaminoglycan) in an organ or tissue, generally from a reparative or reactive process. Stimuli to initiate fibrosis include: sustained presence of pro-sclerotic cytokines, overcrowding of protein traversing the proximal tubule, and renal capillary vasoconstriction; all of which predominate in patients with diabetes and hypertension. The sequelae of persistent high blood pressure or high concentrations of blood sugar can induce an inflammatory state within the kidney, mobilizing macrophages, dendritic cells, and lymphocytes to infiltrate renal parenchyma and secrete pro-inflammatory cytokines such as tumor necrosis factor (TNF) and Transforming growth factor β (TGF-β1). Baseline proliferative activity, though low, is rapidly replaced by progressive increase in apoptotic activity, particularly in the tubular endothelium. In the glomeruli, the reduced ability of endothelial proliferation contributes to the glomerular and peritubular capillary loss observed in fibrosis and glomerulosclerosis. Chronic inflammatory processes are followed by myofibroblast proliferation with a corresponding creation of a degenerative extracellular matrix environment associated with chronic kidney disease and loss of function. At present, no treatment exists for the reversal of renal fibrosis.
B. Effect of Lasers and Radiation on Tissue Regeneration
Low level laser therapy (LLLT) is currently being used to alter cellular activity in clinical applications including pain reduction, inflammatory relief, liposuction, and acne clearance by stimulating cellular proliferative activity. Laser-mediated improvement in wound healing is characterized by both enhanced tissue repair and inhibition of tissue degeneration. The overall mechanism by which low level light laser therapy affects cells is not well-characterized. One component of phenomenon is believed to be the transfer of energy to the cell which then can be used for various activities which otherwise may not occur with the rapidity or efficiency due to limits of cell energy. At the molecular level, such photobiomodulation is based on the ability of molecular chromophores and photo-acceptors to absorb the photons presented by the laser. Chromophore and photo-acceptor distribution may vary according to tissue type; therefore, tissue specific therapies are required to optimize energy delivery. Additionally, there are many molecules that are able to absorb the photons, including hemoglobin, melanin, and water, each molecule type prefers to engage a specific range of light color. Red, green, and violet wavelengths have been reported to promote proliferation of a variety of cells in vitro with results that demonstrate the cell specific preference to a certain wavelength. For example, red light was shown to promote proliferation in mouse skin fibroblasts, but chicken embryo fibroblast increased proliferation in response to green light. Cytochrome c oxidase of the mitochondrial respiratory chain can absorb nearly 50% of infrared light produced by a laser making this molecule the predominant target of laser therapy. Photon absorption can lead to electron transfer reactions, with subsequent increased production of ATP and nitric oxide (NO). Nitric Oxide (NO), serves to activate vasodilation, can operate as a neurotransmitter, and inhibits cell apoptosis through alterations on the enzymatic work of multiple caspases.
Efforts to use low level laser therapy in patients has seen some success, for example U.S. patent application Ser. No. 13/902,749 to Zhu et al. discloses a method of treating neuronal conditions in a patient. This method requires implantation of an optical element in the patient. LLLT has also been used to treat fibrosis, such as in the methods disclosed by U.S. Pat. No. 5,913,884 to Trauner et al. where laser irradiation is used to treat fibrotic tissue after administering a photosensitizing agent to the subject. This method relies on the photosensitizing agent, when photoactivated by laser light to produce a cytotoxic effect, to kill specific cell populations such as macrophages, thereby inhibiting fibrosis.
C. Mesenchymal Stem Cells and Tissue Regeneration Following Fibrosis
Bone marrow derived mesenchymal stem cells (MSC), multipotent adult stem cells, exhibit significant potential as therapeutic agents due to their ability to differentiate into a number of tissue types as well as their ability to reduce inflammation, promote regenerative signals amongst other cell types such as macrophages and endothelial cell, and enhance the orderly production of matrix. When MSCs encounter sites of inflammation, several cytokines and growth factors are produced including nerve growth factors as well as endothelium growth factors such as vascular endothelial growth factor VEGF which promotes endothelial and vascularity remodeling. MSCs also initiate the transition of pro-inflammatory M1 macrophages into suppressor M2 macrophages which work to restore matrix deposition into a healthy, organized microenvironment. Transforming growth factor β (TGF-β1), is an important cytokine in the initial immune response to injured tissue secreted by M2 macrophages; yet, when abnormally sustained in the microenvironment, pathological amounts of extracellular matrix is laid down leading to fibrosis demonstrating dysregulated TGF-β production as a prominent feature of kidney fibrosis. Interleukin 10 (IL-10), an anti-inflammatory cytokine produced by M2 macrophages, may reduce the fibrotic effects of TGF-β, preventing collagen synthesis and further fibrotic progression. MSCs tend to home towards acute inflammation, and are less able to migrate through fibrotic tissues, thereby, reducing their influence on regeneration in fibrosis. Facilitating the regenerative attributes of therapeutic MSCs may provide a new strategy to address and reverse tissue fibrosis.
By way of example, U.S. patent application Ser. No. 13/264,755 to Oron et al. discloses administering phototherapy to an injured subject by irradiation of bone marrow to stimulate mesenchymal stem cell migration to the site of tissue injury. This method does not involve direct irradiation of the damage tissue itself, but rather irradiation at a site removed from the place of injury. U.S. patent application Ser. No. 14/534,779 to Lichtbroun et al. further discloses the administration of a composition and the subsequent irradiation of various tissues with laser light which increase mesenchymal stem cell migration to a wound site.
Despite these advances in the use of low level laser therapy and mesenchymal stem cells to treat conditions such as fibrosis in a subject, each of the disclosed methods suffer from various drawbacks such as the use of photosensitizer or similar compounds, which may have some side effects, as well as the need to build up a certain level of photosensitizer in the target tissue for maximum effectiveness. In other methods, there is no direct irradiation of the damaged tissue itself, or require the implantation of a diode. Accordingly, there is a need for a low level laser light treatment of various diseases, including fibrosis, which does not rely on photosensitizers or other composition, and can allow for direct irradiation of the damages tissue. The present disclosure addresses these needs.
The present invention and its attributes and advantages will be further understood and appreciated with reference to the detailed description below of presently contemplated embodiments, taken in conjunction with the accompanying drawings.

Use of lasers for treating and reversing fibrosis

THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS


A Winding for high voltage transformer having a predetermined number of spaced winding groups joined to form a single winding transformer, each spaced winding group being solenoid wound from a predetermined number of turns. A method of forming the winding and a transformer including the winding are also disclosed.

Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.
The conventional windings in transformer coils for the most common high voltage transformers (132 kv: 11 kV or similar) use a disk type winding. In this winding, the wound cable consists of a number of insulated conductors (up to 32, but usually 4 to 8). The conductors are transposed so that each presents the same impedance to the line to ensure a uniform current distribution among the conductors within the cable.
A disk type winding is employed so that the voltage is across the-coil is distributed evenly from top to bottom and that no two disks experience a greater voltage stress than any other disk under normal operating conditions. This type of winding is shown schematically in FIG. 1. In this type of winding the turns 5 of the winding lie on top of each other to form an axially extending disk 6 rather than cylinder formed in a typical solenoid type winding. As shown, the top disk 7 of the coil is at a higher voltage, and the bottom of the disk will be at zero voltage in a star-type connected three-phase transformer, or at the line voltage in a delta-type connected transformer. The disk windings are connected without the need for joints or brazing of any kind, at one end in an alternating manner down the height of the disk stack.
The primary coil (high voltage side) is usually wound in this manner, and the secondary coil is usually wound in a single layer solenoid type winding, because its voltage is less (11 kV), and so does not suffer the same electric stresses. However, if a second layer is required, it cannot be placed on top of the first and is usually placed a sufficient distance away with appropriate press board spacers and oil ducts sufficient to meet the inter-layer voltage stress and cooling requirements.
Solenoid type windings typically consist of a conductor wound so that the turns of the conductor lie side by side to form a helical layer (usually cylindrical), once a layer is completed, further layers may be wound over the first layer in a reciprocal manner until the desired number of layers is formed.
Transformers are not designed to only meet their normal operating voltage stresses. The clearances are decided so that the transformer can withstand the voltage stresses at the prescribed testing conditions set out in the local standards. For example, in the Australian standard, the clearances and barriers must be designed to withstand approximately twice the voltage stress at the power frequency (the so called power frequency or AC test) and an appropriate lightning impulse test. For a 132 kV transformer, the peak of the lightning impulse test will be 550 kV or 650 kV as specified by the customer.
For the above reasons, it is not practical to wind the high voltage primary coil as a solenoid because the voltage stress between the layers at the top and bottom of the coils is high, and increases in proportion with the number of layers times the number of turns per layer. The worst case normal voltage stress will be between the first turn and the last turn at the top of the winding which will have the full 132 kV normal voltage across the annular thickness of the coil (defined as the difference in the outside radius and inside radius of the coil) and under test conditions, significantly more depending on the test. Hence, disk windings are used. A solenoid-type winding is shown in FIG. 2 where the conductor 10 is wound to and fro vertically to form a number of vertically extending layers 11.
In a disk winding the greatest voltage stress during any test is between the top two disks, but these only have a fraction of the total turns in them, so the voltage will only be of the order of kilovolts or tens of kilovolts during L1, not the full 230 (AC test) or 550 kV (L1).
Disk windings require significant handling and physical contortions of the disks and individual copper conductors in order to be wound in a single length in a neat and tidy manner suitable for transformer coils. For example, each second disk must be turned inside out after winding (so that the inner turn becomes the outer and outer one becomes the inner). This is to facilitate winding in a continuous manner, not to ensure transpositioning. In addition, the conductors must be kinked in plane parallel to the width of the conductor in order to go from one disk to the other.
The abovementioned disadvantages are of more concern in the field of High Temperature Superconductors (HTS). It is most likely that HTS transformers will only replace those very large transformers where the savings in weight and size justify the cooling overhead. Hence, the discussion is limited to those cases where the primary voltage is at 110 kV or greater (132, 230, 350, 500 kV for example), however, it will be appreciated the invention is also applicable to other high voltage windings.
HTS conductors cannot be subjected to the level of mechanical manipulation which copper conductors are subjected to during the winding of transformer coils. The unit length of HTS may also not be available in more than 1000 m lengths which means a completely continuous HTS winding is not possible.
One way to wind a high voltage HITS primary coil and avoid the above-mentioned manipulations is to use a series of electrically connected double pancakes. A pancake is analogous to a disk type winding. The double pancakes could be then connected in series with normal conductors or other HTS conductors with resistive joints. Double pancakes must be used instead of single pancakes to avoid connections that run down the side of the plane of each pancake. Double pancakes allow connections to be all on the outside or inside of the stack avoiding cross leads traversing down the radial length of the coils which will pick up flux.
The disadvantage of this type of arrangement, however, is that in large transformers, the number of connections could be quiet large and approach hundreds. The connections are sources of dissipation which add to the losses, and can be sources of bubbling in liquid nitrogen, or thermal instabilities in other types of cooled methods due to the concentrated nature of the loss.
Another way to wind a high voltage coil is to use a continuous solenoid type winding. However, as stated above, this results in a high voltage stress across a short creep distance at the top of the coil. This is further compounded by the fact that HTS windings have significantly less annular thickness and so the electrical stress is increased many fold.
The voltage between layers within the winding is of not much concern because the interlayer insulation is a solid dielectric, preferably Kapton™, which has a high breakdown strength (>80<90 kV/mm at 77K) sufficient to meet the test requirements. However, at the top end of the coil, the layer to layer voltage stress can breakdown along a creepage path 20 through the liquid nitrogen or gaseous nitrogen where no solid dielectric exists. Gaseous nitrogen at 77 K has a corona on-set point of just 5 kV for distances of between 10 and 30 mm and all liquid nitrogen cooled coils will have a gaseous portion above the liquid.
The addition of a solid inter-layer dielectric which extends beyond the top of each layer is possible, however, the liquid nitrogen would still have significant stress because it has the lower relative dielectric constant (1.4 at 77K compared to 3.0 to 3.6 for Kapton™).
The interlayer dielectric would have to be very thick or very long to the extent where the complete winding becomes very large.
Manufacturers typically take significant and costly precautions to pass the lightning impulse test. The additional benefit of a solenoid type winding is that the L1 pulse is distributed more uniformly between the layers within each solenoid and so can prevent the requirement for a shielding winding or an interleaved winding. In a disk winding, without shielding windings or interleaved windings, the L1 produces a very large stress between the top two disks and would fail without the countermeasures in place. However, these countermeasures are expensive to wind, and complicate the winding considerably.


A process for making a light hydrocarbonaceous liquid in a delayed coker comprising:. (A) providing a hydrocarbonaceous feed to the coke drum and heating the feed to a temperature of about 800.degree. F. to about 1200.degree. F. to provide an intermediate product; and PA1 (B) introducing said intermediate product into the coke drum, operating the coke drum to convert the intermediate product to a final comprising light liquid and coke, and separating the light liquid from the coke; PA1 step (A) being conducted in combination with either step (A) (i) or step (A) (ii); PA1 Step (A) (i) comprising maintaining the feed during step (A) in an enclosed space and subjecting the feed to a pressure that is at least about 500 psig and is sufficient to maintain the specific gravity of the contents of the enclosed space at least about 0.05 to convert said feed to said intermediate product, the intermediate product containing fractions having a lower boiling point than the initial boiling point of the feed and/or a higher boiling point than the final boiling point of the feed, then reducing the pressure on the intermediate product below about 500 psig prior to step (B); PA1 step (A) (ii) comprising contacting the intermediate product from step (A) prior to and/or during step (B) with at least one preheated stripping gas and dissolving at least part of the intermediate product in the stripping gas.

The term "light hydrocarbonaceous liquid" as used herein refers to any hydrocarbonaceous liquid that boils at a temperature below about 1000.degree. F. at atmospheric pressure.
Delayed cokers are used on low value hydrocarbonaceous feeds to obtain higher-value, lower-boiling cracked products. Coking is a high severity thermal cracking or destructive distillation process. It is typically used on vacuum residuum to generate lighter components. In a delayed coker, the hydrocarbonaceous feed is held at an elevated temperature (e.g., about 825.degree. F. to about 925.degree. F.) to deposit coke in the coke drum while cracked vapors containing light hydrocarbonaceous liquids are taken overhead. In general, coking processes that minimize coke yield and maximize light hydrocarbonaceous liquid yield are advantageous.
U.S. Pat. No. 2,271,097 discloses a process for converting high boiling hydrocarbons into lower boiling hydrocarbons. The process includes the step of heating the bottoms from a fractionator in a viscosity breaker at a temperature of 850.degree.-950.degree. F. and a pressure of 75-500 psig.
U.S. Pat. No. 3,172,840 discloses a process for converting hydrocarbonaceous materials such as petroleum oils to gasoline and middle distillates. The process includes the step of cracking a product stream boiling in the range of 750.degree.-950.degree. F. from a coker bubble tower in a thermal cracking furnace at a temperature of 850.degree.-1000.degree. F. and a pressure of 300-1000 psig.
U.S. Pat. No. 4,213,846 discloses a delayed coking process that employs a hydrotreating step wherein gas oil from the coker fractionator is hydrotreated at a temperature of 315.degree.-400.degree. C. (599.degree.-752.degree. F.) and a hydrogen partial pressure of 350-2000 psig.
U.S. Pat. No. 4,519,898 discloses a delayed coking process wherein the oil feed is preheated to a temperature in the range of about 775.degree. F. to about 920.degree. F. and a stripping gas (e.g., steam, nitrogen, normally gaseous hydrocarbons, natural gas) is introduced into the coking drum to form coke containing 5 to 15 weight percent volatile matter.
U.S. Pat. No. 4,547,284 discloses a delayed coking process wherein the feedstock is continuously heated in a coking heater and introduced into a coke drum, the heater is operated to provide a coke drum temperature of from 415.degree.-455.degree. C. (779.degree.-851.degree. F.), and after filling of the drum to the desired level, feedstock introduction is discontinued and the coke drum contents are heated to a temperature of 450.degree.-500.degree. C. (849.degree.-932.degree. F.) and which heating temperature is at least 10.degree. C. (18.degree. F.) greater than the coking temperature, by passing a non-coking vapor (e.g., coker distillate, naphtha, coker gas) through the contents of the drum to reduce the volatile combustible matter content thereof.
U.S. Pat. No. 4,758,329 discloses a delayed coking process wherein the feedstock is an aromatic mineral oil, and the coke CTE is reduced and the coke particle size is increased by sparging with a gas (e.g., nitrogen) during the coking cycle.
U.S. Pat. No. 4,784,746 discloses a process for upgrading crude oil (whole crude or topped crude) by combining the crude oil with a low boiling component that boils below 330.degree. F. and has an aromatic content of at least 20%, then heating the resulting mixture at 400.degree.-500.degree. C. (752.degree.-932.degree. F.) and a pressure sufficient to maintain the feed stream in the liquid phase. The reference discloses pressures in the range of 100-1000 psig. The process is conducted for an effective period of time to increase the proportion of non-residual components in the crude oil using a transalkylation process.
U.S. Pat. No. 4,840,725 discloses a process for converting high boiling hydrocarbons to lower boiling materials characterized by an increase in aromatic content and a lower pour point which comprises contacting said high boiling hydrocarbons with water at a temperature of from about 600.degree. F. to about 875.degree. F. and a pressure of at least about 2000 psig in the absence of any externally supplied catalysts, and wherein the weight ratio of water to high boiling hydrocarbons is from about 0.5:1 to about 1:1, and the water and high boiling hydrocarbon form a substantially single phase system under the elevated temperature and pressure conditions used.

Process for making light hydrocarbonaceous liquids in a delayed coker


Systems and methods are operable to concurrently present images on a small display of a mobile media device and a large display of a media presentation system. An exemplary method receives emulated information from a mobile media device, wherein the emulated information corresponds to at least one image that is being currently presented on a display of the mobile media device; generates at least one image based upon the received emulated information, wherein the at least one image is configured for presentation on a display of a media system; and communicates the at least one image to a display of the media system. The image presented on the display of the media system is substantially the same image presented on the display of the mobile media device. The image presented on the display of the media system is substantially larger than the image presented on the display of the mobile media device.

Mobile media devices, such as a cellular phone, a small touch sensitive communication device, a small portable music player, or the like, are often configured to present information to the user on a relatively small display component. However, the information presented on the small display may be relatively hard to discern and/or understand. For example, when a video clip is presented on the relatively small display, or presented on a small portion of the small display, the subject matter of the presented video clip may be hard to discern. As another example, text presented on the display using small letters may be difficult to see and read.
Further, the difficulty in discerning and understanding presented information on a small display may make operation of the small mobile media device relatively difficult. For example, if identifiers of virtual touch sensitive buttons presented on a touch sensitive display are not easily read because of the small text size, the user may have difficulty in identifying the proper virtual touch sensitive buttons to operate the small mobile media device. Further, if the user has relatively large fingers and/or does not have a sufficient amount of dexterity, such users may find it difficult to touch and/or navigate about the presented virtual touch sensitive buttons that are used to control the small mobile media device.
Accordingly, there is a need in the arts to improve the ability of a user to discern and understand information presented on a relatively small display of a mobile media device.

This patent is subject to a terminal disclaimer.

Apparatus, systems and methods for presenting displayed image information of a mobile media device on a large display and control of the mobile media device therefrom


A ceramic electronic component includes a multilayer chip having a substantially rectangular parallelepiped shape and including dielectric layers and internal electrode layers that are alternately stacked, the internal electrode layers being alternately exposed to two edge faces of the multilayer chip facing each other, and a pair of external electrodes respectively formed on the two edge faces so as to be connected to the internal electrode layers exposed on the respective edge faces, each external electrode extending to at least one side face of the multilayer chip, wherein in the multilayer chip, oxides including Zn and Ni are present around the internal electrode layer in a vicinity of a connection part connecting the internal electrode layer to the external electrode.

To achieve a smaller size and a larger capacitance of the multilayer ceramic capacitor, it has been promoted to thin the internal electrode layers and the dielectric layers to increase the number of the internal electrode layers and the dielectric layers that are stacked and to thin the top cover layer and the bottom cover layer.
When the number of the internal electrode layers and the dielectric layers that are stacked is increased and the thickness of the cover layer is reduced, cracks may occur in the area where the cover layer, a side margin, and an end margin overlap when external electrodes are baked. The side margin is a region located from each of the two side faces of the multilayer chip to the internal electrode layer, and the end margin is a region where the internal electrode layers connected to the same external electrode face each other without interposing the internal electrode layer connected to the other external electrode therebetween.
To inhibit occurrence of the crack, the length of the region where the metal component of the external electrode is diffused in the internal electrode layer (the diffusion length) is controlled as disclosed in, for example, Japanese Patent Application Publication No. 2011-135079.

Ceramic electronic component and method of manufacturing the same


A storage system includes plural storage units having respective storage controllers and associated caches. A first one of the storage units further includes an internal workload generator to initiate a data operation with respect to at least one destination storage unit, where the data operation is associated with tag information to affect a caching algorithm used by the cache of the at least one destination storage unit. The at least one destination storage unit includes at least one of the plural storage units.

Increasingly, to store large amounts of data, distributed storage systems are provided. Distributed storage systems can be implemented with a storage area network (SAN). Hosts (such as file servers, database servers, client computers, and so forth) coupled to a SAN are able to perform data operations (such as read and write operations) with respect to storage devices (e.g., disk-based storage devices, tape-based storage devices, storage library systems, etc.) coupled to the SAN. Other forms of distributed storage systems are also available, such as storage array systems that have multiple nodes containing respective sets of storage devices.
The throughput of a storage system is determined by access speeds of the storage devices in the storage system, communications speeds of links interconnecting the storage devices, and efficiency in retrieving and writing data from and to storage devices. If insufficient throughput is provided by a storage system, then a host may experience delays when performing data operations with respect to the storage system.

Affecting a caching algorithm used by a cache of storage system

Hewlett-Packard Development Company, L.P.


A method for detecting faults in plates includes the steps of: transmitting an acoustic signal towards the plate from a transmitting transducer, and receiving the acoustical signal from the plate in a receiving transducer. The receiving transducer is mounted at a distance from the transmitting transducer. The method includes the further steps of identifying zones of the plate wherein energy levels of the received signals are attenuated compared to other zones of the plate, and comparing the energy levels of the A2 and S3 guided Lamb modes in the received signals in the identified zones.

In the oil and gas industry, there is a need for efficient testing of pipelines. The pipelines are subject to wear from corrosive fluids and sand, and deformation from movements on the seabed or in the ground. Said pipelines are also prone to developing cracks, in particular near the welding seams. Welding seams are inherent weak points due to the changes of the steel structure caused by the welding process. Cracks may develop due to stress caused by temperature or pressure cycling, movements in the ground, coating disbondment, and consequent intrusion of mineral water to the areas under stress.
The structural integrity of pipelines may be tested using inspection pigs which travel inside the pipelines measuring the condition of the pipe wall. Acoustical transducers mounted on the pig are used for ultrasonic detecting of corrosion and cracks in the pipeline walls. A problem with present ultrasonic testing methods is that it is difficult to differentiate between indications of corrosion (thinning of the wall) and cracks. Even though corrosion must be considered an important factor affecting the health of the pipeline, cracks are considered to be more crucial for the pipeline, as a crack may develop and eventually cause a fatal breakdown of the pipe wall. Corrosion is handled in special ways, but cracks must be handled immediately. A scan of the pipeline wall may give an indication of the presence of a fault, but the pipeline must be physically engaged in order to determine the nature of the fault. This involves the replacement of a section of the pipeline. Often one then finds that the indicated fault is due to corrosion, which means that it was unnecessary to replace the pipeline section, as the corrosion could have been remedied in a less costly way.


A method of obtaining an enantioenriched organic compound comprising the steps of: 1) generating from a starting racemic, non-enantiopure or achiral compound a first mixture comprising at least one fluorous-tagged compound and at least one other non-fluorous tagged compound, at least one of these two compounds being enantioenriched relative to the starting compound; 2) contacting a first non-fluorous phase including the first mixture with a fluorous phase at a first phase interface, the fluorous-tagged compound distributing between the first non-fluorous phase and the fluorous phase; and 3) contacting the fluorous phase with a second non-fluorous phase at a second phase interface. The method further includes the step of having a third compound in the second non-fluorous phase that reacts with the fluorous-tagged compound to produce a second compound and the step of generating the first mixture by chemical or enzymatic kinetic resolution of a racemic or non-enantiopure compound.

1. Field of the Invention
The present invention relates to fluorous triphasic reaction and separation processes and, especially, to the applications of these processes to the resolution of racemic or partially enantiopure organic compounds such as alcohols, amines, carboxylic acids and derivatives of carboxylic acids.
2. Description of Related Art
Resolutions of racemic organic compounds into their enantioenriched or enantiopure component enantiomers are an important and commonly used process in chemical, pharmaceutical, biotechnological, agricultural and other industries. In the pharmaceutical field, for example, racemic drugs are frowned upon because one enantiomer of a racemate typically predominately or exclusively induces the decided physiological or pharmacological effects. Accordingly, highly enantioenriched or enantiopure drug substances are almost always preferred over racemates.
Highly enantioenriched or enantiopure compounds are generally obtained by one of three basic strategies: 1) they can be prepared from other enantiopure compounds such as natural products by chemical synthesis; 2) they can be prepared from achiral compounds by asymmetric synthesis, or 3) they can be prepared from racemic compounds by resolution. Because many racemic compounds are commercially available or easily prepared, the resolution strategy is especially important. See, for example, J. Jacques, A. Collet, S. H. Wilen, Enantiomers, Racemates and Resolutions; Wiley: New York, 1981; E. L. Eliel, S. Wilen, Stereochemistry of Organic Compounds; Wiley-Interscience: New York, 1994, Chapter 7; and A. Collet, "Resolution of racemates: Did you say 'classical'?," Angew. Chem., Int. Ed. Eng., 37, 3229 (1998). However, resolutions can often be expensive, wasteful and environmentally unfriendly processes. The problem is especially acute for the general class of resolutions called kinetic resolutions, in which a mixture of a starting compound and a chemical derivative or product must be separated. This separation is often time consuming and expensive, especially when chromatography and related separation processes are used. Such processes often generate large amounts of waste solvent that must be disposed of or destroyed. Improvements in reaction and separation processes are therefore desirable.
Fluorous techniques for chemical synthesis have recently emerged as powerful new reaction and separation tools; see, for example, D. P. Curran, Stimulating Concepts in Chemistry; F. Vögtle, J. F. Stoddard and M. Shibasaki, Ed.; Wiley-VCH: New York, 2000, p. 25. Most fluorous techniques can be classified by the separation method employed. Processes such as fluorous biphasic reactions and more recently fluorous triphasic reactions are typical of liquid-liquid based separations. See, for example, I. T. Horvath, "Fluorous biphase chemistry," Acc. Chem. Res. 31, 641 (1988). The present inventors have discovered that new fluorous triphasic reaction and separation processes provide powerful and practical new methods for chemical resolution and other processes.

Fluorous triphasic reaction and separation processes for the generation of enantioenriched alcohols, amines, carboxylic acids and related compounds