A spinning reel includes a reel body having a rear section; a rotor; a spool; a spool shaft; a bushing; and rotation control element for controlling the relative rotation between the reel body and the bushing. The spool has an axis of rotation. The spool shaft has a front end fixed to the spool and a rear end that extends into the rear section of the reel body, the rear end having a peripheral surface. The bushing includes a cylindrical member which has a peripheral surface, and which has defined therein an opening. The opening has a configuration that conforms to the peripheral surface of the rear end of the spool shaft, and supports the spool shaft such that rotation of the spool shaft relative to the cylindrical member is prevented, and such that the cylindrical member is capable of rotation relative to the reel body as well as motion in the direction of the axis of rotation. The bushing also includes a flange which is located rotatably at the peripheral surface of the cylindrical member, and connection element for linking the cylindrical member and the flange such that relative rotation between the cylindrical member and the flange is prevented while tilting of the flange relative to the cylindrical member in the direction of the axis of rotation is permitted.

A spinning reel, in general, is provided with a reel body, a rotor which is rotatably supported on the reel body, and a spool on which the fishing line is wound. Furthermore, the spinning reel is provided with a drag mechanism whereby the spool is stationary and does not rotate with respect to the reel body, but allows the spool to rotate when force in excess of a specified level is applied. In a rear drag type of spinning reel wherein the drag mechanism is provided at the back end of the reel body, the spool shaft, which is fixed to the spool, extends towards the rear into the drag mechanism. The drag mechanism is provided with a bushing which supports the spool shaft such that it cannot rotate relative to the reel body, but can move in the axial direction.
The use of a split-type of bushing is known in these drag mechanisms. Such bushings are composed of a flange which is a disk plate that can frictionally engage the reel body, and a cylindrical member whose shape is virtually cylindrical and that supports the spool shaft so that it cannot undergo relative rotation but can slide in the axial direction. A through-hole having an oval cross section is formed through the center of this cylindrical member to slidably support the spool shaft so that it does not rotate relative to the reel. In addition, the cylindrical member is provided on its peripheral surface with a chamfered section parallel in the direction of its axis, and thus the peripheral surface of the cylindrical member has an oval shape. An engagement hole of an oval shape is formed in the center of the flange member so that it can be fitted around the peripheral surface of the cylindrical member.
In spinning reels, generally, feel is impaired during operation of the handle and such if the spool shaft should wobble in the direction of rotation with respect to the bushing. For this reason, in the aforementioned split-type bushing, the gap between the engagement hole in the flange and the peripheral surface of the cylindrical member must be kept to a minimum. However, if the space between the flange member and the cylindrical member is made small, depending on how the bushing is attached, the flange may be pushed in at an angle so that the cylindrical member gouges the spool shaft. When this occurs, the spool shaft cannot slide smoothly. In order to prevent this situation, either a space be formed between the cylindrical member and the spool shaft so that the cylindrical member can push against the spool shaft, or a space can be formed between the cylindrical member and the flange member to allow the flange to tilt. However, if this kind of space were to be formed, wobbling would be generated in the direction of rotation, as was stated previously.
Bushings in which the cylindrical member and the flange member are a single piece are also known. However, in this single-piece type of bushing, as well, if the flange member is pushed at an angle, it grinds against the cylindrical member, and thus it is necessary to leave a certain amount of space between the cylindrical member and the spool shaft. For this reason, even in a single-piece type of bushing, wobbling is generated in the direction of rotation when a smooth sliding action of the spool shaft is attempted.
An object of the present invention is to obtain a smooth sliding action of the spool shaft as well as to reduce wobbling in the direction of rotation.

Spinning reel with bushing including tiltable flange


An information processing unit of the present invention includes a display panel capable of displaying a video image; and a casing having a rear face panel that covers at least a back side of the display panel, the back side being opposite to a display face of the display panel. In the information processing unit, the rear face panel has an opposed face opposed to the display panel, and the opposed face includes a wall-thinned portion having a small thickness, and a wall-thickened portion that is a part of the wall-thinned portion having a thickness increased in a direction toward the display panel, and the wall-thickened portion is formed continuously from one side to an opposite side of the opposed face, the one side and the opposite side forming a perimeter of the opposed face and being opposite to each other.

1. Field of the Invention
The present invention relates to a display device such as a monitor used in a personal computer (hereinafter referred to as a PC) or the like, and particularly relates to an information processing unit having portability, such as a notebook PC.
2. Description of Related Art
Recently, a portable information processing unit such as a notebook PC has faced contradictory requirements: the improvement of resistance against an external force such as an impact when dropped or a static pressure, and the reduction of size and weight. An effective means of achieving the reduction of weight is to decrease a wall thickness of a casing. When a casing has a smaller wall thickness, however, the mechanical strength thereof decreases. JP 9(1997)-62400 A discloses a casing that is provided with reinforcing ribs over a front-side internal face in order to increase the mechanical strength, the reinforcing ribs being extended diagonally toward the inside. JP 2007-272860 A discloses a structure as follows: in order to increase the mechanical strength of a casing having a domed structure, reinforcing ribs that are substantially parallel in a direction in which a portion is raised for forming the domed structure are provided on internal surfaces of the casing.
A configuration in which diagonal reinforcing ribs are provided over a front-side internal face, as disclosed by JP 9(1997)-62400 A, has the following problem: in the case where an area of a casing is increased, such as the case where the area of the casing is increased as a screen size is widened, diagonal ribs increase for the increase in the area of the casing. In other words, there is a problem that a weight unavoidably increases in proportion to the area. Further, what usually is carried out in order to make the thin-walled casing resistant against an external force is to use a metal material. Still further, in the manufacturing aspect, so-called casting, in which a molten metal material is poured into a die and molded by casting, is preferable from the viewpoint of volume production. In the case where an approximately rectangular casing is formed by molding, usually a molten metal flows from one side forming a perimeter of the casing toward another side opposite thereto, and thereafter is cooled. The diagonal ribs disclosed by JP 9(1997)-62400 A, however, are formed in directions crossing the direction in which the molten metal flows (hereinafter this direction is referred to as a flow direction), and therefore the flow is hindered. This causes, for example, the molten metal to be supplied insufficiently to a downstream part with respect to the ribs in the flow direction, thereby making it difficult to achieve uniform molding. Particularly, in the case where a metal having a high melt viscosity or a metal that is easily solidified when cooled is used, it is difficult, or substantially impossible in fact, to mold a casing having ribs crossing the flow direction.
Further, as to the casing disclosed by JP 2007-272860 A, there is a possibility that ribs could come into contact with a display part when the raised part deforms in response to a static pressure applied to.

Panasonic Intellectual Property Management Co., Ltd.


A compound of the formula: ##STR1## and its pharmaceutically acceptable salts, wherein A.sup.1 and A.sup.2 are each halo or H; X.sup.1 is CH.sub.2, CO, SO or SO.sub.2 ; X.sup.2 is CH.sub.2 or CO; Y is piperazinyl-(CH.sub.2).sub.n --, 2,3,4,5,6,7-hexahydro-1H-1,4-diazepinyl-(CH.sub.2).sub.n --or --N(R.sup.5)--(CH.sub.2).sub.n -- wherein R.sup.5 is H or C.sub.1-4 alkyl, and n is 0, 1, 2, 3, or 4; R.sup.1 is selected from the following: (a) N-morpholino-C.sub.1-4 alkylphenyl, C.sub.1-4 alkoxycarbonyl, C.sub.2-5 acyl, dihydroimidazolyl, formamidino, guanidino or dihydroimidazolylamino, etc.; (b) hydrogen, C.sub.1-4 alkyl, etc.; (c) piperidinyl; (d) C.sub.5-14 cycloalkyl, bicycloalkyl or tricycloalkyl; (e) C.sub.7-14 azacyclo-, azabicyclo- or azatricyclo-alkyl; and (f) C.sub.7-10 bicycloalkenyl, benzo C.sub.5-7 cycloalkyl or heterocyclic, etc., with proviso that when Y is piperazinyl, at least one of A.sup.1 and A.sup.2 is H; X.sup.2 is CH.sub.2 ; and/or R.sup.1 is a group selected from group (a); R.sup.2 is hydrogen, C.sub.1-4 alkyl, optionally substituted phenyl, or heterocyclic; and R.sup.3 and R.sup.4 are each C.sub.1-5 alkyl. The novel dihydropyridine compounds of this invention have excellent bradykinin antagonistic activity and are thus useful for the treatment of inflammation, cardiovascular disease, pain, common cold, allergies, asthma, pancreatitis, burns, virus infection, head injury, multiple trauma or the like in mammalian, especially humans.

Bradykinin ("BK") is generated under normal conditions in mammalia by the action of various plasma enzymes such as kallikrein on high molecular weight kininogens. It is widely distributed in mammals, as are its two receptor subtypes, B.sub.1 and B.sub.2. The actions of BK at the B.sub.1 receptor include mainly contraction of arterial and venous preparations, although it can cause relaxation of peripheral resistance vessels as well.
Many of the more important functions of BK, such as increases in vascular permeability, pain, and vasodilatation, however, are mediated by the B.sub.2 receptor. These effects at the B.sub.2 receptor are believed to be responsible for BK's role in numerous diseases, such as inflammation, cardiovascular disease, pain, and the common cold. Hence antagonists at the B.sub.2 receptor should find considerable therapeutic applications. Most of the efforts in this area thus far have been directed at peptidic analogues of the BK structure, some of which have been studied as analgesics and antiinflammatory agents.
It would be desirable if there were provided a non-peptide antagonist of the B.sub.2 receptor, having a good B.sub.2 antagonistic activity and a good metabolic stability.


A monitor/analyzer for an alternating current (AC) electrical system responds to power line disturbances by generating a trigger signal when a change in voltage with respect to time electrical parameter is greater than a programmed threshold. The monitor/analyzer includes a sensor for sensing an AC waveform in the electrical system, an analog-to-digital converter for sampling the AC waveform, and a microcomputer. Firmware of the microcomputer cooperates with the A/D converter and provides a plurality of digital samples of the AC waveform for each of some of its AC cycles. The firmware generates each of plural dV/dt parameters of the AC waveform from a corresponding adjacent pair of the digital samples within one of the waveform's AC cycles. A trigger signal is generated when one of the dV/dt parameters is greater than the programmed threshold. The digital samples of the AC waveform before and after the power line disturbance are captured and output to a display in response to the trigger signal.

1. Field of the Invention
This invention relates to an apparatus for monitoring electric power systems and, more particularly, to an apparatus for digitally capturing a portion of a waveform of an electric power system in response to a waveform disturbance trigger condition.
2. Background Information
State of the art monitors for alternating current (AC) power systems incorporate microcomputers for calculating various electrical parameters such as RMS currents and voltages, peak currents and voltages, power, energy, power factor and the like. One such monitor is disclosed in U.S. Pat. No. 5,587,917. In addition to monitoring the various electrical parameters of the AC system, this monitor also digitally captures portions of the waveform for harmonic analysis. This places a very high burden on the microcomputer in the monitor. Accordingly, this monitor uses a slow sampling rate for gathering the data needed for performing the monitoring functions and operates at a second, higher rate for waveform capture in response to a manual command or automatically in response to values of selected ones of the electrical parameters which exceed predetermined thresholds.
A monitor/analyzer for an AC electrical system, disclosed in commonly owned U.S. patent application Ser. No. 08/608,387, filed on Feb. 28, 1996, responds to selected events by generating trigger signals when selected monitored electrical parameters, including neutral current, exceed programmed thresholds. The trigger signals initiate simultaneous waveform capture of multiple waveforms in the AC system. Multiple trigger signals result in sequential waveform capture so that if a plurality of triggers are programmed for the same event, extended waveform data is captured for the event.
Commonly owned U.S. patent application Ser. No. 08/608,386, filed on Feb. 28, 1996, discloses a monitor for an AC electrical system which generates on-line a display presenting the values, either in magnitude or as a percent of the fundamental, of fifty harmonics of any of the currents and voltages in the system.
A circuit interrupter, disclosed in commonly owned U.S. patent application Ser. No. 08/342,208, filed on Nov. 18, 1994, provides waveform capture in addition to protection functions. The circuit interrupter microcomputer operates in a protection mode to provide the protection functions and in a waveform capture mode to record the waveform data.
It is also known to employ a rate of change of current, di/dt, in tripping a circuit breaker. See, for example, U.S. Pat. Nos. 3,673,455; and 5,224,006.
Known monitors for AC electrical systems detect disturbances in such systems by employing information obtained from plural AC cycles.
There is a need, therefore, for an improved monitor for AC electrical systems which provides an improved capability for monitoring sub-cycle disturbances in such systems.

Apparatus for waveform disturbance monitoring for an electric power system


The invention provides a method of targeting T-cells to tumor cells using a tumor-associated antigen (TAA) specific antibody and a T-cell specific antibody, wherein the two antibodies can bind to each other through a high affinity avidin/biotin or streptavidin/biotin connection. The invention further provides methods to target activated T-cells to different tumor types by using a T-cell specific antibody that is specific to an activated T-cell surface molecule like CTLA-4.

Within the next decade, cancer is likely to replace heart disease as the leading cause of U.S. deaths, according to forecasts by the NCI and the Centers for Disease Control and Prevention. Apparently, new ideas are desperately needed for tumor cells destruction.
One possible solution is to deliver tumor specific T-cells to patients. Porter et al. (Porter et al., N. Engl. J. Med., (2011)) have solved the problem of retargeting and co-stimulation by demonstrating that efficient retargeting of T-cells can be achieved by a genetically engineered chimeric "bipartite" antigen receptor. Such a bipartite receptor consists of two signaling modules, (i) an antibody conferring new antigen specificity for the B-cell antigen CD19 and (ii) a co-stimulatory domain that expanded tumor-reactive T-cells, which retained their functional phenotype, including in vivo cytolytic activity and the ability to travel to tumor sites without prematurely succumbing to apoptosis. A low dose (˜1.5×105 cells/kgbw) of autologous chimeric antigen receptor-modified T-cells reinfused into a patient with refractory chronic lymphocytic leukemia (CLL) expanded to a level that was more than 1000 times as high as the initial engraftment level in vivo and was able to eliminate about 1012 tumor cells in a CLL patient.
Unlike with other therapeutic approaches, chimeric antigen receptor modified T cells have the potential to replicate in vivo. The long-term persistence of such chimeric T cells could lead to sustained tumor control and obviate the need for repeated infusions of antibodies.
A major problem with adoptive T-cell therapy is, however, that essentially a new reagent needs to be created for each patient. Such a labor-intensive therapy does not easily fit into current modes of commercial practice of pharmaceutical and biotechnology companies (Rosenberg et al., Nat. Rev. Cancer, 8, 299-308 (2008)).
Monoclonal antibodies (mAbs) are emerging as one of the major class of therapeutic agents in the treatment of many human diseases, particularly in cancer and immunological disorders. As of 2010, 28 mAbs have been approved by the United States Food and Drug Administration for clinical applications. Therapeutic mAbs target tumor associated antigens (TAA) expressed by tumor cells (Scott et al., Nat Rev Cancer, 12, 278-287 (2012)).
Tumor cell killing by therapeutic antibodies is mediated by several mechanisms such as direct tumor cell killing (e.g. delivery of a cytotoxic payload by chemotherapy drug, catalytic toxin, radioisotope, or enzyme), immune-mediated tumor cell killing (e.g. via opsonization triggering cytotoxic cells) or vascular and stromal cell ablation (e.g. by modification of biological processes such as growth and apoptosis) as it is demonstrated on FIG. 1 and described in (Scott et al., Nat Rev Cancer, 12, 278-287 (2012)).
Conjugated antibodies are a form of biological guided missiles that combine a targeting moiety with a potent effector molecule that can deliver a payload such as a drug, toxin, small interfering RNA or radioisotope to a tumor cell. Conjugating cytotoxic agents to mAbs has enhanced targeted therapeutic delivery to tumors. Antibody-drug conjugates are now one of the most successful and important new treatment options for lymphomas and solid tumors.
Monoclonal antibodies (mAb) and their fragments, labeled with therapeutic radionuclides, have been used for many years in the development of anticancer strategies, with the aim of concentrating radioactivity at the tumor site and sparing normal tissues. When delivered at a sufficient dose and dose rate to a neoplastic mass, radiation can kill tumor cells. Because cancer frequently presents as a disseminated disease, it is imperative to deliver cytotoxic radiation not only to the primary tumor but also to distant metastases, while reducing exposure of healthy organs as much as possible.
Over 85% of human cancers are solid tumors, which makes them hard to target by antibodies. The largest percentage of the dose of mAb is in the plasma because whole-body distribution predominantly targets organs that are highly perfused with blood. Therefore, mAbs directed against tumor-specific antigens largely remain in the blood; no more than 20% of the administered dose typically associates with the tumor. In addition, anatomical and physiological properties of solid tumors make them particularly hard to penetrate. Generally only on the order of 0.01% of the injected mAb dose penetrates the tumor (Beckman et al., Cancer, 109, 170-179 (2007)).
Molecular genetics and chemical modifications to mAbs have, however, advanced their clinical utility by improving their pharmacokinetic profiles. Penetration is improved by structural modifications. Ab constructs include Fab and Fab′2 fragments, scFvs, multivalent scFvs (e.g., diabodies and tribodies), minibodies (e.g., scFv-CH3 dimers), bispecific Abs, and camel variable functional heavy chain domains. A suitable balance must be found between Ab properties that promote tumor penetration and those that promote tumor retention. Low-affinity Abs penetrate more deeply into the tumor than high-affinity Abs. Due to their smaller size scFv fragments diffuse approximately 6 times faster than IgG (Beckman et al., Cancer, 109, 170-179 (2007)).
The methods of pretargeting involves separating the targeting antibody from the subsequent delivery of an imaging or therapeutic agent that binds to the tumor-localized antibody. This provides enhanced tumor/background ratios and the delivery of a higher therapeutic dose than when antibodies are directly conjugated with radionuclides, as currently practiced in cancer radioimmunotherapy. There are promising clinical results using streptavidin-antibody constructs with biotin-radionuclide conjugates and bispecific antibodies (bsAbs) with hapten-radionuclides in therapy of tumors, (described in, e.g., International Patent Application WO 01/97855, U.S. Pat. No. 7,229,628, and the references cited therein).
Via their Fc-receptors antibodies are also capable to induce immune-mediated tumor cell killing by the induction of phagocytosis, complement activation, or antibody-dependent-cellular cytotoxicity (ADCC).
T-cells are the strongest force of the immune system capable of rejecting entire organ grafts (e.g. kidneys, livers, etc.). In addition, healthy humans carry approximately 3-times more T-cells than NK-cells in their circulation such that their numbers may be sufficient to eliminate most cancer cells after recruitment.
T-cells, however, do not carry activating Fc-receptors, therefore cannot be recruited for the direct elimination of a tumor cell by antibody-mediated cellular cytotoxicity. This shortcoming can be overcome by creating bispecific antibodies (bsAbs) capable of simultaneous binding to two different targets. The idea of using T-cells to efficiently kill tumor cells using bsAbs emerged in the 1980. BsAbs directed against a tumor marker and CD3 have the potential to redirect and activate any circulating T-cells against tumors.
Various bispecific antibody formats such as recombinant tandem bispecific scFvs, bispecific diabodies and tandem bispecific diabodies have been developed. These constructs can specifically bind both the tumor cell and a trigger molecule on a T-cell (e.g. CD2, CD3, CD5, TCRα, TCRβ, TCRγδ and CD28). The best-studied trigger is CD3. The most prominent member of the novel class of recombinant bispecific T-cell engagers (BiTEs) is the CD19- and CD3-directed agent blinatumomab (MT103), which is studied in five ongoing clinical trials.
BsAbs directed against the CD3 of T-cells have a major drawback. Without the secondary signal provided by the interaction between CD28 and one of its ligands (e.g., B7), T-cells are not fully activated, and might even become anergic. The first anti-CD3 bsAbs were thus administered in combination with anti-CD28 antibodies, but the combination yielded mixed results.
The B7-CD28/CTLA-4 co-stimulatory pathway of T-cells plays a pivotal role in maintaining health. Microbes and cytokines produced during innate immune responses induce expression of co-stimulators, such as B7 (CD80/86) molecules, on the antigen presenting cells (APCs). The B7 co-stimulators are recognized by the CD28 receptors of naïve T-cells, providing "signal 2" and in conjunction with antigen recognition ("signal 1") initiate T-cell responses.
Lack of co-stimulation, and the concomitant inadequacy of IL-2 production, prevent subsequent proliferation of the T-cell and induce a state of non-reactivity termed "anergy". This is associated with a block in IL-2 gene transcription and a lack of responsiveness of the affected T-cells to IL-4. Anergy may be overcome with prolonged IL-2 stimulation.
CTLA-4 is a T-cell surface molecule that was originally identified by differential screening of a murine cytolytic T-cell cDNA library. The CTLA-4 is a second receptor for B7. It is a CD28 homologue and is expressed only on activated T-cells. It binds with high affinity to the CD28 ligands, B7-1 (CD80) and B7-2 (CD86).
It is suggested that CTLA-4 can function as a negative regulator of T-cell activation. CTLA-4 receptors of T-cells work as a braking mechanism on T-cell activation that is indispensable to ensure tolerance to self-tissues. If CTLA-4 does not function due to a genetic deficiency or it is blocked by various manipulations, CD28 functions unopposed and swings the balance in favor of immune stimulation resulting in breakdown of tolerance.
Thus, the B7-CD28/CTLA-4 co-stimulatory pathway of T-cells plays a pivotal role in maintaining health. Not surprisingly, both the accelerator (CD28) and the brake operator (CTLA-4) on the immune system were apparently targeted by new therapeutic initiatives in autoimmune disorders and cancer, respectively (Bakacs et al., Pharmacol. Res., 66, 192-197 (2012)). Immunomodulatory antibodies directly targeting receptors involved in checkpoint regulation of immune cells have, however, achieved controversial clinical results.
TGN1412, a monospecific 'superagonistic' CD28 antibody induced systemic T cell activation and severe cytokine release syndrome when injected into six healthy volunteers, and since then concerns have been raised about the use of immunomodulatory molecules.
Anti-CTLA-4 antibodies on the other hand block the T-cell inhibitory receptor CTLA-4. Methods and compositions were provided for increasing the activation of T-cells through a blockade of CTLA-4 signaling. For example, U.S. Pat. No. 7,229,628 discloses binding molecules that specifically interact with the CTLA-4 antigen, but do not activate signaling (blocking agents), were combined with T-cells, in vitro or in vivo. When CTLA-4 signaling is thus blocked, the T-cell response to antigen is released from inhibitory state. As demonstrated in FIG. 2a, B7 ligation of CTLA-4 triggers apoptosis or anergy in T-cell populations. Inhibition of CTLA-4 signaling also prevents apoptosis or anergy in the activated T-cell population as demonstrated in FIG. 2b. Therefore, an anti-CTLA-4 antibody in the presence of tumor specific antigens could provide a superior anti-cancer drug. Unfortunately, the simple delivery of an anti-CTLA-4 mAb like ipilimumab is fraught with problems.
The safety data from 14 completed phase I-III clinical trials of anti-CTLA-4 antibody in 1498 patients with advanced melanoma indicated that immune related adverse events (irAEs) occurred in 64.2% of the patients. The previously proposed mechanism of action of anti-CTLA-4 antibody (i.e., tolerance breakdown) is consistent with the large numbers of irAEs and cannot be reconciled with the basic assumption that in an otherwise healthy individual suffering from cancer, most CTLA-4 expressing T-cells are either effector cells engaged in an anti-tumor response or regulatory T-cells actively opposing that response (Curran et al., Immunobiology, (2012)). This assumption comes from the conventional "two-signal" T cell activation model, which claim that until a foreign antigen (e.g. virus, tumor cell) is present in the body the immune system is at rest, as it is described in (Szabados et al., Journal of Biological Systems, 19, 299-317 (2011)). This model cannot explain the high rate of irAEs in the clinical trials.
There remains a need for novel methods to target activated T-cells to specific cancer cells efficiently and without serious side effects, whose commercialization is feasible. The availability of an off-the-shelf therapy composed of non-cross-resistant killer T cells has the potential to improve the outcome of patients not only with B cell malignancies as described in (Porter et al., N. Engl. J. Med., (2011)) but many others applications which carry a TAA. The present invention provides such a method related to tumor specific and T-cell specific antibodies, as well as their delivery and high affinity binding to each other in vivo. These and other advantages of the invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.
Our invention provides a new, commercially feasible antibody-based method for T cell targeting relying on an alternative explanation for the high rate of irAEs in the anti-CTLA-4 antibody clinical trials.
Such alternative explanation is provided by the "one-signal" T cell model, which assumes that in order to discriminate self and non-self, T lymphocytes need to recognize the much smaller set of self-antigens, rather than the practically unlimited non-self antigen universe. Positively selected T cells form a homeostatic coupled system via internal dialogue with tissue cells through continuous, low affinity complementary TCR-MHC interactions such that a dynamic steady state is achieved. Therefore, a significant (though constantly changing) fraction of T-cells is never at rest, which explains the high rate of irAEs in the above described ipilimumab clinical trials. The existence of such self-reacting activated T cells was predicted by the "one-signal" model several years ago. However, their presence was proved only by the dose-dependent escalation of irAES during the anti-CTLA-4 antibody clinical trials.
The reason for this that the CTLA-4 receptor is a common molecular target that is expressed on both the targeted as well as on the non-targeted T-cells. Since the blockade occurs dose-dependently on all activated CTLA-4 positive T-cells, clearly, the receptor blockade cannot be restricted to the targeted tumor (e.g. melanoma)-specific T-cell population. With an increasing dose of antibody, the kinetics of the interaction is pushed in favor of widespread uncontrolled T-cell expansion causing serious side effects (Farzaneh et al., Cancer Immunol Immunother., 56, 129-134 (2007)). Mechanistically, the immune-related adverse events associated with CTLA-4 blockade represent a transient breakthroughs of otherwise contained pre-existing self-reactive T-cells.


A method and apparatus for cardioversion and defibrillation. The apparatus is provided with two pairs of cardioversion or defibrillation electrodes, and delivers pulses sequentially between said first and second pairs of electrodes, such that the first pulse overlaps the second pulse for a time interval of at least about one millisecond. During the overlap time of the first and second pulses, a defibrillation pulse vector intermediate that defined by the two electrode pairs individually is provided.

This invention relates generally to the field of electrical stimulators, and more particularly to cardioverters and defibrillators.
The earliest cardioverters and defibrillators generated either a single burst of alternating current or a single pulse for application to the heart to cause cardioversion or defibrillation. However, the use of multiple pulses to accomplish cardioversion or defibrillation has also been extensively researched. For example, U.S. Pat. No. 3,605,754 issued to Jaros, et al., on Sep. 20, 1971 discloses an early double pulse heart defibrillator employing two capacitors which are successively discharged between a single pair of electrodes. Later, the use of multiple electrode systems, in which defibrillation pulses were delivered successively between different electrode pairs chosen from among the electrodes available was suggested. For example, U.S. Pat. No. 4,727,877 issued to Kallok on Mar. 1, 1988 and U.S. Pat. No. 4,708,145 issued to Tacker, Jr. et al., on Nov. 24, 1987, both disclose a variety of implantable, multiple electrode systems adapted for use in conjunction with a sequential pulse defibrillator, in which pulses are applied sequentially to different pairs of electrodes.
French Patent Application No. 74/01383, Publication No. 2,257,312 by Zacouto discloses internal and external sequential pulse defibrillators employing multiple electrodes arranged in and around the heart. In the Zacouto application, A.C. defibrillation pulses are sequentially delivered such that each successively activated electrode pair defines a pulse vector, and such that the pulse vectors scan in a rotational fashion through the heart tissue. Pulses are delivered immediately following one another, or may overlap one another for some unspecified period. More recently, delivery of pulses simultaneously between multiple electrode pairs has been extensively pursued. For example, U.S. Pat. No. 4,953,551, issued to Mehra et al., on Sep. 4, 1990, discloses simultaneous delivery of pulses between the superior vena cava and the right ventricle and between the right ventricle and a subcutaneous electrode.
The ability to deliver sequential and simultaneous pulses to different pairs of electrodes is incorporated in the Medtronic implantable pacemaker/cardioverter/defibrillators presently in clinical evaluation in the United States. The pulse generation circuitry in these devices corresponds to that disclosed in allowed U.S. patent application Ser. No. 07/612,758 for an Apparatus for Delivering Single and Multiple Cardioversion and Defibrillation Pulses, filed Nov. 14, 1990 by Keimel, now U.S. Pat. No. 5,163,427 incorporated herein by reference in its entirety. In these devices, two capacitor banks are provided which are simultaneously charged and then successfully or simultaneously discharged between different pairs of electrodes.
It has also been proposed to apply biphasic pulses to individual electrode pairs, in which a positive pulse is followed by a negative pulse, typically having an initial amplitude equal to the trailing edge amplitude of the first pulse, but at a reversed polarity. Apparatus for delivering such biphasic pulses are disclosed in U.S. Pat. No. 4,850,357 issued to Bach, Jr. on Jul. 25, 1989, U.S. Pat. No. 4,953,551 issued to Mehra et al., on Sep. 4, 1990, and in U.S. Pat. No. 4,800,883 issued Jan. 31, 1989 to Winstrom, all of Which are incorporated herein by reference in their entireties. In all three references, it is proposed to deliver the biphasic pulse by the use of a single capacitor or a capacitor bank in which capacitors are charged and discharged together to deliver the biphasic pulse.
The electrode configurations and pulse regimens described in the above-cited patents have all been tested clinically, and all, in at least some patients, provide a benefit as compared to a monophasic pulse regimen delivered between a single pair of electrodes. Some researchers have found that the use of a biphasic pulse regimen provides a reduction in the energy required to defibrillate, when the biphasic pulse is used in either a two electrode system or a three electrode system as proposed in Mehra, with two electrodes tied together during delivery of the biphasic pulse. Some researchers have also found that sequential delivery of monophasic pulses between two different 5 electrode pairs, as described in the above-cited Kallok and Tacker Jr., references provides a reduction in energy thresholds as compared to a single delivered monophasic pulse. Nonetheless, there is still a substantial desire for further reductions in overall energy thresholds associated with defibrillation, in the context of implantable defibrillators. Reduction of energy threshold allows for the use of smaller batteries or provides for increased longevity in these devices, and is an area of on-going research activities, both within the medical community and by manufacturers of implantable cardioverters and defibrillators.

Overlapping pulse cardioversion or defibrillation


Provided herein is an in vitro granuloma model and methods of its use. Methods of detecting and/or diagnosing latent tuberculosis in a subject are also provided, as are latency-specific antigens (and antibodies thereto), such as α-crystallin, and methods of identifying and using such molecules. Also provided are immunostimulatory compositions, for instance for use in eliciting an immune response in a subject, such as an immune response to a latent tuberculosis infection. Kits for carrying out the provided methods are also described.

Approximately every ten seconds, a person dies of tuberculosis somewhere in the world. Tuberculosis is the world's number one killer among infectious diseases and the leading cause of death among women of reproductive age. Although developing countries bear the greatest burden of disease, the United States is greatly affected by tuberculosis, reporting 16,377 cases in 2000.
The infectious agent causing almost all cases of tuberculosis is Mycobacterium tuberculosis (M. tuberculosis). M. tuberculosis is easily spread between individuals through the air. A single cough by an infected individual can generate as many as 3000 infected droplet nuclei, while less than 10 bacilli may initiate a pulmonary infection in a susceptible individual. Because simply inhaling an airborne pathogen may infect individuals, tuberculosis outbreaks are difficult to contain and require isolating the infected individuals in negative air pressure rooms.
Although it was believed that tuberculosis would eventually be eliminated after the development of antibiotics in the 1950s, in 1999, tuberculosis was labeled as a global health emergency by the World Health Organization. One of the major reasons for the perseverance of tuberculosis is the evolution of multi-drug resistant strains. Multi-drug resistant strains have evolved in part due to infected patients' poor compliance with drug therapy, which lasts for a period of at least six months. One multi-drug resistant strain, strain W, has evolved resistance to all first-line drugs (isoniazid, rifampin, ethambutol, and pyrazidine), as well as one second-line drug (kanamycin). It is therefore evident that tuberculosis continues to be a serious health threat to individuals worldwide.
Initial infection with M. tuberculosis only rarely leads to immediate disease because the infection is typically controlled by the host's immune system. Among people infected with M. tuberculosis, approximately 5% manifest the disease within a few years after infection. Upon initial infection, the mycobacteria enter unactivated macrophages and multiply therein. Following a rapid growth phase, infected macrophages and their bacilliary cargo are surrounded and walled off by newly recruited activated macrophages. This walling off of the infected macrophages results in the characteristic granuloma. The granuloma is a compact, organized collection of activated macrophages, including epithelioid and multinucleated giant cells; surrounded by T lymphocytes, and later by fibroblasts and collagen, which aggregate around the macrophage core.
Mycobacterial dormancy results in a disease stage termed latent tuberculosis. An individual with latent tuberculosis may later develop a case of reactivated tuberculosis, and in fact, the majority of the tuberculosis cases reported in the United States are the result of reactivation of a mycobacterial infection and not an initial infection. (Am. Rev. Respir. Dis. 146:1623–1633, 1992). Reactivation of the M. tuberculosis bacilli usually occurs in the apex of the lung where large numbers of tubercle bacilli cause necrosis of the small bronchi of the lung. The characteristic bloodstained sputum of tuberculosis results from the erosion of small blood vessels during this necrotic process.
Approximately one-third of the population worldwide has been estimated to be latently infected with M. tuberculosis. (Sudre et al., Bull. W.H.O. 70:149–159, 1992). Currently, the tuberculin skin test is the only available diagnostic for those infected with M. tuberculosis. Unfortunately, no currently available test can specifically identify latently infected individuals. The tuberculin test is only capable of identifying all individuals either exposed to the pathogen or vaccinated against the pathogen. Due to the high number of latently infected individuals and the risk of reactivation of tuberculosis in those individuals, diagnostics and therapeutics targeted to latent tuberculosis need to be developed. In addition, the development of an in vitro granuloma model for the study of mycobacteria and for the development of tuberculosis drug and vaccine candidates would be desirable.

Latent human tuberculosis model, diagnostic antigens, and methods of use

The United States of America as represented by the Department of Health and Human Services


A power module with low thermal resistance buffers the stress put on a substrate during a package molding operation to virtually always prevent a fault in the substrate of the module. The power module includes a substrate, a conductive adhesive layer formed on the substrate, a device layer comprising a support tab, a power device, and a passive device which are formed on the conductive adhesive layer, and a sealing material hermetically sealing the device layer. The support tab is buffers the stress applied by a support pin to the substrate, thereby virtually always preventing a ceramic layer included in the substrate from cracking or breaking. As a result, a reduction in the isolation breakdown voltage of the substrate is virtually always prevented and the failure of the entire power module is do to a reduction in the breakdown voltage of the substrate is virtually always prevented.

1. Field of the Invention
The present invention relates to a power module, and more particularly, to a power module for improving a substrate characteristic and a low thermal resistance characteristic.
2. Description of the Related Art
When isolated power modules are fabricated, one or two semiconductor chips are mounted on a lead frame die pad and packaged using a molding resin such as an epoxy molding compound. The epoxy molding compound is used as an isolation material and simultaneously used as a heat transfer path.
To achieve low cost, compactness, lightness, low noise, and high reliability of power conversion systems with high speed, large capacity, and high degree of integration of electronic devices, which are used in automobiles, industrial machinery, home appliance, etc., heat generated in a semiconductor chip should be efficiently discharged.
Accordingly, a direct bonding copper (DBC) substrate or an insulated metal substrate (IMS) is widely used for power modules. The DBC substrate is fabricated by pressing and bonding a copper layer to bottom and top surfaces of a ceramic insulating substrate. The top surface may be partially formed in a designed pattern. The IMS is fabricated by forming a polymer insulating layer on an aluminum substrate and forming a copper layer in a designed pattern on the polymer insulating layer.
FIG. 1A is a cross-sectional view of a power module using a conventional DBC substrate for low thermal resistance. Referring to FIG. 1A, the power module includes a conductive layer adhesive 20 disposed on a DBC substrate 10, a device layer 30 fixed by the conductive layer adhesive 20, and a sealing material 40 hermetically sealing each of devices included in the device layer 30.
As described above, the DBC substrate 10 is fabricated by bonding an upper copper layer 16 and a lower copper layer 12 to top and bottom surfaces, respectively, of a ceramic layer 14. The device layer 30 includes a passive circuit 34 and a power semiconductor device 32. The device layer 30 may also include a pad for connection to a lead line 50.
The sealing material 40 may be usually made using a molding resin, for example, epoxy, in a transfer molding process. A support pin hole 45 is formed in the sealing material 40 by a support pin pressing against the DBC substrate 10 during the transfer molding operation. The support pin is removed after the molding operation. During the molding process the flatness of the DBC substrate 10 is maintained by the support pin pressing against the DBC substrate, and the generation of a mold residue or mold flash is prevented.
However, when the support pin presses the DBC substrate 10, a stress is applied to the DBC substrate 10, which sometimes causes a fault like break of the ceramic layer 14 in the DBC substrate 10.
FIG. 1B is an enlarged perspective view of part A illustrated in FIG. 1A. Referring to FIG. 1B, a support pin 60 is pressing the DBC substrate 10. Thus, a stress induced by a compressive force is applied to the DBC substrate 10. As a result, the ceramic layer 14, which is brittle and has little ductability, sometimes partially cracks or breaks as shown in part B illustrated in FIG. 1B, thereby reducing isolation breakdown voltage. Consequently, the entire power module fails.

Power module for low thermal resistance and method of fabricating the same


A clock including a screen having graduations therealong representing time periods, and light bands representing hours, minutes and seconds hands traveling along the screen to indicate current time. When at least two of the three hands overlap one another, light flashes are displayed.

Means for displaying time, such as clocks, watches and the like, are well known. From the ancient sundial to modern digital clocks, many different configurations and ways of displaying time have been contemplated throughout history.
There are two general forms of clocks. One is the more traditional analog clock in which the hour, minute, and second hands rotate about a center. An example of this form of clock is the clock on Big Ben in London, England. The other is the more modern digital clock which numerically displays the hours, minutes, and seconds. Typically, this form of clock displays a six-digit representation of time, which is generally displayed by six seven-segment displays.
Aside from the aesthetic design of the clock face or the housing, conventional clocks only display time. Furthermore, conventional clocks generally do not provide any visually stimulating and exciting displays to attract people to view the clock at certain times.

Clock having a linear array of graduations and light bands indicating hours, minutes, and seconds


The present invention relates to a multi-specific binding conjugate, a related composition and use. The binding conjugate comprises binding moieties for two or more different receptors, co-receptors, antigens or cellular markers which moieties are coupled by a nanomaterial. The multi-specific binding conjugate can be used to modulate an immune response, treat or prevent a disease or condition (e.g., a cancer, autoimmune disease, pathogen infection or inflammatory disease).

Some antibody conjugates, such as multi-specific antibodies (such as bispecific antibodies), can bind to two or more different antigens. A number of recombinant strategies have been developed to synthesize a bispecific antibody, including a single-chain variable fragment (scFv)-derived form such as a diabody, a tandem diabody, BiTes (a bispecific T cell adaptor) and DART (double affinity re-targeting) as well as a form based on immunoglobulin G (IgG), such as Triomab, DVD-Ig (double variable domain antibody) and a two-in-one antibody. However, a bispecific antibody may have poor pharmacokinetic and physical properties (such as immunogenicity) as well as difficulty in manufacture. Therefore, improvement or alternative technique to such prior art is required.

Multi-specific binding conjugate, related pharmaceutical compositions and use

Benhealth Biopharmaceutic (Shenzhen) Co., Ltd.


A laser device, for example, a diode, is provided which has an oscillation wavelength shorter than 600 nm by using III-V semiconductor materials. This is achieved by using nitrogen doping with GaInP material on a GaP substrate to increase the critical layer thickness of the strained layer. As one example, the following layers can be epitaxially-grown in order on an n-type GaP substrate 1 by a molecular beam epitaxy (MBE) method: a Si-doped n-type Al.sub.y Ga.sub.l-y P optical waveguide layer; a multiple quantum well layer made by repeatedly forming four nitrogen-doped Ga.sub.x1 In.sub.1-x1 P quantum barrier layers and three nitrogen-doped Ga.sub.x2 In.sub.1-x2 P quantum well layers; a Zn-doped p-type Al.sub.y Ga.sub.1-y P optical waveguide layer; a Zn-doped p-type Ga.sub.x3 In.sub.1-x3 P thin layer; and a Zn-doped p-type Al.sub.y Ga.sub.1-y P optical waveguide layer. Next, the thin Ga.sub.x3 In.sub.1-x3 P layer is processed to form a ridge stripe. Then, an n-type Gap current constriction layer is selectively grown and a p-electrode and an n-electrode are formed. Using such a structure, it is possible to obtain a yellow laser element having a threshold current of 100 to 150 mA and an oscillation wavelength of 565 to 580 nm controlled in the transverse mode under continuous-wave (CW) room-temperature operation. Other embodiments use either a single quantum well layer or superlattice layers to obtain either yellow-green light or orange light of very short wavelengths.

The present invention relates to a short-wavelength visible semiconductor laser device suitable for optical information processing or for a light source for optical measurement processing.
In a first known example disclosed in an article by Ishikawa et al. in Electronics Letters, Vol. 26 (1990), page 211, an Al GaInP LD (Laser Diode) is described, in which an active layer of a high Al (aluminum) content is used to increase the band gap energy. This previous device realizes continuous-wave (CW) room temperature oscillation at a 630 nm band, which has been the shortest so far, prior to the present invention.
For III-V semiconductor materials, however, a specific semiconductor material and laser structure to obtain an oscillation wavelength of 600 nm or less at room temperature is not described in the Ishikawa article, or in the prior art in general. Also for a laser device manufactured by II-VI semiconductor materials, a satisfactory material for realizing an oscillation wavelength between 550 and 590 nm has not yet been discovered, and such a laser structure has not been successfully studied.
For the above prior art, only AlGaInP for lattice-matching with a GaAs substrate is considered among III-V semiconductor materials, and a shorter wavelength of 630 nm or less has not previously been obtained as an oscillation wavelength under continuous wave (CW) room-temperature conditions.

Very short wavelength semiconductor laser


A system and method for restricting access to a wireless network is disclosed herein. One or more access points are generally associated with the wireless network (e.g., an IEEE 802.11 wireless network), and a visitor gateway for automatically preventing visiting user from directly entering the wireless network. A command and control center communicates with the access points and the visitor gateway and controls data transfer and routing thereof. The visitor gateway can communicate with a remote computer network (e.g., the Internet) and restricts access to the wireless network by a visiting user through or from the remote computer network. The command and control center also can automatically route the visiting user to the visitor gateway when the visiting user attempts to access an access point associated with the wireless network.

Wireless local area networks (WLAN) can be used in a variety of commercial, industrial and consumer applications, thereby permitting mobile and portable user computers and devices to efficiently transmit and receive data between a user computer or device and a remote system without requiring a wired connection therebetween. Many mobile and portable users, particularly in businesses, factories, universities and other professions can benefit tremendously both in terms of efficiency and productivity with the enhanced capabilities of a WLAN.
A number of systems for implementing WLANs have been proposed and implemented. One class of systems is those conforming to, and/or interoperable with, one or more IEEE 802.11 standard. The IEEE 802.11 is a popular and well-known standard and comprises several extensions to date, with additional extensions likely. The extensions include 802.11a, 802.11b, etc. and it should be understood herein that general references to the 802.11 standard encompass the currently adopted extensions and extensions that follow.
Wireless signals conforming to the IEEE 802.11 standard propagate in a 2.4–2.5 GHz ISM (industrial, scientific and medical) band, a 5 GHz band, infrared bands and others. The ISM band in particular is currently available worldwide and generally permits unlicensed operation for spread spectrum systems. For the US and Europe, the 2,400–2,483.5 MHz band has been allocated, while for some other countries, such as Japan, another part of the 2.4–2.5 GHz ISM band has been assigned.
Networks, protocols and standards are typically designed and specified according to a now standard seven-layer ISO/OSI network model. Within that model, the 802.11 standard generally focuses on the MAC (medium access control) layer and the PHY (physical) layer.
802.11-compliant communication occurs between stations. Some stations serve as access points between a wireless medium and a distribution system other than the wireless medium, while other stations only use the wireless medium to communicate 802.11 data. An example of a distribution system is a wired local area network (LAN), such as an Ethernet-protocol LAN, the Internet, or other network. The distribution system might even be another wireless system (which might be useful to support a number of nodes that can access the access point wirelessly, but not the wireless medium that is used as that access point's distribution system). The same wireless network might also serve as the distribution system (DS) using "wireless DS" transport.
While an access point is a station according to the 802.11 standard if it interacts with the wireless medium, the term "station" is often informally used to refer to a network node that is not connected to a distribution system and the term "access point" is used to refer to a station/node that is connected to a distribution system, thus allowing a distinction between nodes that can access a distribution system outside the wireless medium and those that cannot. That convention is used hereinafter, unless otherwise indicated.
Wireless networks with multiple stations but no access points are referred to as "ad-hoc" networks. Without more, an ad-hoc network allows for communication among stations accessible via a wireless medium, but not for communications beyond that ad-hoc network.
In an 802.11 wireless network with at least one access point, a station located within a group or cell sends packets of data to the access point, which in turn forwards messages/packets/data to a destination such as a station within the same cell or, via the access point's distribution system, to a destination outside the wireless medium.
The 802.11 standard generally supports several data signalling schemes: DSSS (direct sequence spread spectrum) with differential encoded BPSK and QPSK; FHSS (frequency hopping spread spectrum) with GFSK (Gaussian FSK); OFDM (orthogonal frequency division multiplexing, infrared with PPM (pulse position modulation) are several examples. DSSS, FHSS and infrared all provide bit rates of 1 Mbs (megabits per second) and 2 Mbs. The 802.11b extension provides for a high rate CCK (Complementary Code Keying) physical layer protocol, providing bit rates of 5.5 and 11 Mbs as well as the basic DSSS bit rates of 1 and 2 Mbs within the 2.4–2.5 GHz ISM band. The 802.11a extension provides for a high bit rate OFDM (Orthogonal Frequency Division Multiplexing) physical layer protocol providing bit rates in the range of 6 to 54 Mbs in the 5 GHz band. The 802.11g extension provides for 802.11a-like signalling, but in the 2.4–2.5 GHz band.
The 802.11 basic medium access control (MAC) behavior allows interoperability between compatible physical layer protocols through the use of the CSMA/CA (carrier sense multiple access with a collision avoidance) protocol and a random back-off time following a busy medium condition. In addition, directed traffic can use an immediate positive acknowledgement (ACK frame) protocol, wherein a retransmission is scheduled by the sender if no positive acknowledgement is received. The 802.11 CSMA/CA protocol is designed to reduce the collision probability between multiple stations accessing the medium at the point in time where collisions are most likely occur. The highest probability of a collision occurs just after the medium becomes free, following a busy medium. This is because multiple stations would have been waiting for the medium to become available again. Therefore, a random back-off arrangement is used to resolve medium contention conflicts. In addition, the 802.11 MAC defines special functional behavior for fragmentation of packets, medium reservation via RTS/CTS (request-to-send/clear-to-send) polling interaction, and point coordination (for time-bounded services).
The IEEE 802.11 MAC also defines beacon frames, sent at a regular interval by an AP to allow STAs to monitor the presence of the AP. IEEE 802.11 also defines a set of management frames including probe request frames that are sent by a station and are followed by probe response frames sent by the AP. Probe request frames allow a station to actively scan whether there is an AP operating on a certain channel frequency, and for the AP to show to the station what parameter settings the AP is using.
A client uses the wireless network by finding an AP, authenticating to that AP and associating with that AP. Normally, a client associates with one AP at a time, but where connection to one AP is lost, the client can associate with another AP (or reassociate with the same one after a connection is lost or closed). The AP's of a network can communicate over a distribution system (DS). One reason for communicating between AP's is where an AP has frames buffered for a client, but loses the client. That AP might discover that the client is now associated with a different AP and will forward the buffered frames to that new AP via the DS. The access points might also connect to a network outside of the 802.11 wireless network. In some cases, the DS is not distinct from that outside network. That outside network could be another wireless network, but a common configuration has the outside network being a local area network (LAN).
When a wireless LAN station is powered on, it first looks for an access point. After it finds an access point, the wireless LAN station registers itself with the access point (authentication, association). The station can then synchronize with the access point and, thereafter, transmit and receive data frames to and from the access point. In a common example, the client station is a portable or mobile computer with a wireless networking card installed therein. 802.11 management frames are used to set up these connections.
Unlike wired networks, where a network is secured at boundaries by which wires connect to the network, wireless networks do not have well-defined boundaries. A company on one floor of a building might have a wireless network that can be reached by a computer on a different floor using a computer unrelated to the company that set up the wireless network. Consequently, it is easier to join into a wireless network, for authorized users as well as unauthorized users.
In some cases, a wireless network could be coupled to a wired network without oversight by the operators of the wired network. For example, many access points have a standard interface and can be easily plugged into a standard wired network connector, thus opening up a previously secured wired network to wireless traffic. Where an uninformed end-user replaces a wired network connection with an access point and does not secure the access point, the wired network would then be open to users within radio range of the access point, even if they were not within the physical space controlled by the organization for which the wired network is being maintained.
Some network operators have attempted to address unexpected access points by physically surveying their network. In one approach, a network administrator would walk with a network sniffer through all of the space controlled by the organization, but for large spaces, this is often impractical.
In large wireless networks, considerable effort is needed to maintain numerous access points and when a large number of access points are needed, for bandwidth reasons, coverage reasons, etc., the cost can be considerable as the full functionality of an access point needs to be repeated in the space where the network is set up.
Another difficulty of wireless networks is that of not necessarily authorized users in the authorized space. For example, if a visitor with a wireless computer or wireless device is in a company building that is covered by the company's wireless network, that visitor might connect to the company network and have access equivalent to that of an employee, and that is generally undesirable.
Yet another difficulty of wireless networks is network overlap. Where a space is to have multiple wired networks, parallel sets of network cabling can be laid down. This can be effected with wireless networks by overlapping access points and programming the access points to be selective with associations, but this necessarily involves more hardware than is necessary to support the space.
In light of the above, the inventors have invented improvements to wireless networks.


A jacquard pattern control mechanism for a circular knitting machine is provided in which a plurality of rocker bar supporting members are each slidable in one of the grooves along which one of the knitting elements move, a plurality of elongate rocker bars are pivotally mounted on one of unsaid plurality of rocker bar supporting members for movement about a medial pivot, the opposite end portions of the rocker bars being selectively movable between operative and inoperative positions and having magnetically attractable sections thereon, magnet attracting devices are operatively associated with the opposite end portions of the elongate rocker bars for selectively attracting one of the magnetically attractable sections at opposite ends of the rocker bars to pivot the rocker bars and selectively move one of the opposite end portions thereof to the other operative position and the other opposite end portion thereof to the inoperative position, the magnetic attracting devices comprising a permanent magnet and a pair of electromagnets disposed on opposite sides of the permanent magnet and connected in series, the permanent magnet having an extension extending outwardly towards the rocker bars and having a pair of wing portions extending outwardly from the center portion of the extension, generally parallel to the rocker bar supporting members and having outer sections disposed in attractable relation to the magnetically attractable sections at opposite ends of the rocker bars.

Jacquard knitting on a circular knitting machine requires needle selection of specific knitting needles being switched between active and inactive positions. Such needle selection is typically provided by jacquard pattern control mechanisms which include pattern selection devices. Such jacquard control mechanisms, including their pattern selection devices, are discussed in co-pending United States patent application, Ser. No. 771,519, now U.S. Pa. No. 5,689,977, commonly owned with this application and incorporated herein by reference.
As is stated in U.S. Pat. No. 5,689,977, prior pattern selection devices combining a permanent magnet and an electromagnet required a plurality of control electromagnets in order to function properly. In addition, such devices were required to limit the size of the electromagnets such that the magnetic attraction generated thereby would not be stronger than that of the permanent magnet. Therefore, both the permanent magnet and the electromagnets had to be quite large which caused spatial problems in the knitting machines.
Applicant solved many of these problems and deficiencies in U.S. Pat. No. 5,689,977 by pattern selection devices embodying both a permanent magnet and an electromagnet working in concert to provide the necessary magnetic attraction while using small magnets. The present invention is an improvement on the invention of U.S. Pat. No. 5,689,977.

Jacquard pattern control mechanism for a circular knitting machine


Subject matter includes exemplary systems and related methods for fully scalable encryption of scalable multimedia. A scalable bitstream encrypted using the subject matter maintains full functionality of scalable features in the encrypted form. The exemplary scalable encryption allows transcoding, rate shaping, and other operations directly on the ciphertext without degradation of scalable compression efficiency and error resiliency.

Scalable video coding imparts flexibility and adaptability to multimedia content so that it can be suited to many different applications and environments. Scalable multimedia formats include, among others, several MPEG stream formats and "scalable media adaptation and robust transport" (SMART and SMART++). (See, e.g., <http://research.microsoft.com/im/>. Microsoft Corporation, Redmond, Washington; Feng Wu, Shipeng Li, Ya-Qin Zhang, "A framework for efficient progressive fine granular scalable video coding", IEEE Trans. on Circuits and Systems for Video Technology, vol. 11, no. 3, pp. 332-344, 2001; Xiaoyan Sun, Feng Wu, Shipeng Li, Wen Gao, Ya-Qin Zhang, "Macroblock-based temporal-SNR progressive fine granularity scalable video coding", IEEE International Conference on Image Processing (ICIP), pp. 1025-1028, Thessaloniki, Greece, October, 2001; and Yuwen He, Feng Wu, Shipeng Li, Yuzhuo Zhong, Shiqiang Yang, "H.26L-based fine granularity scalable video coding", ISCAS 2002, vol. 4, pp. 548-551, Phoenix, USA, May 2002).
MPEG-4 has adopted profiles to provide scalability to different devices. One such MPEG-4 profile is called the "Simple" profile. "Simple" provides a video base layer upon which other profiles, such as "Simple Scalable" can add an enhancement layer to provide the scalability. Another profile called "Advanced Simple" performs rectangular video object coding by adding some coding tools to the "Simple" profile. This "Advanced Simple" profile, while having the latest MPEG-4 coding efficiency tools, provides no scalability. Yet another MPEG-4 profile that provides a scalable video coding scheme by adding a fine-grained enhancement layer to the "Advanced Simple" base layer is called "Fine Granularity Scalability (FGS)." FGS has become a standard.
The base layer used in some of these scalable MPEG-4 profiles is encoded in a non-scalable manner at the lowest bound of bitrates. The FGS profile includes an enhancement layer predicted from the low bitrate base layer that strives to achieve the optimal video quality for each bitrate in a spectrum of bitrates possible with the same enhancement layer. The enhancement layer is encoded in a scalable manner: the discrete cosine transformation (DCT) coefficients of a frame's residue II are compressed bit-plane wise from the most significant bit to the least significant bit. A video is compressed by MPEG-4 FGS only once. When it is transmitted over a network, a server can discard the enhancement layer data associated with the least significant bit(s) should the transmitting network lack required bandwidth. Other rate shaping operations can also carried out on the compressed enhancement layer data directly without resorting to either compression or decompression. The above-described FGS profile will be referred to herein as MPEG-4 FGS, or just "FGS."
Multimedia encryption techniques for multimedia streams conforming to the various scalable MPEG-4 profiles ideally have the same features that are desirable in non-scalable codecs, namely high security, low complexity, low compression overhead, error resilience, rate shaping adaptability, and random play ability. Some of these will now be discussed in greater detail.
Security is an essential requirement for multimedia encryption. Compared with other types of encryption for more critical applications, such as military and banking processes, multimedia encryption has its own particular issues, including the relatively large amount of (video) data to be encrypted and the characteristically low value of the data, compared with military and banking data.
Low complexity is a feature because any encryption or decryption process adds processing overhead. Since a multimedia stream has a relatively vast amount of data, it is desirable or mandatory in many applications that the complexity of an encryption system be very low, especially during decryption, since many applications require real time decryption of the vast amount of multimedia data, and usually on a user's limited equipment.
Compression overhead is also a feature since encryption inevitably affects compression efficiency by reducing the compression algorithm's coding efficiency or by adding bytes to the already compressed file. Thus, the compression overhead is ideally minimized for multimedia encryption algorithms.
Error resilience is important for encryption because faults occur during multimedia storage and transmission. Wireless networks are notorious for transmission errors. Data packets may be lost in transmission due to congestion, buffer overflow, and other network imperfections. Encryption schemes should ideally be resilient to bit error and package losses. They should also allow quick recovery from bit errors and fast resynchronization from package losses to prevent extensive error propagation. Many multimedia encryption algorithms, typically designed under perfect transmission environments, propagate great perceptual degradation when bit errors or package losses occur during transmission.
Rate shaping describes the ability to vary the transmission bitrate (number of bits in one second of a stream) to suit various conditions. During multimedia stream delivery from the content owner to the user, many middle stages typically process the data. Transcoding, for example, may change the bitrate to adapt to transmission bandwidth fluctuation or even application requirements. If the data is encrypted, these middle stages typically must call for encryption and decryption keys and then execute cycles of decryption and encryption in order to process the data. This increases processing overhead and reduces security since encryption secrets have to be shared with these middle stages.
Associated with the security feature discussed above, it is often desirable to encrypt a multimedia stream for digital rights management (DRM). Such encryption can help a content owner enforce copyright and other property rights, such as licensing of multimedia content.
Many algorithms have been proposed to encrypt non-scalable video. The most straightforward method is the naive algorithm which applies standard encryption schemes such as DES on the compressed stream in the same way as if it were text data (I. Agi and L. Gong, "An Empirical Study of Secure MPEG Video Transmissions," Proc. Symp. Network & Distributed System Security, 1996, pp. 137-144). A naive algorithm usually has a large processing overhead due to the large amount of video data to be processed. It has minimal error resilience, and does not allow rate shaping on the ciphertext directly.
Another method is the selective algorithm which exploits the video stream structure and encrypts only part of the compressed video data (T. B. Maples and G. A. Spanos, "Performance Study of a Selective Encryption Scheme for the Security of Networked, Real-time Video," Proc. 4th Int. Conf. Computer Communications & Networks, 1995; and J. Meyer and F. Gadegast, "Security Mechanisms for Multimedia Data with the Example MPEG-1 Video," http://www.gadegast.de/frank/doc/secmeng.pdf, 1995). The partial data to be encrypted can be I-frames, I-frames plus all I-blocks in P and B frames, or the DC coefficients and lower AC terms of the I-blocks. Encrypting only I-frames does not provide sufficient security due to exposed I-blocks in the P and B frames as well as interframe correlation (see the Agi and Gong reference, above).
A method to reduce the data to be encrypted is proposed in (L. Qiao and K. Nahrstedt, "Comparison of MPEG Encryption Algorithms," Int. J. Computers & Graphics, Special Issue: "Data Security in Image Communication and Network", vol. 22, no. 3, 1998) which encrypts only the bytes at even indexes for a chunk of an I-frame, and the rest is replaced by the result of XORing the odd-indexed subsequence with the even-indexed subsequence.
Another selective algorithm pseudo-randomly changes the sign bits of all DCT coefficients (C. Shi and B. Bhargava, "A Fast MPEG Video Encryption Algorithm," Proc. of ACM Multimedia'98, 1998, pp. 81-88) or the sign bits of differential values of DC coefficients of I blocks and sign bits of differential values of motion vectors (C. Shi and B. Bhargava, "An Efficient MPEG Video Encryption Algorithm," IEEE Proc. 17th Symp. Reliable Distributed Systems, 1998, pp. 381-386).
A third approach is the scrambling algorithm which scrambles some compression parameters or shuffles codewords to prevent unauthorized users from correct decompression. A simple scheme uses a random permutation instead of the normal zigzag order to map a 2D block to a 1D vector (L. Tang, "Methods for Encrypting and Decrypting MPEG Video Data Efficiently," Proc. ACM Multimedia'96, 1996, pp. 219-230). Motion vectors and selected DCT coefficients can be shuffled before entropy coding (W. Zeng and S. Lei, "Efficient Frequency Domain Video Scrambling for Content Access Control," Proc. ACM Multimedia'99, 1999, pp. 285-294; and "Efficient Frequency Domain Selective Scrambling of Digital Video," a preprint to appear in IEEE Trans. Multimedia).
VLC (variable length coding) codes can also be shuffled in a format-compliant way (J. Wen, M. Severa, W. Zeng, M. H. Luttrell, and W. Jin, "A Format-compliant Configurable Encryption Framework for Access Control of Video," IEEE Trans. Circuits & Systems for Video Technology, vol. 12, no. 6, 2002, pp. 545-557). These schemes change the data's statistical properties, and thus lower compression efficiency. A scheme that performs without incurring the bit overhead has also been proposed. (W. Zeng, J. Wen, and M. Severa, "Fast Self-synchronous Content Scrambling by Spatially Shuffling Codewords of Compressed Bitstreams," IEEE Int. Conf. Image Processing, 2002, vol. 3, pp. 169-172) which spatially shuffles codewords of the compression bitstream.
While some of the schemes mentioned above and others, for example most scrambling algorithms, are equally applicable to MPEG-4 FGS, most encryption schemes developed for non-scalable multimedia, when applied to a scalable multimedia stream, often diminish or destroy the scalability features. To apply a scalable manipulation to such an encrypted scalable stream, intermediate transmission stages often have to decrypt the stream, apply rate shaping, such as transcoding and/or bit reduction, and then re-encrypt the stream. Thus, a technique for encrypting scalable multimedia streams while maintaining the scalability features is needed.
Schemes specifically designed for scalable formats have been reported recently. Wee et al., propose a secure scalable streaming (SSS) scheme that enables transcoding without decryption. (S. J. Wee and J. G. Apostolopoulos, "Secure Scalable Streaming Enabling Transcoding Without Decryption," IEEE Int. Conf. Image Processing, 2001, vol. 1, pp. 437-440.) For MPEG-4 FGS, the approach encrypts video data in both base and enhancement layers except header data. Hints for rate distortion optimal (RD-optimal) cutoff points have to be inserted into the unencrypted header for an intermediate stage to perform RD-optimal bitrate reduction. Encryption granularity depends on the way a video stream is packetized. More precisely, encryption is applied to each packet. This means that when encryption is applied in SSS, the packet size has to be known. No modification on the packet size is allowed after encryption is done in SSS. In real applications, a packet size designed for one type of transmission channel may not be appropriate for another. For example, the video packet size for wireless transmission has to be small since the channel is error-prone. For Internet transmission, a video packet should be large for efficient transmission since the error rate for the Internet is very small. Any intermediate stage that wants to change the packet size to best fit into the transmission channel needs to resort to the decryption/re-encryption cycle in SSS.
Grosbois et al., propose a scalable authentication and access control scheme for the image compression standard of JPEG 2000. (Raphael Grosbois, Pierre Gergelot, and Touradj Ebrahimi, "Authentication and Access Control in the JPEG 2000 compressed domain," Proc. of SPIE 46th Annual Meeting, Applications of Digital Image Processing XXIV, San Diego, 2001.) It is based on modification and insertion of information in the bit steam. A keyed hash value is used to generate a pseudo-random sequence that is used to pseudo-randomly invert the signs of high-frequency band wavelet coefficients. Layered access structure allows adaptation to different applications. One of its major drawbacks is the insertion of extra information to aid decryption, which reduces compression efficiency.

Fully scalable encryption for scalable multimedia


The invention provides a method of manufacturing a photothermographic material excellent in coating stability with less haze in images, wherein the photothermographic material has, on at least one side of a support, an image forming layer containing at least a photosensitive silver halide, a non-photosensitive organic silver salt, a reducing agent, and a binder and at least one non-photosensitive layer above the image forming layer relative to the support, wherein (1) both the image forming layer and the non-photosensitive layer are formed with an aqueous coating solution, and (2) the coating solution for the image forming layer contains a phthalic acid salt or a salt of a derivative thereof, as well as a photothermographic material formed therewith.

1. Field of the Invention
The present invention relates to an aqueous coating system manufacturing method for a photothermographic material, and a photothermographic material prepared therewith. More specifically, the invention relates to an aqueous coating system manufacturing method for a photothermographic material of high image quality excellent in coating stability and with improved haze in images, as well as a photothermographic material prepared therewith.
2. Description of the Related Art
In recent years, decreasing the amount of processing liquid waste in the field of films for medical imaging has been desired from the viewpoints of protecting the environment and economy of space. Technology is therefore required for photosensitive thermal developing image recording materials which can be imagewise exposed effectively by laser image setters or laser imagers and thermally developed to obtain clear black-toned images of high resolution and sharpness, for use in medical diagnostic applications. An image forming system using photosensitive thermal developing image recording materials does not require liquid processing chemicals and can therefore be supplied to customers as a simpler and environmentally friendly system.
While similar requirements also exist in the field of general image forming materials, images for medical imaging in particular require high image quality excellent in sharpness and granularity because fine depiction is required, and further require blue-black image tone from the viewpoint of easy diagnosis. Various kinds of hard copy systems utilizing dyes or pigments, such as ink jet printers and electrophotographic systems, have been marketed as general image forming systems, but they are not satisfactory as output systems for medical images.
Photothermographic materials utilizing organic silver salts are described in many documents. Photothermographic materials generally have an image forming layer including a catalytically active amount of a photocatalyst (for example, silver halide), a reducing agent, a reducible silver salt (for example, an organic silver salt), and if necessary, a toner for controlling the color tone of developed silver images, dispersed in a binder. Photothermographic materials form black silver images by being heated to a high temperature (for example, 80° C. or higher) after imagewise exposure to cause an oxidation-reduction reaction between a silver halide or a reducible silver salt (functioning as an oxidizing agent) and a reducing agent. The oxidation-reduction reaction is accelerated by the catalytic action of a latent image on the silver halide generated by exposure. As a result, a black silver image is formed on the exposed region. The Fuji Medical Dry Imager FM-DPL is an example of a medical image forming system that has been made commercially available.
Methods of manufacturing such photothermographic material include a method of manufacture by a solvent coating, and a method of coating an aqueous coating solution using an aqueous dispersion of fine polymer particles or an aqueous solution of a water soluble polymer as a main binder followed by drying. Since the latter method does not require a process of solvent recovery or the like, a production facility therefor is simple, environmental burden is small, and the method is advantageous for mass production.
However, in the method of manufacturing the photothermographic material by an aqueous coating system, since the coating solution for the image forming layer contains many components required for image formation, there is a significant problem with regard to uniformly coating and drying the same. Particularly, in a case of coating a solution at a high speed and rapidly drying the same to prepare a photothermographic material in order to enhance productivity, there are various problems such as increase of haze due to partial lack of balance among the components in the coated layer and occurrence of unevenness in the coated surface state due to fluctuation of drying wind.
Further, in a case where the binder of the image forming layer is a polymer latex, since the coating solution has no setting property, these problems are significant. "Having setting property" in the present specification means that a coating solution can form a state in which it does not substantially deform physically even when an external pressure such as drying wind is applied when it is coated in a sol state and then the temperature is lowered below a gelation temperature, in a case where the coating solution has "sol-gel transformability", that is, a case where the coating solution attains a sol state and maintains fluidity when the temperature thereof is equal to or higher than a certain temperature (usually, about 30° C.) but gels and loses fluidity at a temperature lower than the certain temperature.
Since the unevenness in the coated surface state results in image unevenness when images are formed and the increase in haze deteriorates the image quality, these are significant problems that particularly affect diagnosis ability for image forming materials for medical use, and improvement has always been demanded.
As means for improvement, the specification of Japanese Patent Application Laid-Open (JP-A) No. 10-186568 discloses use of a polymer having setting property as a binder for a surface protective layer disposed above the image forming layer and coating the same by a simultaneous double-layer coating method together with the image forming layer.
In addition, while the specification of JP-A No. 10-186571 discloses a method of improving the coated surface state by providing a non-photosensitive layer between the image forming layer and the surface protective layer, and the specification of JP-A No. 11-133543 discloses a method of using a hardener for the surface protective layer, none of these methods have been satisfactory.

Method of manufacturing a photothermographic material by aqueous coating and a photothermographic material prepared therewith


A method for a wireless network node to support an extended control signaling is provided. The method comprises configuring a control signaling message over extended control symbols on a layer 1 (L1) downlink control channel, the control signaling message encoded over an increased aggregation of control channel elements (CCEs) in a time domain; placing the controlling signaling message in a designated set of subframes on the L1 downlink control channel; indicating a support for the extended control signaling to one or more UEs; indicating to the one or more UEs a position of the designated set of the subframes in a spare field of the Master Information Block (MIB); and transmitting the control signaling message to the one or more UEs over the L1 downlink control channel.

A support for a MTC-capable UE in a LTE network is gaining attention because integrating the MTC capabilities into a LTE network has an advantage of supporting two widely deployed network devices in a single network. A low-cost solution may involve using only single receiving RF chain because it may significantly lower the costs of LTE MTC devices. It is known that there will likely be about 3 dB coverage loss with single receiver RF chain compared to regular LTE UEs. So a solution to compensate for control signaling coverage loss due to use of a single receiving RF chain is needed.
Some of the proposed solutions to the issue of control signaling coverage loss may require either an increased densification of sites or remedial solutions at the receiver such as small home area networks, meshes, or external antennas with additional antenna feeds. These solutions may be impractical, require additional spectrum, and lead to higher cost. Therefore a coverage improvement solution is desirable that can meet the lost-cost requirement of MTC-capable devices such as smart-metering devices, while utilizing LTE sites and RF hardware, and efficiently sharing the same spectrum/carrier as LTE to reduce costs for network deployment.
A signaling coverage improvement may involve downlink control channel coverage improvement because downlink control signaling is the bottleneck of the LTE in downlink coverage. A downlink control signaling is located at the start of each downlink subframe up to the first three OFDM symbols. Downlink control signaling may be carried by a Physical Downlink Control Channel (PDCCH) which may carry DL scheduling assignment and uplink scheduling grants. Thus, there is a need to extend the PDCCH signaling channel to support MTC-capable UEs.
The following abbreviations are used in this application.    A/N Acknowledge/Non-Acknowledge    BS Base Station    CCE control channel element    CSS Common Search Space    DL Downlink    ePDCCH enhanced Physical Downlink Control Channel    eNB Enhanced Node B. Name for Node B in LTE    FDM Frequency Domain Multiplexing    HARQ Hybrid Adaptive Repeat and Request    LTE Long Term Evolution    LTE-A Long Term Evolution Advanced    M-ePDCCH MTC-capable extended PDCCH    M-PDCCH MTC-capable PDCCH    MIB Master Information Block    MTC Machine Type Communication    NCT New Carrier Type    OS OFDM Symbol    PDCCH Physical Downlink Control Channel    PDSCH Physical Downlink Shared Channel    RF Radio Frequency    RRC Radio Resource Control    SIB1 System Information Blocks    USS User Search Space    TA Timing Advance    UE User Equipment    UL Uplink    UMTS Universal Mobile Telecommunications System    UTRAN UMTS Radio Access Network    WCDMA Wideband Code Division Multiple Access

Method and apparatus for extending control signalling in an LTE network


A chuck mechanism (2) for holding a pipette head (3) is attached to an output end of a reciprocating drive mechanism (1). A chuck control mechanism (5) for controlling the head holding and releasing operations of the chuck mechanism (2) is disposed at one side of each of head support members (41) of a head stowing device (4) for accommodating replaceable pipette heads (3). The chuck control mechanism (5) comprises a control piece (54) engageable with and disengageable from the chuck mechanism (2) for effecting the holding and releasing operations, and a plurality of magnets (81), (82), (8) for reciprocatingly driving the control piece (54) with the reciprocating movement of the chuck mechanism (2) when the pipette head (3) as held by the chuck mechanism (2) is thereby moved toward or away from the head support member (41). The pipetting apparatus is adapted to automatically and rapidly replace the pipette head by another.

For example in an immunoassay, a sample in a container is tested for an immunoreaction first by placing a liquid such as physiological saline into the container and then placing a reagent thereinto. FIG. 24 shows a pipetting apparatus conventionally used for placing such a liquid and reagent (hereinafter referred to collectively as the "reagent") into a container.
The illustrated pipetting apparatus comprises a pipette table 90 for mounting a reaction container 7 thereon, a head drive device 9 mounted on the table 90 and a pipette head 91 attached to the output end of the drive device 9. The pipette head 91 is connected to a plunger mechanism (not shown), and has a pipette tip 92 fitted to its lower end and directed downward for drawing in and discharging a reagent.
The reagent is placed into each of cavities 71 of the reaction container 7 by controlling the drive device 9 by a controller 93 to bring the pipette head 91 close to the container cavity 71 and drawing off the reagent from the pipette tip 92 into the cavity 71.
When the reagent is to be diluted or mixed with another reagent 72 already placed in the cavity 71, the reagent to be added dropwise from the pipette tip 92 is brought into contact with the liquid surface of the reagent 72 within the cavity 71 to free the surface tension, whereby the reagent is drawn off.
If the pipette tip 92 itself comes into contact with the reagent 72 in the cavity 71 at this time, the reagent adhering to the tip 92 becomes mixed with other reagent in the subsequent pipetting step. Accordingly, the reagent within the pipette tip 92 needs to be drawn off with the extremity of the tip 92 positioned slightly above the liquid surface of the reagent 72.
Pipette tips of different capacities are used for applying the reagent in different quantities of 0.5 .mu.l to 200 .mu.l by the pipetting apparatus. Prepared for the apparatus are a pipette head of small inside diameter for mounting pipette tips having a small capacity of 0.5 .mu.l to 10 .mu.l, and a pipette head of large inside diameter for use with pipette tips having a large capacity of 5 .mu.l to 200 .mu.l, and these pipette heads are alternatively used by replacement.
With the conventional pipetting apparatus, however, the pipette head is fixed to the apparatus main body by fastening means as by screwing. The apparatus therefore has the problem that the procedure for replacing the pipette head is not only cumbersome but also difficult because the head is as small as about 20 mm in outside diameter.
When the reagent is to be diluted or mixed with the reagent 72 in each cavity 71 of the reaction container 7 as stated above, the pipette head 91 is lowered to position the pipette tip 92 as close to the liquid surface of the reagent 72 as possible, whereas since the liquid level of the reagent 72 differs from cavity to cavity, the liquid level in each cavity must be measured to adjust the level of the pipette tip 92. At this time, an accuracy of about 0.1 mm is required of the measurement of the reagent liquid level.
Although it is advantageous to use a laser measuring instrument from the viewpoint of accuracy of distance measurements, the instrument is not usable for transparent reagents or reagents which are likely to undergo a photochemical reaction since the reagent is irradiated with a laser beam in this case.
Accordingly, it is practice to measure the distance to the liquid surface of the reagent 72 by an ultrasonic sensor attached to one side of the pipette head 91 and to feedback the measurement to the control of the head drive device 9. The sensor emits ultrasonic waves toward the object of measurement, receives the ultrasonic waves returning upon reflection at the object and measures the time taken for the emitted waves to return to the sensor to determine the distance to the object based on the time measurement.
While the level of the pipette head is controlled according to the distance thus measured by the ultrasonic sensor, the pipette tip 92 is likely to become damaged when an erroneous movement is involved in measuring the distance for one cause or another and if the pipetting operation is continued based on the result of measurement then obtained. For example, in the case where the measurement obtained is greater than the distance to the bottom face of the cavity 71 of the reaction container 7, the controller for the head drive device 9 sets as a target position for lowering the pipette head 91 a position where the extremity of the pipette tip 92 will be located further below the bottom face of the container cavity 71, with the result that when the head is lowered, the extremity of the tip 92 comes into striking contact with the bottom face of the cavity 71, bending the end portion and rendering the tip unable to draw off the reagent. The impact resulting from the striking contact of the pipette tip 92 with the reaction container 7 is also likely to cause damage to the pipette head 91.


A PWM circuit is disclosed in the application, which includes: a PWM counter, a reference value setting register, a frequency multiplier and a comparator, where the frequency multiplier is adapted to increase the frequency of a clock signal input and to output the clock signal with the increased frequency to the PWM counter. An LED drive circuit is further disclosed in the application. The frequency of a PWM input clock signal is increased to N times of the original frequency of the PWM input clock signal by the frequency multiplier, so that the counting cycle of the PWM counter is shortened to 1/N of the original counting cycle of the PWM counter. Therefore, in the dynamic LED display screen, the refresh frequency can be increased to N times of the original refresh frequency while the original resolution is maintained.

PWM is an effective technique to control an analog circuit using digital outputs of a microprocessor, and it is widely used in many fields, such as fields of measurement, communication, power control and conversion.
Referring to FIG. 1, in the prior art, a PWM circuit 10 generally includes: a PWM counter 11 adapted to perform up/down counting for a clock signal; a reference value setting register 12 adapted to set a comparison reference value which determines the duty cycle of a PWM signal; and a comparator 13 adapted to compare the count value of the PWM counter with the comparison reference value set by the reference value setting register and generate an effective PWM signal.
In LED display screen, the PWM technique is adopted in order to improve the display resolution. Usually the PWM is 16 bit. In the conventional LED display screen, a serial bus including SDI (Serial Digital Input), DCLK (Serial Data Input Clock), LE (Latch Enable), GCLK (Graph Clock Input) and SDO (Serial Data Output) is usually adopted, in which the GCLK is an input clock of the PWM and the frequency of the GCLK is less than 30 MHz. There are two types of the LED display screen: dynamic display screen and static display screen. For the static display screen, each LED pixel is driven by a separate constant current source; whereas for the dynamic display, time-sharing driving is adopted, in which LEDs of each column share the same constant current source for driving. The display brightness of the LED is determined by the duty cycle output by the PWM.
In a dynamic scanning system, a display refresh frequency greater than 2 KHz is required. And generally, the PWM has a resolution of 16 bit. Due to effect of the frequency of the GCLK, the number of GCLKs for forming a pulse cycle of a 16 bit PWM is: 216=65536. If the frequency of GCLK is 30 MHz, then the length of one cycle of the 16 bit PWM is: 65536/30M=2.19 ms; and the refresh frequency is 458 Hz. If the dynamic scanning is "4-scan", then the refresh frequency of the LED display screen is 458/4=114.5 Hz. In order to meet practical requirements of application and increase the dynamic refresh frequency, it can only reduce the cycle length of the PWM, i.e., reduce the bit length of PWM. For example, if the bit length of the PWM is 12 bit, the refresh frequency may be 1824 Hz. However, the reduction of the bit length may cause a decrease in resolution, therefore the contradiction between the refresh frequency and the resolution of the dynamic display screen can not be solved in the conventional solution.

Dynamic LED display screen with increased frequency of input clock signals