The present invention relates to methods for diagnosing hematological cancers. In particular, the present invention relates to a method for diagnosing a hematological cancer in a patient comprising i) detecting the presence of CD45RARO NK cells in a sample obtained from the patient and ii) and concluding that the patient suffers from a hematological cancer when the presence of CD45RARO NK cells is detected in the sample and the presence of at least one phenotypic marker indicates the nature of the haematological cancer.

Natural Killer (NK) cells are members of the lymphocyte lineage and belong to the innate immune system. They show natural cytotoxicity and produce cytokines1,2. The majority of human NK cells in peripheral blood are CD3−CD56dim cells while the minority shows a CD3−CD56bright phenotype. The last population shines at cytokine production whereas CD56dim cells show mainly cytotoxic activity3. In contrast CD3−CD56bright cells are majority in lymph nodes and tonsils. In vitro evidence indicates that CD56bright cells are precursors of CD56dim cells, which can also be the case in vivo4. In addition, CD16 expression suggests that NK cell development follows this pathway: CD56brightCD16−→CD56brightCD16dim→CD56dimCD16dim→CD56dimCD16+. Additional markers can identify additional subsets in these populations5,6. In contrast, identification of activated NK cells in vivo has been probed more difficult. CD69 expression increases after NK cell stimulation and is considered a bona fide marker of activation including in humans7, although its long-lasting expression is unknown. In mice, the stable expression of CD69 after long-term stimulus is disputed: after murine CMV infection CD69 expression is transient8 whereas after IL-15 treatment is stable9.
NK cells are activated after encountering their targets, which are mostly cells with altered expression of the major histocompatibility complex-I (MHC-I), which include transformed or virus-infected cells, which down regulate MHC-I expression to evade recognition by cytotoxic T lymphocytes (CTL). The "missing self" hypothesis proposes that NK cells distinguish target cells from other healthy "self" cells based on MHC-I expression. NK cell activation depends on a complex signaling mechanism mediated by both activating and inhibitory receptors. The main NK cell inhibitory receptors recognize MHC-I, called HLA in humans, complexes and include NKG2A, which recognizes HLA-E, and Killer-cell Immunoglobulin-like Receptors (KIRs), which recognize the self classical class I molecules HLA-A, -B and -C. Activating NK cell receptors perceive stress and/or non-self ligands on cells, i.e. the stress-induced ligands UL16-binding protein (ULBP) and MHC class I polypeptide-related sequence (MIC) are recognized by the activating receptor NKG2D2.
NK cells recognize and eliminate blood-borne cancer cells. However, these tumor cells found different mechanism for immune escape10,11 and a significant number of these patients show limited long-term survival. Some options to treat these patients include new chemicals that can be associated to immunotherapy12. The first clinical trial using an anti-KIR that can block KIR-mediated inhibition of NK cells has recently been published7. It shows absence of toxicity and favorably overall and relapse-free survival compared to reports in comparable patient populations of acute myeloid leukemia (AML). An interesting alternative to this therapy is using allogeneic NK cells because clinical-grade production has proven efficient13, and NK cell-mediated therapy after hematopoietic cell transplantation seems safe14-16. However, NK cells are not a homogenous population, there are different subsets keeping different physiological activities. Moreover, different pattern of NK cell activation, e.g. cytokines vs targets cells, originates different transcriptional patterns17. It would be interesting to identify the populations with higher anti-tumor activity and select them for expansion and/or patient infusion.
Protein tyrosine phosphatases (PTPs) regulate cellular processes including differentiation, mitotic cycle, cell growth and oncogenic transformation18. CD45 is a PTP encoded by the PTPRC gene, which is specifically expressed in hematopoietic cells19. CD45 regulates receptor signaling by direct interaction with components of the receptor complexes or by dephosphorylating and activating various Src family kinases (SFK) i.e. Lck20. But it can inhibit cytokine receptor signaling by inhibiting JAK kinases21 or by dephosphorylating the activating residues of Src20. CD45 activity is critical for an efficient immune response, because its deficiency results in a severe combined immunodeficiency (SCID) phenotype in both mice22-24 and humans25,26. This could explain the high expression of this phosphatase and its complex regulation.
CD45 expression increases with cell maturation27. The CD45 family comprises several members derived from a single complex gene27. Naive T lymphocytes are usually positive for the long CD45RA isoform. Activated and memory T cells express CD45RO, the shortest CD45 isoform by activation-induced alternative splicing of CD45 pre-mRNA27-30. It has been proposed that CD45RO expression also identifies memory NK cells31.
Most studies in CD45 function have been developed in T cells. Much less is known about its function on NK cells, although it is commonly accepted that CD45 positively regulates the activation of these cells through its ability to dephosphorylate the inhibitory site of SFKs, leading to cytokine and chemokine production. However, in vitro cytotoxicity is only slightly impaired in NK cells derived from CD45-deficient mice32-34. Moreover, in contrast to T and B cells, CD45-deficient NK cells show increased basal phosphorylation of multiple phosphoproteins suggesting that CD45 dephosphorylates multiple substrates in NK cells, including the activating tyrosine residue of SFKs34. In vivo studies show that CD45-deficient NK cells do not protect mice from cytomegalovirus infection due to impaired function of all immunoreceptor tyrosine-based activation motif (ITAM)-dependent NK cell functions, including degranulation35. Most of the results cited above were obtained in mouse models and could not reflect the human sketch. Hence, the role of CD45 in human NK cells is an open issue, which could depend on the type and strength of the activation.

Methods for diagnosing hematological cancers

INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LARECHERCHE MÉDICALE)

CENTRE HOSPITALIER UNIVERSITAIRE DE MONTPELLIER


The method of the present invention is a method of including forming an oxide layer on the substrate. A nitride layer is subsequently formed on the oxide layer. A photoresist layer is formed on the nitride layer to define isolation regions that uncovered by the photoresist layer. A liquid phase deposition oxide is deposited on the isolation regions. Then the photoresist layer is removed. After removing the photoresist layer, an oxygen ion implantation is performed through the oxide layer and the nitride layer into the substrate by using the liquid phase deposition oxide layer as implant mask to form relative high oxygen ion contained regions in the substrate. After the ion implantation is done, the liquid phase deposition oxide layer is removed. An annealing process is carried out to form isolation regions in the substrate and recover implant-induced damage.

Conventional LOCOS isolation process will suffer from bird's beak enroachment and local field oxide thinning effect for deep sub-.mu.m technology as mentioned in the reference "A. Bryant, et al., in IEDM, p679,1994". By 1980, LOCOS was the standard MOSFET isolation technology. However, the scalability of LOCOS for sub-half-micron CMOS technologies was a question. The issues were the lateral extent of the LOCOS bird's beak, non-planarity, thinning, and the stress-induced silicon defects. Over a decade later, as we prepare for the 0.25 .mu.m 256 Mb DRAM generation and beyond, the CMOS isolation technology becomes critical. Insulator thinning at narrow dimensions, bird's beak formation, and field-implant encroachment are the key challenge to LOCOS scaling. Insulator thinning contributes to non uniform global planarity and reduced isolation depth. Post etch-back the bird's beak encroachment and field-implant boron encroachment into active regions degrade conduction at MOSFET edges. The result is narrow channel effect (NCE) that increases MOSFET thresholds.
Conventional shallow trench isolation process can solve the above problems, however, the plasma etching induced substrate damages and poor planarization are new issues. These problems has been discussed in references "A. Bryant, et al., in IEDM, p679,1994" and "J. Y. Cheng et al., J. of Electrochem., vol. 144,p.315,1997". As mentioned in the reference "J. Y. Cheng et al., J. of Electrochem., vol. 144,p.315,1997", the LOCOS-based isolation process results in a large encroachment of field oxide (bird's beak) into the devices' active regions, narrow width effect due to high-temperature oxidation, field oxide thinning effect, and nonplanar surface topology. The oxide-filled trench isolation technology is the most promising candidate to circumvent these problems. However, the conventional resist planarization and reactive ion etching (RIE) etchback process has cumulative tolerances associate with large film thickness and easily results in nonplanar surface topography.

Method to form global planarized shallow trench isolation


A junction block assembly includes a junction block holding at least two first connectors, and at least two second connectors that mate with the first connectors. To reduce the force required to assemble the connectors, first and second cam levers are rotatably mounted to the junction block. The first and second cam levers each engage one of the second connectors and pull the engaged second connector into connection with a mating one of the first connectors. An arm of the second cam lever travels past an arm of the first cam lever during rotation.

This invention relates to a junction block assembly, such as an electrical connection box assembly mounted on a vehicle or the like.
In various assembly processes, such as automobile assembly processes, many cable connections must be made, e.g., within the electrical system of a vehicle. Connections are often made using connectors, such as plug-in-type connectors. In some configurations, it is difficult to see whether proper alignment of the connectors has been achieved prior to pressing the connectors together. If the alignment is incorrect, damage to components such as terminal pins or surrounding plastic parts, and/or improper connection resulting in a "no-start" condition, can occur. Additionally, it is sometimes difficult for an assembly technician to determine whether the connectors have been completely engaged with each other.
Force multiplying technology has been applied to connectors to reduce the actual force that must be applied by a human operator to connect connectors together. For example, in some assemblies, a cam lever fixed relative to one connector includes a cam groove that engages a cam post fixed relative to a mating connector. When the cam lever is rotated, the interaction of the cam groove and cam post pulls the connectors into engagement with each other.

Sumitomo Electrical Wiring Systems - Detroit Technical Center, Inc.


A wireless network having a radio frequency access point and a plurality of isochronous devices wirelessly connected to the radio frequency access point. Each of the isochronous devices receives information from the radio frequency access point including isochronous device identification data and transmission timing data. A microprocessor is connected to the radio frequency transceiver and creates a transmission time-ordered list of the plurality of isochronous devices from the isochronous device identification data and the transmission timing data. A timer provides a timed reference for each isochronous device to transmit to the radio frequency access point according to the transmission time-ordered list. The time-ordered list prevents collision of information being transmitted to the radio frequency access point.

1. Field of the Invention
The present invention relates to media access control and a method for handling transmission of data from a plurality of isochronous devices in networks, and more particularly to distributed media access control and a method that prevents data collisions during transmission over a network.
2. Statement of the Problem
In any network, whether wired or wireless, a need exists to prevent data collisions during transmission over the network. This is particularly true with respect to data transmitted in wireless networks such as cellular telephone systems.
Conventional wireless data networks typically contain a number of spatially distributed cells. Each cell has an access point that is, essentially, a radio transmitter and receiver. Each access point can transmit over a predetermined frequency range, and each access point has a distinct transmission area which defines the cell boundary. A number of devices are provided that can travel from cell to cell. When a device is within a specific cell, the device can transmit data to the access point of that specific cell.
When a number of devices are within a specific cell, each device can desire to transmit data to the access point of the specific cell. In order to handle these transmissions without losing data, the transmission times of each device in the cell must be properly timed so that the devices do not transmit at the same time, thereby, causing a collision of data.
Recently, conventional wireless data networks have been used for local area telephone networks. These local area telephone networks include mobile devices that travel from cell to cell. Due to the nature of the telephonic data, these mobile devices transmit isochronous data. The proper timing of data transmissions becomes even more important when the data is isochronous. Isochronous data signals have the time characteristic of recurring at known, periodic time intervals (see, The New IEEE Standard Dictionary of Electrical and Electronic Terms, Fifth Edition, at page 686 (IEEE Publishing 1993)).
Conventional networks have used a variety of transmission schemes to handle collision of data, especially isochronous data. This is even more important in wireless networks, where detection of collisions is difficult and untimely. In these networks, avoidance of collisions becomes paramount. The IEEE 802.11 standard for wireless networks has adopted a data collision avoidance mechanism that is similar to the mechanisms used in wired data networks. This data collision avoidance mechanism involves listening to other mobile devices that are transmitting to the access point and attempting collision avoidance through the use of random back-off timeouts. Collision avoidance is accomplished by requiring each device desiring to transmit to first choose a random value from within a range specified in the IEEE 802.11 standard. Each such device must then wait this random period of time following the previous transmission before commencing. Although this technique does help avoid collisions, due to the randomness of the algorithm collision avoidance is only achieved probabilistically, collisions still occur often enough to degrade system performance noticeably.
Another failing of this technique is that it is only usable when all the mobile devices within a cell are capable of receiving the previous transmission, so that all devices can time the random back-off timeout from the same point. When mobile devices are widely dispersed within the cell boundary this is often not the case. Also, since IEEE 802.11""s basic collision avoidance technique requires periods of non-use of the medium, it wastes useful bandwidth.
Based on the difficulties involved with data collision avoidance, the IEEE 802.11 standard recognizes an alternate collision avoidance technique that can be used in conjunction with the collision avoidance technique previously mentioned. In this alternate technique, the access point controls the transmission of the data from the mobile devices. In this technique, the access point creates a list of devices that are present in the cell. The access point then prompts each mobile device to transmit data at an appropriate time according to the device list. In this manner, the access point has full control of all mobile devices in its specific cell. In addition, the access point keeps track of the mobile units that enter and leave the cell boundary and revises the device list, accordingly. Also, when using the alternate technique, the access point allocates transmission time periods for other devices not participating in the alternate technique to access the wireless network using the collision avoidance with random back-off technique described herein above.
Several problems are also associated with this collision avoidance technique. This technique requires specific protocols and programming at the access point to compile the device list and to direct the mobile devices to transmit data according to the list. In addition, this technique uses valuable bandwidth because the access point must send a signal to the mobile device before data is transmitted. The bandwidth is further limited when the access point reserves transmission time periods for other devices that are not placed on the device list.
In another technique for avoiding collision of data, specifically isochronous data, each device transmits a xe2x80x9cjammingxe2x80x9d signal that follows an intricate timing algorithm. Each device is required to listen to all the other devices that transmit the xe2x80x9cjammingxe2x80x9d signal. Based on information gathered from listening to the other devices, each device individually determines a time to transmit data, preferably, when no other device is transmitting. This technique also has associated problems. First, it wastes valuable bandwidth during the times when the mobile devices transmit the xe2x80x9cjammingxe2x80x9d signal. Second, the technique requires each individual mobile device to xe2x80x9chearxe2x80x9d all other devices that are in the cell. It can become impossible for the mobile devices to xe2x80x9chearxe2x80x9d all transmissions in the cell when the mobile devices are located at polar ends of the cell or when obstacles create interference.
Therefore, a need exists to control media access to a wireless network that prevents collisions between the transmission of isochronous data by the mobile devices in a cell. Also, a need exists for a technique and an apparatus to control media access that does not require the access point to use additional protocols and programs to determine device transmission times. In addition, a need exists for a technique and apparatus to control media access that does not require the use of additional bandwidth in the wireless network. A need also exists for a technique and apparatus for controlling media access to a wireless network that allows non-participating devices to access the network without reducing the available bandwidth by allocating transmission time periods solely for the non-participating devices. Further, a need exists for a technique and apparatus for controlling media access to a wireless network that does not require each mobile device to xe2x80x9chearxe2x80x9d all other mobile devices that are transmitting to the access point of a cell.
1. Solution to the Problem
These and other problems are solved by the present invention. The present invention contains an apparatus and method for controlling media access that prevents collision of data transmitted by the mobile devices in the cell. In this regard, the apparatus and method of the present invention do not require the access point to use additional protocols or programs to determine transmission times of the mobile devices. Further, the present invention has media access control that is distributed to each mobile device rather than being centralized at the access point of the cell, and allows access by non-participating devices.
Additionally, the apparatus and method of the present invention controls media access to a wireless network that does not require extra bandwidth to be used for determining transmission times. Also, the apparatus and method of the present invention does not require each mobile device to xe2x80x9chearxe2x80x9d all other mobile devices in the cell.
In the present invention, the participating mobile devices xe2x80x9clistenxe2x80x9d to data transmitted from the access point. Based on these data transmissions from the access point, the mobile devices each individually create their own time-ordered list resident in each mobile device. Using these time-ordered lists, the mobile devices are able to determine when to transmit isochronous data to the access point without causing a collision of the isochronous data.
Finally, the present invention provides a novel method which can be utilized in any type of network whether wireless or wired.
2. Summary
The present invention, in a preferred embodiment, provides a wireless network having a radio frequency access point. The wireless network also contains a plurality of mobile devices communicating with the radio frequency access point. The mobile devices are isochronous devices. Each of the mobile devices comprise a radio frequency transceiver that communicates with the radio frequency access point. The radio frequency transceiver transmits and receives information from the radio frequency access point. The information includes, at least, mobile device identification data.
A microprocessor is provided in each mobile device and is connected to the radio frequency transceiver. The microprocessor creates a transmission time-ordered list of the mobile devices in the cell communicating with the radio frequency access point. The transmission time-ordered list is created from, at least, the mobile device identification data and transmission timing data.
A timer is provided in each mobile device and is connected to the microprocessor. The timer provides a timed reference in determining a time for each mobile device to transmit to the radio frequency access point according to the transmission time-ordered list. An input device is connected to the microprocessor for entering data to each mobile device, and an output device is also connected to the microprocessor for providing data from each mobile device.
In each mobile device, a memory device is provided and is connected to the microprocessor. The memory device stores, at least, the transmission time-ordered list which is used individually by each of the plurality of mobile devices to determine a time to transmit information to the radio frequency access point. The transmission time-ordered list prevents collision of information being transmitted to the radio frequency access point.
Finally, the method and apparatus of the present invention finds application for any wireless or wired network environment and the preferred embodiment finds a use for wireless network environment of mobile devices is but one approach.

Control system and associated method for coordinating isochronous devices accessing a wireless network


The present invention is to provide a method of producing an N-alkylaminoalkyl (meth)acrylate containing a small amount of low boiling components, especially, containing a small amount of raw components, without any complicated operations or special apparatuses. The method of producing an N-alkylaminoalkyl (meth)acrylate comprising the steps of: (A) performing the reaction between the (meth)acrylic acid ester and the N-alkylaminoalkyl alcohol in a presence of a catalyst to obtain a reaction solution containing the N-alkylaminoalkyl (meth)acrylate; (B) distilling out components which have lower boiling points than the N-alkylaminoalkyl (meth)acrylate from the reaction solution obtained by the step (A); and (C) distilling the N-alkylaminoalkyl (meth)acrylate; and further comprising the step of: (D) adjusting water concentration at a range from 0.01 to 1 wt %. in the reaction solution which is located after the step (A) and before the step (C).

N-alkylaminoalkyl(meth)acrylates are widely used as raw materials of polymer flocculating agents, lubricating additives, paper strength additives and the like. Above all, when manufacturing a polymer flocculating agent, in some cases, it has to be made to have a high molecular weight to improve its performance, and then there is a problem that a water insoluble gel material is formed. The mechanism of the formation of this gel material has not been fully understood, however, low boiling components contained in an N-alkylaminoalkyl (meth)acrylate, especially (meth)acrylic acid esters and N-alkylaminoalkyl alcohols that are reaction raw materials, are presumed to be a cause of it, and N-alkylaminoalkyl(meth)acrylates containing a small amount of these low boiling components are highly demanded. For example, a concentration of low boiling components contained in an N-alkylaminoalkyl(meth)acrylate is preferably not greater than 0.06 wt %, more preferably not greater than 0.05 wt %, and still more preferably not greater than 0.04 wt %, though it differs depending on a purpose of use and cannot be absolutely said.
Therefore, as a method of producing an N-alkylaminoalkyl (meth)acrylate, the following method is known, wherein an transesterification between a (meth)acrylic acid ester and an N-alkylaminoalkyl alcohol is performed in the presence of a catalyst, then, unreacted raw materials are distilled out from the reaction solution by distillation, and then, distillation of the target product N-alkylaminoalkyl(meth)acrylate is performed. However, there exist by-products of so-called Michael addition reaction (hereinafter referred to as Michael adducts) in the reaction solution formed by an addition reaction of the raw N-alkylaminoalkyl alcohol or a by-product alkyl alcohol to the double bonds of the raw (meth)acrylic acid ester or the target product N-alkylaminoalkyl (meth)acrylate. This Michael addition reaction is a reversible reaction and a decomposing reaction of the Michael adducts takes place not only during the transesterification but also during the following stages of distilling out the raw materials and distilling the target product, therefore, there is a problem that low boiling components such as the raw materials mix with the target product N-alkylaminoalkyl(meth)acrylate. To cope with this problem, various measures have been taken.
As a method of producing an N-alkylaminoalkyl(meth)acrylate containing a small amount of low boiling components, Patent document 1 and Patent document 2 disclose a method of producing a high purity N-alkylaminoalkyl(meth)acrylate, separating a catalyst from a reaction solution in advance to distilling out the low boiling components and refining a target product in a stage of refining after performing an transesterification in a presence of a catalyst.
Further, Patent document 3 and Patent document 4 disclose a method of reducing low boiling components in an N-alkylaminoalkyl(meth)acrylate by pyrolysis treatment of by-products.
In addition, Patent document 5 discloses a method of suppressing side reactions by adding the raw N-alkylaminoalkyl alcohol to the reaction system with a passage of time.
Patent document 1: Japanese Patent Application Laid-Open No. 11-322680.
Patent document 2: Japanese Patent Application Laid-Open No. 3-112949.
Patent document 3: Japanese Patent Application Laid-Open No. 11-222469.
Patent document 4: Japanese Patent Application Laid-Open No. 10-279540.
Patent document 5: Japanese Patent Application Laid-Open No. 4-95054.
Patent document 6: Japanese Patent Application Laid-Open No. 8-268938.

Process for the production of n-alkylaminoalkyl (meth)acrylates


The present invention is a fuel vaporizer that will greatly increase power and economy in fuel powered engines while producing far less pollution. The present invention has a fuel chamber, air inlet, vibrator and heating element that aerate fuel by vibrating and heating the fuel from a liquid to a more combustible gaseous vapor.

The present invention generally relates to the field of fuel vaporizers. More specifically, the present invention relates to a fuel vaporizer that will greatly increase power and economy in fuel powered engines while producing far less pollution.
There is a need for conserving gas while increasing power and creating less pollution. The present invention has a fuel chamber, air inlet and heating element that aerate fuel by vibrating and heating the fuel from a liquid to a more combustible gaseous vapor. Other designs use many moving parts that can breakdown also heat is used but they do not use vibration to complete the vaporization process. Other attempts at vaporization make the mistake of saying that vapors are dry, this in not correct because they are damp. Before the computer age another attempt at vaporization was a float. The present invention includes heat, air, and vibration along with being usable at any angle compared to another design that attempts vaporization with heat only and a fuel level that would fail at extreme angles.


A fuel injector for the direct injection of fuel into the combustion chamber of a mixture-compressing internal combustion engine having external ignition includes a valve housing formed by a nozzle body, and a seal which seals the fuel injector from a cylinder head of the internal combustion engine. The seal has a sleeve-type design with a structured cross section and extends across the axial length of the nozzle body.

Published European patent document EP 0 828 075 describes a fuel injector for the direct injection of fuel into the combustion chamber of an internal combustion engine, which has a device for adjusting the temperature in the region of the valve tip so as to reduce deposits in this area. The device is embodied in the form of a coating made of a thermally conductive material on the valve tip.
Disadvantages of the fuel injector described in the European patent document EP 0 828 075 are the high demands regarding the accuracy of fit of the components and the complicated installation, which is involved and thus cost-intensive.
Furthermore, a fuel injector for the direct injection of fuel into the combustion chamber of a mixture-compressing internal combustion engine having external ignition is described in published German patent document DE 101 09 407. It includes a valve housing formed by a nozzle body, and a sealing ring which seals the fuel injector from a cylinder head of the internal combustion engine. The sealing ring has a convexly arched profile, the two ends of the sealing ring axially overlapping in the form of a step.
Particularly disadvantageous in the fuel injector described in published German patent document DE 101 09 407 is the air gap between the fuel injector and the cylinder head, which allows only limited heat transfer. This is disadvantageous in reducing deposits on the valve tip since the temperature in the region of the spray-discharge orifices must be as low as possible so as to avoid deposits.


An apparatus and method for depositing objects at separated locations on a movable belt. The device includes at least one channel through which objects enter the apparatus. A sensor measures separation between adjacent objects approaching the apparatus and a reject mechanism prevents object that are too close to adjacent objects from entering the apparatus. Each channel includes a plurality of gates disposed therein. These gates operate sequentially to incrementally move the objects individually through the channel towards the movable belt. A sensor locates empty spaces along the movable belt, into which the objects are deposited. The movable belt is usually part of a conveyor system and may be a slotted belt or a smooth belt.

1. Field of the Invention
The present invention relates to a device for inputting objects to a system. More particularly, the present invention relates to a device for organizing objects from a conveyor on a movable belt and further including a reject mechanism for rejecting objects moving along the conveyor that are too close to adjacent objects moving along the conveyor.
2. Description of the Related Art
In feeding systems such as those used in conjunction with grading equipment that classifies objects based on either weight or appearance (such as computer-vision systems), it has been necessary for the individual objects to be fed to the equipment in a single line with a certain minimum distance between adjacent objects to ensure an accurate classification of the objects and also to provide the ability to direct the object to a desired location after it has been classified. The objects usually have a random orientation when fed to the system, and may be spaced too closely to each other to permit them to be accurately place in the system.
Today, one manner of accomplishing this single-line infeeding is to have an operator manually feed the objects to a feeding system or directly to a grading system. Such manual infeeding is labor-intensive and correspondingly very expensive. It is also easy for an operator to be careless and deposit more than a single object at a time to a grading system, thus producing errors in correct grading of the objects. As a result, feeding speed is limited.


A divider circuit comprises at least two clock edge controlled differential buffer store elements, each being clocked by complementary input clock signals, each comprising internal storage nodes which are pre-chargeable to a pre-charge potential, and each comprising a differential data input. The internal storage nodes of the buffer store elements are either pre-charged at the pre-charge potential or store a logic level, depending on the relevant input clock signals. The differential data inputs of one of the buffer store elements is connected to the internal storage nodes of the other buffer store element and pulsed signals can be tapped off at the internal differential storage node.

The present invention relates to a divider circuit.
Signal processing frequently requires output clock signals which are derived from high frequency signals, for example input clock signals, and whose frequency is divided in comparison with the input clock and which have a prescribed phase relationship among one another. What are known as IQ signals, which are required in reception circuits for mobile radio applications, for example, have two real signal components which are 90° out of phase with one another, the I component (Inphase) preceding the Q component (Quadrature) by 90° for positive frequencies and following it by 90° for negative frequencies.
Corresponding frequency divider circuits usually use flip-flops, where a signal is fed back from a data output to a data input, which, in the case of D-type flip-flops, for example, changes the output state upon every positive clock edge. At particularly high input clock frequencies, e.g. in the Gigahertz range, the DQ delay time, that is to say the delay between the application of an input signal level D and the presence of the corresponding signal level at an output Q of the respective flip-flop used, has a disadvantageous effect on the operation of the divider circuit. In this context, the maximum possible input frequency is limited at the top by the DQ delay time of the flip-flops used and any logic circuits which are required.
The delay time of flip-flops designed using conventional CMOS circuitry may be longer than the length of half an input clock cycle. In the past, high input frequencies have therefore prompted a change to embodiments using CML (Current Mode Logic), which has higher associated power losses as a result of constantly flowing currents, however. Particularly mobile radio applications require circuits with very low power consumption and hence very little power loss, however. The majority of complex circuit arrangements in the mobile radio sector are therefore designed using static CMOS technology. If CML circuit parts are then used for fast divider circuits, it is additionally necessary to perform level conversion for CMOS signals. This is associated with additional circuit complexity and further power loss.
To increase the speed of flip-flops designed using CMOS technology, the article "Improved Sense-Amplifier-Based Flip-Flop: Design and Measurements" B. Nikolic et al. in IEEE Journal of solid-state circuits, volume 35, No. 6, June 2000, for example, proposed sense-amplifier-based flip-flops (SAFFs). The article describes an SAFF comprising a differential sense amplifier as master latch and an RS-type flip-flop as slave latch, the sense amplifier stage producing a change from logic High to logic Low level at one of its outputs upon every rising clock edge. The corresponding SAFF is particularly suitable for use in pipeline stages in microprocessors at clock rates of up to 1 GHz.
In the case of frequency divider circuits in receiver or transmitter circuits, for example for mobile radio, ADSL, serial ATA or other wired transmissions, even higher frequencies of a few Gigahertz need to be processed, however. In addition, a duty cycle of 0.5 needs to be provided, as far as possible, for the output clock signal produced at a divided frequency. In this case, it is also beneficial to output a plurality of signals with a prescribed phase shift among one another. By way of example, these may be used as sample control signals in sample/hold circuits or analog-digital converters. Other use options are IQ transmission and reception circuits, which require orthogonal signals.
Embodiments using conventional CMOS logic are also possible, since in that case particularly no static current sources are required, in contrast to Current Mode Logic implementations.


A source driver which can control the spatial cycle of inverting the polarity of offset voltage in response to the spatial cycle of inverting the polarity of data signal. The liquid crystal display device according to the present invention has an LCD panel, having data lines, and source drivers for supplying data signal to the data lines. The source driver includes an offset cancel control circuit for generating an offset cancel control signal and an amplifier used for generating the data signal, which is configured so as to invert the polarity of the offset voltage in response to the offset cancel control signal OCC. The offset cancel controller circuit receives the pattern select signal PSEL specifying the cycle of inverting the polarity of the offset voltage of the amplifier to generate the offset cancel control signal in response to the pattern select signal PSEL.

One of technologies most commonly used in driving a liquid crystal display panel is the inverted drive. The inverted drive is a method of driving the liquid crystal display panel, in order to prevent a so-called burning phenomenon, by inverting the polarity of data signals to be supplied in the data lines (signal lines) in a predetermined spatial cycle and in a predetermined temporal cycle. It should be noted here that in the present specification the polarity of data signal is define based on the reference to the voltage level in a common electrode in a liquid crystal display panel (the common voltage). If a given data signal has a signal level higher than the common voltage Vcom, the polarity of that data signal is defined as "positive". On contrary, if a given data signal has a signal level lower than the common voltage Vcom, then the polarity of the data signal is defined as "negative". The inverted drive is devised to effectively prevent the burning by decreasing the DC component of the voltage applied to the liquid crystal capacity of a pixel.
The period of cycling time for the polarity of the data signal to be inverted in the inverted drive may be selected in a various manner. In the most typical inverted drive, referred to as the dot inverted drive, a data signal having an inverted polarity is written in the adjoining pixels, both in horizontal direction and in vertical direction. More specifically, in the dot inverted drive, both in the horizontal direction and in the vertical direction, the polarity of the data signal is inverted for every one pixel. When driving a large scaled liquid crystal display panel, the polarity of the data signal is inverted for every one pixel in the horizontal direction, while on the other hand the polarity of the data signal is often inverted for every two pixels in the vertical direction. In the present specification, the type of inverted drive where the cycle for the plurality of the data signal to be inverted in the vertical direction is the number alpha pixels will be referred to as alpha H inverted drive. For instance the inverted drive method for inverting the polarity of the data signal for every one pixel in the vertical direction (as is done in the dot inverted drive) will be described as the 1H inverted drive, and the inverted drive method for inverting the polarity of the data signal in the vertical direction for every two pixels will be described as the 2H inverted drive.
The data signal in general is generated as follows. In the driver for generating the data signal (often referred to as a source driver), a grayscale voltage generator circuit, a D/A converter and a power amplifier are integrated. The grayscale voltage generator circuit generates one set of grayscale voltages having voltage levels each corresponding to a grayscale that a pixel may be set. The D/A converter selects a desired grayscale voltage in response to the display data from within the one set of grayscale voltages, and outputs thus selected grayscale voltage to the power amplifier. The display data in the present context is the data indicative of the grayscale of the pixel to be driven. The power amplifier outputs to the data line the data signal having the same voltage level as the grayscale voltage supplied from the D/A converter. In most of cases, for the power amplifier, a differential amplifier having the output from the output stage connected to one of two inputs in the input differential stage, or a voltage follower, is used.
In general, to generate the grayscale voltage in the grayscale voltage generator circuit, a resistance ladder together with an amplifier (an op-amplifier) for supplying the bias voltage to the ladder is used. By dividing the bias voltage by means of the resistance ladder one set of grayscale voltages may be generated. Since the bias voltage output from the amplifier connected to the resistance ladder is determined so as to be at the voltage level that the grayscale voltage reflects the gamma curve of the liquid crystal display panel, the amplifier to be connected to the resistance ladder is often referred to as a gamma amplifier. A voltage follower may be often used for the gamma amplifier.
One difficulty seen in the driver of a liquid crystal display panel is such that the amplifier integrated therein has an offset voltage; therefore the voltage actually output from the amplifier may or may not be different from the desired voltage. For example, when an offset voltage is present in the power amplifier, the voltage level of the data signal may be deviated from the desired level, as a result the voltage to be written in a pixel will also be deviated from the desired level. Consequently the actual grayscale expressed by the pixel will be differed from the desired grayscale, and eventually the image quality of the image will be degraded. In particular, the offset problem may be worsening if the offset voltage is not constant from one amplifier to another. The inconsistency of the offset voltage will be recognized by the naked human eye as the vertical striping irregularity extending in the direction of the data line. In a same manner if there is present an offset voltage in the gamma amplifier, then the actual grayscale expressed by the pixel may be deviated from the desired grayscale so that the image quality of the image will be degraded.
One effective approach to avoid the problem of the offset voltage in the amplifier is to invert the polarity of the offset voltage at an appropriate cycle. It is worth noting here that the polarity of the offset voltage in the present specification is the relationship between the voltage expected to be output from the amplifier (hereinafter, "desired voltage"), and the voltage actually output from the amplifier (hereinafter "actual voltage"), and that the concept is different from the polarity of the data signal. By inverting the polarity of the offset voltage at an appropriate cycle, it may be possible for the influence of the offset voltage not to be recognized by the naked human eye. In the following description, the polarity of the offset voltage is defined as "positive" when the actual voltage is higher than the desired voltage; the polarity of the offset voltage is defined as "negative" when the actual voltage is lower than the desired voltage.
In comparison with the reduction of the offset voltage, the inversion of the polarity of the offset voltage is easier in the technical view, and may be a more reasonable approach. The offset voltage of an amplifier is most often due to the dispersion of the threshold voltage seen in the MOS transistor pair which forms the input differential stage, and the dispersion of the threshold voltage seen in the MOS transistor pair which forms the active load connected to the input differential stage (such as for example the current mirror circuit). Thus, switching the connection between the input node of the amplifier and the MOS transistor pair forming the input differential stage, as well as the connection to the MOS transistor pair forming the active load may allow inverting the polarity of the offset voltage while maintaining the amplitude of the offset voltage.
More specifically, the patent publication JP-A-H11-305735 discloses a technology for avoiding the problem of the offset voltage by swapping the MOS transistor pair in the offset input differential stage at a cycle of 4 frame interval to invert the polarity of the offset voltage (see for example paragraph [0125] of the reference).
In addition, the Japanese patent publication JP-A-2002-108303 discloses a technology for avoiding the problem of offset voltage by inverting the polarity of offset voltage for a predetermined number of horizontal lines from within a predetermined number of frame intervals. In this patent, when one frame interval is formed of eight horizontal lines, as an example, the polarity of the offset voltage is inverted for every seven horizontal lines to cancel the offset voltage thereby for the 14 frame intervals as one cycle.
To further improve the image quality, it maybe preferable, as disclosed in the patent publication JP-A-H11-249623, to invert the plurality of the offset voltage for a predetermined number of horizontal lines within each frame interval. JP-A-H11-249623 publication discloses a technology for avoiding the problem of the offset voltage, by inverting the polarity of the offset voltage for every n horizontal lines in each frame interval and every n frame intervals. The foregoing patent publication also discloses a source driver, for generating a control signal (A, B) for controlling the polarity of the offset voltage of the power amplifier from the output timing controlling clock (CL1) for outputting the display data stored in the data latch circuit to the signal line of the liquid crystal display panel and from the frame interval recognizing signal (FLMN) for acknowledging each frame interval, then inverting the polarity of the offset voltage for every two horizontal lines within each frame interval, and for every two frame intervals (see for example paragraphs [0017], [0055], and FIG. 24). The circuit disclosed in this patent publication has the spatial cycling interval for inverting the polarity of the offset voltage fixed to two horizontal lines, because it uses the output timing controlling clock (CL1) and the frame interval recognizing signal (FLMN) for generating the control signal (A, B).

Liquid crystal display device, source driver, and method of driving a liquid crystal display panel


A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, wherein: •B is an aryl or heteroaryl group optionally substituted by one or more R10 groups; and *X is selected from 0, (CR11R12)p and (CR11R12)p CO. Said compounds are capable of inhibiting PAICS and are useful in the treatment of proliferative disorders. Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing compounds of formula (I).

PAICS (phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase) is a bifunctional 46 kD enzyme catalysing the 6th and 7th steps of the de novo purine pathway (see FIG. 1).
PAICS converts 5-aminoimidazole ribonucleotide (AIR) to 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) in an ATP dependent reaction, before finally generating 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide (SAICAR) in a carboxylation reaction (see FIG. 2). This reaction series feeds into the overall generation of inositiol monophosphate (IMP), a nucleotide that forms the substrate for AMP and GMP production, from phosphoribosyl pyrophosphate (PRPP). The inhibition of folic acid, pyrimidine and purine biosynthetic pathways has proved an attractive drug target for cancer chemotherapy as rapidly dividing cancer cells have a high biosynthetic requirement in comparison to non-transformed cells.
Recent literature has highlighted PAICS as an emerging novel target for cancer therapeutics. PAICS was identified as an anti-apoptotic oncogene, with PAICS shRNA protein knock-down reducing the proliferation of a melanoma cell line in vitro. Furthermore, subcutaneous injection of PAICS knock-down cells in a xenograft model significantly reduced the rate of tumour growth (Eißmann et al., PLoS One, 2013 May 22; 8(5):e64873).
PAICS expression is significantly upregulated in lung cancer, and moreover expression levels were related to the prognosis of the patient population; increased expression of PAICS was coupled with tumours of a more aggressive nature. Xenograft models performed using lung cancer PAICS knock-down cells led to a significant reduction in tumour volume and weight after several weeks (Goswami et al., Oncotarget, 2015 September 15; 6(27):23445-61). PAICS over-expression has been also associated with a wide range of other tumour types.
Further studies indicated that PAICS may be a useful biomarker too for poor prognosis prostate cancer, with heightened expression found in prostate cancer and the severe castration-resistant form, relative to benign prostate hyperplasia samples (Barfeld et al., Oncotarget, 2015 May 20; 6(14):12587-602).
During the recent emergence of PAICS as a potential target for cancer therapeutics, studies have demonstrated that the PAICS gene is overexpressed as part of a nine gene-expression signature that is strongly associated with poor-prognosis in triple negative breast cancer (TNBC) patients. Experimental knock-down of any one of these genes had a marked inhibitory effect on cancer cell growth and metastasis in vitro and in vivo. Specifically, shRNA inhibition of PAICS expression strongly impaired primary tumour growth when breast cancer cells were injected orthotopically in the mammary fat pad of mice. Down regulation of PAICS expression in highly metastatic human breast cancer cells abolished the ability of these cells to form metastases to the lungs when injected intravenously into immunocompromised mice. Of note, this highly predictive gene-expression signature has a similar prognostic power in breast cancer patients as the gene-expression signatures, MammaPrint® or OncotypeDX®, currently used in the clinic.
The present invention seeks to provide small molecule inhibitors of PAICS. In a preferred aspect, the invention seeks to provide small molecule inhibitors of PAICS that target the SAICAR synthetase domain. Such small molecule inhibitors have potential therapeutic applications in the treatment of proliferative disorders such as cancer.

Oxazole derivatives for use in the treatment of cancer


Compositions and methods for attracting, capturing and killing populations of cotton boll weevils (Anthonomus grandis Boh.) in boll weevil traps are disclosed. With respect to the attraction and capture of boll weevils with Grandlure, the synthetic pheromone of the cotton boll weevil, there is generally an increased number of boll weevils captured in the trap cylinder when an insecticide dispenser is included in the trap cylinder to kill the weevils and thus prevent their escape. Additionally, dead boll weevils are more accurately counted than live boll weevils. The compound dichlorvos (2,2-dichlorovinyl dimethyl phosphate or DDVP) is the most preferred among those few insecticides that can be used in traps for killing and preventing weevil escapes. This is also the preferred insecticide when combined with Grandlure in a single dispenser to kill boll weevils or inhibit their ability to develop normally and reproduce. The single Grandlure dichlorvos dispenser provides for significant savings in labor expenses in large area trapping and eradication programs and significantly reduces the disposal of waste materials from spent dispensers.

1. Field of the Invention
This invention involves slow release delivery systems for use in the monitoring and the control of cotton boll weevils and other insects that over-winter or inhabit crop and nearby non-crop areas where host crops are present and not present.
2. Description of the Art
Boll weevils are coleopteran insects that feed on cotton plants; causing serious damage to the plants and reducing yield. As a consequence, multiple applications of insecticides are required to maintain populations below economically damaging thresholds. Boll weevils are generally found in cotton growing regions of North, Central, and South America.
All life stages except the adult stage are spent inside cotton squares or bolls. Male boll weevils release an aggregating pheromone after feeding on cotton squares and both males and females are attracted to this pheromone. In general, adult, over-wintered females feed for 3 to 7 days, mate with males and start laying eggs. Starting in the spring, females lay one egg per square, but at the end of the crop lay several in a boll. Each female usually lays an average of 150 eggs in her lifetime, each of which hatch in about three to five days. The resulting grubs or larvae feed about a week inside squares or bolls before changing into pupae; this stage lasts three to five days. Adults develop from pupae and cut their way out of squares or bolls. New adults feed from three to five days, mate, and begin laying eggs for the next generation. These cycles are repeated during the season until the cotton plants are either destroyed or killed by frost. It is estimated that a single pair of weevils, left uncontrolled, can generate up to two million offspring per year.
The boll weevil is a non-indigenous pest to the United States and there have been active programs to eradicate the boll weevil from the United States for more than twenty years. Currently there are about 12.5 million acres in active eradication programs, about four million acres in post-eradication programs and 300,000 acres in pre-eradication zones. The eradication programs have been financed by federal and state government funding and producer fees. Upon completion during the next 10 years, the total cost of these programs will have exceeded $2.5 billion. The eradication programs use special traps to monitor populations of boll weevils, to determine when cotton fields are to be treated with insecticide for killing boll weevils, and to eliminate very low populations of boll weevils. The traps typically include separate dispensers of Grandlure (a synthetic, four component version of boll weevil aggregation pheromone) to attract and dispensers of dichlorvos (DDVP) to kill trapped weevils. Dichlorvos prevents most of the weevils trapped in the capture cylinder of the trap from escaping and dead weevils are more easily tabulated when the trap is serviced than are live weevils.
Examples of boll weevil attractant compositions including Grandlure are described, for example, in U.S. Pat. No. 3,803,303. Grandlure has been used in combination with feeding stimulants, poisons and other compounds, in a variety of different types of devices, for example, those described in U.S. Pat. No. 4,027,420. Polymeric compositions for attracting boll weevils using a sex attractant in combination with polyethylene glycol and a toxicant such as p-dichlorobenzene are disclosed, for example, in U.S. Pat. No. 3,803,303. The contents of these patents are hereby incorporated by reference. Plant attractants such as caryophylline oxide and beta-bisabalol have been used in some of these devices, where the attractant is applied to cotton dental-rolls. Other controlled-release dispensers have been developed to give long-term release of Grandlure (McKibben and Davich, Environmental Entomology, 6(6):804-806 (1977). Volatile compounds present in the cotton plant have been shown to attract boll weevils, although not when they are diapausing. Grandlure has been used in combination with volatile compounds present in dead plan material, such as described in U.S. Pat. No. 6,183,733.
Examples of a cotton boll weevil trap suitable for use with this invention are described, for example, in U.S. Pat. No. 6,430,868. The content of this patent is hereby incorporated by reference.
The pheromone and dichlorvos dispensers should each be dated and replaced on a regular basis (each 7 to 28 days) throughout the growing season in traps that are deployed from 1 per acre to 1 per 10 acres. The labor required for replacing and disposing of each type of dispensers is a significant cost to eradication programs. In an average year of an active eradication program on 12,500,000 acres, an estimated 160 metric tons of spent dispensers are collected from traps for disposal in landfills.

Composition of grandlure and dichlorvos for attracting and killing boll weevils in boll weevil traps


Some embodiments of the present invention generally relate to the novel method, compositions and applications of mechanosensitive channels in therapeutics for visual, neurological and other disorders. Specifically, some embodiments of the invention relate to exploitation of mechanosensitive channels' intrinsic property as a transgenic pressure modulator and alternative outflow actuator in the treatment of different diseases such as glaucoma, dry eye disease and other diseases involving of cells prone to mechanical or osmotic stress. Furthermore, some embodiments of the invention relate to exploitation of mechanosensitive channels for stimulation of cells as well as molecular delivery to cells triggered by internal as well as external mechanical stimuli.

Cells of different organs in the body undergoes range of mechanical and osmotic pressures which changes in various diseases including neurological, cardiovascular, ophthalmological, and renal diseases. While, in bacteria, the mechanosensitive channel of large conductance (MscL) functions as an osmoregulator and protects cells from lysis upon hypo-osmotic shock, such channels are not present in mammalian cells.
As an example of a targeted pressure-related disorder, vision loss due to glaucoma is the second leading cause of blindness in America1. The livelihood, independence and quality of life of millions of glaucoma patients and their families are being disrupted by this pervasive disease.
Glaucoma is defined as a group of eye conditions, which cause damage to the optic nerve usually due to elevated intraocular pressure (IOP). The most common form of glaucoma is primary open angle glaucoma (POAG) and it is characterized by poor drainage of aqueous humor through the conventional outflow pathway. In the conventional outflow pathway, aqueous humor drains through the trabecular meshwork (TM), into Schlemm's canal and on into the episcleral vein. Several studies have characterized distinct changes in TM cellular processes and proteinaceous structures in glaucomatous eyes, which purportedly account for increased (TM) stiffness and aqueous humor outflow resistance2.
The eye must maintain a healthy internal pressure to preserve its form and function. A healthy intraocular pressure (IOP) is maintained by continuous upkeep of vitreous and aqueous humor processing. Aqueous humor is responsible for the structure, nutrition and hygiene of the tissues in the anterior chamber and proper regulation of its inflow and outflow balance is critical. Aqueous humor is produced by the ciliary body, flows through the pupil and drains out through either the conventional outflow pathway or the uveoscleral pathway. In the conventional outflow pathway aqueous humor flows through the trabecular meshwork (TM), into Schlemm's canal, and out into episcleral blood vessels through ducts that branch out of the canal. Glaucoma is defined as a group of eye conditions which cause damage to the optic nerve, usually due to elevated IOP. There are four main avenues by which IOP can be decreased; i) reduce aqueous humor production, ii) increase outflow through the uveoscleral pathway, iii) improve drainage through the conventional pathway, or iv) create an alternate outflow pathway.
The currently available pharmacological and surgical treatments for glaucoma have significant limitations and side effects. These undesirable side effects include, systemic reactions to medications, patient non-compliance, eye infections, surgical device failure, and damage to other structures of the eye. To forestall disease progression, most glaucoma cases will need multiple medical interventions over time. For example, even after surgery some glaucoma patients will still need to take daily eyedrops for an indefinite period. The development of a safe effective long-lasting single-dose therapeutic for the ubiquitous treatment of glaucoma.
The other treatment option for uncontrollable glaucoma is surgery. The most common glaucoma surgery is a trabeculectomy, where an alternative outflow pathway is created by removing a section of the sclera, Schlemm's canal and TM and fashioning a filtration bleb out of a conjunctival tissue flap. Other surgical methods include, canaloplasty, laser trabeculoplasty, laser peripheral iridotomy, deep non-perforating sclerectomy, and drainage device implantation. As with all surgeries, there are risks of infection, systemic side effects and human/device failure. Post-surgical scarring at the procedure site is common and scar tissue can block or shift the newly created drainage pathway. With the added considerations of the expense, patient recovery time and inconsistent outcomes of surgery, it becomes clear that new and innovative treatments for glaucoma are needed.

Method, compositions and applications of mechanosensitive channels in visual disorders and other applications thereof


Systems, apparatuses, and methods are disclosed for receiving downlink control information (DCI) that may include an indication of a reference measurement resource (RMR), receiving an indication of a measurement configuration, and receiving an indication of a feedback resource configuration. A measurement report based on the indication of an RMR, an indication of a measurement configuration, and an indication of a feedback resource configuration may be generated and may be transmitted to a network device.

Cell-specific reference signals (CRSs) may be used in wireless systems for channel estimation to perform coherent demodulation of physical channels, to acquire channel state information (CSI) for transmission modes (TMs), and/or for higher-layer measurements that may be used in cell-selection and handover decisions. It may be desired that reference signal overhead be reduced to limit unnecessary interference to neighboring transmission/reception points (TRPs) and/or to reduce power consumption at a TRP.

Systems and methods for reference signal measurements in wireless systems


A pull handle that is ergonomically designed to avoid unnatural stresses and/or discomfort to the user's body and joints through the range of motion. The invention enables a user to perform exercises that cannot be accomplished with existing handles or may be more difficult or uncomfortable to do so. These objects are achieved by providing one or more axes of rotation or flexibility in the pull handle so that the user's hand, wrist and/or arm (or foot, ankle and/or leg) may bend and/or rotate more naturally through the user's range of motion.

Many forms of exercise equipment involve pull handles connected to cables, weights and other forms of resistance. The user typically grasps the pull handle to lift the weight, pull the cable or effect some other type of movement against the resistance. A problem with existing pull handles is that they have a fixed point of attachment to a source of resistance and therefore offer a limited range of mobility and do not account for the rotation of the user's hand, wrist and/or arm (or foot, ankle and/or leg) as the user extends through the range of motion associated with the particular exercise. This may create unnatural stress on the user's joints, ligaments and/or tendons that may result in injury. It also limits the type of exercises that can be performed using the handle. Another problem with existing pull handles is that their forms lead to discomfort when performing certain exercises and preclude the performance of other exercises altogether, especially functional exercises that focus on the human body's natural movements.
These issues exist with single pull handles that may be held in either of the user's hands, as well as with exercise bars that may be used with lat pull-down or other similar exercises where two pull handles are used at the same time in each of the user's hands.
In view of the foregoing, there is a need for a pull handle that addresses the above described issues such as relieving unnatural stress on the user's joints when performing exercises. There is also a need for a pull handle that relieves or mitigates the discomfort caused by existing pull handles during the performance of certain exercises. There is also a need for different methods of exercise that may be performed with one or more pull handles that address these issues.

Ergonomic pull handle and associated exercise methods


A system and method that effectuates dynamic mass mail throttling utilizing an upstream network device. The system and method includes intercepting messages from sending mail server, determining whether the message relates to mass mailing advertising emails, and based the determination automatically and dynamically directing upstream network devices to gradually retard communications between the sending mail server and the upstream network devices.

There are many and various factors that can cause email servers to experience stress due to information overload. Examples are spam storms (and other mail related attacks), denial of service attacks, legitimate and illegitimate (albeit not illegal) mass marketing mailings, to name a few. Nevertheless, there are many instances where legitimate enterprises in furtherance of their business goals will want and need to disburse advertising and marketing information to interested consumers/customers.
Loyalty programs are marketing contrivances employed in many commercial sectors, such as, for example, retail (e.g. supermarket rewards cards, points cards, club cards, and the like) and commercial aviation (e.g. frequent flyer programs, etc.), that reward band loyalty. Typically, customers/consumers enrolled in the program accrue points and are entitled to discounts and/or rewards based upon pre-established criteria (e.g. distance flown on a particular airline, amount of produce purchased from a particular retail establishment, etc.). In order for loyalty programs and other mass marketing programs to keep their members apprised of various available offers, discounts, rewards and developments associated with these programs, many, if not most, have adopted electronic mail (email) as one of the preferred methods of communication to contact their members.
Typically, enterprises (e.g., commercial, educational, institutional, governmental, etc.) have substantial electronic mail infrastructure that for the most part is specifically constructed to satisfy a particular enterprise's unique requirements. While such electronic mail infrastructure may be perceived as being considerable, the electronic mail infrastructure utilized by organizations involved in mass marketing and/or loyalty marketing campaigns can be many orders of magnitude larger and more powerful than those ever conceived and/or required by typical enterprises. Thus when electronic mail infrastructure utilized by organization involved in mass marketing and/or loyalty marketing campaigns commence disseminating electronic mail related to the marketing campaign the volume of messages (e.g. in the tens of thousands to hundreds of thousands) that can be received by a typical enterprise electronic mail infrastructure can be so overwhelming that the typical enterprise electronic mail infrastructure will generally issue a transient error message. Transient error messages typically inform sending systems to try sending their messages later. This however has two major problems. First, there is no control as to when the sending system might try to resend the message; it might be 10 minutes, 4 hours, 1 day or never. Second, transient error messages cause a yo-yo effect since all global systems are effectively told to re-send their messages at some later time. So once the receiving mail server has recovered sufficiently to start accepting connections again, those systems that were told to re-send at a later time immediately re-send causing the receiving system to vacillate between issuing transient error messages and accepting connections for a period from anywhere between 24 to 48 hours.

Throttling of mass mailings using network devices


A system and method for behavior modification through dynamic identification of behavior patterns, assistance in finding and implementing healthy alternatives to undesirable behavior patterns, preparation of dynamically variable user-specific programs, monitoring of current user activities, and presenting feedback and information to the user. The system and method further support incorporation of professional and other information into a user-specific package from which the user-specific program is determined, and synchronization and data integrity across the platforms of the system.

The present invention relates to an adaptive behavior modification method and system for modifying behavior and, more particularly, to such a system for modifying behaviors that could have an influence on the physical, emotional, psychological, etc. well-being of a person.
Human behavior is a product of environmental factors interacting with pre-disposing individual genetic endowments. Most people have acquired a range of maladaptive behaviors that prevents them from living healthy, satisfied, and fulfilling lives. These maladaptive behaviors can result from, for example, birth order, relationships (or the lack thereof) with siblings, relationships with others, and inadequate or incomplete early emotional connections with authority figures, including the opposite gender parent. These developmental deficits create needs that the adult seeks to fulfill in various adaptive and maladaptive ways. The maladaptive compensations can include the failure to positively self-actualize potential as well as various compulsive dependencies on, for example, food and various substances, such as, for example, among other things, alcohol, tobacco, and drugs, and addictive activities such as gambling, and the like.
It has been generally believed possible to modify, if not alleviate, the undesired behaviors, and, accordingly, various methods for doing so have been developed. These methods include diet programs, drug-dependency programs, smoking cessation programs, and other behavioral modification devices and practices that have enjoyed various levels of popularity in the last one hundred or so years.
For example, there are disclosed in the art hand-held computing devices to log exercise, for example, weightlifting routines, as a way of recording exercises performed and assisting the user in his or her workout program. In a somewhat different manner, there are also disclosed in the art wristwatch-like devices that exhibit indicia (e.g., the word "stop") to serve as a conscious and/or unconscious reminder to the user to stop or otherwise modify an undesired behavior.
While it is probable that a multitude of such programs and behavior-adjusting systems are available, such programs oftentimes are not effective for their intended purpose for long periods of time. Their lack of efficacy may be linked to an inability of the programs/system to adapt to the particular behavioral profile or pattern of the user over time.
An object of the present invention is to provide a system and method to assist a user in dynamically identifying his/her undesirable behavior.
A further object of the present invention is to provide simultaneous data updating for multiple users of mobile interactive systems.
A further object of the present invention is to assist the user in finding and implementing healthy alternatives to undesirable behavior by offering to the user dynamically variable user-specific plans, monitoring and feedback rules, and information.
A still further object of the present invention is to coordinate the use of user physiological and psychological data to determine effective healthy alternative behavior for the user, and dynamically variable paths for the user to reach the healthy alternative behavior.
A yet still further object of the present invention is to provide to the user and a professional or the like with a dynamic interface, allowing the professional to modify the user's information and plan to incorporate professional advice and comments.
A yet still further object of the present invention is to provide the capability to monitor and modify the information received by multiple users operating remotely based on dynamic user profiles.

Self-attainable analytic tool and method for adaptive behavior modification


An absorption cool-water machine including a high quality fuel system and an exhaust heat utility system and apparatus and method for controlling the same is described in which the control has improved effectiveness in preventing the occurrence of crystallization in the exhaust heat exchanger tubing and/or corrosion resulting from an increase in high temperature regenerator temperatures and to otherwise prevent the production of unavailable refrigerant, save energy in an exhaust heat charge mode of operation, and to insure refrigerating ability even when exhaust water temperatures are low without reducing the effectiveness of the machine. In the described organization, a determination is made of the operative state of the exhaust heat utility system and adjustments are automatically made in supremum limiters for controlling the degree of opening of throttle valves for adjusting the supply of fuel and combustion air to the high quality fuel system that supplies heat to the high temperature regenerator.

As an absorption cool-warm water machine or an absorption refrigerating machine in which a high-quality fuel system and a exhaust-heat utility system are provided and a heat exchanger is provided to be charged with exhaust-heat from outside through the heat exchanger into the tubing of the exhaust-heat utility system there is, for example, Japanese Patent Application Ser. No. 6-73428 previously filed for an application by the present applicant.
Here, in the cool-warm water machine, there is a case which a solution pump is interrupted in response to various signals (such as, a signal detecting a cool water temperature lower than a predetermined value) produced during an operation.
However, in the case of providing the heat exchanger, through which the exhaust-heat is charged from outside into the tubing of the exhaust-heat utility system, even after interrupting the solution pump, there is a case in which the exhaust-heat is charged from outside through the heat exchanger. In this case, the solution is not circulated, so that the solution inside the heat exchanger is inspissated, resulting in a fear that the solution is crystallized in the heat exchanger. If the crystallizing is produced, the subsequent system to the heat exchanger cannot be used. Consequently, it is required to avoid producing crystallization, however, in a conventional art, an effective preventive measure has not been proposed yet.
The other well-known art will be further explained with reference to FIG. 23 (a drawing showing one of the embodiments of the present invention).
In the absorption cool-warm water machine, a vaporizer 2, an absorber 3, a condenser 4, a high-temperature regenerator 10 and an exhaust-heat heat-exchanger 20 are provided, in which cool-warm water is fed through a cool-warm water circulation line 5 to a cooling load (not shown). Further, a cooling water circulation line 6 is provided to feed cooling water to the absorber 3 and the condenser 4.
An exhaust-heat charge line 22 is provided to feed the exhaust-heat from an exhaust-heat line 21 to the heat-exchanger 20, in which a three valve V1 capable of adjusting the flow is provided at a confluent point of the exhaust-heat charge line 22 and the exhaust-heat line 21.
As a condition for the cool-warm water circulation line 5 in the aforementioned absorption cool-warm water machine 1, for example, a cool-warm water entrance-temperature T.sub.Lin in is adapted to be 12.degree. C., and a cool-warm water exit-temperature T.sub.Lout is adapted to be 7.degree. C. The high-temperature regenerator 10 and a burner for combustion of high-quality fuel 11 provided to the high-temperature regenerator 10 are designed to meet a reference fixed by the aforementioned temperatures in a non-charging state of the exhaust-heat.
Comparing with an operation at the aforementioned condition or reference, there is a case for increasing the temperature of high-temperature regenerator 10. For example, when the overload acts by the cooling load connected to the cool-warm water circulation line 5, the cool-warm water entrance-temperature T.sub.Lin becomes higher (e.g., 13.degree. C.) than 12.degree. C. In order to control the cool-warm water exit-temperature T.sub.Lout to be 7.degree. C. in the aforementioned over-load state, it is required to operate for high-load or over-load from a normal operation, so that the temperature of the high-temperature regenerator 10 increases more than (a required value) in the normal operation.
Further, the temperature of the high-temperature regenerator 10 increases more than the required value when a cooling water circulation temperature TMin circulating in the cooling water circulation line 6 returning from a cooling tower (not shown) to the cool-warm water machine 1 is increased more than a set value.
The aforementioned increase of the temperature of the high-temperature regenerator 10 is remarkable in an exhaust-heat charge operation mode charging the exhaust-heat fed from outside.
However, there is a disadvantage that corrosion of the high-temperature regenerator 10 is facilitated when the temperature of the high-temperature regenerator 10 is increased more than the required value.
In answer to the aforementioned disadvantage, art is proposed, in which a limiter is provided in order that the operation of the high-temperature regenerator 10 is interrupted by action of the limiter when the temperature of the high-temperature regenerator 10 is increased more than-the required value. However, use of the aforementioned art causes the ability of the cool-warm water machine 1 when the operation of the high-temperature regenerator 10 is interrupted to sharply reduce, therefore, a disadvantage is produced, in which the smooth operation of the cool-warm water machine 1 is impeded.
Further, another conventional art will be explained with reference to FIG. 27 (a drawing showing one of the embodiments of the present invention).
Like the absorption cool-warm water machine 1 shown in FIG. 23, the cool-warm water entrance-temperature T.sub.Lin of the cool-warm water circulation line 5 is 12.degree. C., and the cool-warm water exit-temperature T.sub.Lout is 7.degree. C. The high-temperature regenerator 10 and the burner for combustion of the high-quality fuel 11 provided to the high-temperature regenerator 10 are designed based on the aforementioned temperatures.
Comparing with an operation at the aforementioned condition or reference, there is a case for increasing the temperature of high-temperature regenerator 10. For example, when over-action of load is produced by the cooling load connected to the cool-warm water circulation line 5, the cool-warm water entrance-temperature T.sub.Lin becomes higher (e.g., 13.degree. C.) than 12.degree. C., so that, in order to control the cool-warm water exit-temperature T.sub.Lout to be 7.degree. C. in the aforementioned over-load state, it is required to operate for the high-load from the normal operation, therefore, the temperature of the high-temperature regenerator 10 is increased more than (a required value) in the normal operation. And, the temperature of the high-temperature regenerator 10 is increased more than the required value when the cooling water circulation temperature returning from the cooling tower (not shown) provided to circulate to the cooling water circulation line 6 to the cool-warm water machine 1 is increased more than the set value.
The aforementioned increase of the temperature of the high-temperature regenerator 10 is remarkable in an exhaust-heat charge operation mode charging the exhaust-heat fed from outside.
However, refrigerant of liquid phase sent from the condenser 4 to the vaporizer 2 is resulted from the amount in response to the fed heating value, in which there is, in the exhaust-heat charge operation mode, a case of an insufficient heating surface area of the vaporizer 2 against the amount of the refrigerant. In this case, there is a disadvantage in which the refrigerant of the liquid phase (unavailable refrigerant) is produced to move to the side of the absorber 3 before evaporating. The unavailable refrigerant is sent to the absorber 3 without absorbing the evaporated heat from the cool-warm water in the vaporizer 2, therefore, the unavailable refrigerant is unable to cool but processes only the action of diluting the refrigerant solution in the absorber 3. More specifically, the presence of the unavailable refrigerant shows that the operation of the absorption cool-warm water machine is not facilitated efficiently.
When the temperature of the high-temperature regenerator 10 is increased more than the required value, there is a disadvantage in which the corrosion of the high-temperature regenerator 10 is facilitated, in answer to the disadvantage of the corrosion, art is proposed, in which limiter is provided in order that the operation of the high-temperature regenerator 10 is interrupted by action of the limiter when the temperature of the high-temperature regenerator 10 is increased more than the required value. However, when the operation of the high-temperature regenerator 10 is interrupted, the ability of the cool-warm water machine 1 is sharply reduced, therefore, another disadvantage is produced, in which the smooth operation of the cool-warm water machine 1 is impeded.
FIG. 62 is another drawing showing a conventional absorption cool-warm water machine which differs from the absorption cool-warm water machine. Comparing with the operation at the aforementioned condition or reference, there is a case for increasing the temperature of the high-temperature regenerator 10. For example, when over-action of the load is produced by the cooling load connecting to the cool-warm water circulation line 5, the cool-warm water entrance-temperature T.sub.Lin becomes higher (e.g., 13.degree. C.) than 12.degree. C., so that, in order to control the cool-warm water exit-temperature T.sub.Lout to be 7.degree. C. in the aforementioned over-load state, it is required to operate at high-load from the normal operation, therefore, the temperature of the high-temperature regenerator 10 is increased more than (the required value) in the normal operation. And, the temperature of the high-temperature regenerator 10 is increased more than the required value when the cooling water circulation temperature returning from the cooling tower (not shown) provided to circulate to the cooling water circulation line 6 to the cool-warm water machine 1 is increased more than the set value. The aforementioned increase of the temperature of the high-temperature regenerator 10 is remarkable in an exhaust-heat charge operation mode charging the exhaust-heat fed from outside.
When the cool-warm water machine 1 is in the over-load state, even though the exhaust-heat held in the warm exhaust-water is charged into the cool-warm water machine 1, the heating surface area of each element (e.g., the vaporizer 2) is insufficient, so that the charged exhaust-heat is wastefully radiated to the cooling tower (not shown) that is provided to circulate to the cooling water circulation line 6. The aforementioned situation is out of step with an effective use of the exhaust-heat or the requirement of saving energy.
And, the temperature of the warm exhaust-water fed through the exhaust-heat line 21 and the exhaust-heat charge line 22 is not fixed. Here, decreasing the temperature of the warm exhaust-water, the effect of charging the exhaust-heat is reduced. When the temperature of the warm exhaust-water is lower than the temperature of the solution in the cool-warm water machine, the flow of the heat results in a counter-current from the solution to the warm exhaust-water, therefore, there is an important disadvantage in which the refrigerant ability of the absorption cool-warm water machine is insufficient. Furthermore, it is possible that the heating value caused by the high-quality fuel charged into the cool-warm water machine is unnecessarily wasted.

Absorption cool-warm water machine and method for controlling the same


The invention relates to a method and system for operating a gaming terminal where the gaming terminal cabinet itself is an active feature or element of the wagering game. The method and system of the invention involve a gaming terminal cabinet that is transformable from a primary external configuration to a secondary external configuration. The transformation of the gaming terminal cabinet may be based on an outcome of a basic wagering game, a bonus wagering game, or both. The secondary external configuration may involve a single transformation or it may involve multiple transformations. At the end of the wagering game, the gaming terminal cabinet may be transformed back into the primary external configuration. The transformation of the gaming terminal cabinet may also be used to attract the attention of passersby when the gaming terminal is idle to thereby generate interest in the gaming terminal.

Gaming terminals, such as slot machines, video poker machines, and the like, have been a cornerstone of the gaming industry for several years. Generally, the popularity of such terminals among players depends on the perceived likelihood of winning money at the terminal and the intrinsic entertainment value of the terminal relative to other available gaming options. Where the available gaming options include a number of competing terminals and the expectation of winning each terminal is roughly the same (or believed to be the same), players are likely to be attracted to the more entertaining and exciting of the terminals.
Consequently, gaming terminal operators strive to employ the most entertaining and exciting terminals available because such terminals attract frequent play and, hence, increase profitability for the operators. Thus, in the highly competitive gaming terminal industry, there is a continuing need to develop new types of games, or improvements to existing games, that will enhance the entertainment value and excitement associated with the games.
One concept that has been successfully employed in existing gaming terminals to enhance player entertainment is the use of progressive games. In the gaming industry, a "progressive" game involves collecting coin-in data from participating gaming device(s) (e.g., slot machines), contributing a percentage of that coin-in data to a progressive jackpot amount, and awarding that jackpot amount to a player upon the occurrence of a certain jackpot-won event. A jackpot-won event typically occurs when a "progressive winning position" is achieved at a participating gaming device. If the gaming device is a slot machine, a progressive winning position may, for example, correspond to alignment of progressive jackpot reel symbols along a certain payline. The initial progressive jackpot is a predetermined minimum amount. That jackpot amount, however, progressively increases as players continue to play the gaming machine without winning the jackpot. Further, when several gaming machines are linked together such that several players at several gaming machines compete for the same jackpot, the jackpot progressively increases at a much faster rate, which leads to further player excitement.
Another concept that has been employed is that of a secondary or "bonus" game which may be played in conjunction with a "basic" game. The bonus game may include any type of game, either similar to or entirely different from the basic game, and is initiated by the occurrence of certain pre-selected events or outcomes of the basic game. Such a bonus game has been found to produce a significantly higher level of player excitement than the basic game alone because it provides an additional chance to play, which increases the player's overall expectation of winning.
In existing gaming terminals, the cabinet that houses the various components (e.g., displays, wager intake, hopper, electronics, etc.) of the gaming terminal has an essentially fixed external configuration. That is, the size, shape, aspect ratio, and other physical attributes of the cabinet does not change during or after the wagering game. Some gaming terminal cabinets may have external configurations that reflect a particular theme and may include lights that flash and change colors according to the outcome of the wagering game, but the external configuration of these cabinets do not change. As such, existing gaming terminal cabinets are not a feature or element, or are only a passive element, of the wagering game.
Accordingly, what is needed is a gaming terminal that is capable of providing increased excitement and entertainment value over existing gaming terminals. More specifically, what is needed is a gaming terminal where the cabinet itself is an active feature or element of the wagering game.

Gaming terminal with transformable cabinet


A high-density impurity diffused layer of an identical conduction type to the semiconductor substrate on which the impurity is doped higher in density than the semiconductor substrate around the diffuse resistance region is provided, one side of the electrodes is formed extending to the high-density impurity diffused layer and the diffused resistance region and the high-density impurity diffused layer are connected in a semiconductor strain gauge that is formed on the surface of the semiconductor substrate of a fixed conduction type and is provided with the diffused resistance region of opposite conduction type to the semiconductor substrate and is provided with electrodes on both ends of the diffused resistance region.

This invention relates to a structure and manufacturing method of a semiconductor gauge using a diffused resistor, which can be used for various acceleration sensor pressure sensor, etc.
A strain gauge is used to detect acceleration and pressure in the prior art and there are various types in the strain gauge. The strain gauge using a semiconductor single crystal is used in many cases, which detects the changes in force applied utilizing the piezoelectric resistance effect of the semiconductor as variation in electric resistance. There are a bulk type gauge and a diffused type gauge in the semiconductor strain gauge using the piezoelectric resistance effect and it is necessary to apply manufacturing work on the semiconductor substrate because the semiconductor substrate itself becomes a gauge in each type.
FIG. 7 shows the structure of a diffused type gauge used commonly and (a) is a vertical sectional view and (b) is a plan view viewed from an arrow A-A line direction in (a). A diffused resistor 2 of opposite conduction type is formed, diffusing a type P impurity into the surface of type N single crystal silicone substrate 1. A surface of the diffused resistor 2 is protected with oxide film 3 such as SiO2, which is an insulated film and a positive (+) electrode 4 and a negative (−) electrode 5 are formed by metallic film of aluminum and the like after etching a part of the oxide film 3. It is not necessary to process the semiconductor substrate mechanically when the resistance layer is formed on the type N single crystal silicone substrate 1 as the semiconductor substrate by diffusion.    [Patent document 1] U.S. Pat. No. 6,635,910    [Patent document 2] JP, 2001-264188, Publication of unexamined patent applications    [Patent document 3] JP, 2004-531699, PCT Publication of unexamined patent applications

Semiconductor strain gauge and the manufacturing method


A battery dispenser system with detachable dispensing units that includes a mounting board having a planar mounting surface, four board mounting apertures formed through the mounting board and at least two sets of dispensing unit snap fastener receiving cavities formed through the planar mounting surface; at least one detachable battery dispensing unit for cylindrical shaped batteries; and at least one detachable battery dispensing unit for rectangular shaped batteries; the battery dispensing unit for rectangular shaped batteries including a planar dispensing ledge, a battery insertion opening, and a feed passageway in connection between the planar dispensing ledge and the battery insertion opening; the battery dispensing unit for cylindrical shaped batteries including a battery feed passageway, a curved forward directing surface partially defining the battery feed passageway, and a battery retaining lip; each detachable battery dispensing unit including a number of dispensing unit snap fasteners that are positionable into one of the at least two sets of dispensing unit snap fastener receiving cavities of the mounting board; each dispensing unit snap fastener including a locking tab portion that engages a projection that partially defines a fastener receiving opening into each dispensing unit snap fastener receiving cavity.

Many individuals and businesses use a large number of batteries to power various portable electronic and electrical tools and devices. It would be a benefit, for these organizations and individuals to have a dispenser system for batteries that could be mounted to a wall to maintain the batteries in an organized fashion. In addition, because the type of batteries needed can vary according to the individual or organization, it would be a benefit to have a dispenser system that included a number of detachable battery dispensing units that could be attached by a user to a universal mounting beard. Because most batteries fall within either a cylindrical shape or a rectangular shape, it would also be a benefit to have detachable battery dispensing units that are adapted to store and dispense either rectangular shaped batteries or cylindrical shaped batteries.

Battery dispenser system with detachable dispensing units


The invention relates to a non-volatile memory device comprising: an input for providing external data to be stored on the non-volatile memory device; a first non-volatile memory block and a second non-volatile memory block, the first non-volatile memory block and the second non-volatile memory block being provided on a single die, wherein the first non-volatile memory block and second non-volatile memory block are of a different type such that the first non-volatile memory block and the second non-volatile memory block require incompatible external attack techniques in order to retrieve data there from; and—an encryption circuit for encrypting the external data forming encrypted data using unique data from at least the first non-volatile memory block as an encryption key, the encrypted data at least being stored into the second non-volatile memory block. The invention further relates to method of protecting data in a non-volatile memory device.

Non-volatile memory devices (ROM, PROM, EPROM, EEPROM, etc) are widely known. Also they have been widely used in applications where the data needs to be protected, like in home applications, mobile applications, and set-top boxes (pay TV, satellite TV, etc). In the last decades various methods of attacking data on non-volatile memory devices have been developed:
front-side de-processing combined with optical imaging
back-side de-processing combined with voltage contrast imaging
microprobing
UV treatment
Software attack
FIB (cut and sense),
etc.
In general non-volatile memories like floating gate-based memories and ONO-based memories have been regarded as very secure to these attacks. However, recently, in C. De Nardi et al., Microelectronics Reliability, Vol. 45 (2005), p 1514-1519, a method has been published which enables retrieval of data from EEPROM memory devices. This publication discloses a method to measure "on site" programmed charges in EEPROM devices. Electrical AFM based techniques (Electric Force Microscopy (EFM) and Scanning Kelvin Probe Microscopy (SKPM) are used to probe directly floating gate potentials. Both preparation and probing methods are discussed. Sample preparation to access floating gate/oxide interfaces at a few nanometers from the back-side without discharging the data reveals to be the key point, more than the probing technique itself. This method will also be referred to as back-side voltage contrast imaging.
So, a drawback of the known non-volatile memory devices is that data stored thereon may no longer be secure enough to external attacks.

This patent is subject to a terminal disclaimer.

Secure non-volatile memory device and method of protecting data therein