A station in the WLAN monitors each transmitted frame to determine whether the frame transmission was protected by an existing outstanding airtime reservation. If a frame is transmitted without an airtime reservation and no response frame is received, the station assumes that the transmission failed due to contention, and monitors the number of contention attempts made to transmit each frame, and the number of failures to receive an acknowledgement. Based on this information, the station dynamically adjusts an RTS/CTS threshold used to determine whether or not an RTS/CTS exchange mechanism should be enabled. If a frame is transmitted during a time interval protected by an outstanding airtime reservation and no response frame is received, the station assumes that the transmission failed due to a bit error, and monitors the number of bit error rate (BER) attempts made to transmit each frame, and the number of BER failures to receive an acknowledgement. Based on this information, the station dynamically adjusts a fragmentation threshold used to determine whether or not a data frame fragmentation mechanism should be enabled.

In a WLAN, wireless communication links are used as a transmission medium to exchange data between various stations. Due to the nature of wireless communications, it is difficult to physically detect a collision event when multiple stations transmit data frames at the same time. As a result, a typical WLAN protocol requires each frame transmission to be acknowledged by the receiver. In response to a received DATA frame, the receiver transmits an acknowledgement (ACK) frame, which indicates to the original transmitter that the DATA frame was received without errors. Accordingly, the transmitter assumes that no significant collision event happened during the DATA frame transmission. If the ACK frame is not received, the transmitter assumes that some collision event causes the DATA frame to be lost.
FIG. 1 illustrates the successful transmission of a DATA frame from Station A to Station B that acknowledges the reception by sending an ACK frame. FIG. 2 illustrates a collision event caused by simultaneous transmission of DATA frames by Station A and Station C. As a result, Station B does not receive data. Station A and Station C will assume that a collision has taken place because neither of them will receive an ACK frame from their intended receivers.
As shown in FIG. 3, Station A may retry to send its DATA frame to Station B. However, a collision with a DATA frame from Station C may again prevent Station B from receiving information. As no acknowledgement is sent, Station A must repeat its DATA frame again. This transmission may be successful, and Station B responds with an ACK frame.
A collision event caused by multiple stations competing for a shared network usually occurs at the beginning of transmission. Because the Medium Access Protocol indicates to stations on the network that the medium is free at approximately the same time, any stations with pending transmissions will begin to transmit at approximately the same time. When this occurs, the resulting transmissions will have a collision event that physically begins at or near the beginning of the transmission. However, the transmitting device is unaware of the occurrence of the collision until it has completed its attempt to transmit the DATA frame, and does not receive the expected ACK frame.
Thus, the collision event cannot be detected until the end of the transmission attempt. The longer the DATA frame, the longer it will take for the transmitting station to determine that the collision event has occurred.
Furthermore, if a collision event occurs at or near the beginning of a long DATA frame, most protocols and physical implementations render the entire DATA frame unreceivable. Therefore, the portion of the DATA frame after the beginning of the collision event wastes network bandwidth. The sooner a collision can be detected by a transmitter, the sooner the transmitter can end the faulted transmission and stop wasting network bandwidth.
To minimize the probability of a collision, some WLANs use a short request-to-send (RTS) frame sent before the actual data transmission to request an airtime reservation. For example, U.S. Pat. No. 5,231,634 to Giles et al. discloses an RTS frame sent by a transmitting station to inform other WLAN stations that the sending station wishes to use the medium for a data transmission. The RTS frame contains a time duration field which indicates to all receiving stations the amount of airtime requested for a data transmission. The requested airtime corresponds to the amount of time required to send the DATA frame plus the time required to send the ACK frame, plus the time required to receive an acknowledgement for the airtime reservation request, plus some additional small amount of time required to provide interframe spacing.
As the RTS frame itself may encounter a collision, an acknowledgement for the RTS frame is sent by a receiving station. A clear-to-send (CTS) frame may be sent in response to the RTS frame to confirm the airtime reservation. The CTS frame repeats the airtime reservation duration information.
Thus, when an RTS/CTS frame exchange mechanism is used, the following sequence of events takes place: the transmission of the RTS frame by transmitting Station A to request an airtime reservation, the transmission of the CTS frame by receiving Station B to provide an airtime reservation confirmation, the transmission of the DATA frame by Station A, and then the transmission of the ACK frame by station B to acknowledge the reception of the DATA frame.
If this frame exchange encounters a collision, it should normally occur at or near the beginning of the exchange, i.e. during the RTS or CTS frame transmission. For example, FIG. 4 illustrates two transmission attempts when the RTS frames sent from Station A were not received by Station B because of collisions with data simultaneously sent by Station C. However, the third RTS frame from Station A is received by Station B, which responds with the CTS frame. After receiving the CTS frame, Station A transmits its DATA frame acknowledged by the ACK frame sent by Station B. The airtime reservation requested by Station A and confirmed by Station B provides a time interval for the transmission of the DATA frame and ACK frame.
As the RTS and CTS frames are made short, a collision that occurs during the transmission of either of these frames results in stopping the transmission after a short time interval. Thus, the RTS/CTS frame exchange mechanism prevents network bandwidth from being wasted. Once the RTS/CTS exchange is successful, the airtime reservation information contained in the RTS and CTS frames is used by other stations in the network to avoid transmitting data during the requested airtime reservation interval. As a result, the DATA frame and ACK frame transmissions can proceed with greatly reduced possibility of encountering a collision event.
It should be noted that the RTS/CTS frame exchange mechanism requires that some of the network bandwidth be sacrificed. In a WLAN having many competing stations, the bandwidth lost to RTS/CTS frame exchanges is more than made up for by the reduction in wasted bandwidth that would have occurred due to collisions during long DATA frame transmissions. However, when the number of competing stations in the WLAN is small, the relatively infrequent long DATA frame losses due to collisions may amount to less overall network bandwidth loss than the loss due to the inclusion of the RTS/CTS frame exchange which preceded each DATA frame.
Therefore, some WLANs use a RTS/CTS threshold that specifies the minimum length of a DATA frame for which the RTS/CTS frame exchange mechanism is used. If the length of a DATA frame queued for transmission exceeds that minimum length, then RTS/CTS frame exchange is enabled for that frame transmission, otherwise the RTS/CTS exchange mechanism is not used.
In the event of the failure of a transmitting station to receive an acknowledgment frame (i.e. a CTS frame or an ACK frame), the transmitting station assumes that a collision took place. However, the transmission failure may be caused, for example, by a noise-induced bit error, or by some other interference source such as a non-WLAN transmitter. Also, the intended recipient may be out of the range of the transmitting station.
In the case of a bit error due to noise, the bit-error rate (BER) of the system is relatively fixed for a given signal/noise ratio. As this ratio changes, the BER may increase or decrease. Because of the fluid nature of the radio environment, the noise (and hence the signal/noise ratio) is constantly changing. When the a noise increases, the probability that a frame transmission experiences an error will increase.
Because of the presence of a changing noise factor, many WLANs employ yet another mechanism intended to improve their performance. That mechanism is the ability to fragment frames.
As illustrated in FIG. 5, before transmission, a larger DATA frame may be divided into smaller DATA frames sent one at a time. The receiver must re-assemble the smaller DATA frames back into the original DATA frame. Each of the smaller DATA frames is called a DATA fragment. The reason that network throughput is improved when fragmenting is performed is that when the BER is high, a long DATA frame will have a greater probability of containing at least one error. In most WLAN systems, there is no recovery from the presence of even a single bit error, and hence, the entire DATA frame must be ignored, no ACK frame will be generated by the recipient, and the transmitter must assume that a collision has taken place and it will backoff and reschedule the DATA frame transmission attempt. The unsuccessful DATA frame transmission represents lost network bandwidth. In addition, it is likely that the long DATA frame may encounter a single bit error on successive attempts, and even more bandwidth is lost.
If a DATA frame is divided into smaller fragments, only one of the fragments will contain a single bit error, and only this fragment will need to be retransmitted. Therefore, the lost network bandwidth is substantially reduced.
In the case of DATA frame fragmentation, each DATA fragment sent by transmitting Station A is acknowledged by an ACK frame produced by receiving Station B. Each DATA fragment and ACK frame contain airtime reservation duration information, which allows the station sending the DATA frame fragments to prevent other stations from data transmission during the indicated airtime reservation interval.
The DATA frame fragmentation may be used together with the RTS/CTS exchange mechanism. The possible frame exchange illustrated in FIG. 5 may consist of the RTS frame acknowledged by the CTS frame, DATA fragment #1 acknowledged by the ACK frame, DATA fragment #2 acknowledged by the ACK frame, DATA fragment #3 acknowledged by the ACK frame, etc.
The total time required to transmit a fragmented DATA frame is greater than the time required to sent a single long DATA frame, because each DATA fragment contains headers and trailer representing its physical layer and its medium access control protocol layer. Moreover, each DATA fragment is individually acknowledged, and interframe spaces exist between each fragment and ACK frame.
However, if a long DATA frame had a reasonable probability of being retransmitted, then the total time required to perform the multiple transmission attempts of the single long DATA frame could be larger than the total time required for transmission of all of the shorter DATA fragments including the additional overhead, the additional ACK frames, and the interframe spaces, even if some of the DATA fragments were retransmitted.
A typical WLAN has the ability to set a fragmentation threshold equal to the minimum length of a DATA frame subject to fragmentation. Any DATA frame having length that exceeds this fragmentation threshold is divided into fragments having length less than the fragmentation threshold.
Thus, it would be desirable to dynamically adjust the RTS/CTS and fragmentation thresholds to provide the highest possible WLAN throughput for the current operating conditions.
Also, it would be desirable to monitor WLAN parameters used for adjusting the RTS/CTS and fragmentation thresholds to maximize the WLAN throughput for the current operating conditions.

System and method for monitoring performance of wireless LAN and dynamically adjusting its operating parameters


Described herein are architectures, platforms and methods for implementing a closed-loop tuner in a receiver circuitry of a portable device. For example, the closed-loop tuner is based upon a configured or an inherent local oscillator (LO) leakage power in the receiver circuitry of the portable device.

An increasing number of wireless communication standards as applied to a portable device and a trend towards ever smaller, slimmer and lighter portable devices may cause major design challenges for antenna or antennas. The antenna represents a category of components that may fundamentally differ from other components in the portable device. For example, the antenna may be configured to efficiently radiate in free space, whereas the other components are more or less isolated from their surroundings.
Actively tuned antennas may be seen as a key technology that enables antenna miniaturization in future mobile communication devices. For example, the actively tuned antennas may support multiple radio frequency (RF) bands and further supports performance optimization. Performance optimization may include antenna impedance measurements and adjustments for purposes of obtaining a matched impedance in a receiver circuitry of the portable device. The impedance matching, for example, may facilitate maximum power transfer between the antenna and the receiver circuitry of the portable device.

Method for closed-loop tuner in a receiver antenna


The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, inhibitors of apoptosis proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The estrogen receptor (ER) is a member of the nuclear hormone receptor family and functions as a ligand-activated transcription factor involved with the up and down regulation of gene expression. The natural hormone for the estrogen receptor is 17-beta-estradiol (E2) and closely related metabolites. Binding of estradiol to the estrogen receptor causes a dimerization of the receptor and the dimer in turn binds to estrogen response elements (ERE's) on DNA. The ER-DNA complex recruits other transcription factors responsible for the transcription of DNA downstream from the ERE into mRNA, which is eventually translated into protein. Alternatively, the interaction of ER with DNA may be indirect through the intermediacy of other transcription factors, most notably fos and jun. Since the expression of a large number of genes is regulated by the estrogen receptor and since the estrogen receptor is expressed in many cell types, modulation of the estrogen receptor through binding of either natural hormones or synthetic ER ligands can have profound effects on the physiology and pathophysiology of the organism.
A variety of diseases have their etiology and/or pathology mediated by the ER. Collectively these diseases are called estrogen-dependent diseases. Estrogens are critical for sexual development in females. In addition, estrogens play an important role in maintaining bone density, regulation of blood lipid levels, and appear to have neuroprotective effects. Consequently, decreased estrogen production in post-menopausal women is associated with a number of diseases such as osteoporosis, atherosclerosis, depression and cognitive disorders. Conversely, certain types of proliferative diseases such as breast and uterine cancer and endometriosis are stimulated by estrogens and therefore antiestrogens (i.e. estrogen antagonists) have utility in the prevention and treatment of these types of disorders.
There are two different forms of the estrogen receptor, usually referred to as α and β, each encoded by a separate gene (ESR1 and ESR2, respectively). Both ERs are widely expressed in different tissue types, but there are some notable differences in their expression patterns. The ERα is found in endometrium, breast cancer cells, ovarian stroma cells, and the hypothalamus. In males, ERα protein is found in the epithelium of the efferent ducts. The expression of the ERβ protein has been documented in kidney, brain, bone, heart, lungs, intestinal mucosa, prostate, and endothelial cells. Development therefore of selective ligands may therefore preserve the beneficial aspects of estrogen.
Breast cancer is the most common malignancy to affect women and the incidence of the disease is increasing worldwide. Estrogens, in particular, act as endocrine growth factors for at least one-third of breast cancers, and depriving the tumor of this stimulus is a recognized therapy for advanced disease in premenopausal women, this is achieved by the ablation of ovarian function through surgical, radio therapeutic, or medical means and, in postmenopausal women, by the use of aromatase inhibitors.
An alternative approach to estrogen withdrawal is to antagonise estrogen with antiestrogens. These are drugs that bind to and compete for estrogen receptors (ER) present in estrogen-responsive tissue. Conventional nonsteroidal antiestrogens, such as tamoxifen, compete efficiently for ER binding but their effectiveness is often limited by the partial agonism they display, which results in an incomplete blockade of estrogen-mediated activity. A specific or "pure" antiestrogen with high affinity for ER and without any agonist effect may have advantages over conventional nonsteroidal anti-estrogens in the treatment of estrogen-dependent disease. Fulvestrant is the first of a new class of potent pure anti-estrogens and is completely free of the partial agonist, estrogen-like activity, associated with currently available antiestrogens like tamoxifen.
As such, there is a need for other approaches to antagonise the ER receptor. One approach would be to develop selective ER down regulators or degraders that reduce ER expression at either the transcript or protein level.
Most small molecule drugs bind enzymes or receptors in tight and well-defined pockets. On the other hand, protein-protein interactions are notoriously difficult to target using small molecules due to their large contact surfaces and the shallow grooves or flat interfaces involved. E3 ubiquitin ligases (of which hundreds are known in humans) confer substrate specificity for ubiquitination, and therefore, are more attractive therapeutic targets than general proteasome inhibitors due to their specificity for certain protein substrates. The development of ligands of E3 ligases has proven challenging, in part due to the fact that they must disrupt protein-protein interactions. However, recent developments have provided specific ligands which bind to these ligases. For example, since the discovery of nutlins, the first small molecule E3 ligase inhibitors, additional compounds have been reported that target E3 ligases but the field remains underdeveloped. For example, since the discovery of Nutlins, the first small molecule E3 ligase mouse double minute 2 homolog (MDM2) inhibitors, additional compounds have been reported that target MDM2 (i.e., human double minute 2 or HDM2) E3 ligases (J. Di, et al. Current Cancer Drug Targets (2011), 11(8), 987-994).
Tumor suppressor gene p53 plays an important role in cell growth arrest and apoptosis in response to DNA damage or stress (A. Vazquez, et al. Nat. Rev. Drug. Dis. (2008), 7, 979-982), and inactivation of p53 has been suggested as one of the major pathway for tumor cell survival (A. J. Levine, et al. Nature (2000), 408, 307-310). In cancer patients, about 50% were found with p53 mutation (M. Hollstein, et al. Science (1991), 233, 49-53), while patients with wild type p53 were often found p53 down regulation by MDM2 through the protein-protein interaction of p53 and MDM2 (P. Chene, et al. Nat. Rev. Cancer (2003), 3, 102-109). Under normal cell condition without oncogenic stress signal, MDM2 keeps p53 at low concentration. In response to DNA damage or cellular stress, p53 level increases, and that also causes increase in MDM2 due to the feedback loop from p53/MDM2 auto regulatory system. In other words, p53 regulates MDM2 at the transcription level, and MDM2 regulates p53 at its activity level (A. J. Levine, et al. Genes Dev. (1993) 7, 1126-1132).
Several mechanisms can explain p53 down regulation by MDM2. First, MDM2 binds to N-terminal domain of p53 and blocks expression of p53-responsive genes (J. Momand, et al. Cell (1992), 69, 1237-1245). Second, MDM2 shuttles p53 from nucleus to cytoplasm to facilitate proteolytic degradation (J. Roth, et al. EMBO J (1998), 17, 554-564). Lastly, MDM2 carries intrinsic E3 ligase activity of conjugating ubiquitin to p53 for degradation through ubiquitin-dependent 26s proteasome system (UPS) (Y. Haupt, et al. Nature (1997) 387, 296-299). As such, because MDM2 functions as E3 ligase, recruiting MDM2 to a disease causing protein and effectuating its ubiquitination and degradation is an approach of high interest for drug discovery.
One E3 ligase with exciting therapeutic potential is the von Hippel-Lindau (VHL) tumor suppressor, the substrate recognition subunit of the E3 ligase complex VCB, which also consists of elongins B and C, Cul2 and Rbx1. The primary substrate of VHL is Hypoxia Inducible Factor 1α (HIF-1α), a transcription factor that upregulates genes such as the pro-angiogenic growth factor VEGF and the red blood cell inducing cytokine erythropoietin in response to low oxygen levels. The first small molecule ligands of Von Hippel Lindau (VHL) to the substrate recognition subunit of the E3 ligase were generated, and crystal structures were obtained confirming that the compound mimics the binding mode of the transcription factor HIF-1α, the major substrate of VHL.
Cereblon is a protein that in humans is encoded by the CRBN gene. CRBN orthologs are highly conserved from plants to humans, which underscores its physiological importance. Cereblon forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1), Cullin-4A (CUL4A), and regulator of cullins 1 (ROC1). This complex ubiquitinates a number of other proteins. Through a mechanism which has not been completely elucidated, cereblon ubquitination of target proteins results in increased levels of fibroblast growth factor 8 (FGF8) and fibroblast growth factor 10 (FGF10). FGF8 in turn regulates a number of developmental processes, such as limb and auditory vesicle formation. The net result is that this ubiquitin ligase complex is important for limb outgrowth in embryos. In the absence of cereblon, DDB1 forms a complex with DDB2 that functions as a DNA damage-binding protein.
Inhibitors of Apotosis Proteins (IAPs) are a protein family involved in suppressing apoptosis, i.e. cell death. The human IAP family includes 8 members, and numerous other organisms contain IAP homologs. IAPs contain an E3 ligase specific domain and baculoviral IAP repeat (BIR) domains that recognize substrates, and promote their ubiquitination. IAPs promote ubiquitination and can directly bind and inhibit caspases. Caspases are proteases (e.g. caspase-3, caspase-7 and caspace-9) that implement apoptosis. As such, through the binding of caspases, IAPs inhibit cell death. However, pro-apoptotic stimuli can result in the release of mitochondrial proteins DIABLO (also known as second mitrochondria-derived activator of caspases or SMAC) and HTRA2 (also known as Omi). Binding of DIABLO and HTRA2 appears to block IAP activity.
SMAC interacts with essentially all known IAPs including XIAP, c-IAP1, c-IAP2, NIL-IAP, Bruce, and survivin. The first four amino acids (AVPI) of mature SMAC bind to a portion of IAPs, which is believed to be essential for blocking the anti-apoptotic effects of IAPs.
Bifunctional compounds such as those that are described in U.S. Patent Application Publication Nos. 2015-0291562 and 2014-0356322 (incorporated herein by reference), function to recruit endogenous proteins to an E3 ubiquiuin ligase for degradation. In particular, the publications describe bifunctional or proteolysis targeting chimeric (PROTAC) compounds, which find utility as modulators of targeted ubiquitination of a variety of polypeptides and other proteins, which are then degraded and/or otherwise inhibited by the bifunctional compounds.
The present disclosure identifies compounds that are capable of inhibiting estrogen receptor function, including compounds which degrade the estrogen receptor.

This patent is subject to a terminal disclaimer.

Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders


A passive keyless entry system is disclosed that is specifically adapted for use with automotive vehicles. The system is designed to automatically unlock the vehicle as the operator approaches the vehicle. The system is further designed to automatically lock the vehicle as the operator, carrying the beacon, moves away from the vehicle. The system includes a portable beacon that is carried by the operator, a receiver/controller located in the vehicle, and an antenna connected to the receiver/controller for receiving the encoded transmission from the beacon. The beacon includes a motion sensor to conserve battery life when the beacon is stationary. Transmission between the beacon and the receiver/controller is characterized by a magnetically coupled radio frequency signal embodying differential phase encoded data with error correction coding of the data to enhance noise immunity and signal discrimination.

The present invention relates to electronic keyless entry systems and in particular to a passive keyless entry system that is particularly adapted for use with automotive vehicles.
Automotive keyless entry systems, when first introduced, typically included a numerical keypad located on the exterior door panel of the vehicle. The operator entered a unique multiple digit code on the keypad to automatically unlock or lock the vehicle. Recently, more sophisticated keyless entry systems for vehicles have been proposed which use a portable remote transmitter that is carried by the operator and a receiver located in the vehicle that is adapted to unlock the vehicle in response to the detection of a coded radio frequency signal or a coded optical signal received from the transmitter. Such systems require that the operator actuate a button or switch on the transmitter to initiate the transmission, similar to the operation of a conventional automatic garage door opener, in order to conserve battery life and prevent inadvertent actuation.
While more convenient to operate than the keypad-type keyless entry systems, the latter transmitter/receiver-type systems nonetheless require that the operator physically locate the transmitter and actuate a button to unlock the vehicle. Hence, the convenience provided by such a system versus a conventional key and lock arrangement is not substantially improved.
In addition, while other types of "keyless" entry systems are known and presently used in other applications, there systems for various reasons are generally not suitable for automotive use. This would include systems employing magnetic card readers, interrogation/transponder-type systems, and conventional automatic garage door openers. A magnetic card-type system is probably adaptable to automotive use, but provides little added benefit to justify the expense. Interrogator/transponder-type systems, though adaptable to operate in a totally passive manner, are more complex and therefore more expensive, and present a power consumption problem as the interrogator therefore must be on and interrogating at all times. In addition, the transponder in such systems must be capable of receiving as well as transmitting data, thus adding to cost. Lastly, automatic garage door systems, while appearing to employ similar technology have substantially different operating requirements which result in significantly different circuit designs. In particular, an automotive keyless entry system must possess a level of noise immunity and signal discrimination that is substantially greater than that required for an automatic garage door opener. This is due to several factors including the many different environments in which vehicles may be located, the greater number of vehicles that may be equipped with comparable systems, and the fact that large numbers of vehicles are frequently located within close proximity to one another, such as in parking lots. In addition, automatic garage door systems require that the operator actuate a transmitter, and therefore are not totally passive. Also, garage door opener-type system have a substantial range and therefore can potentially activate a function, such as unlocking the trunk of the vehicle, when the operator is some distance away from the vehicle and unaware the trunk has been opened.
Accordingly, it is the primary object of the present invention to provide a totally passive keyless entry system that is especially adapted for use with automotive vehicles.
It is also an object of the present invention to provide an automotive keyless entry system that is adapted to automatically unlock the vehicle as the operator approaches the vehicle.
In addition, it is an object of the present invention to provide a passive keyless entry system having a beacon-transmitter that is extremely small in size and includes a motion sensing switch that automatically activates the transmitter in the beacon whenever movement of the beacon is sensed.
It is a further object of the present invention to provide a passive keyless entry system that employs electronic circuitry which permits the system to function in the micropower range while in its quiescent state.
Additionally, it is an object of the present invention to provide a passive keyless entry system having an acceptable operating range between the beacon and receiver while providing a projected beacon battery life in excess of one year.
Further, it is an object of the present invention to provide a passive keyless entry system that employs signal transmission and coding techniques which provide a high level of noise immunity and signal discrimination.
It is also an object of the present invention to provide a passive keyless entry system that is reliable and yet is relatively inexpensive to manufacture.
In general, the passive keyless entry system according to the present invention comprises three basic components: a transmitter or beacon, a receiver/controller, and a receiving antenna. The beacon, which is small enough to be attached to keychain, is carried by the operator and incorporates a motion sensor that is used to energize the transmitter portion of the beacon. The transmitter in the beacon is adapted to emit a coded radio frequency signal that contains both identification and function information and an error correction code. The beacon is designed to continue to transmit repeatedly its coded signal until no motion is detected for a predetermined period of time. Thus, the motion sensor serves to promote beacon battery life and enables the present system to function in a totally passive manner.
The receiving antenna comprises a simple coil of wire, wound to be sensitive at the transmitted frequency of the beacon. The antenna is located at a position on the vehicle to optimize the performance of the system. It has been found desirable to adapt the system so that the receiver/controller is responsive to the signal from the beacon when the beacon comes within 3-6 feet of the vehicle.
The receiver/controller is mounted inside the vehicle and is adapted to operate on the vehicle's 12 volt negative ground battery. Upon receipt of a radio frequency signal from the antenna, the receiver/controller is adapted to process the coded radio frequency signal and evaluate the serial data contained therein. If the signal is determined to be valid, the receiver/controller automatically unlocks the driver's-side vehicle door.
Optionally, the beacon may be provided with function switches which, when depressed by the operator, change the function code contained in the radio frequency signal, thus directing the receiver/controller to open the vehicle trunk and/or perform other functions. In addition, the receiver/controller in the present system is adapted to automatically lock the vehicle doors when the operator leaves the vehicle and carries the beacon out of range of the receiver/controller, assuming the proper status of the ignition and doorjamb switches.
Additional objects and advantages of the present invention will become apparent upon reading the following description of the preferred embodiment of the present invention which makes reference to the drawings in which:


This patent discloses compositions and methods of use thereof to normalize the blood glucose levels of patients with type 2 diabetes. It relates particularly to a plasmid comprising a chicken β actin promoter and enhancer; a modified GLP-1 (7-37) cDNA (pβGLP1), carrying a furin cleavage site, which is constructed and delivered into a cell for the expression of active GLP-1.

Type 2 diabetes is characterized by hyperglycemia, insulin resistance, absolute or relative insulin deficiency, hyperglucagonemia, and increased hepatic glucose production. Although many treatment trials for type 2 diabetes have been held, there is still no definitive treatment for the disease. Insulin secretion is modulated by incretin hormones which are produced by the intestinal enteroendocrine cells and constitute one arm of the enteroinsular axis. There are two major incretins. One is glucose-dependent insulinotrophic polypepetide (GIP) and the other is glucagon like peptide-1 (GLP-1). These two incretin hormones account for 20% and 80% respectively, of the intestinal incretin effect. Holst J J: Glucagonlike peptide 1: a newly discovered gastrointestinal hormone. Gastroenterology 107:1848-1855, 1994 GIP, but not GLP-1, tends to lose its actions in patients with type 2 diabetes. Nauck M A, Heimesaat M M, Orskov C, Holst J J, Ebert R, Creutzfeldt W: Preserved incretin activity of glucagons-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 91:301-307, 1993. GLP-1 was recently used for the treatment of type 2 diabetes. See U.S. Pat. Nos. 5,614,492; 5,545,618 and 6,048,724 which are incorporated herein by reference.
GLP-1, produced by intestinal L-cells, stimulates glucose induced insulin secretion and inhibits glucagon secretion. GLP-1 has two active forms, GLP-1 (7-36) amide and GLP-1 (7-37), that are products of posttranslational processing of proglucagon in mammalian intestinal cells. The active forms of GLP-1 are degradable in the plasma by the action of dipeptidyl peptidase IV. During degradation, the active form of GLP1(7-36 or 7-37) loses its N-terminal amino acid residues and results in an inactive form of GLP-1 (9-36 amide). Therefore, the active forms of GLP-1 have very short plasma half lives (about 5 minutes) and metabolic clearance rates. Fehmann H C et. al: Endocr Rev 16:390-410, 1995 There have been several studies on administration of GLP-1 to type 2 diabetic patients which have shown that GLP-1 effectively reduces hyperglycemia in type 2 diabetic patients. Nauck et. al. J Clin Invest 91:301-307, 1993; Nauck et. A1: Diabetes Care 21:1925-1931, 1998; and Rachman J et. al Diabetologia 40:205-211, 1997. However, it is very difficult to consistently deliver the active form of GLP-1 because of its short half-life. Even when using the long acting form of GLP-1, exendin-4, twice daily administration is required to maintain a normal glucose level. Szayna M, Doyle M E, Betkey J A, Holloway H W, Spencer R G, Greig N H, Egan J M: Exendin-4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology 141:1936-1941, 2000
Gene therapy is generally considered as a promising approach, not only for the treatment of diseases with genetic defects, but also in the development of strategies for treatment and prevention of chronic diseases such as cancer, cardiovascular disease and diabetes. However, nucleic acids, as well as other polyanionic substances are rapidly degraded by nucleases and exhibit poor cellular uptake when delivered in aqueous solutions. Since early efforts to identify methods for delivery of nucleic acids in tissue culture cells in the mid 1950's, steady progress has been made towards improving delivery of functional DNA, RNA, and antisense oligonucleotides in vitro and in vivo.
The gene carriers used so far include viral systems (retroviruses, adenoviruses, adeno-associated viruses, or herpes simplex viruses) or nonviral systems (liposomes, polymers, peptides, calcium phosphate precipitation and electroporation). Viral vectors have been shown to have high transfection efficiency when compared to non-viral vectors, but due to several drawbacks, such as targeting only dividing cells, random DNA insertion, their low capacity for carrying large sized therapeutic genes, risk of replication, and possible host immune reaction, their use in vivo is severely limited.
An ideal transfection reagent should exhibit a high level of transfection activity without the need for any mechanical or physical manipulation of cells or tissues. The reagent should be non-toxic, or minimally toxic, at the effective dose. It should also be biodegradable in order to avoid any long term adverse side effects on the treated cells. When gene carriers are used for delivery of nucleic acids in vivo, it is essential that the gene carriers themselves be nontoxic and that they degrade into non-toxic products. To minimize the toxicity of the intact gene carrier and its degradation products, the design of gene carriers needs to be based on naturally occurring metabolites.
As compared to viral gene carriers, there are several advantages to the use of non-viral based gene therapies, including their relative safety and low cost of manufacture. There are several polymeric materials currently being investigated for use as gene carriers, of which poly-L-lysine (PLL) is the most popular, but few of them are biodegradable. In general, polycationic polymers are known to be toxic and the PLL backbone is barely degraded under physiological conditions. It remains in cells and tissues and causes an undesirably high toxicity. In addition, like most cationic polymers, PLL/DNA complexes have drawbacks including precipitation as insoluble particles and the tendency to aggregate into larger complexes under physiological conditions.
In view of the foregoing, there is a need for the development of a composition and a gene therapy method for the treatment of type-2 diabetes wherein the gene carrier is soluble and biodegradable, meaning that the non-viral polymer gene carrier can break down or degrade within the body to non-toxic components after the genes have been delivered.

GLP-1 gene delivery for the treatment of type 2 diabetes


A system and method are provided for streak detection in an image scanning system. The disclosed systems and methods may be particularly applicable to constant velocity transport (CVT) digital scanning systems by comparing multiple scans of a simply-produced test pattern passed over the sensor in multiple orientations. Image information from each pass of the test pattern through the image scanning system may be compared to image information from other passes in which the orientation of the test pattern is changes. The data may be normalized and compared to discern image quality defects introduced by the image scanning system including image defects presented in the form of streaks in an output image based on the scanned data. Cumulative data regarding detected image defects and defect correction measures applied in the image scanning system may be collected and stored for a user to access.

1. Field of Disclosed Subject Matter
This disclosure relates to systems and methods for implementing a simple scheme of intelligent streak detection in constant velocity transport (CVT) image array scanning devices.
2. Related Art
A variety of systems and methods are conventionally used in digital scanning. Typical scanning systems employ full width imaging arrays that are stationary with respect to the devices in which they are housed, or which are caused to move relative to a stationary substrate to be scanned. In such systems, constant or variable rate movement is effected between the image to be scanned and the imaging array. The imaging array takes a rapidly sequential series of pictures of the image medium that is presented to be scanned as the relative movement is effected. The scanning system then digitizes the scanned image for storage and/or reproduction.
Typical full width imaging arrays include one or more rows of individually-pixilated sensors, each discrete pixel sensor being disposed to take the rapidly sequential series of digital images of the column of the scanned image which is presented within that pixel sensor's field of view.
A difficulty in such systems where the imaging point is stationary and the paper is moved past the sensor is that any imperfection in the field of view of the imaging array over a single pixel sensor or over a group of pixel sensors is repeatedly scanned and digitized as a dark or light spot in the scanned image. Relatedly, a defective sensor at a given pixel sensor location, in its failure to be able to scan image data to be digitized, will likewise potentially be digitized as a dark or light spot. The result is that the reproduced output image from the device can include a streak or line corresponding with the position of the imperfection or the defective sensor as the image of the dark spot is repeatedly reproduced to form the streak or line. Unlike a single pixel in the image being affected when the sensor array moves across a stationary image giving just a single or small group defect, a streak or line across the entire image is much more visible and objectionable.
Various exemplary scanning devices employ stationary what those of skill in the art recognize as Full-Width Imager Arrays (FWA) or linear Charge-Coupled Device (CCD) arrays. In such systems in which the imaging arrays are stationary, the arrays are often separated from the image medium or substrate to be scanned by a platen glass, or other transparent surface or lens, overlying the imaging array. Various exemplary methods are employed in these devices to move the image medium or substrate to be scanned across the transparent surface. One such exemplary method, commonly referred to as constant velocity transport (CVT) scanning, employs a belt, drum or other like device to move the image medium or substrate to be scanned across a linear sensor, such as, for example, an imaging array of individually pixilated sensors, and FWA or a CCD array.
As briefly discussed above, these imaging array scanning systems, including, for example, CVT scanning devices, may experience difficulties when dirt particles, stray paper fibers, contaminants, imperfections, obstructions and/or other objects, generally referred to throughout this disclosure as "obstructions," appear on the transparent surface, or otherwise in the field of view of the imaging arrays. Such obstructions remaining stationary on the transparent surface, or otherwise in the field of view over the imaging array sensors, are repeatedly imaged and digitized as though it were part of the scanned image. The result is that the image reproduced by the exemplary CVT scanning device will include a streak or a line on the output image.
A variety of systems and methods are employed to ensure that a platen glass or other overlying transparent surface is kept free of obstructions. These systems and methods are directed to improving reproduced image quality by keeping the transparent surface obstruction free. Often the methods are manual, requiring visual inspection, and manual cleaning, of an exemplary system's platen glass or transparent surface. These methods can be mechanically automated in that a wiper blade, or the like, may be employed to routinely, automatically "wipe down" the platen glass or transparent surface. While limitedly effective in removing surface contaminants from a transparent surface, none of these methods account for obstructions or imperfections actually on an individual sensor, or for the potential of a defective sensor, providing the same sort of false scanned image data as an obstruction in the field of view of the array would produce on the overlying transparent surface. Also, obstructions can be on the underside of the glass or other hard to clean areas.
Other systems and methods for improving reproduced output image quality include automated system steps that review the reproduced output image in comparison with the scanned image in order to detect, and optionally compensate for, differences before the reproduced image is ultimately displayed, or transferred to an image receiving substrate for output. One complication with such an approach is that it is difficult to determine whether a line, which is digitized and reproduced as part of the output image, is actually part of the image that was scanned or whether it was produced because the imaging array repeatedly scanned an imperfection stationary in its field of view, or otherwise input false or non-image data from one or a series of defective sensors, and then reproduced the non-image data as a line or streak in the reproduced image.
Difficulties in detecting obstructions are particularly acute as elements of foreign matter which commonly produce streaks in conventional and exemplary CVT scanning systems are extremely small. Any "deposited" obstruction on the platen glass large enough to be detected by simple visual inspection is, most often, large enough to be picked up by the scanned image medium as the scanned image medium is moved across the platen glass or other overlying transparent surface. The obstruction is moved out of the way as being swept away with the movement of the image medium being scanned. Obstructions that are very small, on the other hand, have a greater tendency to adhere to the transparent surface and to resist being swept away by the movement of the scanned image medium.
Among other systems and methods employed to remove streaks from digital images produced in CVT scanning systems, software algorithms exist that review stored image data representing the scanned image in its entirety. Such software algorithms apply image data revisions before reproducing a digitally scanned image in an output display device. A disadvantage in such methods is that full scanned image review algorithms require the scanning of the entire image and storage of the data representing the entire scanned image before reviewing the data and applying necessary image data revisions. In high speed scanning applications, this requirement to record an entire image and then review and revise that image before reproducing the image has the potential to slow the scanning and reproduction process to an unacceptable level.
Despite the processing overhead, such systems are available. U.S. Pat. Nos. 6,393,161 and 6,522,431 describe variations in software systems for minimizing image defects in a hard-copy input scanner. These patents, which are commonly assigned to the Assignee of this application, commonly disclose scanners in which an image-bearing sheet is moved over a relatively narrow window, through which the image is recorded by a photosensitive chip. The patents specify the problem as involving conditions when "a spot of dirt attaches to the window, a streak results in the image data." See Abstracts. In one instance, this streaking problem is addressed by detecting image data consistent with such a streak, and applying a suitable correction algorithm to the image data. The suitable correction algorithm is described as being chosen based on the thickness of the streak and the nature of the image data. In another instance, the streaking problem is addressed by having the scan line viewed by the photosensitive chip move a small distance within the window of the document handler, so that any spot on the window will not be repeatedly exposed by the photosensitive chip.
Separately, U.S. Pat. No. 7,528,997 discloses various methods for detecting streaks, such as streaks caused by imperfections in scanning systems that employ linear imaging arrays where the scanned image is sampled a minimum of two times by separate positionally discrete rows or sets of sensors in the imaging array. The at least two samples, though very close together, correspond to separate discrete linear scan locations. The scanned image data obtained from each of the two discrete rows is then normalized to adjust for different filtering capabilities, particularly color filtering in multi-spectral imaging arrays, in the discrete rows of the imaging array. The normalized scanned input image data from at least two discrete rows is then compared on a one-for-one basis in an attempt to detect imperfections overlying one or more rows of sensors in the imaging array.
U.S. Pat. No. 7,359,093 discloses systems and methods for streak detection in image array scanning using overdetermined scanners and column filtering. This streak detection method and system in a fixed imaging array digital scanning system obtains image data from each of the plurality of rows in the at least one full color spectrum channel set of rows of positionally discrete sensors and integrates this data to produce an estimate of image data recorded by at least one clear channel row of positionally discrete sensors. A clear channel error signal is generated by the comparison to alert the operator to the presence of non-image data. The clear channel error signal may be refined to through a low pass column filtering process in order to filter out potentially erroneous clear channel error resulting from thermal, mechanical or other noise sources unrelated to image scanning Stationary obstructions in the field of view of the imaging array, or defects in one or more sensors in the imaging array, are detected through this comparison which would otherwise appear repeatedly reproduced as streaks or lines in the reproduced output image.
Common to each of the above four patented methods of streak detection, isolation and/or correction are the complexity, computing overhead, additional expense, processing time and potential to miss the obstruction or defect.

Systems and methods for streak detection in image array scanning


In order to automatically determine colors representing characteristics of an image, a color table including a plurality of colors is provided, and a color group table including color groups are obtained by classifying the colors included in the color table according to a first standard. Colors included in an image are sampled in image data to be processed based on an image data of the image. Then, a first frequency is counted for each color in the sampled colors belonging to the color table based on the result of the sampling, and a second frequency is counted by summing the first frequencies for the colors included in a color group for each of the color groups belonging to the color group table. Characteristic colors of the image are determined according to the first and second frequencies.

1. Field of the Invention
The present invention relates to an apparatus for automatically deciding colors representing characteristics of an image.
2. Description of Prior Art
An image database system is used to store and manage a large amount of image data. In such an image database system, retrieve keys are added to each image data, and a desired image data can be retrieved by using the keys. In addition to a word, an icon or the like, a color representing characteristics of an image is used as the keys. The color means a color specified for example with hue, value and chroma (HLS space).
Previously, colors for the keys representing characteristics of images are decided manually by evaluating each image with eyes by an operator. This work for the evaluation is a large burden when a large amount of image data are dealt for an image database. Further, because the evaluation depends on judgement of the operators, the standards for deciding the colors representing characteristics of images are spread in the operators. Therefore, when such keys are used, it is afraid that proper retrieving result cannot be obtained.
In order to solve the problem, it is proposed to automatically decide colors representing characteristics of an image (hereinafter referred to as "characteristic colors"). For example, in Japanese Patent laid open Publication 5-274372/1993, all the colors in an image are classified by several representative colors, and deviations relative to the entire image are calculated for each representative color based on the frequencies thereof, and the representative color having large (or small) deviation is determined as a characteristic color of the image.
However, because all the colors in the image are classified in several representative colors and characteristic colors are selected among them, this process has a problem that if the number of representative colors is small, the number of characteristic colors to be decided is limited. On the other hand, if the process increases the number of representative colors, then the process will increase the number of characteristic colors. Since the process can utilize more characteristic colors, the process will select only colors that are similar to each other and that have large areas.

Apparatus for automatically deciding characteristic colors of an image


A plasma arc torch that includes a torch body having a nozzle mounted relative to a composite electrode in the body to define a plasma chamber. The torch body includes a plasma flow path for directing a plasma gas to the plasma chamber in which a plasma arc is formed. The nozzle includes a hollow, body portion and a substantially solid, head portion defining an exit orifice. The composite electrode can be made of a metallic material (e.g., silver) with high thermal conductivity in the forward portion electrode body adjacent the emitting surface, and the aft portion of the electrode body is made of a second low cost, metallic material with good thermal and electrical conductivity. This composite electrode configuration produces an electrode with reduced electrode wear or pitting comparable to a silver electrode, for a price comparable to that of a copper electrode.

Plasma arc torches are widely used in the cutting or marking of metallic materials. A plasma torch generally includes an electrode mounted therein, a nozzle with a central exit orifice mounted within a torch body, electrical connections, passages for cooling and arc control fluids, a swirl ring to control fluid flow patterns in the plasma chamber formed between the electrode and nozzle, and a power supply. The torch produces a plasma arc, which is a constricted ionized jet of a plasma gas with high temperature and high momentum. Gases used in the torch can be non-reactive (e.g. argon or nitrogen), or reactive (e.g. oxygen or air).
In operation, a pilot arc is first generated between the electrode (cathode) and the nozzle (anode). Generation of the pilot arc may be by means of a high frequency, high voltage signal coupled to a DC power supply and the torch or any of a variety of contact starting methods.
One known configuration of an electrode for a plasma arc torch includes an emitting insert (e.g., hafnium) which is press fit into a bore in the electrode. An objective in electrode design is to transfer heat from the hafnium insert and into a cooling medium, which is usually water. Another objective is to control arc root attachment to minimize erosion caused by undesirable arc root attachment to the electrode instead of the hafnium insert.
Electrodes for plasma arc torches are commonly made from copper. Copper is a low cost material that offers good thermal and electrical conductivity. Electrodes for plasma arc torches can also be made from silver. While silver electrodes provide excellent heat transfer characteristics, they tend to be very expensive and not cost effective to use. Copper electrodes are cost effective, but do not have the superior heat transfer characteristics of a silver electrode and thus have a shorter electrode life than silver electrodes.
Several companies manufacture silver and silver/copper composite electrodes using a variety of manufacturing techniques including brazing, soldering, swaging, press fitting and other methods. One company has developed a vacuum brazed copper/silver composite design with a through-hole hafnium insert. Another company has developed a press-fitted silver annulus design with a blind hole hafnium insert. Another company has developed a swaged silver annulus design in a copper holder with copper on the front portion. Another company has developed coined silver electrode design. However, these methods of manufacturing silver/copper electrodes do not produce a sufficiently high-strength joint at the silver/copper interface. In addition, these manufacturing methods result in electrodes that can leak cooling fluid at the silver/copper interface. More significantly, these silver/composite electrodes do not offer the heat transfer characteristics of an all silver electrode.

Composite electrode for a plasma arc torch


A fast modular port switching device is described. The device can be used with an optical microscope to facilitate using multiple devices with the microscope. The port switching is done with a galvanometer for switching very fast. The device is modular so it can be combined with any number of similar devices for building a complex, multi-modal imaging system. Also described is the combination of a port switcher with automated spherical aberration correction. Even further described is a similar device where the outputs are recombined, thus making the device a fast filter switcher.

Modern digital microscopy is more and more multi-modal. More frequently there are found multiple imaging devices and specialized illumination devices. For example, it is not uncommon for a light microscope to be capable of wide-field imaging as well as optical sectioning. Lasers, detectors, scanners, and other devices are now added in ever increasing numbers to a single system. The benefit is that a single specimen can be analyzed in many different ways to increase the amount of information collected. Modern motorized microscopes often are equipped with multiple documentation ports to accommodate multiple devices. These documentation ports are automated and can be switched between with the controlling computer. Currently these devices take several seconds to perform a switch. In many cases this is too slow to see transitory signals. Switching times becomes important for multi-modal systems.
Modern microscopy also takes advantage of high NA (Numerical Aperture) objectives and high resolution imaging. Spherical aberration limits the use of such objectives to only ideal imaging situations. A separate patent application, "Spherical Aberration Correction for an Optical Microscope using a Moving Infinity-Conjugate Relay," U.S. patent application Ser. No. 12/887,869, filed 22 Sep. 2010, which is incorporated herein by reference in its entirety, describes means for correcting spherical aberration.
In fluorescence microscopes, it is also more common to perform multi-channel imaging, meaning that fluorophores of different colors are sequentially imaged. In multi-channel imaging, a common method of separating the colors is to move different color filters into the optical pathway. During rapid acquisition, the time for the filter to change is often the rate limiting step.

Fast, modular port switcher for an optical microscope using a galvanometer


A charge coupled device is provided with: an output gate; a main CCD region operated in response to a set of clock signals; and an output region positioned between the output gate and the main CCD region and designed to transfer electric charges received from the main CCD region to the output gate. The main CCD region includes first and second transfer electrodes. The output region includes third and fourth transfer electrodes receiving clock signals which are phase-reversed from each other. The set of clock signals received by the main CCD region and the clock signals received by the output region are outputted from different driver circuits.

1. Field of the Invention
The present invention relates to a solid-state image sensing device, more particularly, to a solid-state image sensing device that incorporates a CCD (charge coupled device).
2. Description of the Related Art
The advance of the semiconductor technology enhances the use of solid-state image sensing devices, which receive light on the light receiving surface from a target body through an optical system typically including a lens and so forth, and photoelectrically convert the intensity of the received light into the corresponding amounts of electric charges to thereby generate electrical signals. A commercially-used solid-state image sensing device usually includes a CCD (charge coupled device). The advance in the fine processing technology of the semiconductor device allows manufacturing a solid-state image sensing device with an increased pixel density, that is, with an improved fineness.
When the solid-state image sensing device converts an image into an electric signal, the CCD is used to transfer electric charges received from light sensitive devices to a circuit that generates the electric signal in response to the amount of the electric charges.
A typical CCD within a solid-state image sensing device is designed to transfer electric charges from light sensitive devices in response to a set of clock signals received from a clock generator circuit. In general, a solid-state image sensing devices uses a pair of clock signals (which may denoted by Φ1 and Φ2, hereinafter) for operating a horizontal CCD that transfers electric charges horizontally, as disclosed in Japanese Laid-Open Patent Application No. 2001-68660.
FIG. 1 discloses the structure of the solid-state image sensing device disclosed in this application. The disclosed solid-state image sensing device incorporates a CCD, denoted by the numeral 100, which is provided with: a plurality of charge transfer electrode pairs 110; first and second clock signal lines 101 and 102 feeding first and second clock signals Φ1 and Φ2, respectively, to the charge transfer electrode pairs 110; an output stage electrode pair 113, a third clock signal line feeding a third clock signal Φ1L to the output stage electrode pair 113; a pair of output gates 104; a floating diffusion 105; an output circuit 106; and a reset gate 107. It should be noted that the charge transfer electrode pairs 110 each consist of first and second polysilicon electrodes 111 and 112. In the CCD 100, the charge transfer electrode pairs 110 receiving the first clock signal Φ1 and the charge transfer electrode pairs 110 receiving the first clock signal Φ2 are alternately arranged.
The floating diffusion 105 is a diffusion layer used for charge detection. Signal charges transferred over an N-well are transferred to the floating diffusion 105 through the output gates 104. The output gates 104 receive a pair of fixed output gate voltages (VOG1 and VOG2), respectively, as described later. The reset gate 107 is used to periodically reset the voltage level of the floating diffusion 105; the reset gate 107 resets the voltage level of the floating diffusion 105 to the voltage level of the reset drain in response to a reset pulse signal ΦR. The output circuit 106 generates an output signal in response to the voltage level of the floating diffusion 105. As shown in FIG. 1, the output stage electrode pair 113 is positioned at the final stage of the charge transfer device transferring the electric charges to the floating diffusion 105 within the CCD 100. The output stage electrode pair 113 forwards the electric charges transferred thereto to the output gates 104 in response to third clock signal Φ1L.
FIG. 2 is a sectional view illustrating a structure of the CCD 100 on the C-C′ section of FIG. 1. The CCD 100 is provided with a P-well formed within an n-type semiconductor substrate and an N-well formed on the P-well. The N-well is used to accumulate and transfer electric charges. Storage regions (or non-barriered regions) are positioned under the first polysilicon electrodes 111 across gate dielectrics, and barrier regions are formed under the second polysilicon electrodes 112 across gate dielectrics through ion implantation of p-type impurities (such as boron ions) to provides voltage level differences within the transfer channel under the same charge transfer electrode pair 110. The floating diffusion 105, which is used for charge detection, incorporates a pn junction between the P-well and the N-well, positioned between the output gates 104 and the reset gate 107.
As described above, the output stage electrode pair 113 receives the third clock signal Φ1L. One of the output gates 104 (which is referred to as the first output gate electrode, hereinafter) receives the first output gate voltage VOG1, while the other of the output gates 104 (which is referred to as the second output gate electrode, hereinafter) receives the second output gate voltage VOG2. The reset gate 107 receives the reset pulse signal ΦR, and the reset drain 108 is biased to a reset drain voltage level VRD. It should be noted that the first output gate voltage VOG1, the second output gate voltage VOG2, and the reset drain voltage level VRD are fixed voltages levels.
FIG. 3 is a timing chart illustrating waveforms of signals fed to the CCD 100. The first to third clock signals Φ1, Φ2 and Φ1L and the reset pulse signal ΦR are voltage signals with signal levels changing on the time scale. FIGS. 3(a) to 3(d) illustrate the waveforms of first, second, third clock signals Φ1, Φ2 and Φ1L and the reset pulse signal ΦR, respectively. The "high" and "low" levels of the first clock signal Φ1 are denoted in FIG. 3(a) as "V1H", "V1L", respectively, and the "high" and "low" levels of the second clock signal Φ2 are denoted in FIG. 3(b) as "V2H", "V2L", respectively. Correspondingly, the "high" and "low" levels of the third clock signal Φ1L are denoted in FIG. 3(c) as "V3H", "V3L", respectively, and the "high" and "low" levels of the reset pulse signal ΦR are denoted in FIG. 3(d) as "V4H", "V4L", respectively, In the time period from the time t1 to t4, as shown in FIG. 3(a), the first clock signal Φ1 is pulled down from the voltage level V1H to the voltage level V1L, and then pulled up to the voltage level V1H. In the meantime, the second clock signal Φ2 is pulled up from the voltage level V2L to the voltage level V2H, and then pulled down to the voltage level V2L, while the third clock signal Φ1L is pulled down from the voltage level V3H to the voltage level V3L, and then pulled up to the voltage level V3H. The reset pulse signal ΦR is pulled up at the time t3.
FIG. 4 illustrates the charge transfer in the time period from the time t1 to t4. FIG. 4(a) illustrates the state of electric charges accumulated in the N-well at the time t1, while FIG. 4(b) illustrates the state of electric charges at the time t2. Correspondingly, FIG. 4(c) illustrates the state of electric charges accumulated in the N-well at the time t3, while FIG. 4(d) illustrates the state of electric charges at the time t4.
At the time t1, signal charges Q1 are accumulated in the storage region under the output stage electrode pair 113. The signal charges Q1 are injected into the floating diffusion 105 at the time t2, after passing through under the output gates 104. The signal charges Q1 are detected as a voltage at the time t2, and then drained outside through the reset drain 108 at the time t3, due to the pull-up of the reset pulse signal ΦR applied to the reset gate 107. At the time t3, next signal charges Q2 are accumulated in the storage region under the output stage electrode pair 113.
This is followed by pulling down the reset pulse signal ΦR to the voltage level VRL at time t4 to return the state of the time t1. Repeating such operation allows sequentially detecting signal charges Q1, Q2, Q3 . . . as the corresponding output voltages.
The inventor has now discovered that an issue of the conventional CCD 100 is that some of the signal charges may remain untransferred. FIG. 5 illustrates the manner in which signal charges remain untransformed. In the conventional CCD 100, the charge transfer electrodes pairs 110 are provided with the first and second clock signals Φ1 and Φ2. Additionally, several charge transfer electrodes pairs 110 adjacent to the output stage electrode pair 113 often have longer electrode lengths than those of other transfer electrodes pairs 110 away from the output stage electrode pair 113. In such a case, the duration of the time necessary for transferring signal charges through the several charge transfer electrodes pairs 110 adjacent to the output stage electrode pair 113 is longer than that necessary for transferring signal charges through other charge transfer electrodes pairs 110 away from the output stage electrode pair 113. Additionally, the increase in the electrode length may causes reduction of the fringing field effect of the output gates 104; it should be noted that the fringing field effect is an effect of the disorder of the electric field at the edge of an electrode. This may cause untransferred signal charges, denoted by the symbol ΔQ2 in FIG. 5(b).
Additionally, the conventional CCD 100 may suffer from coupling noise on the output thereof. FIG. 6 is a timing chart illustrating the waveforms of the clock signals and the output voltage. During the time period from the time t4 to the time t6, the first clock signal Φ1 is pulled down, and the second clock signal Φ2 is pulled down. In the meantime, the third clock signal Φ1L is pulled down during the time period from the time t4 to the time t5.
The load capacitances of the first and second clock signal lines 101 and 102, connected with the repeatedly-arranged charge transfer electrode pairs 110 (See FIG. 2), are usually in the order of several hundreds picofarads, while the load capacitance of the third clock signal line 103, connected with the output stage electrode pair 113, is usually in the order of several tens picofarads or less. Therefore, the CR time constant in the transfer of the third clock signal Φ1L is largely smaller than that in the transfer of the first and second clock signals Φ1 and Φ2. Therefore, the edges of the clock signals Φ1 and Φ2 are duller than that of the clock signal Φ1L.
As a result, the clock signal Φ1L is pulled down more rapidly in the time period from the time t4 to the time t5, while the clock signals Φ1 and Φ2 are switched more slowly in the time period from the time t4 to the time t6. This undesirably causes coupling noise applied to the floating diffusion 105 from the output stage electrode pair 113 fed with the third clock signal Φ1L, resulting in that the output voltage suffers from the coupling noise as shown in FIG. 6(d). The coupling noise caused by the third clock signal Φ1L undesirably reduces the allowed signal transfer period, and may result in the shortage of the signal stabilization period, especially when the CCD 110 is operated at a high operation speed.

Solid-state image sensing device and method of operating the same


A method of constructing a surgical implant is provided. The method comprises providing a multiplicity of substantially identical blocks, each having features thereon to allow blocks to be mechanically joined together. A surgical implant may then be constructed by using these features to join the blocks together into a desired configuration.

This section is intended to provide background or context to the invention recited in the claims. The description of the background art may include insights, discoveries, understandings or disclosures, or associations of disclosures not known in the prior art. Some contributions of the invention may be specifically pointed out below, whereas other contributions of the invention will be apparent from their context.
Surgical implants such as degradable tissue scaffolds can be used to fill defects in soft tissue or bone. These defects may be caused by removal of a tumour, or by bone or cartilage loss in a hip or knee replacement procedure, for example. Orthopaedic tissue engineering is a field concerned with the development of tissue scaffolds which are used to treat injuries or diseases in bone, and which are compatible with the patient's own biology. Tissue scaffolds may be utilised for both humans and animals.
Orthopaedic injuries or diseases vary significantly on a case by case basis. Highly invasive surgical procedures such as hip replacements can result in significant bone loss, leaving a defect in the bone. Each patient is different, not only in the size of the bone in question but also in the dimensions of the defect. Custom built scaffolds may therefore be desirable. However, their design and manufacture can be extremely expensive. The patient concerned must undergo detailed MRI or CT scans, which must be interpreted by both a surgeon and a tissue engineer with 3D modelling experience. The tissue scaffold must then be manufactured in advance of the surgery, at significant cost to the patient or to the healthcare provider.
FIG. 1 shows a degradable polymer tissue scaffold produced in line with recent developments, as discussed above. Computed tomography (CT) imaging data was used to reconstruct a defect in the jaw of a dog with an aggressive type of bone cancer. After designing a scaffold to fill the defect using the CT imaging data, a polymer implant was fabricated using 3D printing techniques. FIG. 2 illustrates the same implant as it appears when implanted in the jaw. The implant is located towards the left hand side of the jaw.
Recent developments in the manufacture of tissue scaffolds utilise 3D printing. For example, CN103977451 discloses a 3D printing manufacturing method for an artificial bone scaffold. However, even where customer scaffolds are produced from scan data and accurately manufactured by a technique such as 3D printing, they still do not always fit accurately. US2012/0271418 describes a biocompatible and implantable tissue scaffold having a modular design comprising a tissue scaffold rack designed to accommodate one or more modules.


Cleansing and multifunctional coating compositions containing an organosilane quaternary compound, nonreactive abrasives, and hydrogen peroxide in aqueous formulations are used to improve water and soil repellency and residual antimicrobial activity on surfaces. Various surfaces may be treated including metal, glass, plastics, rubber, porcelain, ceramic, marble, granite, cement, tile, sand, silica, enameled appliances, polyurethane, polyester, polyacrylic, melamine/phenolic resins, polycarbonate, painted surfaces, wood, and the like.

Rain and coastal spray from lakes and oceans contain enough dissolved gases, carbonic acid, chlorides, sulfates, nitrates, ammonia and particulate matter to make them chemically active. Similarly, most ground and municipally supplied water, while generally safe for drinking, cooking, washing and bathing, still contains enough salts, hard water minerals, bacteria, organic and inorganic contaminates and chlorinated water treatment chemicals to also be chemically active.
When either source of water is allowed to evaporate on most siliceous and nonsiliceous surfaces such as glass, porcelain, ceramic, marble, granite, polyurethane, polyester, polyacrylic, melamine/phenolic resins and polycarbonate, it combines with ordinary soil to promote the formation, adhesion and build-up of insoluble mineral deposits, lime scale, rust, soap scum and foodstuff. This ongoing exposure to chemically active water contributes directly to increased soil buildup and to the costly surface damaging cycle that results from scraping and scrubbing with harsh cleaners and cleansers to remove the insoluble soil.
Thus, until rain, ground and municipally furnished water is completely deionized and demineralized, any exterior glass (such as windows, patio doors and store fronts) exposed to rain or spray from oceans, lakes and ground sprinklers, etc. and any kitchen and bath surface (such as windows, sinks, counters, ranges, ovens, cooking and washing appliances, bathtubs and shower enclosures) exposed to tap water and water-containing spills and splatters that are allowed to evaporate on the surface remain subject to the formation, adhesion and buildup of insoluble soil.
To remove insoluble soil, homemakers and cleaning professionals have turned to stronger and stronger cleaning aids including powerful acids, alkalis and a broad range of abrasive cleansers. The inevitable result of using such harsh cleaning aids is a surface destroying cycle. The stronger the cleaning action, the more it opens the microscopic pores and increases the hydrophilicity of the surface. The more open and vulnerable the pores, the deeper the new soil penetrates and the greater its adhesion and build-up, and the stronger the cleaning action required to remove the soil with greater and greater destruction of the surface finish. Although microscopic at first, this cycle ultimately leads to surfaces that are visibly rough, exhibit the loss of color and sheen, and become more prone to soiling and microbiological contamination.
Traditional abrasive powders and creams (such as Kitchen Kleanser®, Comet®, Ajax®, Bon Ami®, Zud®, Bar Keepers Friend®, Soft Scrub®, Glass Scrub® and Miracle Scrub®) cleanse the surface of buildup by scraping and scrubbing the soil primarily with a surfactant and mechanical action. While such cleansers are more or less effective in removing the soil and microbial buildup, they typically leave a surface that has become more microscopically irregular, more water wettable (hydrophilic) and more prone to the adhesion and buildup of new soil and microbial contamination.
Also, it is well known that bacteria (like e-coli and salmonella, etc.), virus (like the nonvirus and herpes, etc.) and fungi (like mold and mildew, etc.) can be effectively mitigated with a broad range of sterilants, disinfectants and sanitizers. It is also known that hydrogen peroxide, ethyl alcohol, isopropyl alcohol and quaternary compounds are effective sterilants, disinfectants and sanitizers.
However, both traditional abrasive cleansers to remove insoluble buildup and sterilants, disinfectants and sanitizers to "kill" disease-producing microorganisms are typically only "one-time" compositions that provide no long term protection against soil buildup or microbial contamination. In fact, in our fast paced, fast moving society, the resoiling and recontamination of everyday surfaces is an ongoing, continuing and virtually instant process.
Although abrasive cleansers also remove microbial contamination while removing insoluble buildup from surfaces, the reverse is not true for sterilants, disinfectants and sanitizers that are usually ineffective against either the formation, adhesion and buildup of insoluble soil or its removal. Consequently, in terms of surface care, the use of abrasive cleansers negates any residual anti-microbial activity that may result from the use of sterilants, disinfectants or sanitizers.
It has been established that water and soil repellent surfaces significantly reduce the formation, adhesion and buildup of insoluble soil and that the water and soil repellency of surfaces can be improved by the use of silicone compositions. There has been extensive research and development involving silicone compositions for rendering surfaces water repellent. For example, U.S. Pat. No. 2,612,458 (Stedman) discloses the application of substituted polysilicanes to windshields to achieve repellency. U.S. Pat. No. 2,923,653 (Matlin et al.) discloses improved compositions employing alkoxy groups in the polysilicane to improve the repellency. U.S. Pat. No. 2,962,390 (Fain et al.) describes a paste containing a solid rubbing agent and an alkyl alkoxy silane which when rubbed on a glass surface provides repellency. U.S. Pat. No. 3,244,541 (Fain et al.) discloses acidic solutions of alkyl alkoxy silane monomers that produce rain repellent films on glass and which are also solvent resistant.
U.S. Pat. No. 3,579,540 (Ohlhausen) discloses water repellent film-forming compositions of alkylpolysiloxanes and acid, or alkylpolysiloxanes, acid and solvent which result in durable and effective water repellent films on various surfaces. It was the practical application of the 1971 '540 patent that spawned hundreds of products, many of which are still being manufactured and marketed for home, auto and commercial uses today. Some non-limiting examples are Rain-X®, Invisible Shield®, Rain Clear®, Shower Shield®, Clear Shield®, Hydro Shield®, Rain Vision®, Rain Away®, Crystal Coat®, Water Shield®, Poly Glass®, Surface Shield®, Glass Coat®, Slick Shield®, Micro Plus® and others.
Further improvements in solvent/VOC free compositions for treating porous and nonporous surfaces have been made as disclosed in U.S. Pat. No. 6,432,181 (Ludwig and Ohlhausen). The '181 patent satisfied a need which existed for soil and water repellent compositions that eliminate solvents and utilize the silicone more effectively and economically. Additional improvements in soil and water repellent compositions were made by providing physiologically acceptable compositions that were non-corrosive and non-irritating to the eyes and skin of the user in accordance with Federal Hazardous Substances Act and Consumer Product Safety Commission 16 CFR 1500 Guidelines as disclosed in U.S. Pat. No. 6,676,733 (Ludwig and Ohlhausen).
Many different types of hard and soft surfaces have also been cleaned of soluble soil, provided with a water and soil repellent finish and rendered antimicrobial by coating with different agents. For example, U.S. Publ. No. 2005/0096250, published May 5, 2005 (Ohlhausen and Ludwig) discloses a "Cleaning and Multifunctional Coating Composition Containing An Organosilane Quaternary Compound and Methods of Using" from aqueous systems with hydrogen peroxide. Although such compositions are exceptionally effective in removing water and oil soluble soil from surfaces while simultaneously providing a water and soil repellent barrier coating for easier cleaning and to reduce microbial contamination, they do not satisfactorily or completely remove insoluble buildup.
Organosilane quaternary nitrogen compounds have been employed effectively in eliminating and/or reducing microbial contamination when applied to a variety of surfaces. For instance, bacterial, viral and fungal contamination may be eliminated or reduced when such organosilane quaternary compounds are applied to surfaces. Commercially available quaternary ammonium organosilanes which have been used for this purpose include 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride, 3-(trimethoxysilyl)propyldidecylmethyl ammonium chloride, and 3-(trimethoxysilyl)propyltetradecyldimethyl ammonium chloride. The following patents and patent applications disclose the use of siliconized and/or non-siliconized quaternaries, solvents and surfactants/detergents for the cleaning and/or water repellent treatment of substrates: U.S. Pat. No. 4,005,028; U.S. Pat. No. 4,005,030: U.S. Pat. No. 6,559,111; U.S. Pat. No. 6,897,191; U.S. Pat. No. 6,809,072; U.S. Publ. No. 2005/0089695; U.S. Publ. No. 2005/0020474; U.S. Publ. No. 2003/0109395: U.S. Pat. No. 6,881,247; U.S. Publ. No. 2003/0091641 and U.S. Pat. No. 5,426,204.
Notwithstanding the improvements that have been made over many decades of research and development regarding cleaning or coating compositions for various surfaces, there still exists the need for further improvements.

Surfactant-free cleansing and multifunctional liquid coating composition containing nonreactive abrasive solid particles and an organosilane quaternary compound and methods of using


An action support apparatus displays a destination specification screen for specifying a destination, and receives from the user a specification of a general destination. If a general destination is specified, then the apparatus determines a detailed destination, referencing a knowledge DB. If there is a plurality of detailed destinations with respect to the general destination, then any one of them is set to the user's destination. Next, the apparatus sets the current location as the starting point, and generates a planned route from the starting point to the destination based on a map DB and an internal clock. Furthermore, the apparatus reads a filtering rule from a filtering DB, and extracts as recommended information facility information of facilities suited to the user from a facility information DB. Depending on the filtering rule, it is also acceptable to use user information in a user DB in the extraction of the recommended information. Subsequently, the apparatus associates the extracted recommended information with the planned route, and outputs them.

1. Field of the Invention
The present invention relates to a system that provides information to a user moving in a vehicle and the like while in the process of moving.
2. Background Information
Car navigation systems are already installed in many personal use vehicles, and can be said to be one type of general information presentation system. A general car navigation system comprises a geographic information storage unit, a processing unit, and an interface unit. The processing unit includes a current position measuring apparatus, such as a GPS (Global Positioning System), and calculates the route. The interface unit displays a planned route calculated by the processing unit, and receives input from the user. For example, if the user inputs a destination into the system, then this system can calculate and present guidance on a route from the current position to the destination based on the information in the abovementioned storage unit, and can produce voice output of the guidance information, with intersections, and entrances and exits of highways. In addition, among car navigation systems, there are those that suggest information related to the vicinity of the current position, and that suggest the nearest restaurants and the like. Examples of vicinity information include lifestyle information useful for shopping and interests; tourist information related to scenic and historic places, special products indigenous to the locale, and the like; geographic statistical information; dictionary information; and information useful for a pleasant journey. However, a car navigation system has not been offered that presents information adapted to the various circumstances surrounding the user, such as the current time and the status of the vehicle.
In addition, if the destination is decided, then a car navigation system that presents route information up to the destination and vicinity information along the route is useful to some extent. However, for a user for whom even the destination is not yet decided, a car navigation system itself is of no assistance from the onset.


A finisher is provide with a folding device which includes paired folding rollers which nip a loop of a sheet formed by a first folding stopper and give a first folding to the sheet, and paired folding rollers, which are disposed in a conveying path between a conveying path, which is located on an upstream side in a conveying direction of the sheet toward the paired folding rollers at the first folding, and a conveying path, in which a second folding stopper is disposed, and nip a loop of the sheet formed by the second folding stopper and give a second folding to the sheet, and sets a distance between the paired folding rollers and the first folding stopper at approximately three quarters of a length of the sheet in the conveying direction when the sheet is folded in three or in a cross section like a letter Z. The finisher temporarily stores the sheet in a state that one side for folding as an image formed surface faces downward and the other side for stapling approximates closely to the stapler. In addition, the finisher stores sheets including the Z-folding sheets in the order of page numbers and staples a sheaf of the sheets easily and accurately, and also utilizes a space efficiently and prevent the size from enlarging.

1. Field of the Invention
This invention relates to a finisher, which is connected to an image forming apparatus such as a printer or a copying machine, giving such additional-workings as sorting, binding, creasing, folding, and punching to a recording medium (hereinafter referred to briefly as "sheet") such as a recording paper outputted from the image forming apparatus. More particularly, it relates to a finisher with a folding device in which a stopper comes in contact with the leading end of the sheet to form a loop and a pair of rollers nips the loop to fold the sheet.
2. Description of the Related Art
Recently, various finishers, which give various additional-workings to a sheet with an image formed surface which are outputted from such image forming devices as printers and copying machines, have been proposed (U.S. patent application Ser. No. 08/821,444). The term "additional-workings" as used herein means various working processes such as sorting sheets according to the number of copies, filing sheets with staples, folding sheets in two (hereinafter referred to as "double-folding"), folding sheets in three or in a cross section like a letter Z (hereinafter referred to as "Z-folding"), and punching sheets for filing.
A finisher, which is illustrated in FIG. 19, has been known as one example of the above finishers. The finisher is provided with a folding mechanism 700. The finisher gives the Z-folding to sheets as follows. First, the folding mechanism 700 receives a sheet with a copied image on the upper surface, which is fed from the direction of right in the diagram. A first folding stopper 704 comes in contact with the sheet to form a loop of the sheet. Then, a pair of folding rollers 701, 702 nips the loop to effect the first folding at a position separated by about one quarter of the size of the sheet in the conveying direction from the leading end of the sheet. Next, the second folding stopper 705 comes in contact with the first folding to form a loop of the sheet. Last, a pair of folding rollers 702, 703 nips the loop to effect the second folding at a roughly central position of the sheet in the conveying direction. Accordingly, the sheet is in three or in a cross section like a letter Z.
The above conventional folding devices adopt a so-called last page system which copies a plurality of original documents sequentially in the reverse order from the last page forward. The last page system, which is provided with the folding mechanism 700 disposed below the finisher as illustrated in the diagram, can change the sheets to be in the order of page numbers.
Incidentally, multifunction machines, which work as a printer, facsimile equipment and the like, have been proposed with the popularization of digital copying machines. Such a multifunction machine is utilized for various purposes of copying, printing, facsimile receiving, facsimile transmitting, etc. A user is possibly confused on the occasion of a series of printing when all functions do not have the same printing order as the order from the first page onward or in the reverse order from the last page forward.
The application programs, which are executed by a computer, normally give a printer instructions of printing in the order from page 1 onward. Accordingly, a large number of multifunction machines adopt a so-called first page system in which a printing starts from the first page onward as the common printing order applied to all functions.
The first page system, however, requires to discharge a sheet having a copied image in a reversed state for adjusting the order of page numbers. A folding device according to the conventional folding device illustrated in FIG. 19, providing with a reversing mechanism 710a on the front of the folding mechanism 700 as illustrated in FIG. 20 (on condition that a reversing mechanism 710b is not incorporated), folds a sheet concerning a surface opposite from an image formed surface C as illustrated in FIG. 21 and does not obtain a proper folding when discharging a sheet having a copied image in a reversed state. A folding device according to the conventional folding device illustrated in FIG. 19, providing with a reversing mechanism 710b on the front of the discharging unit as illustrated in FIG. 20 (on condition that a reversing mechanism 710a is not incorporated), folds a sheet concerning the image formed surface C. However, the folding device has to staple a sheaf of temporarily stored sheets as illustrated in FIG. 22, at a stapling position S as the farthest position in a conveying direction of the sheaf when the folding device takes the sheaf out in a direction opposite to a receiving direction of the sheets for temporarily storage. Namely, the folding device has the problem that the stapling is difficult.
In the first page system, it is preferable to store sheets in such a manner as illustrated in FIG. 23 for the purpose of fixing the stapling position S in the conveying direction for all the sizes of sheets. It results in shortening the conveying distance of sheets or a sheaf necessary for stapling on the downstream side, securing the accuracy of positioning steadily and reducing the deviation of sheets during the conveyance, for example.
An arrangement as illustrated in FIG. 24, which reverses a sheet P, irrespectively of the necessity for a folding, may store sheets in such a manner as illustrated in FIG. 23.
In the arrangement, the conveying path is not easily laid out unless the folding mechanism 700 is disposed above the finisher. In generally, a finisher stores sheets P temporarily, staples a sheaf of stored sheets and discharges a stapled sheaf into another receiving tray unit. A position of the receiving tray unit which stores a stapled sheaf is preferably lower than a position of the stapler for stapling a sheaf for the purpose of attaining the conveyance of the sheaf steadily. A tray, which temporarily receives sheets, must be inevitably disposed on the upper section for the purpose of enlarging a storage capacity for stapled sheaves. A finisher including the folding mechanism 700 disposed on the upper section as well as the tray is of large size as a whole, and loses balance because a component density is high in the upper section.

Sheet folding and finishing apparatus and method