A dispensing device for use in extracting liquid, such as water, from a container of the type which is inverted into a position above a reservoir. The device includes probe which is of simple construction and wherein the surfaces of the probe are exposed and readily observed or inspected. In a preferred embodiment, the probe has a cruciform cross-section through which water may flow when the probe is inserted into an inverted water bottle to separate an inner cap from a sleeve in the center of the closure of the bottle. The probe is supported by and projects from a base which has apertures through which water may flow into a reservoir of the dispenser with which the probe is used. If the probe is a replacement part for an existing dispenser, as opposed to being designed and sold as part of a new dispenser, the base which supports the probe may have an externally threaded cylindrical or cup-shaped portion extending in a direction opposite to that of the probe. The threaded portion of the probe enables a older style tubular probe of an existing dispenser to be replaced by a probe of the present invention. The tip of the probe has a groove for engaging an internally directed bead or rib on the inside surface of the inner cap element (or the plug), whereby the inner cap and the sleeve may be brought into a sealing relationship when the bottle is removed from the dispenser. To assist in maintaining the shape of sleeve of the closure as it is brought into sealing relationship with the inner cap, the probe has a series of discs just below the groove. The discs hold the sleeve in a cylindrical shape as the sleeve is lifted into engagement with the inner cap.

The present invention relates to dispensers of the type which are used in conjunction with inverted bottles of water. In particular, the invention relates to dispensers which are intended to operate a valved closure which seals the opening of a bottle, commonly containing water.
For many years, it has been and continues to be common to see around offices and factories an inverted 5-gallon container sitting atop a cooler to provide drinking water to office and factory workers. In the past, such containers of water were placed on the coolers after removing the closure on the container. This process often resulted in at least some spillage of water when replacement of the supply container became necessary.
In the early 1990's, substantial numbers of bottlers began to offer dispensing systems which included a valved closure and a feed tube built into the cooler for operating the valved closure. These features, and others, addressed and solved the spillage problem referenced above. Examples of such systems are shown in U.S. Pat. No. 5,121,778 and No. 5,647,416. Such systems include elaborate componentry and structures designed, among other things, to filter the air which replaces dispensed fluid. A further example of a system which filters air entering the container as fluid is dispensed is shown in U.S. Pat. No. 4,699,188. Bottlers, and more particularly, consumers, have come to recognize the advantages of systems which eliminate the difficulty associated with inverting a bottle of water with an open and large diameter spout. However, the advantages of air-filtering are open to question. Indeed, the elaborate and expensive componentry needed to control air entering the container has given rise to the need for a simpler non-spill dispensing arrangement. The closed fluid paths associated with complicated systems used in air-filtered dispensing create an environment which may be conducive, under certain circumstances, to the growth of bacteria and other detrimental pathenogenic agents.
Consumers have become more interested in the use of bottled water in their homes, as well as in offices and factories. Crock-type dispensers, which are not refrigerated, have become commonplace in kitchens throughout the country, particularly in regions where tap water is either expensive or of questionable quality. Even where tap water is inexpensive and of high quality, many consumers feel that bottled water is a significant improvement over water obtained from a municipal source. It is therefore desirable to provide a dispensing system for use in homes which takes advantage of the non-spill convenience of a valved container of bottled water.
In accordance with the present invention, a probe is provided wherein all of the surfaces of the probe are in plain sight and can be easily seen and cleaned. The probe of the present invention has flutes, rather than enclosed feed tubes. The probe has a cruciform cross-section which defines the flutes and which create fluid pathways for the entry of air into a container and the exit of water from a container through a passageway in a valved cap. The probe is supported by a base which contains apertures through which the water may fall into the reservoir of a cooler or crock-type dispenser. The probe includes a grooved tip for retaining that portion of the valved cap which reseals the central tube upon removal of the bottle from the dispenser. In a preferred embodiment of the invention, the probe includes lateral disc-shaped supports at the upper end of the probe to support the walls of the central tube as the resealing element of the closure is positioned on the central tube when the container is removed from the dispenser.

Dispensing system with fluted probe and valved closure


A multi-colored electrophoresis pattern reading apparatus is capable of labelling each of plural samples separately with each of plural fluorescent substances having different fluorescence wavelengths, by electrophoresing the plural samples to develop a pattern, exciting the fluorescent substances labelled on the samples to emit fluorescence, and reading a fluorescent pattern emitting the fluorescence. The apparatus contains a source for the light for exciting the fluorescent substances; a light scanning mechanism for scanning the light to irradiate a gel in the direction of its thickness with the light; a light receiving section for receiving fluorescence resulting from the light source separated from the scattered light resulting from a reading surface on the basis of a spatial position relationship of a light receiving path by setting a light receiving surface in a direction different from an optical axis of the irradiating light; an optical filter section for separating the resulting optical signals section into plural wavelengths; an optoelectric conversion section for converting optical signals into electrical signals; and an amplifier for amplifying the electrical signals by an integrating operation corresponding to scanning of the irradiating light, and for generating electrical signals indicative of fluorescence from the pattern one after another.

The present invention relates to a multi-colored electrophoresis pattern reading apparatus and, more particularly, to a multi-colored electrophoresis pattern reading apparatus appropriate for the comparison of a plurality of electrophoresis patterns by labelling each of a popularity of samples with fluorescent pigments having different fluorescent wavelengths simultaneously, subjecting the samples to electrophoresis other, and reading the resulting electrophoresis pattern.
Generally, electrophoresis analysis methods using labels with a radioactive isotope have been employed for analyzing the sequence of various genes, including diagnosis of diseases deriving from genes, the structures of proteins such as amino acids, etc. The electrophoresis analysis method is a method for analyzing samples by labelling or replacing fragments of a sample with or by a radioactive isotope, subjecting the fragments of the sample to electrophoresis with a gel, and analyzing a pattern of distribution of the fragments of the sample developed by means of electrophoresis.
Description will now be made of the diagnosis of hereditary diseases as an exemplary application for reading and analyzing the electrophoresis patterns. The human genome DNA consists of pairs of bases numbering approximately 3.times.10.sup.9 and the sequence of the bases is generally constant among all human beings, although there is a deviation in the sequence of the bases for certain individuals. This deviation is called a polymorphism of DNAs. The polymorphism of DNAs is seen in the non-hereditary region as well as in the hereditary region, and the polymorphism of DNAs appears in many occasions as a polymorphism of proteins, that is a phenotype of the polymorphism of DNAs. Many variations seen among human beings, such as blood types, histocompatible antigens, the difference of skin and hair colors among peoples, etc. are based on the polymorphism of DNAs. The polymorphism of the DNAs has been created on the basis of variations that have been accumulated in the DNAs of the genocytes of the human groups up to the present time from the time when the human being developed as an individual biological species in the course of evolution. When such a variation exists in the site that has the function of significance in terms of the existence as an individual person, and when a nosogenic phenotype resulting from the variation occurs as a pathologic state, the pathologic state is called a hereditary disease. It is said that there are currently more than 3,000 kinds of hereditary diseases in the human group.
The nosogenesis of the hereditary disease is an abnormality appearing on the DNA sequence. However, it is recognized for the first time as a disease in several stages ranging from DNA through mRNA and proteins to pathogenic phenotype., The diagnosis as a disease is conducted usually in the last stage and the diagnosis can be implemented at the DNA level or at the protein level if the disease would occur simply in the course of the several stages as described hereinabove.
The basic technique for the diagnosis of DNAs is called Southern plotting that basically consists of six steps
Step 1: Extraction of DNAs as a sample; PA0 Step 2: Fragmentation of DNAs with restricting enzymes; PA0 Step 3: Fractionation of molecular weights of the DNAs through gel electrophoresis; PA0 Step 4: Migration of DNA fractions to filter; PA0 Step 5: Hybridization of DNA fractions with probe DNA (obtained by labelling DNA having the homeomorphous sequence of the gene to be detected); and PA0 Step 6: Detection of the hybrid by autoradiography.
For the diagnosis of the hereditary diseases, DNAs extracted from any organ are employed, and the sample required for that purpose is usually the peripheral blood of the order of several milliliters. DNAs are extracted from the leukocytes separated from the peripheral blood as the sample. Approximately five days are usually required from step 1 to step 6. In diagnosing the hereditary diseases, a fraction pattern of a person tested is compared with a fraction pattern of a normal person. The person tested is decided as normal when the fraction pattern of the person tested is determined to be identical to the fraction pattern of the normal person.
Recently, attempts have been made to conduct tests by using a probe DNA labelled with a fluorescent pigment, in place of a radioactive isotope, exciting the fluorescent pigment and reading the electrophoresis pattern, from the point of view of safety and other environmental problems. However, highly sophisticated optical and signal processing techniques are required to give a signal-to-noise ratio equivalent to the radioactive isotope method, because the quantity of the sample required for diagnosis of the hereditary disease and determination of the sequence of bases is of the order of approximately 10.sup.-15 mole.
Japanese Patent Laid-open Publication (kokai) No. 61-62,843/1986 discloses an electrophoresis apparatus capable of detecting a minute quantity of a sample labelled with a fluorescent pigment.
Description will now be made of such an electrophoresis apparatus based on a fluorescence detection method.
FIG. 16 is a perspective view showing an appearance of a conventional electrophoresis apparatus of a fluorescent type. The electrophoresis apparatus comprises an electrophoresis and instrumentation unit 51 for implementing electrophoresis of a sample and measuring the distribution of fluorescence, data processor 52 for performing data processing on the basis of measured data, and a cable 53 connecting the electrophoresis and instrumentation unit 51 to the data processor 52. The electrophoresis and instrumentation unit 51 has a door 51a through which are poured a gel serving as a base for performing electrophoresis for DNA fragments and a predetermined quantity of a sample for electrophoresis. As the door 51a is closed a switch for starting electrophoresis on an operation display panel 51b is pressed to start electrophoresis. After the electrophoresis has been started, a monitor of the operation display panel 51b of the electrophoresis and instrumentation unit 51 displays an operational state. The data measured is transmitted to the data processor 52 in which the data is processed on the basis of a predetermined program stored in advance. The data processor 52 comprises a computer body 54, a keyboard 55 for entering an instruction from the operator, a display unit 56 for displaying the processing state and results, and a printer 57 for recording the processed results.
FIG. 17 is a block diagram showing the configuration of the inside of the electrophoresis and instrumentation unit. As shown in FIG. 17, an overall configuration of the electrophoresis and instrumentation unit 51 (FIG. 16) comprises an electrophoresis unit section 63 and a signal processor unit section 64. The electrophoresis unit section 63 comprises an electrophoresis section 5 for implementing electrophoresis, a first electrode 2a and a second electrode 2b each for applying voltage to the electrophoresis section 5, a support plate 3 for supporting the electrophoresis section 5 as well as the first and second electrodes 2a and 2b, a power plant unit 4 for applying voltage to the electrophoresis section 5, a light source 11 for emitting light for exciting a fluorescent substance, an optical fiber 12 for leading the light from the light source 11, a light collector 14 of an optic system for condensing and collecting fluorescence 13 generated by the fluorescent substance, an optical filter 15 for selectively passing light having a particular wavelength therethrough, and an optical sensor 16 for converting the condensed light into electric signals. The signal processor unit section 64 comprises an amplifier 17 for amplifying the electric signals from the optical sensor 16, an analog-digital converting circuit 18 for converting analog signals of the electric signals into digital data, a signal processing section 19 for pre-processing the digital data, for example, by performing addition average processing or the like, an interface 20 for implementing interface processing for feeding the pre-processed data to an external data processor, and a control circuit 10 for implementing overall control of the electrophoresis unit section and the signal processing system. The digital signal OUT generated from the signal processor unit section 64 is transmitted to the data processing unit 52 (FIG. 16), thereby implementing the data processing such as analysis processing and so on.
Description will now be made of the operation of the electrophoresis apparatus with reference to FIGS. 16 and 17.
After the door 51a of the electrophoresis and instrumentation unit 51 is opened, a gel is poured into the electrophoresis section 5 disposed within the electrophoresis and instrumentation unit 51 and thereafter a sample of DNA fragments labelled with a fluorescent substance is poured thereinto. After a switch of the instrument panel 51b is pressed to give an instruction to start electrophoresis, voltage is applied from the first and second electrodes 2a and 2b of the power plant unit 4 to the electrophoresis section 5, thereby starting the electrophoresis. The electrophoresis allows the sample labelled with the fluorescent substance to migrate, for example, in lanes 71, 72, 73 and 74, as shown in FIG. 20, gathering the molecules having the same molecular weights together form bands 66. The molecules having lower molecular weights migrate faster than those having higher molecular weights so that the former migrate a distance longer than the latter within the same time unit.
The bands 66 are detected in a manner as shown in FIG. 18a by leading light from the light source through the optical fiber 12 to a light path 61 and irradiating the gel on the light path 61 with the light, exciting the labelled fluorescent substance concentrated on the bands 66 in the gel to generate fluorescence 13, and detecting the fluorescence 13. The fluorescence 13 is generated form the fluorescent substance in concentration as low as approximately 10.sup.-16 mole per band, although the quantity of fluorescence may depend upon an absorptivity, or extinction coefficient, of the fluorescent substance used, quantum efficiency thereof, intensity of exciting light, etc. For instance, fluorescein isothiocyanate has a peak of wavelength of excitation at 490 nm, a peak of its fluorescent wavelength at 520 nm, an extinction coefficient of 7.times.10.sup.4 mole.sup.-1.cm.sup.-1, and a quantum efficiency of approximately 0.65. If fluorescein isothiocyanate exists in the concentration of 10.sup.-16 mole per band, the fluorescence generated contains photons of the order of as low as 10.sup.10 /S, when calculated by postulating the use of argon ion laser of a wavelength of 488 nm at an output of 1 mW as a fluorescent substance, although it may vary to some extent with the thickness of the gel or the like.
Referring to a front view as shown in FIG. 18a and to a longitudinally sectional view as shown in FIG. 18b, the electrophoresis section 5 comprises a gel member 5a composed of polyacrylamide or the like and gel supporting members 5b and 5c, each made of glass for supporting and interposing the gel member 5a from the both sides. A sample of DNA fragments is poured into the gel member 5a of the electrophoresis section 5 from its upper portion and the electrophoresis is carried out by applying electrophoresis voltage to the first electrode 2a and the second electrode 2b (FIG. 17).
While the electrophoresis is being carried out, the fluorescent substance contained in the bands of the electrophoresis pattern in the gel member 5a along the light path 61 is irradiated with rays of light sent out from the light source, such as laser light, which pass through the optical fiber 12 onto the light path 61 of the gel member 5e. This allows the fluorescent substance present on the light path 61 to be excited to emit fluorescence 13 that is led to a light collector 14 of optics consisting of a combination of lenses, and then selected by the optical filter 15 after having been condensed, followed by conversion into electrical signals by means of a one-dimensional optical sensor 16.
In order to convert a faint quantity of light into electrical signals in an efficient fashion, the light is amplified 10.sup.4 to 10.sup.5 times with an image intensifier or the like, and the image is converted into electrical signals by the optical sensor 16, such as a one-dimensional CCD optical sensor or the like. The electrical signals converted by the optical sensor 16 are then amplified to signals of a desired level by the amplifier 17, and the analog signals are converted into digital signals by the analog-digital converting circuit 18, followed by transmission to the signal processing section 19. The digital signals transmitted from the analog-digital converting circuit 18 are then subjected to signal processing, such as addition average processing, or the like, in order to improve the signal-to-noise ratio (an S/N ratio), and the resulting digital data are transmitted to the data processor unit section 52 through the interface 20.
FIGS. 19a and 19b are schematic representations for describing an example of signals of a pattern indicative of a fluorescent intensity of DNA fragments transmitted from the electrophoresis and instrumentation unit 51. For instance, as shown in FIG. 19a, the fluorescent substance present on the light path 61 is excited upon irradiation of the gel member 5a of the electrophoresis section 5 with the laser light in the course of electrophoresis, thereby emitting fluorescence. The fluorescence is detected at predetermined positions of each lane in the direction of electrophoresis, as indicated by 62, as the time of electrophoresis elapses. In other words, the fluorescence is detected as the bands 66 of each lane passes through the positions of the light path 61, thereby detecting a pattern signal of fluorescence intensity in each of the lanes, as shown in FIG. 19b. As a peak of the fluorescence intensity is given when each of the bands 66 passes through the position of the light path 61, the pattern signal of the fluorescence intensity as shown in FIG. 19b represents a pattern signal indicating the magnitude of fluorescence intensity of the bands 66 located in the direction of electrophoresis, as indicated by 62.
The computer body 54 of the data processing unit 52 implements data processing for comparing molecular weights and determining a sequence of bases of a DNA chain on the basis of data of the pattern indicative of fluorescence intensity in response to data of the pattern signals for the fluorescence intensity of the DNA fragments transmitted from the electrophoresis and instrumentation unit 51. The sequence of the bases and so on determined by the data processing is symbolized and then generated, thereby displaying the symbolized data on a display screen by the display unit 56 or printing it out by the printer 57.
The aforesaid embodiment is directed to an example of the apparatus in which the fluorescent pigment is employed for labelling the sample. Japanese Patent Laid-open Publication (kokai) No. 1-167,649/1989 discloses another example of an apparatus capable of reading a fluorescent electrophoresis pattern. This apparatus reads a fluorescent pattern of the electrophoresis section as a whole after the end of electrophoresis, unlike the aforesaid electrophoresis apparatus, which reads the distribution of the fluorescent pattern passing through a reading section in the course of electrophoresis.
It is to be noted herein that the gel electrophoresis method employed for the electrophoresis pattern reading apparatuses on the basis of the fluorescence detection method is the same as the gel electrophoresis method which has been employed for the conventional apparatuses in which the sample is labeled with the radioactive isotope. The gel electrophoresis method may cause a warp in the electrophoresis pattern because the speed of migration of bands may vary with the position of an electrophoresing plate due to irregularities in temperatures within the gel and for other reasons, thereby causing a warp in the electrophoresis pattern. Hence, for example, when electrophoresis of two kinds of samples or two dimensional electrophoresis is to be performed to compare two kinds of electrophoresis patterns for the diagnosis of hereditary diseases, the electrophoresis positions may be deviated between the electrophoresis results due to the warp and a comparison between the two electrophoresis patterns may be rendered difficult, regardless of the method adopted, as long as the conventional gel electrophoresis method is employed. Further, implementation of the correction of such electrophoresis patterns by means of data processing is also rendered laborious and difficult.
Further, as the electrophoresis and instrumentation unit for implementing electrophoresis and simultaneously measuring the distribution of the fluorescent substance passing through the reading unit adopts two-dimensional electrophoresis, it requires the one-dimensional electrophoresis to be implemented by one device and the two-dimensional electrophoresis to be conducted by another device, so that this operation is laborious.

Multi-colored electrophoresis pattern reading apparatus


Solid-state storage management for a system, the management including establishing, externally to a solid-state storage board, a correspondence between a first logical address and a first physical address on solid-state storage devices located on the solid-state storage board. The solid-state storage devices include a plurality of physical memory locations identified by physical addresses. The correspondence between the first logical address and the first physical address is accepted by the solid-state storage board. The correspondence between the first logical address and the first physical address is stored in a location on a solid-state memory device that is accessible by an address translator module, the address translator module and the solid-state memory device located on the solid-state storage board. The first logical address is translated to the first physical address by the address translator module based on the previously established correspondence between the first logical address and the first physical address.

The present invention relates to computer storage, and more specifically, to solid-state storage management.
Solid-state drives (SSDs) are data storage devices that use solid-state memory to store persistent data. SSDs are most commonly connected to a host computer via a high speed link. SSDs usually implement some form of management of the storage medium, i.e., the underlying solid-state storage devices. Such management usually includes translating from a logical address space into a physical address space. Many SSDs use "not-and" (NAND) based flash memory which must be erased in blocks before being rewritten with new data. Address translation is commonly used with NAND flash devices due to the difficulty of erase operations.
In some contemporary systems that use NAND flash devices, all of the management functionality is performed on the host computer. In these systems, the address translation table is placed in the main memory of the host computer such that during a read operation the host computer determines the physical address corresponding to the logical read address (address translation). During a write operation, the host computer decides the physical write address to which the data is written (physical data placement), and logs the logical-to-physical address correspondence in the address translation table. A shortcoming of this approach is that it requires the expenditure of computational cycles and main memory at the host in order to perform the address translation. Thus, it is well-suited for computer systems with large amounts of dynamic random access memory (DRAM) and processing capabilities, and is not well suited for lower cost systems with limited amounts of DRAM and processing capabilities, or for large-scale data-centric systems with high ratios between storage and system memory.
Other contemporary systems place all of the management functionality on the physical SSD board. In this case, SSD does both data placement and address translation. A shortcoming of this approach is that it suffers in terms of cost/performance because it does not leverage the host processor and instead requires another processor to be incorporated into the SSD.

This patent is subject to a terminal disclaimer.

INTERNATIONAL BUSINESS MACHINES CORPORATION


A Network Node (NN) 208 and a method therein for beam selection. When an upcoming ability to serve a Wireless Device (WD) 210 using a current NN beam is predicted to be lost based on historic data, the NN selects an upcoming NN beam out of one or more candidate NN beams that are able to serve the WD when the NN has lost ability to serve the WD using the current NN beam. The NN configures a dedicated Beam Reference Signal (BRS) for the upcoming NN beam, which is to be detected in beam selection by the WD when the NN loses ability to serve the wireless device using the current NN beam. By means of the current NN beam, the NN transmits, to the WD, a configuration of the dedicated BRS. Further, by means of the upcoming NN beam, the NN transmits, to the WD, the dedicated BRS.

Communication devices such as terminals or wireless devices are also known as e.g. User Equipments (UEs), mobile terminals, wireless terminals and/or mobile stations. Such terminals are enabled to communicate wirelessly in a wireless communication system or a cellular communications network, sometimes also referred to as a cellular radio system or cellular networks. The communication may be performed e.g. between two wireless devices, between a wireless device and a regular telephone and/or between a wireless device and a server via a Radio Access Network (RAN) and possibly one or more core networks, comprised within the wireless communications network.
The above terminals or wireless devices may further be referred to as mobile telephones, cellular telephones, laptops, or tablets with wireless capability, just to mention some further examples. The terminals or wireless devices in the present context may be, for example, portable, pocket-storable, hand-held, computer-comprised, or vehicle-mounted mobile devices, enabled to communicate voice and/or data, via the RAN, with another entity, such as another terminal or a server.
The cellular communications network covers a geographical area which is divided into cell areas, wherein each cell area being served by an access node such as a base station, e.g. a Radio Base Station (RBS), which sometimes may be referred to as e.g. an "eNB", an "eNodeB", a "NodeB", a "B node", or a Base Transceiver Station (BTS), depending on the technology and terminology used. The base stations may be of different classes such as e.g. macro eNodeB, home eNodeB or pico base station, based on transmission power and thereby also cell size. A cell is the geographical area where radio coverage is provided by the base station at a base station site. One base station, situated at the base station site, may serve one or several cells. Further, each base station may support one or several communication technologies. The base stations communicate over the air interface operating on radio frequencies with the terminals or wireless devices within range of the base stations. In the context of this disclosure, the expression Downlink (DL) is used for the transmission path from the base station to the mobile station. The expression Uplink (UL) is used for the transmission path in the opposite direction i.e. from the mobile station to the base station.
A Universal Mobile Telecommunications System (UMTS) is a third generation (3G) telecommunication network, which evolved from the second generation (2G) Global System for Mobile Communications (GSM). The UMTS terrestrial radio access network (UTRAN) is essentially a RAN using wideband code-division multiple access (WCDMA) and/or High-Speed Packet Access (HSPA) for user equipment. In a forum known as the Third Generation Partnership Project (3GPP), telecommunications suppliers propose and agree upon standards for third and higher generation networks, and investigate enhanced data rate and radio capacity. In some RANs, e.g. as in UMTS, several radio network nodes may be connected, e.g., by landlines or microwave, to a controller node, such as a radio network controller (RNC) or a base station controller (BSC), which supervises and coordinates various activities of the plural radio network nodes connected thereto. This type of connection is sometimes referred to as a backhaul connection. The RNCs and BSCs are typically connected to one or more core networks.
Specifications for the Evolved Packet System (EPS), also called a Fourth Generation (4G) network, have been completed within the 3GPP and this work continues in the coming 3GPP releases, for example to specify a Fifth Generation (5G) network. The EPS comprises the Evolved Universal Terrestrial Radio Access Network (E-UTRAN), also known as the Long-Term Evolution (LTE) radio access network, and the Evolved Packet Core (EPC), also known as System Architecture Evolution (SAE) core network. E-UTRAN/LTE is a variant of a 3GPP radio access network wherein the radio network nodes are directly connected to the EPC core network rather than to RNCs. In general, in E-UTRAN/LTE the functions of an RNC are distributed between the radio network nodes, e.g. eNodeBs in LTE, and the core network. As such, the RAN of an EPS has an essentially "flat" architecture comprising radio network nodes connected directly to one or more core networks, i.e. they are not connected to RNCs. To compensate for that, the E-UTRAN specification defines a direct interface between the radio network nodes, this interface being denoted the X2 interface.
In the 3GPP LTE, base stations, which may be referred to as eNodeBs or even eNBs, may be directly connected to one or more core networks.
The 3GPP LTE radio access standard has been written in order to support high bitrates and low latency both for uplink and downlink traffic. All data transmission is in LTE controlled by the radio base station.
Multi-antenna techniques may significantly increase the data rates and reliability of a wireless communication system. The performance is in particular improved if both the transmitter and the receiver are equipped with multiple antennas, which results in a Multiple-Input Multiple-Output (MIMO) communication channel. Such systems and/or related techniques are commonly referred to as MIMO systems.
Beamforming will be an important technology in future radio communication systems since it may improve performance. The performance may be improved both by increasing the received signal strength, thereby improving the coverage, and by reducing unwanted interference, thereby improving the capacity. Beamforming may be applied both in a transmitter and a receiver. In a transmitter, beamforming amounts to configuring the transmitter to transmit the signal in a specific direction or in a few directions, and not in other directions. In a receiver, beamforming amounts to configuring the receiver to only receive signals from a certain direction or from a few directions, and not from other directions. When beamforming is applied in both the transmitter and the receiver for a given communication link, we refer to the link as a Beam Pair Link (BPL) comprising a combination of beams selected in the both ends. A BPL may also be referred to as a Beam-Tracking Process (BTP) since it may be subject to different procedures for its maintenance. Generally, the beamforming gains are related to the widths of the used beams. For example, a relatively narrow beam provides more gain than a wider beam.
FIG. 1 is a combined flowchart and signalling scheme schematically illustrating a normal BPL setup according to prior art. As shown in FIG. 1, a UE transmits a detected Beam Reference Signal (BRS) report to the network (NW), e.g. to a network node. The report comprises information relating to newly detected network beams based on received reference signals from the NW. The NW instructs the UE to start searching for suitable UE beams, to set up a BPL (referred to as tracking process set up in FIG. 1), and to report a tracking set up completion back to the NW. The NW starts sending dedicated BRS or continues to send BRS.
For a more general description of beamforming, one typically talks about "beamforming weights" rather than "beams". On the transmission side, the beamforming weights are the complex constants that the signal to be transmitted are multiplied with before being distributed to the individual antenna elements. There is a separate beamforming weight for each antenna element, which allows maximum freedom in shaping the transmission beam given the fixed antenna array. Correspondingly, on the receiving side, the received signal from each antenna element is multiplied separately with the beamforming weights before the signals are combined. However, in the context of the present text, the description is easier to follow if the somewhat simplified notion of beams, pointing in certain physical directions, is adopted.
Beamforming requires some form of beam management, such as beam search, beam refinement, and/or beam tracking, to determine what transmit and receive beams, e.g. directions, to use for communication between a transmitter and a receiver. Beam search may involve the transmitter sweeping a signal across several beams, to allow a receiver in an unknown direction to receive the signal. Beam search may also involve the receiver scanning across several receive beams, thereby being able to receive a signal from an initially unknown direction. Beam search typically also involves the receiver sending a message to a transmitter to indicate which transmit beam or beams are best suited for transmission to that receiver.
Beam refinement and/or tracking is applied when a working beam or a beam pair is already selected. Beam refinement is to improve an already selected beam, for instance changing its beamforming weights such that a narrower beam that provides a better gain is obtained. Beam tracking is to update the selected beams, i.e., to replace the Tx- or Rx-beam in an existing BPL when the conditions change, e.g., due to mobility. Beam refinement and tracking are typically performed by temporarily evaluating a different beam than the one that is currently used for communication, and switching to that beam if it is deemed better than the current.
Beam search may take considerable time, if there are many beams to search for on both the transmitter and receiver side, and during this time communication is typically not possible. Beam refinement and tracking, on the other hand, are usually ongoing activities that cause little or no disturbance to ongoing communication.
Communications networks, e.g. by means of a network node, may transmit periodic or continuous reference signals that are semi-statically configured to support mobility and beam management, e.g. by sweeping across several transmit beams as described above. Such transmissions are here referred to as Beam Reference Signals (BRS) or Mobility Reference Signal (MRS). It is here envisioned that some aspects of beam management may then be performed by a terminal with little or no explicit involvement from the network, if the terminal may assume that the network is transmitting the BRS periodically or continuously. For instance, in some candidate realizations of 5G, terminals perform beam search as part of the system-acquisition procedure, resulting in the selection of a terminal beam such that by using this beam the terminal is able to sufficiently well receive BRS transmitted on a certain network beam. Then the terminal performs a random-access transmission using its selected terminal beam using a transmission resource, e.g. a time and/or a frequency resource, where it expects the network to be able to receive random-access transmissions using that certain network beam. Terminals may continue to receive BRS even when communication is ongoing, to search for new communication paths and to perform refinement and tracking of currently used beams.
Many radio communication systems include some kind of radio-link supervision, whereby the quality of the communication is regularly evaluated, and some action is taken in case the quality is unacceptable or the communication is lost. Radio-link supervision often involves a receiver checking the presence and/or evaluating the quality of a sync signal or a reference signal. It can also involve monitoring the number of retransmissions in a retransmission protocol, and monitoring the time it takes to receive a response to an earlier transmitted request message. In case any of these evaluations indicate a severe problem, the terminal often declares a radio-link failure and initiates some action. In case of a network node having lost communication with a terminal, the action can involve releasing some or all network resources related to that terminal. In case of a terminal having lost communication with a network, the action may involve searching for sync and reference signals from the network and, in case such signals are found, attempting to access the network again. In a beamforming system, this typically involves beam search.
In addition, communications networks schedule and transmit terminal-specific reference signals that, among other things, can be used for beam searching, beam tracking, and beam refinement. Such signals are here referred to as dedicated Beam Reference Signals (BRS) or Beam-Refinement Reference Signals (BRRS). Another example of a terminal-specific reference signal is the Channel-State Information Reference Signal (CSI-RS). This is a reference signal scheduled by the network for one (or possibly, several) specific terminal (or terminals) with the intention of providing measurement opportunities in the terminal such that more detailed channel knowledge may be obtained and reported back to the network.
Finally, communications networks schedule reference signals transmitted in the UL that, among other things, also may be used for beam searching, beam tracking, and beam refinement. Such signals are here referred to as Sounding Reference Signals (SRS).
To sustain a transmission link between the communications network, e.g. the network node, and the terminal over time-varying conditions (e.g. due to mobility) terminals typically consider several possible BPLs for which the beams are tracked and refined. Such BPLs that are identified jointly by the network and the terminal are here referred to as monitored BPLs.
Out of the monitored BPLs, the communications network and terminal agree to use at least one BPL for data and control channel reception and transmission, herein referred to as an active BPL. Depending on its capabilities, a terminal may support one or more active BPL. Whether two BPLs may be simultaneously active or not depends on the terminal implementation. If the terminal-side (UE) beams associated with two BPL are realized using the same processing components such as antenna panels, analog and/or digital circuitry, software units, etc., the UE may not be able to transmit and receive using those UE beams simultaneously. If that is the case, the BPLs are regarded as incompatible. Whether BPLs are compatible or not has to be known by the communications network, since it typically selects which BPLs to be active or monitored. This is solved during the initialization of the BPL based on a compatibility indication from the UE to the network.
Tracking a BPL implies beam tracking and/or beam refinement at the communications network as well as the terminal. To track a BPL (active or monitored) there must be some transmissions on which to measure and evaluate the link quality. In DL, the more persistent BRS may enable tracking of the DL Tx-beam and, more slowly, of the DL Rx-beam. For faster DL Rx-beam tracking scheduled BRRS may be used. In the event of DL/UL reciprocity, the BRS may be sufficient to track a BPL and no UL transmissions are thus needed.
As described above, before being able to use a new BPL a number of procedures are required such as beam search, detection and signaling to the communications network, configuring of BPL, beam refinement, and/or beam tracking to determine what transmit and receive beams (directions) to use. This may take considerable time.
In scenarios where the radio environment changes fast, and the signal from a used BPL is quickly degraded, there might be too little time to detect and configure a new BPL, in which case there is a risk of losing the connection and thereby also a risk of losing an ongoing communication, e.g. an ongoing call.
According to developments of wireless communications networks an improved beam selection is needed for improving the performance of the wireless communications network.

Network node, a wireless device, and methods therein for beam selection


An AC type plasma display panel having a first and a second electrode, each extending along a line direction and aligning along a row direction across a discharge gap therebetween, where is formed a display discharge cell. A third electrode extends along the row direction and intersects the first and second electrodes. Thus a display matrix is formed with the lines and the rows, and an address discharge cell is formed with the second electrode and the third electrode. Each of the first and second electrodes comprises a laminate of an electrically conductive transparent film stripe having a first side distant from the discharge gap and a second side near to the discharge gap with a metal film stripe thereon. A width of the metal film stripe is narrower than a width of the transparent film stripe. The metal film stripe has a third side distant from the discharge gap, and a fourth side near to the discharge gap. The metal film stripe of at least the first electrode is located such that a first distance between the second side and fourth side is smaller than a second distance between the first side and third second side, whereby a reliable long term operation can be accomplished while reducing the load of the driving circuit without decreasing the luminous efficiency.

1. Field of the invention
This invention relates to a plasma display panel, referred to hereinafter as a PDP, of a matrix display of an AC driving type, and more particularly, relates to a surface discharge form, in which the discharge is generated along the display surface.
2. Description of the Related Arts
PDP is a thin matrix display panel of self-luminous type of a display, and has been widely employed in the application to television pictures and computer monitors upon the achievement of the color display. PDPs have also been remarkable for the large size flat display device, such as for the use in the HDTV, High Definition Television.
A memory effect is utilized in sustaining the lighting state of the cells of the display elements in the PDP of the matrix display type. The AC type PDP is constituted such that the structure has a memory function by coating an insulating material upon electrodes. In the display of the AC type PDPs, a line sequential addressing is performed to accumulate wall charges only in the cells to be luminous, i.e. to be lit; next, sustain voltages of alternating polarization are simultaneously applied onto the entire cells. The sustain voltage is of a predetermined voltage lower than the discharge firing voltage. In the cells having the wall charges therein the sustain voltage superposed with the wall voltage makes the effective voltage applied to the cell exceed the firing voltage resulting in generation of the discharge. Shortening of the sustain voltage application interval provides a visually continuous lighting state.
AC type PDPs of surface discharge form have been commercially on market as color display devices. The surface discharge form is such that pairs of sustain electrodes which are arranged in parallel on a single substrate and one of the pair alternately becomes anode and cathode during a sustain period, that is a display period. The surface discharge form PDP allows us to expect a long operating life by arranging fluorescent material layers for color display on an opposing substrate so as to reduce electron bombardment thereon during the discharge.
FIG. 10 schematically illustrates an internal structure of a prior art PDP 90. FIG. 11 schematically illustrates a luminous strength distribution along the aligning direction of the prior art sustain electrodes.
In PDP 90, on an inner surface of a front glass substrate 91 are arranged pairs of sustain electrodes, that are a first and a second electrode 93 & 94 for each single line of the display matrix. These sustain electrodes 93 & 94 are insulated from a discharge space 99 by a dielectric layer 96. Upon a surface of dielectric layer 96 is provided a protection layer 97 formed of a material having a high secondary emission coefficient. Upon an inner surface of a back glass substrate 92 are arranged the third electrodes 95, that are address electrodes, for each row orthogonal to sustain electrodes 93 & 94. There is provided a fluorescent material layer 98 so as to cover the back glass substrate 92 including the upper surface of address electrodes 95. The type of the fluorescent material layer 98 arranged on the back substrate is called a reflection type. The type of the fluorescent material layer 98 is arranged on the front substrate is called a transmission type. The reflection type is more advantageous than the transmission type in the brightness and the view angle characteristics because the lighting surface of the fluorescent material layer 98 can be directly observed.
First sustain electrode 93 is a composite electrode in which an electrically conductive transparent film 931 is stacked with a metal film 932 as a supplemental conductor which is narrower in the width than electrically conductive transparent film 931, and extends along the line direction. Second sustain electrode 94 is also a stack of an electrically conductive transparent film 941 and a metal film 942, similar to sustain electrode 93. Widths of transparent films 931 & 941 are chosen according to the cell size so that an appropriate electrode spacing is secured between the adjacent lines and the surface discharge can extend widely within the cell. Widths of metal films 932 & 942 are chosen depending on the length so as to secure the electrical conductivity more than the allowable lowest limit. Electrode spacing S2 between the adjacent lines is called an inverse slit.
In the display using PDP 90 a line-sequential addressing is performed. In lighting a cell, address electrode 95 and second electrode 94 are respectively biased appropriately so as to cause an opposing discharge therebetween along the substrate thickness direction so that the surface of the dielectric layer 96, where protection layer 97 is included therein, is appropriately electrically charged, which is called a wall charge. After the addressing operation to determine the lighting/non-lighting of each cell by thus generated wall charge, sustain voltages are applied to first and second sustain electrodes 93 & 94 where the polarity of the applied potential difference is alternately changed, whereby the surface discharges are cyclically generated in the display cells in which the wall charges have been formed. Fluorescent material layer 98 emits a predetermined visible light by being locally excited by an ultraviolet light generated in the surface discharge. The light transmitted through the glass substrate becomes the display light.
As shown in FIG. 11, the luminous strength of the emitted light within each cell becomes maximum at the center of the surface discharge gap S1, which is referred to as a discharge slit, and becomes smaller as leaving along the row direction from the center. In the prior art technique, the metal films 932 & 942 are arranged so as to shift to an extreme end from the surface discharge gap S1, i.e. the side near to the inverse slit S2, of transparent films 931 & 941 in order to minimize the decrease in the luminous strength.
It has been constantly required that the driving voltages of PDPs be lowered from the view points of power consumption, thermal matters and minimization of the driving circuits.
However, on the other hand the display has been required to be finer; accordingly, the cell size must become smaller. In a smaller cell, the discharge firing voltage rises due to the suppression of the movement of the charged particles. This fact is considered that the plasma confined into a small area is likely to cause the reunion to the wall charges, and the amount of the wall charges are so insufficient as to maintain the effective voltage.
In the prior art structure, it has been a problem in that though the shadowing by the metal films 932 & 942 can be kept minimum the luminous efficiency, i.e. brightness/power consumption, is decreased as the cell size is decreased.

Electrode structure of an AC type plasma display panel


A method and apparatus is provide for receiving a first set of optical data from a first field of view and receiving a second set of optical data from a second field of view. A portion of the first set of optical data is communicated and a portion of the second set of optical data is reflected, both toward an optical combiner. The optical combiner then focuses the portions onto the image plane such that information at the image plane that is associated with the first and second fields of view is received by an optical detector and used to determine an attitude characteristic.

This invention relates in general to the field of optical imaging, and more particularly to, a system and method for determining attitude based on optical imaging.
Optical imaging has become increasingly important in today""s society. One area associated with optical imaging relates to attitude determination or precision pointing. Attitude determination generally refers to measurements that relate to the optical orientation of an object based on optical data collected from a light emitting source proximate to the object. In some circumstances, optical cameras or imaging systems may be used to collect such optical data. These imaging systems generally may be attached to the object or the unit for which attitude determination is sought. Optical data collected by these imaging systems are invariably collected from a single field of view that captures the light energy from the light emitting source. While these imaging systems have been adequate for their intended purposes, they have not been satisfactory in all respects. Such imaging systems can be generally expensive, cumbersome, and often lacking in accuracy, for example.
According to one embodiment of the present invention an improved system and method for imaging optical data comprises receiving a first set of optical data from a first field of view and receiving a second set of optical data from a second field of view. A portion of the first set of optical data is communicated and a portion of the second set of optical data is reflected, both toward an optical element. The optical element focuses the portions onto the image plane such that information at the image plane that is associated with the first and second fields of view is communicated to an optical detector and used to determine an attitude characteristic.
Certain embodiments of the present invention provide a number of technical advantages; embodiments of the present invention, may enjoy some, all, or none of these advantages. For example, according to one embodiment of the present invention by collecting optical data from two fields of view, the imaging system of the present invention may achieve high precision pointing and optical orientation determination for an associated unit. This allows increased accuracy in attitude calculation by taking advantage of the ability to examine two fields of view simultaneously. Additionally, collection of optical data from two fields of view is achieved without the need for two separate imaging systems. The implementation of two optical cameras may be undesirable for at least reasons such as: expense, lack of flexibility, increased complexity, structural constraints or limitations, and poor accuracy, for example.
Other technical advantages of the present invention are readily apparent to one skilled in the art from the following figures, the description, and the claims.

System and method for attitude determination based on optical imaging


An apparatus and method for the non-intrusive testing of evaporative fuel vapor systems of motor vehicles. A portable pressure control and monitoring unit is inserted into the fuel filler neck of a vehicle. The vapor vent line, leading from the fuel tank to the charcoal canister of the evaporative system, is temporarily clamped off. Pressurized gas is introduced into the unit from an operator's console, expanding a ring bladder and sealing an annular volume between the unit and the filler neck. Gas is then passed through the unit into the contained volume of the evaporative system. After the neck cap is replaced, an automatic timer deflates the ring bladder, charging the remaining volume of the evaporative system. Pressure decay data is collected and stored in the unit's digital storage device. Initially, this data is used in a pass/fail determination made by a microprocessor in the unit. Later, the data is downloaded into a separate computer for archival purposes.

New federal regulations have established standards for the integrity, or worthiness of the airtight seals included in the evaporative fuel systems of motor vehicles. In response, many state regulatory agencies are requiring periodic testing of the evaporative fuel systems of vehicles so equipped. Such testing is typically done at centralized stations employing a plurality of inspection and testing lanes. The "through-put", or average time required to complete the required inspection and testing at such facilities is always under review for improvement. However, certain testing procedures have heretofore required a certain amount of physical disassembly and reassembly of vehicle components to complete testing.
For example, a current method for testing evaporative systems requires that the fuel vapor vent hose, leading from the fuel tank to the system's charcoal canister, be disconnected at the canister. Then, the hose is connected to a testing device which pressurizes the fuel tank and the remainder of the system for a predetermined period, during which pressure is monitored to detect possible leaks in the system's seals. After the test is complete, the hose must again be restored to its original connection to the canister. Such a testing method is classified as "intrusive" in the industry, and exhibits a number of significant disadvantages.
It is estimated that in approximately ten to twenty percent of the vehicles, the charcoal canisters of the evaporative systems are simply inaccessible. Such vehicles would require a waiver from testing, resulting in a significant number of vehicles never being tested for harmful or unsafe fuel vapor leaks. Also, the process of locating, disconnecting, testing, and reconnecting the correct canister hose is time consuming, increasing through-put time for the testing facilities. Finally, there is a risk of damaging some of the components which must be detached, moved, and reattached to complete the testing. Component damage is particularly likely for older vehicles and for vehicles which have an awkward canister location.
The intrusive method does have one advantage, however, in that it tests the seal integrity of all of the evaporative system components of interest, as a functioning, integrated system. These components typically include the vapor vent hose interconnecting the charcoal canister and the fuel tank, the fuel tank, the fuel filler neck, and the fuel tank filler cap. Representative U.S. Patents showing these components as a system, together with a dedicated testing or fault detection device for certain aspects of the fuel system, include U.S. Pat. Nos. 4,962,744, issued to Uranishi et al., and 5,143,035, granted to Kayanuma.
The prior art also includes non-intrusive testing devices, designed to eliminate most of the above-identified problems associated with the intrusive approach. Thus far, such non-intrusive testing systems contemplate the removal of the fuel tank filler cap and the connection of a pressurization and metering device to the filler neck opening. For example, U.S. Pat. No. 5,239,858, issued to Rogers et al., shows the connection of a helium cylinder and a flow meter to an evaporative system, using a connector cap on the filler neck. Such a testing apparatus still requires that the fuel tank filler cap be tested separately for sealing abilities on a "dummy" filler neck, connected to additional testing apparatus.
Separate testing of the filler cap is the prime disadvantage of this non-intrusive technique, as it does not test the sealing capability of the vehicle's actual filler cap against its own filler neck. In other words, it does not test these components as an operating system, and thus may produce inaccurate, unpredictable results. And, since the filler cap and filler neck components are those which are subject to the greatest wear in an evaporative system, the inability of this prior art apparatus to test these components as a system is a serious deficiency.

Apparatus and method for non-intrusive testing of motor vehicle evaporative fuel systems


Compounds of the formula

The present invention relates to integrin inhibitors useful for their ability to antagonize/block biological processes mediated by xcex1vxcex23 and related integrin receptors, to combinatorial and solid phase methods for preparing libraries of compounds, and utilization of libraries of the compounds for drug discovery. The present invention further provides pharmaceutical compositions for administration to mammals, including man, and methods for their use in the treatment of various disorders including, but not limited to, cancer (tumor metathesis, tumorgenesis/tumor growth), angiogenesis (as in cancer, diabetic retinopathy, rheumatoid arthritis), restenosis (following balloon angioplasty or stent implantation), inflammation (as in rheumatoid arthritis, psoriasis), bone diseases (osteopenia induced by bone metastases, immobilization and glucocortocoid treatment, periodontal disease, hyperparathyroidism and rheumatoid arthritis), and as antiviral agents.
The solid phase synthesis of non-peptidic small organic molecules is a rapidly evolving area of research with applications in the preparation of combinatorial libraries. While the solid phase synthesis of peptides is well established, the solid phase synthesis of non-peptidic small organic molecules is still evolving (Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527-4554). In particular, methods for solid phase synthesis of molecules of biological significance is of importance to drug discovery and is an active area of research.
The integrin xcex1vxcex23 has been shown to mediate the invasion of cancerous melanoma cells into healthy tissue and to protect these cells against natural cell death cycle (apoptosis). Vitronectin receptor(xcex1vxcex23) antagonists have been shown to inhibit the growth of various solid tumors of human origin. More recently, xcex1vxcex23 has been shown to be involved in liver metastasis. Although angiogenesis is an important and natural process in growth and wound healing, it is now appreciated that a variety of clinically relevant conditions are pathologically related to these processes, and that the integrin xcex1vxcex23 is involved. For example, xcex1vxcex23 was shown to be expressed on human wound tissue but not on normal skin and is preferentially expressed on angiogenic blood vessels, such as those feeding a growing/invading tumor. It has also been shown that antagonists of xcex1vxcex23 promote tumor regression by inducing apoptosis of the tumor cells. This process of neovascularization (new blood vessel growth, angiogenesis), which is critical for tumor growth and metastasis, is also an important event in occular tissue, leading to diabetic retinopathy, glaucoma and blindness and in joints, promoting rheumatoid arthritis.
xcex1vxcex23 has been shown to play a pivotal role in the proliferation and migration of smooth muscle and vascular endothetial cells, a pathological process leading to restenosis after balloon angioplastly (Choi et al., J. Vasc. Surgery, 1994, 19, 125-134; Matsumo et al., Circulation, 1994, 90, 2203-2206). At least one type of virus (adenovirus) has been shown to utilize (xcex1vxcex23 for entering host cells (White et al., Current Biology, 1993, 596-599).
Various bone diseases involve bone resorption-the dissolution of bone matter, which is mediated by only one known class of cells, the osteoclasts. When activated for resorption, these motile cells initially bind to bone, a process well known to be mediated by asps (Davies et al., J. Cell. Biol., 1989, 109, 1817-1826; Helfrich et al., J Bone Mineral Res., 1992, 7, 335-343). It is also well known that blockade of xcex1vxcex23 with antibodies or RGD containing peptides block osteoclast cell adhesion and bone resorption in vitro (Horton et al., Exp. Cell Res. 1991, 195, 368-375) and that echistatin, an RGD containing protein, inhibits bone resorption in vivo (Fisher et al., Endocrinology, 1993, 132, 1411-1413). More recently, an RGD peptidomimetic has likewise been shown to inhibit osteoclats in vitro and, by i.v. administration prevents osteoporosis (Engleman et al., J. Clin. Invest., 1997, 99, 2284-2292). Numerous patents/applications have claimed various non-peptide xcex1vxcex23 inhibitors for some or all of the above applications (e.g.WO 95/32710, WO 97/08145, WO 97/33887, U.S. Pat. No. 5,681,820).
Combinatorial chemistry is becoming an important tool for drug discovery and lead optimization (Borman, S. Chemical and Engineering News 1997, 75 (8), 43-63). A combinatorial synthesis requires that at least two components of the product molecules be independently variable, so that all of the combinations of these components can be prepared. A synthesis with three independently variable components is preferable since greater diversity in structure can be produced in the resultant library. Thus to prepare a combinatorial library of integrin inhibitors with a high degree of potential diversity and wide utility for drug discovery using solid phase techniques, it is important to identify a synthesis in which three components can be independently varied.
Most of the reported integrin inhibitors are RGD mimics and they use a xcex2-amino acid like substituted 2,3-diaminopropionic acid as the carboxylic acid terminus. While a cyclic or acyclic guanidino moiety is preferred for the basic end of the molecule, substituted ureas and amidines are used as well. The central scaffold, connecting these two pieces, itself can be varied widely. By developing a convenient route to appropriately protected fragments and a mild solid phase synthesis that incorporates all the three components in an independent fashion, it is possible to prepare combinatorial libraries of this important class of integrin inhibitors.
A solid-phase synthesis of integrin antagonist has been reported recently (Corbett, J. W.; Graciani, N. R.; Mousa, S. A.; DeGrado, W. F. Bioorganic and Med Chem Lett. 1997, 7, 1371-1376). However, this synthesis on solid phase does not provide a means of varying the substitutions on the xcex2-amino acid of the carboxy terminus and uses the commercially available xcex1-N-CBZ-diaminopropionic acid as the only fragment. Hence, a combinatorial library synthesized using this method has limited utility in the drug discovery process lacking structure-activity data for all the regions of the molecule that can be independently varied. It is important to optimize this region of the inhibitors since the lipophilic substitutents in this region and the linkers used to connect these substituents have a significant effect on the activity of this class of molecules.
Multiple compounds can be generated simultaneously by solid phase synthesis. The solid phase synthesis detailed in the present invention for the simultaneous generation of a library of integrin inhibitors where all three components can be varied is not known. The preparation of libraries of compounds of the present invention is useful because it provides rapid structural variation and structure-activity information.
Accordingly, the present invention discloses a solid phase synthesis process for producing compounds represented in formula (I):
wherein:
R1 and R2 independently are alkyl of 1-8 carbon atoms, alkenyl of 2-8 carbon atoms, alkynyl of 2-8 carbon atoms, cycloalkyl of 3-12 carbon atoms, aryl, aralkyl of 6 to 10 carbon atoms, heterocycloalkyl of 5-10 members consisting of carbon atoms and from 1 to 3 heteroatoms selected from N, S and O;
R3 is H, alkyl of 1-6 carbon atoms, aralkoxy of 1-6 carbon atoms;
X is NHCOO, NHCO, NHCONH, NHSO2;
Y is CH2, NH;
Z is CH, N, S
m is 0-4; and
n is 0-3; or pharmaceutical salts thereof.
In some aspects of the invention G may preferably be pyrimidinyl, guanidine, pyridyl-urea, benzyl-urea, azepinyl, imidazolinyl or tetrahydropyrimidinyl.
In other aspects of the invention R1 may be methyl, ethyl, n-propyl, i-propyl, allyl, homoallyl, propargyl, pentyl, n-hexyl, octyl, neopentyl, trichloroethyl, n-butyl, i-butyl, butynyl, phenyl, methylphenyl, dimethylphenyl, halophenyl, methoxyphenyl, acetylphenyl, biphenyl, naphthyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, trimethylcyclopropyl, phenylcyclopropyl, adamantyl, adamantylmethyl, cinnamic, pyridyl, or dimethylfuranyl.
In some preferred aspects of the present invention are provided compounds of Formula (I) wherein G, W, R1, R2, R3, X, Y, Z, m and n are defined above, with the proviso that when W is
and R3 is H, then G is not:
In still other preferred embodiments of the present invention G is
In other embodiment of the present invention it is preferred that W is
In yet other embodments of the present invention G is
and W is
xe2x80x9cAlkylxe2x80x9d, whether used alone or as part of a group such as xe2x80x9calkoxyxe2x80x9d, means a branched or straight chain having from 1 to 10 carbon atoms. Exemplary alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl and hexyl. Lower alkyl refers to alkyl having from 1 to 6 carbon atoms. In some preferred embodiments of the present invention alkyl is from 1 to 8 carbon atoms. Alkyl groups may be substituted with one or more substituents selected from halogen, lower alkyl, lower alkoxy, lower alkylthio, amino, nitro, cyano, carboxy, alkylamino, perhaloalkyl, hydroxy, oxy, phenyl, phenylalkyl, or naphthyl.
xe2x80x9cCycloalkylxe2x80x9d as used herein refers to mono or polycyclic alkyl group of 3-12 carbon atoms. Exemplary cycloalkyl groups include cyclopropyl, cyclohexyl and adamantyl. Cycloalkyl groups may be substituted. One preferred substitution is phenyl.
xe2x80x9cArylxe2x80x9d whether used alone or as part of a group such as xe2x80x9caralkylxe2x80x9d, means mono or bicyclic aromatic ring having from 5 to 10 carbon atoms. Exemplary aryl groups include phenyl and naphthyl. The aryl may be substituted with one or more substituents. Substituents include halogen, lower alkyl, lower alkoxy, lower alkylthio, amino, nitro, cyano, carboxy, carboxyalkyl, alkanoyl, alkylamino, perhaloalkyl, hydroxy, oxy, phenyl, phenylalkyl, or naphthyl. One preferred aryl group is phenyl which may be denoted as Ph in some instances.
xe2x80x9cHeterocycloalkylxe2x80x9d whether used alone or as part of a group such as xe2x80x9cheterocycloalkyl-alkylxe2x80x9d means a stable 5 to 10 membered mono or bicyclic ring of carbon atoms and from 1 to 3 heteroatoms selected from N, O and S. Exemplary heterocycloalkyls include pyrazinyl, pyrazolyl, tetrazolyl, furanyl, thienyl, pyridyl, imidazolyl, pyrimidinyl, tetrahydropyrimidinyl, isoxazolyl, thiazolyl, isothiazolyl, quinolinyl, indolyl, isoquinolinyl, oxazolyl and oxadiazolyl. Preferred heterocycloalkyl groups include pyrimidinyl, tetrahydropyrimidinyl, pyridyl, azepinyl, and imidazolyl. Most preferred heterocycloalkyls include pyridin-2yl, and tetrahydropyrimidine. The heterocycloalkyl may also be substituted with one or more substituents. Substituents include halogen, lower alkyl, lower alkoxy, lower alkylthio, amino, nitro, cyano, carboxy, carboxyalkyl, alkanoyl, alkylamino, perhaloalkyl, hydroxy, oxy, phenyl, phenylalkyl or naphthyl. Preferred substituents include amino and oxy. Preferred substituted heterocyloalkyls include 6 aminopyridin-2yl and tetrahydropyrimid-4-one.
xe2x80x9cAralkylxe2x80x9d means an aryl-alkyl group in which the aryl and alkyl are as previously described. Exemplary aralkyl groups include benzyl and phenethyl. Used in this context, the alkyl group may include one or more double bonds.
xe2x80x9cHeterocycloalkyl-alkylxe2x80x9d means an heterocycloalkyl-alkyl group in which the heterocycloalkyl and alkyl are as previously described. Used in this context the alkyl group may include one or more double bonds. Exemplary heterocycloalkyl-alkyls include pyridylmethyl, pyridylethyl, thienylethyl, thienylmethyl, indolylmethyl, and furylmethyl.
xe2x80x9cAlkoxyxe2x80x9d means an alkyl-O group in which the alkyl group is as previously described. Exemplary alkoxy groups include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, and t-butoxy.
xe2x80x9cAralkoxyxe2x80x9d means an aryl-alkoxy group in which aryl and alkoxy are as previously described.
xe2x80x9cHalogenxe2x80x9d includes fluorine, chlorine, iodine and bromine.
xe2x80x9cProdrugxe2x80x9d, as used herein means a compound which is convertible in vivo by metabolic means (e.g. by hydrolysis) to a compound of Formula I.
Compounds of the present invention include all crystalline forms, pharmaceutically acceptable salts, enantiomers, racemic mixtures, and diasteromeric mixtures thereof.
Some preferred compounds of the present invention include:
2-benzyloxycarbonylamino-3-(2-{4-[2-(3-benzylureido)-ethyl]-piperazin-1-yl}acetylamino)-propionic acid; and
2-benzyloxycarbonylamino-3-(2-{4-[2-(3-benzylureido)-ethyl]-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl}acetylamino)-propionic acid and pharmaceutically acceptable salts thereof
Compounds of the present invention may be prepared in accordance certain solid phase methodology. In one aspect of the present invention, compounds of Formula (I) where
may be prepared in accordance with the steps of:
a) attaching a xcex2-amino acid of the formula
xe2x80x83to a solid support P to produce a compound of formula (1)
xe2x80x83wherein P is preferably a polystyrene resin cross-linked with divinylbenzene and functionalized with a linker such as a hydroxymethylphenoxy group, which is more preferably Wang""s resin:
b) deblocking the fluorenylmethyloxy carbonyl group of said compound of formula (1) with piperidine to produce a compound of formula (2);
c) acylating compound of formula (2) with a chemical species selected from chloroformates, isocyanates, sulfonyl chlorides, carboxylic acid chlorides or carboxylic acids to produce a compound of formula (3)
xe2x80x83wherein X and R1 are as defined above;
d) deblocking the 4,4-dimethyl-2,6-dioxocylohex-1-ylideneethyl protecting group of said compound of formula (3) with hydrazine to produce a compound of formula (4);
e) reacting said compound of formula (4) with a Fmoc protected amino carboxylic acid of formula (5)
xe2x80x83wherein W is as defined above, to produce a compound of formula (6);
f) deblocking the fluorenylmethyloxy carbonyl group of said compound of formula (6) with piperidine to produce a compound of formula (7);
g) reacting said compound of formula (7) with guanidilation reagents of formula (8) or (9) or (10) or amidation reagent of formula (11)
xe2x80x83to produce a compound of formula (12)
xe2x80x83and
h) reacting said compound of formula (12) with a cleaving reagent like trifluoroacetic acid to produce a compound of formula (I)
xe2x80x83wherein R1, X, W and G are as defined above.
Also in accordance with the present invention, where
compounds of Formula I may be prepared in accordance with steps a) through f) to produce compound of formula (7). This aspect of the methods of the invention further comprises the steps of:
i) reacting said compound of formula (7) with isocyanates or with p-nitrophenyl chloroformate, followed by amine to produce a compound of formula (12)
xe2x80x83and
i) reacting said compound of formula (12) with a cleaving reagent like trifluoroacetic acid to produce a compound of formula (I)
xe2x80x83wherein R1, X, W and G are as defined above.
The compounds of the present invention may be prepared according to the general process outlined in Scheme I.
Thus, the orthogonally protected 2,3-diaminopropionic acid is attached to a solid support P, which is preferably a resin of polystyrene cross-linked with divinylbenzene and with a linker such as 4-hydroxymethylphenoxy, most preferably Wang""s resin as described below, in the presence of a coupling reagent such as 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU)/N-hydroxybenzotriazole (HOBT) to produce a compound of formula (1). The compound of formula (1) is deprotected using 20% piperidine in DMF to yield a compound of formula (2), which provides the first handle for diversification.
A compound of formula (2) is reacted with either chloroformates or isocyantes or carboxylic acid chlorides or sulfonyl chlorides in a solvent like dichloromethane or tetrahydrofuran to yield a compound of formula (3). Alternatively, in the case of amide formation, a carboxylic acid is coupled directly with the compound of formula (2) in the presence of a coupling reagent like 1,3-diisopropylcarbodiimide (DIC) to produce the compound of formula (3). A compound of formula (3) is treated with 2% hydrazine to deprotect the (4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl (dde) protecting group to yield a compound of formula (4), which provides a second handle for diversification. A compound of formula (4) is reacted with a Fmoc protected amino carboxylic acid of formula (5) in the presence of a coupling reagent like DIC to produce the compound of formula (6). The compound of formula (6) is deprotected using 20% piperidine in DMF to yield a compound of formula (7), which provides the third handle for diversification. The compound of formula (7) is reacted with N,N-bis-Boc-S-ethylthiourea or 2-(3,5-dimethylpyrazolyl)-4,5-dihydroimidazole or 2-bromopyrimidine or 1-methoxy-2-azacylohept-1-ene to give a compound of formula (12). Alternatively, the compound of formula (7) is reacted with p-nitrophenyl chloroformate and the resulting carbamate was reacted with amines to give ureas of formula (12).
The compounds of the present invention are integrin inhibitors useful for their ability to antagonize biological processes mediated by xcex1vxcex23 and related integrin receptors including, but not limited to, cancer (tumor metastatis, tumorgensis, tumor growth), angiogenesis (as in cancer, diabetic retinopathy, rheumatoid arthritis), restenosis (following balloon angioplasty or stent implantation), inflammation (as in rheumatoid arthritis, psoriasis), bone diseases (osteopenia induced by bone metastases, immobilization and glucocortocoid treatment, periodontal disease, hyperparathyroidism and rheumatoid arthritis), and as antiviral agents. The effect of the compounds to inhibit integrin is determined by standard pharmacological tests.
The purpose of this assay is to measure the effect of various compounds on the xcex1vxcex23-ligand interaction.
Reagents
Plasma Membrane Isolation: 15 confluent T150 flasks of 512P5 cells (xcex1vxcex23 -over expressing cell line) are washed 2xc3x97 with Dulbecco""s phosphate buffered saline (D-PBS) without calcium or magnesium, pH 7.1. Cells are harvested with 10 mL of trypsin/EDTA and collected by centrifugation. The cell pellet is washed 2xc3x97 with 0.5 mg/mL of soybean trypsin inhibitor, and resuspended at 10% weight/volume in homogenization buffer (25 mM Tris-HCl, pH=7.4; 250 mM sucrose). The cell suspension is homogenized with 2xc3x9730(seconds bursts of a Polytron homogenizer. The homogenate is centrifuged at 3000 g for 10 minutes at 4xc2x0 C. The supernatant is collected, measured, and made 100 mM in NaCl and 0.2 mM in MgSO4. The supernatant is centrifuged at 22,000 g for 20 minutes at 4xc2x0 C., the pellet is resuspended in 7 mL of membrane buffer (25 mM Tris-HCl, pH=7.4; 100 mM NaCl; 2 mM MgCl2) by 5 strokes of a Dounce homogenizer (tight pestle) and recentrifuged at 22,000 g for 20 minutes at 4xc2x0 C. The pellet is resuspended in 0.5 mL/flask of membrane buffer (stock membranes) and frozen at xe2x88x9280xc2x0 C. Prior to use, stock membranes are Dounce homogenized and diluted 2 xcexcL to 1000 xcexcL in membrane buffer. See References
Compound Dilution: The stock compounds are dissolved in an appropriate vehicle (typically DMSO) and subsequently diluted in assay buffer composed as follows: 25 mM Tris-HCl (pH=7.4), 100 mM NaCl, 2 mM MgCl2, 0.1% BSA.
Plate Preparation
Wells of Multiscreen-FB assay plates (Millipore MAFB NOB 50) are blocked with 150 mL of 0.1% polyethylenimine for 2 hours at 4xc2x0 C. Following incubation the wells are aspirated and washed with isotonic saline solution.
Binding Assay
125 xcexcL of assay buffer is added to each well. Next, 25 xcexcL of labeled ligand is added to each well. 25 xcexcL of unlabeled ligand is added to non-specific binding wells (NSB). 25 xcexcL of assay buffer is added to all other wells. 2 xcexcL of compound is added to appropriate sample wells, and 2 xcexcL of DMSO is added to NSB and total binding (TB) wells. Finally, 25 xcexcL of membrane is added to each well.
The plates are covered and incubated at 37xc2x0 C. for 2 hours in a humidified incubator. Wells are aspirated on a Millipore vacuum manifold, and the wells are washed with 150 xcexcL isotonic saline solution. Wells are again aspirated. The plates are then dried for 1 hour in an 80xc2x0 C. vacuum drying oven. Plates are placed on a Millipore filter punch apparatus, and filters are placed in 12xc3x9775 mm polypropylene culture tubes. The samples are counted on a Packard gamma counter.
Using 125I-Echistatin (specific activity=2000 Ci/mmol) supplied by Amersham at a final concentration of 50 pM, the following parameters are routinely observed;
Analysis of Results
The individual well activity is expressed as a percentage of the specific binding; % Max, and reported as the meanxc2x1standard deviation. Dose-inhibition relationships are generated for dose (X-axis) vs. % Max (Y-axis) for active compounds using a non-linear regression computer program (PS-NONLIN), and IC50 values with corresponding 95% confidence intervals are estimated from 50% of maximal attachment.
Reference Compounds
Various Arginine-Glycine-Aspartic Acid (RGD)-containing peptides were assessed for the ability to inhibit avb3 binding and the corresponding IC50 values with 95% confidence intervals were generated; peptide structures are given by the standard single letter designation for amino acids. Values obtained compared favorably with adhesion assay results.
1. Nesbitt, S. A. And M. A. Horton, (1992), A nonradioactive biochemical characterization of membrane proteins using enhanced chemiluminescence, Anal. Biochem., 206 (2), 267-72.
The purpose of this assay is to measure the effect of various compounds on the RGD-dependent attachment of cells to osteopontin mediated by the xcex1vxcex23 integrin.
Reagents
Cell Suspension Media
The cells are suspended for assay in the tissue culture media used for normal culture maintenance buffered with 25 mM HEPES (pH 7.4) without serum supplementation.
Compound Dilution Media
The stock compounds are dissolved in an appropriate vehicle (typically DMSO) and subsequently diluted in the tissue culture media used for normal culture maintenance buffered with 25 mM HEPES (pH 7.4) supplemented with 0.2% BSA (no serum); final vehicle concentration is xe2x89xa60.5%.
Plate Preparation
Human recombinant osteopontin (Structural Biology Group, W-AR) is diluted to an appropriate concentration in Dulbecco""s phosphate buffered saline (D-PBS) without calcium or magnesium, pH 7.1. 100 mL of this solution is incubated in the wells of PRO-BIND assay plates (Falcon 3915) for 2 hours at 37xc2x0 C. Following incubation the wells are aspirated and washed once with D-PBS; plates can either be used immediately or stored for up to 1 week at 4xc2x0 C. Prior to assay, the wells are blocked with 1% bovine serum albumin (BSA) in cell suspension media for 1 hour at 37xc2x0 C. Following the blocking period, wells are aspirated and washed once with D-PBS.
Cell Suspension
xcex1vxcex23-expressing cell lines are maintained by standard tissue culture techniques. For assay, the cell monolayer is washed three times with D-PBS, and the cells are harvested with 0.05% trypsin/0.53 mM EDTA (GIBCO). The cells are pelleted by low-speed centrifugation and washed three times with 0.5 mg/mL trypsin inhibitor in D-PBS (Sigma). The final cell pellet is resuspended in cell suspension media at a concentration of 106 cells/mL.
Attachment Assay
Incubation
100 mL of diluted test compound is added to osteopontin-coated wells (in triplicate) followed by 100 mL of cell suspension; background cell attachment is determined in uncoated wells. The plate is incubated at 25xc2x0 C. in a humidified air atmosphere for 1.5 hours. Following the incubation period, the wells are gently aspirated and washed once with D-PBS.
Cell Number Detection
The number of cells attached is determined by an MTT dye conversion assay (Promega) according to the manufacturer""s instructions. Briefly, MTT dye is diluted in cell suspension media (15:85) and 100 mL is added to each well. The assay plates are incubated for 4 hours at 37xc2x0 C. in a humidified 5% CO2/95% air atmosphere, followed by the addition of 100 mL stopping/solubilization solution. The assay plates are covered and incubated at 37+ C. in a humidified air atmosphere overnight. After the solubilization period, the optical density of the wells is measured at a test wavelength of 570 nM with a reference measurement taken simultaneously at 630 nM.
Analysis of Results
The individual well optical density is expressed as a percentage of the maximal attachment (% Max) wells minus background attachment, and reported as the meanxc2x1standard deviation. Dose-inhibition relationships are generated for dose (X-axis) vs. % Max (Y-axis) for active compounds using a non-linear regression computer program (PS-NONLIN), and IC50 values with corresponding 95% confidence intervals are estimated from 50% of maximal attachment.
Reference Compounds
Various Arginine-Glycine-Aspartic Acid (RGD)-containing peptides, and monoclonal antibodies were assessed for the ability to inhibit osteopontin-xcex1vxcex23 attachment and the corresponding IC50 values with 95% confidence intervals were generated in the SK-MEL-24 human malignant melanoma cell line; peptide structures are given by the standard single letter designation for amino acids:
Ruoslahti, R. Fibronectin and its receptors. Ann. Rev. Biochem. 57:375-413, 1988.
Hynes, R. O. Integrins: Versatility, modulation, and signaling in cell adhesion. Cell. 69: 11-25, 1992.
Osteoclast Pitting Assay
The assay is conduct ed as described in Murrills and Dempster (1990) Bone 11:333-344. Briefly, 4xc3x974xc3x970.2 mm slices of devitalized bovine cortical bone are numbered, placed in the wells of 96-well culture plates and wetted with 100 ul of Medium 199 containing Hanks salts, 10 mM HEPES, pH 7.0 (Medium 199/Hanks). Bone cell suspensions containing osteoclasts are prepared by mincing the long bones of neonatal rats (Sprague-Dawley , 4-6 days old) in Medium 199/Hanks. 100 uL of the suspension are then plated onto each slice and incubated 30 minutes to allow osteoclasts to adhere. The slices are rinsed to remove non-adherent cells and incubated 24 h in Medium 199 containing Earle""s salts, 10 mM HEPES and 0.7 g/L NaHCO3, which equilibrates at pH 6.9 in a 5% CO2 atmosphere. At this pH the adherent osteoclasts excavate an adequate number of resorption pits for assay purposes. Slices are fixed in 2.5% glutaraldehyde and osteoclasts counted following tartrate-resistant acid phosphatase staining. In experiments in which osteoclast numbers are significantly reduced in a particular treatment, a check is made for non-specific cytotoxicity by counting the number of contaminant fibroblast-like cells following toluidine staining. All cells are stripped from the slice by sonication on 0.25M NH4OH and the resorption pits formed by the osteoclasts during the experiment stained with toluidine blue. Resorption pits are quantified by manually counting.
Statistics
The experiments are conducted according to a block design with osteoclasts from each animal exposed to each treatment. Three replicate slices are used per treatment per animal, such that a total of 96 slices are examined for an experiment involving four animals and eight treatments (including control). Several parameters are recorded on a xe2x80x9cper slicexe2x80x9d basis: number of pits, number of osteoclasts, number of pits per osteoclast, number of fibroblast-like bone cells. SAS or JMP statistical software are used for statistical analysis. If analysis of variance reveals significant effects in the experiment, those treatments differing significantly from control are identified using Dunnett""s test. IC50s are calculated for active compounds using dose-response curves.
Reference Compound: Rat Calcitonin
Clinical Relavence
Osteoclasts are responsible for the bone loss that occurs in the onset of osteoporosis and anti-resorptive drugs directed against the osteoclast are a requirement for patients losing bone. Calcitonin and bisphosphonates, both used as anti-resorptives in the clinic, show significant osteoclast inhibitory activity in this assay. Hence it is a reasonable assay in which to identify novel anti-resorptives.

Methods for solid phase combinatorial synthesis of integrin inhibitors

Abstract: Compounds of the formula

Abstract: are useful in the treatment of various disorders including, but not limited to, cancer (tumor metathesis, tumorgenesis/tumor growth), angiogenesis (as in cancer, diabetic retinopathy, rheumatoid arthritis), restenosis (following balloon angioplasty or stent implantation), inflammation (as in rheumatoid arthritis, psoriasis), bone diseases (osteopenia induced by bone metastases, immobilization and glucocortocoid treatment, periodontal disease, hyperparathyroidism and rheumatoid arthritis), and as antiviral agents. Novel method of making compounds of formula I are also provided.


This invention is a polymerizable nematic monomer composition comprising (A) 20 to 80 weight % of at least one monomer having the following general formula wherein n is 10, 12 or 14, and (B) 80 to 20 weight % of at least one monomer having the following general formula wherein n is 4, 6 or 8: ##STR1## wherein R is CH.sub.3 or H and Y is covalent bond or --CO.sub.2 --.

Liquid crystalline monomers and mixtures of monomers in combination with photoinitiators can exhibit nematic mesophases. Under ultraviolet ("UV") irradiation these nematic mesophases can undergo rapid photopolymerization, in the presence of UV-photoinitiators, to freeze-in the structure and orientation (alignment) of the nematic mesophase into a polymer matrix.
For instance, Japanese 62 70,406 describes the polymerization of nematic monomers in the liquid crystalline state in the presence of a polymerization initiator with ultraviolet radiation. One or more of the monomers are heated to melt and then cooled into their nematic mesophase. The mesophase is aligned and photopolymerized to obtain an aligned polymer film. The monomers disclosed have the following structure: ##STR2## wherein n is 2, 3, 4, 5, 6, 8 or 11, X is -CN, H, Cl, etc., R is CH.sub.3 or H, and Y is covalent bond or --CO.sub.2 --.
It has been found that compositions disclosed in the cited patent are of limited usefulness in photopolymerization processes because single monomers or mixtures of the monomers disclosed undergo rapid crystallization from the monotropic nematic phase, thus destroying the desired oriented nematic structure before photopolymerization can be performed. Therefore, it is desirable to have polymerizable nematic monomer mixtures that resist crystallization at room temperature.

Polymerizable nematic monomer compositions


The present technology relates to a solid-state imaging element, an imaging device, and an electronic device that can improve transfer efficiency of a charge accumulation unit (MEM) and can increase the number of saturation electrons Qs. In a case where a charge voltage conversion unit (FD) is connected to a center of a charge accumulation unit (MEM) in each pixel and pixels are arrayed in an array, a column in which photoelectric conversion units (PD) are arrayed and a column including charge voltage conversion units (FD) and pixel transistors are arrayed in parallel. The present technology can be applied to a CMOS image sensor.

Conventionally, a complementary metal oxide semiconductor (CMOS) image sensor (CIS) in which a photoelectric conversion unit (photodiode: PD), a charge accumulation unit (MEM), a floating diffusion (FD), and a pixel Tr. (transistor) are formed in an own pixel region and a pixel array is formed has been proposed (see Patent Document 1).
In such a complementary metal oxide semiconductor (CMOS) image sensor (CIS) including a charge accumulation unit (MEM) in a pixel, the charge accumulation unit (MEM) is arranged in an own pixel region, and a change accumulated in the charge accumulation unit (MEM) is transferred to a charge voltage conversion unit (floating diffusion: FD).

Solid-state imaging element, imaging device, and electronic device


An enclosure for operationally retaining a plurality of electronic modules has a housing comprising front, side, upper, lower, and rear walls, and housing enclosing an inner volume. The enclosure has an inner wall running between the side walls and attached to the lower wall. The inner wall is positioned between the front and back walls, and splits the inner volume into a first inner volume and a second inner volume. The inner wall extends from the bottom wall to a height less than that of the height of said top wall, and defines an opening between the first inner volume and the second inner volume. An exhaust vent is disposed through the rear wall of the housing. Openings exist in the housing into the first inner volume. This allows an airflow into the first inner chamber. An environmental flow mechanism, such as a fan, is coupled in proximity to the exhaust vent. The environmental flow mechanism is directionally oriented to create an airflow from the upper portion of the housing outwards through the exhaust vent. The interaction of the directionally drawn air from the top of the casing and the inner wall of blocking an air flow in a lateral direction produces a flow of air in a particular orientation. The flow of air originates from the openings of the housing, moves upwards and laterally to the environmental flow opening, and outwards through the vent.

In many typical computer systems, a so-called "rack" system is implemented. In such a rack system, an electronic bus is provided and cards containing electronic circuits are attached thereto. In this manner, the individual electronic cards may be swapped in and out as needed.
During operation of the electronic equipment, one problem that is encountered is heat buildup within the environment. The circuits used in electronic components radiate heat. This heat can be transferred to the immediate environment, but if the immediate environment heats up, far less heat transfer between the circuits and the environment is possible.
When operating in such an elevated temperature, such circuits are more prone to operational failure. In extreme cases, the circuit may fail completely and be rendered permanently inoperable.
Typically, to effectuate heat transfer from the electronic circuits, an airflow is created in the casing that houses the components. This airflow typically allows for greater heat transfer when more air is in contact with the heated circuit components. With this technique, heat is dissipated from the elements into the air, which is in turn heated. This heated air is then removed from the casing, allowing for cooler air to be drawn into the casing. In this manner the airflow allows for both an enhanced heat transfer between the circuits and interior environment, as well as maintaining an effective heat transfer between the interior and exterior environments is accomplished.

Enclosure for the storage and operation of electronic components having increased airflow characteristics