A bar handle with incorporated lock having a tubular element for gripping a handle, installed on a face of a door by way of interposition of at least one spacer element, and    a lock which is at least partially contained inside the tubular element. The handle includes a release device for releasing the lock, which is configured to be operated manually with a pusher element installed on the tubular element.            the handle comprises a release device for releasing the lock, which is configured to be operated manually with a pusher element installed on the tubular element.

Bar handles with incorporated locks are nowadays widespread and are particularly adapted to be applied to glass doors, often of offices, public places and commercial concerns, both on sliding doors and on leaf doors.
Typically such handles comprise:                two tubular gripping elements, on opposite faces of a same door, each extending longitudinally and being typically positioned vertically,        spacer elements which are adapted to support and connect the tubular element with the door; typically such spacer elements have an extension perpendicular to that of the tubular element.
The two gripping bars and the spacer elements are positioned on opposite faces of a same door at corresponding positions. In the present description reference is made to a "first tubular element" in order to indicate the grip element on the face of the door adapted to be directed toward the outside of the room in the closed configuration, and to a "second tubular element" in order to indicate the element on the face of the same door which is adapted to be directed toward the inside of the room, again in the closed configuration.
Locking elements are contained inside the tubular elements and spacer elements, for joining to each other and for connection to the door.
Normally, in bar handles with an incorporated lock, a cylinder with a security key is arranged in one of the spacer elements of the first gripping bar, while a device for actuating the lock is arranged in the corresponding spacer element of the second gripping bar.
The elements of the lock are placed typically in the tubular element of the second bar, the bar inside the room.
Such elements of the lock comprise an upper tip element and/or a lower tip element, which is/are adapted to be inserted into a corresponding dead hole located on the door threshold area.
Each tip element is moved by a rack element with which it is integral, optionally with the interposition of a transmission element/bar.
The rack element, in turn, is moved by a gearwheel which can be operated both by the cylinder and by the actuation knob.
The coupling between the gearwheel and the rack element converts the circular movement of the cylinder and/or of the actuation knob to a linear movement of the tip element.
The movement of the cylinder is generally transmitted to the gearwheel via a shaft, with which the two components are integral, while the movement of the knob is transmitted to the gearwheel via a pin, with which they are integral.
Such handles, although nowadays widespread, have a drawback in that in order to open a door that has been locked, the tip elements must be retracted from the corresponding dead holes by rotating the key in the cylinder or by rotating the lock actuation knob. These operations are not immediate and on the contrary are an impediment if the user needs to rapidly get outside, especially in emergency situations.
Furthermore, such operations are even more difficult for users with reduced motor capacities. As prescribed by the ADA2010 regulations, which defines the standard known as "the 2010 ADA Standard for Accessible Design", the usable parts must be capable of being actuated with one hand and without forcibly gripping, tightening or turning. The force required to activate the usable parts must be a maximum of 5 pounds (22.2 N).

M. ARTHUR GENSLER, JR. & ASSOCIATES, INC.


A method of using radio frequency identification (RFID), in particular ultra high frequency (UHF) RFID, is described, which keeps pets from accessing forbidden areas. The pet wears a device which is preferably powered by the animal's own activity, converted to electrical power by a motion harvesting system to recharge a battery. The device uses an RFID reader to detect and identify RFID tags placed at boundaries of areas to which the pet is forbidden to enter, and sets off an alarm to warn the pet if it is approaching such an area. Because the RFID tags are individually identifiable, the forbidden area alarm can be configured to the pet, allowing use in a multiple-pet household.

1. Field of the Invention
The invention pertains to the field of animal training. More particularly, the invention pertains to training animals to remain in or avoid a selected area using wireless alarm devices.
2. Description of Related Art
Over 30 million homes in the United States have house pets such as cats, dogs, rabbits or ferrets which are permitted access to some or all of the house. Worldwide, that number is in the hundreds of millions. A typical problem with having a house pet live in your home is that there are certain areas of the home the owner does not want the animal to enter. The area may be a danger to the pet or the pet may not be fully trained and can soil an expensive rug or couch. A further reason may be that the pet can inadvertently damage a display or piece of furniture.
The simplest way to keep a pet out of an area of the house is to close a door or put up physical barricade that will restrain the pet from entering or leaving a certain area. In a conventional house layout with physically divided rooms, this approach could solve some portion of the problem. However, in a house with an "open landscape" interior architecture, where one room flows into another with few dividing walls, this approach does not work well.
There are devices on the market that use a motion sensor to detect the presence of the pet and then sound an ultrasonic alarm. This makes the pet uncomfortable and could make it leave the area. A drawback to this approach is the pet needs to come into the vicinity of the device to be detected. Also, differentiating human motion from animal motion is difficult and the ultrasonic alarm can be on for an extended amount of time, so that the pet becomes accustomed to the sound, making the pet think that the sound is part of its environment rather than a warning. This prevents any learning about acceptable areas and unacceptable areas where the pet can venture.
Another device on the market to solve this problem is to have the pet wear a transmitter that gets detected by a stationary receiver. Whenever the transmitter gets in the vicinity of the receiver, indicating the pet is approaching a forbidden area, an ultrasonic noise is emitted or the pet gets electric shocks through its collar in differing implementation. A problem with these approaches is that the ultrasonic noise must be loud enough to prevent the pet from entering and the receiver is always a distance away from the pet. Using the shock treatment can be considered cruel to the pet, but if the shock is not strong enough to be a deterrent than it could be totally ineffectual. Another problem is that the transmitter in the pet's collar must be transmitting at all times and requires power from rechargeable or expendable batteries. If the batteries are not changed or recharged often, the device will not reinforce the pet's behavior and could become useless. A further problem with all of these devices is that there is no differentiation between pets in a multi-pet household. As an example, an older pet may be allowed in certain areas, but a puppy should be excluded, or the cat is allowed in rooms forbidden to the rabbit and vice-versa.
The Invisible Fence® system made by Invisible Fence, Inc., of Knoxville, Tenn., effectively is the reverse of this last system—the area within which a pet is to be confined is surrounded by a wire which continuously transmits a signal, and the pet (usually a dog) wears a receiver which picks up the signal from the wire. The pet is warned, as described above, when the receiver detects that it has approached the wire too closely. This system has the same drawbacks of the systems which have the pet carrying a transmitter, as well as requiring the entire area to be surrounded by the "fence" wire. In the typical outdoor installation, the wire can be buried, but it could be problematic to conceal the wire within a home.


A method of notifying one or more network nodes in a communications network, comprising an Internet Protocol Multimedia Subsystem, IMS, of a change in RAT used by a user equipment for a communications session, the method comprising at a CSCF prior to set-up of the communications session, indicating by the CSCF to a PCRF that the CSCF requires RAT change notifications for the user equipment, providing a capability indication by the CSCF to the one or more network nodes that the CSCF supports RAT change notifications and receiving from at least one of the one or more network nodes a requirement indication, which indicates that the network node requires RAT change notifications. The method further comprises on receipt of a RAT change notification by the CSCF propagating the RAT change notification to each of the nodes from which a requirement indication has been received.

The increasing availability of Wi-Fi capabilities in wireless devices such as smartphones combined with the free and wide unlicensed spectrum of Wi-Fi networks has led to an increasing use of offloading network traffic onto Wi-Fi networks. Early deployments of Voice over Wi-Fi calling for VoLTE users are now taking market presence.
The mobility of users means that moving between different Radio Access Technologies, RAT, within a single communications session is very common. A problem arises however in that certain parameters related to a communication session set up for on RAT are not optimal when the session is moved to another technology, in particular the codec and the charging regime.
Currently charging differentiation based on the access network used is limited to the type of network in which the call originates. There is no mechanism to apply charging differentiation based on access mobility between Wi-Fi, Long Term Evolution (LTE) and circuit switched legacy networks. This limitation applies to both on-line and off-line charging. There is also no mechanism to trigger a codec change in response to a RAT change.
A possible mechanism to change codec or charging regime would be for the user equipment to send a new Session Initiation Protocol (SIP) INVITE message upon the initiation of a RAT change. However, although this would provide a simple and effective mechanism, there are serious trust issues in allowing the user equipment to initiate a change in charging regime.

Notifying changes in radio access technology


One embodiment of a method of providing ventilation to electronic equipment comprises receiving exhaust air flow from first electronic equipment positioned next to a ventilation structure; directing the exhaust air flow out of exhaust fan assembly of the ventilation structure; receiving cold air from an intake fan assembly of the ventilation structure; and directing the cold air to an intake vent of second electronic equipment positioned next to the ventilation structure.

Data centers and network rooms have been experiencing problems with heat for several years. In network rooms, computer hardware is installed in computer racks and cabinets. Generally, computer racks are lined up in alternating rows with cold-air intakes all facing one aisle (a cold aisle) and hot-air exhausts all facing another aisle (a hot aisle). One potential problem is hardware that features side-to-side ventilation having a right-to-left airflow pattern does not match up with the layout of the cold and hot aisles in the network room that is designed for a front-to-back airflow pattern.

This patent is subject to a terminal disclaimer.

Integrated ventilation system for electronic equipment


There is provided a novel method of forming uniform viral particles under physiological conditions. The method of forming uniform-sized viral particle aggregates composed of viral protein is characterized by incubating a viral protein such as SV40 virus VP1 at pH 5.0 to 7.0, room temperature, in the presence of 130 mM to 170 mM sodium chloride and 1.5 mM to 2.5 mM divalent cation, and in the presence of a particle formation acceleration factor such as SV40 VP2. For encapsulation of a substance to be encapsulated in the viral particles, the substance to be encapsulated is included during the incubation.

Conventional formation of viral particle-like structures has involved recovering virus-like particles formed within cells.
In some methods, the virus-like particles are purified from the cells and are first dissociated into particle structure units (for example, VP1 pentamers in the case of SV40 virus), and then reconstituted into virus-like particles in a test tube.
Conventional reconstituting methods have been conducted under non-physiological conditions with high salt concentration, but because of problems such as inactivation or poor solvent solubility of bioactive substances included in the particles, the conditions have not been suitable for taking up bioactive substances into particles. Moreover, it has been difficult to efficiently reconstitute virus-like particles of uniform size by such methods.

Viral particle-like structure in physiological conditions, and method of forming it


A magneto-inductive flow measuring device having a measuring transducer, which includes a measuring tube a magnet system for producing a magnetic field, and at least one electrode inserted into a bore of the measuring tube for registering an electrical voltage. A securement device is provided, which serves for securing the electrode on the measuring tube. The securement device is at least partially composed of plastic, and is connected with the measuring tube by a plastics welding technology.

For volumetric flow measurement, magneto-inductive flow measuring devices utilize the principle of electrodynamic induction: charge carriers of the medium moved perpendicularly to a magnetic field induce a voltage in electrodes arranged essentially perpendicular to the flow direction of the medium and perpendicular to the direction of the magnetic field. The measurement voltage induced in the electrodes is proportional to the flow velocity of the medium averaged over the cross section of the measuring tube, and, thus, proportional to the volume flow rate. If the density of the medium is known, the mass flow in the pipeline or the measuring tube can be determined. The measurement voltage is usually tapped via the electrode pair, which is arranged in the region of the measuring tube in which the maximum magnetic field strength and, thus, the maximum measurement voltage is to be expected. The electrodes are usually galvanically coupled with the medium; however, magneto-inductive flow measuring devices with contactless, capacitively coupling electrodes are also known.
The measuring tube can, in such case, be manufactured either from an electrically conductive material, e.g. stainless steel, or from an electrically insulating material. If the measuring tube is manufactured from an electrically conductive material, the portion coming in contact with the medium must then be lined with a liner made from an electrically insulating material. The liner is, depending on temperature and medium, for example, made of a thermoplastic, a thermosetting plastic or an elastomeric, synthetic material. However, magneto-inductive flow measuring devices with a ceramic lining are also known.
An electrode can essentially be subdivided into an electrode head, which at least partially comes in contact with a medium flowing through the measuring tube, and an electrode shank, which is almost completely encased in the wall of the measuring tube.
The electrodes are, along with the magnet system, the central components of a magneto-inductive flow measuring device. With regard to the embodiment and arrangement of the electrodes, it is to be ensured that they can be installed in the measuring tube as easily as possible, and that, subsequently during measurement operation, no leakage problems occur; moreover, the electrodes should be characterized by a simultaneously sensitive, and low-disturbance, registering of measurement signals.
In addition to the measuring electrodes, which serve for picking up a measurement signal, additional electrodes in the form of reference or grounding electrodes, which serve to measure an electrical reference potential or to detect partially filled measuring tubes, are often installed in the measuring tube.
U.S. Pat. No. 4,279,166 shows an electrode arrangement of a magneto-inductive flow measuring device for sealing an insert into the flow measuring device. The sealing is achieved, in such case, essentially by a threaded cap, which is screwed onto a screw thread of the insert, and the electrode is affixed in the insert. The arrangement is sealed by an O-ring placed under the shoulder of the electrode.
U.S. Pat. No. 5,224,394 also shows an arrangement for sealing electrodes inserted into the wall of a ceramic measuring tube of a magneto-inductive flow measuring device. For such purpose, the electrode is held in a particular position by a spring, so that the electrode seals off the measuring tube.
U.S. Pat. No. 3,171,990 shows an arrangement for securement of electrodes in a measuring tube. In such case, the electrode is inserted in an insert into the measuring tube, and affixed in assembly by means of a nut and a screw thread on the electrode shank.
These embodiments have, however, the disadvantage, that the radial bores in the measuring tube form weak points, which, in the case of measured substances flowing through under high pressure, lead to cracks and failures. Furthermore, in the case of small nominal diameters of measuring tubes, it is difficult to install the electrodes in the measuring tube and to seal the bores.
Additionally, in the case of measuring tubes made of plastic or synthetic material, the conventional types of securement of electrodes in the measuring tube used in the state of the art are not practical.

Magneto-inductive flow measuring device having a securement means to secure an electrode to the measuring tube


Apparatus for recognizing left-behind objects 2 has a sensor device 3 designed to generate sensor signals 4 upon sensing a left-behind object 2, a control unit 5 designed to receive and process the sensor signals 4 and generate control signals 6 in reaction to the processed sensor signals 4, and a warning device 7, designed to receive the control signals 6 and output a warning signal 8 in reaction to the received control signals 6. A module arrangement 13 of individual component units having pairs of LED sensors and emitters may be arranged in a vehicle 14 to scan a storage region.

The invention relates to a component and a module arrangement for recognizing left-behind objects and a vehicle having such a component or such a module arrangement. In addition, the invention relates to a method for recognizing left-behind objects by means of such a component or such a module arrangement and also a computer program.
It frequently happens that vehicle users forget objects, for example, bags, pieces of clothing, keys, mobile terminals, etc., in the vehicle when leaving the vehicle used by them. This represents a problem in particular for transportation companies, for example, public transit companies, shuttle services, taxi companies, etc., since the forgotten objects have to be stored and managed in order to possibly enable a return to the vehicle user. Moreover, it can happen that forgotten objects are not found by the corresponding transportation company, since, for example other vehicle users have removed the object in the meantime or taken it for themselves. This can in turn have a negative effect on the reputation of the transportation company, since forgotten objects can no longer be given back in such cases.
In addition to inadvertently forgetting objects, intentionally leaving behind is also significant for safety reasons and is also to be prevented.
One approach for avoiding such problems is to take measures meant to prevent leaving behind objects in the utilized vehicle. One example of this is known from patent publication DE102012022318A, which discloses a method and a device for recognizing an object left behind in a vehicle which has been placed in a storage device of the vehicle. A sensor signal for detecting the object is generated by means of a sensor device and is analyzed by a control unit. If a user intentionally leaving the vehicle is sensed, an optical and/or acoustic warning is generated if a sensor signal indicates that a deposited object is present. For example, a light barrier device, a photodetector device, a pressure sensor device, an ultrasonic sensor device, or a device having microswitches can be used as the sensor device.
A similar device is known from U.S. Pat. No. 10,303,961B1, which moreover provides the option of identifying and/or classifying the left-behind objects. International publication WO2018/208315A1 also discloses a similar device, wherein the measurement principle of the sensor device is based on LiDAR (light detection and ranging). A device is described in publication WO2018/203910A1, in which a forgotten object is detected by means of an object sensor, which can be designed, for example as a light barrier, and which activates the interior lighting of the vehicle accordingly upon detection of a left-behind object.
These known methods have the disadvantage that the sensor device is arranged separately and remotely from the device generating the optical and/or acoustic warning. In particular in the case of larger means of transportation, for example buses, this can result in confusion in that a generated warning cannot directly identify a particular left-behind object in the case of multiple left-behind objects and/or the specific location of the left-behind object cannot be uniquely specified by the warning. However, this may be possible by way of complex signal processing methods, which require a correspondingly equipped control unit and therefore cause additional costs and occupy installation space. Moreover, the separate arrangement of sensor device and the device generating the warning makes retrofitting vehicles with these features more difficult.

Recognizing left-behind objects in a transportation vehicle


A method of spatially filtering an image using an adaptive convolution filter is disclosed. The adaptive convolution filter has two major properties. First, size of the convolution filter adapts to the resolution density of the image being filtered. Second, values of the filter dynamically vary depending on an adaptive value that, in turn, depends on the output resolution.

The present invention relates to the art of processing digital images. More particularly, the present invention relates to the art of image filtering techniques for visual enhancement of digital prints and photographs.
Many techniques exist for processing and filtering signals, especially signals representing two-dimensional (2D) images. As the 2D images are increasingly digitized and computerized, it becomes easier to apply many more different filtering techniques than before. Digitized images are typically represented by an array (typically but not necessarily rectangular) of pixels, each pixel represented by a digital value and representing a smallest unit of the digital image.
Spatial filtering is the filtering of an image in the spatial domain. That is, the value of each pixel of the image is modified in contextual relationship to neighboring pixels. Typically, spatial filtering is used to remove noise, to enhance the image, to manipulate the image into some more visually attractive form, or any combination of these. For example, a low pass filter, applied to an image, smoothes the image by removing finer details such as noise but will also blur image detail.
On the other hand, a high pass filter removes low spatial frequencies while retaining (xe2x80x9cpassingxe2x80x9d) high frequency information. This tends to highlight edges and other sharp boundaries. Because of human visual perception consideration, an image having enhanced high frequency components appears sharper than an image without enhanced high frequency components. The following is a typical high pass filter in a 3xc3x973 (conservative) kernel:
Filters are not limited to 3xc3x973 in size, and the values of each component of the kernel may be different to achieve different filtering effects. However, because such filters are rectangular in configuration, they tend to amplify the grid-nature, or digital-ness, of the image they are filtering.
Further, filters of this nature are not necessarily matched in either scale (or strength) or spatial extent to the natural visual scale that is optimum for viewing the digital form of the image.
Consequently, there is a need for a technique and apparatus for filtering images overcoming these shortcomings of the current art and matching the digital image in scale and extent to the optimum visual characteristics as viewed.
The need is met by the present invention. According to one aspect of the present invention, a method of processing an image includes spatially filtering the image using an adaptive convolution filter.
According to another aspect of the invention, an apparatus for processing an image includes a processor and storage connected to the processor. The storage includes instructions for the processor to filter the image using an adaptive convolution filter.
Other aspects and advantages of the present invention will become apparent from the following detailed description, taken in combination with the accompanying drawings, illustrating by way of example the principles of the invention.

Method and apparatus for image processing using adaptive convolution filters

Hewlett-Packard Development Company, L.P.


There is provided a mobile terminal including a movement information acquisition section for acquiring movement information of a mobile terminal possessed by a user, a picked-up image acquisition section for acquiring a peripheral image of the mobile terminal, which is imaged by an imaging device, a transmission section for transmitting the movement information acquired by the movement information acquisition section to a server device which is connected to the mobile terminal via a network, a reception section for receiving community information which is generated by the server device based on a history of the movement information and which can be shared between the user possessing the mobile terminal and another user other than the user possessing the mobile terminal, and a display control section for displaying, on a display screen, a displayed image included in the community information in a superimposed manner on a peripheral image of the mobile terminal.

1. Field of the Invention
The present invention relates to a mobile terminal, a server device, a community generation system, a display control method, and a program, and more particularly relates to a mobile terminal, a server device, an information processing system, a display control method, and a program for generating a community based on a movement log of a user.
2. Description of the Related Art
Lately, Social Networking Service (hereinafter, referred to as SNS) is becoming widespread, which is a web site of community type which promotes and supports the interactions of people with each other.
In the case of establishing a community place such as SNS on a network, a user creates a community by, for example, releasing his/her own profile or photograph, registering a friend, and setting a viewing limitation. Further, as part of augmented reality, there is disclosed a technique of superimposing additional information of the created community or the like on a photographed image (for example, Japanese Patent Application Laid-Open No. 2000-194726).

Mobile terminal, server device, community generation system, display control method, and program


Disclosed herein is a parallel capacitor of a semiconductor device. According to the present invention, a first capacitor and a second capacitor are formed in different layers of the same region, wherein a metal layer connected to an upper electrode of the first capacitor is formed in the same layer as a metal layer connected to a lower electrode of the second capacitor. Thus, twp capacitors can be connected in parallel only with a metal layer composed of three layers. Accordingly, the present invention is advantageous in that it can reduce process steps for forming multiple metal layers, lower a step and cut manufacture cost.

1. Field of the Invention
The present invention relates to a parallel capacitor of a semiconductor device, and more specifically, to a parallel capacitor of a semiconductor device in which two capacitors are connected in parallel to enhance capacitance of the capacitors.
2. Discussion of Related Art
As the level of integration in semiconductor devices increases, researches have been actively made into fabrication of a capacitor having high capacitance in a narrow area. As one of methods, there has been made an attempt on a method in which capacitors are formed in different layers in the same region and are then connected in parallel to increase capacitance.
FIG. 1 is a cross-sectional view showing the structure of a conventional parallel capacitor.
Referring to FIG. 1, the conventional parallel capacitor includes a first capacitor C1, which is formed between a first metal layer 102 and a second metal layer 109a formed on the first metal layer 102, and a second capacitor C2, which is formed between a third metal layer 113b and a fourth metal layer 120a formed on the third metal layer 113b. Each of the first to fourth metal layers 102, 109a, 113b and 120a is formed in a different layer.
In the above, a lower electrode 103 of the first capacitor C1 is electrically connected to the first metal layer 102, and an upper electrode 105 is electrically connected to a second metal layer 109a by means of a via plug 107a. Furthermore, a lower electrode 114 of the second capacitor C2 is electrically connected to the third metal layer 113b, and an upper electrode 116 is electrically connected to a fourth metal layer 120a by means of a via plug 118b.
Meanwhile, the first and third metal layers 102 and 113, which are respectively connected to the lower electrodes 103 and 114 of the first and second capacitors C1 and C2 are electrically connected to second and fourth metal layers 109b and 120b by means of via plugs 107b, 111b and 118c. Furthermore, second and fourth metal layers 109a and 120a connected to the upper electrodes 105 and 116 of the first and second capacitors C1 and C2 are electrically connected to a third metal layer 113a by means of via plug 111a and 118a.
An unexplained reference numeral 101 indicates a semiconductor substrate, 104 and 115 indicate dielectric films, and 106, 108, 110, 112, 117 and 119 indicate interlayer insulating films.
Through the above structure, the first capacitor C1 and the second capacitor C2 are formed to have a parallel structure while being formed in different layers of the same region.
In the above structure, in order to fabricate the two capacitors C1 and C2 in a parallel structure, at least four metal layers 102, 109a, 113b and 120a are required. Such a large number of the metal layers requires a large number of process steps, and also cause a high step to occur. Moreover, if the level of integration in a device becomes high and a design rule thus becomes small, there is a limit to formation of a multi-metal wiring. Furthermore, reliability of a process is degraded and the cost is also increased.

Parallel capacitor of semiconductor device


A decrease in the accuracy after switching of the heating state can be reduced. The physical quantity detecting device includes: a flow rate detecting unit configured to include a heating element to measure a flow rate of a fluid to be measured; a heating element control unit configured to switch a control state of the heating element to any one of a heating state and a heating suppression state; and a signal processing unit configured to process a measured value of the flow rate detecting unit. When the heating element control unit switches the control state, the signal processing unit processes an estimated value determined based on a measured value of the flow rate detecting unit before the switching for a predetermined period immediately after the switching.

A physical quantity detecting device that measures a flow rate by heating a heating element is known. PTL 1 discloses a flow rate measuring method for controlling a flow sensor including a heat source for intermittently heating or cooling a fluid flowing through a flow path and a temperature sensor for measuring the temperature of the fluid and for measuring two fluid flow rates having different physical property values based on a fluid temperature measured by the temperature sensor or a sensor output being a value corresponding to the fluid temperature obtained when a predetermined measurement time has elapsed from the start of heating or cooling of the heat source. The two fluids have a cross point at which the sensor output obtained when one of the fluids flows through the flow path, and the sensor output obtained when the other fluid flows through the flow path at the same flow rate as the one fluid become equal after a predetermined cross time has elapsed from the start of heating or cooling of the heat source. The measurement time is set to the cross time determined in advance.


The present application provides a method of quantifying an amount of a derivatized peptide displayed on a phage by phage display, the method comprising: providing a phage containing a target peptide thereon; reacting the phage containing the target peptide with a first reagent to derivatize the target peptide to form a derivatized peptide, reacting the derivatized peptide with a capture agent comprising a detection marker, thereby incorporating the detection marker within the derivatized peptide; and determining an amount of the detection marker, thereby quantifying the amount of the derivatized peptide dis-played on the phage. A kit comprising a capture agent compris-ing a detection marker for quantifying the phage displayed derivatized peptides is also provided.

The generation of libraries of small molecules and selection of those molecules that bind uniquely to a target of interest is important for drug discovery. The production of genetically-encoded libraries, in which each library member is linked to an information template, such as DNA or RNA, makes it possible to process large chemical libraries without separating individual library members into individual solutions and reaction vessels. One can select target molecules from mixtures of genetically-encoded molecules and identify or amplify the selected molecule of interest using its information template.
Phage display is one example of a genetically-encoded library. Phage display is a well known technique used in the analysis, display and production of protein antigens, especially human proteins of interest. Phage display is a process during which the phage, a bacterial virus, is made to expose or "display" different peptides or proteins including human antibodies on its surface. Through genetic engineering, peptides or proteins of interest are attached individually to a phage cell surface protein molecule (usually Gene III protein, g3p). In such a phage population (phage library), each phage carries a gene for a different peptide or protein-g3p fusion and exposes it on its surface. Through a variety of selection procedures, phages that "display" binders to specific target molecules of interest can be identified and isolated. These binders can include interaction partners of a protein to determine new functions or mechanisms of function of that protein, peptides that recognize and bind to antigens (for use in diagnosis and therapeutic targeting, for example), and proteins involved in protein-DNA interactions (for example, novel transcription factors).
The phage display technique can be very useful in discovery and development of pharmaceutical and/or diagnostic products. In phage display the entire phage binds and can be eluted from an immobilized target molecule. Since the phage remains infective it can inject its DNA into bacterial cells and is amplified. The main limitation of phage display, however, is the occurrence of non-specific adsorption of phages during the binding stage, which necessitates enrichment over several rounds and individually tailored washing and elution conditions. Phage display methods are usually restricted to the production of libraries, which can be encoded by direct DNA-RNA-protein information transfer. These methods are typically limited to linear sequences of peptides, made of only 20 natural amino acids.
Typically, the amplification of libraries of peptides on the surface of the phage requires an in vitro translation system, in which DNA is modified to express the displayed peptides of interest. The generation and use of such translation systems can be expensive and time consuming. The use of self-replicating species such as phage or bacteria simplifies amplification of libraries because each library member is amplified "spontaneously", when given the appropriate resources. For example, for phage displayed libraries, adding one phage to a simple culture broth with bacteria can produce an arbitrarily large population of phage for a very low cost.
Several methods exist which involve conversion of libraries of phage-displayed polypeptides to libraries of peptide derivatives. Typically, these methods use organic synthesis on the peptides to make peptide derivatives. The characterization and improvement of reaction yields is an important cornerstone of organic synthesis. Bulk biochemical methods, such as western blot and mass spectrometry, are often used, to quantify the amount of product obtained or to determine the success of generating the desired reaction products. However, in the absence of this characterization, the synthesis cannot be claimed to be reliable or reproducible. Reactions used for synthesis of such libraries of peptide derivatives have typically been validated using one phage clone or one purified peptide. The actual synthesis of libraries is typically done "blindly", and the efficiency of such synthesis is unknown. The quality of the libraries generated by this method is, thus, usually unknown. While selection from these libraries can provide useful non-peptidic molecules, overall the efficiency of such selection is unclear.
Jesper at al. in U.S. Pat. No. 6,017,732, describe chemical modification of point residues in antibodies displayed on phagemid. This patent discusses a limited set of reactions including the alkylation of a Cys residue within an antibody, and subsequent detection with fluorescence and radioactive probes. The technique described in Jesper is designed for estimating the yield in large (>1010 copies) clonal populations of phage. However, there is no teaching or suggestion of the quantification or optimization of a derivative library synthesis.
U.S. Pat. No. 7,141,366 to Noren et al, describes the production of phage with a unique chemical residue, selenocysteine (Sec), incorporated in a specific location in a phage-displayed peptide. Phage-displayed peptide libraries that contain Sec were generated, thus creating modified peptide libraries. Bulk biochemical methods, such as western blot, were used to qualitatively characterize the chemical modifications that occur on the Sec residue. However, this method cannot be extended to Sec-free peptide libraries, and, further, there is no teaching or suggestion of the quantification or optimization of a derivative library synthesis.
US Patent Publication 2009/0137424 to Schultz et al, describes the production of phage with non-natural amino acids incorporated at a specific location within a phage-displayed peptide using orthogonal tRNA and aminoacyl tRNA synthase. Phage-displayed peptide libraries that contain azido phenyl alanine (AzPhe) are generated. Bulk biochemical methods, such as western blot and mass spectrometry, are used to qualitatively characterize the chemical modifications that occur on AzPhe residues. No methods for quantification of chemical yields in single or multi-step reactions in the synthesis of the library are described, nor strategies for improvement of chemical yields.
U.S. Pat. No. 6,642,014 to Pedersen et al, describes the use of capture agents to select enzymes with improved or new activities. This patent discusses the generation of chemicals by enzyme catalysis, not by direct chemical transformation. Specially-engineered phagemid is used and required to display both enzyme and substrate on the surface of phage.
US Patent Publication 2010/0317547 to Winter and Heinis, describes methods for the generation of a library of bicyclic peptides displayed on phage from a linear peptide, which contains random amino acids flanked by three cysteine residues.
Typically, and as indicated in the above references, the phage display methods known in the art are not designed for efficiency and success of the reactions during synthesis. These previous systems are often characterized on purified protein from phage well after the derivatizing reaction has taken place. The yields of reactions on phage, and the quality and purity of the library are, thus, generally unknown.
Thus, there remains a need for quantitative characterization of peptide-derivative phage display to determine the quality of the phage display procedure and a corresponding optimization of the procedure to ensure optimal yields of reaction products.
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present application. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.

Method of quantifying peptide-derivative libraries using phage display


Methods for the diagnosis and treatment of ischemic spinal conditions, degenerative disc disease, back pain and/or other tissue pathologies. Patients with ischemic spine disease can be categorized into subsets that are deemed to have potential to respond to therapy. In particular, therapies are disclosed which involve stimulation of neovascularization so as to increase perfusion of spinal and other anatomies.

Field of the Invention
The various embodiments herein pertain to the field of diagnosing and treating spinal disorders and/or other tissue disorders, which may including disorders that present with lower back or other pathology. Embodiments relate to methods for diagnosing and/or treating disorders causative, or being precursors to, degeneration of spinal and/or other anatomy. In particular embodiments, treatments include methods of increasing angiogenesis in response to specifically diagnosed conditions.
Description of the Related Art
Musculoskeletal disorders of the spine are an extremely common occurrence associated with debilitating back pain, leading to enormous psychosocial and economic ramifications. Lower-back pain is the leading source of disability in people under 45 years of age, and it results in significant economic losses. Eighty percent of people in the United States will experience back pain at some point in their lifetime, and it is the second most common reason for symptomatic physician visits. Causes of back pain range from injury induced, which often presents as a minor problem, accelerating to a chronic disorder, as well as degenerative spine diseases that lead to degenerative spondylolisthesis and spinal stenosis. The vast majority of chronic back pain is associated with degeneration of the intervertebral disc, which can manifest in many different clinical conditions including spinal stenosis and instability, radiculopathy, myelopathy, and disc herniation.
The human spine is composed of bony structures called vertebrae, separated by intervertebral discs. One of the main functions of the vertebrae is to provide structural support and protection for the spinal cord. Each vertebra is comprised of a spinous process, a bony prominence behind the spinal cord, which shields the cord's nervous tissue on the back side, two bony protrusions on the sides called transverse processes, and a "body" in front of the spinal cord which provides a structural support for weight bearing. The average adult has 24 vertebrae, although at birth 33 are present. Reduction in the number of vertebrae is primarily due to fusion during normal development. The vertebrae are divided by anatomical locations with 7 in the neck, also called the cervical vertebrae, 12 in the middle back, called the thoracic vertebrae, 5 in the lower back, called the lumbar vertebrae, and the sacrum, which is actually formed from five fused vertebrae. The tailbone, called the coccyx is made of three fused vertebrae. Of these, the lumbar vertebrae are the largest, in part since they are responsible for carrying the majority of body weight. In general, the lumbar area is associated with the highest level of degeneration and is believed causative for a wide variety of pain-inducing syndromes.
Separating the vertebrae are soft intervertebral discs that, together with the two facet joints, allow for movement of the vertebrae and therefore provide the ability of the spine to move in various directions. The complex of two facet joints posteriorly and the disc anteriorly is referred to as a spinal segment. The intervertebral disc includes the annulus fibrosus, the nucleus pulposus, and the cartilage endplates. The nucleus pulposus includes anionic proteoglycans, such as aggracan, that have high affinity for water, and provide a cushioning and shock-absorbing function. The annulus fibrosus encapsulates the nucleus pulposus, and includes concentrically organized layers of collagen fibrils (lamellae). The composition of the nucleus pulposus is distinctly different than the annulus fibrosus since the former primarily includes a jelly-like substance and high collagen type I, whereas the latter is made of a solid, fibrotic-like texture, primarily containing collagen type II. In an adult, the cartilage endplate is composed primarily of hyaline cartilage and serves to separate the nucleus pulposus and annulus fibrosus from the adjacent vertebral bone. Discogenic pain often arises from areas of the annulus fibrosus. As a matter of fact, pain-associated molecules such as Substance P and TNF (Tumor Necrosis Factor) have been identified in large concentrations in biopsy samples of patients suffering discogenic pain, but not in controls.
Each disc provides motion and binds the segments together through its 95% non-cellular and 5% cellular components. Nutrition to the disc cells (or chondrocytes) is primarily provided by arteries that arise off of the major blood vessel in the body (called the aorta) and wrap around each vertebral body, penetrating the bone along its circumference. The arteries course through the vertebral body (bone) and then turn towards the disc at either end. The oxygen, glucose and other nutrients are "dropped off" where the disc attaches to the bone and the capillaries and venules form a vascular loop. The cartilage that is in contact with these vascular loops is called the "endplate." The nutrients "diffuse" (or move through the endplate and disc tissue without being transported in blood vessels) into the middle of the disc (or nucleus). In addition to this pathway, arterioles deliver nutrients to the outer edge of the disc (annulus) directly (this pathway provides minimal nutrients to the nucleus in normal discs, but might be exploited in angiogenic treatment). Once the nutrients reach the cell, they are taken up and utilized for the manufacture of materials that make up the disc (extracellular matrix: collagen and proteoglycans). Recent studies have demonstrated that cartilage cells require oxygen to produce enough energy for the proper manufacture and maintenance of the extracellular matrix. If the cells do not receive enough oxygen, the manufacturing process stops and the disc becomes acidic (pH drops). As the nutrient supply is cut off, the cells in the disc begin to die and the disc tissue begins to breakdown. This loss of nutrients is thought to be the initial cause of degenerative disc disease. As the disc continues to degenerate and the cell population decreases, the oxygen concentration may return to normal due to less demand. At this stage, regeneration may be a possibility. However, excessive mechanical loading on a weakened structure precipitates further degeneration which may lead to structural defects such as endplate fracture, radial fissures and herniation. As cells continue to produce energy through anaerobic processes, low pH creates further cell death and possibly ultimate irreversible processes.
Although disc degeneration continues to have a tremendous and ever-increasing impact worldwide, current treatment options do not address the underlying cause. Current treatments include bed rest, nonsteroidal anti-inflammatory medication in the early phases of pathology, and procedures such as discectomy, arthroplasty (joint replacement), injection of artificial nucleus pulposus and fusion in the later phases when the prior approaches did not ameliorate pain. Such approaches are unpredictable, and deal almost exclusively with end-stage clinical manifestations, and therefore do nothing to alter the disease process itself. Additionally, procedures such as vertebral fusion result in the increased incidence of disc degeneration in the adjacent discs due to alterations in the biomechanical distribution of work-load.
Recent advances in both biotechnology and our understanding of the biochemical makeup and environment of the intervertebral disc have led to increased interest in the process of degeneration and the possibility of developing novel treatments aimed directly at disc preservation. Certain genes found to have significant impact on matrix synthesis and catabolism within the disc have provided targets for scientists seeking to alter the balance between the two. To this end, much attention over the past several years has centered on gene therapy, and these efforts have yielded some promising preclinical results with regard to its use in treating disc degeneration. Unfortunately, none of these approaches are near clinical implementation at this time. Additionally, it is important to note that even in the circumstance that disc regeneration alone can be achieved through gene therapy or other interventional means, the underlying process that originally caused the degeneration must be addressed in order to prevent recurrence.
Currently, no biological treatment is widely available for disc degeneration. However, many different molecules of potential therapeutic benefit are being investigated. The focus of molecular therapy has been to prevent or reverse one or more aspects of these changes in the disc extracellular matrix. At least four different classes of molecules may be effective in disc repair. These include anticatabolics, mitogens, chondrogenic morphogens and intracellular regulators. Hallmarks of disc degeneration include loss of proteoglycans, water, and Type II collagen in the disc matrix. Furthermore, other qualitative changes in the matrix are less well defined, including loss of the higher molecular weight proteoglycans, and other changes that are more difficult to quantify (collagen cross-linking, organization of the proteoglycan, etc). An important process in disc degeneration seems to be the change of the differentiated chondrocyte phenotype in the nucleus pulposus into a more fibrotic phenotype. Together these changes in the disc matrix lead to alteration of the disc and vertebral anatomy that ultimately is associated with a pathologic condition.
Because matrix loss is a balance between matrix synthesis and degradation, it is possible to increase disc matrix by increasing synthesis or by decreasing degradation. One approach is to prevent matrix loss by inhibiting the degradative enzymes. Degenerated discs have elevated concentrations of matrix metalloproteinases (MMPs). Within the matrix, MMP activity is normally inhibited by tissue inhibitors of MMPs (TIMPs). Wallach, et al. (Spine 28:2331-2337, 2003) tested whether one of these anticatabolic molecules, TIMP-1, could increase the accumulation of matrix proteoglycans with in vitro experiments. The researchers found that indeed TIMP-1 expression in disc cells increased accumulation and also increased the "measured synthesis rate" of proteoglycans. Chondrogenic morphogens are cytokines that not only possess mitogenic capability but are characterized by their ability to increase the chondrocyte-specific phenotype of the target cell. Most of the research in chondrogenic morphogens has been performed with transforming growth factor-β (TGF-β), bone morphogenetic proteins (BMPs) or growth and differentiation factors (GDFs). Chondrogenic morphogens are particularly attractive because they may reverse the fibrotic phenotype of disc cells to the more chondrocytic phenotype of disc nucleus cells in younger and more "normal" discs. By definition, these molecules are secreted molecules and hence can potentially act in autocrine, paracrine and endocrine fashion. TGF-β1 is one of the first disc morphogenic molecules to be studied. TGF-β1 is a mitogen, but also appears to be highly anabolic molecule leading to significantly increased proteoglycan synthesis per cell. Gene transfer of TGF-β using an adenoviral/CMV vector may be capable of reversing radiological signs of disc degeneration in rabbit models.
BMP-2 is another prototypic chondrogenic morphogen. Recombinant human BMP-2 has been reported to increase production of rat disc cell proteoglycans and significantly increase the chondrocytic phenotype of the disc cells as shown by increased aggrecan and Type II collagen gene expression, with no change in Type I collagen gene expression. BMP-2 has been reported to partially reverse the inhibitory effect of nicotine on the synthesis of disc cell proteoglycan. BMP-7, also known as OP-1 (Osteogenic Protein-1), is another disc cell morphogen that has demonstrated potent in vitro activity in terms of enhancing matrix formation in disc cells. Growth differentiation factor 5 (GDF-5) is also known as CDMP-1 (Cartilage-derived morphogenetic protein 1) has also been considered for regeneration of disc cells.
Intracellular regulators are a distinct class of molecules because they are not secreted and do not work through transmembrane receptors. These molecules are neither cytokines nor growth factors in the classical sense, and yet they can have effects that are quite similar to the secreted molecules discussed previously. This class of molecules typically controls one or more aspects of cellular differentiation. For instance, Sma-Mad (SMAD) proteins are intracellular molecules that mediate BMP-receptor signaling. Although there are no specific published papers on the effect of SMAD proteins on disc cells, proteins such as Smad-1 and Smad-5 are predicted to induce similar effects on disc cells as BMP-2, such as increasing proteoglycan and Type II collagen synthesis. Sox9 (transcription factor) is a chondrocyte marker that is a positive regulator of Type II collagen mRNA transcription. It has also been shown that Sox9 delivered by adenovirus can increase Sox9 expression and disc cell production of Type II collagen in in vitro experiments.
The success of a disc tissue engineering strategy can be dependent on molecular cues to direct the differentiation of cells and affect their biosynthetic function. Many growth factors, including members of the transforming growth factor beta superfamily, affect the differentiation process of disc cells. This group of related proteins directs the induction of mesenchymal precursors to form mature skeletal tissues. The activity of these molecules is complex and affects intercellular signaling pathways. In addition, concentration and timing of presentation of the growth factor influences its activity. Depending on the tissue, the effects of a given morphogen may be different. For instance, the osteogenic molecule bone morphogenetic protein-7-osteogenic protein-1 (BMP-7/OP-1) has been shown to have a dramatic effect on disc cells, increasing their metabolic output of matrix proteins and rescuing them from the detrimental effects of Interleukin 1 (IL-1). This data suggests that growth factors could play a useful role in a cell-based tissue engineering strategy.
Other yet to be identified factors direct cell-to-cell communication and appear to play an important role in the viability and metabolic activity of disc cells. It has been shown that cell proliferation and proteoglycan synthesis can be significantly enhanced in disc cells cultured in a system that allows direct cell-cell contact with bone marrow-derived stromal cells. Other studies have reported that enzymatic disruption of gap junctions can produce a negative effect on cell viability, suggesting that cellular communication plays a vital role in cell viability and function, and therefore interventions supporting their enhancement may be beneficial.

Therapeutic angiogenesis for treatment of the spine and other tissues


A process for treating a sulfur-containing cell by employing an oxidant, such as a hypochlorite, in conjunction with an alkaline hydrolysis solution, such as a sodium hydroxide solution, to react with the sulfur-containing products to produce sulfides and sulfites and then have the oxidant convert the sulfides and sulfites to soluble sulfates followed by neutralization of the solution with a suitable acid, such as sulfuric acid, to produce a solution safe for conventional disposal.

The advent of new laws concerning the disposal of hazardous waste materials may impose problems for the safe disposal of high energy density lithium cells employing a sulfur-containing component. Lithium-sulfur dioxide (Li/SO.sub.2) and lithium thionyl-chloride (Li/SOC12) cells are now being manufactured with safety devices such as fuses, vents, diodes, etc. which allow them to be safely used under various conditions. The advantages of lithium-thionyl chloride cells are their high energy density, flat discharge characteristics, excellent shelf life and operability over a wide temperature range. To promote wide use of these types of cells, it is necessary that they can be safely disposed of whether they are fully discharged, partially discharged or fresh cells. In addition to a sulfur-containing component in the cells, other components such as cyanide may be present from the use of cyanide-containing electrolyte solutions.
Various chemical means have been employed by the battery industry to dispose of toxic or hazardous waste products. Simple neutralization methods have been employed in the lead-acid battery industry. For example U.S. Pat. No. 4,652,381 discloses a battery plant waste water treatment process in which a process of treating industrial waste water contaminated with environmentally unacceptable amounts of sulfuric acid and heavy metals such as lead, copper or zinc is disclosed which permits lowering of the concentration of the contaminants to a level permitting discharge to the sewer. Waste water resulting from floor wash and spray washing of lead acid batteries prior to shipment from the manufacturing facility contains sufficient sulfuric acid to cause the pH to normally be at a level of about 2 along with heavy metal contaminants present in concentrations which require treatment for removal before the discharge water will meet EPA standards. The water to be treated is directed to a first reaction and settling vessel where calcium carbonate is added along with an oxidation medium such as air which also functions to stir the stored waste water. Sufficient calcium carbonate is added to bring the pH of the solution to a level of about 5 and at the same time react with the heavy metals present such as lead, copper or zinc. Calcium sulfate and respective heavy metal carbonates precipitate and settle to the bottom of the treatment zone where they may be readily removed. In a second treatment vessel, calcium hydroxide, along with enough calcium carbonate to maintain an excess of carbonate ion, is added to complete separation of the heavy metals. Final removal of precipitate from the solution is accomplished through a suitable filter.
Reactive liquids have been used to safely dispose of residues of active metals such as sodium, potassium and lithium. For example, U.S. Pat. No. 3,459,493 discloses a process that provides a controlled method for the conversion of the active metal to the corresponding metallic compound (e.g., hydroxide, chloride) by contacting said metal with a two-layer liquid system, the top layer being a low specific gravity nonreactive liquid and the bottom layer being a high specific gravity reactive liquid. The presence of the nonreactive liquid phase limits the reaction rate between the metal and the reactive liquid, and provides a heat sink for the heat of reaction. Depending upon the objects to be achieved, the various process parameters may be altered in such a way as to insure that the reaction is always kept under control and that no dangerous buildup of byproduct hydrogen occurs. These parameters include: ratio of reactive liquid to nonreactive liquid, system temperature, choice of liquid phases, and salts present. Simple two-layer liquid systems consisting of an inert hydrocarbon oil as the top layer and water as the bottom layer are generally preferred, but in some cases it may be desirable to add other reactants, stabilizers, or antifoam agents to produce other desired results.
Chemical scrubber units have been employed to contain and neutralize corrosive fluids such as SOCl.sub.2 and SO.sub.2. For example, U.S. Pat. No. 4,303,745 describes a chemical scrubber 327.0? for containing and neutralizing toxic, corrosive thionyl chloride and sulfur dioxide acid fluids vented by a primary electrochemical cell. The scrubber unit includes an inlet tube coupled to the electrochemical cell by which thionyl chloride and sulfur dioxide vented by the cell are conveyed to an elongated, generally rectangular distribution trap disposed within a housing of the scrubber unit. The distribution trap contains sodium carbonate or sodium bi-carbonate for reacting chemically with and neutralizing thionyl chloride vented by the cell and received within the trap and is itself surrounded within the housing by soda lime for chemically reacting with and neutralizing both sulfur dioxide and thionyl chloride vented by the cell and received within the trap. The distribution trap distributes and disseminates thionyl chloride and sulfur dioxide received thereby over a substantial volume for increasing the exposure of the thionyl chloride and sulfur dioxide to the neutralizing materials (sodium carbonate or sodium bi-carbonate and soda lime) thereby increasing the material utilization of the neutralizing materials.
U.S. Pat. No. 4,448,859 describes a method for deactivating a thionyl chloride cell by introducing a solution of aluminum chloride in thionyl chloride into a discharged cell and allowing the solution to react with the negative active material in the cell.
U.S. Pat. No. 4,637,928 discloses a method for neutralizing reactive material of articles such as batteries. Specifically, a method and apparatus are disclosed for treating batteries in a manner permitting safe disposal thereof, each of the articles comprising a casing having reactive material therein, wherein the article casing is opened to allow access to the interior thereof, fluid is introduced to the interior of the opened casing, and any evolved gas is removed. The steps of opening the casing, introducing fluid and removing gas are performed simultaneously in a reaction vessel which is supplied with the fluid and which is in communication with gas collecting and scrubbing means. The reaction vessel preferably comprises a deluged hammermill and a tank. The hammermill is supplied with articles by a remotely fed conveyor and which discharges into a tank, fluid is supplied to the hammermill and to the tank, and the gas collecting and scrubbing means is in communication with both the hammermill and tank. The fluid preferably is water or an alkaline neutralizing solution. The gas scrubbing means can include a first stage for removing acid gases and a second stage serving as a demister. Liquid is withdrawn from the tank, filtered to remove solids and then returned. A portion of the returned liquid is supplied to the hammermill and another portion is passed through a heat exchanger for cooling and then returned to the tank.
It is an object of the present invention to provide a method for treating high energy density sulfur-containing cells to render the cells safe for disposal.
It is another object of the present invention to provide an improved chemical disposal method for lithium cells containing a sulfur-containing component to render the cells safe for disposal.
It is another object of the present invention to provide an improved chemical disposal method for Li/SOCl.sub.2 and Li/SO.sub.2 cells to render the cells safe for disposal.
It is another object of the present invention to provide a chemical disposal method for sulfur-containing cells also containing toxic components such as cyanide to render the cells safe for disposal.
Other objects and advantages of the present invention will become apparent to those skilled in the art from a reading of the following detailed disclosure and the appended claims.

Process for neutralizing sulfur-containing cells


A device and a method for measuring at least one surface section of an object that is mounted on a carrier includes at least one reference object that can be fixed relative to the carrier, and a holder that can be moved relative to the reference object in at least one first direction and on which a reference body and a distance measuring device are arranged. The reference body and the distance measuring device are mounted in a rotatable manner relative to each other. The distance measuring device is designed to determine a first distance to a first point of the surface section of the object and a second distance to a second point of the reference body wherein the second point corresponds to the first point.

In quality control and also for monitoring industrial production processes, particularly in the field of precision engineering, optics and in the production engineering of mechanical and electrical microstructures, there is an increasing demand for measurements of work piece surfaces with the highest possible resolution and level of precision.
Thus, for example, DE 10 2008 033 942 B3 discloses a distance sensor operating on the principle of multi-wavelength interferometry, which uses a plurality of laser light sources, the emitted wavelengths of which lie in the optical telecommunication range between 1520 nm and 1630 nm. The signals of the lasers used herein are combined in a common fiber by multiplexers and routed to a multi-wavelength sensor head. In principle, such a multi-wavelength distance measuring method enables interferometric scanning of topologies and surfaces of any objects using reflection geometry, wherein the multi-wavelength method provides a comparatively large, uniquely assignable measurement region and wherein it is moreover possible to achieve measurement accuracy in the nanometer or even in the sub-nanometer range.
Furthermore, DE 60 2004 004 916 T2 has disclosed an optical free-form surface measuring device, in which a contour-scanning distance sensor is placed substantially orthogonally in relation to a surface to be measured. Here, the distance sensor is placed on a rotatable device, which itself is arranged on a platform that can be moved in relation to a measurement frame. Furthermore, a measurement surface is provided on the rotatable device that holds the distance sensor, the distance of which measurement surface to the measurement frame is measured by means of an apparatus for contactless distance measurement. Finally, provision is made for a rotational measurement apparatus for measuring the rotational angle between two measurement directions, wherein the first measurement direction is prescribed by the movement direction between the platform and the measurement frame and the second measurement direction is prescribed by the distance between the distance sensor and the surface of the element to be measured.
In the case of such a sensor, which, for example, scans the surface of an object without contact in one scanning movement, the movement and the accuracy of the positioning of the sensor in relation to the object to be measured play a decisive role.
In order to be able to establish precisely the distance between the distance sensor and the surface to be measured, the sensor must be aligned substantially orthogonally to the surface to be measured and must adapt the alignment thereof in accordance with the contour of the object to be measured. For this adaptation, both translational and rotational movements of the sensor are to be carried out.
Although a translational movement of the sensor in relation to a fixed reference can be established with a sufficiently high accuracy by means of further distance sensors, it is precisely a rotation or tilt of the sensor that was found to be problematic.
In the case of the demanded measurement accuracy in the nanometer or sub-nanometer range, a rotation of the sensor furthermore always also brings about a non-negligible translational displacement of the sensor in relation to the platform carrying the sensor. Thus, the measurement signal from the sensor must be corrected by at least the positional displacement of the sensor caused by the rotational movement of the sensor. The mechanical tolerances of the sensor bearing cause non-reproducible positional changes of the sensor in different angular positions. It is therefore necessary to determine precisely the position of the sensor for each possible alignment of the sensor.

Method and device for measuring surfaces in a highly precise manner


Fields such as sequence numbers and length indicators of protocol layers are extended in extended headers so as to be backwards compatible with corresponding legacy headers. The existing fields of the legacy headers are not directly extended. Instead, existing fields are logically concatenated with other fields of the extended header. Whether the extended fields or legacy fields will be used can be determined dynamically based on current transport block size or semi-statically by higher layers.

Examples of 3GPP (3rd Generation Partnership Project) LTE (Long Term Evolution) protocol stacks for control and user planes are illustrated in FIG. 1. One or more of these layers are implemented in nodes in LTE. For example, in a typical UE (user equipment), all layers of both control and user plane protocol stacks are implemented. In a typical eNB (or more generically a network node), all user plane protocol layers and all control plane protocol layers except for the NAS layer are implemented.
According to 3GPP, the new LTE Rel-10 UE categories have recently been defined so that data rates up to 3 and 1.5 Gbps can be reached in the downlink and uplink, respectively. This is enabled by increasing the number of layers for spatial multiplexing and the number of carriers that can be configured for the single UE. With these enhancements, the maximum Transport Block (TB) size is increased to 299852 bits (37482 octets) at the physical (PHY) layer, and the number of transport blocks that can be sent in a single subframe is increased to 10.
However, the U-plane protocol formats defined for LTE Rel-8/9 do not fully support transmission at the high data rates offered by the improved physical layer. This applies to all three sublayers of the L2 (link) layer, i.e., the MAC (Media Access Control) layer, the RLC (Radio Link Control) layer and the PDCP (Packet Data Convergence Protocol) layer.
A size of a MAC SDU (Service Data Unit) contained in a MAC PDU (Protocol Data Unit) can be signalled in a length field (L) of a MAC subheader except when a MAC SDU is included last in the MAC PDU (i.e., not followed by any other data, control or padding) for which no L field is included. Examples of existing MAC subheader structures are illustrated in FIGS. 2A, 2B and 2C
The MAC subheader includes of two reserved bits (R), a 1-bit extension field (E), a 5-bit logical channel field (LCID). The E field is used to indicate whether more fields are present in the MAC subheader. When the E field is not set, then the MAC subheader includes fields R/R/E/LCID as illustrated in FIG. 2C. The last subheader in the MAC PDU and subheaders for fixed size MAC control elements conform to this structure.
For other MAC SDUs, i.e., when the E field is set, the corresponding MAC subheader also includes a 1-bit format field (F) and a 7- and 15-bit L field as illustrated in FIGS. 2A and 2B, respectively. That is, when the E field is set, the MAC subheader includes R/R/E/LCID/F/L fields. The F field indicates the size of the L field. When the F field is set, the L field size is 15 bits as illustrated FIG. 2B, and when the F field is not set, the L field size is 7 bits as illustrated in FIG. 2A.
As illustrated in FIG. 3, a MAC PDU includes a MAC header, zero or more MAC control elements, zero or more MAC SDUs, and an optional padding. The MAC PDU header includes one or more MAC subheaders in which each MAC subheader corresponds to one of a MAC SDU, control element, or padding. The entire MAC PDU—header, control elements, SDUs and padding—is transported in a transport block of the physical (L1) layer.
Referring back to FIGS. 2A-2C, note that the L field is at most 15 bits long. Thus, the maximum supported size of a MAC SDU including the L field is 32767 octets. The L field is included in all MAC PDUs having more than one MAC subheaders. For example, if a MAC PDU includes more than 2 octets of padding in addition to data, the size of the MAC SDU for the data needs to be indicated with the L field. According to the Rel-8/9 specification, each L1 code-word contains exactly one MAC PDU (transport block). Taking the L field limitations into account, the MAC layer cannot fill the MAC PDU with one MAC SDU for the data. On the other hand, having multiple MAC SDUs for new data per logical channel and per transport block is not allowed. With these limitations, a consequence is that the MAC layer cannot make use of the large transport formats offered by the physical layer.
In certain systems supporting RLC, each of the RLC SDUs in an RLC PDU is associated with an 11-bit length indicator field "LI". This limits the possibility of concatenation when RLC SDUs or a remainder of a segmented RLC SDU exceeds 2047 octets. The last RLC SDU does not have the LI field, and it is therefore only limited by the maximum size of the RLC PDU. If concatenation of RLC SDUs is not possible, the RLC layer may generate multiple RLC PDUs instead. Unfortunately, this consumes more RLC SNs (sequence numbers).
This can be problematic since the RLC SN is a 10-bit field (1024 values) which limits the usable window size to 511 RLC PDUs. That is, the RLC transmitter can generate and transmit up to 511 RLC PDUs before receiving an accumulative status message. As will be discussed later, this becomes particularly limiting when concatenation of RLC SDUs is not possible. Further, the RLC PDU size is limited by the RLC SO (segmentation offset) fields—SOstart and SOend—which are 15 bits each. Thus the size of an RLC PDU is limited to the size of the maximum size of a MAC SDU with the L field.
PDCP supports PDCP SDUs of up to 8188 octets in size, which results in a maximum PDCP Data PDU size of 8190 octets including the header. Note that the PDCP SDU size can only be upper-bounded, but it is hardly possible to enforce a lower limit. Typical PDCP SDU (e.g., IP packet) sizes are in the order of 1500 octets. It should further be noted that PDCP PDUs exceeding 2047 octets require special handling at the RLC layer as indicated above.

Backwards-compatible approach to fields of a protocol layer


An error correction encoding system (20) is provided for use in an in-flight programmable spacecraft. The error correction encoding system (20) includes a first data routing switch (22) which receives an uncoded data stream and directs the uncoded data stream to either of a first encoding device (26) or a second encoding device (24). The first encoding device (26) receives the uncoded data stream from the first data routing switch (22) and applies a first encoding function. Alternatively, the second encoding device (24), having a plurality of programmable logic blocks, receives the uncoded data stream from the first data routing switch (22) and applies a second encoding function. A controller (30) is connected to the second encoding device (24) for configuring the plurality of programmable logic blocks to perform the second encoding function. Lastly, a second data routing switch (22) receives a coded data stream from either of the first encoding device (26) or the second encoding device (24) and outputs a coded data stream.

1. Field of the Invention
This invention relates generally to satellite communication systems and, more particularly, to an error correction encoding system for use in an in-flight programmable spacecraft.
2. Discussion of the Related Art
Modern spacecraft routinely exhibit useful lifetimes in excess of ten years. This extended operating life poses a problem for the designers of satellites which transmit digital data that either originated on board or is being retransmitted after on-board demodulation. Rapid advances in coding theory and applicable technology has revolutionized satellite transmission and comparable advances are anticipated in the future. However, once the spacecraft is launched, the downlink encoding scheme cannot be changed.
Today, an on-board computer may be used to perform encoding aboard some spacecraft. Although a software-based encoder might be used for certain types of encoding, it would require a processor architecture that was optimized with respect to both the logic operations associated with encoding and the spacecraft's operational environment (especially temperature and radiation). In other words, the computer-based approach is not suited to high speed data transmission because of processing speed limitations and power penalties imposed by the execution of software instructions and the processor's input/output structure.
Therefore, it is desirable to provide a technique which allows the satellite designers and operators to exploit improved coding techniques for high speed data transmission and reductions in ground terminal decoding costs that may occur after launch. In particular, the present invention permits the satellite designers and operators to change the downlink encoding scheme after the spacecraft had been launched. This enables the future use of coding schemes whose decoding at the receiving terminal was considered impractical at the time of launch, coding schemes that were not developed until after the satellite had been launched or, if it is determined that operating conditions permit, coding schemes simpler than originally deployed.
Over the lifetime of the satellite, the processor costs (i.e., MIPS/dollar) will continue to diminish. As these costs fall, computationally intensive decoding algorithms that initially could not be implemented in an acceptable form will become more attractive. The system designers will then be able to exploit future coding performance improvements in several ways, including: (1) improve overall system availability (i.e., the percentage of time at which the downlink performs at or below a specified bit error rate), (2) increase average throughput by reducing the ratio of coding bits to data bits, and (3) maintain current performance levels while operating terminals with smaller reflectors.

In-flight programmable spacecraft error correction encoder


A flow regulating system can include multiple flow restrictors, at least one of which selectively restricts flow between an interior of a tubular string and an external annulus, a plug which prevents flow through a respective one of the flow restrictors, the plug being aligned substantially perpendicular to a longitudinal axis of the flow restrictor. A method of variably restricting fluid flow in a well can include installing one or more plugs in selected one(s) of multiple openings in a housing, each installed plug preventing fluid flow through a respective flow restrictor, and externally accessing the openings, without removing any cover. An externally adjustable inflow control device can include a housing having multiple openings, multiple flow restrictors, a plug in selected one(s) of the openings, each plug preventing fluid flow through a respective flow restrictor, and each plug being externally accessible, without removal of any cover.

This disclosure relates generally to equipment utilized and operations performed in conjunction with a subterranean well and, in an example described below, more particularly provides for convenient external adjustment of an inflow control device.
An inflow control device is used to restrict flow of fluid produced from an earth formation. It would be beneficial to be able to conveniently and quickly adjust a restriction to flow through an inflow control device. Such improvements in adjustability would also be applicable whether fluid is produced from, injected into, or otherwise flowed in a well.

Externally adjustable inflow control device


The invention relates to an arrangement for reading an information carrier (2). The arrangement comprises a read head (4) for scanning the information carrier along a scanning path. The read head thus generates one or more electric signals (VA, VB, VC, VD) in response to a physical pattern recorded along the scanning path. The arrangement comprises one or more electrical conductors (6.2, 6.3, 6.4, 6.5, 6.6) for conveying these signals to a signal processing unit (8). The electrical conductors include one or more signal conductors (6.2, 6.3, 6.5, 6.6) and at least one reference conductor (6.4). The one or more signal conductors (6.2, 6.3, 6.5, 6.6) are coupled to the at least one reference conductor (6.4) via a resistive impedance (R1, R2, R3, R4) and a capacitive impedance (C), which are connected in series.

The invention relates to a arrangement for reading an information carrier, including a read head for scanning the information carrier along a scanning path and thus generating one or more electric signals in response to a physical pattern recorded along the scanning path, electrical conductors for conveying the one or more electric signals to a signal processing unit.
Such an arrangement is described in U.S. Pat. No. 5,103,439. The arrangement disclosed therein is suitable for reading an optical information carrier. The read head has a radiation source for the generation of radiation, means for imaging the radiation onto a scanning spot on the information carrier and for imaging radiation that leaves the scanning spot onto a detector. The detector has a first to fourth sub-detector and a current-voltage converter for the generation of voltage signals in response to current signals generated by the sub-detectors. In practical versions of the known arrangement the transimpedance amplifier is coupled to a signal processing unit via a flexible cable. From the signals supplied by the current-voltage converter this unit derives an information signal, as well as error signals for servo systems for the control of the position of the read head and of the focusing of the scanning spot.
At high read speeds, for example 10 to 20xc3x97DVD, disturbing reflections may appear at the input of the signal processing unit, as a result of which the signals conveyed via the flexible cable are unreliable. The reflections can be counteracted by terminating the respective conductors of the flexible cable with a resistive impedance near the input of the signal processing unit. However, this gives rise to a substantial increase of the load of the current-voltage converter.
It is an object of the invention to provide an arrangement of the type defined in the opening paragraph, which is suitable for comparatively high reading speeds and in which the load of the current-voltage converter is yet limited.
To this end, the arrangement in accordance with the invention is characterized in that the electrical conductors include one or more signal conductors and at least one reference conductor, the one or more signal conductors being coupled, near the signal processing unit, to the at least one reference conductor via a series connection of a resistive impedance and a capacitive impedance.
In an arrangement for reading an optical information carrier the signals generated by the current-voltage converter have both low-frequency components and high-frequency components. The first-mentioned components are of importance for the servo systems for radial and axial control. The last-mentioned components are indicative of the information read from the information carrier.
In the arrangement in accordance with the invention the impedance formed by the series connection of the resistive and the capacitive impedance is comparatively low at high frequencies. On the one hand, this results in a correct termination for the high-frequency components. On the other hand, the series connection has a comparatively high impedance for the low-frequency components, as a result of which the load of the current-voltage converter is limited.
An attractive embodiment of the arrangement in accordance with the invention has the characteristic feature defined in claim 2. In practice, the signals from the read head are transferred to the signal processing unit with the aid of various signal conductors. The inventor has found that it is possible to use a common capacitive impedance without any appreciable loss in signal quality. This enables the number of component parts to be reduced.
A practical embodiment of the arrangement in accordance with the invention is characterized as defined in claim 3. The read head generally includes a preamplifier, for example in the form of a transimpedance amplifier, also referred to herein as current-voltage converter. In the embodiment defined in claim 3, each signal conductor is disposed adjacent an auxiliary conductor, which itself does not conduct a signal. This limits electromagnetic interference.
This embodiment is particularly favorable in the variant defined in claim 4. In this variant of the detector a radial error signal can be derived by means of the DPD method. In said method the signals corresponding to the first and the third sub-detector are added to one another. Then, it is not a problem if there is crosstalk between these signals in the cable with the conductors. The same applies to the signals from the second and the fourth sub-detector.

Arrangement for reading an information carrier


An inspection system of an embodiment includes: a planar illumination unit that temporally varies an intensity of light in a periodic manner by spatially moving a stripe pattern of the intensity of light; a time-correlation image generator that generates a time-correlation image with a time-correlation camera or an image capturing system that performs an operation equivalent to that of the time-correlation camera; and a calculation processor that calculates a characteristic from the time-correlation image, the characteristic corresponding to a distribution of normal vectors to an inspection target surface and serving to detect an abnormality based on at least either a difference from a surrounding area or a difference from a reference surface.

Conventionally, there have been developed techniques to irradiate an inspection subject with light, to capture the light reflected from a surface of the inspection subject as image data, and to detect abnormalities of the inspection subject based on a luminance variation of the image data.
In addition, there have been developed techniques to periodically vary the intensity of the light irradiating the inspection subject during the image caption and to detect the abnormalities based on the luminance variation of the captured image data.

Kochi Prefectural Public University Corporation


An internal combustion engine has a catalytic converter in its exhaust gas path. In the catalytic converter, two exhaust gas emission measuring probes are provided spatially separated from one another. The phase shift between the output signals of these two measuring probes is used as a measure of the aging of the catalytic converter.

The invention relates to a method and device for detecting an operational condition of catalytic converters.
For internal combustion engines having a catalytic converter and exhaust gas emission measuring probes for post-treatment of exhaust gas, German Published, Unexamined Patent Application 3,224,347 disclosed the analysis of a partial oxygen pressure with the aid of these probes and the control, in dependence thereupon, of a fuel/air ratio of a fuel mixture fed to the internal combustion engine to an almost stochiometric value. For this analysis, the known behavior of an oxygen probe is utilized, i.e. that of changing its output voltage in dependence on the presence of oxygen in the exhaust gas. In this connection, a very steep change in the output voltage within a narrow range around the stochiometric ratio (.lambda.=1) is characteristic of the oxygen probe.
If, during the comparison of the signal emitted by the probe with a predetermined threshold value, a low partial oxygen pressure is detected, that is to say a rich mixture is detected, the composition of the fuel mixture is uniformly made leaner with the aid of an integrator contained in a control device. Conversely, the fuel/air ratio is uniformly enriched when a high partial pressure is detected, that is to say a lean mixture is detected. If a change between the two ranges, i.e. rich and lean, is detected in the fuel/air ratio, the fuel mixture composition is changed by a constant amount. This control behavior described above is produced, for example, via a proportional integral (PI) controller.
In the control method discussed above, it is possible to adapt the control system to various operating conditions of the internal combustion engine in that, for example, the speed of integration of the PI control is selected in dependence on load and rotational speed of the internal combustion engine. It is also possible to select the control parameters in dependence on the operating time of the catalytic converter in order to compensate for the decreasing conversion rate of the catalytic converted with increasing operating time. The operating time can be detected via the operating hours and via the distance travelled. In both possibilities, however, the actual state of activity of the catalytic converter is not detected since this is additionally influenced by various load/speed collectives.
Thus, it is an object of the present invention to detect an actual state of operational activity of a catalytic converter and to provide running time dependent interventions for a control arrangement of an internal combustion engine.
According to preferred embodiments of the invention, this object and other objects are achieved by providing, at the catalytic converter volume, two probes for detecting the exhaust gas composition, the probes being spatially separated from one another. These probes are usually oxygen probes with the aid of which a transition from a rich to a lean fuel/air ratio and conversely is detected. The spatially separated arrangement of the two probes results in a time delay between the two probe signals during the exhaust gas emission measurement. This time delay that is to say the phase shift between the two probe signals, is a measure of the activity of the catalytic converter and thus of its state of aging which influences the conversion rate of the catalytic converter. The result of the measurement of the phase shift is used as additional input parameter for a conventional control system and thus enables running time dependent interventions to be carried out.
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.

Method for detecting the condition of catalytic converters