A method of providing a mobile application is disclosed. In accordance with the method of the present invention, a transmission time and a loading time of the mobile application, and a limitation on a number and a size of the mobile application are minimized, and providing the personalized mobile application is possible.

As a processing performance of a mobile communication terminal is improved, the mobile communication terminal is capable of executing various applications.
For instance, an application provider creates the application based on an execution environment such as WIPI, SKVM and GVM. A user of the mobile communication terminal connects to a mobile communication network to download the application to the mobile communication terminal. The mobile communication terminal executes the application based on the execution environment such as WIPI, SKVM and GVM to provide the application to the user.
Hereinafter, the application executable in the mobile communication terminal is referred to as a "mobile application".
Hereinafter, a mobile application providing server refers to a system of a mobile communication provider that transmits the mobile application to the mobile communication terminal through the mobile communication network or a system of a mobile application provider.
Hereinafter, the mobile communication terminal hereinafter refers to a terminal for receiving the mobile application from the mobile application providing server and executing the received mobile application, which provides the execution environment for the mobile application such as WIPI, SKVM and GVM.
A conventional method for providing the mobile application has following drawbacks.
Firstly, a limitation due to limited resource of the mobile communication terminal exists.
Although latest mobile communication terminals has a high performance, a size of the mobile application that may be stored in the mobile communication terminal and a size of the mobile application that may be processed by the mobile communication terminal are limited.
Secondly, a limitation due to a limited bandwidth of the mobile communication network exists.
The bandwidth provided by the mobile communication network is limited. Therefore, the mobile application provider should optimize a configuration of the mobile application such that the user of the mobile communication terminal may receive the mobile application in a short time. That is, the mobile application provider should minimize a screen configuration or an image configuration of the mobile application such that the mobile application is optimized for the bandwidth of the mobile communication network. Therefore, the mobile application provider cannot use various configurations when creating the mobile application.
Accordingly, a provision of the mobile application for processing various functions is suppressed, and only a simple game mobile application having a small size is provided.
Moreover, a time required to load the mobile application in the mobile communication terminal after a selection of the mobile application by the user is excessively long.
That is, since an entirety of the mobile application is received through the mobile communication network and is loaded as a whole, a time required for an execution of the mobile application is excessively long.


The invention concerns a method and an apparatus for the automatic control of a guided vehicle (2) and proposes a new safety concept which, if breakdowns and/or emergencies arise, prevents the vehicle from being stopped in tunnels, on bridges or on pathless terrain. The invention lies in that between preselected stopping regions (11, 12, 13) provided with system for evaluation of passengers and for intervention by rescue services, the vehicle is always operated at such a high speed that even if the driving force fails, travel can still continue from every point of the line on account of its instantaneous momentum at least as far as a preselected subsequent stopping region in the direction of travel, and if a breakdown and/or emergency situation arises the vehicle (2) is brought to a standstill by initiation of automatic train stop or target automatic train stop in this preselected stopping region (FIG. 1).

The invention concerns a method for the automatic control of a guided vehicle, e.g. a magnetic suspension vehicle, which during its travel is advanced along a predetermined line with a driving force dependent on the line profile and successively passes through stopping regions. The invention also concerns an apparatus with a line on which guided, automatically controllable vehicles, e.g. magnetic suspension vehicles travel, with stopping regions installed along the line and with a device for automatic control of the vehicles.
When employing methods and apparatuses of this kind, up to now it has been usual, if emergency or breakdown suituations arise, to perform automatic train stop or emergency braking immediately until the vehicle comes to a standstill (German patent application Nos. 17 63 748 and 28 49 008). Here, an "emergency situation" means a situation which threatens the lives of the passengers, e.g. a fire breaking out in the vehicle, and a "breakdown situation" on the other hand means a situation which considerably impairs the serviceability or operational reliability of the vehicle, e.g. failure of the drive or power supply. The result of the safety concept pursued up to now is that on account of automatic train stop the vehicle comes to a standstill in a more or less random place, i.e. uncontrolled, and therefore requires that along the while line at the very least ways are provided for the passengers to get out, and preferably also means of evacuating the passengers as well as access routes for rescue services of all kinds.
In case of above-ground wheel/rail vehicles, the fitting of escape and access routes alongside the line involves considerable expanditure, particularly in the region of tunnels, bridges, crossings with roads or pathless terrain. In case of underground vehicles, the expenditure is even greater. Finally in case of suspension, particularly magnetic suspension railways or the like, which are guided on tracks which are supported on stands at a height of several meters above ground, then the problems are multiplied on accound of the fact that to carry out rescue measures, steps, ladders, chutes, footbridges, mobile cranes or the like are required as well.
The many problems which arise particularly when emergency situations occur have already been described a great number of times ("Fire prevention," Deutsche Feuerwehr-Zeitung, 7/1987, pp. 275-277; VFDB (Association for the Promotion of German Fire Prevention) 1/86, pp. 20-24). Now and then it has also been pointed out in this connection that stopping a vehicle in a tunnel when an emergency situation arises is almost never justified and can only aggravate the situation (Railway Gazette International, January, 1988, pp. 27, 28). This has also been recognised by the Federal German Railways; according to their safety concept, if emergnecy and breadkown situations arise, the vehicles should still be capable of running "for a certain minimum period," operation of the emergency brakes by the motor coach driver should make it possible to continue travelling to a "convenient" stopping position, i.e. not lead to immediate stopping of the train on account of automatic train stop, and stopping in tunnels should be avoided (Die Bundesbahn 7/1986, pp. 491-494; 112 Magazin der Feuerwehr, 11 (1986) 7, pp. 338-348).
Even a safety philosophy of this kind cannot meet all requirements in emergency and breakdown situations, as it presupposes reliable functioning of the drive systems. If these fail partly or completely, then it is not possible to reach the end of a tunnel, bridge or the like, so that there are no discernible advantages over immediate stopping by automatic train stop.
By contrast it is the object of the invention to propose a novel safety concept and for this purpose to design the method and apparatus mantioned hereinbefore in such a way that with comparatively simple means and comparatively little expenditure, a large number of difficulties which arise in emergency and breakdown situations can be met.

Method and apparatus for the automatic control of a guided vehicle


A population of nanoparticles is disclosed. The population is comprised of a plurality of core/shell nanocrystals, each including: a semiconductor core, an intermediate semiconductor shell layer disposed over the semiconductor core, an external semiconductor shell layer disposed over the intermediate semiconductor shell layer, and a hydrophilic organic layer in direct contact with the external semi-conductor shell layer. The population of nanoparticles has a αon value of less than about 1.4.

Nanoparticles that fluoresce when excited by an appropriate energy source, such as a laser are powerful detection tools in a variety of life science applications ranging from Western blot detection of proteins, visualization of cell migration, flow cytometric analysis to in vivo imaging. Such nanoparticles also form foundational components in LEDs, solar cells, transistors, and diode lasers. However, the fluorescent nanoparticles currently available suffer from intermittent fluorescence or a stochastic blinking on and off of their fluorescence when the nanoparticles are excited. This blinking on and off limits the robustness of the signal as both the timing and duration of the on/off periods are unpredictable. For single particle or single molecule analysis, the blinking properties limit the usefulness of the fluorescent nanoparticles. Similarly, blinking results in significant hurdles (that can be insurmountable) in ultra high-throughput applications using a population of nanoparticles, due to unpredictable variations in signal intensity resulting from the nanoparticles intermittently toggling between an on/off state.
While not being bound to a particular theory, one premise attributes the blinking behavior to the steep electronic interface between the particle and the "outside world." Blinking therefore may result from the temporary loss of a photo-electron or Auger electron (or a hole) from the particle core to the surrounding matrix, for example by Auger ejection or charge tunneling, or to electron capture by surface-related traps, producing a charged state. When the nanoparticle is in a charged state, emission is turned off. Once charge neutrality is restored, emission turns on, resulting in the characteristic blinking. A key observation driving these theories is that blinking worsens as a function of excitation power. In other words, as the excitation power increases, the blinking typically increases as well. Such observations suggest that blinking occurs with either simultaneous or sequential excitation by two or more photons per excited state. Thus, one useful approach to suppress blinking can be to prevent electrons from escaping the particle core during or following a multi-photon event.
There is a need to develop approaches to provide small (such that they are useful in fluorescence resonance energy transfer applications) and stable nanoparticles which address the problems posed by nanoparticle fluorescent intermittency (as this intermittency complicates the reliable use of "blinking" nanoparticles as a single photon light source for quantum informatics and as biolabels for real-time monitoring of single biomolecules).

Stable nanoparticles and methods of making and using such particles


The present invention is related to a process for preparing safinamide and salts thereof, preferably safinamide methanesulfonate, with high yields and high enantiomeric and chemical purity without the need of using highly pure intermediates. The process of the present invention is suitable for the production of safinamide and its salts, preferably safinamide methanesulfonate, at industrial scale.

Safinamide (compound I) is the international commonly accepted non-proprietary name (INN) for (S)-2-[4-(3-fluorobenzyloxy)-benzylamino]propanamide, and has an empirical formula of C17H19FN2O2 and a molecular weight of 302.34 g/mol.

Safinamide (compound I) is a monoamine oxidase type B (MAO-B) inhibitor. The methanesulfonate salt of safinamide, hereinafter referred to as safinamide methanesulfonate (compound Ia), is known to be therapeutically useful as adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease (PD) experiencing "off" episodes. In Europe and the United States, safinamide methanesulfonate (compound Ia) is marketed under the name of Xadago™.

Safinamide methanesulfonate (compound Ia) was first described in WO90/14334, wherein safinamide (compound I) was prepared, analogously to Example 1, by reductive alkylation of (S)-2-aminopropanamide (compound III) in the form of its hydrochloride salt with 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) using sodium cyanoborohydride as a reducing agent as shown here as follows (scheme 1):

The process disclosed in WO90/14334 is a one-pot process where the iminoalkylation and the reduction with sodium cyanoborohydride are simultaneously performed in the same reactor.
In WO2007/147491A1 safinamide (compound I) is obtained by a three step process which comprises: a) the preparation of 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) by alkylation of 4-hydroxybenzaldehyde (compound V) with 3-fluorobenzyl chloride (compound VI); b) preparation of the imine (S)-2-({4-[(3-fluorobenzyl)oxy]benzylidene}amino)propanamide (compound IV) by reaction of 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) with (S)-2-aminopropanamide (compound III) base or its hydrochloride salt and c) catalytic reduction of the imine (S)-2-({4-[(3-fluorobenzyl)oxy]benzylidene}amino)propanamide (compound IV) with hydrogen and a heterogeneous catalyst (see scheme 2). In the process disclosed in WO2007/147491A1, the iminoalkylation and the reduction are performed sequentially and not simultaneously, either in the same reactor or the imine obtained in step b) is isolated before being catalytically reduced.

WO2009/074478A1 discloses the preparation of safinamide (compound I) by the three steps of scheme 2, but in this case the reduction of the imine (S)-2-({4-[(3-fluorobenzyl)oxy]benzylidene}amino)propanamide (compound IV) is performed with sodium borohydride in methanol, wherein the ratio of methanol to the imine (compound IV) ranges from 0.8 L to 2.0 L per each mole of the imine (compound IV), in order to have a significant portion of the imine (compound IV) present in the reaction medium undergoing the reduction step in the form of a solid during a substantial part of the reaction course.
The processes disclosed in WO2007/147491A and WO2009/074478A1 lead to safinamide (compound I) or its salts, e.g. safinamide methanesulfonate (compound Ia), with a content of (S)-2-[3-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)-benzylamino]propanamide (impurity a) or its salt, e.g. (S)-2-[3-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)-benzylamino]propanamide methanesulfonate (impurity a1), of less than 0.01% by weight.

This impurity is present in safinamide (compound I) or its salts, e.g. safinamide methanesulfonate (compound Ia), due to the formation of 3-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)benzaldehyde (impurity b) in the preparation of the intermediate 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) due to the side reaction of di-alkylation of the 4-hydroxybenzaldehyde (compound V) with 3-fluorobenzyl alkylating agents, e.g. 3-fluorobenzyl chloride (compound VI).

Impurity b present in 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) is converted to impurity a or its salts, e.g. methanesulfonate (impurity a1), when 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) is converted to safinamide (compound I) or its salts, e.g. safinamide methanesulfonate (compound Ia), according to the synthetic strategy depicted in scheme 3:

The processes disclosed in WO2007/147491A1 and WO2009/074478A1 describe that the intermediate 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) has tiny amounts, e.g. not more than 0.01% by weight, of the corresponding impurity 3-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)benzaldehyde (impurity b) in order to obtain safinamide (compound I) or a salt thereof, e.g. safinamide methanesulfonate (compound Ia), with also a tiny amount, e.g. less than 0.01% by weight, of impurity (S)-2-[3-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)-benzylamino]propanamide (impurity a) or a salt thereof, e.g. (S)-2-[3-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)-benzylamino]propanamide methanesulfonate (impurity a1).
Example 6 of WO2007/147491A1 discloses one pot preparation of safinamide (compound I), i.e. without isolation of the imine (compound IV), from 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) having 0.005% by weight of impurity b. Safinamide (compound I) obtained according to this example 6 contains 0.005% by weight of impurity a. Example 7 of WO2007/147491A describes the conversion of safinamide (compound I) obtained in example 6 to safinamide methanesulfonate (compound Ia) having 0.005% by weight of the impurity a1.
Analogously, Examples 12a) and 12a1) of WO2009/074478A1 disclose the one pot preparation of safinamide (compound I) having respectively 0.008% and 0.009% by weight of impurity a, starting from 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) having 0.01% by weight of impurity b. Examples 12b) and 12b1) disclose the conversion of safinamide (compound I) obtained respectively in the examples 12a) and 12a1) to safinamide methanesulfonate (compound Ia) having 0.005% by weight of the impurity a1.
Therefore, the processes disclosed in WO2007/147491A1 and WO2009/074478A1 for preparing safinamide (compound I) or salts thereof, in particular safinamide methanesulfonate (compound Ia), involve the use of the intermediate 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) having very low amounts of impurity b, i.e. not more than 0.01% by weight.
WO 2019/167085 A1, IN 2856/MUM/2009 A, CN 106565520 A, CN 109942451 A, CN 107915656 A and CN 106220525 A disclose processes for preparing safinamide (compound I) or its salts, for example safinamide methanesulfonate (compound Ia), by reducing the imine (S)-2-({4-[(3-fluorobenzyl)oxy]benzylidene}amino)propanamide (compound IV), which in turn is formed by reaction of 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) with (S)-2-aminopropanamide (compound III) base or its hydrochloride salt. Nevertheless, these references are completely silent about the amount of impurity b in 4-[(3-fluorobenzyl)oxy]benzaldehyde (compound II) and the amount of impurity a or its methanesulfonate a1 in respectively safinamide (compound I) or safinamide methanesulfonate (compound Ia).
There is the need to provide a process for preparing safinamide (compound I) or its salts, e.g. safinamide methanesulfonate (compound Ia), in high yields and high enantiomeric and chemical purity, without the need of either using very pure intermediates or having to perform additional purification steps of safinamide or its intermediates.


An improved process for the production of linear alternating polymers of carbon monoxide and at least one ethylenically unsaturated hydrocarbon employs a novel catalyst composition formed from a compound of palladium, the anion of a strong non-hydrohalogenic acid and a bidentate ligand of phosphorus wherein the divalent group bridging the two phosphorus atoms is 2-hydroxy-2-alkyl-1,3-propylene.

The class of linear alternating polymers of carbon monoxide and at least one ethylenically unsaturated hydrocarbon is now well known in the art. These materials, also known as polyketones or polyketone polymers, are represented by the repeating formula ##STR1## wherein A independently is a moiety derived from at least one ethylenically unsaturated hydrocarbon. The polyketone polymers are typically produced by contacting the carbon monoxide and hydrocarbon monomers under polymerization conditions in the presence of a reaction diluent and a catalyst composition formed from a compound of a Group VIII metal, the anion of a strong nonhydrohalogenic acid and a bidentate ligand of phosphorus, arsenic, antimony, nitrogen or sulfur. Without wishing to be limited, a preferred class of catalyst compositions is formed from a bidentate ligand of phosphorus wherein the divalent group bridging the two phosphorus atoms is linear and has three carbon atoms, i.e., the bridging group is 1,3-propylene (trimethylene).
The use of bidentate phosphine ligands containing a bridging group other than 1,3-propylene is known. The nature of catalyst compositions containing such substituted 1,3-propylene bridging groups has been examined, particularly when the bridging group is substituted on the central carbon atom. See, for example, U.S. Pat. No. 4,877,861 and U.S. Pat. No. 4,933,311 as well as copending U.S. patent application Ser. No. 684,109, filed Apr. 12, 1991. In general, the catalyst compositions formed from bidentate phosphine ligands containing 2-substituted-1,3-propylene bridging groups do not provide advantages over the ligands without substituents other than hydrogen in either or both of the two most important consideration for the polymerization process, i.e., faster reaction rate or high molecular weight polymer. It would be of advantage to have an improved process for the production of linear alternating polymers of carbon monoxide and at least one ethylenically unsaturated hydrocarbon which employs a bidentate phosphine ligand with a different type of substitution on the group bridging the two phosphorus atoms.


The invention provides a one piece shingle for use on roof ridges and hips. Shingles of the invention are preferably formed from synthetic materials and preferably comprise a blend of high and low molecular weight polyethylene resins. The unique blend of materials provides a shingle that is both strong while retaining sufficient flexibility to permit the shingle to bend to accommodate a variety of pitches at a ridge or hip. Unique features of the shape and structure of the shingle also make it particularly suited to hip and ridge applications. Furthermore, methods of manufacturing hip and ridge shingles are also disclosed.

Roof hips and ridges present special challenges for the roofing professional. Particularly challenging are applications using synthetic shingles, e.g., shingles constructed from plastic resins. These shingles may be thicker than more traditional shingle materials, such as shingles constructed from metal or bitumen compounds. Furthermore, such synthetic shingles may have a substantially open underside that would be exposed if the shingle were cut and that would be undesirable if visible. In addition, such shingles may have an upper portion that is not intended to be visible, but that may be difficult to obscure with an adjacent shingle in certain ridge or hip applications.
One method of ridge or hip installation that can be successful in some instances is to lay a double course of shingles along the center point of the ridge or hip. Although this installation method can produce an aesthetically pleasing result, it can be time consuming to achieve.
Thus, a need exists for a hip and ridge shingle, suitable for use with shingles constructed from synthetic materials, that (1) is easier to install than traditional hip and ridge shingles, (2) provides an aesthetically-pleasing result, and (3) otherwise overcomes the deficiencies of prior art hip and ridge shingles and methods of installing them.
The terms "first," "second," and the like in the description and in the claims, if any, are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances such that the embodiments of the invention described herein are, for example, capable of operation in sequences other than those illustrated or otherwise described herein. Furthermore, the terms "include," "have," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements is not necessarily limited to those elements, but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
The terms "front," "back," "top," "bottom," and the like in the description and in the claims, if any, are used for descriptive purposes and not necessarily for describing permanent relative positions. It is to be understood that the terms so used are interchangeable under appropriate circumstances such that the embodiments of the invention described herein are, for example, capable of operation in other orientations than those illustrated or otherwise described herein.


The present application discloses a method of manufacturing airtight vessel. More specifically, here is disclosed a method of manufacturing airtight vessel having two substrates, and a frame portion fixed to the two substrates and forming a prescribed space between the two substrates, the method comprising a step of keeping a frame member for the frame portion in a prescribed shape by applying a tension to at least a part of the frame member for the frame portion, and a step of adhering the frame member to at least one of the substrates in a state in which the prescribed shape is kept.

1. Field of the Invention
The present invention relates to a method of manufacturing airtight vessel whose inside is to be kept airtight, and more particularly to a method of manufacturing airtight vessel which can be suitably applied to display panels of image displaying apparatus. The invention also relates to an image displaying apparatus, and a method of manufacturing image displaying apparatus. It also relates to a method of manufacturing television sets.
2. Related Background Art
Usually, an image displaying apparatus utilizing electron emission requires an envelope for maintaining a vacuum ambience, an electron source provided with a plurality of electron-emitting devices and a drive circuit therefor, an image-forming member having a phosphor or the like which is caused to emit light by the collision of electrons, and accelerating electrodes for accelerating the motions of electrons towards the image-forming member and a voltage source or the like therefor. An image displaying apparatus using a flat envelope, such as a thin image displaying apparatus or the like, may use supports (spacers) as structures to endure the atmospheric pressure.
Two types of the electron-emitting devices are already known, including hot cathode devices and cold cathode devices. Of these two types, known cold cathode devices include field-emission electron-emitting devices (hereinafter abbreviated to the FE type), metal/insulator/metal type electron-emitting devices (hereinafter abbreviated to the MIM type) and surface conduction electron-emitting devices.
FIG. 10 schematically shows the configuration of an example of display panel of an image displaying apparatus using conventional surface conduction electron-emitting devices.
In FIG. 10, reference numeral 103 denotes a rear plate; 104, an external frame and 110, a face plate. The rear plate 103, the external frame 104 and the face plate 110 constitute an envelope (airtight vessel) for keeping the inside of the display panel vacuum. An electron source substrate 101 is fixed to the rear plate 103, and N×M surface conduction electron-emitting devices 106 are formed over the electron source substrate 101 (N and M are positive integers not smaller than 2, whose number is appropriately set according to the intended number of display pixels). The N×M electron-emitting devices 106 are wired with M X-directional wires 102 and N Y-directional wires 105 as shown in FIG. 10. Between the X-directional wires 102 and the Y-directional wires 105, at least where they cross, an insulating layer (not shown) is formed to maintain electric insulation.
A fluorescent film 108 consisting of phosphors is formed over the under face of the face plate 110, differentiated in color by phosphors (not shown) of three primary colors including red (R), green (G) and blue (B). Black components (not shown) are provided between the phosphors of different colors constituting the fluorescent film 108, and a metal back 107 consisting of Al or the like is formed on the face of the fluorescent film 108 toward the rear plate 103.
Dx1 through Dxm, Dy1 through Dyn and a high voltage terminal Hv are airtight-structured terminals for electrical connection, provided to electrically connect the display panel to an electrical circuit (not shown). Dx1 through Dxm are electrically connected to the X-directional wires 102 of the electron source, Dy1 through Dyn to the Y-directional wires 105 of the electron source, and Hv to the metal back 107.
The inside of the envelope 111 is maintained in a vacuum of around 1.3×10−4 Pa. As the display area of the image displaying apparatus expands, the need increases for means to prevent deformation or destruction of the rear plate 103 and the face plate 110 due to the pressure difference between the inside and the outside of the envelope 111. Increasing the thicknesses of the rear plate 103 and the face plate 110 would not only make the image displaying apparatus heavier but also give rise to image distortion and parallax when the display panel is viewed obliquely. In view of this problem, the configuration shown in FIG. 10 is provided with structural supports (known as spacers or ribs) 112 consisting of relatively thin glass plates and intended to stand the atmospheric pressure. In this way the gap between the substrate 101 on which electron source is formed and the face plate 110 on which the fluorescent film 108 is formed is usually kept between sub-millimeters to a few millimeters, and the inside of the envelope 111 is kept at a high degree of vacuum.
In an image displaying apparatus using the display panel, when voltages are applied to the electron-emitting devices 106 through extra-container terminals Dx1 through Dxm and Dy1 through Dyn, electrons are emitted from each of the electron-emitting devices 106. At the same time, a high voltage of hundreds to thousands of volts is applied to the metal back 107 via the extra-container terminal Hv to accelerate the motions of the emitted electrons and cause them to collide against the inner face of the face plate 110. The phosphors of different colors constituting the fluorescent film 108 are thereby excited to emit light and display an image.
In addition to ones of the configuration described above, there also are other displays, such as liquid crystal displays, plasma displays and EL displays, in which the internal space is defined by a frame, a face plate and a rear plate, the latter two being two members opposite each other, and a desired atmosphere is maintained in the internal space.
Examples of the prior art realizing such displays are disclosed in Patent Documents 1 and 2.
Patent Document 1: U.S. Pat. No. 5,813,893
Patent Document 2: Japanese Patent Application Laid-Open No. 11-135018

Method of manufacturing airtight vessel for image displaying apparatus


A client computer and a server computer communicate via a network; the server computer receives user identification via the client computer that is selectively a first device or a second device. The server computer stores at least first and second application services for a single predetermined application class, wherein the first and second application services are adapted to client computer type. Upon receiving user identification, the server computer further receives a device attribute from the client computer, compares the device attribute with reference attributes, and selectively sends a representation of the first application service or of the second application service to the client computer according to the device attribute.

Client/server describes a relationship between two computer programs in which one program, the client, makes a service request from another program, the server, which fulfills the request. Although programs within a single computer can use the client/server model, it is a more important idea in a network. In a network, the client/server model provides a convenient way to interconnect programs that are distributed efficiently across different locations.
The client/server model has become one of the central ideas of network computing. Most business applications being written today use the client/server model. In the usual client/server model, one server, sometimes called a daemon, is activated and awaits client requests. Typically, multiple client programs share the services of a common server program. Both client programs and server programs are often part of a larger program or application. For example, a web browser such as Netscape Navigator or Microsoft Internet Explorer is a client program that requests services (the sending of Web pages or files) from a Web server in another computer somewhere on the Internet.
In a distributed network, users interact with front-end computers to call application services from a remote computer. Usually, both front-end computers and remote computers are client-server related, with the front-end computer being the client computer and the remote computer being the server computer.
While the server computer often requires a user interface for administrative functions, such a user interface is more crucial for the user of the front-end computer. Front-end computers can be implemented by a variety of devices, such as, desktop computers, notebook computers, palm size computers, and mobile phones. The user may switch between these devices, but the data from the server computer might fit device properties of different front-end computers only partly or might not fit at all.

Automatically selecting application services for communicating data


An interbody spinal implant made of cortical bone or a bone composite adapted for placement across an intervertebral space formed across the height of a disc space between two adjacent vertebral bodies. The implant has a leading end that includes at least a portion of an arc of a circle from side to side, and sides that are at least in part straight or a trailing end having a radius of curvature of another circle from side to side.

The present invention relates generally to interbody spinal implants preferably adapted for placement into an implantation space created across the height of a disc space between two adjacent vertebral bodies for the purpose of correcting spinal disease at that interspace. The spinal implants are made of an implant material that is bone or a bone composite. The implants are adapted such that fusion occurs at least in part through the implants.
The diaphysis is the shaft of a major long bone between the epiphyses, the ends of the bone forming the joints. Human cadaveric diaphyseal bone is used to form implants made of bone utilized in interbody spinal fusion surgery.
A diaphyseal ring is formed by making two spaced apart cuts approximately perpendicular to the long axis of the diaphyseal portion of a major long bone with the medullary canal forming an opening through the ring. Such rings are generally harvested from femurs for use in the lumbar spine. Other bones from the arm or leg or other part of the human skeleton may be useful in various regions of the spine.
The cuts are generally spaced apart so as to form a ring of bone having a height corresponding to the restored disc space or slightly greater. Diaphyseal ring bone grafts are placed into the spine within and across the height of the space previously occupied by a spinal disc between adjacent vertebral bodies to achieve interbody fusion of those vertebral bodies through the disc space. The diaphyseal ring bone graft is incorporated into the bony fusion over time.
Interbody spinal fusion with diaphyseal bone rings, however, has had limited success in the past. While all the causes for failure may not yet be appreciated, it is nevertheless believed that a failure to gain congruity at the interfaces of the bone ring implant to the adjacent vertebral bodies, and a failure to achieve stability of the bone ring implant, may be two of the more significant factors subject to the surgeon""s control contributing to such failures.
At the time of surgery, where fusion is intended to occur between adjacent vertebral bodies of a patient""s spine, the surgeon typically prepares an opening at the site of the intended fusion by removing some or all of the disc material that exists between the adjacent vertebral bodies to be fused. Because the outermost layers of bone of the vertebral end plate are relatively inert to new bone growth, the surgeon must work on the end plate to remove at least the outermost cell layers of bone to gain access to the blood-rich, vascular bone tissue within the vertebral body. In this manner, the vertebrae are prepared in a way that encourages new bone to grow into or through an implant that is placed between the vertebral bodies.
Present methods of forming this space between adjacent vertebral bodies generally include the use of one or more of the following: hand held biting and grasping instruments known as rongeurs; drills and drill guides; rotating burrs driven by a motor; osteotomes and chisels, and a double wheel cutter or vertebral interspace preparation device. In particular, the double wheel cutter or vertebral interspace preparation device, as disclosed by Michelson in WO 99/63891, incorporated herein by reference, is adapted for linear insertion, i.e., insertion along a single axis, and without the need to substantially move the device from side to side within the disc space along a second axis. In such a preferred embodiment, the device has at its working end an abrading element having a width generally corresponding to the width of the implant to be implanted.
There is a desire to improve congruity at the interfaces of the implant to the adjacent vertebral bodies, and to achieve stability of the implant. Therefore it is advantageous for the contour of the implants to closely match the implantation space formed between and at least in part into the adjacent vertebral bodies to allow a more uniform load transfer across the implant between the vertebral bodies.
Interbody spinal implants that are entirely or almost entirely made of cortical bone or a bone composite material offer the advantages of that material including an appropriate modulus of elasticity and strength for the prescribed use, the capacity to be bioactive, including being osteoconductive, osteoinductive, osteogenic, and to more generally provide a good substrate for the formation of new bone as fusion occurs. Further, by being bioabsorable the bone material is replaced by the patient""s own bone over time, thereby preventing stress shielding and leading to the eventual elimination of any foreign body from the implantation site.
As it is desirable to take advantage of all these benefits, there exists a need for an improved interbody spinal fusion implant made of bone or a bone composite material having a configuration that provides for an improved congruity of the implant to the vertebral bodies and improved implant stability.
In accordance with the purposes of the present invention, as embodied and broadly described herein, an interbody spinal fusion implant made of cortical bone is provided for insertion at least in part into an implantation space formed across the height of a disc space between adjacent vertebral bodies of a human spine. The implant includes a leading end for insertion first into the disc space and a trailing end opposite the leading end. The implant has a length from the leading end to the trailing end. The leading end is configured in the shape of half a circle from side to side. The implant also includes opposed upper and lower portions between the leading and trailing ends that are adapted to be placed within the disc space to contact and support the adjacent vertebral bodies. The upper and lower portions are non-arcuate along at least a portion of the length of the implant. The implant also includes opposite sides between the upper portion and lower portion, and between the leading and trailing ends. At least one of the opposite sides is at least in part straight along at least a portion of the length of the implant.
In accordance with the purposes of the present invention, as embodied and broadly described herein, an interbody spinal fusion implant made of cortical bone is provided for insertion at least in part into an implantation space formed across the height of a disc space between adjacent vertebral bodies of a human spine. The implant includes a leading end for insertion first into the disc space and a trailing end opposite the leading end. The implant has a length from the leading end to the trailing end. The leading end is configured from side to side in the shape of approximately one half of a first circle. The trailing end has a radius of curvature of a second circle from side to side. The second circle has a radius greater than the radius of the first circle. The implant also includes opposed upper and lower portions between the leading and trailing ends that are adapted to be placed within the disc space to contact and support the adjacent vertebral bodies. The implant has a maximum width that is greater than one-half of the width of the adjacent vertebral bodies into which the implant is adapted to be inserted.
The implants of the present invention are preferably manufactured from a bone ring obtained from a major long bone of a human having a medullary canal. The implant includes at least a portion of the medullary canal passing through the upper and lower portions to form a passage adapted to hold bone growth promoting material for permitting for the growth of bone from vertebral body to vertebral body through the passage. In another preferred embodiment, the implants of the present invention are manufactured from a bone composite material.
Additional objects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims.

Contoured spinal fusion implants made of bone or a bone composite material


A false pallet top hingedly connected to a printed work receiving station for a printing press is disclosed, the printing press having a printed works outlet, the station including an apparatus for raising an empty pallet to receive printed work from the outlet and for lowering the pallet as it becomes loaded with printed work. The false pallet top, comprising a single substantially rectangular sheet of rigid material covered with a low friction coating, can easily be moved from a stored vertical position into a horizontal position and slid between printed works within the receiving station allowing a full pallet to be removed and replaced with an empty pallet without stopping the printing press. After an empty pallet is properly positioned, the false pallet can be easily pulled out and placed in the stored position.

It is most economical to operate high speed presses continuously because downtime not only increases labor and other operating costs but it also can increase the chances of producing unusable printed material. While press manufacturers have eliminated one possible source of downtime by providing means for insuring a continuous supply of paper to be printed, downtime can still result because of the need to stop the press to remove accumulated printed work.
One approach to handling the output of printed work from a press is to provide a printed work receiving station at the outlet of the press which includes motorized means for both raising an empty pallet to the outlet of the press to receive printed work and lowering a fully loaded pallet for removal. This approach has many advantages and it works well for smaller runs. However on long runs, it is still necessary that the press be shut down when a pallet becomes fully loaded so that it can be replaced with an empty pallet.
An apparatus which enables long printing runs without shutting down the printing press includes a thin piece of plywood that is received between two horizontal support tracks, the tracks being pivotally positioned at the outlet of the printing press above and parallel to the top of a loaded pallet. Once a pallet is fully loaded, without turning off the printing press, the sheet of plywood is inserted between the two support tracks in a horizontal printed work receiving position permitting printed work to be collected on the sheet of plywood. After insertion of the plywood sheet the loaded pallet is lowered and replaced with an empty pallet. The empty pallet then can be raised up into a receiving position for the printed work directly under the plywood sheet. The support tracks are pivotally moved out of the their supporting position along the edges of the plywood sheet allowing the plywood sheet and the collected printed work thereon to fall onto the empty pallet. New printed work exiting from the outlet of the press then accumulates on the new pallet.
Although an apparatus of the above kind enables long printing runs without the need to turn off the press, the large quantities of plywood necessary for long runs can be very expensive. Each time a plywood sheet is inserted into the receiving area, because of the friction between the plywood and the accumulated printed work thereon, the plywood must remain underneath the printed work and cannot be easily removed until the printed work is taken off the sheet. In many instances, printed work will remain on a loaded pallet for days and even weeks at a time, thus rendering the plywood sheet between the printed work and the pallet unusable for a second pallet exchange.
Long printing runs that do not use plywood have been accomplished by employing a large metallic multi-pronged fork like apparatus (fork) that is inserted above a loaded pallet in place of the plywood. Utilizing this apparatus, after a full pallet is replaced with an empty pallet, and the empty pallet is raised up below the fork, the fork is removed from under the printed work collected thereon to permit that printed work and additional printed work exiting the press outlet to collect upon the top of the previously empty pallet. The fork, instead of being supported by support tracks that outwardly pivot, is supported on its peripheral edges by linear bearings that are supposed to allow the fork to be inserted and removed easily. Using a multi-pronged fork instead of a full plywood sheet, the actual surface area of the temporary printed work collector that frictionally contacts the printed works is minimized and therefore, removal of the collector, without the printed work following, is facilitated.
One problem with the fork apparatus is that many printed works may exit the printing press with a certain degree of curl or bow in them. When the fork like apparatus is inserted, printed work having curl or bow many times may come off the press under some of the fork prongs and on top of others, in effect woven between the prongs of the fork. When a printed work is woven under even a single fork prong, the friction between the prong and the printed work increases substantially. Upon removal of the fork, interwoven printed works follow the apparatus out of, or partially out of, the printed work receiving station and many times are destroyed or rendered unusable.
Another problem with the fork apparatus is that the linear bearings that support the apparatus quickly wear out. Worn linear bearings either have to be replaced or the fork operator must struggle to insert and remove the fork apparatus.
It would be advantageous to have an improved durable work receiving station that would permit a full pallet to be replaced by an empty pallet without shutting down the press and without destroying any of the printed works.


A nozzle of an air supply device is accommodated in a hole (17) in a wall (15) of the device, such as to enable the nozzle to be rotated about a first axis extending through the center of the hole, and pivoted about a second axis that extends perpendicularly to the first axis through two engagement points (6a) on the nozzle. The nozzle includes two or more guide vanes or baffles in the form of tongues (2,3) that have rear deflecting parts (2a,3a) of mutually different curvature, and a front, generally flat outflow part (2b,3b). The nozzle also includes a central tongue-holding part (5) which has resilient hook-shaped engagement elements (6a) at opposite ends. The nozzle may also include a third guide vane or baffle (4) that lacks a curved deflecting part. The air flow exiting from the nozzle can be directed in different planes. The invention also relates to an air supply device provided with one or more such nozzles (1).

The present invention relates to a nozzle for an air supply device for capturing and deflecting an air flow passing through the device, and more particularly to a nozzle of the kind defined in the preamble of Claim 1. The invention also relates to an air supply device provided with one or more such nozzles.
Nozzle-equipped air supply terminal devices of the kind concerned in this document, e.g. devices marketed under the trade name REPUS(copyright), find versatile use for the draught-free supply of attemperated air to different types of locales, including offices and living accommodations. The air blown into the locale from device has a low impulse and the device can therefore often be placed in the immediate vicinity of a working place and therewith ensure that the air present therein will be of a much better quality than would otherwise have been the case.
When cooled air is delivered to an air supply terminal device of the aforesaid kind, it is preferred to mix air from the occupied zone of the room in question with the cooled air in suitable proportions, which is expedient in avoiding cold draughts in the proximity of the floor of the room.
The air jets or nozzles used in such air supply devices for capturing and deflecting air flowing through the device in a main stream direction are either fixed or moveable, e.g. rotatably mounted in a wall of the device and normally including one or more tongues which form guide vanes or baffles and which project into the air flow and therewith deflect the same.
The wall that is equipped with one or more nozzles may be mounted within the device, although the nozzle or nozzles may, alternatively, be disposed in the outer wall of said device. In this latter case, device may have the form of an air supply duct, e.g. in classrooms, for equalizing the temperature gradient in storage locales or for defrosting windows.
The nozzles may be round and divided into chambers by partition walls which, for instance, define angles of 120xc2x0 therebetween. The tongue or tongues projecting into the air flow may have mutually different lengths.
Alternatively, the nozzles may have a generally rectangular shape with one or more curved tongues or baffles, in which case the nozzles are normally fixedly mounted.
SE-C-9600939-4 (Publication No. 508 846) (Lind) describes an air supply device in the shape of a box or a screen that includes a front wall which has disposed therein groups of slots where the groups of slots and the slots in each group are mutually equidistant. Each group of slots is provided on the inside of the wall with a nozzle module in which the number of nozzles equals the number of slots and where said nozzles are intended to deflect sub-flows repeatedly from a supplied main flow through an angle of 90xc2x0. Each nozzle is provided to this end with curved deflecting parts which project progressively further out in the direction of the main flow. The deflected sub-flows collide and exit outwardly through the slots associated with respective nozzles with a low impulse.
EP-B1-0 507 756 (Stifab) describes an air supply terminal device which comprises a distribution plate that includes a plurality of circular openings that accommodate nozzles provided with deflecting elements in the form of guide vanes or baffles that project out beyond the plane of the plate. The nozzles are mounted in the hole for both rotatable and pivotal movement, so that in one nozzle position the exiting air flow will be directed upwards and in another position will be directed horizontally.
SE-C-9600635-1 (Publication No. 511 340) (Stifab Farex) describes a further development thereof, in which the rotatable nozzles are set in different positions such that the exiting air will be caused to rotate resulting in high entrained ejection of room air.
Although these known nozzle designsxe2x80x94which have the characteristic features set forth in the preamble of Claim 1xe2x80x94enable an adjustable near zone to be achieved for directing the flow of exiting air in a desired direction, they are unable to produce uniform flow distribution. This is due, among other things, to the fact that all the tongues or baffles of the nozzle have the same shape, meaning that at least a part of the tongues will not follow the flow lines of the air.
This also applies to the nozzle described in DE 888 308 (Fourtier), which lacks outwardly projecting, curved deflecting parts on the guide vanes.
Other drawbacks with known nozzles are that such nozzles have a limited directional effect, that they can only be accommodated in a flat plate provided with holes for accommodating respective nozzles, and are expensive to produce as a result of being comparatively material consuming.
With a starting point from the aforesaid, an object of the present invention is to provide a nozzle of the aforedescribed kind that has uniform flow distribution and which allow the exiting air flow to be directed in several different planes.
Another object is to provide a nozzle which, as a result of said uniform flow distribution, enables low sound generation to be achieved and which is also inexpensive to produce. owing to the material-saving design of the nozzle.
A further object of the invention is to provide a nozzle that can be accommodated in a perforated wall of an air supply terminal device, wherein the wall may be either planar or curved to some degree without influencing the intended function of the nozzle.
Yet another object of the invention is to provide a nozzle that can be readily mounted and that can be releasably fixated in desired positions, i.e. so as to enable adjustments to be easily made when necessary.
These and other objects are fulfilled by an inventive nozzle of the kind earlier described and having the characteristic features set forth in the characterizing clause of claim 1.
Because the nozzle can be swung about a pivot axis that is perpendicular to the rotational or turning axis of the nozzle, regardless of the position to which the nozzle has been turned, the nozzle will enable the exiting flow to be directed in several different planes, therewith providing considerable improvement with respect to nozzle properties. Consequently, the nozzle can be used in several different types of air supply terminal devices with improved control possibilities.
In practice, the nozzle is suitably provided with a central tongue-holding part which extends perpendicularly to the plane of the outflow parts, and two opposing attachment elements for engagement with opposing parts of the edge surrounding the hole.
In other words, the nozzle is pivotal about said second axis, which may fall in the plane of the hole or in a plane parallel with the hole-plane.
A simple and reliable construction is obtained therewith, provided that the attachment elements are so constructed as to allow pivoting of the nozzle from a starting position through an angle of at least 30xc2x0, suitably at least 45xc2x0 and preferably at least 60xc2x0, in both directions, regardless of the position of rotation of the nozzles. A Coanda effect will occur at larger pivot angles and therewith cause will cause the air flow to adhere to the wall of the device in which the nozzle is mounted.
In one preferred embodiment, the attachment elements include hook elements that springingly engage the circumferential edge of the hole.
Such attachment elements enhances the use possibilities and flexibility of the nozzle. For example, the same nozzle can be used in holes that are not fully round and, for instance, have an oval shape and also in air supply terminal devices that have curved walls such that the hole provided in said wall will not lie in a unitary plane. The statement to the effect that the nozzle can be rotated or turned about xe2x80x9can axis passing through the center of the hole generally at right angles to the plane of said holexe2x80x9d is intended to cover the case when the wall surrounding said hole is curved.
The nozzle construction becomes particularly simple and expedient when the opposing hook elements are joined to the central holder part of the tongues and are located in the same plane as said part. The hook elements may therewith be integral with said holder part and project resiliently therefrom.
In a further embodiment, the nozzle includes two circular or approximately circular side walls parallel with the central holder part and at mutually the same distance therefrom, each of said side walls being joined to the tongues in the region of their outer ends.
These sides contribute towards stiffening the nozzle construction, so as to obviate the need of a surrounding casingxe2x80x94which represents a significant saving in material. At the same time, the nozzle will lack pockets and similar areas in which dirt, dust, etc., can collect. Instead, all parts of the nozzle are easily reached, e g. for cleaning purposes, therewith improving the hygienic properties of the nozzle.
The outside of the side walls may include centrally positioned arcuate and possibly saw tooth-configured hole-engaging parts that extend out perpendicularly to the side walls and that function to releasably fixate the nozzle in its rotational and pivotal positions. These structural features of the inventive nozzle also contribute towards its simplicity and reliability. Each side wall may include one, two or more such engagement parts.
If, as in accordance with one preferred embodiment, the curved parts of the tongues have mutually different radii, there is obtained an embodiment in which the shape of the tongues or guide vanes follows the lines of the air flow, therewith contributing towards the desired uniform flow distribution and reducing the nozzle noise.
In the case of an embodiment preferred in practice, the nozzle has three tongues, of which the third tongue or the last tongue in the direction of the main air flow lacks a curved deflecting part. Practical trials have shown that a nozzle of this design obtains optimal properties adapted to air deflection in different planes afforded by the nozzle.
It is preferred that the distances between the engagement points of the diametrically opposed hook elements and the outer points of the arcuate hole-engaging parts in their respective positions of engagement essentially correspond to one another and to the diameter of the hole. However, said distances may conveniently slightly exceed the diameter of the hole. The aforementioned outer points can therewith be said to be located on the cylindrical surface of an imaginary sphere surrounding the nozzle, the diameter of said sphere corresponding to the diameter of said hole.
It will be evident from the aforegoing that the nozzle can be fitted into the hole and removed therefrom quite easily, and that the position of the nozzle can be readily adjusted to obtain a desired flow pattern. The resilient attachment of the nozzle contributes towards the simplicity of these latter operations.
The invention also relates to an air supply terminal device of box-like, screen-like or tubular configuration, comprising a body that includes a top and a bottom wall and one or more outer and/or inner walls extending between said top and bottom walls, and means for supplying an air flow in a main flow direction parallel with one of said walls, wherein said device is characterised in that said wall includes one or more holes in which a nozzle of the aforesaid kind is accommodated.

Nozzle for an air supply device and an air supply device having one or more such nozzles


A method and system for treating body structures or tissue allows treatment by any of ablation, coating, expansion, plumping, shaping, and shrinking. Treatment sitesinclude any of a sphincter, sinus or orifice. During treatment, electrodes emerge from apertures in a balloon. The balloon with liquid from a circulating bath cools tissue in direct contact with electrodes and immediately adjacent, so that discrete regions are treated, with minimal damage to adjacent structures. Sensors, coupled to electrodes, measure treatment properties such as: temperature, impedance and nervous activity. Measurements are used for: diagnostic assessment, determining treatment parameters, providing nervous stimulation and/or blocking, and feedback for controlling energy delivery. The catheter includes an optical path that can be coupled to external viewing apparatus. Endoscopic methods, including fluoroscopic, fiber optic, or radioscopy allow examining tissue and determining position of electrodes. The catheter includes a suction apparatus used to remove liquids obscuring treatment area and to gently conform treatment area to electrodes.

1. Field of the Invention
This invention relates to treatment of tissue in the urinary, digestive, respiratory, reproductive and circulatory systems. Such treatment can be performed using ablation, coating, expansion, plumping, shaping, shrinking, or related techniques.
2. Related Art
Human beings and other animals such as livestock and small animals are subject to a number of disorders that affect the digestive, urinary, respiratory, circulatory and reproductive systems. Frequently, these disorders (such as urinary and fecal incontinence) involve the relative tone of sphincters and other muscles. Other disorders (such as aneurysms) involve changes in the integrity of the wall of an artery or other body structure. Still other disorders (such as cancers, hemorrhoids and pilonital cysts) involve uncontrolled or improperly regulated growth of tissue. Many other disorders, particularly reproductive disorders, involve occlusions in otherwise healthy tissue.
Known methods for the treatment of these disorders include surgery, pharmaceutical remedies, chemotherapeutic regimens, radiation, photodynamic therapy and lifestyle modification. These methods only occasionally achieve the goal of successful treatment of disorders in circulatory, urinary, respiratory, reproductive and digestive systems. Moreover, these methods suffer from several drawbacks.
Drawbacks to surgical treatment include its highly invasive nature, associated risks, possible iatrogenic effects, and high cost. Drawbacks to pharmaceutical and chemotherapeutic treatments include their relative ineffectiveness (particularly in the oral cavity and adjacent respiratory structures) and associated side effects. Moreover, these approaches are contraindicated for many patients. Drawbacks to lifestyle modification include relatively poor patient compliance and relative ineffectiveness. Drawbacks to photodynamic therapy include its frequent unavailability and limited applicability. Drawbacks to radiation include side effects such as exhaustion, radiation burns, chronic dry mouth and permanent distortion of the taste buds. Accordingly, it would be advantageous to provide techniques for treatment of these disorders that are not subject to these known drawbacks.
The use of radio frequency (RF) to ablate tissue in the body (such as heart muscle tissue) is known in the art of cardiac treatment. However, known systems that rely on RF energy are still subject to several drawbacks. One drawback is that it can be difficult to target very small areas of tissue for treatment without causing thermal damage to adjacent structures.
A second problem involves controlling the flow of bodily fluids and gases into an area of the body where tissue ablation is taking place. Controlling the flow of bodily fluids and gases is critical because they can dissipate and detrimentally absorb the energy to be applied to the tissue to be ablated.
A third problem in the art involves directing and positioning the electrodes in the body cavity or orifice. Difficulties in accurately positioning the electrodes in the target orifice detract from treatment. Frequently, unhealthy tissue remains untreated while healthy tissue is removed. Difficulties in directing and positioning the electrodes are particularly problematic because one of the goals of treatment is to minimize collateral damage to healthy tissue and to completely ablate diseased tissue.
A fourth problem in the art involves difficulty in the simultaneous use of complimentary technology. Known systems do not provide for optimal, simultaneous use of auxiliary tools for nerve stimulation, visualization, feedback technology and drug administration.
A fifth problem in the known art involves the simultaneous heating and cooling of adjacent tissues. Frequently, it is desirable to prevent thermal damage to adjacent tissues. One way of preventing such damage is by controlling the temperature of the adjacent tissues. Known systems to not provide for the simultaneous heating and cooling of adjacent tissues.
A sixth problem in the known art involves conforming the interior of an organ such as a bladder to as to be in optimal contact with the electrodes. This inability makes it difficult to predict with any accuracy the overall degree of shrinkage that may result from RF treatment.
Accordingly, it would be advantageous to provide improved techniques for treatment of disorders in the circulatory, respiratory, urinary, digestive and reproductive systems. For example, it would be advantageous to provide devices bearing different arrays of curvilinear or straight electrodes such that each electrode is surrounded by saline. It would be particularly advantageous if such devices could also support apparatus for drug administration and tissue visualization. Such devices would allow medical personnel to (1) visualize the tissue to be treated, (2) seal off the area from fluids and gases that would disturb the area to be treated, (3) target very small areas for treatment, (4) treat all diseased tissue while sparing healthy tissue and (5) provide for the localized administration of drugs to numb the area and treat the disorder. These advantages are achieved in an embodiment of the invention in which medical personnel use a catheter bearing multiple controls for visualization and drug administration, balloon-like air sacs for sealing the area and multiple arrays of curvilinear or straight electrodes that extend out of a holes in a multiporous balloon.
In one aspect of the invention, an environment proximate to or surrounding the targeted treatment region can be isolated or controlled by blocking the flow of gases or liquids using an inflatable, microporous balloon positioned immediately adjacent to the tissue that is to be ablated. The inflatable microporous balloon also serves to anchor the catheter in place and prevent the catheter from being expelled from-the body. The inflatable microporous balloon can also insure that locally administered drugs remain in the area where most needed.
In a second aspect of the invention, straight or curvilinear electrodes emerge out of small apertures in the balloon. Inflation of the balloon with liquid from a constantly circulating bath of chilled fluid has the effect of cooling tissue, including tissue that is immediate adjacent to tissue in direct contact with an electrode. This permits treatment of small, discrete regions while minimizing collateral damage to immediately adjacent structures.
In a third aspect of the invention, the electrodes are coupled to sensors that measure properties of the target region such as temperature, impedance and nervous activity. These measurements are useful both in making diagnostic assessments as well as in determining treatment parameters. Moreover, they can be used to provide for nervous stimulation and/or blocking, and permit the use of feedback technique to control delivery of the RF energy.
In a fourth aspect of the invention, the catheter includes an optical path that can be coupled to external viewing apparatus. A wide variety of endoscopic methods, including fluoroscopic, fiber optic, or radioscopic techniques can be used to examine tissue and determine the position of the electrodes in the body.
In a fifth aspect of the invention, the catheter includes suction apparatus. This suction apparatus can be used to draw away liquids that obscure the treatment area and to gently conform the treatment area to the electrode.

Treatment of discrete tissues in respiratory, urinary, circulatory, reproductive and digestive systems


The present invention relates generally to Activity Dependent Neurotrophic Factor (ADNF). More particularly, the present invention relates to a family of polypeptides derived from ADNF that exhibit neuroprotective/neurotrophic action on neurons originating in the central nervous system and to uses thereof for the treatment of neurological deficiencies and for the prevention of cell death. The present invention also relates to pharmaceutical compositions designed to prevent neuronal cell death.

Neuronal cell death is characteristic of most developing neural systems in vertebrates. The extent (30-80%) of neuronal death that occurs during development indicates that the regulation of this process is of fundamental importance to the determination of nervous system structure. Although a great deal of descriptive data has been reported concerning the magnitude and ubiquity of this neuronal cell loss, little is known of the mechanism that regulates this process during development. It is clear, however, that electrical activity plays an important role in determining neuronal survival during this regressive phase of development. It has been found, for example, blockage of electrical activity with .alpha.-bungarotoxin attenuates the naturally occurring cell death in spinal motoneurons (Pittman and Oppenheim, Nature (Lond.) 271, 364-366 (1987)) and in trochlear nucleic in vivo (Creazzo and Sohal, Exp. Neurol. 66, 135-145 (1979)).
Studies with cultured spinal cord-dorsal root ganglion (SC-DRG) neurons have shown that during development in vivo, neuronal cell death also occurs in a predictable and activity-dependent manner (Brenneman, et al., Peptides 6, 35-39 (1985)). Analysis of the effects of activity blockage on neuronal survival in culture has indicated an interaction between conditioning substances and electrical activity. When endogenous conditioning substances were removed before electrical blockade, neuronal cell death was accelerated (Brenneman, et al., Dev. Brain Res. 9, 13-27 (1983)). In contrast, when conditioning substances from SC-DRG cultures were supplied during blockage of electrical activity, neuronal cell death was prevented (Brenneman, et al., Dev. Brain Res. 15, 211-217 (1984)).
Further studies have indicated that part of the molecular basis of this activity-dependence is the action of vasoactive intestinal peptide (VIP), a neuropeptide which is released during electrical activity (Brenneman, D. E. and Eiden, L. E., Proc. Natl. Acad. Sci. U.S.A. 83, 1159-1162 (1986); and Brenneman, et al., Peptides 6, 35-39 (1985)). Moreover, studies have indicated that VIP increases the survival of activity-dependent spinal cord neurons by releasing protein growth factors from non-neuronal spinal cord cells (Brenneman, et al., J. Cell Biology, 104, 1603-1610 (1987)). More specifically, it has been determined that VIP interacts with its receptors on glial cells (Gozes, et al., Soc. Neurosci. Abs. 15, 216 (1989)) to induce the secretion of neuronal survival factor(s) (Brenneman, et al., J. Neurosci. Res. 25, 38&394 (1990); and Gozes, I. and Brenneman, D. E., Molecular Neurobiology, 3, 201-236 (1989)).
Among the growth factors released from non-neuronal spinal cord cells by VIP is Activity Dependent Neurotrophic Factor (ADNF). This glia-derived, VIP-released growth factor has been isolated from conditioned medium of rat cerebral cortical astroglia stimulated by VIP (Gozes, 1. & Brenneman, D. E., Molecular Neurobiology 3, 1-36 (1989); and Brenneman, D. B. & Eiden, L. E., Proc. Natl. Acad Sci. U.S.A. 83, 1159-1162 (1986)). Sequential chromatographic separations by ion exchange, gel permeation and hydrophobic interaction have been utilized to obtain about a 1650-fold purification of a single, 14,000 Dalton protein (apparent pI: 8.3.+-.0.25) that increases survival (EC50, 0.075 pg/ml) of electrically blocked spinal cord neurons and, accordingly, this glia-derived, VIP-released growth factor has been named: Activity Dependent Neurotrophic Factor. ADNF has been shown to protect neuronal cells against death. More particularly, ADNF has been shown to increase the growth and survival of developing spinal cord neurons, hippocampal neurons and cerebral cortical neurons. In addition, ADNF has been found to protect neuronal cell viability by preventing neuronal cell death produced by the external envelope protein of the HV virus.
Although ADNF effectively protects against neuronal cell death, it would be advantageous to have polypeptides which are shorter than the full length amino acid sequence of ADNF, but which exhibit the same neuroprotective/neurotrophic action of the intact ADNF growth factor. Quite surprisingly, the present invention provides such polypeptides.

Neurotrophic peptides of activity dependent neurotrophic factor

Ramot University Authority for Applied Research and Industrial Development, Ltd.

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


A recording device may comprise a recording head comprising a discharge port configured to discharge a liquid droplet. The recording device may also comprise a head supporting member. The recording device may yet further comprise a securing member configured to secure the recording head to the head supporting member such that a positional relationship between the head supporting member and the recording head is changeable in a direction intersecting a liquid droplet discharging direction. The recording device may yet further comprise a light emitter, and a light receiver configured to receive the light from the light emitter. The recording device may yet further comprise a position detector configured to detect the positional relationship on the basis of an intensity of the light received by the light receiver. The recording device may yet further comprise an outputting unit configured to output a signal of the positional relationship.

1. Field of the Disclosure
The features herein relate to a recording device including a recording head that discharges liquid droplets, a method of positioning the recording head, and a method of manufacturing the recording device.
2. Description of the Related Art
As a method of positioning a recording head that discharges liquid droplets, a method of adjusting the position of a recording head while confirming the position of a nozzle that discharges the liquid droplets using an optical microscope is known.

Recording device, method of positioning recording head, and method of manufacturing recording device


The present invention provides methods and non-fluorescent carbocyanine quencher compounds having the general formula:

Fluorescence Resonance Energy Transfer (FRET) is a process whereby a first fluorescent dye (the "donor" dye) is excited, typically by illumination, and transfers its absorbed energy to a second dye (the "acceptor" dye) that has a longer wavelength and therefore lower energy emission. Where the second dye is fluorescent, energy transfer results in fluorescence emission at the wavelength of the second dye. However, where the second dye is non-fluorescent, the absorbed energy does not result in fluorescence emission, and the fluorescence of the initial donor dye is said to be "quenched". The proximity of the donor and acceptor molecule and the overlap in spectra of the energy emitted by the donor and the absorption spectra of the acceptor molecule are critical for efficient energy transfer.
When the acceptor molecule is a quencher, the FRET pair can be used in assays to detect the interaction, assembly, cleavage, dissociation and conformation of proteins, nucleic acids and other biomolecules. This can be accomplished when the donor and acceptor are conjugated to different substances wherein the resulting signal is determined by the proximity of the donor and acceptor molecules. Cleavable conjugates are also widely used to detect proteases wherein the donor and acceptor are conjugated to the same substance and the appropriate protease cleaves a bond that changes the proximity of the donor and acceptor (U.S. Pat. Nos. 6,323,337; 6,348,596 and 6,399,392).
In addition, FRET is used in bioassays wherein it is beneficial to have energy emitted at a longer wavelength that does not interfere with the autofluorescence of the bioassay sample. Typically in these bioassays a FRET pair, commonly referred to as a tandem, is conjugated to an antibody or other ligand for the detection of an analyte. These tandem conjugates are also widely used with flow cytometers and confocal laser scanning microscopes that are equipped with separate epifluorescence filter sets wherein a larger Stokes shift is beneficial for multicolor applications. Phycobiliproteins are well known fluorescent proteins that are used as a donor conjugated to a protein such as an antibody wherein a xanthene based dye such as Texas Red (Molecular Probes, Inc.) or a cyanine dye is used as the acceptor (U.S. Pat. Nos. 4,859,582 and 4,542,104; RICHARD P. HAUGLAND, MOLECULAR PROBES HANDBOOK OF FLUORESCENT PROBES AND RESEARCH PRODUCTS; 9thedition, CD-ROM, 2002). In this way, with the Texas Red conjugate of R-phycoerythrin (R-PE), the resulting tandem conjugate can be excited at 488 nm using the widely available argon-ion laser and the energy is re-emitted at about 620 nm or longer after having been transferred to the acceptor dye. Importantly, this permits the simultaneous use of a second conjugate of R-PE that is not a tandem conjugate as a label for a different target. These tandem conjugates find wide use in bioassays; however, in systems that utilize flow cytometry the signal from the fluorescent protein is not fully transferred to the acceptor and therefore must be compensated for when determining multiple targets with labels that absorb and emit in the same range as the fluorescent protein. Thus, there is a need to reduce this compensation determining multiple targets in a sample using R-PE tandem conjugates.
The idea of using a quencher to form a ternary conjugate wherein the quencher compound accepts the residual energy of the R-PE donor compound goes against the current teaching and understanding of FRET. However, we have unexpectedly demonstrated that a compound absorbing in the emitting range of the R-PE can accept the residual fluorescense of the fluorescent protein. This unexpected improvement allows for detection of multiple targets using R-PE tandem conjugates by lowering the need for compensation. Ideally these compounds will be non-fluorescent, or essentially non-fluorescent, and will accept energy in the range that the donor emits the residual fluorescence.
The compounds of the instant invention represent a new and highly useful class of non-fluorescent energy acceptors, including chemically reactive versions, and the conjugates prepared therefrom.

Cyanine compounds and their application as quenching compounds

Abstract: Wherein the A moiety is a substituted pyridinium, unsubstituted pyridinium, substituted quinolinium, unsubstituted quinolinium, substituted benzazolium, unsubstituted benzazolium, substituted indolinium, or unsubstituted indolinium. The invention further provides luminescent donor molecule-quencher pairs and luminescent donor molecule-quencher-luminescent acceptor molecule conjugates wherein the quencher is a cyanine compound of the present invention. The energy transfer pairs are used to detect an analyte of interest in a sample.


Provided herein is a new class of cyclic lactadherin peptides (cLac) that mimic the natural phosphatidylserine (PS)-binding activity of the parent lactadherin protein. These cLacs are useful as small molecule indicators of early stage of apoptosis and of treatment efficacy evaluation.

The lipid composition and distribution of cell membranes play an important role in regulating the physiology of the cell. For example, numerous signaling proteins can be recruited to the membrane by clusters of negatively charged lipids. Live mammalian cells actively maintain an asymmetric lipid distribution on their plasma membrane (see FIG. 1B), with phosphatidylserine (PS), the most abundant anionic lipid, completely confined to the cytosolic leaflet. PS externalization has been observed for cells under abnormal development, including apoptotic cells, activated platelets, and virus-infected cells. In fact, imaging PS exposure has been a benchmark approach to detect apoptotic cells in research laboratories.
Among the limited number of PS-targeting ligands, annexin V is best established for detecting apoptotic cells in vitro and in living organisms. This naturally occurring 36 kDa protein have been labeled with fluoro-chromes or radioactive nuclides and used to studies such as imaging cell death in animal models of human cancer, as well as in humans. However, there are some drawbacks with using annexin V. Annexin V is less ideal as an indicator molecule for the presence of PS because of its large size, high cost, and calcium dependence for PS recognition (see FIG. 2). In addition, the moderate stability and slow clearance severely limit its application in vivo. Small molecules that specifically target PS may circumvent the problems afflicting annexin V and their development has captured increasing attention. There is a class of bivalent organozinc complexes that functionally mimic annexin V and selectively associate with negatively charged membranes. Recently, screening of phage-displayed peptide libraries has also yielded promising lead sequences for PS recognition.

Cyclic lactadherin peptide mimetics and their uses


Aspects of the present invention are related to methods comprising contacting an endothelial cell in an endothelial cell population with a non-thermal plasma to release an angiogenic growth factor. The released angiogenic growth factor may induce endothelial cell proliferation. In certain embodiments, the angiogenic growth factor is fibroblast growth factor-2. Preferably, the non-thermal plasma may be an atmospheric pressure dielectric barrier discharge. Additional aspects of the present invention are directed to methods for treating a disease comprising promoting angiogenesis by contacting an endothelial cell in a endothelial cell population with a non-thermal plasma to release an angiogenic growth factor. The angiogenic growth factor may induce endothelial cell proliferation. Further aspects of the present invention are directed to methods for treating a disease comprising inhibiting angiogenesis by contacting an endothelial cell in a endothelial cell population with a non-thermal plasma to reduce the number of endothelial cells in the population.

Endothelial cells, which line all blood contacting surfaces in the body, control many aspects of the vasculature ranging from vascular tone to coagulation to inflammation. Endothelial cells also play a guiding role in angiogenesis, the growth of new blood vessels from existing vessels. Endothelial cells produce and secrete angiogenic growth factors such as fibroblast growth factor-2 (FGF2), which in conjunction with many other signals induce endothelial cells to invade the surrounding tissue, proliferate, and develop into new blood vessels. Angiogenesis can be both helpful and harmful. In wound healing, angiogenesis is required in the wound site for rapid healing, whereas in cancer, angiogenesis blockade can starve a tumor and prevent its growth.
Recently, various treatment techniques have been explored to accelerate angiogenesis and endothelial cell proliferation. One such technique is the addition of exogenous angiogenic growth factors, such as FGF2 or vascular endothelial cell growth factor (VEGF). However, these techniques have had limited success due to challenges in creating the optimal dose, dose gradient, and timing. Exogenous growth factors are also expensive. Other techniques have been shown to release endogenous angiogenic growth factors from cells. These techniques include low dose laser, inductively coupled pulsed electromagnetic fields, pulsed electromagnetic fields (PEMF), and low dose ionizing radiation (LDIR). Although these techniques are useful for endothelial cell proliferation, they are not desirable because they result in damage to surrounding tissue and cells and/or they need extensive and expensive setup to be generated safely and applied to human tissue. Accordingly, a technique useful for endothelial cell proliferation which does not damage tissue and can be controlled to treat specific areas and specific depths of real tissue would be highly desirable.

Plasma treatment for growth factor release from cells and tissues