A method and system for spacecraft navigation using distant celestial gamma-ray bursts which offer detectable, bright, high-energy events that provide well-defined characteristics conducive to accurate time-alignment among spatially separated spacecraft. Utilizing assemblages of photons from distant gamma-ray bursts, relative range between two spacecraft can be accurately computed along the direction to each burst's source based upon the difference in arrival time of the burst emission at each spacecraft's location. Correlation methods used to time-align the high-energy burst profiles are provided. The spacecraft navigation may be carried out autonomously or in a central control mode of operation.

For space vehicles venturing beyond Earth orbit into deep space, current methods require frequent interaction and communication with Earth stations, which can significantly increase mission scheduling and operational costs.
The NASA Deep Space Network (DSN) is the primary provider of navigation and communication for the U.S. and its partnering nations on deep-space missions. DSN's capability has achieved mission success throughout its over fifty years of operation. However, as exploration initiatives increase and operational usage expands, the DSN has the potential for over-subscription due to its many ongoing and future planned missions, and thus stands to benefit from supplemental navigation augmentation capabilities designed to reduce DSN operations cost.
In addition to improved operational support, expanded exploration of the Solar System beyond current day capabilities requires innovative, non-conventional techniques for vehicle navigation. Very few existing systems can provide this additional service while reducing DSN workload. Therefore, new methods are required that support the DSN system by alleviating any operational interruptions and providing for increased operational autonomy of deep space vehicles.
A previous study of a navigation system based on variable celestial X-ray sources (in the range 0.1-20 keV), referred to as the X-ray Navigation and Autonomous Position Verification program, or XNAV, has shown the capability to support DSN measurements for deep space missions. XNAV relies on pulsars located at known positions on the sky and a pulse-timing model of the expected arrival time of each pulse. The periodic nature of these pulsar sources provides a reliable signal that can be continually detected and tracked. An XNAV range measurement is calculated using an observed pulse profile on a spacecraft and the predicted pulse arrival time from each pulsar's model. The observation time required to produce each XNAV measurement depends on each pulsar's unique characteristics and the spacecraft's detector qualities. A shortcoming of the XNAV technique is that many X-ray pulsars are faint and require extended observation times to generate sufficient usable data.
It would be desirable to provide a system capable of addressing the challenges of future DSN operations and enhancing position accuracy for deep space vehicles, as well as extending the XNAV navigation concepts to celestial sources emitting much higher energy photons than the celestial X-ray sources.
Gamma-ray bursts (also referred to herein as GRBs) are the most powerful explosions known in the Universe. They are extremely luminous, with many orders of magnitude more energy output in a few seconds than the Sun emits in a year. GRBs are theorized to be produced during the evolutionary end-stages of single and binary star systems. This includes the unusually energetic supernova explosions (so-called hypernovae), the merger of two neutrons stars, or when a small star is consumed by a black hole.
GRBs have been detected approximately once per day by past and existing science missions, although they are theorized to occur at a much higher rate due to the concept of beaming, in which the emissions from a burst are focused into only 1/100th of the total sky.
Thousands of GRBs have been detected since they were initially discovered in 1967 by the Vela satellites. GRB events are typically named and catalogued according to their detection date, in the format GRBYYYYMMDDx, where x is an optional letter designation for cases in which multiple bursts occur on a given day. These sources are typically detectable via their emissions in the tens of keV to MeV, and often higher, photon energy bands.
GRBs are typically classified morphologically into a few distinct classes, based on temporal and flux characteristics. Using the Term T90 as the time over which the burst emits from 5% to 95% of its total photon counts, long bursts are those with T90>2 sec, and are thought to be related to massive star collapse. Short bursts exhibit duration of T90<2 sec.
Another classification approach is fluence, S, which is the photon flux integrated over time. High fluence bursts exhibit S>1.6×10−4 erg/cm2/T90, whereas low fluence bursts are those with S<1.6×10−4 erg/cm2/T90. Most bursts exhibit some degree of a fast-rise and exponential-decay, referred to as FRED, behavior.
Short bursts are known to have harder spectra than long bursts, where a greater proportion of the detected photons are of higher energy. The importance of spectral properties, coupled with the sensitive energy band, E, of a given detector, can be seen in the relative statistics of GRB detection between instruments and missions.
As an example, the mission Fermi spacecraft's Gamma-ray Burst Monitor (GBM), with an effective area a factor of ˜3 smaller than that of Swift's Burst Alert Telescope (BAT), detects 1.5 times more GRBs per year. The reason for this dramatic difference is, in part, GBM's greater sky coverage, but also that GBM's sensitivity extends over a much broader energy band (8 keV≦E≦30 MeV) than does BAT (15 keV≦E≦150 keV).
Because the GBM's higher-energy response is a better match to the hard-spectrum emission from short bursts, a significantly larger fraction of bursts detected by GBM are short, compared to BAT.
The gamma-ray emissions of nearby neutron stars are visible as their radiation beams are swept across the Earth's line of sight by the stars' rotations. Both young neutron stars—with spin periods of tens of milliseconds and magnetic field strengths of order 1012 G—and those that have been recycled in a past mass-accretion evolutionary episode (leaving them with spin periods less than 10 ms and 109 G magnetic fields) are visible as sources of pulsed gamma-rays. The latter exhibit highly predictable timing behavior, enabling applications that rely on the regularity of their pulsations.
Catalogues of rotation-powered pulsars from which pulsed γ-rays have been detected from the Fermi and INTEGRAL missions detail basic properties and γ-rays fluxes that drive exposure times required for useful navigation precision. The catalogue includes both rotation-powered pulsars and soft-gamma repeaters (SGRs), which are bright, flaring, recurring sources.
The Fermi team has reported, in its published Second Source Catalog, 83 rotation-powered pulsars from which pulsed γ-rays have been detected. Among the pulsed sources, fluxes are typically at the level of 10−8 photons/cm2/sec. The brightest, the Vela pulsar, has a flux of 3.4×10−6 photons/cm2/sec. These fluxes are integrated over the energy band 0.3 MeV to 1 GeV, where the (hard) γ-ray emissions of rotation-powered pulsars are brightest—below a hundred MeV. Galactic background emission reduces signal-to-noise ratios considerably. Above a few GeV, pulsar spectra cut off exponentially.
The Fermi Large Area Telescope (LAT) effective collecting area in the 0.3-1 GeV band is approximately 6,000 cm2, so that for the Vela pulsar, the detected photon flux is 0.02 counts/sec. While this flux level is potentially conducive to navigation analysis in the manner of XNAV, scaling the large sized LAT down to a detector size that would be appropriate to a navigation subsystem would significantly reduce the photon detection rate. Additionally, for a more-typical fainter γ-ray pulsar, the photon flux is two orders of magnitude lower.
In the energy band at the low end of GRB emissions (tens to 100 keV), the INTEGRAL satellite provides a good measure of typical fluxes for both rotation-powered pulsars and so-called magnetars (SGRs and anomalous X-ray pulsars that are believed to be powered by the slow decay of their enormously strong magnetic field). In its survey mode, INTEGRAL detected three pulsars, two AXPs (Anomalous X-ray pulsars), and two SGRs (Soft Gamma Repeaters). These pulsars are among the brightest in their classes (pointed, non-survey INTEGRAL observations are much more sensitive to dimmer sources). Typical fluxes in both the soft (20-40 keV) and hard (40-100 keV) INTEGRAL bands for these seven objects are in the vicinity of 3×10−4 ph/cm2/sec. With INTEGRAL's effective area of 2,600 cm2, a detected photon flux of ˜1 count/sec is produced.
These detected INTEGRAL fluxes are for sources in their quiescent state. Rotation-powered pulsars are not variable in flux, but both magnetar varieties exhibit sporadic, unpredictable flares; those from SGRs can be exceedingly bright. These SGR flares are believed to recur every few years. AXP flares, on the other hand, increase the quiescent flux by a factor of a 2-5, and recur every few days-to-weeks, with larger flares being less frequent.
These low photon flux rates make the use of γ-ray pulsars an extreme challenge for a practical navigation system. Thus, the more useful γ-ray sources are those of the high flux GRB type.
It is therefore desirable to provide a new technique for determining spacecraft navigation solutions using high-energy events photons from distant celestial gamma-ray burst (GRB) sources.

Method and system for gamma-ray localization induced spacecraft navigation using celestial gamma-ray sources


In order to facilitate the transport of 1 Gbit/s Ethernet signals over an Optical Transport Network using the Optical Transport Hierarchy as specified by ITU-T G.709, a new OTH entity referred to as Optical Channel Data Unit-0 (ODU0, 101) with a capacity of approximately 1.22 Gbit/s is defined. This new entity fits perfectly into the existing OTH multiplexing structure, allowing the transport of two times a 1 Gbit/s Ethernet client layer signal within the capacity of one ODU1 (110), while being individually switchable. A 1 Gbit/s Ethernet signal (102) can be mapped into the ODU0 payload (103) using the Transparent Generic Framing Procedure (GFP-T) encapsulation technique as specified in Rec. G.7041.

Current transmission networks are mainly based on the Synchronous Digital Hierarchy abbreviated as SDH, see ITU-T G.707, 12/2003. A new hierarchy, the Optical Transport Hierarchy abbreviated as OTH has been standardized in ITU-T G.709 03/2003, which is incorporated by reference herein. The purpose of OTH is to deal more economically with very large bandwidths, which are termed Optical Channel Data Units and abbreviated as ODUs. Currently defined are ODU1 (˜2.7 Gbit/s), ODU2 (˜10.7 Gbit/s), and ODU3 (˜43 Gbit/s). New efficient overlay networks can be defined, build and used by network operators based on this hierarchy. The architecture of optical transport networks is described in ITU-T G.872 (11/2001), which is also incorporated by reference herein.
As Ethernet is more and more upcoming as the primary transport format for data signals, 1 Gbit/s Ethernet signals would be a natural client signal for the business of OTH network operators.
The currently standardized method to transport a 1 Gbit/s Ethernet signal through an Optical Transport Network includes to map the 1 Gbit/s Ethernet signal into a concatenation of SDH Virtual Containers (SDH VCs) and than to map the framed SDH transport signal into an ODU. This can be seen for instance from ITU-T G7041 (12/2003) on page 47. The existing mapping of 1 Gbit/s signals into SDH Virtual Containers (SDH VCs) is, however, expensive as it requires to operate a functionally independent SDH network. This in many cases would not be necessary for backbone network operators only dealing with large capacities.
On the other hand, a mapping of a single 1 Gbit/s Ethernet into the smallest OTH entity (˜2.7 Gbit/s) would, however, encompass an enormous waste of bandwidth.
As 1 Gbit/s Ethernet signals are currently gaining much importance as a main client signal to be transported in long-haul networks, there exists a need to ensure a cost effective transport of these signals.
It is therefore an object of the present invention to provide a method and related network element, which allows a more efficient transport of client signals over an optical transport network and which is particularly suited for the transport of 1 Gbit/s Ethernet signals.

Method and apparatus for transporting a client layer signal over an optical transport network (OTN)


Methods and apparatuses for fixing a bone fragment or a bone prosthesis onto a bone. To affix a bone fragment to the bone, an internal fastener is attached from within the interior of the bone to a bone fragment with a length of flexible, inelastic cord extending within the bone interior and attached to the fastener and passing outwardly through an opening in a second bone fragment. An axially rigid tubular support may be placed along the cord to reduce particulate shedding, to reduce ingrowth of bone into the cord, to provide compressive resistance to the cable, or to deliver antibiotics or other pharmaceuticals. The fastener and cord are so positioned as to draw respective fracture surfaces together to reduce the fracture when the cord is pulled outwardly of the opening in the second bone fragment. A second fastener desirably is attached to the bone opening, this fastener including an open bore to receive the cord and a lock to secure the cord to this fastener and maintain the cord under tension.

Simple fractures of bones are readily treated by bringing the fracture surfaces together and holding them in the desired orientation with respect to one another through the use of splints, casts and the like. Bones in general have dense outer, strong cortical portions and interior, non-cortical portions that may include cancellous bone.
Comminuted fractures and fractures involving the breakage of a bone into numerous bone fragments are especially difficult to deal with since one must attempt to reposition each bone fragment in an orientation relative to each other bone fragment such that the fragments may knit together properly. For this purpose, physicians have often used metal plates that attach to the outer cortical surfaces of the bones and which utilize bone screws to hold the bone fragments in the desired position.
Another method for treating such fractures involves the use of cerclage procedures in which a wire is, in effect, wrapped about a broken bone to hold the fragments in place, the cerclage wire occasionally penetrating through the bone. Reference is made to Johnson et al., U.S. Pat. No. 4,146,002. Yet another method taught in Berger, U.S. Pat. No. 5,658,310, involves anchoring the balloon portion of a balloon catheter in the medullary cavity at one end of a long bone having a transverse fracture, and stretching the remaining portion of the elastic catheter across the fracture interface within the bone to maintain the fracture interface in compression. It would appear that unless the elastic catheter traverses the precise center of the bone at the fracture site (which may be difficult to accomplish, considering the bowed or curved nature of most bones), compressive forces will be uneven across the fracture site. That is, the compressive forces on the side of the bone nearest the catheter will be greater than the compressive forces on the opposite side of the bone, generating an unwanted bending moment across the fracture site.
With cerclage procedures, one must entirely encircle a bone in order to hold the bony parts together. Surgical procedures used to mount bone plates and cerclage elements to a bone often require supportive tissue that is normally joined to the bone to be cut from the bony tissue to enable direct visual access to the bone.
Procedures using bone plates and cerclage elements often tend to interrupt blood flow to the damaged bone fragments, thus hindering the healing process. Moreover, the use of bone plates and cerclage elements, particularly the former, can lead to stress shielding of the fracture site. While Wolff's Law teaches that bone growth is stimulated when stress is applied, continuous, excessive pressure applied to a bone may cause unwanted resorption of bone at the pressure site. In order to promote healing of bone fractures, the fracture surfaces that are brought together during reduction of the fracture should be subject to cyclic or periodic compressive forces so as to stimulate the growth of new bone across the fracture interface without causing bone resorption. When a fracture interface is immobilized, as by a cast, the bone material that is deposited at the fracture interface may have a collagen fiber matrix that is random rather than aligned with the fiber matrix of bone on either side of the fracture, the healed fracture interface being weaker in tension than bone on either side of the interface.
Some bone fractures result in the production of many bone fragments, and proper reduction of the fracture requires the fragments to be carefully reassembled next to each other with their fracture surfaces in contact. Bone screws and bone plate devices commonly are used for this purpose. Using bone screw techniques, two bone fragments may be joined together, and these two fragments as a unit may be moved into approximation with a third fragment and joined to it, and so on. Fragments that are thus joined together by rigid screws cannot move with respect to other fragments, and mismatching of the fracture surfaces as the first several fragments are joined together can have a compounding effect, causing mal-union or non-union of fracture surfaces and resulting in far less than perfect bone fragment assembly and healing.


A method is provided for activating a transmission means comprised in a mobile device to operate in a manner compatible with at least one wireless communication protocol such as a Bluetooth or Wi-Fi standard. The activation of this transmission means is carried out in response to receiving a pre-defined indication at that mobile device denoting that an emergency communication is to be forwarded to an emergency center.

Today, when an emergency call is placed from a landline telephone, the address of the landline telephone is automatically displayed at the emergency center or at the Public Safety Answering Point (hereinafter "PSAP") operator's screen. However, when such a call is placed from a cellular telephone, the caller's location is not shown on the operator's screen, and the caller must identify his/her location to the operator, otherwise, the location at which the call was initiated is not passed along to the operator. In other cases, even though the caller is able to communicate with the emergency center operator, still, he/she may be unable to provide the operator with his/her current location. Accordingly, all cell phone users are at a disadvantage when contacting emergency operators as compared with those who place such a call from a landline telephone. This is not a problem to be taken lightly particularly with the ever growing number of people using their mobile telephones as their first and foremost means of communication.
In a NENA (National Emergency Number Association) i3 Technical Requirements Document (TRD), NENA 08-751, Issue 1, Sep. 28, 2006, the routing of calls to the correct PSAP is based upon the location of the caller known at the time of the call. The main reason being that many people when calling the emergency line for any of a number of reasons do not provide (or unable to provide) to the PSAP operator their exact location, a fact that adds an undue delay while making an attempt to trace the caller.
The US Federal Communications Commission (FCC) requires that cell phone carriers must automatically provide the location of 911 calls made from a cell phone to PSAPs within certain accuracy parameters (specifically, within 50 meters 67% of the time and within 100 meters 95% of the time). The FCC has raised additional requirements with respect to providing precise location data for a 911 call made from inside a building, structure or facility as failure to provide precise location data of the caller may place him/her life in jeopardy. For example, upon responding to a 911 call based upon GPS location data, one might still have to search dozens or even hundreds of apartments or offices before being able to locate the 911 caller.
In order to find the location of a mobile device caller who placed an emergency 911 call, the PSAP operator retrieves data from the mobile network, and from the retrieved data one may be informed which base station serves that mobile device. However, since a base station coverage in urban areas extends to a radius of up to about 500 meters to 1 km away from the base station, it might still be difficult and sometimes even impossible to locate the caller within the accuracy required. In order to overcome this problem several attempts have been made while using Global Positioning Signal ("GPS") or Time Distance of Arrival ("TDOA") between base stations to provide location data. Other proposed systems rely on the employment of triangulation methods to locate the device by comparing signal strength and/or angle-of-arrival information from multiple antennas.
However, all these solutions are able to provide only limited answer to the problem of providing accurate location data and particularly in urban areas, and do not solve the problem when the cell phones are used in establishments such as hotels, apartment and office buildings, factories, schools and the like.
Furthermore, even when an emergency call is made from a landline telephone in an office that is connected via a Private Branch eXchange ("PBX"), then typically, only the street address appears at the operator's screen. The operator would therefore only know the residential address from which the call was placed but not the exact apartment/office/room where it was made, unless the caller is able to speak with the responding operator and to provide the missing information.
Following are a number of examples of solutions that are known in the art.
US2002005804 discloses a system for determining the location of a mobile station in a cellular communications network. The solution disclosed, relies on a plurality of locator units fixedly positioned for tracking and measuring communications between a base station and a mobile station initiating an emergency communication. Each such locator unit comprises a receiving means for monitoring a control channel of the base station in order to detect and receive identifying information including a voice channel assigned for the particular mobile device initiating the emergency communication.
U.S. Pat. No. 7,260,186 describes an emergency 911 voice-over-IP (VoIP) solution. The 911 call is initiated from a mobile VoIP device and routed directly to the correct PSAP via dedicated trunks, together with correct location information and call-back number. VoIP gateways are implemented locally, accept VoIP packetized data inbound, and convert it into standard landline voice call. The call is then routed to an IP address at the VoIP gateway, which then egresses the call to a voice port at a selective router. The location of the VoIP is validated using HTTP based protocol by pushing location information to a VoIP location server, and comparing it against a geographic location database to confirm that a contained street address is valid.
U.S. 20070004379 describes a method for providing location data to a 911 operator of a cell phone caller who initiated a 911 call. When a cellular 911 call is made within proximity of a landline telephone or a stand-alone unit, an interaction takes place between the enabled cell phone and the landline telephone. Upon receiving and decoding the cellular transmission, the landline telephone or stand-alone unit transmits a 911 call which provides more precise location data to a 911 operator than if the 911 call was simply connected to the operator from the cell phone.
U.S. Pat. No. 7,315,735 discloses a location detection system for locating a mobile device placing an emergency 911 call within a facility having a distributed antenna system. The location detection system includes detection units located within the distributed antenna system where each detection unit monitors a dedicated emergency 911 channel for activity and alerts a monitor unit if activity is detected. The monitor unit determines the location of the antenna receiving the emergency 911 call based upon the identity of the detection unit.
Due to the difficulties associated with providing 911 operators with precise location data from cell phones and office phones in the circumstances described above, it is required to provide a system, device and method for providing more precise location data to an emergency center operator without requiring the caller to verbally communicate location data to the operator.
Notwithstanding the above, one other problem associated with placing a call to an emergency center from a mobile device, and particularly in crowded urban areas such as hotels, office towers and the like, is the availability of a communication path for the caller to place that call. When a caller wishes to place such an emergency call in such areas, he/she could very well find himself/herself in a situation where there is no available link to reach the cellular network for placing the call. This will be the typical case if the caller is for example in a hotel when a fire, terrorist attack and the like takes place. In any of these cases most of the people present at that location would try to use their cellular telephones, and consequently the base station servicing that area will be unable to cope with the congestion.
Therefore, there is a need for reliable method and means to allow identifying the location of a mobile device caller who places a call to the emergency service where the caller is located in a room of a multi-tenant complex such as an office building or hotel, and the like.

Method and device for identifying the location of an indoor mobile telephone user


Methods, systems, and media are disclosed for improved granularity of a response-request communication on a networked computer system. One example embodiment includes receiving the request-response communication by the networked computer system, and associating the request-response communication with a port, having a nodelay setting, from a set of ports on the networked computer system. Further, the example embodiment includes enabling, based upon the associating, the nodelay setting upon connection of the request-response communication with the port. Further still, the example embodiment includes sending, in accordance with the enabling, the request-response communication to a destination in communication with the networked computer system. In addition, further example embodiments include configuring the ports on the networked computer system with nodelay values indicating whether a particular port is assigned nodelay or no nodelay for a request portion or request portion of a request-response communication connecting to that particular port.

Personal computer systems are well known in the art. They have attained widespread use for providing computer power to many segments of today's modern society. Personal computers (PCs) may be defined as a desktop, floor standing, or portable computer that includes a system unit having a central processing unit (CPU) and associated volatile and non-volatile memory, a display, an input-output device such as a keyboard and/or a mouse, a storage device such as a hard disk storage drive, and, in many instances, a network interface adapter. One of the distinguishing characteristics of these systems is the use of a motherboard or system planar to electrically connect these components together. Examples of such personal computer systems are IBM's PC 300 series, Aptiva series, and Intellistation series.
The widespread use of PCs in conjunction with networks has resulted in a reliance on the network resources, or other computer systems, for, just to name a few, telecommuting, obtaining news and stock market information, trading, banking, shopping, shipping, communicating in the form of Voice Internet protocol (VoiceIP) and email. For many, PCs represent an essential tool for their livelihood. In today's networked world, the availability and performance of the network is as important as the availability and performance of the personal computer. Thus, it is desirable to minimize loss of productivity by increasing availability of network resources.
Computer systems typically communicate with network resources via local area networks (LANs), such as campus-area networks (CANs) or home-area networks (HANs), or via wide area networks (WANs), such as metropolitan-area networks (MANs) or the Internet. More specifically, each computer system includes or is connected to a network switch to transmit transactions to other computer systems and each operating system running on the multiple computer systems has its own Transmission Control Protocol/Internet Protocol (TCP/IP) stack to coordinate transmission and receipt of the transactions. For instance, when data is being transmitted out of a computer system, the data is first forwarded to the TCP/IP stack, which packages packets of the data with headers. The headers, such as TCP headers or User Datagram Protocol (UDP) headers, identify the application programs running on the source and the destination computer systems that are involved in the transaction.
Unlike TCP, which requires an acknowledgment at the receiving end (handshaking) before the session can begin, UDP just sends out packets in a one-way transmission. UDP is more efficient, for instance, in real-time audio and video transmissions in which lost packets are preferably ignored. The lost packets are preferably ignored in such situations because there is insufficient time to retransmit the packet.
The headers identify sockets for the source and destination computer system, which are a combination of (1) the computer system's IP address and (2) the application's port. If the actual IP address is unknown but the computer system is known by name, a Domain Name System server (DNS server) converts the name into the IP address. In Windows® networks, for example, a Windows® Internet Name System server (WINS server) converts NetBIOS names into IP addresses. For clarity's sake, a socket is part of an operating system and is a software object that connects an application to a network protocol. In UNIX, for example, a program can send and receive TCP/IP messages by opening a socket and reading and writing data to and from the socket. This simplifies program development because the programmer need only worry about manipulating the socket and can rely on the operating system to actually transport messages across the network correctly. Note that a socket in this sense is completely soft—it is a software object, not a physical component.
A port is a portion of the configurable socket enabling communication connections over a networked computer system. Ports are logical numbers assigned to applications that communicate with other computer systems. Some common applications like FTP, SMTP, and HTTP have agreed-upon or well-known port numbers. For example, HTTP applications accessible via the Internet are at port 80, so a web server may be identified by its IP address and port 80. See more examples of ports and their common port numbers at FIG. 1.
With this background, it is time to turn to request-response ("RR") communications over a networked computer system such as a request, e.g., a URL, from the Internet, e.g., a webpage. Currently, networked computer systems wait a finite amount of time, such as 50-200 ms, before sending the packets of data that collectively make up the request or response in an RR communication. This finite amount of time is for filling the packets with information with a mindset towards efficient load balancing and bandwidth utilization. Sometimes, however, the request or response is so small that the RR communication is waiting for no purpose. That is, there is no more information to put in the packets that make up the request or response; the packets, even if not full, are ready to go through the port to the other side. As a result, the remainder of the finite amount of time is idle time, i.e., needless delay, adversely affecting throughput efficiency, and, in such a case, throughput efficiency is better served by enabling such packets with no delay, or "nodelay" as this is commonly termed in the industry. On the other hand, however, the information filling the packets comprising the response or request in a RR communication is large, and bandwidth utilization, as well as throughput and load balancing are ill-served by immediately sending incompletely filled packets without allowing a standard finite amount of time to fill the packets. In this situation, delay, rather than nodelay, is preferred.
Presently, granularity to address RR communication through ports on a computer system is lacking. A present solution for rigidly addressing "nodelay"/delay dilemma to optimize connectivity is on a per adapter basis, which means all communications are happening within a nodelay or delay mode. Often, however, there are a mix of communications occurring over a networked computer system, wherein some communications require nodelay and others require delay in order to maximize bandwidth utilization and throughput efficiency. As a result, a per adapter basis is a one-size-fits-all solution that, in reality, does not fit all communications occurring over a networked computer system, and thereby, results in inefficiencies not solved by the prior solutions.
A need, therefore, exists, for methods, systems, and media for improved granularity of request-response communications over a networked computer system.

This patent is subject to a terminal disclaimer.

Granularity on a per port basis of request-response communications over a networked computer system

International Business Machines Corporation


The invention relates to a widely applicable process for identifying chemical compounds, which modulate G-protein-coupled receptors, by means of novel hybrid G-proteins with broad receptor specificity and very high expression and also to chemical compounds which can be identified by such a process.

G-protein-coupled receptors (GPCRs) play an important role in a multiplicity of physiological processes. They are one of the most important protein families known to date, and it is assumed that in the human genome about 1000 genes code for members of this receptor class. GPCRs have a characteristic structure: they are peptide threads which meander in the form of α-helices seven times through the phospholipid bilayer of the cell membrane, arranging themselves in a circle. It is estimated that about 60% of the pharmaceuticals presently available through prescription bind to GPCRs. This underlines the importance of this receptor class to the pharmaceutical research industry.
G-protein-coupled receptors share a common mechanism of action. Binding of an extracellular ligand leads to a conformational change in the receptor protein that allows it to make contact with a guanine-nucleotide binding protein (G-protein). G-proteins are located on the cytoplasmic side of the plasma membrane and mediate the extracellular signal in the cell interior to trigger various intracellular reactions.
GPCRs are the most important therapeutic target proteins to date. An estimated 40% of the pharmaceuticals prescribed by doctors act as agonists or antagonists of GPCRs. Owing to the size and importance of this protein family and in view of the fact that chemical binding partners for many GPCRs are unknown (orphan GPCRs), it can be assumed that this receptor class will be one of the most important reservoirs for suitable target proteins in the search for novel medicinal substances in the future.
GPCRs are integral membrane proteins that transfer a signal mediated via a mostly hydrophilic signal substance bound to the outer side of the cell into the cell interior via a family of G-proteins. Depending on the receptor specificity and the G-proteins activated thereby, activated GPCRs trigger various signal transduction pathways. Depending on the receptor type, various actions are evoked, all of which lead to the formation of second messengers. Second messengers are intracellular messenger molecules, such as, for example, cAMP, cGMP, and Ca2+, formed in or released into the cytosol in response to an extracellular signal and which trigger reactions in the cell through the activation or deactivation of intracellular proteins. Thus, activation of a membrane-bound adenylate cyclase may lead to an increase in the intracellular cAMP level, and inhibition may lead to a decrease. Stimulation of a cGMP-specific phosphodiesterase may lead to a reduction in the cGMP level. The activated G-protein can also lead, for example, to an increase of Ca2+ or K+ ions by binding to an ion channel. Furthermore, an activated G-protein can affect activation of a phospholipase and thus formation of inositol 1,4,5-trisphosphate and diacylglycerol. This, in turn, leads either to a Ca2+ increase or to activation of a protein kinase C, with further effects in both cases.
The heterotrimeric G-proteins are located on the inside of the plasma membrane. They comprise the three subunits α, β and γ. When an activated receptor makes contact with the G-protein heterotrimer, it dissociates into an α subunit and a βγ complex. Both the activated α subunit and the βγ complex can influence intracellular effector proteins. The G-protein α subunit family is presently divided into four different classes (Gαs, Gαi, Gαq and Gα12 classes).
GPCRs are classified according to the G-proteins that they contact. GPCRs of the Gs class mediate adenylate cyclase stimulation via activation of Gαs and increase the intracellular cAMP concentration. GPCRs of the Gi class mediate adenylate cyclase inhibition via activation of Gαi and decrease intracellular cAMP. GPCRs of the Gq class mediate stimulation of various phospholipase C beta (PLCβ) isoforms via activation of Gαq and lead to hydrolysis of membrane-bound phosphatidylinositol 4,5-bisphosphate to give diacylglycerol and inositol 1,4,5-trisphosphate (IP3). IP3 releases Ca2+ from intracellular depots.
Most GPCRs can make contact only with one G-protein α subunit family, and, therefore, are selective for a particular signal transduction pathway. This narrow specificity is a great hindrance to the identification of chemical compounds capable of modulating GPCR-dependent signal transduction pathways.
Moreover, a suitable signal which can be utilized in a screening assay with high sample throughput is obtained only from those signal transduction pathways in which, for example, G-protein activation leads to an increase in the intracellular Ca2+ level.
Hybrid G-proteins with altered receptor specifity and signal transduction pathway linkage may be constructed by joining together parts of various G-proteins using known molecular biology and biochemistry methods.
Hybrid G-proteins are fusion constructs which combine sequences of various Gα subunits within one protein. Thus it is possible, for example by fusion of the Gαi receptor recognition region to the Gαq effector activation region, to prepare a Gαq/i hybrid which receives signals from Gi-coupled receptors but switches on the Gαq-PLCβ signal transduction pathway. Such a hybrid, in which the C-terminal 5 amino acids of Gαq is replaced by the corresponding Gαi sequence (Gαqi5), was first described by Conklin et al., Nature 363, 274-276 (1993).
This "recoupling" of receptors has the advantage that the assay endpoint (increase in intracellular Ca2+ concentration in comparison with adenylate cyclase inhibition) is more readily accessible through measurement methods and can be used in high throughput screening.
However, the disadvantage of the Gαq/Gαi fusion constructs is that they are unable to activate some GPCRs, such as, for example, the SSTR1 receptor qi5 (Conklin et al., Mol. Pharmacol. 50, 885-890 (1996)).
Similarly, fusion constructs between Gαq and Gαs have been described. These too have the disadvantage that they cannot link all Gs-coupled receptors to the PLCβ signal transduction pathway, such as the β2-adrenergic receptor and the dopamine D1 receptor, for example.
Besides C-terminal modifications for altering the linking of receptors to particular signal transduction pathways, an N-terminal modification of Gαq has been described which allows the G-protein to receive and pass on signals from several different receptors. In this Gαq protein, the 6 highly conserved N-terminal amino acids were deleted (Kostenis et al., J. Biol. Chem. 272, 19107-19110 (1997)). This deletion allows the resulting Gq (also called −6q) to receive signals not only from Gq- but also from Gs- or Gi/o-coupled receptors and to pass them on to PLCβ.
This mutant Gα subunit also recognizes receptors such as the SSTR1 somatostatin receptor, the dopamine D1 receptor and the adrenergic β2 receptor. However, even this mutant is unable to recognize the receptor edg5. Moreover, the signal intensity of this mutant is so weak that it is unusable in practice (Kostenis et al., J. Biol. Chem. 272, 19107-19110 (1997)).
Another known Gα subunit is Gα16 which links GPCRs from various functional classes to the PLCβ-Ca2+ signal transduction pathway. Gα16 is a G-protein with broad receptor specificity and has been disclosed in WO 97/48820 (title: Promiscuous G-protein compositions and their use). Gα16 is practically nonselective by nature. But even this subunit is not universally applicable, because receptors such as the edg5 receptor or the SSTR1 somatostatin receptor couple to it only weakly, if at all.
Thus, it would be very useful if a G-protein were available that could be activated by other functional GPCR classes, could also give a sufficiently strong signal in the cell. Such a G-protein could be utilized in a screening assay, such as a high throughput screening assay, to identify compounds modulating GPCRs and/or the appropriate dependent signal transduction pathways, for example a signal such as the increase or decrease in the intracellular Ca2+ concentration.
The object of the present invention is therefore to provide further hybrid G-proteins characterized by having recognizable broad specificity with respect to GPCRs. These G-proteins can be used in screening processes to identify chemical compounds by the coupling of the G-proteins to a signal pathway leading to an increase in the intracellular Ca2+ concentration. In addition, these proteins can be expressed at such a high level that signal intensity is improved.

Process for identifying modulators of G-protein-coupled receptors


A memory card connector includes an insulating housing having a top wall and two sidewalls and defining conductive terminal grooves and a switch terminal groove. One sidewall extends upward and then extends toward the other sidewall to define an anti-mismating portion having a transverse portion above the top wall and a vertical portion connecting with the transverse portion and the sidewall. A metallic shell coupling with the insulating housing to form a card cavity has two side sections. One side section extends rearward to form a touching portion. Conductive terminals received in the conductive terminal grooves have a base portion, a soldering portion and a contacting portion. A switch terminal assembled in the switch terminal groove has a main body extending rearward to form a resilient arm received in the card cavity. The resilient arm defines a contacting projection facing the touching portion and a pressing portion facing the inner of the card cavity.

1. Field of the Invention
The present invention relates generally to a memory card connector, and more particularly to a memory card connector having an anti-mismating portion to prevent incorrect insertion of a memory card.
2. The Related Art
Recently, electronic devices, such as digital cameras, MP3 players, cellular phones, etc., are required with larger capacity of storage to store data. A memory card, such as a Memory Stick Duo card, a SD card, a Mini SD card, a MMC card, a M2 card, etc., which has larger capacity of storage and a small size, is extensively used to expend the capacity of storage of the electronic devices. The data transmission between the electronic device and the memory card is through a memory card connector mounted on a PCB (printed circuit board) of the electronic device for connecting with the memory card. The memory card connector has an insulating housing. The insulating housing includes a receiving cavity for receiving the memory card and a plurality of grooves for respectively receiving a plurality of terminals. One end of the terminal forms a soldering portion for being soldered to the PCB, and the other end of each terminal forms a connecting portion for mating with the memory card. A metallic cover couples with the insulating housing. The memory card is inserted and held in the receiving cavity of the memory card connector for being used in storing various data and taken by the electronic device as a recording medium. If not in use, the inserted memory card can be pulled out from the receiving cavity of the memory card connector.
However, the memory card connector described above has no structure to prevent incorrect insertion therein of the memory card. Once the memory card is inserted in a wrong way, the terminals of the memory card connector are crushed and broken. Therefore, the connection between the memory card and the memory card connector is susceptible to being interrupted, resulting in unstable signal transmission between the memory card and the memory card connector.
In addition, such memory card connector is incapable of identifying whether the memory card is fully inserted therein or not. If the memory card is not fully inserted in the memory card connector, but partially inserted into the memory card connector, the connection between the memory card and the memory card connector is interrupted, resulting in unstable signal transmission between the memory card and the memory card connector. In order to solve the problem, a memory card connector is described in U.S. Pat. No. 6,805,566. The memory card connector has two detecting terminals that are brought into contacting with each other only when the memory card is fully inserted into the memory card connector. Otherwise, the two detecting terminals do not connect with each other. So the memory card connector is able to detect full insertion of the memory card. But such detecting structure makes the memory card connector swollen. Therefore, the memory card connector is not suitable for compact electronic devices.


A base for fixing the safety seating system in a passenger car has an external guiding member that more than equatorially encompasses an internal guiding member for a direct spherical guiding of a removable seated newly born infant. The infant is seated with respect to the geometrical pivoting center and an overall mass axis of the rotating portions such that neck bending and head whip lashing are minimized during a vehicle crash. The encompassing spherical and direct guiding provides for a free impact aligned reorientation of the seated infant unimpeded by adjacent elements of the car that are eventually forced into contact during crash. The direct spherical guiding provides also for a lightweight construction of the rotating portions with low momentum of inertia and consequently high responsiveness of the safety seating system.

Safety seating of humans in vehicles and devices moving with ever increasing speeds has been addressed in the prior art in manifold ways. Besides most commonly used seat belts and air bags, pivoting seats have been introduced to adjust the sitting position to off-vertical gravitational loads. For example, a number of aircraft and car seats have been described in U.S. Pat. Nos. 2,227,717; 3,112,955; 2,823,730; 3,357,736 that provide a pivoting movement around an axis perpendicular to a vehicle's movement direction. Such seat designs were thought to adjust a seated persons position in response to a frontal impact.
Significant dynamic gravitational load changes away from vertical orientation have been recognized also for example in fly simulating devices. There, varying centrifugal loads resulting from undulating rotational movements of the seated person are compensated by seating capsules hinging around two perpendicularly acting joints. The capsules overall center of gravity is kept in an offset to both axes such that the capsule is aligning itself with varyingly directed gravitational accelerations. In that way, gravitational loads may be experienced by a person seated in the capsule predominantly in vertical direction with respect to the person's seating position irrespective the spatial orientation of a sum gravitational acceleration vector acting from the outside via the two axes onto the capsule. See for example U.S. Pat. Nos. 2,282,763; 2,357,781; 4,898,377.
The concept of such double axes suspension of a seating capsule has been applied in the prior art to a child safety seat to be mounted in a car as described in U.S. Pat. Nos. 6,439,660 and 6,634,708 both invented by John Guenther. Guenther attempts to safely seat a child also against other than frontal vehicle impacts. Guenther as well as the above listed hinging safety seats fail to address the particularities of rotational impact response characteristics of a human seated with respect to a primary impact vector or primary impact plane of a vehicle. By not taking into account these particularities and as described in detail below and in reference to the Prior Art FIGS. 1A, 1B, most prior art hinging safety seating devices in fact expose the seated person to increased risks of neck injuries and well known head whip lashing compared to rigid safety seating systems.
The main difference between fly simulating devices and safety seating devices are gradients of acceleration and deceleration force direction changes. Such gradients may be more than a magnitude higher in case of a sudden vehicle impact during which decelerations occur in multiples of the common gravitational acceleration experienced on earth as is well known to anyone skilled in the art. In a hinged capsule or seat 11, the deceleration VXN is transferred onto the seat/capsule 11 via hinge(s) AC1, (AC2). In single hinge prior art safety seats, naturally only one hinge AC1 is employed. In double hinge prior art seating capsules, two hinges AC1, AC2 are employed. In a freely suspended seat/capsule 11, an overall center of gravity GO including the gravity centers of the seated human 100 and the seat/capsule 11 is resting vertically below the hinge(s) AC1, (AC2) in an impact initial position where only gravitational acceleration acts on the seat/capsule 11 and human.
During an impact where the vehicle is rapidly decelerated, an overall mass reaction force FXO acts in direction opposite and parallel with respect to the deceleration VXN. The overall mass reaction force FXO introduces a main torque around the hinge(s) AC1, (AC2) on the seat/capsule 11. The overall mass may include the mass of the human 100 and the seat/capsule 11. The main torque resulting from the overall mass reaction force FXO multiplied with a main normal distance DG between deceleration vector VXN and overall gravity center GO rotationally accelerates the seat/capsule 11 with the seated human 100 around the axis AC1. The main normal distance DG is the distance between the overall gravity center GO to the acting hinge AC1 in direction normal the impact deceleration VXN vector.
In the example of Prior Art FIGS. 1A, 1B, the main rotational acceleration results in a counterclockwise rotation CCR of the seat/capsule 11 and those human 100 body portions belted on the seat/capsule 11. The rotational acceleration is opposed by an overall momentum of inertia of the seat/capsule 11 and all rotationally rigidly connected portion(s) of the human 100 resulting in a response time it takes for the seat/capsule 11 to move from an impact initial orientation depicted in Prior Art FIG. 1A into a impact aligned orientation where the overall center of gravity GO is again aligned with deceleration VXN vector as depicted in Prior Art FIG. 1B.
The main human body part rigidly connected with the seat/capsule 11 may be the torso 105 commonly belted up the seat/capsule 11. Head 101, arms 103 and legs 102 hinge on the torso 105 and receive their rotational acceleration around hinge AC1 via neck 104 and respective shoulder and hip joints. The head 101 has the largest mass with its head gravity center GH being in head normal distance DH with respect to an approximate neck center NC. Head normal distance DH are is normal with respect to a resulting head mass force FRH.
At the impact initial position of Prior Art FIG. 1A, the resulting head mass force FRH is composed in a well known manner of an impact head reaction mass force FXH and a rotational acceleration head reaction mass force FTH both described in the below. As the angular speed of the seat/capsule 11 ramps up from zero at the impact initial orientation, a centrifugal head reaction mass force FCH occurs and contributes to the resulting head mass force FRH as well. At the impact aligned orientation of Prior Art FIG. 1B, rotational acceleration is down to zero and only impact head reaction mass force FXH and dependent on a residual rotational speed of the seat/capsule 11 an eventual centrifugal head reaction mass force FCH may contribute to the resulting mass force FRH.
As can be seen in Prior Art FIG. 1A, the resulting head mass force FRH is oriented clockwise with respect to the neck center NC and in head normal distance DH, which together resulting in a clockwise rotation CR that is in opposite direction than the counterclockwise rotation CCR of the sea/capsule 11 and the belted up torso 105. The neck 104 has to compensate the two opposing rotations CR, CCR which may cause excessive neck bending. As the rotational speed of the seat/capsule 11 ramps up, centrifugal head reaction mass force FCH increases, while impact head reaction mass force FXH and/or rotational acceleration head reaction mass force FTH may decrease to a point where the orientation of the resulting head mass force FXH becomes oriented also in counterclockwise direction with respect to the neck center NC. The head 101 is consequently rotated back around the neck center NC until it is stopped by the seat's/capsule's 11 upholstery. During a crash related impact, this takes places within a fraction of a second resulting in a well known whip lashing of the head, which may be significantly stronger compared to a conventionally seated child due to the initial excessive neck bending and additional centrifugal head reaction mass force FCH that is not present in a conventionally seated child's head.
The clockwise rotation CR of the head 101 resulting from the opposite rotational acceleration continues as long as the head gravity center GH remains above the neck center NC while the torso is already in counterclockwise rotation CCR. This oppositely acting head 101 tilting torque induced during the time span it takes for the head normal distance DH to decrease to zero produces an counter rotating head 101 tilting energy that may cause excessive bending of the neck 104. Once the rotation of the seat/capsule 11 and the torso 105 has progressed to the extent that the head gravity center GH moves below the neck center NC the rotational acceleration of the head 101 is reversed and the head whip lashes back. The whip lashing may be even amplified by centrifugal forces acting on the head 101 at that moment.
Also not addressed in the Prior Art is another particularity of the rotational impact response characteristic of pivotally seated human 100 that may be related to an neck center angle ON between the overall gravity center GO and the approximate neck center NC. The closer to or even worse larger than ninety degrees the neck center angle ON, the longer and initially larger are the effects of the deceleration VXN transmitted onto the neck 104. This is because the closer or larger the neck center angle ON to ninety degrees, the more the neck 104 initially moves perpendicular with respect to the deceleration VXN vector while the seat/capsule 11 rotates. This again prolongs the time span and overall amount of the deceleration VXN transmitted onto the neck center NC resulting in prolonged impact head reaction mass force FXH and ultimately increases a counter rotating head 101 tilting energy that the neck 104 has to absorb as may be well understood by anyone skilled in the art.
Referring to Prior Art FIG. 1B, another unfavorable result of the neck center angle ON being close to or larger than ninety degrees may be a non perpendicular final orientation of the neck 104 during impact aligned orientation of the seat/capsule 11 in which the overall gravity center GO is aligned with the deceleration VXN vector through the hinge AC1. The larger the neck 104 center angle ON the more the final neck 104 orientation may be out of perpendicularity.
In summary, prior art pivoting safety seats or capsules 11 may adversely effect a seated human's safety particularly against neck injuries, resulting from excessive neck bending, excessive rotating head 101 tilting energy, head whip lashing and non perpendicular final neck 104 orientation. Therefore, there exists a need for a safety seating system that minimizes the risk of excessive neck 104 bending, excessive rotating head 101 tilting energy, and head 101 whip lashing of a rotationally seated human. The present invention addresses this need.
In a real case of a vehicle crash, decelerations and eventual accelerations acting on the hinges AC1, AC2 may be of complex primarily two dimensional nature resulting from varying impact directions. Probabilities of impact directions of a passenger car known to the inventor at the time this invention was made are shown in Prior Art FIG. 2. In some cases, like during a rollover, the decelerations may even be of a three dimensional nature. Such complex primarily two dimensional and eventually even three dimensional decelerations may result in rapidly reorienting torques initiating rotational movements in varying directions around the hinges AC1, AC2. The torso 105 belted up to the capsule 11 follows these movements directly whereas the head 101 with its mass may lag behind, which again may cause undesirable neck 104 bending. The further the head gravity center GH is horizontally away from an intersection of the hinges AC1, AC2, the more violent the head 101 may dangle in such situations with respect to the belted up torso 105. Therefore, there exists a need for a safety seating system in which head 101 dangling due to multi dimensional deceleration patterns that eventually occur during a vehicle crash are kept to a minimum. The present invention addresses also this need.
Child safety seats are commonly fixed on top of the upholstery of either a rear or a front passenger seat. The inherent softness of the upholstery renders a rigid fixing of the child safety seat practically impossible. In case of a prior art child safety seat 10 having a capsule 11 double hinged via a cardan arm 12 on a base 13, the rotational movement of the capsule 11 during an impact is likely impeded by adjacent objects such as door handles, front seat backrest in case of a backseat mounting or a dashboard in case of a front seat mounting of the child safety seat 10. In addition, a deploying air bag may push the capsule 11 into an unfavorable orientation. Therefore, there exists a need for a child safety seat that may rotationally reorient itself during an impact unimpeded by eventual contact with adjacent objects and/or unimpeded by an eventually deploying air bag. The present invention addresses also this need.
The use of hinges and an eventual cardan arm 12 to rotationally hold a seat/capsule 11 with respect to the base 13 requires increased stiffness of the seat/capsule 11 to channel the extreme mass forces that may occur during a crash onto the relatively small hinges AC1, AC2 as may be clear to anyone skilled in the art. This in turn results in increased mass and momentum of inertia of the seat/capsule 11. In addition, deformation in the hinges and in the eventual cardan arm 12 need to be accounted for as well and sufficient spacing between the seat/capsule 11 needs to be provided between the individual parts that move with respect to each other. For a given installation space available in a passenger car, the size of the seat/capsule 11 is consequently limited by such spacing constraints, which in turn forces a positioning of the child close the hinges AC1, AC2 resulting in a large neck center angle ON. Therefore, there exists a need for a rotationally reorienting child safety seating system in which rotational guiding may be provided without use of hinges or intermediate structures in a direct fashion between a rotating capsule and a fixed base that provides for low momentum of inertia and maximum space of the rotating capsule and seating of the child with reduced neck center angle ON. The present invention addresses also this need.
Finally, the rotational speeds induced on a rotating seat/capsule 11 during crashes at varying impact speeds may vary with at least one order of magnitude as may be well appreciated by anyone skilled in the art. A generic brake without any means to adjust itself to the large bandwidth of rotational speeds of the seat/capsule 11 most likely will cause a stopping of the seat/capsule 11 at an unintended final orientation diminishing or even canceling the intended operation of the seat/capsule 11. Therefore, there exists a need for a braking feature that responds to varying rotational speeds of the seat/capsule 11 for an increased reorientation precision. The present invention addresses also this need.

Spherically guided safety seating system


An optical scatterometer system enables analysis of a sample material at various wavelengths without rotating or otherwise moving the sample material.

This invention relates generally to scatterometer analysis and more particularly to a scatterometer method that provides a practical means for analysis of a sample which eliminates the requirement of rotating, tilting or otherwise moving the sample during the course of a scatterometer measurement.
Scatterometer arrangements, like those described in the prior art patents and patent application cited above, have been used for characterizing the microstructure of microelectronic and optoelectronic semiconductor materials, computer hard disks, optical disks, finely polished optical components, and other materials having lateral dimensions in the range of tens of microns to less than one-tenth- micron.
Exemplary of the prior art are three publications. The first is by Michael R. Murnane, et.al., "Developed Photoresist Metrology Using Scatterometry", Proceedings of the SPIE, Integrated Circuit Metrology, Inspection, and Process Control VIII, Vol 2196, pp 47-59 (1994); the second is by Michael R. Murnane, et. al., "Scatterometry for 0.24 .mu.m-0.70 .mu.m Developed Photoresist Metrology", Proceedings of the SPIE, Integrated Circuit Metrology, Inspection, and Process Control IX, Vol 2439, pp 427-436 (1995); the third is by Christopher J. Raymond, et. al., "Metrology of Subwavelength Photoresist Gratings Using Optical Scatterometry", Journal of Vacuum Science and Technology, B, Vol 13(4), July/August, pp 1484-1495 (1995). This referenced prior art extends the capability of the scatterometer measurements to enable characterization of structure having lateral dimensions that are sub-micron. The prior art scatterometer arrangement discussed in the literature is disadvantageous in that it requires rotation of the sample while performing a scatterometer measurement. This requirement precludes their use in applications in which the sample must remain stationary. In addition, the rotation stages employed in this prior art scatterometer represents a mechanical complexity, which can result in undesirable optical and mechanical misalignment. Finally, the sample rotation required in this prior art scatterometer necessitates increased sample handling, thus increasing the risk of damage to the sample.
It is therefore the principle object of the present invention to provide a scatterometer method that provides a practical means of sample analysis, This is accomplished by illuminating the sample with light that has a broad spectral composition, characterizing the spectral composition of the light that is diffracted from the sample, and analysis of the diffracted light using techniques that are based upon multivariate statistical techniques and theoretical techniques; collectively the elements of this method eliminates the requirement to rotate or otherwise move the sample.

Method for broad wavelength scatterometry


A catheter for delivering an agent to an area of treatment is presented. The catheter includes a catheter body, a balloon assembly coupled to the catheter body, a first lumen, and a second lumen. The balloon assembly has spaced-apart balloons that define an area between the balloons. The first lumen extends along the catheter body to pass an inflation material to the balloons to control an inflation level of the balloons. The second lumen extends along the catheter body and having an outlet in the area between the balloons. There may be a third lumen for bypassing a biological fluid such as blood while the catheter is being used. The method of using this catheter is also presented. The method entails simultaneously inflating the balloons to isolate a treatment area and adding an agent to the treatment area through one of the lumens.

Catheters have been widely used to access the vascular system and other anatomical spaces in medical procedures. Catheters may be used for infusion of therapeutics and for the insertion or placement of substances or apparatuses for treating various disorders. Catheters may also be modified, for example, by the addition of balloon systems, for the treatment of arterial plaques and aneurisms.
Arterial plaques grow on arterial walls as cholesterol circulates in the blood, and as the plaques enlarge the arteries become narrow and stiffened. This process is called atherosclerosis, commonly known as "hardening of the arteries" because the plaque buildup thickens the walls of the arteries, narrowing the space through which blood flows. The narrowing or blockage of the vessel is also referred to as "stenosis."
One of the common methods for treating arterial plaques is balloon angioplasty. As an established procedure in the management of a variety of obstructive disorders of the vascular system, balloon angioplasty has been applied to obstructive lesions of the iliac, femoral, renal, coronary and cerebral vascular systems. Typically, a small flexible guide wire is advanced through a guiding catheter into the vessel and across the stenosis. A balloon catheter is then advanced over the wire and positioned across the stenosis. The balloon is usually inflated for a short period of time to dilate the vessel and is then deflated. Alternatively, stenosis may be treated by chemical means. For example, U.S. Pat. No. 4,636,195 to Harvey Wolinsky describes a catheter with distal and proximate balloon segments expandable to produce a chamber around an arterial plaque and a conduit for delivering a solubilizing liquid into the chamber to dissolve the plaque. U.S. Pat. No. 6,056,721 to John Shulze also describes a balloon catheter device for treating an obstructing material within a vascular conduit. The device comprises an elongate catheter body extending between a proximal end and a distal end. A balloon is attached at the distal end to block the flow of a body fluid and a drug is released from the catheter body to treat the obstructing material. Other methods for treating stenosis include ionizing radiation and laser evaporation.
All these procedures usually cause some degree of biological reaction of the vessel wall and often result in new growth and significant reduction of the vessel lumen (restenosis) at the treatment site. Therefore, it is a common procedure to place a stent at the treatment site after balloon angioplasty to prevent restenosis. The stent is usually introduced to the target area in a compressed form by an insertion catheter and then expanded in situ by means of a special balloon catheter. The stent will remain in position in its expanded state, supporting the wall of the vessel in a manner that essentially restores the original form of the vessel. The stent may also be formed in situ. For example, U.S. Pat. No. 6,039,757 to Stuart Edwards et al. generally describes a device for forming a fenestrated stent in situ in a body lumen. Briefly, the body lumen and the stent-forming device form a mold space within which a fluent composition is provided and transformed into a non-fluent composition in the shape of a stent with a series of fenestrations.
The term "aneurysm" refers to the abnormal enlargement or bulging of an artery caused by damage to or weakness in the blood vessel wall. Although aneurysms can occur in any type of the body's blood vessels, they almost always form in an artery. A ruptured aneurysm can lead to internal bleeding that often results in severe impairment of body functions and even death. Traditional treatment for aneurysms is surgical clipping which requires major surgery and cannot be performed on aneurysms inside vital organs, such as the brain. A much less-invasive technique, endovascular coiling, has been developed as a viable alternative to surgery for many patients whose aneurysms might otherwise go untreated. In an endovascular coiling procedure, a microcatheter is inserted into the femoral artery in a patient's groin area. The microcatheter is tracked through the patient's blood vessels (arteries), from the femoral artery up to the site of the aneurysm. Matrix coils are fed through the catheter and into the aneurysm, filling it and sealing it off from the artery. In animal studies, the coils were found to promote the development of connective (scar) tissue inside the aneurysm. The connective tissue excluded the aneurysm from arterial blood flow. An aneurysm occluded from blood circulation may have a decreased risk of rupture.
In order to treat an aneurysm effectively with an endovascular coil system, the coil must be inserted into the aneurysm and positioned inside the aneurysm in a proper configuration. The process, however, is often time-consuming and requires experienced operators.
Another illness that is currently not treated effectively is cancer. Most current efforts to eliminate tumors include systematic approaches such as chemotherapy, radiation, and surgical removal of tissues. When a tumor is vascular, chemotherapy and radiation treatments are less effective than desired because it is difficult to target the tumor with an effective level of specificity and only a small percentage of the chemotherapy and radiation get "pushed" into the capillaries that feed the tumor. With only a small percentage of the chemotherapy and radiation actually getting to the tumor, more of the chemotherapy and radiation end up reaching the healthy tissues instead of the tumor. A treatment method that allows a more targeted approach to kill the tumor is desirable.
Most catheters are specialized and can only be used for a specific medical procedure. For example, an angioplasty catheter cannot be used for treating aneurysms and, vice versa, catheters designed for treating aneurysms cannot be used for stenosis. In the case of balloon angioplasty, the angioplasty and stent installation typically require two different disposable, low profile guiding catheters. The insertion and removal of the catheters are time-consuming processes and the catheters are expensive.
In order to reduce costs and improve efficiency, it would be desirable to have one catheter that could be used to treat multiple illnesses such as stenosis, aneurysm, and vascular cancer.


A method for producing silicon microneedle arrays with drilled holes includes producing a silicon microneedle array. For each microneedle in a plurality of microneedles in the microneedle array, a laser is positioned relative to a microneedle and a drilled hole is drilled into the microneedle array by laser drilling. The drilled holes are drilled in microneedles, in flanks of the microneedles or alongside microneedles. A microneedle array includes a substrate composed of a micromechanical semiconductor material. The microneedle array has microneedles that project from the substrate and has drilled holes. The microneedles are composed of a porous micromechanical semiconductor material.

The present disclosure relates to a method for producing silicon microneedle arrays with holes and to a microneedle array.
Microneedle arrays with through-holes are used in the cosmetic field and the medical field. Numerous processes exist for producing microneedles composed of metal, polymer and silicon. The microneedles composed of silicon are produced by methods of microsystems engineering, inter alia by lithography or mask processes and etching methods or patterning processes. Methods for producing silicon microneedle arrays with through-holes are likewise already known, for example from US 2005 011 858 A1, US 2006 172 541 A1 or CN 1 526 454 A. All the methods mentioned above use the mask processes and patterning processes from semiconductor fabrication to produce the through-holes. The known processes which produce needles with through-holes for filling the needles from the rear side, involve a very high outlay.
Furthermore, JP 2011 072 695 A discloses a method for producing polymer microneedle arrays with through-holes. The microneedle array is produced by means of a heat imprint method. Through-holes are subsequently produced in the needles by means of a femtosecond laser, wherein the laser beam coming from the flat substrate side penetrates through the substrate and subsequently penetrates into the needles.

Method for producing silicon microneedle arrays with holes and microneedle array


An automatically actuated shunt valve system opens and closes a passage between two chambers of a powered element operated by a power source. The shunt valve system includes a coupler connecting the powered element with the power source through two mating coupling elements. One of the coupling elements includes a valve contact and the other includes a shunt valve assembly. The shunt valve assembly includes a valve chamber connected with both chambers of the powered element, a valve element opening or closing a flow path between the conduits, and a shaft for moving the valve element. The shaft engages the valve contact to move the valve element to close the flow path when the coupling elements are mated together, and moves the valve element to open the flow path when the shaft disengages from the valve contact as the coupling elements are disconnected from one another.

Work vehicles, such as those used in the agriculture, construction and forestry industries, and other vehicles, equipment and machinery may include connectors for releasably coupling power lines between the work vehicle and an implement or other equipment. The power lines may communicate hydraulic or other fluids, electric current, mechanical motion, or other forms of transmissions. One such application involves loaders such as those mounted on an agricultural tractor. When the loader is not needed, it can be removed from the tractor and parked. During parking, the power lines between the tractor and loader need to be decoupled. The connections typically require manual coupling and decoupling, often involving multiple steps. These steps may involve climbing off and reboarding the tractor, moving around to access various mechanisms, and operating various mechanisms. Accordingly, simplifying the connection process would be beneficial.

Automatically actuated shunt valve system


Compositions and processes for the preparation of printed circuits from epoxy compositions are provided. The epoxy compositions exhibit low viscosity in the uncured state and low coefficient of thermal expansion in the cured state. The low dielectric constant compositions of the invention are well-suited for use in multi-layer printed circuit boards.

So called "epoxy resins" are polymeric materials characterized by the presence of more than one epoxide ring per molecule on average. Epoxies have a tremendous range of applications in modern day society. These applications include coatings on metal cans, automotive primers, printed circuit boards, semiconductor encapsulants, adhesives, and aerospace composites. Epoxies are, in general, thermoset polymers which, in the presence of a curing agent, or cross-linking agent, undergo extensive cross-linking to form a three dimensional polymer network. Most cured epoxy resins form relatively dimensionally stable amorphous networks with excellent mechanical strength and toughness; outstanding chemical, moisture, and corrosion resistance; and good thermal, adhesive, and electrical properties. The highly useful combination of properties, along with versatility in formulation and low cost, have led to the widespread use of epoxies in a plethora of adhesive, structural, and coatings applications.
Great demands are placed upon the epoxy employed for the built up layers in the multilayer printed circuit board application. The dielectric layer is desirably matched in coefficient of thermal expansion (CTE) to that of the silicon chip (3-4 ppm/° C.), to avoid the creation of misalignments during thermal cycling, and to that of the copper (ca. 17 ppm/° C.) to avoid stress-induced delamination. Recently, CTE in the out-of-plane direction has taken on increasing importance. The uncured composition must be of sufficiently low viscosity at the lamination temperature that it will fill all the space between conductors; and the cured epoxy must retain sufficient toughness (usually measured as elongation to break) to endure being dropped in use (as in, e.g., a cellular phone). It is also desirable that a simple chemical etching of the surface provide the desired degree of roughness—ca. 0.1 micrometers—for copper deposition by electroless and electrolytic methods and exhibit an adhesive strength of ca. 6 N/cm.
Commonly, dielectric layers employed in the art are epoxy resins which exhibit CTE values of 70 ppm/° C. and higher. One approach to achieving reduction of CTE has been to employ heavy loadings of inorganic fillers on the order of 1-20 micrometers in average particle size. While reducing CTE, high loadings of inorganic fillers have resulted in increased brittleness, increased viscosity, poor adhesion strength, and degraded dielectric properties.
There is a clear need in the art for improved property trade-offs in epoxies employed in building up multilayer printed circuits.
Nakamura, US Patent Publication 2005/0129895 discloses the use of 30% by weight of spherical silica of unstated size in an epoxy composition. Nakamura provides no determinations of viscosity or flow performance, no measurement of CTE, and no determination of impact toughness.
Yasu, Japanese unexamined patent application JP 02263858 (abstract only), discloses epoxy compositions comprising ca. 60% by weight of hydrated alumina. No information about viscosity or flow is provided; no information regarding impact toughness, nor adhesive strength is provided.
Cochrane et al., Modern Paint and Coatings (October, 1983), discloses incorporation of a mixture of fumed silicas differing in particle size into epoxy compositions for the purposes of rheology control. Loadings of silica are 5% by weight or less.

Printed circuits prepared from filled epoxy compositions


The present invention relates to a pressure regulator and in particular to a closed active pressure regulator gas coupled to an acoustic device which is disposed underwater. The pressure regulator comprising an internal pressure sensor, a valve, and a gas supply each coupled to a processor, at least said valve, gas supply and processor disposed within a fluid tight housing, said pressure regulator including an external pressure sensor coupled to the processor though the housing, whereby said pressure regulator is gas coupled to an acoustic device disposed underwater, said acoustic device contained within a pressure sealed and fluid tight container, said pressure regulator is a closed active system for removing gas from the container to the gas supply or supplying the gas from the gas supply to the container thereby regulating the pressure in the container.

An acoustic device, such as a speaker, can be deployed underwater for many uses such as guiding fish, providing entertainment etc. However, as the depth of the acoustic device or underwater speaker increases, the external pressure increases proportionally. This pressure increase affects the acoustic response of the underwater speaker due to the external and internal differential pressure. As such the effectiveness of the speaker is reduced.
In response to this problem, the internal pressure around the speaker system can be increased to reduce the pressure differential. It has been proposed that this could be achieved through a passive pressure regulation system by way of a pressurised, compressible external vessel. As the depth and pressure increases, the pressurised vessel is compressed and air is forced into the internal acoustic chamber.
This method of passive gas pressure regulation is limited by the properties of the external vessel and can only be used at low depths. For example, when a speaker is disposed in a neoprene bag in salt water and depths of no more than 25 m, under long term use, i.e. periods of 9 months or so, the neoprene bag loses pressure and the gas therefore needs to be replaced.
In response to increasing pressure at depth, alternative methods of passive pressure compensation have been developed: see for example the pressure compensators from Link: Fathom Systems Ltd. Typically, these systems operate at depths of greater than 1000 m where pressures exceed 1×107 Pa. These systems are designed for use with electronic or hydraulic systems that can be submerged in hydraulic fluid due to the compressibility of air at these extreme depths limiting the pressure compensation systems working range. As the pressure increases with depth, the piston, which is exposed on one surface to the water, compresses the hydraulic fluid and increases pressure inside the electronics chamber. A disadvantage of a passive oil filled pressure compensation system is that they do not allow pressures to be regulated to high resolution e.g. tens of Pascals. In addition, the systems require a fluid filled enclosure for the electronic equipment.
In JPH8-251687, there is disclosed a pressure equalizing device for an underwater sound source. This pressure equalizer includes a diaphragm for generating the sound open to the water. A compression tank together with flow rate control valves and gas injection and gas exhaust lines are used to try and maintain the pressure to the other side of the diaphragm.
Again such pressure equalizing is limited due to poor sealing of the sound source such that a constant gas supply is needed and the equalization occurs through varying the flow rate of the gas supplied or when exhausted, released to the sea. Accordingly, such a system is relatively crude and is unable to be used at greater depths with any degree of accuracy. In particular, the system is not a closed system, requiring constant recharging of the gas supply leading to its inability to be located at certain sites where constant recharging is not possible through operational difficulties such as depth or access.
Thus, it is the aim of the present invention to mitigate such disadvantages of passive gas or oil pressure equalizing systems
The present invention thus relates to a pressure regulator comprising an internal pressure sensor, a valve, and a gas supply each coupled to a processor, at least said valve, gas supply and processor disposed within a fluid tight housing, said pressure regulator including an external pressure sensor coupled to the processor though the housing, whereby said pressure regulator is gas coupled to an acoustic device disposed underwater, said acoustic device contained within a pressure sealed and fluid tight container, said pressure regulator is a closed active system for removing gas from the container to the gas supply or supplying gas from the gas supply to the container, thereby regulating the pressure in the container.


The present invention provides a rapid RT-PCR detection method and a diagnostic kit for differentiating field isolates of classical swine fever virus (CSFV) from lapinized CSF vaccine viruses in samples. In order to detecting different genotypes of CSF virus, this invention uses a pair (or pairs) of CSF virus specific primers designed from the conserved sequences within the 3′-untranslated region of CSFV which contains an insertion of 12˜13 nucleotides (poly T) in the region of the lapinized CSF vaccine virus, in comparison with the corresponding region of field isolates of CSFV. By the RT-PCR or the RT-PCR followed by a nest-PCR, field isolates of CSFV and lapinized CSF vaccine viruses in samples could be detected directly and quickly and/or differentiated in electrophoresis without further enzymatic digestion or DNA sequencing.

Classical swine fever (CSF), previously referred to hog cholera (HC), is an important infectious disease of swine caused by CSFV. Domestic pigs and wild boar are susceptible to CSFV. The virus belongs to the genus Pestivirus within the family Flaviviridae, which also includes bovine viral diarrhea virus (BVDV) and border disease virus (BDV) (Matthaeus, Zbl. Vet. Med. 328: 126-132, 1981). They are antigenically and structurally closely related but CSFV can be distinguished from BVDV and BDV in serological and nucleotide differences (Paton, J Comp pathol 112: 215-236, 1995). The most commonly used in laboratory CSF diagnostic methods, such as immuno-fluorescence stain, enzyme linked immunosorbent assay (ELISA) and RT-PCR, can hardly distinguish the field isolates of CSFV from the lapinized CSF vaccine viruses. Records of CSF in Taiwan date back to 1938 (Lee, Scientific Agri (Taiwan), 2(11): 4-14). In an effort to control this highly contagious disease, a live attenuated vaccines made from a lapinized CSF vaccine virus, LPC strain, have been widely used in the field since 1958 in Taiwan (Lin, National Science Council Special Publication Number 5, 1-42, 1981). Vaccination significantly decreased the incidence. However, sporadic outbreaks were still reported occasionally. According to the current legislation on CSF in Taiwan, each piglet has to be vaccinated twice with the LPC vaccine virus in 3, 6 or 6, 9 weeks old, it depend on the decrease level of maternal antibody. Unfortunately, the vaccine virus can be detected and can't be differentiated from field isolates of CSFV by ELISA and RT-PCR in samples of pigs. Since the LPC vaccine virus interfered with the laboratory diagnosis of CSF, the RT-PCR amplicons always proceed with nucleotide sequencing to exclude the interference by LPC vaccine virus in Taiwan.
A tentative assignment of world isolates of CSFV by genotyping has been divided it into three groups with three or four subgroups: 1.1, 1.2, 1.3; 2.1, 2.2, 2.3; 3.1, 3.2, 3.3, 3.4 (Paton, Vet. Microbiol. 73: 137-157, 2000). Phylogenetic analysis of the Erns and E2 sequences of 158 CSFVs, which were isolated in the field in Taiwan between 1989 and 2003, shows that four distinct CSFVs genotypes existed in Taiwan including one endemic strain (subgroup 3.4) and three introduced strains (subgroup 2.1a, 2.1b and 2.2). The analysis also shows the LPC strain doesn't belong to the aforementioned four subgroups, but to the subgroup 1.1. (Pan, Arch Virol, 150(6): 1101-19, 2005).
There are four lapinized CSF vaccine viruses, namely LPC, HCLV, Chinese C and Riem C, widely utilized in the world nowadays. The LPC strain was derived from the Rova strain of CSFV, which had already undergone about 250 serial passages in rabbits by Lederle Laboratory in Philippines and was introduced into Taiwan by Dr. Chung-Tao LEE in 1952 (Lee, Scientific Agri (Taiwan), 2(11): 4-14). The pigs inoculated with this virus showed a severe post-vaccinated reaction and a few of them even died of CSF after vaccination. In order to obtain a highly safe and potent strain for CSF vaccination, the virus was then rapidly and carefully serial-passaged through native Taiwan rabbits. After more than 800 passages in rabbits, it proved extremely safe for pigs and highly effective against CSFV (Lin, National Science Council Special Publication Number 5, 1-42, 1981). Nowadays, the LPC vaccine is widely utilized to protect pigs from CSF in Taiwan. The HCLV strain was derived from the wildtype strain Shimen by 480 passages in the bodies of rabbits in China in 1950s. (Wu, Virus Genes, 23(1): 69-76, 2001). The Chinese C strain is a cell culture adapted derivative of HCLV strain. (Oleksiewicz, Veterinary microbiology, 92:311-325, 2003). The Riem C strain is a cell culture adapted derivative of HCLV strain and used as bait vaccine in Europe (Oleksiewicz, Veterinary microbiology; 92:311-325, 2003). Wu et al. (Virus Genes, 23(1): 69-76, 2001) have sequenced HCLV strain and discovered one notable insertion of 12 continuous nucleotides, CTTTTTTCTTTT (SEQ ID NO:8) in the 3′-untranslated region of HCLV genomic cDNA when compared with its parental virulent Shimen strain. Wong et al (Virus Genes; 23(2): 187-92, 2001) also sequenced the whole genome of LPC vaccine strain and found that an insertion 0113 nucleotides, TTT(C/T)CTTTTTTTT SEQ ID NO:9, in the 3-untranslated region of LPC vaccine strain. The inventors of the present invention had also compared all the CSFV sequences from the GenBank and found that only the four lapinized CSF vaccine viruses, LPC, HCLV, Chinese C and Riem C strains, have an insertion of 12˜13 nucleotides in their 3-untranslated regions and the insertion is not found in the field isolates of CSFV. Other non-lapinized CSF vaccine viruses, such as Japanese GPE- and Russian CS vaccine strains, also do not have the insertion.
Vaccination is one of the most successful tools for the prevention of CSFV infection. Unfortunately, the use of laboratory diagnostic methods to detect CSFV could be interfered by vaccine virus when attenuated vaccines are in use. For this reason it is of interest to know how long after vaccination can the vaccine strain be detected in samples that are commonly used for diagnostic procedures. To study the duration of vaccine virus distribution in piglets, Lorena et al. (Veterinary microbiology, 81: 1-8, 2001) inoculated piglets with the Chinese C strain vaccine virus and studied the distribution of vaccine virus in organ samples of inoculated piglets. He found that the virus can be detected in tonsil on post-inoculation day (PID) 6, 8, 10, 13 and 16 using ELISA and in blood samples on PID 2, 4, 6, 8, 10, 13, and 16 using RT-PCR. Therefore, he emphasized that this factor must be considered in routine diagnostic procedure, when vaccination against CSF with a live vaccine is carried out. In Germany, CSF was present in wild boar in different federal states (Veterinary microbiology, 82: 301-310, 2001). Infection in domestic pigs was usually caused by direct or indirect contacts with infected wild boars. Wild boars distributed in the woods and they are difficult to be caught for injecting CSF vaccine. Therefore, Oral application of CSF vaccines (lapinised or cell culture vaccines) is necessary and has been investigated in Europe (Veterinary microbiology, 73: 239-252, 2000). Kaden et al. (J Vet Med B Infect Dis Vet Public Health, 51(6): 260-2, 2004) studied the persistence period of the Chinese C strain vaccine virus in immunized animals after oral vaccination. The results show that the C strain virus can be found in organs until day 8 post-vaccination (pv) in domestic pigs and until day 9 pv in wild boars. In the CSF endemic countries like Taiwan where vaccination program with live vaccine is carried out, the vaccine virus can probably be detected in the blood and lymphatic tissue samples such as tonsil, lymph nodes and spleen. Therefore, diagnosis with the commonly used diagnostic methods such as immuno-fluorescence stain, ELISA and RT-PCR can be interfered by the vaccine virus.
Virus isolation, ELISA and RT-PCR are the most commonly used methods for CSF laboratory diagnosis. Paton et al. (Veterinary microbiology 73: 159-174, 2000) show that the order of the sensitivity was RT-nested PCR>RT-PCR>virus isolation>ELISA when applying these methods to clinical samples in CSF diagnosis. Dewulf et al. (Journal of Virological Methods 119: 137-143, 2004) compare several CSF laboratory diagnostic techniques on live animals for detection of infection. He concluded that the RT-nPCR technique is the best diagnostic tool available for early detection of a CSF infection. A real-time RT-PCR for the simple and rapid diagnosis of CSF has been developed and evaluated in experimentally infected swine and clinical samples (Risatti, Journal of Clinical Microbiology; 41(1): 500-505, 2003; Risatti, Journal of Clinical Microbiology, 43(1): 468-471, 2005). Accordingly, real-time RT-PCR is recognized as a sensitive method for rapid diagnosis of CSF. However, no real-time RT-PCR for distinguishing the field isolates of CSFV from the lapinized CSF vaccine viruses has been established.
The RT-PCR and nucleotide sequencing are widely used as the methods to solve this problem. The disadvantage of these methods includes the laborious process of the methods and the incapability of screening large field samples. Zaberezhny et al. (Dtsch Tierarztl Wochenschr. September; 106(9): 394-7, 1999) have used RT-PCR and restriction enzyme digestion for differentiation between Russian vaccine strain from field isolates of CSFV. Vilcek et al. (Acta Vet Scand. 39(3): 395-400, 1998) also used restriction endonuclease cleavage of PCR amplicons to distinguish the vaccine strain from European field strains. These are the two documents available about the utilization of the RT-PCR and restriction enzyme digestion method to differentiate the vaccine virus and field isolates of CSFV; besides, the prior art can only distinguish the two viruses by RT-PCR followed by nucleotide sequencing. Thus there is no prior disclosed information concerning the utilization of the characteristic of one 12˜13 nucleotides inserting in the genome of the 3′-untranslated region of the lapinized CSF vaccine viruses to establish a differential RT-PCR without combination with other technique. CSFV specific primers are designed to amplify the aforementioned 3′-untranslated region and then the size of the RT-PCR amplicons can be compared directly by electrophoresis without further processing the complicated enzymatic digestion and nucleotide sequencing to determine the existence of the field isolates of CSFV and lapinized CSF vaccine viruses and to differentiate between them. The diagnosis of CSF can thus be more rapid, convenient and the interference from the vaccine virus can be more correctly excluded.

RT-PCR detection for differential diagnosis of field isolates or lapinized vaccine strain of classical swine fever virus (CSFV) in samples

Animal Health Research Institute, Council of Agriculture, Executive Yuan