text:
|Publication number
|Publication type
|Application number
|Publication date
|Jul 26, 1988
|Filing date
|Jun 19, 1987
|Priority date
|Aug 6, 1986
|Fee status
|Also published as
|Publication number
|Anthony Acampora, Michael G. Hluchyj, Yu S. Yeh
|Original Assignee
|American Telephone & Telegraph Company, At&T Bell Laboratories
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (6), Non-Patent Citations (10), Referenced by (60), Classifications (9), Legal Events (7)
|External Links: USPTO, USPTO Assignment, Espacenet
This application is a continuation-in-part, application Ser. No. 893,617, filed Aug. 6, 1986 now abandoned.
The present invention relates to a switching arrangement for routing high-speed, time multiplexed, fixed-length packets of information from N inputs to N outputs in a high-performance packet switching system. More particularly, the present switch uses distributed control and a fully interconnectable configuration to route arriving fixed-length packets to their appropriate outputs using a single stage of switching which includes a minimum amount of buffering and provides the lowest packet latency in any switching arrangement.
Every type of communication network interconnecting more than two users depends on some form of switching to efficiently route information among the various users. In such switches, the traffic presented at two or more inputs may be destined for a common output. There are basically only two ways that such a situation can be managed.
First, the switch may require a controller that schedules the arrivals of packets to avoid conflict. The classic Time-Space-Time switch shown in FIG. 3.6 at page 95 of the book by H. Inose entitled "An Introduction To Digital Integrated Communications Systems", University of Tokyo Press, Tokyo, Japan, 1979 falls into this category. There, each input to the switch is preceded by a Time Slot Interchange to rearrange the time sequence of the time-multiplexed traffic so that, when presented to the switch, the data appearing at the N inputs are, at all times, destined for distinct separate outputs. However, scheduling is a difficult task, as shown by T. Inukai in IEEE Transactions on Communications, Vol. COM-27. No. 10, October 1979 at pages 1449-1455 and, although feasible and adequate for circuit switching, requires too much time to determine permissible input/output combinations to be applicable for packet switching.
The second way, and perhaps the more attractive approach for managing contention, employs decentralized control and distributed routing wherein each packet or burst of traffic contains a header bearing the destination port of the switch for that packet, where the header is used in routing the packet through the switch. Without the coordination afforded by the central scheduler, the switch must now recognize conflict among its inputs and internally store, or buffer, all but at most one of several simultaneous arriving packets destined for a common output, thereby leading to statistical delay, or latency, within the switch. Such self-scheduling switches, as shown in the article by D. M. Dias et al. in GLOBECOM '84, Vol. 1, Atlanta, Ga., Nov. 26-29, 1984, pages 5.2.1-5.2.7, typically employ binary switching elements appropriately interconnected and arranged to form a multistage switch. These switches have tended to emphasize a reduction in the number of switch elements needed to a value below that of a fully connected arrangement, one wherein each input has a dedicated path to each output and thereby requiring N2 elements. In addition to congestion at the outputs, these element-efficient switches can also congest at each of the binary switch points, thereby requiring that additional measures be taken, such as buffering within each element. Because these autonomous buffers cannot be shared among elements, the complexity of the buffering is typically much greater than that of the binary switching elements themselves. Moreover, the delay encountered within the network is greater than the unavoidable component caused by destination congestion alone.
The problem remaining in the prior art is to provide a switch which can be used for packet switching and avoids (1) the scheduling problems encountered with switches requiring controllers, and (2) the buffering complexity and delays encountered by the decentralized control and distributed routing switches.
The foregoing problem in the prior art has been solved in accordance with the present invention which relates to a switching arrangement for routing high-speed, time multiplexed fixed-length packets of information from N inputs to N outputs in a high-performance packet switching system. The present switch uses distributed control and a fully interconnectable configuration to passively route arriving fixed-length packets to their appropriate outputs using a single stage of switching.
It is an aspect of the present invention to provide a switching arrangement for routing multiple simultaneous high-speed, time-multiplexed fixed-length packets of information from the N inputs to the N outputs using decentralized control and distributed routing. The switching arrangement comprises two basic characteristics: (1) each input has a separate broadcast bus, and (2) each output has access to the packets of information arriving on all inputs. More particularly, each output passively interfaces to the complete set of N input buses and provides several important features. First, no switch blocking occurs where packets destined for one output interfere with packets going to other outputs. Second, the broadcast buses can reside on an equipment backplane with the circuitry for each of the N input/output pairs placed on a single plug-in circuit card. Third, with each bus being driven by only one input it allows for a higher transmission rate on the buses than found with a shared parallel bus accessed by all inputs. Lastly, since every input is available at the interface to every output, arriving packets can be addressed to, and received by, multiple outputs and thereby lends itself to broadcast and multicast features.
It is a further aspect of the present invention to provide a "Knockout" switching arrangement for routing high-speed, time-multiplexed fixed-length packets of information from N inputs to N outputs using decentralized control and distributed routing. Structurally, the N input signals are propagated along separate buses to each of N bus interface units which include N packet filters, a concentrator and a shared buffer. Each bus interface unit is associated with a separate one of the N outputs, and the N packet filters therein are each associated with a separate one of the N buses for detecting if a packet on the associated bus is destined for the associated output. The concentrator is used at each output to reduce the number of separate buffers needed to receive simultaneously arriving packets. The contending packets are stored in the shared buffer before placement on the output line on a first-in, first-out basis.
Other and further aspects of the present invention will become apparent during the course of the following description and by reference to the accompanying drawings.
Referring now to the drawings in which like numerals represent like parts in the several views:
FIG. 1 illustrates a block diagram of an N-input, N-output time slotted packet switching arrangement in accordance with the present invention including typical fixed length packets arriving in a time-slotted sequence at the N inputs and routed to the appropriate N outputs;
FIG. 2 is a block diagram of one of the N bus interface units of the switching arrangement of FIG. 1;
FIG. 3 illustrates an exemplary packet format for transmission through the switching arrangement of FIG. 1;
FIG. 4 is a circuit diagram of an exemplary arrangement of the N packet filters associated with each one of the bus interface units shown in FIG. 2;
FIG. 5 shows a simple 2�2 contention switch forming the basic building block of the concentrator in each bus interface unit of FIG. 2;
FIG. 6 illustrates the two states of a 2�2 contention switch of FIG. 5;
FIG. 7 is a block diagram of an exemplary 8 input/4 output concentrator for use in the bus interface unit of FIG. 2 using the contention switches of FIG. 5;
FIG. 8 is a block diagram of an exemplary 128-to-8 concentrator constructed from 32-to-8 concentrator chips for use in the concentrator in the bus interface unit of FIG. 2;
FIG. 9 shows an alternative exemplary block diagram of a shared buffer arrangement for the bus interface unit of FIG. 2;
FIG. 10 illustrates a shifter function within the shared buffer in the bus interface unit of FIG. 2 to achieve a first-in, first-out packet queuing discipline; and
FIG. 11 illustrates, by a block diagram, how the present switching arrangement can be made to grow modularly.
The switching arrangement in accordance with the present invention includes an N-input, N-output packet switch using decentralized control and distributed routing with all inputs and outputs operating at the same bit rate. Fixed-length packets arrive at the N inputs 10l to 10N of the present N-by-N switch 11 in a time-slotted manner in which each input includes packets having destinations as determined by the individual remote N transmitters sending the packets, as shown in the exemplary sequences shown in FIG. 1. Each packet in such arrangement contains, somewhere therein, the address of its destination output as shown in the exemplary packet format of FIG. 3.
Aside from having control over the average number of packet arrivals destined for a given output, no control over the specific arrival times of packets on the inputs and their associated output addresses is assumed. In other words, there is no time-slot specific scheduling that prevents two or more packets from arriving at different inputs in the same time slot and destined for the same output, as shown in FIG. 1 for the first arriving time slot for inputs 101 and 102 which are both destined for output 121. The addressing information is used by N-by-N packet switch 11 to route the incoming packets to their appropriate outputs 121 to 12N. Hence, to avoid lost packets, or at least provide a sufficiently small probability thereof, at a minimum, packet buffering must be provided in switch 11 to smooth fluctuations in packet arrivals destined for the same output.
The interconnection arrangement for N-by-N packet switch 11 has two basic characteristics: (1) each input 101 to 10N is associated with a separate broadcast bus 141 to 14N, respectively, and (2) each output 121 to 12N has access to all packets arriving on all inputs. As shown in FIG. 1, packets arriving at each of the N inputs 10i are placed directly on a separate broadcast bus 14i, and each output 121 to 12N passively interfaces to the complete set of N buses 14 via a separate bus interface unit 151 to 15N, respectively. This simple structure provides several important features. First, with each input having a direct path to every output, no switch blocking occurs where packets destined for one output interfere (i.e., delay or block) with packets going to other outputs. The only congestion in the switch takes place at the bus interface unit 15i to each output 12i, where packets can arrive simultaneously on different input lines 10 destined for the same output 12.sub. i. Without a priori scheduling of packet arrivals, this type of congestion is unavoidable, and dealing with it typically represents the greatest source of complexity within a packet switch. This complexity is minimized by the present N-by-N packet switching arrangement 11.
The broadcast bus structure of FIG. 1 has the desirable characteristic that each bus 14i is driven by only one input 10i. This allows for a higher transmission rate on the buses and a design more tolerant of faults compared with a shared parallel bus accessed by all inputs. In addition, the packet buffering and bus access control circuitry of the known shared parallel bus architecture is replaced in the present switch 11 by, at most, an elastic buffer at each input which is used to synchronize the time slots from the individual input lines.
FIG. 2 is a block diagram of an exemplary bus interface unit 15i associated with each output 12i of N-by-N packet switch 11. The bus interface unit 15i shown has three major components. First there is a row of N packet filters 201 to 20N, with each packet filter receiving the packets propagating on a separate one of broadcast buses 141 to 14N. In each packet filter 20i, the address of every packet broadcast on the associated broadcast bus 14i is examined, with packets addressed to the associated output of switch 11 being allowed to pass through packet filter 20i while all other packets are blocked. A concentrator 21 receives the outputs of all associated packet filters 201 to 20N at separate inputs and achieves an N-to-L (L≦N) concentration of the input lines, where up to L packets making it through the packet filters in each time slot emerge at the L outputs of concentrator 21. These L concentrator outputs then enter a shared buffer 22 comprising a shifter 23 and a plurality of L First-In, First-Out (FIFO) buffers 241 to 24L. The structure of shared buffer 22 allows complete sharing of the L FIFO buffers and provides the equivalent of a single queue with L inputs and one output, operating under a first-in, first-out queuing discipline.
FIG. 3 shows the format of the packets as they enter the packet filters 201 to 20N from the broadcast buses 141 to 14N, respectively. The preamble of each packet preferably contains the address 26 associated with the output on packet switch 11 for which the packet is destined, followed by a single activity bit 27. The destination output address 26 contains log2 N bits with each output 121 to 12N having a unique address. The activity bit 27 indicates the presence (logic 1) or absence (logic 0) of a packet in the arriving time slot and plays an important role in the operation of concentrator 21.
FIG. 4 shows exemplary components for each of the packet filters 20i. Each packet filter 20i comprises an Exclusive-Or (EX-OR) gate 30 which has one input from the associated broadcast bus 14i and the other input from a shift register 31 which is common to a bus interface unit 15i and stores the unique address for that bus interface unit. The output from each EX-OR gate 30 provides one input to a separate associated AND gate 32, with the second input providing a "Compare Enable" signal which is active during the arrival time of the output address 26 in each time slot. The output from AND gate 32 is provided as a first input to a flip-flop (FF) 33, with the second input being a "Start" enable signal which resets each FF 33 at the beginning of a time slot so that FF 33 outputs a logic "1" to a first input of an associated AND gate 34. The second input to AND gate 34 is from the broadcast bus 14i associated with that packet filter 20i.
In operation, at the start of every time slot, FF 33 in each packet filter outputs a logic "1" because of the "Start" control signal, and the path through each of the N packet filters 20 is open, initially allowing all arriving bits of the packets to pass through AND gate 34 to concentrator 21. As the address bits 26 for each arriving packet enter packet filters 20i, the address bits are compared bit-by-bit against the output address for that bus interface unit 15i as received from shift register 31. If all bits of an output address 26 match the address bits provided by shift register 31, then EX-OR gate 30 will output a logic "0" at all times to the K input of FF 33. If, however, any one of the address bits 26 does not match the corresponding address bit from shift register 31, then EX-OR gate will output a logic "1" and enable AND gate 32 to output a logic "1" to the K input of FF 33. Such enable of the K input of FF 33 will cause a logic "0" to be transmitted to the input of AND gate 34 and inhibit the further progress of the packet through AND gate 34 to concentrator 21 of that bus interface unit 15. That is, the output of the filter 20i is set at logic "0" for the remainder of the time slot.
By the end of the output address 26, the filter 20i will have either blocked the packet, and hence also set its activity bit 27 to 0 since it follows the output address 26 in the packet format, or, if the address matched, allowed the packet to continue on to the associated concentrator 21. Where two or more packets arrive simultaneously on separate broadcast buses 14 for the same output 12i, then the associated packet filters 20 will provide simultaneous transmission of those packets through to the associated concentrator 21 in the bus interface unit 15i. It should be noted that even though a portion of the output address bits 26 of a blocked packet may pass through the filter 20 and into concentrator 21, these bits no longer serve any useful purpose and are ignored by the rest of bus interface 15i. It should also be noted that it is the time-slotted nature of switch 11, where the starting time of all packets are synchronized and defined by the system clock, which allows a simple design for packet filters 20.
All packets making it through the associated packet filters 201 to 20N enter the associated concentrator 21, which achieves an N-to-L concentration. Specifically, if k packets simultaneously arrive in a time slot for a given output, these k packets, after passing through concentrator 21, will emerge therefrom on outputs 1 to k, when k≦L. If k>L, then all L outputs of concentrator 21 will have packets and k-L packets will be dropped or lost within concentrator 21. As with any packet switching system, packet loss is inevitable since it can be caused by transmission line errors (e.g., in the address portion of packet), buffer overflows, and network failures. In all cases, recovery is made possible by retransmission protocols, which, as the probability of losing packets in the network decreases, are more efficiently handled end-to-end rather than link-to-link. What must be assured, is that the probability of losing a packet within concentrator 21 is no greater than that of losing a packet elsewhere in the network.
The basic building block of concentrator 21 is a simple 2�2 contention switch 35 shown in FIG. 5. The two packets at inputs 36 and 37 contend for the "winner" output 38 according to their activity bits 27. If only one input has an arriving packet, as indicated by an activity bit=1, it is routed to the winner, or left, output 38. If both inputs have arriving packets with activity bits=1, the left input 36 is routed to the winner output 38 and the right input 37 is routed to the loser output 39. If both inputs have no arriving packets, one should not care except that the activity bit for both should remain a logic 0 at the switch outputs 38 and 39.
The above requirements are met by a switch 35 with the two states shown in FIG. 6. There, the switch 35 examines the activity bit 27 for only the packet arriving at the left input 36. If the activity bit=1, the left input is routed to the winner output 38 and the right input is routed to the loser output 39. If the activity bit=0 for the packet arriving at the left input 36, then the right input 37 is routed to the "winner" output 38 and no path is provided through the switch 35 for the left input 36. Such a switch can be realized with as few as 16 gates, and has a latency of at most one bit. Since the concentrator 21 can be designed for a lost packet rate of, for example, no greater than 10-6, the priority given to a packet on the left input 36 on each 2�2 switching element 35 is inconsequential. However, if this is of concern, the 2�2 switching element 35 can be designed so that it alternates between selecting the left and right inputs as winners when packets arrive at both inputs in the same time slot.
FIG. 7 shows an exemplary design of an 8-input, 4-output concentrator 21 composed of the simple 2�2 switching elements 35 of FIG. 5 and single-input/single-output 1-bit delay elements 40, indicated with a "D". At the input to concentrator 21, the N outputs from the associated packet filters 20 are paired and enter a row of N/2 switching elements 35. This may be viewed as the first round of a tournament with N players, where the winner of each match emerges from the left side of each of the 2�2 switching elements 35 and the loser at the right side. The N/2 winners from the first round advance to the second round where they compete in pairs as before using a row of N/4 switching elements 35. The winners in the second round advance to the third round and this continues until two compete for the championship; that is, the right to exit the first output of concentrator 21. It should be noted that if there is at least one packet arriving on an input to concentrator 21, a packet will exit the first output of concentrator 21.
A tournament with only a single tree-structured competition leading to a single winner is sometimes referred to as a single "knockout" tournament: lose one match and you are knocked out of the tournament. In a double "knockout" tournament, the N-1 losers from the first section 41 of competition compete in a second section 42, which produces a second place finisher and N-2 losers. As shown in FIG. 7, the losers from the first section 41 can begin competing in the second section 42 before competition is finished in first section 41. Whenever there is an odd number of players or packets in a round, one player or packet must wait and compete in a later round in a section. In concentrator 21, a simple delay element 40 serves this function.
For a concentrator with N inputs and L outputs, there are L sections of competition, one for each output. In essence, a packet entering concentrator 21 is given L opportunities to exit through a concentrator output. A packet losing L times is "knocked out" of the competition and is discarded by concentrator 21 in the last section 43. For the above reasons, the present switching arrangement can be called a "Knockout" switch. In all cases, however, packets are only lost if more than L packets arrive in any one time slot which can be designed to be a low probability occurrence. For the example where N>>L, each section of concentrator 21 contains approximately N switching elements 35 for a total concentrator complexity of 16NL gates. For N=64 and L=8, this corresponds to a relatively modest 8000 gates. FIG. 8 illustrates how several identical N=32, L=8 chips 47 can be interconnected to form a larger N=128, L=8 concentrator 21.
As will be shown, for values of N that are of interest, the complexity of packet buffering is greater by several orders of magnitude than all other components of the switch 11 combined. For this reason, the architecture of the bus interface unit 15 focuses, to the extent possible, on reducing the complexity of packet buffering. This is done first by using a concentrator 21 to reduce the number of inputs that must be buffered simultaneously. Second, through the use of a shared buffer 22, complete sharing of all packet buffer memory within a bus interface unit 15 is made possible. This is accomplished while still providing a first-in, first-out queuing discipline for the arriving packets and keeping the latency through a bus interface 15 to a minimum.
Since in any given time slot, up to L packets can emerge from concentrator 21, the shared buffer 22 within bus interface unit 15 must be capable of storing up to L packets within a single time slot. FIG. 9 illustrates that this can be done by using a separate exemplary serial-to-parallel converter 50 to receive each output signal from concentrator 21, and then multiplex the L outputs from converters 50 on a common parallel memory bus 51 which is read by a random access memory (RAM) 52. A controller 53 for RAM 52 ensures that the individual parts of each packet multiplexed on memory bus 51 are appropriately stored in RAM 52 for later transmission via parallel-to-serial converter 54 onto the output 12 of bus interface unit 15. By making the memory bus 51 at least L lines wide, no single wire on memory bus 51 has to operate at a rate greater than the transmission rate of the switch inputs 10 and outputs 12. However, RAM 52 will be required to operate at the speed of the arriving data. This may present a problem, since memory performance is typically the bottleneck in most systems, with access speeds an order of magnitude slower than other components such as buses and gates. The throughput of the memory 52 can be increased by increasing the size of the stored word, which cannot be made larger than the size of the arriving packets, but this involves increasing the width of memory bus 51 and serial-to-parallel converters 50, which in turn adds to the overall latency through the bus interface unit 15.
To permit high-speed, low-latency operation of the present "Knockout" switch 11, the bus interface unit 15 uses L separate FIFO buffers 241 to 24L as shown in FIG. 2. A simple technique provides complete sharing of the L buffers 24 and at the same time provides a first-in, first-out queuing discipline for all packets arriving for an output 12i. The latter ensures fairness for access to the output and, more importantly, that successive packets arriving on an input 10 do not get out of sequence within switch 11.
As FIG. 2 shows, the L outputs from concentrator 21 first enter a shifter 23 having L inputs and L outputs. The purpose of shifter 23 is to provide a circular shift of the inputs to the outputs so that the L separate buffers 24 are filled in a cyclical manner. This is illustrated in FIG. 10 for L=8. There, in the first time slot, five packets arrive for the output and, after passing through concentrator 21, enter the first 5 inputs of shifter 23. For this time slot, shifter 23 simply routes the packets straight through to the first 5 outputs, from which they enter buffers 241 to 245. In the second time slot, four packets are shown arriving for the output and enter shifter 23 on inputs 1 to 4. Having left off in the previous time slot by filling buffer 245, shifter 23 circular shifts the inputs by 5 outputs to the right so that the arriving 4 packets now enter packets buffers 24 associated with the 6, 7, 8 and 1 outputs of shifter 23. In the third time slot, the inputs are shifted one output to the right so that packet buffer 242 will receive the next arriving packet from the first output of concentrator 21.
The flow of packets, stored in packet buffers 241 to 24L, onto the output line 12i from bus interface 15i of switch 11 may be viewed as being controlled by a token. The buffer 24 holding the token has the right to transmit one packet in the next time slot, with buffer 241 initially holding the token in the first time slot. If a buffer 24 is empty, it will hold the token indefinitely until a new packet arrives and is transmitted. After such transmission, the token is handed to the next buffer 24 and wraps around in a cyclical manner.
With the above described buffering means for storing and removing packets for the L buffers 24, the shared buffer 22 architecture has the following two characteristics. First, packets are stored in and removed from the L buffers 24 in a cyclical manner. At any time the number of stored packets in each buffer 24 does not differ by more than one among the L buffers. Buffer overflow only occurs when all L buffers 24 are full. Therefore, the equivalent of a single buffer is achieved and shared by all L outputs of concentrator 21. Second, the token is held by the buffer 24 with the largest number of stored packets, and the packet to be transmitted next is the one that has waited the longest in bus interface unit 15i. In cases where more than one buffer 24 fits the criteria, the lower numbered buffer 24 has priority since the transmission discipline starts at buffer 241 and goes up in consecutive order. As a result, the shared buffer 22 architecture forms the equivalent of a single-server, first-in, first-out queue with L inputs. The total amount of buffering required in each bus interface unit 15 depends on the assumed model for packet arrivals and the restrictions on lost packets resulting from concentration and buffer overflows.
The "Knockout" switch 11 can grow modularly from N-by-N to JN-by-JN, where J=2,3, . . . . This is illustrated in FIG. 11 where each concentrator 60 in switch 11 is provided with L additional inputs for a total of N+L inputs and L outputs. The interface for each output in a JN-by-JN Knockout switch 11 comprises J separate N-bus interfaces daisy-chained together. Specifically, each of the J bus interfaces 15 for one switch output 12 contains a row of N packet filters 20 and an (N+L)-to-L concentrator 60, with only the first interface (for buses 1 to N) providing a switch 11 output 12 also containing the shared buffer structure 22 with shifter 23 and L FIFO packet buffers 24. The J individual components for each switch output 12 are connected together by coupling the L outputs of the concentrator 60 in the jth interface 15 (j=2,3, . . . , J) to the L extra inputs on the concentrator 60 in the j-lth interface 15. In effect, a convenient way of growing the Knockout switch 11 is provided using a single (N+L)-to-L concentrator design and the same shared buffer 22, one for each output 12, independent of the size of switch 11. To grow modularly, the N broadcast buses 14 can be placed on an equipment backplane with the circuitry for each of the N input-output pairs placed on a single plug-in circuit card. Hence the switch can grow modularly by adding additional circuit cards.
It is to be understood that the above-described embodiments are simply illustrative of the principles of the invention. Various other modifications and changes may be made by those skilled in the art which will embody the principles of the invention and fall within the spirit and scope thereof. For example, it should also be noted that the interconnection architecture of the present "Knockout" switch 11 lends itself to broadcast and multicast features. Since every input 10 is available at the bus interface units 15 to every output 12, arriving packets can be addressed to, and received by, multiple outputs. Additionally, for the example where L=N, the concentrator 21 of FIG. 2 has N outputs which shifter 23 places into N packet buffers 24 in the manner as described hereinbefore to provide the first-in, first-out function to the associated output.
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|Gte Laboratories Inc
|Merged buffer signal switch
|Sep 27, 1996
|Feb 23, 1999
|Law; Ka Lun
|Asynchronous transfer mode switching system
|Dec 29, 1997
|Jun 8, 1999
|Mmc Networks, Inc.
|Memory interface unit, shared memory switch system and associated method
|Jul 30, 1997
|Nov 30, 1999
|Hitachi, Ltd.
|Distributed type switching system
|Apr 23, 1997
|Dec 7, 1999
|Hitachi, Ltd.
|Packet switching system having self-routing switches
|May 11, 1995
|Dec 21, 1999
|Hitachi, Ltd.
|Time-division channel arrangement
|Aug 12, 1998
|Feb 1, 2000
|Mmc Networks, Inc.
|Memory interface unit, shared memory switch system and associated method
|Oct 28, 1997
|Jan 2, 2001
|Mmc Networks, Inc.
|Accessing a memory system via a data or address bus that provides access to more than one part
|Oct 7, 1999
|Mar 20, 2001
|Mmc Networks, Inc.
|Memory access with plural memories written with the same data
|Aug 13, 1999
|Oct 16, 2001
|Hitachi, Ltd.
|Distributed type switching system
|Dec 20, 1999
|Nov 6, 2001
|Hitachi, Ltd.
|Packet switching system having self-routing switches
|Aug 13, 1999
|Jan 1, 2002
|Hitachi, Ltd.
|Distributed type switching system
|Jun 5, 2001
|May 14, 2002
|Hitachi, Ltd.
|Distributed type switching system
|Jul 2, 1999
|Aug 12, 2003
|International Business Machines Corporation
|Packet switch employing dynamic transfer of data packet from central shared queue path to cross-point switching matrix path
|Jun 28, 1999
|Sep 9, 2003
|Hitachi, Ltd.
|Packet switching system having-having self-routing switches
|Mar 22, 2002
|Oct 28, 2003
|Hitachi, Ltd.
|Distributed type switching system
|Nov 22, 2000
|Aug 24, 2004
|Nortel Networks Limited
|Signaling aggregator and method for use in a signaling network
|Oct 17, 2000
|Sep 7, 2004
|Nec Corporation
|Output buffer type asynchronous transfer mode switch
|Jan 9, 2002
|Jun 6, 2006
|Hitachi, Ltd.
|Packet switching system having self-routing switches
|Dec 23, 2002
|Mar 11, 2008
|International Business Machines Corporation
|Input port routing circuit that performs output port filtering
|Sep 23, 2003
|Apr 20, 2010
|Motorola, Inc.
|Distributed automatically-configuring switching system
|Jan 8, 2008
|Jul 20, 2010
|International Business Machines Corporaiton
|Input port routing circuit that performs output port filtering
|Oct 22, 2013
|Aug 1, 2017
|Seiko Epson Corporation
|Serial communication circuit, integrated circuit device, physical quantity measuring device, electronic apparatus, moving object, and serial communication method
|Jan 9, 2002
|May 16, 2002
|Shirou Tanabe
|Packet switching system having self-routing switches
|Dec 23, 2002
|Jun 24, 2004
|International Business Machines Corporation
|Input port routing circuit that performs output port filtering
|Sep 23, 2003
|Dec 23, 2004
|Ladden Gregory C.
|Distributed automatically-configuring switching system
|Jan 8, 2008
|May 22, 2008
|International Business Machines Corporation
|Input port routing circuit that performs output port filtering
|Oct 22, 2013
|Apr 24, 2014
|Seiko Epson Corporation
|Serial communication circuit, integrated circuit device, physical quantity measuring device, electronic apparatus, moving object, and serial communication method
|Sep 4, 1992
|Oct 11, 1994
|At&T Bell Laboratories
|Interconnect fabric providing connectivity between an input and arbitrary output(s) of a group of outlets
|Sep 4, 1992
|Dec 27, 1994
|At&T Bell Laboratories
|Growable packet switch architecture
|Feb 9, 1990
|Apr 4, 1991
|Siemens Aktiengesellschaft
|Circuit arrangement with at least one input and one output for transmitting a signal which can be filtered, parallelized and digitized
|Nov 10, 1998
|May 20, 1999
|Nokia Networks Oy
|A frame discard mechanism for packet switches
|Nov 10, 1998
|Aug 5, 1999
|Nokia Telecommunications Oy
|A frame discard mechanism for packet switches
|U.S. Classification
|International Classification
|Cooperative Classification
|European Classification
|Jul 22, 1988
Owner name: AMERICAN TELEPHONE AND TELEGRAPH COMPANY, 550 MADI
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Ron Passarelli Inducted Into Echo Magazine's Hall of Fame
Class of 2016
By KJ Philp, November 2016 Issue. Meet the rest of the Class of 2016 here.
Ron Passarelli was a humble man. He was not the sort of person who sought to be recognized for his work, other than in the normal credit for doing something. I consider him a role model in terms of how giving he was, his love of showing hospitality to others, and his ability to use humor to get through challenging situations. All of those things made him a classy human being, who didn't know a stranger and who would do what he could to make anyone who started out as a stranger into a friend.
– Liz Massey
In July 2006, Ron presented Eric Moore with a ring and, because he failed to do so, Eric popped the question. They were married in the eyes of their family, friends, and the universe April 7, 2007. Then they renewed their vows for the state of Arizona April 7, 2015. They were a couple for 10 years and would have celebrated their 10th wedding anniversary this coming spring.
Echo: Ron was originally from Trinidad, Colo. What year did he move to Phoenix? Was there a defining moment when he knew that this was HIS home/community?
Moore: Ron moved to Phoenix in 1989 when he accepted the position of director of design and construction with the Unispec Development Corporation … He started working in the LGBTQ community starting with the Arizona Committee for Progress which was the precursor organization to the Arizona Human Rights Fund (now Equality Arizona) … Ron was "at home" wherever he lived at the time. He took an interest in local government and politics. He loved historic preservation and was passionate about equal treatment under law for everybody. In reality, Ron took two seemingly opposite views of community. On the one hand, was the large scale: cities, states, nations. All of us are part of a greater whole. At the same time, community is local: city, neighborhood, block. For Ron, community is about good governance, transparency, and inclusiveness in every sense of the word.
Echo: One thing Ron is most-remembered for is his work to preserve the David and Gladys Wright House. What did this landmark mean to him and what does this effort say about Ron's passion for architecture and dedication to community?
Moore: Ron was a huge proponent of the idea and practice of adaptive re-use, especially concerning historic properties. The idea is that, once a building (like a warehouse) outlives its purpose, the building can be adapted for a different use (like event space or loft apartments).
The David and Gladys Wright House is the final residential masterpiece designed by legendary architect Frank Lloyd Wright. Like most architects, Ron was a fan of Frank Lloyd Wright.
When it was announced that the house was threatened with destruction, Ron was aghast. When the property was purchased with a mind to preserving and restoring the house, Ron was elated. He became a leading proponent of and advisor to the Wright House because he recognized the significance of the structure and fully supported its proposed adaptation into event space and a neighborhood landmark. After all, it is in this structure that we see the prototype for the Guggenheim Museum. Ron was thrilled that the house would be managed by a non-profit foundation as an asset for the Arcadia Neighborhood and the City of Phoenix.
Ron's dedication to the vision of the David and Gladys Wright House was and is consistent with his view of community – as an asset to be enjoyed by all for the benefit of all.
Echo: Readers may not know that the future Phoenix AIDS Memorial was founded and designed by Ron. What did this project mean to him?
Moore: Like many of us, Ron lost many friends to this modern plague. Those losses included his little brother Jimmy, who died of AIDS in 1994. As a 30-year survivor of AIDS, Ron lived through those early dark days when thousands of gay men all over the United States were abandoned by their communities, their families and their nation.
When Ron learned that an AIDS Memorial was proposed as part of the master plan for the redevelopment of the Margaret T. Hance Park in central Phoenix, he became the driving force for the creation of the memorial. Ron volunteered his architectural skills and talents in order to design a Phoenix AIDS Memorial to serve as a reminder of the past and as a beacon of hope for the future.
This project, when it is built (and it will be built), will be Ron's final gift to the people of Phoenix.
Echo: What was it about Ron that made him so loved by this community?
Moore: Ron was deeply concerned about the injustice we continue to experience around us every day. Whether thinking about the LGBTQ community or people living with HIV or the plight of migrant farmworkers, Ron considered it his civic responsibility to be concerned about others … He was always ready to offer advice and counsel or the hours needed to achieve to help others achieve their goals.
One recent example, of hundreds that could be cited, is his unsung role regarding the preservation of the legacy of the 307 bar in downtown Phoenix. For decades, the 307 served as a safe haven for our community. When the building was purchased and slated for destruction to make way for mixed use space, there was concern that the history would be lost.
Ron realized that the building that housed 307 was going to be demolished. There was no practical way to save it or the mural painted by renowned Arizona artist Ettore "Ted" DeGrazia. Working with the developer and other members of the community, Ron brokered a compromise that included a plaque at the new building commemorating the history of the 307, the creation of a life-size high-resolution photograph of the DeGrazia mural, and a cash donation to the Pride Center.
This is what makes Ron a beloved member of the community. Working with others to achieve a goal that satisfies everybody.
Echo: What would Ron have considered his greatest feat?
Moore: I think his greatest feat pre-dates his time in Phoenix. Ron was elected to the City Council in his hometown of Trinidad, Colorado, in 1975. He served one term from 1976 through 1980.
About the time he took office, the Denver Post published an expose about corruption in Trinidad city government. Due to his dedication as a public servant and his belief in open and transparent government, Ron supported a grand jury investigation of the allegations.
As a result of this support, Ron was subjected to a recall petition and election. He was blamed for the bad press, despite the fact that he was not in office at the time the allegations were made. The recall was rejected by a three-to-one margin and Ron served out the rest of his term fighting for transparency and good governance.
I consider this his greatest feat because it encapsulates everything Ron favored and worked for: fairness, good governance, transparency, equal justice under the law, open debate and discussion, and public service.
Echo: What is Ron's family like? Would you care to share a little bit about what his relationship was like with some or all members?
Moore: Ron was the oldest of four children born to his parents Mike and Rose Passarelli. Throughout his life, the family was a close-knit unit that loved and respected all members.
Ron's father fought in World War II in the Pacific theater. His mother work, briefly, for a ship builder in California before she returned to Trinidad where she worked at the Prisoner of War Camp erected just outside of town. This spirit of public service was inherited from Ron's grandparents and passed to him. All the photographs and stories from Ron's childhood display an intelligent, curious, and idyllic period. Yes, I know this sounds kind of unbelievable and saccerine. But in latter years, after I had joined the family, these qualities were still evident.
Echo: Who were some of Ron's role models/inspirations and why?
Moore: Ron had many role models: His grandpa Andy was a member of and organizer for the International Workers of the World (the IWW) which fought for the human rights of miners in the coal fields around Trinidad. He also admired Mother Jones and Cesar Chavez in their work to make life better for working people.
He was an admirer of Franklin Roosevelt because of the work he did to pull the United States of out depression and preserve our way of life against totalitarian ideologies. In his wallet, Ron carried the following quotation from FDR: "The test of our Progress is not whether we add more to the abundance of those who have much; it is whether we provide enough for those who have too little."
But the biggest role models in Ron's life were John and Robert Kennedy. John Kennedy because president when Ron was in junior high. The rhetoric Kennedy spoke resonated with Ron in a way that inspired him to be a better person and to work to be a better nation.
Ron's first work for a major political campaign came in 1968 when he was an organizer for Notre Dame Students for Kennedy. As happens from time to time, a candidate comes along that inspires young people to get involved in something larger than themselves. For Ron, that candidate was Robert Kennedy. Kennedy's endorsement of the rights of the poor and down-trodden fit perfectly with Ron's world view that, collectively, we could be a better people and a better nation.
Echo: Did Ron consider himself a role model? Do you consider him a role model?
Moore: I would say that Ron would not have considered himself a role model. I think that he would have said that he was just doing what he thought needed to be done to make the world a better place.
Echo: Do you consider him a role model?
Moore: Absolutely. I say that for the same reason Ron would have said he was not a role model. He did what he thought needed to be done to make the world a better place. There are far too many people who see problems in the world and choose to do nothing. But not Ron. If he saw a problem, he wanted that problem fixed and would do what he needed to realize a solution.
Echo: How would you summarize Ron's character? And personality?
Moore: Ron never met a stranger. He could, and often did, strike up conversations with people he just met. When you were in conversation with him, there was nobody else in the world as important as you were in that moment.
Ron was an intelligent, vivacious, gregarious and compassionate man. He laughed easily at himself and at a good joke. He was deeply concerned about some of the absurdities around us these days (think Donald Trump or the tortured logic of Antonin Scalia). But despite discouragements, he was optimistic that right and justice will prevail.
Echo: What is Ron's legacy?
Moore: Ron's legacy is one of tenacity and justice. When he saw so many other gay men dying from AIDS, he did not walk away. He joined boards and raised funds and worked to make a difference. And with the memorial, he will provide future generations with a place to learn and remember.

subset: commoncrawl


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Aileen's Kids has been helping families dress their kids for every occasion since 1995.
With unparalleled dedication to quality, we take great pride in offering personalized service, unmatched selection and a pleasurable shopping experience in store 2330-2332 Merrick Road, Merrick NY 11566 and online www.Aileenskids.com. Aileen's Kids remains committed to the same high standards, which we have maintained since 1995. Without our valued customers continued support, none of this would be possible. We thank all our customers who shop in store and online.
Holiday season 2009 will be no different, with beautiful special occassion fashion from Les Tout Petits, be'be'monde, Isobella & Chloe and more... Designs from your favorite Bedtime Books "Twas the Night Before Christmas", stories to share and wear. Encouraging children to read, by printing all-time favorite books on their pajamas. Aileen's Kids has great gift ideas for any special occassion!
Give the gift of choice with the Aileen's Kids Gift Certificate. Our gift certificates can be redeemed in-store and online. The perfect choice for any occasion.
We think every great gift deserves great packaging. For a gift that's ready to be opened the moment it's received, choose our complimentary gift wrap. We'll package your gift in a wrapped box with tissue and personalized gift message. Most purchases can be gift wrapped. We gift wrap year-around!
We hope you have an enjoyable shopping experience in Merrick and online at www.Aileenskids.com and are completely satisfied with your purchase. Thank you for shopping with us and we hope you come back soon.
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IMAGE Networking Breakfast: February
IMAGE hosted an early morning networking breakfast?at The Merrion Hotel in late February for 80 Irish businesswomen from all over the country. Minister of State for European Affairs, Lucinda Creighton opened the event, speaking about the importance of networking and women empowering each other before IMAGE editor Melanie Morris interviewed Whelan about her her career in international luxury retail and at Leicester City Football Club. After a Q&A session with guests, speakers and attendees mingled over a delicious breakfast buffet of croissants, fruit skewers, coffees and teas, courtesy of The Merrion. All agreed it was a wonderful start to the day and the first of many IMAGE Networking Breakfasts to come. The next event, sponsored by Brown Thomas and Enterprise Ireland, will focus on Digital and Social Media and Your Business. It features a panel of industry experts April 23rd at the newly revamped Morrison Hotel.


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Mental health concerns in aftermath of Puerto Rico hurricane
The hurricane that pummeled Puerto Rico two weeks ago and the scarcity-marked aftermath are taking a toll on islanders' equilibrium.
The hurricane that pummeled Puerto Rico two weeks ago and the scarcity-marked aftermath are taking a toll on islanders' equilibrium.
After pointedly refusing to answer whether he once called the president a "moron," Tillerson had a spokeswoman deny he used such language.
The crash happened about 11 miles from Clay Center.
Those seeking to know the motive of Las Vegas gunman Stephen Paddock have had little more to chase than hints and shadows.
Senior congressional Republicans say they are open to considering legislation banning "bump stocks" like the shooter in Las Vegas apparently…
U.S. officials said three U.S. Army special operations commandos were killed Wednesday and two others were wounded when they came under fire…
Turkish archaeologists believe they may have discovered the remains of St. Nicholas — from whom the legend of Santa Claus emerged — beneath …
All of the animals featured this week are up for adoption at the Helping Hands Humane Society in Topeka.
flooded inventory will be arriving on the showroom floors of local dealerships, over the next 2 months.
Tracking more wet weather heading into the holiday weekend.
If you're looking for a fun, unique event on Saturday, October 7, head out to Heartland Park Topeka for the annual 'Battle of the Brands'.
KU volleyball improved to (4-0) in the Big 12 with a win against West Virginia. K-State lost to TCU.
"The night of the election, I screwed in a light bulb for the first time in a year."
Sylvia Fowles had 17 points and broke her own WNBA Finals record by grabbing 20 rebounds to lead the Minnesota Lynx to their fourth champion…
Beginning Monday, Oct. 9 at 7:00 a.m., Shawnee County will be starting an asphalt mill and overlay project for both the east-bound and west-…
Washburn hosts Missouri Southern at 1:00 p.m. on Saturday.
Former "Glee" actor Mark Salling has reached a deal with prosecutors to plead guilty to possession of child pornography.
"Our stomachs dropped," she said. "We just knew something was wrong."
A Panthers spokesman says quarterback Cam Newton has "expressed regret" for his response to a female reporter's question at a news conferenc…
Two Topekans received recognition for their acts of selflessness.
Members of the Topeka media had a chance to catch up with happenings in the Topeka School District.
Children in the Capital City have a reason to smile today as the United Way of Greater Topeka was recognized for its work in helping more ki…
Seventeen year old Lamero Dunstan will be charged as an adult in the June 26 shooting of 18-year-old Justice Mitchell.


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Posts Tagged 'Turkey Neck Treatment'
As we age, our skin changes. Youthful skin has a great deal of natural collagen and elasticity, making it firm and holding it tight. With age, skin loses its elasticity and collagen production eventually comes to a halt, leaving wrinkles and sagging skin. No area of the body is immune to this change, and often the area above the shoulders shows the first signs of aging. Neck lift surgery is a cosmetic procedure done to tighten the skin of the lower jaw and the neck in order to add definition to the jaw line and reduce sagging skin of the neck.
Neck lift surgery is often done in combination with other facial plastic surgical procedures such as a facelift and/or neck liposuction. The entire area of the chin, jaw line, and neck are connected by many of the same muscles resulting in astonishing results when certain procedures are combined.
Dr. Mark Mitchell Jones of Atlanta Plastic Surgery Specialists is an excellent provider of neck lift surgery, neck lift liposuction, and double chin liposuction. All of these procedures can take years off of a person's appearance. The results are a tighter, more youthful appearance that is attractive and confident. With Dr. Jones' specialized techniques, he is able to hide scars in the hair line so that people will wonder what you've had done, but will never be able to tell!
Neck lift surgery can tighten the muscles and skin; combined with a neck liposuction procedure it can reduce fat in the neck and create a defined and attractive appearance. Atlanta Plastic Surgery Specialists is a proven leader in neck life and neck liposuction surgeries. Please contact our Atlanta neck lift surgeon today to schedule a consultation. We look forward to helping you achieve your goals and put your best face forward.
Posted on behalf of Dr. Mark Mitchell Jones, Atlanta Plastic Surgery Specialists, P.C.
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The neck is often an under considered feature that actually has a great deal of influence regarding how old a person appears. Excess skin that hangs from the neck, often referred to as a "turkey waddle," can add years to a person's face. The lessening definition between the jawline and the neck is also a significant age qualifier, and the less definition the older a person appears. At Atlanta Plastic Surgery Specialists, Dr. Mark Mitchell Jones is an experienced neck lift surgeon with double board certification by the American Board of Plastic Surgery and the American Board of Otholaryngology (ear, nose, and throat). continue reading


text: trying to do some things at work and these pc's use winxp. I have no problem connecting at home on my win7 pc as the drivers and all install just fine. i plug it it, and it just charges. doesn't prompt me to use a charge/mount sd etc etc. are there drivers for this for winxp? or is there something im missing? Thanks for any help


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Minimum Fee: $100 per performance
Full Length Play
Dramatic Comedy
Experimental, Romantic Comedy
105 Minutes
Time Period - Contemporary, Present Day
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Friendship, Love, Marriage, Parenting/Family
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From Off-Broadway
Someone sneezes. Someone can't get a signal. Someone won't answer the door. Someone put an elephant on the stairs. Someone's not ready to talk. Someone is her brother's mother. Someone hates irrational numbers. Someone told the police. Someone got a message from the traffic light. Someone's never felt like this before.In this fast moving kaleidoscope, more than a hundred characters try to make sense of what they know.
Love and Inforamtion premiered at the Royal Court Theatre in London in September 2012 under the direction of James Macdonald.
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"Love and Information" - New York Theatre Workshop
Caryl Churchill (born 1938) wrote her first play, Downstairs, while at Oxford University. It was staged in 1958 and won the award at the Sunday Times National Union of Students Drama Festival. Her plays have been performed on international stages, on the BBC radio, and adapted for BBC television. They include Light Shining in Buckinghamshire, Cloud Nine, Fen, Three More Sleepless Nights, Top Girls ... view full profile
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I would like to dedicate this column to my month-old daughter, Mazey, who just spit up on me. And, no, I will not be changing my shirt.
I thought it might be appropriate to discuss how becoming a parent changes your life. By your life, of course, I mean mine.
The obvious disruption everyone talks about in the months leading up to parenthood is sleep. All summer, countless people would smile knowingly and say, "Sleep while you still can."
At which point I would smile back and resist throwing nearby objects.
Many websites will tell you that newborns sleep between 15 and 18 hours a day. It should be pointed out that the 18 hours is divided between two three-hour stretches, one two-hour interval, and around 100 five-minute naps.
So we follow the age-old wisdom of "sleep while you can." For me, this includes time spent driving on the highway, in the shower, shaving, and actually right now. It explains a lot.
Next is the issue of crying, and here we are very lucky. Mazeyis a sweet baby. She is rarely fussy or has cowlick, whichaccording to the old reliable Wikipedia, is "a section of hair thatstands straight up or lies at an angle at odds with the style inwhich the rest of an individual's hair is worn." (There's even apicture.) Thankfully, as I've heard this can lead to seriousconsequences, her hair is usually pretty matted down.
Then, there's feeding. Things were a little bumpy at first, but have recently progressed more smoothly. We owe a great deal of gratitude to a lactation consultant. If I had known such a profession existed in college. ...
Instead I latched on to a journalism program. What was I thinking?!
Babies eat, sleep, and, of course, poop. To my surprise, though still gross, the diapers don't really smell. I'm told they won't until Mazey starts eating regular food. Is it possible for a teenager to still be on breast milk?
Which brings me to teenagers. As a former high school teacher, my threat level toward teen behavior previously had been set at blue, or "guarded." Then I went to get the mail the other day, and a neighbor's teenager almost hit me doing an unexpected, tire-screeching U-turn.
After he cut me off that same week, I decided to talk to him about his driving and the life-threatening near-miss. He said, "Oh, were you in the street?" Threat level: red, or "matador."
Change trickles down to all parts of your life. The chance of going to a good friend's out-of-state bachelor party changes from 95 percent likely to, um, can you have a negative percentage? You get to use fun words like "hangry" when Mazey is so hungry she gets angry, and "cumtigue", when we feel the cumulative fatigue of no REM sleep since August.
If Palin can refudiate Obama, I can blame being snippy on cumtigue.
The biggest change of all, though, is ... wait, hold on. Yes, dear, I'm coming.


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Hello and welcome to the Official Site of Jalles Franca. Our goal at MJ THE LEGEND is not only to give the audience the utmost entertaining experience, but to be lost in the magic of Michael Jackson, as if you were watching the man himself. We respect and love the legendary Michael Jackson as well as his fans, and it means the world to us that we have the honor and privilege of keeping his legacy alive while pursuing our dreams.
Jalles Franca has been a Michael Jackson tribute artist for nearly 7 years, performing in Las Vegas, across the United States and around the world. He currently stars in the #1 Michael Jackson tribute in the world, MJ Live! at the Stratosphere Hotel & Casino on the Las Vegas strip. Please take a moment to check out his bio, performance schedule, photos, videos, and client reviews. Follow him on instagram @mjthelegend_ and "like" the Facebook fan page!
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The pathophysiological alterations in patients with familial hemiplegic migraine (FHM) are not yet fully known. The headache characteristics in patients with FHM mutations have been examined in a series of glyceryl trinitrate (GTN) provocation studies in FHM patients, but the cortical vascular response to GTN in FHM patients has never been investigated before.
To investigate changes in spontaneous low-frequency oscillations (LFO) of cortical vessels in response to the nitric oxide donor GTN by near-infrared spectroscopy in FHM patients.
Twenty-three FHM patients without known mutations and 9 healthy controls received a continuous intravenous infusion of GTN 0.5 μg/kg/minute over 20 minutes. Using near-infrared spectroscopy, we recorded oxygenated hemoglobin (oxyHb) LFO amplitude bilateral at the frontal cortex at baseline and 15 minutes and 40 minutes after start of the GTN infusion.
GTN changed oxyHb LFO amplitude in FHM patients (P = .002), but not in healthy controls (P = .121). Only in FHM patients with coexisting common migraine types did GTN infusion induced changes in LFO amplitudes (P < .001), where post-hoc analysis revealed an increase in LFO amplitude 15 minutes (P = .003) and 40 (P = .013) minutes after start of infusion compared with baseline. Interestingly, GTN infusion induced no changes in LFO amplitude in patients with a pure FHM phenotype (P = .695).
FHM patients with a mixed phenotype (coexisting common type of migraine) showed an increase in oxyHb LFO amplitude during GTN infusion, whereas FHM patients with pure phenotype showed no changes. These data suggest possible differences in frontal cortical nitric oxide vascular sensitivity between FHM patients with a mixed phenotype and patients with pure FHM.
Familial hemiplegic migraine (FHM) is a dominantly inherited subtype of migraine with aura (MA), characterized by cortical alterations resulting in fully reversible half-sided weakness and other aura symptoms preceding or accompanying migraine headache.1 Mutations in 3 different genes can cause the FHM phenotype.2-4 In a large proportion of FHM patients (40-80%), no mutations have been identified to date.5,6 Clinically, the migraine features of FHM with and without identified mutations are similar,7 but the differences in genetic constitution might result in different molecular migraine mechanisms. FHM1 mutations have been explored in a mouse knock-in model and revealed enhanced excitatory transmission at cortical synapses8 and decreased triggering threshold for cortical spreading depression (CSD).8,9
It is known that FHM attacks have a statistically longer duration of visual and sensory aura than typical migraine aura attacks and motor symptoms with a mean duration close to 6 hours.10 Furthermore, in attacks of hemiplegic migraine, changes in regional cerebral blood flow have been recorded in conjunction with cerebral angiography11 and showed that blood flow fluctuated rapidly possibly because of instability of cerebrovascular tone, defined as transient constriction of cerebral arterioles alternating with a normal caliber for these vessels and/or short periods of vasodilatation. When vasoconstriction was present, the blood flow decreased to values consistent with ischemia and was suggested to be the cause of the neurological deficits. Thus, FHM patients may have an altered cortical vascular regulation, which make them more susceptible to prolonged aura phenomena. Therefore, it is of key interest to study cortical vascular responses in FHM patients.
Recording of spontaneous low-frequency oscillation (LFO) amplitudes of oxygenated hemoglobin (oxyHb)12 may be used for assessment of cortical vascular responses to glyceryl trinitrate (GTN). Hence, nitric oxide (NO) modulates LFO13,14 in experimental animal models, and cortical vascular changes in humans can be monitored non-invasively in vivo by near-infrared spectroscopy (NIRS).15
Therefore, the aim of the present study was to investigate the LFO in frontal cortical vessels in response to GTN infusion by NIRS in patients with FHM without known mutations and healthy controls.
We recruited 23 patients with FHM (6 male/17 female, mean age 41 years, range 21-67 years) and 9 healthy controls with no personal or family history of migraine (5 male/4 female, mean age 37 years, range 22-53 years). The patients were recruited from 15 families from a population-based sample.10 Genome-wide linkage scan failed to show any new or known FHM mutations in these patients. Twelve patients exclusively had FHM (4 male/8 female, mean age 40 years, range 21-67 years), and 11 had previously had attacks of other types of migraine (2 male/9 female, mean age 42 years, range 27-63 years) (Table 1). The headache data of the study have previously been published.16 Due to technical issues, only 9 healthy subjects were studied in the present as compared with 12 in the previous study.16 The Ethics Committee of the County of Copenhagen approved the study, and written informed consent from all patients participating in the study was received. The study was registered at www.clinicaltrials.gov (NCT00541736).
All subjects received a continuous intravenous infusion of GTN 0.5 μg/kg/minute over 20 minutes. The subjects were informed that GTN might induce headache, but the timing or the type of headache was not discussed. None of the subjects had previously participated in headache provocation studies. All subjects reported headache-free to the laboratory. All procedures were performed with the subjects in the supine position, a venous catheter inserted into an antecubital vein, GTN infused over 20 minutes using a time- and volume-controlled infusion pump (B. Braun Perfusor, Melsungen, Germany). NIRS recordings lasting 5 minutes each were obtained at 3 time points: 10 minutes before the infusion, 15 minutes after the beginning of the infusion period, and 40 minutes after the beginning of the GTN infusion (ie, 10 minutes after the end of the infusion period).
Measurement of oxyHb LFO was performed using continuous wave NIRS (NIRS2; TechEnInc, Milford, MA, USA). The NIRS optodes were placed bilaterally on the forehead with 1 source (2 wavelengths: 690 nm and 830 nm) and 2 detectors on each side, avoiding the midline sinus. The distance between sources and detectors were 3 cm, with the detectors lateral to the source. Thus, the detectors were measuring at the frontal cortex in the territory supplied primarily by the middle cerebral artery. Optode placement and recording were performed by H.W.S. and D.P., who were blinded to the disease status and grouping of the included subjects.
Power spectra were estimated by computing the Fourier transform of the NIRS signal time series (Fig. 1). The relative LFO amplitude of oxyHb was then extracted from a narrow frequency band around 0.1 Hz. All data processing was performed in MATLAB (The MathWorks, Inc., Natick, MA, USA). NIRS intensity time series were first divided into windows of 100 seconds duration with 50 seconds overlap. Within each 100-second window, intensity variations at 690 and 830 nm were converted into relative changes in oxyHb using the modified Beer–Lambert law17 with a differential pathlength factor of 6 at both wavelengths. No correction for partial volume effect was employed because the NIRS-measured oscillations are not expected to be very much localized. The oxyHb signals were then Fourier transformed to obtain their power spectra (MATLAB function pwelch). The LFO frequency was defined as the frequency within the 0.09-0.11 Hz range. The LFO amplitude of oxyHb was extracted as the value of the oxyHb spectrum at the LFO frequency. The values of oxyHb amplitude were then averaged over all 100-second windows and over the 2 NIRS channels on each side of the head. We converted the NIRS data into oxyHb concentration. NIRS is sensitive to cerebral blood volume and oxygenation changes in the microvasculature, with mixed contribution from arterioles, capillaries, and venules. The measured oscillations in cortical oxyHb can arise from oscillations in cerebral blood flow and metabolic rate of oxygen.
Heart rate (HR) and mean arterial blood pressure (MAP) were measured with an auto-inflatable cuff (ProPac Encore® Welch Allyn Protocol, Beaverton, OR, USA), and electrocardiogram (ECG) was monitored (Cardiofax V, Nihon-Kohden, Shinjuku-ku, Tokyo, Japan).
Data are presented as median values with quartiles. NIRS data processing was performed by J.S., who was blind with respect to patients (including pure FHM and FHM + MA/migraine without aura [MO] status) and controls. The subjects were divided into healthy subjects and the FHM group as a whole. The FHM subjects were also subdivided into 2 groups consisting of pure FHM and FHM + MA/MO subjects. There are no previous data on variability to allow for exact sample size calculations, but previous NIRS data from 10 healthy subjects detected amplitude changes in the LFO range following posture changes,18 which justify the chosen sample sizes in the present study.
The primary end-points were: (1) differences in LFO amplitude at baseline and following GTN infusion (15 and 40 minutes) within the healthy subjects and the FHM group as a whole; (2) differences in LFO amplitude at baseline and following GTN infusion (15 and 40 minutes) within pure FHM and FHM + MA/MO subjects.
The secondary end-points were: (1) differences in baseline LFO amplitude, HR, and MAP between the healthy subjects and the FHM group as a whole and also between the 3 groups of healthy subjects, pure FHM, and FHM + MA/MO; (2) differences in LFO amplitude change from baseline at 15 minutes and 40 minutes between male and female FHM patients; (3) changes in HR and MAP correlated to the change in LFO amplitude from baseline to infusion of GTN (15 minutes).
Given that the data were not normally distributed (the Shapiro–Wilk test), we used the Friedman test to test difference in LFO amplitudes within groups. If Friedman test revealed statistical significance, we performed a post-hoc analysis to test difference between baseline and after infusion by the Wilcoxon signed-rank test for paired samples. To test the first and second secondary end-points, non-parametric Mann-Whitney U-test for 2 independent samples on differences between groups was applied. For the third secondary end-point, Spearman's rank correlation coefficient was applied.
All analyses were performed with SPSS for Windows 17.0 (SPSS Inc., Chicago, IL, USA). Five percent (P = .05) was chosen as the level of significance.
All 32 subjects completed the study. None of the participants reported headache at baseline. In 1 subject with pure FHM, 40-minute recording was not performed due to a technical error. We found no difference between hemispheres for any group, and therefore, the amplitude was analyzed as a mean of the 2 hemispheres. There were no differences in baseline LFO amplitude (P = .090), HR (P = .166), and MAP (P = .216) between FHM patients and controls. There were no differences in changes of LFO amplitudes compared with baseline at 15 minutes (P = .609) and 40 minutes (P = .249) between female or male FHM patients.
Intravenous infusion of GTN induced change in LFO amplitudes in FHM patients (P = .002). Post-hoc analysis revealed a significant increase in LFO amplitude 15 minutes (P = .006) and 40 minutes (P = .020) after start of GTN. Intravenous infusion of GTN did not change LFO amplitudes in healthy controls (P = .121). To investigate the second primary endpoint, we divided FHM patients into 2 groups according to phenotype: pure FHM and FHM + MA/MO. We found significant changes in LFO amplitudes after GTN infusion in FHM + MA/MO patients (P < .001). Post-hoc analysis revealed a significant increase in LFO amplitude 15 minutes (P = .003) and 40 (P = .013) minutes after start of GTN infusion compared with baseline. However, there were no changes in LFO in patients with pure FHM (P = .695) (Table 2 and Figs. 1 and and2).2). Statistical analysis included visual identified outliers (Fig. 2), and removal of outliers did not change the results. Correlation analysis revealed no correlation between LFO amplitude changes from baseline to infusion (15 minutes) and HR (r = 0.039, P = .831) or MAP (r = 0.059, P = .747) changes.
The major outcome of the study is that we found an increase in frontal cortical vessel LFO amplitudes in response to intravenous infusion of GTN in FHM patients without known mutations. Interestingly, only FHM patients with coexisting common types of migraine showed an increase in cortical vessel LFO amplitudes following GTN infusion, whereas patients with the pure FHM phenotype did not. These data suggest that only FHM patients with mixed phenotype exhibit increased cortical arterial responses to GTN.
FHM patients have hemiplegic and aura symptoms that most likely are caused by CSD.19,20 Experimentally, a single episode of CSD in the rat frontal sensory cortex induces impaired neurovascular coupling with reduced vascular reactivity for at least 1 hour.21 Thus, failure of neurovascular coupling following CSD may explain the prolonged neurological deficits during hemiplegic migraine aura. Interestingly, CSD-induced vasoconstriction and reduced reactivity are ameliorated by high doses of L-arginine, the substrate for NO synthase22 or topical application of NO donors.23 It is also known that FHM attacks have a statistically longer duration of visual and sensory aura than MA attacks and motor symptoms with a mean duration close to 6 hours.10 Surprisingly, the present study shows that pure FHM patients have the same vascular reactivity to NO as healthy controls, while in the presence of MO and MA, we found an increased cortical vascular reactivity to NO. It seems that the increased vascular reactivity is related to the common migraine phenotypes and not directly linked to the FHM phenotype. To confirm this, future studies should examine the LFO amplitude changes of cortical cephalic vessels in response to GTN in patients with typical migraine with and without aura.
GTN induces migraine attacks in 50-80% of patients with migraine with and without aura.24-26 Cerebral hemodynamics in response to GTN infusion have been extensively studied in migraineurs and healthy volunteers.24,25,27 Intravenous GTN infusion in humans does not alter global or regional cerebral blood flow (CBF)28 and therefore changes in cerebral blood flow velocity are likely to reflect vasodilatation. In migraine patients without aura, GTN causes a more pronounced dilatation in both intra- and extracranial arteries than in controls.29 These findings suggest a possible link between arterial hypersensitivity and migraine induction.30 Provocation studies have revealed that FHM patients with (50% not reporting MO and/or MA) and without known mutations (52% not reporting MO and/or MA) do not experience more migraine attacks following GTN infusion than healthy controls.16,31,32 These findings raise an important question: why do the majority of FHM patients not experience migraine attacks in response to GTN? The answer is complex, and at present, we can only speculate that pathophysiological mechanisms in FHM may be distinct from the common migraine subtypes. Hence, mutations could have functional consequences that remain to be clarified.
Some interesting observations came from the provocation studies. We previously reported no difference in dilatation of intra- and extracranial arteries after GTN infusion between FHM1 and FHM2 patients and controls.31,32 Interestingly, GTN-induced dilatation of the superficial temporal artery was less pronounced in FHM2 patients compared with healthy controls.32 It seems that the FHM patients without known mutation and with coexisting MA/MO are more sensitive to the migraine-inducing effects of GTN when compared with the pure FHM phenotype and controls.16 These findings and the present data, showing that following GTN, only patients with FHM and coexisting MO/MA had an increase in cortical vascular low-frequency amplitude, indicate differences between FHM patients with coexisting MA/MO and patients with pure FHM in terms of both migraine and vascular induction to GTN. Thus, the present results indicate differences in pain as well as vascular pathways across the migraine spectrum and investigating this pathophysiological heterogeneity will be very interesting to explore in future migraine research.
This is the first time an NO donor is given systemically to detect LFO amplitude changes of cortical vessels in human. Our results are in contrast to experimental models in anesthetized rats, where NO synthase inhibitors increase cerebral LFO amplitude.13,14 This difference may be explained by the fact that in the animal studies, the NO synthase inhibitor constricts cephalic vessels and thereby markedly lowers the cerebral blood flow by up to 18%13 and raises the systemic blood pressure up to 26%.14 The increase in LFO amplitude in the present study might have been caused by a reflex increase in sympathetic tone,18 even though we could not show a significant correlation between changes in systemic hemodynamics and the LFO amplitude changes.
Some limitations to this study need to be acknowledged. GTN infusion induces an increase in HR and a decrease in blood pressure.31,32 Thus, changes in cortical vessels might also reflect systemic changes. Continuous wave NIRS technique lacks precise depth resolution, which does not allow to clearly separate signals from the skin and cortex. The differential pathlength factor and the partial volume error may vary between subjects due to different head anatomy, which can introduce errors and intersubject variation in the absolute hemoglobin oscillation amplitudes we are reporting. Because NIRS is a surface measurement, it shows some level of contamination by hemodynamics in superficial tissues.33 In this study, we have not characterized the contamination by skin vasculature, which can be a confounding effect in the results. In healthy subjects, we did not find a statistically significant increase in LFO amplitude during GTN infusion, even though visually Figure 2 on healthy subject seem to show an increase. This might be a type-2 error due to a low number of subjects or caused by outliers. The optodes might move slightly on the forehead throughout the study, which might have contributed to the high variability at the 40-minute recording. The unknown intersubject variability may account for the extreme outliers found in the study. Based on the circumstances, we chose to use the Friedman test to control for any intersubject variation. Experimental animal models have shown that cerebrovascular reactivity might be affected by estrogen via NO pathways.34,35 However, we found no differences in vascular responses between males and females in patients with FHM.
The present study showed that following GTN infusion, only patients with FHM and co-occurring common migraine had an increase in frontal cortical oxyHb LFO amplitude as opposed to patients with pure FHM and healthy controls. The experimental model indicates possible differences in frontal cortical NO sensitivity between FHM patients with a mixed phenotype and patients with pure FHM.
Category 1
Category 2
Category 3
The authors thank all participating FHM patients and healthy volunteers. The authors thank Dr. Henning Piilgaard, for very useful comments to the manuscript. The study was supported by the Lundbeck Foundation via the Lundbeck Foundation Center for Neurovascular Signaling.
Study funding: Supported through the Lundbeck Foundation Center for Neurovascular Signaling.
Conflict of Interest: H.W. Schytz, J.M. Hansen, D. Phillip, J. Selb, D.A. Boas, and M. Ashina report no disclosures.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


text:
- Film, radio & TV
Film, radio & TV
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