The present invention relates to methods of visualizing cells especially although not exclusively in vivo using a dye, such as a dendrimer-dye molecule or polybranched-dye molecule which is internalized by the cells and thus permits subsequent visualization by confocal fluorescence endomicroscopy or other optical detectors. There is also provided internally quenched probes for use in visualizing cells especially although not exclusively in vivo by confocal fluorescence endomicroscopy and the use of internally quenched probes in combination with confocal fluorescence endomicroscopy, for visualizing cells by virtue of internalization and dequenching of a probe by the cells. In a particular embodiment the cells are activated neutrophils, such as within the lung of a subject.

Neutrophil predominant lung inflammation is a major cause of morbidity and mortality11. Yet despite decades of investigation, accurate stratification of patients with neutrophil predominant lung injury on intensive care has been hindered by the lack of bedside point of care diagnostics that can reliably and rapidly distinguish acute neutrophilic inflammation2. The ability to perform bedside diagnostics has the potential to accurately stratify such patients for further neutrophil specific interventions. Excessive neutrophil activity degrades matrix and cellular receptors, activates profibrogenic mediators and contributes to epithelial and endothelial cell damage3,4,5. The involvement of neutrophils in several diseases such as acute lung injury, ischemia-reperfusion injury6,7, cystic fibrosis8 and chronic obstructive pulmonary disease, makes them important targets for modulation.
In situ in vivo detection of neutrophilic inflammation in human pulmonary inflammation has been reliant upon FDG PET imaging. PET imagine10, although offering exquisite sensitivity, is cumbersome, expensive and is difficult to implement as a bedside molecular imaging modality. Conversely the advent of confocal endoscopy, such as probe based confocal laser endoscopy has revolutionised the ability to directly visualise the alveolar space in both preclinical and clinical arenas. However, as yet this modality has only been used to image autofluorescent structures within the alveolar space or using non-specific fluorescent dyes11,12.
The optical detection of activated neutrophilic activity is feasible with imaging enzymatic activity in whole animals13. These approaches require substrate specificity
with internally quenched molecular beacons. Often the dequenching may take hours and the substrate may be cleaved by non neutrophil proteases.
Dendrimers are a class of macromolecules possessing a well-defined structure and molecular composition14,15.
They are created by the stepwise attachment of monomer units in repeating unit layers, termed generations, which creates branches built upon a central core. These branches terminate in a specific chemical functional group that can be used for further dendrimer growth or modification, or attachment of specific compounds as required.
WO2003014743 describes the use of dendrimers and polybranched molecules to enhance signals in in vitro fluorescent assay systems16.
The molecules disclosed in WO2003014743 comprise cleavage sites which when treated with an appropriate chemical or enzyme lead to cleavage of selective bonds within the molecules and a subsequent change in the fluorescent properties of the molecule, most notably an increase in fluorescence. However, WO2003014743 only shows the results of in vitro data and there is no suggestion or teaching of how one might use the molecules in an in vivo setting, or indeed if this would in fact be possible.
It is an object of the present invention to obviate and/or mitigate at least one of the aforementioned disadvantages.
It is an object of the present invention to provide means of visualising cells in vivo, such as activated neutrophils within the lung of a subject, using confocal microendoscopy.
In a first aspect there is provided a dye construct which prior to cell internalisation displays substantially no detectable or only a low amount of fluorescence, but upon cell internalisation displays a detectable increase in fluorescence using confocal endoscopy for use in imaging cells in vivo.
The dye construct may be a poly-branched molecule with surface groups linked to a fluorescent dye, such as disclosed in WO/2003/014743, or a molecule as further described herein.
"Detectable increase in fluorescence" is understood to relate to fluorescence which can be detected by confocal microendoscopy techniques. If the dye constructs initially display a low, but detectable level of fluorescence, then a detectable increase can be observed following internalisation by a cell or cells. Initially the dye constructs for use in the present invention are internally quenched. That is, the dye constructs do not fluoresce or fluoresce poorly due to the fluorescent groups or groups being quenched. However, following internalisation by cells, dequenching occurs and an increase in fluorescence can be detected.
Typically fluorescence detection is understood to be related to fluorescence intensity, fluorescence lifetime and polarisation may also be detected. Typically the "low or little" amount of fluorescence" is practically not detectable using confocal microendoscopy techniques, or is sufficiently low to permit a clear identification of the "increase" in fluorescence. Typically a suitable increase is understood to be an increase by a factor of 1.2 or more.
The present inventors have observed that combining confocal endoscopic visualisation techniques with the localised administration of a dendrimer dye molecule or poly-branched molecule linked fluorescent dye, it is possible to observe in vivo, by way of fluorescence, specific cells which internalise a dye construct of the present invention or poly-branched molecule linked fluorescent dye, with a distinct increase in fluorescence. Without wishing to be bound by theory, it is thought that the dye contructs/polybranched-dye molecules of the present invention are internalised or taken up by cells before internal cellular mechanisms act upon the constructs causing an increase in fluorescence.
The present inventors have observed that through the use of the dye construct/poly-branched molecules described herein, that such molecules are capable of being internalised, by certain specific cells within seconds or a few minutes. However, over time many different cell types may internalise the dye construct/poly-branched molecules described herein and as such, in order to observe the desired cells which rapidly internalise the dye construct/poly-branched molecules described herein, the detection of fluorescence should be carried out within a few minutes of administering the dye construct—typically within seconds to minutes, such as 1-30 minutes, typically 1-10 minutes. In this manner, cells which may internalise such constructs over a much longer time period, such as within hours, are not detected and hence the cells which rapidly internalise the dye constructs are readily discernable, from other cells. This is also advantageous to the patient, as they are subjected to the diagnostic procedure for as short a time as possible. Moreover, if the endoscope were removed, the site of administration of the dye construct may be difficult to relocate.
The confocal endoscope or microendoscope enables real-time in vivo human and animal imaging. The instrument couples a custom built fluorescence slit-scan confocal microscope to a fibre-optic catheter. Further teaching may be found in Thiberville et al17 and WO2008020130, to which the skilled reader is directed and the contents of which are hereby incorporated by way of reference.
In a further aspect there is provided a method of visualising a particular cell or cells within a mixture of cells in vivo using confocal endomicroscopy, comprising the step of adding a dye construct or poly-branched molecule linked fluorescent dye to said mixture of cells and observing a cell or cells which have internalised the dye construct or poly-branched molecule linked fluorescent dye by observing fluorescence from said cell or cells using a confocal fluorescence endomicroscope. Conveniently the dye construct or poly-branched molecule linked fluorescent dye may be one of the constructs described herein.
Typically the cells which may be detected by way of internalising the dye construct or poly-branched molecule linked fluorescent dye are activated neutrophils. Activated neutrophils which are characterised by degranulation and protease release may be found at sites of inflammation and may therefore be detected using confocal endoscopy techniques at a variety of locations within the body of a subject such as within in the lung, within the gastrointestinal tract, within the reproductive tract or any other endoscopically accessible orifice.
In a preferred embodiment activated neutrophils are detected in the lung of a subject. Typically the subject may be a subject already hospitalised, such as a patient in intensive care, where early detection of such activated neutrophils would be desirable.
The dye construct or poly-branched molecule linked to fluorescent dye may be of the form described in, for example, WO/2003/014743 (to which the skilled reader is directed and the entire contents of which are incorporated herein, by way of reference) which comprise one or more cleavage sites which are cleavable by appropriate chemical or enzyme means. Preferred molecules comprise three or more, typically six or more branches, such that a significant increase in fluorescence may be observed following dequenching of the fluorescent moieties.
In addition to the molecules described in WO2003/014743, preferred poly-branched molecules of the present invention have the generalised structures as follows:

Where R is selected from NH2, CONH2, NH2CONH—, an amino acid, OH, amino acid —CONH2, CONH2— amino acid, alkylamino, alkoxyamino, urea, thiol, carboxylic acid, or a further fluorophore moiety which may be the same or different to the other fluorescent moieties. All such groups may be directly attached to the branch point, or may be separated from the branch point by a spacer, which may be a PEG group, an alkyl or alkenyl chain, such as a C1-C10 alkyl or alkenyl. Other linking groups are described in WO2003/014743 and reference 14.
The above generalised structures schematically represent probes which may be suitable for use in the present invention. The use of a peptide and/or polyethylene glycol (PEG) portion is intended to improve the solubility of the dendrimer/branched molecules. When present the peptide sequence may comprise an enzyme or chemical cleavage recognition sequence or may be random in the sense of not including a recognisable enzyme or chemical cleavage recognition sequence. As an alternative to the peptide and/or PEG moiety, any suitable solubilising group known in the art may be used. Without wishing to be bound by theory, when a random peptide sequence is employed, the peptide sequence is not thought to be cleaved by an enzyme present in the cell to be detected. Thus, the increase in fluorescence observed following internalisation of the molecules of the present invention comprising random peptide sequences is not thought to be due to cleavage of the peptide moiety and release of previously quenched fluorescent moieties, in contrast to previous teachings.
When an enzyme cleavable sequence is employed, the peptide sequence may be cleaved by an enzyme which may be present outside of the cell and this may result in a low amount of fluorescence being observed. However, a far greater observable increase in fluorescence is observed upon internalisation of the molecules/probes. In this manner the separation of the dequencher moiety from the fluorescent moiety, as well as other cellular mechanisms results in a significant increase in fluorescence being observed. Thus, in an embodiment where a degree of fluorescence may be observed outside of the cell it is to be understood that a detectable increase is observed (such as greater than a factor of 1.2 as compared to any fluorescence which is observed outside of the cell) when the construct in internalised. This may in fact be an advantage, as it may allow cells to be generally identified by way of a level of fluorescence being observed outside any cells, but desired cells can more easily be identified once the constructs are internalised and an increase in fluorescence observed.
Particularly preferred molecules of the present invention are selected from one of the following structures:

(AA)nPEG is to be understood as a peptide and/or PEG moiety being present. That is one or the other or both. Indeed more than one PEG may be present. The above molecules comprise a plurality of fluorescently quenched moieties, designated *F. One such fluorescent moiety is FAM, but it is to be understood that the molecules of the present invention are not limited to the use of FAM as many other fluorescent moieties may be used, such as rhodamine, cyanine dyes and BODIPY dyes. Q* is a dark quencher moiety such as DABCYL, Methyl Red, BHQ1, BHQ2 and BHQ3.
The molecules of the present invention may comprise a peptide linkage, represented in the above structures as (AA)n, where AA means any amino acid and n may be zero or is a positive integer from 1-30 such as 1-20, or 1-15. Such peptide sequences may therefore be random sequences, or conform to known sequences contained within peptides or proteins. Sequences which are recognised by the enzyme neutrophil elastase include A-A-P-V, A-A-A-P-V-K, E-E-I-Nle-R-R. Many other peptide sequences are known to the skilled addressee and may be used in probes of the present invention, examples include G-P-K-G-L-K-G (for MMP-9), V-A-D-C-A-D-Y (for proteinase 3), A-A-P-F, or F-V-T-Gnf-S-W where Gnf=nonproteinogenic 4-guanidine-1-phenylalanine) (for cathepsin G) and D-C-V-D (for Caspase). In a further aspect, the present invention provides novel dye constructs as described above for use in visualising cells, such as activated neutrophils, in vivo. There is also provided methods of preparing such molecules as described hereinafter.
The molecules of the present invention and indeed molecules described in WO/2003/014743 are initially quenched, that is they display little or no fluorescence in terms of fluorescence which may be detected from the fluorescent moiety following appropriate excitation. However, following internalisation of the molecules by the cell or cells to be detected, a de-quenching of the molecules occurs and an increase in fluorescent signal, following excitation using light of a suitable wavelength, can be detected18.
Additionally, the present inventors have observed that certain molecules of the present invention which do not have recognisably cleavable peptide sequences are nevertheless internalised by certain cells, such as activated neutrophils and a de-quenching i.e. increase in fluorescence can be observed. Without wishing to be bound by theory, it is thought that the probes may be internalised into acidified vacuolar structures that directly effect internal quenching efficiency.
Thus, in a manner different to that described, for example, by WO2003014743, the molecules of the present invention do not necessarily have to possess recognisable enzyme cleavable peptide sequences in order to visualise cells and in particular activated neutrophils.
The present inventors are able through confocal endoscopy to visualise cells in situ in vivo. As such the term "in vivo" is to be understood to relate to cells within the living body and hence is to be distinguished from visualising cells obtained from tissue samples which have been extracted or excised from the body. The present methods may be conducted on or within any organ into which an endomicroscopic catheter may be inserted. This may be, for example, the gut including the large and small intestine; arteries and veins; the respiratory system including the lungs, the brain such as via an intracranial catheter; and the reproductive system including the womb and fallopian tubes.
In a particularly preferred embodiment, the methods of the present invention may be carried out whilst visualising cells in the lung, such as in the alveolar space.
The present inventors have observed that through the use of the dye constructs/poly-branched molecules described herein, that such molecules are capable of being internalised, by activated neutrophils. Such internalisation by activated neutrophils occurs very rapidly, within a few seconds or minutes and as such activated neutrophils may be visualised within 1-30 minutes, typically 1-10 minutes of the molecules of the present invention being administered to the subject at the site of investigation, such as within the lung. As mentioned above, the methods of detection as described herein should typically be conducted within a short period of time, following local administration of the initially quenched molecules, typically within a few minutes of administration, so that only cells, such as activated neutrophils, which internalise or take up the molecules of the present invention rapidly, are detected. Other cell types may also internalise the molecules, but over a much longer period of time. Thus, following the techniques of the present invention, it is possible to rapidly detect activated neutrophils in a mixed population of cells. In a particularly preferred embodiment, it is possible to detect activated neutrophils within the lung, such as in the alveolar space, of a subject.
Moreover, due to the sensitivity and increase in fluorescence following dequenching of the fluorescent moieties, it is possible to detect fluorescence from only microdosed amounts (typically less than 100 μg) such as less than 50 μg or even 10 μg or less of the dye construct which has been administered. This is particularly advantageous in terms of certain possible regulatory issues concerning the use of larger quantities and toxicity concerns when administering any exogenous molecule—although the molecules of the present invention may not in fact be significantly toxic in any case. It is in fact particularly surprising that such low microdose amounts of molecule when administered are capable of eliciting a signal which is detectable using microendoscopy techniques.
Thus, in a further embodiment, the present invention provides a method of visualising a particular cell or cells (such as activated neutrophils) within a mixture of cells in vivo using confocal endomicroscopy, comprising the step of adding a microdose (i.e. less than 100 μg, 50 μg, or 10 μg or less) of a dye construct or poly-branched molecule linked fluorescent dye to said mixture of cells and observing a cell or cells which have internalised the dendrimer dye molecule or poly-branched molecule linked fluorescent dye by observing fluorescence from said cell or cells using a confocal endomicroscope.
The present invention also provides use of a dendrimer dye molecule or poly-branched molecule linked fluorescent dye of the present invention in an amount of less than 100 μg, 50 μg, or 10 μg or less, for visualising cells in vivo using confocal endoscopy.
There is also provided a catheter or other suitable administration device comprising a microdose (i.e. less than 100 μg, 50 μg, or 10 μg or less) amount of a dye construct or poly-branched molecule linked fluorescent dye of the present invention, for administration to a subject, such that a cell or cells is capable of being visualised by confocal endoscopy.
One potential advantage of the present invention is that it may be carried out on subjects who are being given respiratory support in terms of being administered oxygen or air and who as such may have a face mask covering their mouth and/or nose or who are being intubated. Even in such a situation, it is possible to insert a confocal microendoscopy catheter into the lungs through the nasal passage or via the endotracheal tube. In this manner the present invention can truly be carried out at the bedside, without necessarily having to move the subject unduly. Moreover, for such subjects, the ability to detect any activated neutrophils, which are a key marker of an inflammatory response is of paramount importance and as such the present invention may find particular use in being conducted on such ill patients where moving them to another location may be undesirable and/or problematic.

THE UNIVERSITY COURT OF THE UNIVERSITY OF EDINBURGH


An integrity management system predicts abnormalities in complex systems before they occur based upon the prior history of abnormalities within the complex system. A topology of the nodes of a complex system is generated and data is collected from the system based on predetermined metrics. In combination with dynamic thresholding, fingerprints of the relevant nodes within a complex system at various time intervals prior to the occurrence of the abnormality are captured and weighted. The fingerprints can then be applied to real-time data to provide alerts of potential abnormality prior to their actual occurrence.

Complex systems are all around us. From weather to ecosystems to biological systems to information technology systems, various tools have been developed in attempt to study and understand these systems in detail, mainly through the use of computer-analyzed data. Using computers, information may be analyzed and presented for human consumption and understanding, even when dealing with complex systems. These computerized tools allow variables in complex systems to be analyzed ranging from biological systems, traffic congestion problems, weather problems, information technology systems and problems, and complex systems that would otherwise be too information rich for human understanding.
As the volumes of information regarding complex systems have increased, the tools for efficiently storing, handling, evaluating, and analyzing the data have evolved. For all of their power in accomplishing these tasks, however, existing tools to date suffer from an inherent inability to predict future events with accuracy in these complex systems. The problem with prior approaches is that computers are only capable of performing the tasks they are programmed to analyze. Consequently, in order to have a computer evaluate and predict outcomes in complex systems, computers must be programmed and instructed how to make the predictions. However, humans must first have a core understanding of the variables at play in a complex system in order to tell the computer how to predict outcomes. In most cases, the human operators are not able to instruct the computer how to model each variable in a complex system with enough precision to tell the computer how to make the predictions. Moreover, many variables in complex systems exhibit behavioral changes depending on the behavior of other variables. Thus, what is needed is a tool that allows humans to evaluate the variables without a complete understanding of every variable at play. In other words, there is a need to establish the ability to generate sui generis truth rules about predicates outside of the limitations of human consciousness and awareness.
Of particular importance are variations that occur within complex systems, such as abnormalities or problems. For instance, in the case of an information technology (IT) infrastructure, these variations from normal or expected operation could lead to failures, slowdown, threshold violations, and other problems. Often, these types of problems are triggered by unobserved variations or abnormalities in one or more nodes that cascade into larger problems until they are finally observable. Prediction of these of variations from the expected can require an understanding of the underlying causes, which may only be observable by accounting for the behaviors of the variables in substantially real-time. Moreover, the more remote in time from the event leading to the variation, the more sensitive the relevant analysis must be to detect the underlying causes. As a result, many tools currently used to address abnormalities in complex systems work close to the time the problem is actually observed to humans. Other tools are based on inefficient thresholding systems that address the potential abnormality when the probability that the abnormality will lead to an actual problem remains small, which triggers responses in many cases where a response is not actually merited.
Existing thresholding systems provide an inefficient and ineffective tool for predicting problems before they actually occur within enough time to address the underlying abnormality so as to be able to prevent the problems, because these systems are generally incapable of differentiating between a minute deviation from normal operational behavior (e.g., a "spike") and deviating trends, which are often indicative of an abnormality. However, because these systems do not address the causes and are activated in close time proximity to actual abnormalities, implementers often set the sensitivity of thresholding systems to be very sensitive, which often produces false-positive abnormality alerts and consequently creates inefficiencies in troubleshooting and addressing the abnormalities.
For abnormalities of nodes in complex systems, however, the sheer number of variables makes prediction of the abnormalities difficult. There is a need for a heuristic that utilizes thresholding functionality to provide a more efficient system for prediction and alleviation of abnormalities before they lead to problem events, without producing high rates of false positive abnormality alerts.

This patent is subject to a terminal disclaimer.

Self-learning integrity management system and related methods


A video circuit including a video amplifier adapted to generate an amplified output video signal from an input video signal; a short detection circuit adapted to generate a first signal indicative of whether there is a short present at an output of the video amplifier; and a load detection circuit adapted to generate a second signal indicative of whether there is a load coupled to the output of the video amplifier. The video circuit may further include an input signal detection circuit adapted to generate a third signal indicative of whether an input video signal is present. The third signal generated by the input signal detection circuit may be used to enable the outputting of the first and second signals in order to prevent the false indication of faults at the output of the video amplifier in the absence of an input video signal.

Video is becoming more prevalent. Many automobiles and airplanes now have DVD players and TV tuners. In addition, casinos, hotels, and public areas have ever more surveillance cameras. Such video systems are also becoming more complex because more devices are connected together. Accordingly, the number of video transmission lines in such complex video systems has grown substantially.
Because of the increasing complexity of video systems, it is now more difficult for a technician to locate and troubleshoot problems occurring in video systems, especially those having extensive routing of video transmission lines. In addressing problems in video systems, a technician has to first determine the source of the problem. For example, the problem may lie in the video input circuitry, video output circuitry, or in the video transmission lines. In addition, the technician has to then determine the nature of the problem in order to find a solution to the problem. For example, the nature of the problem may be a short or an open on a particular video transmission line.
The time needed for a technician to locate and troubleshoot such problems in video systems is often long. Accordingly, the labor cost of locating and troubleshooting problems is also likely to be relatively high.

System and method for video transmission line fault detection


A wireless communication system including dispatch call controllers, signaling gateways, base stations, a first network coupling the dispatch call controllers to the signaling gateways, and a second network coupling the signaling gateways to the base stations. The signaling gateways serve as intermediaries between dispatch call controllers and base stations by translating messages received from dispatch call controllers intended for the base stations from the protocol used in the first communications network to the protocol used in the second communications network, and translating messages received from base stations intended for dispatch call controllers from the protocol used in the second communications network to the protocol used in the first communications network. The system may be configured such that each dispatch call controller has individual logical links to each of the signaling gateways, and each signaling gateway has logical links to a distinct subset of the base stations.

Wireless communication systems allow users to communicate with other entities while allowing them to be geographically mobile. Also, today's wireless communication systems allow users to communicate with other entities in a variety of different communication modes. For example, some wireless communication systems allow users to communicate with each other in interconnect (cellular) mode, where the communication link is full-duplex, allowing all parties to transmit simultaneously. Other, or the same, wireless communication systems allow users to communicate with each other in dispatch mode (walkie-talkie mode), where the communication link is half-duplex, only allowing a single party to transmit at a particular time.
A typical wireless communication system providing dispatch communication services generally includes one or more dispatch call controllers, one or more voice packet duplicators, and a plurality of base stations (cell sites) all coupled together by way of a communications network. As discussed in more detail below, the dispatch call controllers generate messages for setting up dispatch communication links, controlling the channel floors of the dispatch communication links, and terminating the dispatch communication links. In addition, the dispatch call controller is also involved in managing the mobility of mobile communication units (MUs) from base station to base station. The voice packet duplicators generate voice packets for transmission via the established dispatch communication links. The base stations provide an interface between a wireless environment in which the MUs reside, and the wired environment of the communications network. The following illustrates an example of a conventional dispatch wireless communication system.
FIG. 1A illustrates a block diagram of a conventional wireless communication system 100. The wireless communication system 100 includes a plurality of dispatch call controllers 102-1 through 102-m, a frame relay/asynchronous transfer mode (ATM) communications network 104, and a plurality of base stations 106-1 through 106-n. The dispatch call controllers 102-1 through 102-m and the base stations 106-1 through 106-n communicate with each other by way of the frame relay/ATM communications network 104. The wireless communication system 100 provides dispatch communication services to a plurality of MUs, two of which are shown as MUs 108-1 and 108-2 assigned respectively to base stations 106-1 and 106-6. The following describes an exemplary process performed by a dispatch call controller in setting up a dispatch communication link, controlling the channel floor, and terminating the dispatch communication link.
In this example, the user of MU 108-1 desires to communicate with the user of MU 108-2 in dispatch communication mode. First, in response to the user of MU 108-1 initiating a dispatch call by selecting the target MU 108-2 and pressing an appropriate button, the MU 108-1 sends a page request targeting MU 108-2 to, for example, dispatch call controller 102-1 by way of base station 106-1 and the frame relay/ATM network 104. In response to receiving the page request, the dispatch call controller 102-1 sends a paging message to the MU 108-2 by way of the frame relay/ATM network 104 and base station 106-6. If MU 108-2 does not respond within a predetermined time interval (meaning that it may not be available), the dispatch call controller 102-1 sends a target unavailable message to the originator MU 108-1 by way of the frame relay/ATM network 104 and base station 106-1. If, on the other hand, the target MU 108-2 is available, it sends a page response to the dispatch call controller 102-1 by way of the base station 106-6 and frame relay/ATM network 104.
In response to receiving the page response from the target MU 108-2, the dispatch call controller 102-1 sends a target available message to the originator MU 108-1 by way of the frame relay/ATM network 104 and base station 106-1, and proceeds to establish the dispatch communication link between the originator and target MUs 108-1 and 108-2. During the dispatch communication call, the dispatch call controller 102-1 initially receives a channel floor request from the originator MU 108-1 by way of the base station 106-1 and frame relay/ATM network 104. The channel floor request informs the dispatch call controller 102-1 that MU 108-1 desires the channel floor to transmit a voice communication to the target MU 108-2. In response to the floor request, the dispatch call controller 102-1 allocates the floor to only the originator MU 108-1. If during the time that the originator MU 108-1 has the channel floor, the target MU 108-2 sends a channel floor request to the dispatch call controller 102-1 by way of the base station 106-6 and frame relay/ATM network 104, the dispatch call controller 102-1 sends a channel floor deny message to the target MU 108-2 by way of the frame relay/ATM network 104 and base station 106-6.
When the originator MU 108-1 completes sending the voice communication, it sends a channel floor open request to the dispatch call controller 102-1 by way of the base station 106-1 and frame relay/ATM network 104. In response to the channel floor open request, the dispatch call controller 102-1 makes the channel floor available until it receives another channel floor request. If no channel floor request is received within a predetermined hang time interval, the dispatch call controller 102-1 terminates the dispatch communication link, and sends appropriate messages to the originator MU 108-1 and target MU 108-2 via the frame relay/ATM network 104 and the respective base stations 106-1 and 106-6.
In addition to setting up dispatch communication links, controlling the respective channel floors, and terminating dispatch communication links, the dispatch call controllers also manages the mobility of MUs between different base stations. For example, if MU 108-1 detects that the RF environment to base station 106-2 is better than the RF environment of its assigned base station 106-1, the MU 108-1 may send a handover request to the dispatch call controller 102-1 by way of base station 106-1 and frame relay/ATM network 104. In response to the handover request, the dispatch call controller 102-1 may send a handover grant message to the MU 108-1 and base stations 106-1 and 106-2. The dispatch call controller 102-1 may also update a home location register (HLR) (not shown) and/or visitor location register (VLR) (not shown) to denote the new assigned base station 106-2 for MU 106-1.
As exemplified above, dispatch call controllers use the frame relay/ATM network 104 to communicate with base stations to establish, control, and terminate dispatch communications links, and also to manage the mobility of MUs between different base stations. As discussed in more detail below, the frame relay/ATM network 104 is configured to form a plurality of logical links connecting each of the dispatch call controllers to each of the base stations. Each of the dispatch call controllers has to manage its own set of logical links to the base stations. This is further explained below with reference to the following example.
FIG. 1B illustrates a link diagram of the prior art wireless communication system 100. As discussed above, the wireless communication system 100 includes the plurality of dispatch call controllers 102-1 through 102-m, and the plurality of base stations 106-1 through 106-n. As discussed above, the frame relay/ATM network 104 is configured to couple each of the dispatch call controllers to each of the base stations by way of individual logical links. Accordingly, dispatch call controller 102-1 is coupled to base stations 106-1 and 106-n by way of respective logical links 110-1-1 through 110-1-n of the frame relay/ATM network 104. Similarly, dispatch call controller 102-2 is coupled to base stations 106-1 and 106-n by way of respective logical links 110-2-1 through 110-2-n of the frame relay/ATM network 104. And likewise, dispatch call controller 102-m is coupled to base stations 106-1 and 106-n by way of respective logical links 110-m-1 through 110-m-n of the frame relay/ATM network 104.
In a particular wireless communication system, there may be 15 dispatch call controllers (m=15) and 3200 base stations (n=3200). In such a system, there would be 48,000 logical links connecting the dispatch call controllers to the base stations (i.e., 15 dispatch call controllers×3200 base stations). Accordingly, the dispatch call controllers have to track and manage the state of 48,000 logical links. Such tracking and management of logical links consume substantial amount of processing power of the dispatch call controllers. Additionally, when a link goes down for any reason, the dispatch call controller attempts to periodically reestablish connectivity via the link. This further results in additional consumption of processing power of the dispatch call controllers. Furthermore, the large amount of logical links makes it relatively difficult to troubleshoot problems within the frame relay/ATM network.

Wireless communication system having a signaling gateway serving as an intermediary between a dispatch call controller and a base station


Multi-layer memory arrays and methods are provided. A memory array has two or more layers of memory material, each layer of memory material having an array of memory cells. A first contact penetrates through each layer of memory material in a first plane and is electrically connected to each layer of memory material so as to electrically interconnect the layers of memory material in the first plane. A second contact penetrates through at least one of the layers of memory material in a second plane substantially perpendicular to the first plane.

Memory devices are available in a variety of styles and sizes. Some memory devices are volatile in nature and cannot retain data without an active power supply. A typical volatile memory is a DRAM that includes memory cells formed as capacitors. A charge, or lack of charge, on the capacitors indicates a binary state of data stored in the memory cell. Dynamic memory devices require more effort to retain data than non-volatile memories, but are typically faster to read and write.
Non-volatile memory devices are also available in different configurations. For example, floating gate memory devices are non-volatile memories that use floating-gate transistors to store data. The data is written to the memory cells by changing a threshold voltage of the transistor and is retained when the power is removed. The transistors can be erased to restore the threshold voltage of the transistor. The memory may be arranged in erase blocks where all of the memory cells in an erase block are erased at one time. These non-volatile memory devices are commonly referred to as flash memories.
Flash memories may use floating gate technology or trapping technology. Floating gate cells include source and drain regions that are laterally spaced apart to form an intermediate channel region. The source and drain regions are formed in a common horizontal plane of a silicon substrate. The floating gate, typically made of doped polysilicon, is disposed over the channel region and is electrically isolated from the other cell elements by a dielectric. The non-volatile memory function for the floating gate technology is created by the absence or presence of charge stored on the isolated floating gate. The trapping technology functions as a non-volatile memory by the absence or presence of charge stored in isolated traps that capture and store electrons or holes.
NOR and NAND flash memory devices are two common types of flash memory devices, so called for the logical form the basic memory cell configuration in which each is arranged. Typically, for NOR flash memory devices, the control gate of each memory cell of a row of the array is connected to a word line, and the drain region of each memory cell of a column of the array is connected to a bit line. The memory array for NOR flash memory devices is accessed by a row decoder activating a row of floating gate memory cells by selecting the word line connected to their control gates. The row of selected memory cells then place their data values on the column bit lines by flowing a differing current, depending upon their programmed states, from a connected source line to the connected column bit lines.
The array of memory cells for NAND flash memory devices is also arranged such that the control gate of each memory cell of a row of the array is connected to a word line. However, each memory cell is not directly connected to a column bit line by its drain region. Instead, the memory cells of the array are arranged together in strings (often termed NAND strings), e.g., of 32 each, with the memory cells connected together in series, source to drain, between a source line and a column bit line. The memory array for NAND flash memory devices is then accessed by a row decoder activating a row of memory cells by selecting the word line connected to a control gate of a memory cell. In addition, the word lines connected to the control gates of unselected memory cells of each string are driven to operate the unselected memory cells of each string as pass transistors, so that they pass current in a manner that is unrestricted by their stored data values. Current then flows from the source line to the column bit line through each series connected string, restricted only by the selected memory cells of each string. This places the current-encoded data values of the row of selected memory cells on the column bit lines.
In order for memory manufacturers to remain competitive, memory designers are constantly trying to increase the density of memory devices. Increasing the density of a flash memory device generally requires reducing spacing between memory cells and/or making memory cells smaller. Smaller dimensions of many device elements may cause operational problems with the cell. For example, the channel between the source/drain regions becomes shorter, possibly causing severe short channel effects.
For the reasons stated above, and for other reasons stated below which will become apparent to those skilled in the art upon reading and understanding the present specification, there is a need in the art for higher density memory devices.


Composite orthopedic devices that facilitate spine stabilization, such as: bone screws, rods, plates, interbodies, and corpectomy cages are disclosed. They are designed to provide both strength and load carrying capabilities, while increasing bio-integration of the devices with the surrounding bone tissue. They are constructed of composite layers of allograft and/or autograft bone and a structural material, such as titanium alloy or carbon/graphite fiber composite. Cannulations within the device are loaded with a mixture of stem cells, particles of allograft and/or autograft bone, and bone growth factors, such as BMP-2. The cannulations are connected to the surface of the device via multiple fenestrations that provide pathways to supply the bone/stem cell mixture to the surface, allowing living bone tissue to grow and insure bio-integration. The devices can also have radiofrequency (RF) stimulation implantation within the structure of the implanted device, capable of responding to external RF stimulation of enhanced bone growth.

1. Field of the Invention
The present invention relates generally to orthopedic fixation devices, fasteners, and implants that are used in orthopedic surgery, neurosurgery, plastic surgery, hand surgery, foot and ankle surgery, and Ear-Nose-Throat (ENT) surgery. These devices, such as: pedicle screws, rods, cross-links, plates, set capping screws, spinal fusion interbody spacers for lumbar/thoracic/cervical spine (both stand alone and with associated interbody and plate combination, and corpectomy cages (both stand alone devices and separate corpectomy and plate combinations), among others, are used, for example, to facilitate spine stabilization and healing after spinal fusion surgery; in addition to being used to stabilize other types of orthopedic bony fractures (such as long-bone or facial fractures) in trauma departments. Some of these devices may also be used in plastic surgery and oral/facial surgery, hand and foot surgery, and ear-nose-throat surgery for a variety of pathologies, including mandibular and facial fractures, extremity fractures, oncologic disease of the skeleton and skull, and traumatic disease of the skeleton and skull.
2. Description of Related Art
Millions of people suffer from a variety of musculoskeletal disorders or traumatic occurrences necessitating the use of methods and devices to provide reliable spinal stabilization and facilitate rapid healing. Stabilization may be accomplished with mechanical fasteners, implants, and fixation devices such as pedicle screws, rods, cross-links, plates, vertebra interbody spacers, and corpectomy cages.
Pedicle screw fixation has been shown to be superior to other methods of instrumentation of the lumbar and thoracic spine for spinal fusion and correction of deformity. However, there are many complications associated with placement of screws within the lumbar and thoracic spine, as well as the entire spinal axis. Pedicle perforation is noted to be as high as 40%, which increases likelihood of dural tears, nerve root injuries, paraplegia, and vascular injury.
Non union and pseudoarthrosis rates have been shown to be as high as 10% to 40%. Screw pullout rates are noted to be as high as 5-20%. Infection continues to be a devastating problem post-operatively in patients with spinal instrumentation and fusion.
Surgical techniques for the treatment of spinal injuries or deformities (e.g., scoliosis) are usually aimed at joining together two or more adjacent vertebrae of the spine, through a procedure that is called spinal fusion. A common approach to spinal fusion adopts a fixation system that is anchored to the spine by way of orthopedic screws implanted into the pedicles of two or more adjacent vertebrae. The single screws (i.e., pedicle screws) are connected together by means of rigid or semi-rigid rods, thereby forming a rigid cage that stabilizes and protects the spine. In previous versions, the connecting rod was housed within a transversal hole provided in the pedicle screw head itself. However, due to the irregularity of bone anatomy, it was unlikely that once the screws had been implanted into the spine pedicles that the transverse holes in their heads would be properly aligned for rod insertion. Hence, in order to facilitate the alignment and insertion of the rod, modern pedicle screws are provided with a rotatable, rod-receiving connecting member (connector) that freely rotates and swivels with respect to the screw's shaft.
Screws of this type, named polyaxial screws, comprise a threaded shaft with a hemi-spherical polyaxial. The polyaxial drive end is typically housed inside a mating, hemi-spherical recess (i.e., as a ball & socket joint) provided in the rod-receiving connecting member (rod-connector). A transversal hole, or U-shaped channel, in the rod-connector houses the connecting rod; and a set-screw or threaded-plug insert is provided above the rod, which clamps the rod into a rigid, locked position. In typical polyaxial pedicle screws, such as the example disclosed in U.S. Pat. No. 5,672,176, the locking action of the set-screw determines the locking of both the connecting rod and the bone screw's orientation, since pressure applied by the set-screw is transmitted to both the connecting rod and the screw's hemi-spherical drive head.
These implantable, orthopedic fixation devices are typically made of a rigid material, such as a titanium alloy or stainless steel. While the use of such rigid materials provides sufficient strength and load-carrying capabilities to avoid fractures or breakage, the interface between the metallic device and the surrounding bone is relatively non-flexible and unyielding.
Alternatively, these devices may be formed of semi-rigid materials, such as polymeric materials (e.g., PEEK). While the use of such semi-rigid materials provides a more flexible or yielding interface between the device and the surrounding bone, the strength and structural load carrying capabilities of polymeric bone anchor are generally less than metal alloys.
Bone autograft and allograft and/or autograft materials are a third alternative, and they are commonly used for vertebra interbody fusion spacers, in part, due to their capability for bio-integration at bone-to-bone interfaces. While bone is quite strong in compressive loading, it is relatively weak in tension and shear. For this reason, structural (load-bearing) orthopedic fixation devices and fasteners (e.g., pedicle screws) are not often made of allograft (cadaver bone) and/or autograft bone tissue.
Thus, there remains a need for improved materials for use in orthopedic fixation devices, implants, and fasteners, especially for spinal stabilization, which optimally combine the best properties of all three types of materials described above; and corresponding methods for implementing same.

Composite metal and bone orthopedic fixation devices


A conversion technique efficiently discovers an optimal path from a source station to a destination station over a computer network. The technique involves converting an explorer frame to a specifically-routed frame at a bridge interconnecting the source's local subnetwork to other subnetworks of the computer network. Such conversion is made possible by providing routing information, comprising at least global topological information, to the bridge. Armed with the routing information, the bridge computes the optimal path and forwards the converted frame to the destination over that path.

A computer network is a geographically distributed collection of interconnected subnetworks for transporting data between stations, such as computers. A local area network (LAN) is an example of such a subnetwork consisting of a transmission medium, such as coaxial cable or twisted pair, that provides relatively short distance communication among interconnected stations. A plurality of LANs may be further interconnected by an intermediate station, called a bridge, to extend the effective "size" of the computer network and increase the number of communicating stations. The stations typically communicate by exchanging discrete packets or "frames" of data according to predefined protocols. In this context, a protocol consists of a set of rules defining how the stations interact with each other.
Most networks are typically organized as a series of hardware and software levels or "layers" within each station. These layers interact to format data for transfer between, e.g., a source station and a destination station communicating over the network. Specifically, predetermined services are performed on the data as it passes through each layer and the layers communicate with each other by means of the predefined protocols. This layered design permits each layer to offer selected services to other layers using a standardized interface that shields those layers from the details of actual implementation of the services.
In an attempt to standardize network architectures, i.e., the sets of layers and protocols used within a network, a generalized model has been proposed by the International Standards Organization (ISO). The model, called the Open Systems Interconnection (OSI) reference model, is directed to the interconnection of systems that are "open" for communication with other systems. The proposed OSI model has seven layers which are termed, in ascending interfacing order, the physical, data link, network, transport, session, presentation, and application layers. These layers are arranged to form a "protocol stack" in each station of the network.
FIG. 1 illustrates a schematic block diagram of prior art protocol stacks 125 and 175 used to transmit data between a source station 110 and a destination station 150, respectively, of a LAN 100. Each protocol stack comprises a collection of protocols, one per layer, and is preferably structured according to the OSI seven-layer model. As can be seen, the protocol stacks 125 and 175 are physically connected through a communications channel 180 at the physical layers 124 and 164. For ease of description, the protocol stack 125 will be described.
In general, the application layer 112 contains a variety of protocol functions that are commonly needed by software processes, e.g., sending process 104, executing on the station, while the presentation layer 114 is responsible for the presentation of transmitted data in a meaningful manner to the application layer. The session layer 116, transport layer 118 and network layer 120 are substantially involved in implementing different forms of connectivity from the source station to the destination station.
IEEE project 802 defines a flexible network architecture oriented to the implementation of LANs. Although it generally conforms with the OSI model, the IEEE approach addresses only the lowest two layers of that model, the physical and data link layers. Specifically, the physical layer 124 is concerned with the actual transmission of signals across the communication channel; in this context, the physical layer defines the types of cabling, plugs and connectors used in connection with the channel.
The data link layer 122, on the other hand, is responsible for transmission of data from one station to another. In the IEEE 802 architecture, the data link layer is divided into two sublayers: logical link control (LLC) and media access control (MAC). The LLC sublayer 180 allows the overlying network layer to access the services of the LAN without regard to the actual network implementation; more specifically, the LLC layer initiates control signal interchange, organizes data flow, interprets commands and generates responses.
The MAC sublayer 182 is primarily concerned with the controlling access to the transmission medium and, to that end, defines rules or procedures by which the stations must abide in order to share the medium. The MAC layer further provides addressing and framing functions, the latter including the addition of header and trailer information needed to identify the boundaries of frames, to synchronize communication between source and destination stations, and to route the frames.
Data transmission over the LAN 100 therefore consists of generating data in, e.g., sending process 104 executing on the source station 110, passing that data to the application layer 112 and down through the layers of the protocol stack 125, where the data are sequentially formatted as a frame for delivery onto the channel 180 as bits. Those frame bits are then transmitted to the protocol stack 175 of the destination station 150, where they are passed up that stack to a receiving process 174. Data flow is schematically illustrated by solid arrows.
Although actual data transmission occurs vertically through the stacks, each layer is programmed as though such transmission were horizontal. That is, each layer in the source station 100 is programmed to transmit data to its corresponding layer in the destination station 150, as schematically shown by dotted arrows. To achieve this effect, each layer of the protocol stack 125 in the source station 110 typically adds information (in the form of a header field) to the data frame generated by the sending process as the frame descends the stack. At the destination station 150, the various headers are stripped off one-by-one as the frame propagates up the layers of stack 175 until it arrives at the receiving process.
Access to the LAN is typically shared among the stations in accordance with various access control methods depending upon the topology of the subnetwork and the type of transmission control employed. A popular subnetwork topology is a ring network that is typically formed by configuring the communication channel as a loop and coupling the stations at intervals around the loop. The stations communicate by transmitting and receiving discrete signals in the form of data frames according to predefined protocols. Acceptance of a frame by each station, in turn, is determined on the basis of an address contained in the frame.
With LANs that employ a ring topology, a commonly used access control method is token passing. Token passing is a form of distributed transmission control wherein all the stations on the subnetwork cooperate in controlling access to the communication channel. Here, a small message or token is passed from one station to the next along the ring. If the token is marked as free, the station receiving it can transmit a message over the ring. A token ring network is an example of a ring topology that uses token passing as an access control method.
Token ring networks may be further interconnected using a bridge whose primary function is to transfer frames between the rings. A route is the path a frame travels through the subnetworks from a source station to a destination station. Depending upon how the rings are interconnected, there may be more than one possible path for a frame to follow. Once the source station has "discovered" an optimal path to the destination, it transmits specifically-routed frames over the subnetworks; as the name implies, these frames include information specifying the route to, along with the address of, the destination station.
Source-Route-Bridge (SRB) is a source routing technique used by a source station to discover the optimal path to a destination. According to this networking technique, the source station specifies the optimal route, which is determined in accordance with routing information acquired from the stations of the network. A special type of frame, called an explorer frame, is typically used by the source to collect and store that information in a routing information (RI) field of the frame.
In one embodiment of SRB networking, the source station issues a broadcast explorer frame that is received by each station on the local ring subnetwork. Here, the source is unaware of the MAC address of the destination station and the path (or paths) for reaching that station, so it issues the explorer frame having a broadcast address that all stations are configured to receive. Each bridge copies the frame and supplies information relating to the route (i.e., bridge and ring numbers) within the RI field; it then distributes the copy to all stations on its interconnected ring. Eventually, a copy of the broadcast explorer frame reaches every station on every LAN of the network. Each station may respond to the source by issuing a response frame containing its MAC address and the routing information. The source station can examine the routes followed by the explorer frames and choose the best path for the particular destination.
In another embodiment, the source creates a unicast explorer frame that includes the MAC address of the destination station. The frame is transmitted over the source's local ring subnetwork, where it is received by bridges connecting the local ring to other ring subnetworks. As the unicast explorer frame passes over these interconnected rings, routing information is again stored in the RI field by the bridges. If there is more than one route, more than one frame will eventually reach the destination, with each frame containing different routing information.
In response to each received explorer frame, the destination station returns a response frame containing the routing information for each possible route. The source station examines the information contained in these response frames and selects an optimal path to the destination based on that information; it then may communicate with the destination by sending data frames over that selected path.
A disadvantage of the conventional explorer techniques involves the exponential overhead of bandwidth that is consumed every time a source station attempts to discover an optimal path to a destination. That is, transmission of the explorer frames consumes a significant amount of bandwidth because copies of those frames are created and distributed by bridges connecting the source station to all possible paths leading to the destination station. In addition, the response frames returned by the destination consume an appreciable amount of network bandwidth.
Moreover, SRB networking constrains the ability of a network administrator to set certain policy decisions for the network, such as cost and load balancing. In other words, because the dispositive routing information is provided by the explorer response frame, the network administrator effectively has no control over the determination of a communication path between the source and destination stations.

Conversion technique for routing frames in a source route bridge network


A fastener system for use with a powder actuated tool. The system include a pin, a metallic washer surrounding a portion of the pin at the second end; and a plastic sleeve disposed between the metallic washer and the pin. The plastic sleeve includes a cap portion and an sleeve portion, the cap portion disposed on the top side of the metallic washer coincident with the head of the pin.

Pressure-treated wood is truly a rugged exterior building product that is rot and insect resistant. Treated wood is used for a number of exterior building applications. Pressure treatment is a process that forces chemical preservatives into the wood. Wood is placed inside a closed cylinder, and vacuum and pressure are applied to force the preservatives into the wood. The preservatives help protect the wood from attack by termites, other insects, and fungal decay.
Hot-dip galvanized or stainless steel fasteners, anchors and hardware are recommended by the Pressure Treated Wood Industry for use with treated wood. This prevents the fasteners from decaying faster than the wood itself. In the past this industry did not address the required levels of galvanizing, however most of those in the industry now provide information regarding the minimum level of galvanizing that should be used.
In general, the thicker the galvanized coating the longer the expected service life of the fastener, connector, anchor, or other hardware will be. Mechanical galvanizing is a process of providing a protective coating (zinc) over bare steel. The bare steel is cleaned and loaded into a tumbler containing non-metallic impact beads and zinc powder. As the tumbler is spun, the zinc powder mechanically adheres to the parts. The zinc coating has "good" durability, but has less abrasion resistance than hot-dip galvanized zinc coatings since it does not metalurgically bond with the steel. Some anchors and fasteners can be mechanically galvanized.
An alternative to mechanical galvanizing is hot-dip galvanizing Hot-dip galvanizing is the process of coating iron or steel with a thin zinc layer, by passing the steel through a molten bath of zinc at a temperature of around 460° C. In general, a heavier/thicker coating would be expected to have a longer service life than standard galvanized connectors.
Typically, pin and washer combinations are used as fastener systems in powder actuated fastening devices. Commonly known as Powder Actuated Tools, these devices force a pin through a washer into the wood with sufficient force to embed the pin in a single stroke. Typically, a fastener is initially coupled to a metallic washer with a through-hole having a diameter smaller than the diameter of a fastener. This ensures that the pin and washer stay in place when loaded in to the fastening device, and are secure when the device is forced downward (toward the wood), typically to deactivate a safety device present in the tool which prevents accidental firing of the fastener. When used with standard applications of washers having a through-hole with a diameter smaller than the diameter of a fastener, the washer can scratch off a galvanized coating, eliminating or reducing the benefits of the zinc layer.


An FEC codeword comprises channel information indicating the reliability of the information contained by the FEC codeword. The channel information can be used to generate an initial error channel estimate. Based on the initial error channel estimate, an FEC decoder can decode the FEC codeword to increase the reliability of the information contained by the FEC codeword. According to the present disclosure, a method and system of decoding comprises: comparing a current codeword to a previous codeword in order to identify bits corrected between the previous and current codewords; revising an error channel estimate based on the identified corrected bits, the revised estimate representing a change in the error channel over time; and decoding the codeword based on the revised error channel estimate.

Forward Error Correction (FEC) is a method of encoding and decoding information for transmission over a noisy communication channel. Various implementations of FEC, such as Low-Density Parity-Check and Turbo codes, are known.
Low-Density Parity-Check (LDPC) decoder systems are current generation iterative soft-input FEC decoder systems that have found increasing popularity in FEC applications where low error floor and high performance are desired. LDPC codes are defined in terms of a two-dimensional parity-check matrix, referred to as an H matrix, that represents a set of parity check equations such that cH=0 where c is a codeword of the LDPC code.
An H matrix is a low-density matrix that can be represented by a sparse bipartite graph, known as a Tanner graph. A Tanner graph includes check nodes and variable nodes (otherwise known as bit nodes). For LDPC codes, the check nodes denote rows of the H matrix and the variable nodes represent the columns of the H matrix. An edge of the Tanner graph connects a check node to a variable node if a nonzero entry (i.e., a one) exists in the intersection of the corresponding row and column of the H matrix.
Decoding an LDPC codeword requires solving a set of parity check equations according to the H matrix. A commonly used decoding method is based on a two-step iterative process that uses soft decisions and is based on a belief propagation method. The process starts by determining soft-values of a LDPC codeword and loading those soft-values, such as log-likelihood ratios (LLRs) of the LDPC codeword, into the variable nodes. In the first half-iteration, each check node takes the output of the connected neighboring variable nodes and calculates a soft value. In the second-half iteration, the soft value at each variable node is updated by combining the soft value at the particular variable node (the variable node information) with the soft values output by the connected neighboring check nodes (the extrinsic information) for use in the subsequent iteration.
A common approach for calculating the soft value output by each check node is the min-sum method, or min-sum algorithm. In the min-sum method, the magnitude of the soft value of each check node is calculated by determining the minimum magnitude of all of the outputs of the connected neighboring variable nodes and the sign of the soft value output by each check node is calculated as the one bit binary multiplication of the signs of the output of the connected neighboring variable nodes.
Soft-decoding a LDPC codeword causes convergence of the solved LDPC codeword with the true LDPC codeword for most communication channels. Convergence is achieved over a number of iterations of the two-step iterative process described above and results in a corrected LDPC codeword without errors.
A category of LDPC codes, known as quasi-cyclic (QC) codes, generates an H matrix with features that improve the ease of implementing an LDPC encoder and decoder. In particular, it is possible to generate a QC-LDPC H matrix where some rows are orthogonal to each other. The orthogonal rows are treated as a layer, and the orthogonal rows within a layer can be processed in parallel (hereinafter referred to as layer processing), thus reducing the iterative cost of the decoder.
Improvements to LDPC and FEC decoder systems that improve the performance, such as decoding time or decoding accuracy, or both, of the LDPC or FEC decoder system are therefore desirable.

Method and system for forward error correction decoding based on a revised error channel estimate

Microsemi Storage Solutions (U.S.), Inc.


A vortex water flow accelerator comprises a joint pipe with a water inlet and a water outlet, a water outlet barrel connected to one end of the joint pipe, and a plurality of spiral blades arranged in the water outlet barrel and connected with the joint pipe, wherein the size of the water outlet is smaller than that of the water inlet, and the inner wall of the joint pipe sequentially forms an annular surface and a first conical surface along a direction from the water inlet to the water outlet, and the outer wall of the joint pipe is formed with a second conical surface, on which a plurality of splitter plates uniformly distributed at the circumference are formed; the splitter plate protrudes from the water outlet end face of the joint pipe, the water outlet barrel has a small diameter end and a large diameter end, and the small diameter end is connected to the splitter plate, so that a secondary water inlet is formed between the second conical surface, the water outlet barrel and two adjacent splitter plates; the water outlet is smaller than the water inlet, the cross-section decreases to increase the flow velocity of the water flow passing through; the first conical surface can well reduce the resistance to the water flow, maximizing the increase of the flow velocity, while the secondary water inlet simultaneously feeds water to further increase the water volume, and the second conical surface also gives the minimum resistance to the water flow.

Vortex water flow accelerators are common in fish culture tanks. The vortex water flow accelerator is usually connected to the nozzle of the water outlet pipe of a suction pump. The flow rate of the water in the water outlet pipe is increased and produces a swirl effect under the function of the vortex water flow accelerator, which can increase the water circulation and enhance the filtration effect. The existing vortex water flow accelerator has a simple structure, in which usually only a plurality of spiral blades are arranged in the direction of water flow, and the water flows through the spiral blades to form vortex water; the existing vortex water flow accelerator can play the function of acceleration, but the acceleration effect is not very good, so it needs to be further improved by structural optimization.


Disclosed are coatings and materials that resist bacterial colonization and encrustation for use in medical devices and urological applications. The coating includes acidic chelating components, reactively bound to a hydrophilic polyurethane prepolymer along with noble metal combinations or antibacterials. The acidic and noble metal combinations can also be incorporated as additives during plastic molding of medical devices. A continuous antibacterial surfaces are provided by such coatings and materials.

This invention relates to medical devices that are resistant to bacterial growth or encrustation such as urological devices and more particularly to urinary catheters constructed of, or coated with, a material which enables the urinary catheters to inhibit urease, and to prevent calcium and magnesium phosphate deposits on the catheters.
Urinary catheters are used in urological surgery and when other methods of managing urinary incontinence fail. These catheters are generally made from a non-toxic, non-irritating material which is flexible but which will withstand collapse. Ideally they should resist colonization by bacteria and encrustation by mineral deposits. Short-term urological devices used to control incontinence such as the plastic urethral inserts suffer from susceptibility to bacterial adherence causing Urinary tract infection. (UTI).
The most common materials used for the catheters are latex, plastic or silicone. All biomaterials, including the most recently tested polyurethane, polyurethane-carbon and silicone-carbon, become encrusted with mineral deposits to varying extents. The degree of encrustation formation on biomaterials exposed to urine is dependent upon the biomaterial, the length of urinary exposure, the presence of infection and the solute content of urine. Several independent studies (e.g. Hukins et al., 1989) of the scraped encrusted material have identified--two major salts, namely apatite Ca.sub.5 (PO.sub.4).sub.3 (OH) and struvite Mg NH.sub.4 PO.sub.4 6H.sub.2 O. A very small amount of brushite CaHPO.sub.4.2H.sub.2 O has also been identified.
The pH increase of urine occurs due to urease producing bacteria, that infect the urine. Urease catalyzes the hydrolysis of urea at an enormous rate (10.sup.14 times as fast as the spontaneous hydrolysis of urea which is not observable in neutral solution) producing ammonia, which in turn precipitates calcium phosphates.
Microbial heterogeneity and structural complexity of the bio-films observed on infected catheter materials by means of scanning and transmission electron microscopy reveal a variety of microflora. It appears that the adherent microcolonies of bacteria are much less susceptible than their planktonic counterparts to antibiotics because the extensive anionic matrix surrounding the cell appears to comprise an ion exchange barrier between charged antibiotic molecules and their cellular targets. Antibiotics should be reserved for symptomatic, febrile infections; otherwise their use produces a change in bacterial flora with the potential for producing resistance.
Bacteriurea in a catheterized patient indicates the urinary tract has become colonized or infected. Administration of anti-bacterials such as nitrofurantoin, methenamine, and naldixic acid are used in practice. Most of these are not very effective in alkaline urine, and to achieve a high concentration in urine, the patient has to be given enormous doses.
Catheter associated Bacteriurea results from ascending bacterial colonization within glycocalyx enclosed biofilm on the inside and/or outside surfaces of the catheter and drainage systems. Urinary tract catheters made from a biomaterial that inhibits bacterial adherence and thus retards upstream colonization of bacteria may reduce acquired urinary tract infection (UTI). While hydrophilic surfaces show reduced protein adhesion, antibacterial surfaces offer better protection. Either a controlled release or an antibacterial immobilized on the surface should offer continuous protection against bacterial colonization. A silver oxide catheter is described in a publication by Shaeffer, A. J., Story, K. O., Johnson, S. M. in "Effect of silver oxide/Trichloroisocyanuric Acid Antimicrobial Urinary Drainage System on Catheter Associated Bacteriurea", J. Urol., 39, 60 (1988). A recent clinical study on silver catheters reported by Johnson, J. R., Roberts, P. L., Olsen, R. J., Moyer, K. A., and Stanni, W. E. in "Silver Oxide Coated Catheters", J. Infect. Diseases, 162, 1145 (1990) indicated the prevention of UTI among women not receiving antimicrobials.
The other problem associated with catheters left in place for long periods of time is the encrustation due to the formation of calcium hydroxyapatite and struvite. Long-term urethral catheterization is frequently necessary for patients with intractable urinary incontinence or retention. This procedure is employed in as many as 16-28% of patients in various chronic care facilities. More than 50% could suffer from blockage of their catheters. This can cause incontinence due to urinary bypassing of the catheter or acute pain and discomfort associated with urinary infection.
Removal of deposits by acidic solution (citric acid-magnesium oxide) has been shown to dissolve encrustation in vitro and is now used extensively in practice. Frequent irrigation could result in the damage of the mucus in the bladder.
A number of U.S. patents describe indwelling urinary catheter systems aimed at preventing urinary tract infection. These are mechanical devices with appropriate valve fittings to keep the drainage open while at the same time preventing ascending infection. U.S. Pat. Nos. 4,946,449 issued to Richard Davis and 4,878,901 issued to Hans Ernst Sachse are two typical examples. However, these do not have any prevention methods for encrustation. In general, mechanical systems are complicated and do not provide adequate protection from infection. U.S. Pat. No. 4,932,948 issued to Kernes et al., discloses the use of a funnel shaped insert at the end of the urinary catheter that serves as a reservoir to antimicrobial agents. The antimicrobial agent is simply mixed with the ethylene/vinyl acetate polymer during the fabrication of the funnel. The catheter surface itself does not carry any antimicrobial nor is it capable of preventing encrustation. U.S. Pat. No. 4,579,554 issued to Jacob Glassman discloses a design that provides for irrigation of the catheter tube. Frequent irrigation, however, could result in the damage of the mucus in the bladder.
U.S. Pat. No. 4,642,104 issued to Sakamoto et al. teaches the use of polymers carrying multicarboxyl, amino or sulfonic acid group capable of binding antibiotics through ion exchange. The ion exchange groups are chemically introduced into the molecules of the inside and outside wall of the urethral catheter by hydrolysis of certain functionalities that are present in the polymer that is coated on the surface of the catheter. Cationic antibiotics such as polymyxins or soap preparations such as benzalkonium chloride or benzethionium chloride, cyclohexidine or povidine-iodine remain on the surface due to the electrostatic binding. In order to introduce anionic groups on the surface of the catheter the surface has to be subjected to a series of chemical reactions and coatings, which could prove tedious and expensive.
U.S. Pat. No. 4,950,256 issued to Luther et al. teaches the use of an intravascular catheter comprising a cannula for insertion into a vascular system of a patient. This catheter is coated with a hydrophilic polyurethane-polyene composition for binding antithrombogenic materials and cationic polymyxin antibiotics. Luther et al., show that the absorption of the polymyxins into the hydrophilic polyurethane can be controlled by varying the initial concentrations, and the catheter is described as a time release intravascular catheter.
Amino phosphonates have been shown to prevent calcification of heart valves, and the process involves covalent bonding of the moieties to the biomaterial (C. L. Webb, et al., Trans. Am. Soc. Artif. Intern. Organs, XXXIV, 1851 1988!). Silver alloys (R. J. McLean et al., Can. J. Microbiol., 39 1993!; Liedberg and T. Lundberg, British Journal of Urology, 65, 379-381 1990!) have been reported to have been coated on urinary catheters and have been shown to be effective in preventing bacterial adherence.
The U.S. Pat. No. 5,295,979 teaches the use of two dissimilar metal coatings such as silver and platinum for creating an ionophoretic galvanic couple for driving silver ions in solution. This is achieved by sputtering a design of dots of the galvanic couple or by electroless plating of the successive metals.
Such coatings are hard to fabricate and require several manufacturing steps if multilayers are involved. The desired ratio of silver surface to volume for complete inhibition is about 25-50 square mm per mL of the growth medium. This is a difficult requirement to fulfill for a coating as the flow volumes are higher for urinary catheters.
The well publicized, ion-beam impregnated silver alloy catheters distributed by Spire Corporation do not provide protection in the lumen as the silver particles are embedded on the outside only. Also, these catheters do not protect against encrustation.
Recently, silver oxide coated Baxter catheters were clinically studied. The results showed that the catheters were not effective in preventing bacteriuria. Gram positive organisms were found to dominate (Riley et al., The American Journal of Medicine, 98, 349 1995!).
Polyethylene oxide coatings have been found to be bacteriostatic and protein-resistant (D. K. Han, S. Y. Jeong, and Y. H. Kim, et al., J. of Biomaterials Science, Polymer Edition, 4(6), 579-89 (1993) and the references therein). Such coatings do not have any antibacterial properties and have temporary anti adhesive properties. Biofilms eventually form on such coatings.
U.S. Pat. No. 5,328,954 issued to Sarangapani and assigned to the assignee of present application discloses a coating for medical applications which is resistant to encrustation and bacteria. While this coating is very effective for short term use when used on some materials, it is not as effective for long term uses. The coating uses high area carbon filler which emparts a blackish grey color to the coating. As a result, for the sake of cosmetic appearance colorants could not be used, while coating on latex or other white polymer devices.
It is therefore a principal object of the present invention to provide a catheter for use in urological surgery for long indwelling situations or for managing urinary incontinence which inhibits the build up of bacterial biofilm and encrustation on the surface of the catheter.
Another object of the present invention is to provide a catheter for use in urological surgery or provide materials for devices used for managing urinary incontinence which causes a lower risk of infection than known catheters.
Another object of this invention is to create an antibacterial surface by blending the additives such as organic acids, Silver and/or Platinum with a dissolved polymer, Titanium dioxide filler, or a prepolymer polyurethane followed by drying the solvent or by a direct melt blending method with the plastic.
Yet another object of this invention is to provide a combination of acidifying chelating compounds that partition between the plastic and the body fluids such as urine, to provide an acidic pH on the surface.

Encrustation and bacterial resistant coatings for medical applications


A method and apparatus for etchback profile control. The method includes performing a first etch through a first dielectric layer to form a first via and a second dielectric layer, filling the first via with a BARC material to form a first BARC layer, and performing a second etch on the first BARC layer to form a second BARC layer. The second etch has a first etch rate in a first peripheral region of the second BARC layer and a second etch rate in a first central region of the second BARC layer. The first peripheral region is located around a sidewall of the first via, and the first central region is located around a center of the first via. The first etch rate is larger than the second etch rate, and the first peripheral region is located higher than the first central region. A first top surface of the second BARC layer has substantially a first convex shape. Additionally, the method includes performing a third etch through a second dielectric layer to form a trench and a third BARC layer. The trench has a trench bottom surface, which is substantially free from any spike around a side surface of the third BARC layer. A second top surface of the third BARC layer has substantially a second convex shape. Moreover, the method includes removing the third BARC layer to form a second via.

The present invention is directed to integrated circuits and their processing for the manufacture of semiconductor devices. More particularly, the invention provides a method and apparatus for controlling etchback profile. Merely by way of example, the invention has been applied to making electrical connections between two metal levels. But it would be recognized that the invention has a much broader range of applicability.
Integrated circuits or "ICs" have evolved from a handful of interconnected devices fabricated on a single chip of silicon to millions of devices. Current ICs provide performance and complexity far beyond what was originally imagined. In order to achieve improvements in complexity and circuit density (i.e., the number of devices capable of being packed onto a given chip area), the size of the smallest device feature, also known as the device "geometry", has become smaller with each generation of ICs. Semiconductor devices are now being fabricated with features less than a quarter of a micron across.
Increasing circuit density has not only improved the complexity and performance of ICs but has also provided lower cost parts to the consumer. An IC fabrication facility can cost hundreds of millions, or even billions, of dollars. Each fabrication facility will have a certain throughput of wafers, and each wafer will have a certain number of ICs on it. Therefore, by making the individual devices of an IC smaller, more devices may be fabricated on each wafer, thus increasing the output of the fabrication facility. Making devices smaller is very challenging, as each process used in IC fabrication has a limit. That is to say, a given process typically only works down to a certain feature size, and then either the process or the device layout needs to be changed. An example of such a limit is to make reliable electrical connections between two metal layers with low resistance.
Fabrication of custom integrated circuits using chip foundry services has evolved over the years. Fabless chip companies often design the custom integrated circuits. Such custom integrated circuits require a set of custom masks commonly called "reticles" to be manufactured. A chip foundry company called Semiconductor International Manufacturing Company (SMIC) of Shanghai, China is an example of a chip company that performs foundry services. Although fabless chip companies and foundry services have increased through the years, many limitations still exist. For example, electrical contacts between two metal layers usually have limited reliability and conductivity. These and other limitations are described throughout the present specification and more particularly below.
FIGS. 1 through 6 are simplified diagrams for a conventional method of making an electrical contact between two metal layers. These diagrams are merely examples, which should not unduly limit the scope of the claims herein. The method includes process 110 for via etching, process 120 for BARC etchback, process 130 for trench etching, process 140 for ashing, process 150 for stop layer removal, and process 160 for trench and via filling. At process 110 for via etching, via 112 is fabricated through silicon oxynitride layer 114 and FSG layer 116. FSG is usually composed of silicon oxide and fluorine. Silicon oxynitride layer 114 is located on FSG layer 116. Via 112 has via bottom 113 formed by a portion of silicon nitride layer 118. Another portion of silicon nitride layer 118 lies under FSG layer 116. Silicon nitride layer 118 is deposited on the surface of metal layer 119. At process 120 for BARC etchback, a BARC layer fills via 112 and is then etched back to form BARC layer 122. BARC stands for bottom anti-reflection coating. The BARC material is a conventional type of photoresist. At process 130 for trench etching, BARC layer 122 is further etched back to form BARC layer 132. Additionally, a portion of silicon oxynitride layer 114 and a portion of FSG layer 116 are removed to form trench 134. Trench 134 has trench bottom 136, a portion of which is composed of BARC and another portion of which is composed of FSG. At process 140 for ashing, BARC layer 132 is removed from via 112. At process 150 for stop layer removal, the part of silicon nitride layer 118 that forms via bottom 113 is removed. Consequently, metal layer 119 is exposed within via 112 and trench 134. At process 160 for trench and via filling, via 112 and trench 134 are filled with conductive material, such as copper, to form conductive filling layer 162. Conductive filling layer 162 forms an electrical contact between metal layer 119 and metal layer 164. Part of metal layer 164 lies on the surface of silicon oxynitride layer 114. The electrical contact usually has limited conductivity and reliability.
Hence, it is desirable to improve technique for making an electrical contact.

Method for making an opening for electrical contact by etch back profile control

Semiconductor Manufacturing International (Shanghai) Corporation


A method and apparatus for making the weight load distribution more uniform over the surface of a processor die and improving the heat transfer between the processor die and a thermal spreader cap is provided. The apparatus includes generally a square-like box shaped thermal spreader cap having a cavity that conforms to the shape of the processor die. The thermal spreader cap fits over the processor die and has a cavity that is dome-like in shape. Additionally, the thermal spreader cap is attached to a thermal dissipative device which may in turn be connected to a heat sink. The apparatus provides a thinner and more uniform thermal interface layer between the processor die and the thermal spreader cap, thereby evening the weight load on the surface of the processor die and improving the heat flux between the processor die and the thermal spreader cap.

1. FIELD OF THE INVENTION
This invention relates generally to a thermal interface between a semiconductor device and a thermal spreader cap, and, more particularly, to a thermal spreader cap that has a complementary shaped surface to that of the semiconductor device.
2. DESCRIPTION OF THE RELATED ART
Microprocessor devices typically include a semiconductor device or silicon die attached to a substrate. The substrate may be formed from a variety of materials including ceramic and printed circuit boards. These surfaces are generally known as substrates, and the printed circuit-like boards are commonly referred to as organic substrates. Because of the different coefficients of thermal expansion between the silicon die and the substrate it is attached to, the die typically bows away from the substrate, and takes on a convex shape when the die becomes heated, such as during operations. When viewed from the side, this die resembles the "crown" on a curved road.
To assist in dissipating heat generated within the die, a thermal spreader cap is placed on top of or around the die. The thermal spreader cap may be in direct contact with the die, or the thermal spreader cap and the die may have a layer between them, which is referred to as a thermal interface layer. This thermal interface layer in turn may contain a thermal interface material, which is in contact with the die and the side of the thermal spreader cap facing the die. Typically, the thermal interface layer is a highly conductive material that dissipates heat away from the die to the thermal spreader cap.
Under the current approach, the side of the thermal spreader cap that is in direct contact with the die, or the thermal interface material, has a cavity that fits over the processor die, but does not conform to the shape of the processor die. Typically, the cavity is rectangular in shape and forms a box over the bowed die.
Because the typical thermal spreader cap has a box shaped cavity, each point on the surface of the bowed die varies in distance from the thermal spreader cap. Consequently, if there is a thermal interface layer, the thickness of the thermal interface material between the die and the thermal spreader cap varies across the surface of the die. That is, there is more thermal interface material between the thermal spreader cap and the die where the die is closer to the substrate, e.g., at the edges of the die attached to the substrate. Correspondingly, there is less thermal interface material over the portion of the die bowed farthest away from the substrate, e.g., at the center of the processor die.
As a result of the uneven thickness and volume of the thermal interface material, the heat from the die does not dissipate away from the die in a substantially uniform manner. There is an uneven heat flux to the thermal spreader cap from the die that negatively impacts the cooling of the die. Additionally, if the thermal interface material is a liquid, e.g., grease, oftentimes the thermal interface liquid pumps away from the portion of the die surface that is generating the greatest amount of heat. The hottest portion of the die is usually the "crown" of the bowed die, because the heat seeks to dissipate to the thermal spreader cap from the point on the die where there is the least thermal interface material between it and the thermal spreader cap. Therefore, the pumping away of the thermal interface material from this point reduces the heat dissipated from the die. In addition to creating heat dissipation problems, this uneven thickness and volume of thermal interface material also results in an uneven weight load distribution on the die.
The present invention is directed to overcoming, or at least reducing, the effects of one or more of the problems set forth above.

Emulative lid/heatspreader for processor die attached to an organic substrate


A substrate cleaning station includes a first index table supporting thereon at least three circumferentially spaced first substrate carriers on which hard disk substrates are mounted respectively. A substrate drying station includes a second index table disposed rearward of the first index table and supporting thereon at least three circumferentially spaced second substrate carriers on which cleaned hard disk substrate are mounted, respectively. Upon rotation of the first index table, each of the first substrate carriers moves successively through a substrate mounting position, a substrate cleaning position and a substrate removing position. Likewise, upon rotation of the second index table, each of the second substrate carriers moves through a substrate mounting position, a substrate drying position and a substrate removing position.

1. Field of the Invention
The present invention relates to an apparatus for cleaning and then drying the substrate of hard disks used in electronic equipment such as computers.
2. Description of the Prior Art
In recent years, with an increasing tendency to use hard disk drives in electronic equipment such as computers, the demand for quick, low cost production of such devices has increased.
As is well known, the substrate of a hard disk (often referred to simply as "substrate") must be cleaned and then dried after lapping and polishing are completed.
In a previously proposed substrate cleaning and drying machine used heretofore, a single substrate is fed into the machine and after cleaning and drying operations are completed, the substrate is removed from the machine and the next substrate is fed in. Following this, the foregoing cycle of operation is repeated. In other words, the substrates are loaded, cleaned, dried and removed, one at a time.
Accordingly, the prior cleaning and drying apparatus exhibits a relatively long processing time and hence a relatively low processing efficiency.

Apparatus for cleaning and drying hard disk substrates