In a magnetron for a microwave oven comprising a plurality of vanes as an anode and an antenna feeder mounted to the vanes, an antenna feeder fixing device comprising a plurality of radially spaced grooves formed at the upper surface of every other vane so that the antenna feeder is engaged with one of the grooves selected depending on the output of the magnetron. The antenna feeder fixing device can be applied to various models of magnetrons having different outputs, without changing the construction of vanes. This enables modular elements to be used for providing various models of magnetrons, irrespective of different outputs of magnetrons. Only one mold is needed for preparing a single vane construction having a plurality of grooves for various magnetron models, thereby enabling the manufacture cost to decrease.

1. Field of the Invention
The present invention relates to a magnetron for a microwave oven, and more particularly to an antenna feeder fixing device for such a magnetron.
2. Description of the Prior Art
Referring to FIG. 1, there is illustrated an example of a conventional magnetron for a microwave oven. FIG. 2 is a sectional view of a vacuum body of the magnetron shown in FIG. 1. As shown in FIGS. 1 and 2, the magnetron comprises a hollow cathode shield body 1 and a filament 2 disposed in the cathode shield body 1 and adapted to emit thermions. The cathode shield body 1 is disposed in a hollow magnetron body constituted by an upper member 5 of a plate shape and a lower member 6 of a cylindrical shape. The cathode shield body 1 also has upper and lower portions protruded beyond upper and lower members 5 and 6, respectively. To seal and support the cathode shield body 1, an A-seal member 3 and an F-seal member 4 are provided at the upper and lower portions of the cathode shield body 1. Around the filament 2, a plurality of vanes 7 are placed to receive microwave energy generated when the thermions emitted from the filament 2 are acceleratively rotated in an interaction spacer 9 which is defined between the wall of the cathode shield body i and the filament 2. The magnetron also comprises an antenna feeder 8 adapted as a microwave transfer path for guiding microwave energy received by the vanes 7 into a cooking chamber of the microwave oven. The antenna feeder 8 is supported to the upper member 5 of magnetron body by the A-seal member 3. In the magnetron body, upper and lower permanent magnets 10 and 10' are attached to upper and lower members 5 and 8, respectively, to generate a magnetic field. The magnetic field is transferred to the interaction space 9, by means of pole pieces 11 and 11'. Around the cathode shield body 1, a plurality of cooling fins 12 are disposed which function to release outwardly heat generated in the interaction space 9 and thus cool the interior of cathode shield body 1. Strap rings are also provided for adjusting frequencies of the thermions rotating acceleratively in the interaction space 9. The strap rings are fitted in strap grooves 25 formed at a desired portion of each vane 7. A center lead 17 and a side lead 18 are supported to the lower member 6 of magnetron body by means of the F-seal member 4 and extend downwardly beyond the cathode shield body 1. The central lead 17 and side lead 18 are connected at their one ends to both ends of the filament 2, respectively, so as to apply electric power to the filament 2. A choke coil 15 is also provided to remove conductive noise generated by lead current. To the other ends of leads 17 and 18, a through type condenser 14 is connected, which functions as a terminal making it possible to apply easily electric power from the external to the filament 2. The condenser 14 cooperates with the chock coil 15 to enhance a shield effect on conductive noise. Beneath the housing, a filter box 13 is disposed to surround the lower portion of the cathode shield body 1. The filter box 13 functions to remove radiation noise emitting through both the center lead 17 and the side lead 18.
In this conventional magnetron with the above-mentioned construction, a magnetic circuit is formed along the upper member 5, the lower member 8 and the pole pieces 11 and 11', by the electric field of permanent magnets 10 and 10' so that a magnetic field is generated in the interaction space 9. Under this condition, as electric power is applied to the filament 2 via the center lead 17 and the side lead 18, an electric field is generated between the filament 2 as a cathode and the vanes 7 as an anode, thereby causing the filament 2 to emit thermions which are, in turn, radiated into the interaction space 9. In the interaction space 9, the thermions conduct a cycloidal movement, that is, an accelerated rotation, by axial magnetic fluxes generated from the pole pieces 11 and 11' and an electric field generated between the filament 2 and the vanes 7. On the other hand, microwave energy transmitted to the vanes 7 is fed into the cooking chamber, via the antenna feeder 8 and a waveguide (not shown) of the oven, thereby heating the food placed in the cooking chamber.
On the other hand, it has been known that in the above-mentioned magnetron, the distance between the antenna feeder 8 and the wall of cathode shield body 1 is one of factors causing a variation in output of the magnetron. In this regard, various magnetrons having different outputs have been conventionally provided by varying the distance between the antenna feeder 8 and the wall of cathode shield body 1 according to the model of magnetron.
FIG. 3 is a plan view showing the cathode shield body and vanes of the conventional magnetron. On the other hand, FIG. 4 is a perspective view of the vanes of the conventional magnetron. As shown in FIGS. 3 and 4, a plurality of vanes 7 are formed to extend radially toward the central axis of the cathod shield body 1. Every other vane 7 has at its upper surface a groove 16 for engaging with the antenna feeder 8. Each vane 7 also has stepped strap grooves 25 at its upper and lower surfaces, respectively. In the stepped strap grooves 25, strap rings are fitted, respectively.
Each groove 16 is spaced apart from the inner wall surface of cathode shield body 1 by a constant distance d. As a result, the antenna feeder 8 which is engaged with the groove 16 is also spaced apart from the inner wall surface of cathode shield body 1 by the constant distance d.
It is known that the output of magnetron is increased upon an increase in the distance d and decreased upon a decrease in the distance d.
In the above-mentioned construction, however, there is a disadvantage that the distance d between the antenna feeder and the inner wall surface of cathode shield body 1 is always constant, because only one groove 16 is provided at the upper surface of every other vane 7 of the cathode shield body 1. As a result, this type of vanes 7 can not be applied to other models of magnetrons having different outputs.
That is, where a magnetron having a different output is desired to be manufactured, there is a requirement of a different type of vanes having different groove position. This causes a difficulty in using modular elements for providing various models of magnetrons. As a result, it is required to prepare various molds for forming respective vanes for various magnetron models, thereby causing the manufacture cost to increase.


In one embodiment, a method for testing a cable includes receiving a read-signal profile read at a receiving-end of a cable upon an initial test signal being input to a sending end of the cable, calculating a cross-correlation function between the read-signal profile and a matched filter output, and determining a peak value of the cross-correlation function. In another embodiment, a system includes a device, the device including logic for receiving a read-signal profile read at a receiving-end of the cable upon an initial test signal being input to a sending end of the cable, logic for calculating a cross-correlation function between the read-signal profile and a matched filter output, logic for determining a peak value of the cross-correlation function, and logic for storing the peak value to a computer readable medium. Other methods, systems, and computer program products are also described according to various embodiments.

Computer systems use cabling in order to transmit and receive information between peripherals, systems, users, sensors, etc. This cabling can take on many forms, including Universal Serial Bus (USB), Ethernet, coaxial, optical, etc. When large amounts of data and information is desired to be transmitted between two devices, Ethernet cabling is typically used. For even more data transmission capability, Fibre Channel over Ethernet (FCoE) may be used along with Ethernet cables.
FCoE is a transport protocol that enables Fibre Channel (FC) to be encapsulated and transmitted over Ethernet while being independent of the Ethernet forwarding scheme. FCoE allows seamless integration of Ethernet cabling with existing FC networks, hardware, and management software.
Ethernet is typically deployed in Server farms, data centers, large enterprise users, etc., for Transmission Control Protocol/Internet Protocol (TCP/IP) networks and FC is typically deployed for Storage Area Networks (SANs). FCoE typically can use two types of cables, copper cables and optical cables.
Copper cables for use with FCoE have different characteristics than optical cables for use with FCoE, and selecting which cable type to use in any given installation can be troublesome. For example, it may be difficult to determine whether copper cabling can handle the distance and data throughput required for a specific application. In another example, it may be difficult to determine if the cable itself has gone bad or if another device (such as a router, server, hub, etc.) in series has gone bad as opposed to the cable.
In medium to large sized hardware installations, there can be anywhere from thousands of feet of cables to miles of cables installed. Much of this installed cabling is, sometimes purposely, not easily accessible, e.g., it is behind walls, in ceilings, under floors, in bundles, etc. The purpose behind making this cabling inaccessible is that it is out of the way and does not obstruct other uses of the spaces, where the cabling might be installed and be accessible, along with a reduction in exposure of the cables to environmental factors. Another reason for installing the cabling in inaccessible areas is that the cabling, in many cases, needs to connect two or more remote systems, thereby allowing transmission between those systems, and these connections cannot be made in areas where environmental factors might disrupt, disconnect, or otherwise harm the cables or obstruct normal use of these areas. Note that for FCoE copper cables, they are typically available in 1 m, 3 m, or 5 m lengths and are generally used to connect to Top of Rack FCoE Fibre Channel Forwarders (FCFs). The FCoE copper cables are typically run within the racks and not under floors or behind walls.
Unfortunately, providing cabling in inaccessible or difficult to access areas also prevents maintenance from being performed on the cabling with any relative case. Cables, although not frequently, do fail and become less efficient at data transmission over time. Cables may also become disconnected, terminated, shorted, severed, or otherwise ineffective at transmitting information. In these cases, when a cable is to be tested to determine if it is transmitting information at an acceptable rate, it would be beneficial to have a method and/or system which can test these cables without requiring access to the entire run of the cable.

Matched filter testing of data transmission cables

International Business Machines Corporation


The present invention discloses a channel state information feedback method and apparatus. User equipment determines a PMI and a CQI, and a feedback expression manner of the PMI and the CQI, where the feedback expression manner includes a first or a second feedback expression manner, and sends the PMI and the CQI to a network device in the determined feedback expression manner of the PMI and the CQI, where the first feedback expression manner includes: using T CQI values to express CQI of M codewords, and using one PMI value to indicate one PMI, where T is less than M, and there is at least one CQI value that can express CQI of at least two codewords; and the second feedback expression manner includes: using M CQI values to express CQI of M codewords. The present invention may be applied to a scenario in which an antenna quantity increases.

In a Long Term Evolution (LTE) LTE/LTE-Advanced (LTE-A) system of the 3rd Generation Partnership Project (3GPP), Orthogonal Frequency Division Multiple Access (OFDMA) is used as a downlink multiple access mode, and therefore a downlink resource of the system is divided into OFDM symbols in terms of time, and is divided into subcarriers in terms of frequency. Each OFDM symbol has a Cyclic Prefix (CP). There are types of CPs: normal CP (normal CP) and extended CP (extended CP). When abase station schedules, in a downlink subframe, User Equipment (UE), that is, the base station needs to transmit, in the downlink subframe, downlink data to the UE, the minimum unit of a physical resource allocated to each UE is a Physical Resource Block (PRB). One PRB includes 12 subcarriers in a frequency domain, and is of half a subframe duration (that is, one timeslot) in a time domain, that is, includes seven OFDM symbols (if the normal CP is used) or six OFDM symbols (in a case in which the extended CP is used). One physical resource block pair includes 12 subcarriers in the frequency domain, and is of one subframe duration (that is, two timeslots) in the time domain.
Currently, in open-loop Multiple Input Multiple Output (MIMO) in the LTE R8, a maximum of four transmit antennas are supported. Rank-2, 3, or 4 transmission is supported. In open-loop MIMO, a Pre-coding Matrix Indicator (PMI) of a pre-coding matrix is not fed back; and when a rank (rank) is greater than or equal to 2, two channel coding codewords (codeword) are used to perform sending when a base station sends data. Four transmit antennas are used as an example; when sending data to UE, a base station performs, in a PRB pair that is scheduled to the UE, pre-coding by fixedly using, according to a rule, four pre-coding matrices of index numbers 12 to 15 rotationally. During feedback, Channel Quality Information (CQI) of only one codeword is fed back. In an open-loop mode, the reason that one piece of CQI may be fed back is that, in the open-loop MIMO mode, it is equivalent that layer shifting exists on adjacent subcarriers for two codewords, so that the two codewords pass through an approximately same channel, and therefore channel quality is also approximately the same. Therefore, CQI of one codeword may be used to express CQI of two codewords. For example, in rank-2 transmission (layers=2), on subcarriers n and n+1, pre-coding is performed by using a pre-coding matrix of an index 12. On the subcarrier n, codeword 1 is mapped to a first layer, codeword 2 is mapped to a second layer; however, on the subcarrier n+1, codeword 1 is mapped to the second layer, and codeword 1 is mapped to the first layer. Channels for adjacent subcarriers are basically the same, and therefore it may be considered that the two codewords pass through a same channel on the two subcarriers, and channel quality is also the same; therefore CQI of the two codewords may be expressed by using CQI of one codeword.
Currently, in LTE Rel.8/9/10/11, sending by using one, two, four, or eight antennas is supported in downlink transmission. In the closed-loop MIMO mode, Channel State Information (CSI) that User Equipment (UE) needs to feed back includes a rank indicator (rank indicator, RI), a PMI, CQI, and the like, where the RI and the PMI respectively indicate a layer quantity and a pre-coding matrix that the UE expects a base station to use to perform downlink data transmission. When the RI is greater than or equal to 2, two channel coding codewords (codeword) are used to perform sending when a base station sends data; in this case, an expression manner for CSI feedback by UE needs to include one PMI value, and CQI of two codewords. In the closed-loop MIMO mode, two codewords are mapped on a same subcarrier to different layers respectively; and a relationship of mapping, on all subcarriers, of either codeword to a layer, is the same, that is, no layer shifting exists. The two codewords pass through different channels; therefore CQI of the two codewords is independent from each other, and CQI of one codeword cannot be used to express the CQI of the two codewords. Therefore, the UE needs to separately feed back the CQI of the two codewords.
However, in the existing closed-loop MIMO mode, the expression manner for CSI feedback by UE is applicable if a quantity of configured antennas does not exceed eight; and when a quantity of downlink transmit antennas increases, for example, the quantity of downlink transmit antennas is 16, 32, or 64, no corresponding CSI feedback solution is provided in the prior art.

Channel state information feedback method and apparatus


The burn-in apparatus includes a water supply system and a sprayer and has a structure such that water is converted into mist and sprayed onto the upper surface of a device attached to a socket of a burn-in board. The amount of heat generated by the device that generates high heat is removed by the amount of heat that includes a large latent heat from when the mist falls on the upper surface and is evaporated. Burn-in of the device is conducted while it is being cooled to the target temperature.

The present invention relates to a burn-in apparatus capable of conducting cooling so as to obtain the target temperature of a semiconductor device that comprises a plane-like surface, generates heat when electric current is passed therethrough, has the temperature thereof rising to above the target temperature, and has the temperature of the surface rising.
A burn-in apparatus for semiconductor devices (referred to hereinbelow as "devices") is generally known in which a multiplicity of devices are mounted on burn-in boards, the boards are stacked in multiple stages in a temperature controlled chamber, electric current is passed through the devices, hot air with a temperature adjusted to the prescribed temperature, for example 125° C., is caused to flow parallel to the burn-in boards inside the chamber and circulate, while uniformly cooling the multiplicity of devices (see, for example, Patent References 1, 2, 3). With such a burn-in apparatus, in the case of conventional devices, the internal temperature of the devices generating heat when a current is passed therethrough is adjusted to a temperature appropriate for the burn-in test, which is about 150° C., in correspondence with the temperature of the circulating hot air and a burn-in test of the multiplicity of devices can be conducted with good efficiency.
Furthermore, Patent Reference 3 describes, as the conventional technology, that detecting the temperature inside the chamber and maintaining it at a constant level is insufficient for directly controlling the temperature of the device itself and, therefore, a diode is formed in a hollow space of a semiconductor chip and the junction temperature of the semiconductor chip is evaluated based on the electric characteristics of the diode (see the same Patent Reference 3).
Furthermore, the Patent Reference 3 also suggests a burn-in test apparatus in which a wiring section for temperature measurements is disposed over the entire integrated circuit section of each semiconductor chip, the average temperature of the chip is detected via a connection pad provided similarly to the connection pad for current supply to the integrated circuit section, the air with adjusted temperature is supplied from air-blow fans disposed in correspondence with each semiconductor chip in a temperature adjusting apparatus, and the air flow amount supplied to each chip is controlled so that the average temperature of the chip becomes the target burn-in temperature.
On the other hand, in recent years, devices generating a large amount of heat, for example, up to about 300 W when an electric current is passed therethrough, have appeared on the market and the burn-in apparatuses have to be adapted to conduct the burn-in test thereof. However, the above-described conventional apparatuses of a general hot air circulation system cannot be adapted for the above-mentioned devices generating a large amount of heat because the air is used therein as a heat transfer medium that has to remove a large amount of heat generated by the device when an electric current is passed therethrough and the air has a low specific gravity and specific heat and can remove but a small amount of heat. For this reason, the temperature of the circulating air is reduced, the blowing speed is raised, and the amount of air is increased to increase the amount of removed heat, but in this case the size of the apparatus itself is increased, a large difference in cooling effect is observed between the upstream and downstream zones of the circulating air, and the accuracy of burn-in temperature decreases. Moreover, even if all the aforementioned measures are taken, the amount of removed heat is still limited to about 30 W. For these reasons, such devices generating a large amount of heat cannot be burn-in tested with the apparatuses of the hot air circulation system.
Furthermore, in the apparatuses where the temperature of each chip is detected and the amount of cooling air supplied to each chip is controlled, the amount of blown air can be somewhat increased and the amount of removed heat can be increased, but because the cooling medium is air, no sufficient increase in the amount of removed heat can be attained and such apparatuses similarly cannot be adapted to burn-in test the devices that generate a large amount of heat.
A temperature control apparatus of an air injection system is known as another example of the apparatuses used, e.g., for burn-in testing the devices. In such an apparatus, air injection nozzles are disposed above and below each object and low-temperature air is ejected therefrom (see Patent Reference 4). In this apparatus, no problems are associated with temperature distribution among the devices even when the flow speed of the air is increased to increase the flow rate thereof, but because the heat transfer medium is air, the amount of the removed heat cannot be greatly increased for the same reasons as described above, and the apparatus cannot be adapted to devices generating a large amount of heat.
A temperature test apparatus is known as a burn-in apparatus using no hot air, wherein a multiplicity of electronic components, which are devices, are carried on a printed board serving as a burn-in board, a cooling plate having circulating therein a cooling liquid that is cooled in a water-cooled heat exchanger is brought into contact with the printed board, and the electronic components are temperature tested, while being cooled if necessary (see Patent Reference 5).
With this apparatus, the amount of heat removed by cooling can be increased because heat is taken from the electronic components to boil and evaporate the liquid coolant. However, in such an apparatus, the entire bottom surface of the plate is covered with the liquid coolant and heat enters only from the portion of this surface that is in contact with the electronic device. For this reason, heat transfer at the liquid coolant side is of a perfect film boiling and evaporation mode and, therefore, a substantially increased value of heat transfer coefficient of this surface portion cannot be obtained. Another problem associated with this apparatus is that because there is a difference between the pressure inside the plate and the external pressure, which is usually the atmospheric pressure, and because the plate surface area increases since all the electronic components have to be cooled with one plate, the plate thickness cannot be decreased and heat penetration ability cannot be improved. Yet another problem is that because the plate has a flat surface with high flexural rigidity, a sufficient contact with all the electronic components cannot be obtained due to the unavoidable small differences in level. Because of the aforementioned problems, cooling performance that enables a burn-in test of devices generating a large amount of heat cannot be obtained.
A cooling structure of mounted semiconductor chips is known in which each individual semiconductor chip is covered with a thick cap and solder joined, bellows having a property of mitigating thermal expansibility are disposed therebetween, a nozzle is disposed above each individual cap, a liquid coolant is supplied thereto from a coolant supply tube, the coolant liquid is atomized by the nozzle and blown onto the cap, the heat generated by the semiconductor chip is passed through the cap that covers it and is absorbed by the coolant, the coolant is evaporated by the heat and released from a release vent, the gas obtained is cooled in a refrigerator to convert it into liquid, and this liquid is again supplied to the coolant supply tube, this cooling structure making it possible to remove the heat from the mounted semiconductor chips with good efficiency (see Patent Reference 6).
With this type of cooling structure, there is no need to attach or detach a device for the purpose of cooling as is the case with a burn-in apparatus, and so the semiconductor chip and the cap are joined; therefore, this structure cannot be used as a burn-in apparatus.
[Patent Reference 1] Japanese Patent Application Laid-open No. H8-211122 (FIG. 1 and relevant explanation in the specification).
[Patent Reference 2] Japanese Patent Application Laid-open No. H 11-231943 (FIG. 1 and Par. No. 25 in the specification).
[Patent Reference 3] Japanese Patent Application Laid-open No. 2000-97990 (FIG. 4 and Par. Nos. 3, 4; FIGS. 1 and 2 and relevant explanation in the specification).
[Patent Reference 4] Japanese Patent Application Laid-open No. H4-321113 (FIG. 1 and relevant explanation in the specification).
[Patent Reference 5] Japanese Utility Model Application Laid-open No. S61-114377 (FIG. 1 and relevant explanation in the specification).
[Patent Reference 6] Japanese Patent Application Laid-open No. H4-61259 (FIG. 1 and relevant explanation in the specification).


There is provided inter alia a compound of formula (I):

Hepatitis C
Hepatitis C virus (HCV) is a positive strand RNA virus, and infection is a leading cause of post-transfusional hepatitis. HCV is the most common chronic blood borne infection, and the leading cause of death from liver disease in United States. The World Health Organization estimates that there are more than 170 million chronic carriers of HCV infection, which is about 3% of the world population. Among the un-treated HCV-infected patients, about 70%-85% develop chronic HCV infection, and are therefore at high risk to develop liver cirrhosis and hepatocellular carcinoma. In developed countries, 50-76% of all cases of liver cancer and two-thirds of all liver transplants are due to chronic HCV infection (Manns et al, 2007).
In addition to liver diseases, chronically infected patients may also develop other chronic HCV-related diseases, and serve as a source of transmission to others. HCV infection causes non-liver complications such as arthralgias (joint pain), skin rash, and internal organ damage predominantly to the kidney. HCV infection represents an important global health-care burden, and currently there is no vaccine available for hepatitis C (Strader et al., 2004; Jacobson et al. 2007; Manns et al., 2007; Pawlotsky, 2005; Zeuzem & Hermann, 2002).
Treatment of HCV
The current standard of care (SoC) is subcutaneous injections of pegylated interferon-α (pIFNα) and oral dosing of the antiviral drug ribavirin for a period of 24-48 weeks. Success in treatment is defined by sustained virologic response (SVR), which is defined by absence of HCV RNA in serum at the end of treatment period and 6 months later. Overall response rates to SoC depend mainly on genotype and pretreatment HCV RNA levels. Patients with genotype 2 and 3 are more likely to respond to SoC than patients infected with genotype 1 (Melnikova, 2008; Jacobson et al., 2007).
A significant number of HCV patients do not respond adequately to the SoC treatment, or cannot tolerate the therapy due to side effects, leading to frequent issues with completion of the full course. The overall clinical SVR rate of SoC is only around 50% (Melnikova, 2008). Development of resistance is another underlying factor for failure of treatment (Jacobson et al. et al. 2007). SoC is also contraindicated in some patients who are not considered candidates for treatment, such as patients with past significant episodes of depression or cardiac disease. Side effects of the SoC, which frequently lead to discontinuation of treatment, include a flu-like illness, fever, fatigue, haematological disease, anemia, leucopaenia, thrombocytopaenia, alopecia and depression (Manns et al., 2007).
Considering the side effects associated with the lengthy treatments using SoC, development of resistance, and suboptimum overall rate of success, more efficacious and safer new treatments are urgently needed for treatment of HCV infection. The objectives of new treatments include improved potency, improved toxicity profile, improved resistance profile, improved quality of life and the resulting improvement in patient compliance. HCV has a short life cycle and therefore development of drug resistance during drug therapy is common.
Novel, specifically targeted antiviral therapy for hepatitis C(STAT-C) also known as direct acting antiviral (DAA) drugs are being developed that target viral proteins such as viral RNA polymerase NS5B or viral protease NS3 (Jacobson et al, 2007; Parfieniuk et al., 2007). In addition, novel compounds also are being developed that target human proteins (e.g. cyclophilins) rather than viral targets, which might be expected to lead to a reduction in incidence of resistance during drug therapy (Manns et al., 2007; Pockros, 2008; Pawlotsky J-M, 2005).
Cyclophilin Inhibitors
Cyclophilins (CyP) are a family of cellular proteins that display peptidyl-prolyl cis-trans isomerase activity facilitating protein conformation changes and folding. CyPs are involved in cellular processes such as transcriptional regulation, immune response, protein secretion, and mitochondrial function. HCV virus recruits CyPs for its life cycle during human infection. Originally, it was thought that CyPs stimulate the RNA binding activity of the HCV non-structural protein NS5B RNA polymerase that promotes RNA replication, although several alternative hypotheses have been proposed including a requirement for CyP PPlase activity. Various isoforms of CyPs, including A and B, are believed to be involved in the HCV life cycle (Yang et al., 2008; Appel et al., 2006; Chatterji et al., 2009; Gaither et al., 2010). The ability to generate knockouts in mice (Colgan et al., 2000) and human T cells (Braaten and Luban, 2001) indicates that CyPA is optional for cell growth and survival. Similar results have been observed with disruption of CyPA homologues in bacteria (Herrler et al., 1994), Neurospora (Tropschug et al., 1989) and Saccharomyces cerevisiae (Dolinski et al. 1997). Therefore, inhibiting CyPs represent a novel and attractive host target for treating HCV infection, and a new potential addition to current SoC or STAT-C/DAA drugs, with the aim of increasing SVR, preventing emergence of resistance and lowering treatment side effects.

Cyclosporine A (Inoue et al. 2003) ("CsA") and its closely structurally related non-immunosuppressive clinical analogues DEBIO-025 (Paeshuyse et al. 2006; Flisiak et al. 2008), NIM811 (Mathy et al. 2008) and SCY-635 (Hopkins et al., 2009) are known to bind to cyclophilins, and as cyclophilin inhibitors have shown in vitro and clinical efficacy in the treatment of HCV infection (Crabbe et al., 2009; Flisiak et al. 2008; Mathy et al. 2008; Inoue et al., 2007; Ishii et al., 2006; Paeshuyse et al., 2006). Although earlier resistance studies on CsA showed mutations in HCV NS5B RNA polymerase and suggested that only cyclophilin B would be involved in the HCV replication process (Robida et al., 2007), recent studies have suggested an essential role for cyclophilin A in HCV replication (Chatterji et al. 2009; Yang et al., 2008). Considering that mutations in NS5A viral protein are also associated with CsA resistance and that NS5A interacts with both CyPA and CypB for their specific peptidyl-prolyl cis/trans isomerase (PPlase) activity, a role for both cyclophilins in viral life cycle is further suggested (Hanoulle et al., 2009).
The anti-HCV effect of cyclosporine analogues is independent of the immunosuppressive property, which is dependent on calcineurin. This indicated that the essential requirement for HCV activity is CyP binding and calcineurin binding is not needed. DEBIO-025, the most clinically advanced cyclophilin inhibitor for the treatment of HCV, has shown in vitro and in vivo potency against the four most prevalent HCV genotypes (genotypes 1, 2, 3, and 4). Resistance studies showed that mutations conferring resistance to DEBIO-025 were different from those reported for polymerase and protease inhibitors, and that there was no cross resistance with STAT-C/DAA resistant viral replicons. More importantly, DEBIO-025 also prevented the development of escape mutations that confer resistance to both protease and polymerase inhibitors (Crabbe et al., 2009).
However, the CsA-based cyclophilin inhibitors in clinical development have a number of issues, which are thought to be related to their shared structural class, including: certain adverse events that can lead to a withdrawal of therapy and have limited the clinical dose levels; variable pharmacokinetics that can lead to variable efficacy; and an increased risk of drug-drug interactions that can lead to dosing issues.
The most frequently occurring adverse events (AEs) in patients who received DEBIO-025 included jaundice, abdominal pain, vomiting, fatigue, and pyrexia. The most clinically important AEs were hyperbilirubinemia and reduction in platelet count (thrombocytopaenia). Peg-IFN can cause profound thrombocytopaenia and combination with DEBIO-025 could represent a significant clinical problem. Both an increase in bilirubin and decrease in platelets have also been described in early clinical studies with NIM-811 (Ke et al., 2009). Although the hyperbilirubinemia observed during DEBIO-025 clinical studies was reversed after treatment cessation, it was the cause for discontinuation of treatment in 4 out of 16 patients, and a reduction in dose levels for future trials. As the anti-viral effect of cyclophilin inhibitors in HCV is dose related, a reduction in dose has led to a reduction in anti-viral effect, and a number of later trials with CsA-based cyclophilin inhibitors have shown no or poor reductions in HCV viral load when dosed as a monotherapy (Lawitz et al., 2009; Hopkins et al., 2009; Nelson et al., 2009). DEBIO-025 and cyclosporine A are known to be inhibitors of biliary transporters such as bile salt export pumps and other hepatic transporters (especially OAT1B1/OAT1B3/MRP2/MRP3/cMOAT/ABCC2) (Crabbe et al., 2009). It has been suggested that the interaction with biliary transporters, in particular MRP2, may be the cause of the hyperbilirubinaemia seen at high dose levels of DEBIO-025 (Nelson et al., 2009, Wring et al., 2010). CsA class-related drug-drug interactions (DDIs) via inhibition of other drug transporters such as P-glycoprotein (Pgp/MDR1), BSEP, OAT1B1 and OAT1B3 (Konig et al., 2010) may also be a concern, potentially limiting certain combinations and use in some patients undergoing treatment for co-infections such as HIV (Seden et al., 2010).
Moreover, DEBIO-025 and cyclosporine A are substrates for metabolism by cytochrome P450 (especially CYP3A4), and are known to be substrates and inhibitors of human P-glycoprotein (MDR1) (Crabbe et al., 2009). Cyclosporine A has also been shown to be an inhibitor of CYP3A4 in vitro (Niwa et al., 2007). This indicates that there could be an increased risk of drug-drug interactions with other drugs that are CYP3A4 substrates, inducers or inhibitors such as for example ketoconazole, cimetidine and rifampicin. In addition, interactions are also expected with drugs that are subject to transport by P-glycoprotein (e.g. digoxin), which could cause severe drug-drug interactions in HCV patients receiving medical treatments for other concomitant diseases (Crabbe et al. 2009). CsA is also known to have highly variable pharmacokinetics, with early formulations showing oral bioavailability from 1-89% (Kapurtzak et al., 2004). Without expensive monitoring of patient blood levels, this can lead to increased prevalence of side effects due to increased plasma levels, or reduced clinical response due to lowered plasma levels.
Considering that inhibition of cyclophilins represent a promising new approach for treatment of HCV, there is a need for discovery and development of more potent and safer CyP inhibitors for use in combination therapy against HCV infection.
Sanglifehrins
Sanglifehrin A (SfA) and its natural congeners belong to a class of mixed non-ribosomal peptide/polyketides, produced by Streptomyces sp. A92-308110 (also known as DSM 9954) (see WO 97/02285), which were originally discovered on the basis of their high affinity to cyclophilin A (CyPA). SfA is the most abundant component in fermentation broths and exhibits approximately 20-fold higher affinity for CyPA compared to CsA. This has led to the suggestion that sanglifehrins could be useful for the treatment of HCV (WO2006/138507). Sanglifehrins have also been shown to exhibit a lower immunosuppressive activity than CsA when tested in vitro (Sanglier et al., 1999; Fehr et al., 1999). SfA binds with high affinity to the CsA binding site of CyPA (Kallen et al., 2005).
Biosynthesis of Sanglifehrins
Sanglifehrins are biosynthesised by a mixed polyketide synthase (PKS)/Non-ribosomal peptide synthetase (NRPS) (see WO2010/034243). The 22-membered macrolide backbone consists of a polyketide carbon chain and a tripeptide chain. The peptide chain consists of one natural amino acid, valine, and two non-natural amino acids: (S)-meta-tyrosine and (S)-piperazic acid, linked by an amide bond. Hydroxylation of phenylalanine (either in situ on the NRPS or prior to biosynthesis) to generate (S)-meta-tyrosine is thought to occur via the gene product of sfaA.
Immunosuppressive Action of Sanglifehrins
The immunosuppressive mechanism of action of SfA is different to that of other known immunophilin-binding immunosuppressive drugs such as CsA, FK506 and rapamycin. SfA does not inhibit the phosphatase activity of calcineurin, the target of CsA (Zenke et al. 2001), instead its immunosuppressive activity has been attributed to the inhibition of interleukin-6 (Hartel et al., 2005), interleukin-12 (Steinschulte et al., 2003) and inhibition of interleukin-2-dependent T cell proliferation (Zhang & Liu, 2001). However, the molecular target and mechanism through which SfA exerts its immunosuppressive effect is hitherto unknown.
The molecular structure of SfA is complex and its interaction with CyPA is thought to be mediated largely by the macrocyclic portion of the molecule. In fact, a macrocyclic compound (hydroxymacrocycle) derived from oxidative cleavage of SfA has shown strong affinity for CyPA (Sedrani et al., 2003). X-ray crystal structure data has shown that the hydroxymacrocycle binds to the same active site of CyPA as CsA. Analogues based on the macrocycle moiety of SfA have also previously been shown to be devoid of immunosuppressive properties (Sedrani et al., 2003), providing opportunity for design of non-immunosuppressive CyP inhibitors for potential use in HCV therapy.
Converse to this, there is also an opportunity to develop immunosuppressive agents with low toxicity for use in such areas as prophylaxis of transplant rejection, autoimmune, inflammatory and respiratory disorders, including, but not limited to, Crohn's disease, Behcet syndrome, uveitis, psoriasis, atopic dermatitis, rheumatoid arthritis, nephritic syndrome, aplastic anaemia, biliary cirrhosis, asthma, pulmonary fibrosis, chronic obstructive pulmonary disease (COPD) and celiac disease. Sanglifehrins have been shown to have a novel mechanism of immunosuppressive activity (Zenke et al., 2001), potentially acting through dendritic cell chemokines (Immecke et al., 2011), and there is therefore an opportunity to develop agents with a mechanism of action different to current clinical agents, such as cyclosporine A, rapamycin and FK506. Sanglifehrin A has been shown to be 10 fold less potent than Cyclosporine A, so the ideal novel agent would have improved potency and/or therapeutic window.
Other Therapeutic Uses of Cyclophilin Inhibitors
Human Immunodeficiency Virus (HIV)
Cyclophilin inhibitors, such as CsA and DEBIO-025 have also shown potential utility in inhibition of HIV replication. The cyclophilin inhibitors are thought to interfere with function of CyPA during progression/completion of HIV reverse transcription (Ptak et al., 2008). However, when tested clinically, DEBIO-025 only reduced HIV-1 RNA levels and >1 log 10 copies/mL in nine and two patients respectively, whilst 27 of the treated patients showed no reduction in HIV-1 RNA levels (Steyn et al., 2006). Following this, DEBIO-025 was trialled in HCV/HIV coinfected patients, and showed better efficacy against HCV, and the HIV clinical trials were discontinued (see Watashi et al., 2010).
Treatment of HIV
More than 30 million people are infected by HIV-1 worldwide, with 3 million new cases each year. Treatment options have improved dramatically with the introduction of highly active antiretroviral therapy (HAART) (Schopman et al., 2010), By 2008, nearly 25 antiretroviral drugs had been licensed for treatment of HIV-1, including nine nucleoside reverse transcriptase inhibitors (NRTI), four non-nucleoside reverse transcriptase inhibitors (NNRTI), nine protease inhibitors (PI), one fusion inhibitor, one CCR5 inhibitor and one integrase inhibitor (Shafer and Schapiro, 2008). However, none of these current regimens leads to complete viral clearance, they can lead to severe side effects and antiviral resistance is still a major concern. Therefore, there still remains a need for new antiviral therapies, especially in mechanism of action classes where there are no approved drugs, such as is the case for cyclophilin inhibitors.
Hepatitis B Virus
Hepatitis B is a DNA virus of the family hepadnaviridae, and is the causative agent of Hepatitis B. As opposed to the cases with HCV and HIV, there have been very few published accounts of activity of cyclophilin inhibitors against Hepatitis B virus. Ptak et al. 2008 have described weak activity of Debio-025 against HBV (IC50 of 4.1 μM), whilst Xie et al., 2007 described some activity of CsA against HBV (IC50>1.3 μg/mL). This is in contrast to HIV and HCV, where there are numerous reports of nanomolar antiviral activity of cyclophilin inhibitors.
Treatment of HBV
HBV infects up to 400 million people worldwide and is a major cause of chronic viral hepatitis and hepatocellular carcinoma. As of 2008, there were six drugs licensed for the treatment of HBV; interferon alpha and pegylated interferon alpha, three nucleoside analogues (lamivudine, entecavir and telbivudine) and one nucleotide analogue (adefovir dipivoxil). However, due to high rates of resistance, poor tolerability and possible side effects, new therapeutic options are needed (Ferir et al., 2008).
Inhibition of the Mitochondrial Permeability Transition Pore (mPTP)
Opening of the high conductance permeability transition pores in mitochondria initiates onset of the mitochondrial permeability transition (MPT). This is a causative event, leading to necrosis and apoptosis in hepatocytes after oxidative stress, Ca2+ toxicity, and ischaemia/reperfusion. Inhibition of Cyclophilin D (also known as Cyclophilin F) by cyclophilin inhibitors has been shown to block opening of permeability transition pores and protects cell death after these stresses. Cyclophilin D inhibitors may therefore be useful in indications where the mPTP opening has been implicated, such as muscular dystrophy, in particular Ullrich congenital muscular dystrophy and Bethlem myopathy (Millay et al., 2008, WO2008/084368, Palma et al., 2009), multiple sclerosis (Forte et al., 2009), diabetes (Fujimoto et al., 2010), amyotrophic lateral sclerosis (Martin 2009), bipolar disorder (Kubota et al., 2010), Alzheimer's disease (Du and Yan, 2010), Huntington's disease (Perry et al., 2010), recovery after myocardial infarction (Gomez et al., 2007) and chronic alcohol consumption (King et al., 2010).
Further Therapeutic Uses
Cyclophilin inhibitors have potential activity against and therefore in the treatment of infections of other viruses, such as Varicella-zoster virus (Ptak et al., 2008), Influenza A virus (Liu et al., 2009), Severe acute respiratory syndrome coronavirus and other human and feline coronaviruses (Chen et al., 2005, Ptak et al., 2008), Dengue virus (Kaul et al., 2009), Yellow fever virus (Qing et al., 2009), West Nile virus (Qing et al., 2009), Western equine encephalitis virus (Qing et al., 2009), Cytomegalovirus (Kawasaki et al., 2007) and Vaccinia virus (Castro et al., 2003).
There are also reports of utility of cyclophilin inhibitors and cyclophilin inhibition in other therapeutic areas, such as in cancer (Han et al., 2009).
General Comments on Sanglifehrins
One of the issues in drug development of compounds such as sanglifehrins is rapid metabolism and glucuronidation, leading to low oral bioavailability. This can lead to an increased chance of food effect, more frequent incomplete release from the dosage form and higher interpatient variability.
Therefore there remains a need to identify novel cyclophilin inhibitors, which may have utility, particularly in the treatment of HCV infection, but also in the treatment of other disease areas where inhibition of cyclophilins may be useful, such as HIV infection, Muscular Dystrophy or aiding recovery after myocardial infarction or where immunosuppression or anti-inflammatory effect is useful. Preferably, such cyclophilin inhibitors have improved properties over the currently available cyclophilin inhibitors, including one or more of the following properties: longer half-life or increased oral bioavailability, possibly via reduced P450 metabolism and/or reduced glucuronidation, improved water solubility, improved potency against HCV, reduced toxicity (including hepatotoxicity), improved pharmacological profile, such as high exposure to target organ (e.g. liver in the case of HCV) and/or long half life (enabling less frequent dosing), reduced drug-drug interactions, such as via reduced levels of CYP3A4 metabolism and inhibition and reduced (Pgp) inhibition (enabling easier multi-drug combinations) and improved side-effect profile, such as low binding to MRP2, leading to a reduced chance of hyperbilirubinaemia, lower immunosuppressive effect, improved activity against resistant virus species, in particular CsA and CsA analogue (e.g. DEBIO-025) resistant virus species and higher therapeutic (and/or selectivity) index. The present invention discloses a novel sanglifehrin analogue which may have one or more of the above properties. In particular, the present invention discloses a novel mutasynthetic sanglifehrin analogue, which is anticipated to have reduced metabolism via P450 or glucuronidation, for example as shown by increased microsome half-life and/or reduced improved potency against HCV, for example as shown by a low replicon EC50.
In addition, there is also a need to develop a novel immunosuppressive agent, which may have utility in the prophylaxis of transplant rejection, or in the treatment of autoimmune, inflammatory and respiratory disorders. Preferably, such an immunosuppressant will have improved properties over the known natural sanglifehrins, including one or more of the following properties: longer half-life or increased oral bioavailability, possibly via reduced P450 metabolism and/or reduced glucuronidation, improved water solubility, improved potency in immunosuppressive activity, such as might be seen in T-cell proliferation assays, reduced toxicity (including hepatotoxicity), improved pharmacological profile, such as high exposure to target organ and/or long half-life (enabling less frequent dosing), reduced drug-drug interactions, such as via reduced levels of CYP3A4 metabolism and inhibition and reduced (Pgp) inhibition (enabling easier multi-drug combinations) and improved side-effect profile. The present invention discloses a novel sanglifehrin analogue which may have one or more of the above properties. In particular, the present invention discloses a novel derivative, which has reduced metabolism via P450 or glucuronidation, for example as shown by increased microsome half-life and/or improved immunosuppressive potency, for example as shown by a low t-cell proliferation IC50.
Thus, as can be seen from the Examples, the compound of the invention has the following favourable therapeutically relevant properties:                improved antiviral potency against HCV and HIV as compared with the prior art cyclophilin inhibitors Cyclosporin A, DEBIO-025 (alisporivir) and Sanglifehrin A;        reduced clearance and increased oral expose as compared with the prior art compound Sanglifehrin A;        more potent inhibition of CypA PPlase activity as compared with the prior art cyclophilin inhibitors Cyclosporin A, DEBIO-025 (alisporivir) and Sanglifehrin A;        improved side effect profile and reduced drug-drug interactions as demonstrated by reduced inhibition of bilirubin transporters (OATP-1B1, OATP-1B3, MRP2 and MRP3) and reduced inhibition of xenobiotic transporters (Pgp and BSEP).

This patent is subject to a terminal disclaimer.

Abstract: for use in treatment of viral infection or as an immunosuppressant.


Systems and methods are directed to an air handler that reduces noise without reducing the pressure of air supplied to a space below minimum levels. The air handler includes a plenum forming a passageway for air. The plenum has a return side, a supply side, a fan within the plenum having a suction side and a pressure side to move air through the plenum, and a conditioning apparatus in the plenum for conditioning air through the plenum. The air handler further includes a sound-attenuating panel having a first side and an opposed second side that extend at least partially across the plenum. The panel is configured and positioned to interact with the flow of air to attenuate sound. The fan provides a pressure boost to air flowing through the plenum to counteract a pressure drop resulting from interaction between the air, the panel, and the conditioning apparatus.

The application relates generally to sound reduction in an air handler for a heating, ventilating, air conditioning and refrigeration (HVAC&R) systems. The application relates more specifically to a panel in an air handler that attenuates sound.
Air handlers are used to supply large volumes conditioned air to an enclosed space, such as living spaces or work spaces in commercial environments. The large volumes of conditioned air, much of which may be recycled, are supplied and removed with large air movers, such as fans within the air handler. Further, the conditioned air must be supplied to the enclosed space by the air handler at a minimum pressure. One of the problems encountered with such air handlers is the generation of undesirable or excessive noise. Various schemes have been used to reduce the noise from air handlers including the addition of components to reduce noise that increase the size and complexity of the air handler, but which reduce the efficiency of the air handler due to associated reductions in pressure.
HVAC&R systems include at least one of a heating source and a cooling source in heat exchange communication with an air handler and an air distribution system. Heat exchange communication means that fluid from the heating source or the cooling source can exchange heat with air flowing in the air handler by either heating or cooling the air, without mixing with the air flowing in the air handler. The air distribution system includes a series of inlets, such as vents, and outlets, such as diffusers or terminals, connected to ducts that remove air from enclosed space of the building and returns the air to the enclosed space of the building, the air distribution system being in fluid communication with the air handler. The enclosed space of the building may be subdivided into a series of zones, rooms offices or combinations thereof that comprise the building space, each in fluid communication with the air distribution system through the vents, terminals or diffusers connected to the ducts in fluid communication with each of the zones, rooms or offices. As used herein, the enclosed space of the building, or simply building space, refers to the living or workspace within a building that comprises the building environment, which is subdivided into zones. The air distribution system provides air from the building space to the air handler where the air may be conditioned prior to being returned to the building space. While the air distribution system is in direct fluid communication with the building space to remove air (return air) and provide air (supply air) to the building space, the air handler may be located outside of the conditioned area. The air handler may be centrally located within the building space or remotely located outside of the building space. The air handler includes at least one conditioning apparatus in the plenum for conditioning air passing through the plenum, usually a coil for cooling and heating.
Intended advantages of the disclosed systems and/or methods satisfy one or more of these needs or provide other advantageous features. Other features and advantages will be made apparent from the present specification. The teachings disclosed extend to those embodiments that fall within the scope of the claims, regardless of whether they accomplish one or more of the aforementioned needs.

Sound attenuating air handler panel apparatus and method


The present invention relates to a biaxially oriented polyester film for magnetic recording medium having a thickness of thinner than 7 .mu.m and satisfying the formula ##EQU1##. wherein .alpha.t (.times.10.sup.-6 /.degree. C.) is the thermal expansion coefficient of the film in transversal direction, .alpha.h (.times.10.sup.-6 /%RH) is the humidity expansion coefficient in transversal direction and P (ppm/g) is the transversal shrinkage of the film under the load (grams) applied to the film in machine direction. It has thin film thickness, excellent dimensional stability and small dimensional change in the direction of width (transversal direction) especially under a load in the direction of the length of the film (machine direction) and useful as a magnetic recording medium, especially a digital data storage tape generating little error in magnetic recording and reproduction, free from the generation of error rate caused by track shift and having excellent output characteristics.

Polyester films are widely used in the fields of magnetic recording medium, electrical insulation material, packaging material, etc., owing to the excellent thermal and mechanical properties.
The development of a magnetic recording medium of digital recording system is recently in progress to enable the recording and reproduction of picture and sound in improved quality compared with conventional analog recording system. The recent progress of the medium for the digital recording system aims at high capacity, high recording density, long recording time and compact-sized cassette as well as high picture quality and sound quality and the requirement on the properties of the base film is increasing according to the improvement of the above qualities.
It is necessary to decease the thickness of a magnetic tape and, accordingly, the thickness of a base film for prolonging the recording time and reducing the cassette size. However, the rigidity of a tape decreases with decreasing thickness of a magnetic tape to deteriorate the contact of the tape with a magnetic head in recording and reproduction, which makes difficult to get high picture quality and sound quality.
The track pitch is selected to be extremely narrow especially in the data-storage use adopting a linear track system such as QIC (Quarter Inch Cartridge) and DLT (Digital Liner Tape) for getting high capacity and high density. The narrow track pitch produces a problem of error by the shift of track caused by the dimensional change in the transversal direction of the tape.
These dimensional changes are supposed to be caused by the changes in the temperature and humidity in the use of the magnetic tape and the variation of tape width induced by the variation of the transport tension of the tape inherent to the recent compact-sized drive. The extent of the influence of each factor is not yet clear to produce a problem in the case of increasing the capacity and density of a magnetic tape.

Biaxially oriented polyester film for magnetic recording media


The present technology relates to novel methods for converting algal biomass material for the production of carbon-based chemicals, in particular carboxylic acids like lactic acid using extremely thermophilic microorganisms.

In general, fermentation products are produced by degradation of starch-containing material into fermentable sugars by liquefaction and saccharification followed by conversion of the sugars directly or indirectly into the desired fermentation product using a fermenting organism.
For example, many carboxylic acids are produced industrially on a large scale. They are also pervasive in nature. Carboxylic acids are used in the production of polymers, pharmaceuticals, solvents, and food additives. Industrially important carboxylic acids include acetic acid (component of vinegar, precursor to solvents and coatings), acrylic and methacrylic acids (precursors to polymers, adhesives), adipic acid (polymers), citric acid (beverages), ethylenediaminetetraacetic acid (chelating agent), fatty acids (coatings), maleic acid (polymers), propionic acid (food preservative), terephthalic acid (polymers). Lactic acid is widely used in food, pharmaceutical and textile industries. It is also used as a source of lactic acid polymers which are being used as biodegradable plastics. The physical properties and stability of polylactides can be controlled by adjusting the proportions of the L(+)- and D(−)-lactides. Optically pure lactic acid is currently produced by the fermentation of glucose derived from corn starch using various lactic bacteria (Kenji Okano, Qiao Zhang, Satoru Shinkawa, Shogo Yoshida, Tsutomu Tanaka, Hideki Fukuda, and Akihiko Kondo (2009). Efficient production of optically pure D-lactic acid from raw corn starch by using a genetically modified L-lactate dehydrogenase gene-deficient and -amylase-secreting Lactobacillus plantarum strain. Applied and Environmental Microbiology, 75, 462-467).
However, the lactic bacteria have complex nutritional requirements and the use of corn as the feedstock competes directly with the food and feed.
Feedstocks not competing directly with food and feed are naturally resistant lignocellulosic biomass. Lignocellulose is the non edible part of plants. Using lignocellulose to produce carboxylic acid avoids competition with the food industry. Lignocellulose is the most abundant renewable biomass. The yield of lignocellulose can reach approximately 200 billion metric tons worldwide per year (Zhang, Y. H. P., S. Y. Ding, J. R. Mielenz, J. B. Cui, R. T. Elander, M. Laser, M. E. Himmel, J. R. McMillan, and L. R. Lynd. (2007). Fractionating Recalcitrant Lignocellulose at Modest Reaction Condition. Biotechnology and Bioengineering. 97(2):214-23). Lignocellulose is a feedstock with a low production cost. Lignocellulose can be found everywhere and is available as waste biomass, including agricultural residues (wheat straw, sugarcane bagasse, and corn stover), energy crops (switch grass), and municipal solid waste (paper and paperboard products) (Hamelinck, C. N., V. H. Geertje, and A. P. C. Faaij. (2005). Ethanol from Lignocellulosic Biomass: Techno-Economic Performance in Short-, Middle- and Long-Term." Biomass and Bioenergy 28(4):384-410.).
However, the characteristics of lignocellulose have different disadvantages for the usage as feedstock not competing with food and feed. Because lignocellulose is mainly made up of lignin, hemicellulose, and cellulose fibers this combines to form a firm, very compact network structure. In a natural state, after size reduction, the access to cellulose is still blocked by lignin and hemicellulose because of the intact cell wall structure. Moreover, cellulose has a highly crystalline structure that is very difficult to break down (Hsu, T. A., M. Ladisch, and G. Tsao. (1980). Alcohol from Cellulose. Chem. Technol. 10(5):315-19.). Therefore harsh pre treatment processes are currently used to destroy the structure of lignocellulosic biomass plant cell walls and make cellulose more accessible to the subsequent process of hydrolysis (during hydrolysis, cellulose is broken down into simple sugars).
Pre treatment methods can be categorized into four types: physical methods (e.g., milling and grinding); physicochemical methods (e.g., steam explosion or hydrothermolysis); chemical methods (e.g., using acids, alkali, oxidizing agents, or organic solvents to treat biomass); and biological methods (e.g., using microorganisms and fungi to treat biomass) (Kumar, P., D. M. Barrett, M. J. Delwiche, and P. Stroeve. (2009). Methods for Pretreatment of Lignocellulosic Biomass for Efficient Hydrolysis and Biofuel Production. Industrial & Engineering Chemistry Research 48(8):3713-29.). However, only those pre treatment methods that employ chemicals currently offer the high yields and low costs vital to economic success. Among the most promising are pre treatments using dilute acid, sulfur dioxide, near-neutral pH control, ammonia expansion, aqueous ammonia, and lime, with significant differences among the sugar-release patterns.
Although pre treatment of naturally resistant cellulosic materials is essential, if high yields from biological operations should be achieved; this operation is projected to be the single, most expensive processing step. For example about 20% of the total cost for the production of ethanol are based on the pre treatment process (Bin Yang and Charles E. Wyman. (2008). Pre treatment: the key to unlocking low-cost cellulosic ethanol. Biofuels, Bioprod. Bioref. 2:26-40). Moreover, pretreatment of lignocellulosic biomass will generally release extractives and other natural products and can form degradation products, such as lignin fragments and derivatives thereof, which are inhibitory or even toxic to downstream enzymes and organisms (Bin Yang and Charles E. Wyman. (2008). Pre treatment: the key to unlocking low-cost cellulosic ethanol. Biofuels, Bioprod. Bioref. 2:26-40). This will reduce the productivity of any subsequent fermentation process with pretreated lignocellulosic biomass as feed stock, if approaches to circumvent this are not used.
Therefore, the availability and use of novel feedstocks for the production of carbon-based chemicals like carboxylic acids would be highly advantageous.

Methods for producing carbon-based chemicals by algal biomass processing


A method and apparatus for conditioning an aluminum billet for extrusion from an extrusion press. The billet is first heated above the solutionizing temperature for the MgSi phases in the aluminum matrix, then the billet is cooled below the solutionizing temperature to an adequate hot working temperature. Preferably, a temperature gradient is created along the length of the billet wherein one end of the billet is at or above the hot working temperature and the other end of the billet is cooled to a temperature below the hot working temperature. Thereafter, the billet is placed into the extrusion die, the hot end adjacent the die and the cool end adjacent the ram of the extrusion press. The billet is then extruded producing an extruded product with uniform properties along the length of the product with minimal defects such as tearing or hot shorting.

The quality of an extrusion of an aluminum billet is dependent upon, among other things, the temperature of the billet during the extrusion operation and the speed with which the extrusion operation proceeds. Generally, it is known that as the temperature of the billet immediately prior to extrusion increases, the speed with which the extrusion process may proceed decreases. However, the lower temperature may also result in defects in the extruded product as a result of the hard and brittle MgSi phases within the aluminum matrix. Obviously, it is most desirable to maximize the extrusion speed to increase the productivity of the extrusion apparatus. However, the extrusion speed is limited by the temperature of the billet and the existence of hard incipient phases in the matrix. As described in an article by Oddvin Reiso entitled, "The Effect of Billet Preheating Practice on Extrudability of AlMgSi Alloys," published in the 1988 Proceedings of the Fourth Intermediate Aluminum Extrusion Technology Seminar, defects in the extruded billet can be minimized by heating an AlMgSi billet above the solutionizing temperature to dissolve any MgSi phases contained within the aluminum matrix prior to extrusion. Thereafter, the billet is cooled somewhat to an adequate working temperature, but not sufficient to allow for significant reformation of the solutionized MgSi phases. At this working temperature, the billet may be extruded at a maximum extrusion speed with minimal defects in the extruded product.
It is also well known to create a temperature differential throughout a metal billet prior to an extrusion operation in order to eliminate defects in the extruded products and to create more uniform properties throughout the extruded product. The temperature gradient is created between the ends of the billet. The temperature gradient may be used to create an extrusion which has a uniform temperature upon exiting the extrusion die by compensating for the heat created in the billet as a result of the extrusion operation. The temperature gradient may also be utilized to help remove impurities such as air from the billet during the extrusion operation through selective deformation of the billet.
The U.S. Pat. No. 2,639,810 to Doan (issued May 26, 1953) discloses the concept of extruding a metal billet having a temperature gradient between the ends. The metal billets are pretreated to establish a temperature gradient extending from a hot working temperature at one end to a materially lower temperature at the other end While this gradient exists, the billet is extruded with the hot end adjacent the die with the result that any air in the cylinder is expelled positively from around the billet rearwardly along the ram and out of the press. The temperature gradient can be created by spraying one end of the billet with water or by standing the billet on one end momentarily in a shallow pool of water after heating the billet to a uniform hot-working temperature.
A further example of creating a temperature gradient throughout a heated workpiece is disclosed in the U.S. Pat. No. 2,409,422 to Egan (issued Oct. 15, 1946). The patent discloses a means for creating a temperature differential in a bi-metallic billet in a hot-rolling operation by subjecting one of the components of the billet to spray from a cooling medium.
Use of a temperature gradient is also disclosed in U.S. Pat. No. 2,480,774 to Rossheim, et al. (issued Aug. 30, 1949) for application in bending of thin walled thermoplastic bodies including tubes. The gradient is created by employing heating means that circumscribe the tube and cooling rings on either side of the heating means. The U.S. Pat. No. 3,902,334 to Stuart (issued Sept. 2, 1975) also discloses the use of heating and cooling rings which circumscribe a tube to allow for uniform bending of the tube.
An extrusion operation which measures the temperature of the extruded product and utilizes sprays from various cooling mediums to cool the extruded product is disclosed in U.S. Pat. No. 2,863,557 to Munker (issued Dec. 9, 1958). The temperature sensing means are used to control the speed of the extrusion. This concept is also found in U.S. Pat. No. 3,212,309 to Wilson (issued Oct. 19, 1965). In the Wilson patent, a temperature sensing device is used to control the speed of a wire drawing machine and the amount of coolant applied to the drawn wire.
The U.S. Pat. No. 2,964,834 to Schober (issued Dec. 20, 1960) also utilizes a temperature gradient within a metal blank to create desired properties in the end product in a forging operation. This patent discloses creating a temperature gradient within a metal blank prior to a forging operation to allow for free and uniform movement of the metal to the extreme portions of the forging die as the force of the press is applied. This method also creates a one-directional grain structure at the extremities of the die.
The concept of applying coolant to an extruded article immediately after the extrusion operation is found in U.S. Pat. No. 3,739,619 to Follrath, et al. (issued June 19, 1973).


A magnetic angular sensing system has a magnet magnetized radially and a magnetic angular sensor for sensing the angular position of the magnet. The magnetic angular sensor is mounted in parallel to the axis of the magnet and is non-coplanar with the magnet. The magnetic angular sensor senses an angular position of the magnet based on a detected axial magnetic field component and a tangential magnetic field component of the magnetic field vector where the sensor mounted. This invention provides a flexible sensing system.

Angular position of a magnet which is magnetized radially such as a cylinder magnet or a ring magnet, is sought to be detected in many applications, for example in vehicle drive system. FIG. 1 illustrates a prior art cylinder magnet 10 which is magnetized radially along the diameter. A magnetic sensor 11 placed at the right bottom of the center of the magnet 10, and the magnetic sensor 11 is used to detect the angle orientation of the magnetic field component B generated by the cylinder magnet 10. In this sensing configuration, the magnetic field component B from a north pole N to a south pole S of the magnet 10 is in an opposite direction (180 degree rotated) to a magnetizing direction M. Thus by detecting the angle orientation of the magnetic field vector B rightly below the magnet 10, the angular position in relating to the magnetizing direction M of the magnet 10 can also be determined.
In some applications, referring to FIG. 2, a magnet magnetized radially such as a cylinder magnet 10 is fixed to a spindle 20 along z axis which is perpendicular to the plane xy of the magnetic. In such situations, a magnetic sensor cannot be placed at the right bottom of the center of the magnet 10 to sense the magnetizing direction M. In such situation, a magnetic angular sensor 21 may be placed at the xy plane along the radius r of the magnet 10. And the radius magnetic field component Br is reflective of the angular position α towards the magnetizing direction M. The angular position α versus the value of the radius magnetic field component Br has a relationship as shown in FIG. 5A. And in some other applications, for example as shown in FIG. 3, a magnet 10 may be fixed on a board 30 or embedded in a device and also with a rotatable spindle 20, and a magnetic sensor is not able to be placed either at right bottom of the center of the magnet 10, nor at the plane xy of the magnetic. Accordingly a sensing system is required to detect the angular position towards the magnetizing direction M during these situations where the magnetic angular sensor is neither placed at right bottom of the center of the magnet, nor at the plane of the magnet. And thus a more flexible sensing system with magnetic angular sensor placed side-shafted at either zone A1, A2, A3 or A4 that can be adapted to various situations is required.

Magnetic angular sensing system with side-shaft mounted sensor and the method thereof


A joint inspection apparatus comprises a light irradiating device for irradiating light to a tape joint at which two tape edge portions are joined together, and a light receiving device for receiving the light irradiated by the light irradiating device to the tape joint and passing through the tape joint or reflected by the tape joint. A judgment device is provided for judging the extent of a deviation of the two tape edge portions from each other in the tape width direction at the tape joint on the basis of information on the optical amount of the light received by the light receiving device on both sides of the tape joint.

1. Field of the Invention
This invention relates to a joint inspection apparatus for automatically inspecting a deviation of tape edge portions from each other in the tape width direction at a tape joint in the case where long tapes are joined together. This invention particularly relates to a joint inspection apparatus for detecting a deviation of edge portions of, for example, a leader tape and a magnetic tape from each other in the tape width direction, which deviation may arise in the case where the leader tape and the magnetic tape are joined together at the edge portions thereof by use of a joining tape for obtaining a video tape, an audio tape or the like.
2. Description of the Prior Art
In the course of making video tape cassettes or audio tape cassettes, a leader tape (or a trailer tape) and a magnetic tape are joined together by use of a joining tape, and a deviation of the edge portions of the leader tape and the magnetic tape from each other in the tape width direction at the joint area heretofore has been judged by visual inspection by the operators.
However, with the visual inspection, criteria of judgment differ among the operators, and defective products may be missed due to fatigue of the operators. Therefore, it is not always possible to make the quality of the products uniform. Also, personnel expenses for the operators cause the product cost to increase, and the production speed is decreased by the presence of the artificial process in the production processes.


A method of transferring data between local and remote computing systems includes the step of transferring data between the local and remote computing systems via a local buffer in the local computing system and a series of steps carried out during transferring of data from the local to the remote computing system. The steps include receiving a statistic from the remote computing system, computing an average transfer rate of the data transfer between the local and remote computing systems based on the statistic, determining whether or not a throttle condition is in effect based on the computed average transfer rate, and upon determining that the throttle condition is in effect, throttling the transferring of data into the local buffer.

Cloud architectures are used in cloud computing and cloud storage systems for offering infrastructure-as-a-service (IaaS) cloud services. Examples of cloud architectures include the VMware vCloud Director® cloud architecture software, Amazon EC2™ web service, and OpenStack™ open source cloud computing service. IaaS cloud service is a type of cloud service that provides access to physical and/or virtual resources in a cloud environment. These services provide a tenant application programming interface (API) that supports operations for manipulating IaaS constructs, such as virtual machines (VMs) and logical networks.
Virtual machines running in host computers are actively managed to improve the overall performance of cloud services. One example is live migration of VMs from one cloud computing system to another cloud computing system. Live migration of a VM involves copying the memory pages of the VM from a source machine to a destination machine. VMs may undergo live cross-cloud migration from a busy server to an underutilized server to achieve load balancing across cloud computing systems. Live migration of VMs also may be carried out to enable machine maintenance.
Cross-cloud migration of VMs and other data is usually performed across a wide-area network (WAN), such as the Internet. To improve latency and throughput over the WAN, WAN optimizers are employed. On the sending side, WAN optimizers compress data and on the receiving side WAN optimizers decompress the data. WAN optimizers also perform deduplication. Because of compression and deduplication, the WAN optimizer on the receiving side often deals with more data than the WAN optimizer on the sending side. This can cause the data buffer of the receiving WAN optimizer to fill faster than the receiving WAN optimizer can free. When a receiving WAN optimizer's data buffer becomes full, it is not able to accept new data until it frees space in its buffer. During this time, no data is sent from the sending WAN optimizer to the receiving WAN optimizer. In addition, the WAN optimizer causes the buffering both on the local and remote side to exhibit a non-linearity in that a constant number of bytes in the buffers holds a variable number of data bytes at different points in time due to the compression and deduplication operations performed by the WAN optimizer. This non-linearity poses a problem for latency sensitive protocols.
Software performing cross-cloud migration of VMs or other data sometimes has a progress requirement to transfer a certain amount of data per unit of time. If the progress requirement is not met, then the migration software concludes that the migration cannot be completed at this time and aborts the migration process. When a receiving WAN optimizer's buffer fills and the WAN optimizer stops receiving data for a certain length of time, that length of time might be too long to satisfy the migrating software's progress requirement. This causes the migration to fail. Thus, there exists a need to control data flow from one cloud to another cloud, when utilizing WAN optimizers, to prevent aborts of data migration processes.

Dynamic flow control for transferring data efficiently and effectively over non-linear buffered network paths


A money transfer system is promoted by providing a user access to a game or contest generated by a promotions engine computer. The user is directed to a customer relations portal accessible via an access device to participate in the game or contest. The customer relations portal comprising a server configured to manage the game or contest and associated with the promotions engine computer. A response is received from the user at the server related to the user's participation in the game or contest. The server determines whether the user is to receive a reward or prize based on the response from the user, and an output is provided to the user on the access device indicating whether the user is to receive the reward or prize.

A number of businesses offer money transfer and other services through a network of agents and computers. A consumer that desires to use these services to transfer money to a third party takes the money to one of the agents or computers associated with the business. The agent or computer accepts the money, obtains necessary information such as the consumer's identity and the identity of the third party transferee, and initiates a transaction. The money is then made available to the third party transferee by another agent or another computer.
Only limited consumer identity information, such as name and/or phone number, is typically collected to initiate a transaction. It can thus be difficult to effectively market money transfer services to relevant groups and individual consumers.

Promotion generation engine for a money transfer system


A display system for an aircraft includes a processing unit configured to determine runway lighting information and lighting status for runway lighting associated with a selected runway and to generate display commands based on the runway lighting information and the lighting status; and a display device coupled the processing unit and configured to receive the display commands and to display symbology representing the runway lighting information.

Landing is one of the most demanding tasks in flying. During the landing approach, the pilot must evaluate if the aircraft may safely land or if the landing attempt should be aborted. In addition to monitoring various flight instruments and navigating the aircraft, Federal Aviation Administration (FAA) regulations require a pilot to visibly identify certain runway environment or runway surface or lighting references in a predefined visual segment in front of the aircraft. Generally, the visual segment is defined by the FAA by the ability to visually identify ground references at a certain distance and aircraft flight deck angle and altitude and under certain visibility conditions.
Portions of the visual segment typically include various types of runway (or airport) lighting systems, such as the lighting associated with approach lights, threshold lights, and touchdown zone lights. As such, at a predetermined approach point (e.g., a decision height), the pilot is required to look out of the window and identify required airport lighting references. Upon positive identification, the pilot may continue the approach and land the aircraft. The time allocated to this task is very limited given the airspeed of the aircraft and the typical or nominal reaction time of the pilot to see and recognize such references at the decision height. Estimating the visual segment and identifying the airport lighting references may be a challenge given the various types of airport lighting and flight circumstances, particularly at all angles of approach and in nighttime, low visibility, turbulent or crosswind situations that may make it difficult for the pilot to quickly locate and identify the references.
Computer generated aircraft displays have become highly sophisticated and capable of displaying a substantial amount of flight management, navigation, and control information that gives flight crews more effective control of the aircraft and a reduction in workload during a normal flight situation and/or a low visibility, instrument situation. In this regard, electronic displays, such as head up displays (HUDs) and head down displays (HDDs), are used in aircraft as primary flight displays. For example, the primary flight display can combine critical flight instrumentation (e.g., altitude, attitude, heading, airspeed, vertical speed instruments) and primary engine instrument indicators into a single, readily interpretable display. Although conventional primary flight displays may provide some assistance to the pilot during normal and instrument situations, such displays are typically not as helpful during landing situations, particularly in tasks such as anticipating and identifying airport lighting information.
Accordingly, it is desirable to provide systems and methods that improve situational awareness and assist the pilot in identifying and interpreting airport lighting information during a landing situation. Furthermore, other desirable features and characteristics of the present invention will become apparent from the subsequent detailed description of the invention and the appended claims, taken in conjunction with the accompanying drawings and this background of the invention.

Aircraft systems and methods for displaying runway lighting information


Undirected cross connects are provided based on wavelength-selective switches. An undirected Cantor network is disclosed where the switch nodes are wavelength selective switches. An undirected Clos cross connect is also disclosed where one or more undirected switches are undirected Cantor networks having at least one wavelength selective switch.

The nonblocking of cross connect switches in a communications network assesses the ability to route connections from input ports to output ports. A cross connect C can be thought of as a directed graph where input ports are nodes with no incoming edges and output ports are nodes with no outgoing edges. A request for a connection from an input port a to an output port b will be a request for a directed path from a to b. For a more detailed discussion of nonblocking cross connects, see, for example, J. Y. Hui., Switching and Traffic Theory for Integrated Broadband Networks, Kluwer Academic Publishers, Norwell, Mass. (1990) and G. M. Masson et al., "A Sampler of Circuit Switching Networks," IEEE Computer, 5:32-48 (June 1979).
For many networks, however, such as long-haul optical networks, connection requests have "bidirectional symmetry." In other words, there is a request to connect i to j if and only if there is also a request to connect j to i and moreover these two connections should be routed on the same bidirectional links. See, J. Simmons et al., "Optical Crossconnects of Reduced Complexity for WDM Networks with Bidirectional Symmetry, IEEE Photonics Technology Letters, 10(6):819-821 (June 1998). This is due to the fact that optical network management is typically designed to connect transceivers in pairs. A restriction to bidirectional demands may allow for simplified cross connect designs. For bidirectional demands, a cross connect will not have input and output ports, instead it will just have ports.
The cross connect will be an undirected network where the ports are leaf nodes and a request for a connection will be a request for an undirected path between two ports. This is of interest when one has symmetric demands (i.e., there is a demand d from node i to node j if and only if there is a demand d′ from node j to node i) and moreover demands d and d′ should be routed along the same undirected path.
A cross connect is said to be strictly nonblocking if all connections from input ports to output ports can be routed without disturbing other connections. A cross connect is said to be widesense nonblocking if there exists a routing algorithm such that if all previous connections have been routed using that algorithm, then that algorithm will find a route for any subsequent connection requests.
A need exists for a modification to traditional cross connect designs for this undirected case. A further need exists for improved cross connect designs for the undirected case that exhibit good nonblocking properties. Yet another need exists for improved cross connect designs based on various four-port switches.

Undirected cross connects based on wavelength-selective switches