A semiconductor device aluminum-containing metallization system that is particularly useful for integrated circuits (ICs) having P-type contact regions and also having a likelihood of extended exposure to elevated temperatures. Use of an aluminum/silicon diffusion barrier formed of an amorphous tungsten/silicon on such ICs is made commercially practical. A titanium or transition metal silicide layer is disposed beneath the amorphous tungsten/silicon layer, to consistently provide durable low resistance electrical contacts to P-type regions of the IC.

1. Field of the Invention
This invention relates to a multilayer metallization system for silicon integrated circuits. This invention more particularly relates to an improved multilayer metallization system that includes an aluminum-silicon alloy.
2. Description of the Prior Art
Aluminum or aluminum alloys are widely used as a single layer metallization for many silicon semiconductor devices, especially integrated circuits. However, an aluminum-containing single layer metallization limits use of a silicon semiconductor device to low and moderate temperature processing conditions and product applications. Higher temperatures cannot be used because aluminum and silicon interdiffuse at elevated temperatures. On extended exposure to higher temperatures, aluminum-silicon interdiffusion and/or silicon precipitation can cause serious degradation of an aluminum-containing metallization layer on a silicon integrated circuit (IC). Unanticipated contact resistances can result. The unanticipated resistances may not allow the associated circuitry to function as designed. It may not even function at all. In any event the problem and its effects are well known, and need not be discussed further here.
Perepezko et al., in their U.S. Pat. Nos. 4,350,994 and 4,494,136, expressly recognize the aluminum/silicon interdiffusion problem. They disclose substituting another metal for aluminum in the metallization pattern. More specifically, they disclose replacing aluminum with a layer of an amorphous refractory conductive material. The amorphous refractory conductive material can be a metal, or a compound or alloy of high-temperature metals and/or metalloids.
Perepezko et al. disclose that the amorphous materials they contemplate do not interdiffuse with silicon, so long as the amorphous materials remain in their amorphous state. Hence, the amorphous state of the material acts as a diffusion barrier to silicon.
Perepezko et al. teach that an amorphous material will transform into a crystalline material upon being heated. The particular temperature at which this occurs is referred to herein as the crystallization temperature. Perepezko et al. also teach that crystallization temperature of refractory materials is higher, and highest for eutectics of refractory materials. Hence, eutectic refractory compositions are preferred.
Perepezko et al. point out that the search for appropriate metallization materials is largely empirical because there is no way to predict, a priori, whether a given metal will form a good quality ohmic or Schottky contact with a given semiconductor.
We agree. In fact, amorphous refractory materials, alone, do not make commercially satisfactory metallization layers. Our experience has shown that their specific conductivity is too low. In U.S. Pat. No. 4,965,656, Koubuchi et al. solve this problem by also using an aluminum layer, over the amorphous layer.
In other words, Koubuchi et al. interpose Perepezko et al.'s amorphous barrier layer between the silicon IC surface and the aluminum metallization layer. Koubuchi et al., like Perepezko et al., are intended to prevent silicon/aluminum interdiffusion. They both describe a wide variety of amorphous refractory metal/metalloids that can might be useful, and that eutectic compositions are preferred.
More specifically, Koubuchi et also state that the aluminum/silicon interdiffusion is a processing problem, not an operational problem. Koubuchi et al. state that detrimental interdiffusion can occur due to heating during fabrication steps following device metallization. We are aware of this problem. However, we recognize a different problem. It occurs if the aluminum metallization layer contains silicon, and it frequently does.
A frequently used aluminum metallization alloy contains 1% silicon and 1% copper, by weight and the balance aluminum. This relatively minor proportion of silicon is used to prevent "spiking" of the aluminum on a silicon IC surface. However, it is also enough to cause the "different" problem referred to above. With such aluminum/silicon alloys, post-metallization heat treatments can cause high resistance silicon precipitate formations to preferentially deposit in the metallization layer in the contact window. These preferential formations are caused by segregation of silicon atoms in the aluminum alloy. These preferential formations also occur in the metallization layer at steps in an underlying dielectric coating. Hence, silicon precipitation is not an interdiffusion problem.
In the past, the high resistance silicon precipitate formations did not pose a serious problem. This is because IC metallization contact sizes were greater than about 1.5 microns. This is fairly large compared to the size of the silicon precipitate formations. In such larger contact size ICs, the silicon precipitate formations occupied only a minor proportion of any given contact area. With IC metallization feature sizes of about 1 micron or less, we find such precipitate formations can occupy a sizable proportion of a contact area. The proportion is enough to raise contact resistance to an objectionable level. Such an occurrence at even one contact area in an IC can cause the IC to no longer perform as intended.
One might think that the solution is to simply reduce or eliminate silicon content of the aluminum alloy. The answer is not that simple. About 1% silicon is desired in an aluminum metallization alloy to avoid spiking when used on a silicon surface. It may also be included to preclude unintended interactions with other substances contacted on the silicon surface. Also, commercial manufacturers may want to use a silicon containing alloy in fine geometry applications for practical reasons. They may have large and small feature size applications and may want to use only one alloy in their facility, and/or they find comfort in using an alloy that is familiar to them. Some manufacturers may even perceive incidental other benefits in using silicon in the aluminum alloy. For such commercial manufacturers, deleting the silicon content from the metallization aluminum alloy is not a preferred choice. In this invention, we firstly solve the aluminum/silicon interdiffusion problem with a particularly effective diffusion barrier. The barrier is amorphous tungsten/silicon. In addition, silicon precipitates do not preferentially form in the contact windows when such a layer is deposited on an amorphous tungsten/silicon layer. Hence, use of the amorphous tungsten silicon also solves the silicon precipitate formation problem. Neither Perepezko et al. nor Koubuchi et al. teach that amorphous tungsten/silicon is special for either purpose in an aluminum metallization system.
On the other hand, our particularly effective amorphous tungsten/silicon material has a problem of its own. It has contact resistance problems with P-type silicon. Amorphous tungsten/silicon has good adhesion to silicon. Accordingly, it should be expected to have low contact resistance with silicon. However, in this invention, we discovered that amorphous tungsten/silicon does not consistently make good contacts to P-type silicon. Silicon integrated circuits usually have both P-type and N-type regions that must be contacted by the metallization. If low resistance contacts cannot be predictably made to all of these regions consistently, the metallization system is unsatisfactory. This invention solves the contact resistance problem of amorphous tungsten/silicon on P-type silicon by interposing an additional layer under the amorphous tungsten/silicon. Our additional layer is thus important to effective utilization of amorphous tungsten/silicon, and will hereinafter be described.
Our invention therefore provides a means for commercially using a highly effective aluminum/silicon diffusion barrier in an aluminum-containing metallization system. Thus, one preserves the option to use of an aluminum-type of system, which is well understood. Still further, our diffusion barrier material also suppresses formation of the objectionable silicon precipitation on aluminum alloy containing silicon. Thus, one can still use the familiar metallization aluminum alloy that contain silicon in current small feature size applications. In addition, an important ancillary benefit results from using an amorphous tungsten/silicon layer as the barrier layer. It is so effective as a barrier layer that it can be used in extremely thin films, which can reduce the overall thickness of the metallization layer. Minimizing the overall thickness of a metallization layer reduces step-height at the edges of the layer. This is important in obtaining most effective coverage of subsequently applied coatings, especially if such coatings are part of a multilevel metallization.

Multilayer metallization for silicon semiconductor devices including a diffusion barrier formed of amorphous tungsten/silicon


An interactive, multi-media presentation viewing system and process for viewing educational or business presentations integrating presentation graphics in the form of presentation slides, video, audio, text, and other streaming media into a powerfully coordinated viewing experience for the end user. The viewing system is an aggregate of synchronized presentation graphics, video, and text displays employing a graphical user interface that allows the user to control all aspects of media playback.

1. Technical Field
The invention is related to an educational or business presentation viewing system having multi-media components, and more particularly to an interactive, multi-media presentation viewing system that integrates presentation graphics in the form of presentation slides, video, audio, text, and other streaming media.
2. Background Art
Multimedia presentations in their simplest form involve the use of a variety of media, such as video, audio, slideshows, and text to present scripted presentations to mass audiences for such purposes as virtual classrooms or other educational and business presentations. Though there has been a recent explosion in the use of such multimedia presentations, very little work is ongoing in the field of interactive multimedia presentations. Interactive multimedia presentations have the promise of providing all new presentation and learning environments. Rather than the traditional canned presentation or lecture, a viewer of an interactive multimedia presentation would be able to play back the presentation while interacting with it to view or review specific sections, access additional information, search and even bookmark the presentation.

Interactive presentation viewing system employing multi-media components


This application discloses a new class of fused tricyclic heterocycles of formula (I), preparation methods thereof, pharmaceutical compositions comprising these compounds, and pharmaceutically acceptable salts, solvates, or prodrugs thereof, and their uses for the treatment of diseases in which modulation of STING is beneficial, for example, cancers, pre-cancerous disorders, and viral infections.

Vertebrates defend against microorganisms or respond to signals from cellular or tissue damage by innate and adaptive immunity. Innate immunity has no antigen specificity and executes the defense mechanisms immediately after an antigen's appearance in the body. Adaptive immunity requires time to generate a full response, but is antigen-specific and long lasting. Once an antigen has been processed and recognized, the adaptive immune system utilizes a set of immune cells specifically designed to attack that antigen. During the course of an adaptive immune response, memory immune cells are generated which allow for a more rapid and effective response to re-exposure to antigens. The innate immune system is required to activate our adaptive immune system. Numerous molecules and cells involved in innate immunity and adaptive immunity function cooperatively (Shanker A. and Marincola F, Cancer Immunol. Immunother., 2011, 60: 1061-1074).
Innate immunity is initiated when the pathogen-associated molecular patterns (PAMPs) present in pathogens are recognized by pattern recognition receptors (PRRs) (Medzhitov, R. J. Immunol. 2013, 191, 4473-4474). Some endogenous damage-associated molecular patterns (DAMPs), including various tumor-derived antigens can also be recognized by these PRRs as well (Matzinger, P., Science 2002, 296: 301-305). The free cytosolic DNA from pathogens and abnormal cells can be recognized by DNA sensors. cGAS (cyclic GMP-AMP Synthase) has been shown to be an important DNA sensor and catalyzes free cytosolic DNA into cyclic di-nucleotides (CDN) 2′3′-GAMP (Ng K W, et al, Trends in Immunology, 2018, 39: 44-54).
Stimulator of interferon genes (STING; also known as MITA and MPYS, and encoded by TMEM173) is a signaling molecule associated with the endoplasmic reticulum (ER). Upon binding to the cyclic dinucleotides (CDNs) generated by cGAS as well as bacterial cyclic di-AMP (c-di-AMP) or c-di-GMP in the cytosol, STING undergoes a conformational change and forms a complex with TBK1. This complex translocates from the ER to the perinuclear golgi and then phosphorylates IRF3, which dimerizes and enters the nucleus to initiate the transcription of type I IFNs. TBK1 also phosphorylates residues on the protein IκB, leading to its degradation, which causes the activation and translocation of NF-κB to the nucleus and transcription of pro-inflammatory cytokines such as TNFα, IL-6 and IL-1β (Ahn J. and Barber G., Current Opinion in Immunology 2014, 31:121-126). Accumulating evidence indicates that STING-dependent signaling is critical in promoting antitumor immunity. STING deficient mice have decreased tumor rejection observed when compared with wild type mice (Woo S. et al, Immunity, 2014, 41:830-842). Activation of STING significantly suppressed the growth of multiple types of mouse tumor (Corrales et al., Cell Reports, 2015, 11:1018-1030).
The antitumor activity mediated by STING is at least partially via type I IFNs (Corrales L. and Gajewski F, Clin. Cancer Res., 2015, 21: 4774-4779). The effect of type I IFNs (IFNα/β) on immune cells has been well established. Upon binding to IFNα/β, the IFNα/β receptor activates a cascade of events and induces the transcription of a wide variety of genes regulated by IFN-stimulated response elements (ISRE), thus modulating multiple types of immune cells. In particular, type I IFNs promote cross-priming, boost effector T cell function and expansion, mediate memory development, thereby coupling innate immunity with adaptive immunity (Zitvogel L. et al, Nature Reviews Immunology, 2015, 15: 405-414). Type I IFNs contribute to antitumor immunity in various types of cancer (Parker B. et al., Nat Rev Cancer, 2016, 16:131-144). TNFα may be another important contributor to the therapeutic effect observed with the activation of STING (Francica B. et al., Cancer Immunol Res., 2018, 6: 1-12).
The patent applications disclosing STING modulators include WO2010017248, WO2013166000, WO2017175147 and WO2017175156.
In summary, STING activation may have significant impact on innate and adaptive immune response and accordingly may have a beneficial impact on the treatment of cancer and other diseases such as viral infection.

Fused tricyclic heterocycle compounds and therapeutic uses thereof

Shanghai Hengrui Pharmaceutical Co., Ltd.


Provided are a base station and a transmission method whereby, even in a case where a cross carrier scheduling is employed, the increase in the number of blind decodings on a PDCCH receiving side can be suppressed without need of signaling of an upper layer at the time of changing PDCCH CC. In the base station (100), a CC setting unit (101) sets, from among a plurality of downstream unit carriers included in a UE CC set, a control channel unit carrier (PDCCH CC) used for transmitting allocation information related to a data transmission resource of each downstream unit carrier included in the UE CC set.

3GPP-LTE (3rd Generation Partnership Project Radio Access Network Long Term Evolution, hereinafter, referred to as "LTE") adopts OFDMA (Orthogonal Frequency Division Multiple Access) as a downlink communication scheme and adopts SC-FDMA (Single Carrier Frequency Division Multiple Access) as an uplink communication scheme (e.g., see Non-Patent Literatures 1, 2 and 3).
In LTE, a radio communication base station apparatus (hereinafter abbreviated as "base station") assigns resource blocks (RBs) in a system band to a radio communication terminal apparatus (hereinafter abbreviated as "terminal") for each time unit called "subframe" and thereby performs, communication.
Furthermore, the base station transmits downlink control information (L1/L2 control information) for reporting results of resource assignment to downlink data and uplink data to the terminal. This downlink control information is transmitted to the terminal using a downlink control channel such as a PDCCH (Physical Downlink Control Channel). Here, each PDCCH occupies a resource made up of one or a plurality of consecutive CCEs (Control Channel Elements). In LTE, one of 1, 2, 4 and 8 is selected as the number of CCEs (CCE aggregation level) occupied by the PDCCH according to the number of information bits of downlink control information or a channel state of the terminal. In LTE, a frequency band having a width of a maximum of 20 MHz is supported as a system bandwidth.
Furthermore, when assigning a plurality of terminals to one subframe, the base station simultaneously transmits a plurality of PDCCHs. At this time, the base station includes a CRC bit which is masked (or scrambled) with a destination terminal ID to identify a destination terminal of each PDCCH in the PDCCH and transmits the PDCCH. The terminal demasks (descrambles) CRC bits in a plurality of PDCCHs which are likely to be addressed to the own terminal with the terminal ID of the own terminal and thereby blind-decodes the PDCCHs and detects the PDCCH addressed to its own terminal.
Furthermore, downlink control information transmitted from the base station is called "DCI (Downlink Control Information)" and includes information on resources assigned by the base station to the terminal (resource assignment information) and MCS (Modulation and channel Coding Scheme) or the like. The DCI has a plurality of formats. That is, examples of such formats include uplink format, downlink MIMO (Multiple Input Multiple Output) transmission format, downlink non-contiguous band assignment format. The terminal needs to receive both downlink assignment control information (downlink related assignment control information) and uplink assignment control information (uplink-related assignment control information). The downlink assignment control information has a plurality of formats (downlink assignment control information formats) and the uplink assignment control information has one format (uplink assignment control information format).
For example, for the downlink control information (DCI), formats of a plurality of sizes are defined depending on a transmitting antenna control method and a resource assignment method of the base station or the like. Of the plurality of formats, a format of downlink assignment control information for assigning contiguous bands (hereinafter referred to as "contiguous band assignment downlink format") and a format of uplink assignment control information for assigning contiguous bands (hereinafter simply referred to as "contiguous band assignment uplink format") have the same size. These formats (DCI formats) include type information (e.g., 1-bit flag) indicating a type of assignment control information (downlink assignment control information or uplink assignment control information). Thus, even when the size of the contiguous band assignment downlink format and the size of the contiguous band assignment uplink format are the same, the terminal can identify which of the downlink assignment control information or uplink assignment control information is the assignment control information by checking the type information included in the assignment control information.
For example, the contiguous band assignment uplink format is called "DCI format 0" (hereinafter referred to as "DCI 0"), whereas the contiguous band assignment downlink format is called "DCI format 1A" (hereinafter referred to as "DCI 1A"). As described above, DCI 0 and DCI 1A have the same size and can be distinguished by type information. Thus, DCI 0 and DCI 1A will be collectively described as DCI 0/1A below.
Furthermore, in addition to the contiguous band assignment downlink format and contiguous band assignment uplink format, there are DCI formats such as: a format of downlink assignment control information for performing non-contiguous band assignment ("non-contiguous hand assignment downlink format": DCI format 1: DCI 1); and a format of downlink assignment control information for assigning spatially multiplexed MIMO transmission and ("spatially multiplexed MIMO downlink format": DCI format 2, 2A: DCI 2, 2A). Here, DCI 1, 2 or 2A is a format used dependently on a downlink transmission mode of the terminal (non-contiguous band assignment or spatially multiplexed MIMO transmission). That is, DCI 1, 2 or 2A is a format set for each terminal. On the other hand, DCI 0/1A is a format that can be used for a terminal in any transmission mode, independently of the transmission mode. That is, DCI 0/1A is a format used in common to all terminals. Furthermore, when DCI 0/1A is used, 1-antenna transmission or transmission diversity is used as a default transmission mode.
Furthermore, studies are being carried out on a method of limiting CCEs to be blind-decoded for each terminal for the purpose of reducing the number of times blind decoding is performed to reduce the circuit scale of the terminal. This method limits a CCE region that can be blind-decoded by each terminal (hereinafter referred to as "search space"). Here, the unit of a CCE region assigned to each terminal (that is, equivalent to the unit for blind decoding) is called "downlink control information assignment region candidate (PDCCH assignment region candidate)" or "blind decoding region candidate."
In LTE, a search space is set randomly for each terminal. The number of CCEs configuring this search space is defined for each CCE aggregation level of a PDCCH. For example, the number of CCEs configuring a search space is 6, 12, 8, 16 in correspondence with CCE aggregation level 1, 2, 4, 8 of the PDCCH. In this case, the number of blind decoding region candidates is 6 candidates (6=6÷1), 6 candidates (6=12÷2), 2 candidates (2=8÷4), 2 candidates (2=16÷8) in correspondence with CCE aggregation level 1, 2, 4, 8 of the PDCCH. That is, the blind decoding region candidates are limited to a total of 16 candidates. Thus, each terminal needs only to perform blind decoding on a blind decoding region candidate group within a search space assigned to its own terminal, and can thereby reduce the number of times blind decoding is performed. Here, a search space of each terminal is set using a terminal ID of each terminal and a hash function, which is a function that performs randomization. This terminal-specific CCE region is called a specific region (UE specific search space: UE-SS).
On the other hand, the PDCCH also includes control information for assignment of data common to terminals simultaneously reported to a plurality of terminals (e.g., assignment information relating to a downlink broadcast signal and assignment information relating to a paging signal (hereinafter referred to as "control information addressed to a common channel"). To transmit control information addressed to a common channel, a CCE region common to all terminals that should receive a downlink broadcast signal (hereinafter referred to as "common region (common search space: C-SS)") is used for the PDCCH. In the search space of C-SS, there are a total of 6 blind decoding region candidates; 4 candidates (4=16÷4) and 2 candidates (2=16÷8) for CCE aggregation levels 4 and 8 respectively.
Furthermore, in the UE-SS, the terminal performs blind decoding on DCI formats of two sizes; a first type DCI format (DCI 0/1A) used in common for all terminals and a second type DCI format (DCI 1, 2, 2A or the like) which is dependent on a transmission mode. For example, in the UE-SS, the terminal performs blind decoding on 16 blind decoding region candidates relating to the above-described first type DCI format (DCI 0/1A) and the second type DCI format (DCI 1, 2, 2A or the like) of different sizes respectively and thus performs blind decoding a total of 32 times. Furthermore, in the C-SS, the terminal performs blind decoding on the above-described six blind decoding region candidates for DCI format 1C which is a common channel assignment format (hereinafter referred to as "DCI 1C") and DCI 1A respectively, and thus performs blind decoding a total of 12 times. Therefore, the terminal performs blind decoding a total of 44 times per subframe.
Here, DCI 1A used to assign a common channel and DCI 0/1A used to assign terminal-specific data have the same size, but the two are distinguished from each other by a terminal ID. Therefore, the base station cart also transmit DCI 0/1A to assign terminal-specific data using the C-SS without increasing the number of times the terminal performs blind decoding.
Furthermore, standardization of 3GPP LTE-Advanced (hereinafter referred to as "LTE-A"), which realizes faster communication than LTE has started. LTE-A realizes downlink transmission rate of a maximum of 1 Gbps or above and an uplink transmission rate of a maximum of 500 Mbps or above. Thus, base stations and terminals communicable at a wideband frequency of 40 MHz or above (hereinafter referred to as "LTE-A terminals") are expected to be introduced. Furthermore, an LTE-A system is required to accommodate not only LTE-A terminals but also terminals supporting an LTE system (hereinafter referred to as "LTE terminals").
LTE-A proposes a carrier aggregation scheme that aggregates a plurality of frequency bands for communication to realize wideband communication of 40 MHz or above (e.g., see Non-Patent Literature 1). For example, a frequency band having a width of 20 MHz is considered as a base unit (hereinafter referred to as "component carrier" (CC)) of communication bands. Thus, LTE-A realizes a system bandwidth of 40 MHz by aggregating two component carriers, for example. Furthermore, both an LTE terminal and an LTE-A terminal are accommodated in one component carrier. In the following description, a component carrier in an uplink will be referred to as an "uplink component carrier" and a component carrier in a downlink will be referred to as a "downlink component carrier."
In LTE-A, studies are being carried out on supporting carrier aggregation using at least five CCs as the system, but the number of CCs actually used differs from one terminal to another depending on a reception capability corresponding to the number of CCs and a required transmission rate of each terminal. Thus, which CC is used is set (configured) for each terminal. A set CC is called "UE CC set." Furthermore, the UE CC set is semi-statically controlled by a required transmission rate of the terminal.
in LTE-A, when data is assigned to a plurality of component carriers for a certain terminal, assignment control information is reported using a plurality of PDCCHs. That is, a result of resource assignment of each component carrier is reported using one PDCCH per one component carrier. Here, as a method of reporting resource assignment information of each component carrier from a base station to a terminal, assigning data of a different component carrier using a PDCCH transmitted by a certain component carrier, i.e., "cross-carrier scheduling" is under study in LTE-A. To be more specific, studies are being carried out on instructing a component carrier to which the PDCCH is assigned using a carrier indicator (CI) in the PDCCH. That is, each component carrier is labeled by the CI. The CI is transmitted in a field in the PDCCH called "CIF (Carrier Indicator Field)" (e.g., see Non-Patent Literature 5).
Furthermore, LTE-A will newly introduce a transmission method using non-contiguous band assignment and a transmission method using MIMO as uplink transmission methods. Along with this, a definition of new DCI formats (e.g., DCI formats 0A, 0B: DCI 0A, 0B) is under study (e.g., see Non-Patent Literature 4). That is, DCI 0A, 0B is a DCI format which is dependent on an uplink transmission mode. In this case, in addition to the above-described blind decoding of LTE, 16 times of blind decoding are further added in the UE-SS and the terminal performs blind decoding a total of 60 times per subframe.

PANASONIC INTELLECTUAL PROPERTY CORPORATION OF AMERICA


Systems and methods are provided to build a machine learned exploitability risk model that predicts, based on the characteristics of a set of machines, a normalized risk score quantifying the risk that the machines are exploitable by a set of attacks. To build the model, a training dataset is constructed by labeling characteristic data of a population of machines with exploitation test results obtained by simulating a set of attacks on the population. The model is trained using the training data to accurately predict a probability that a given set of machines is exploitable by the set of attacks. In embodiments, the model may be used to make quick assessments about how vulnerable a set of machines are to the set of attacks. In embodiments, the model may be used to compare the effectiveness of different remediation actions to protect against the set of attacks.

Many companies operate private computer networks that are connected to public networks such as the Internet. While such connections allow its users to easily access resources on the public networks, they also expose the company network to potential cyberattacks. For example, company users may unwittingly download malicious content (e.g. data, files, applications, programs, etc.) onto the company network from the Internet. As another example, interactions between company users and outsiders on the public network may result in leaks of proprietary information to allow malicious actors to gain unauthorized access to the company network. Different types of cyberattacks can be used to achieve a variety of different ends, for example, to obtain sensitive information, gain control of the company's computing systems, or damage the company's resources. As a result, enterprise security management systems have become increasingly important to protect private company networks against these types of vulnerabilities.
Many enterprise security management systems provide some form of risk assessment functionality to quantify the risk of computing assets for cyberattacks. Existing processes for cybersecurity risk assessments are based primarily on human-defined formulas. However, human-defined formulas are subject to potential human biases (e.g., incorrect opinions or blindness about risk factors), which can be difficult to detect and eliminate. Moreover, quantitative results generated by these human-defined formulas tend to lack any real-world meaning, so they cannot be easily or intuitively understood by users. The produced risk scores are typically unnormalized and unbounded, so that it is impossible to meaningfully compare two generated risk scores. These issues with existing approaches for cybersecurity risk assessment negatively impact the accuracy of the assessments and limit the usefulness of these assessments. Better approaches are needed to generate risk scores that are more semantically meaningful and less impacted by human biases.

Automatic evalution of remediation plans using exploitability risk modeling


It is shown that the potency of anti-cancer drugs, here exemplified by doxorubicin, can be increased by the use of polyunsaturated fatty acid amides and in particular specific combinations of such compounds, forming complexes with doxorubicin. Further, a modified form of doxorubicin is presented.

Cytostatic or cytotoxic compounds are widely used in the treatment of cancer. Doxorubicin is an aminoglycosidic anthracycline antibiotic and will be used as a typical representative of this group of compounds.
The cell membrane represents a physical barrier and there are some factors that determine the rate of uptake of doxorubicin. The main factors are hydrophobicity (an increase will increase the rate of uptake) and protonation degree of amino group--pKa (a decrease will increase the rate of entry). The doxorubicin inhibits cell growth and has a marked effect on the nuclear material, which becomes non-specifically thickened, agglutinated or broken. The major binding force between doxorubicin and DNA is intercalation of the planar chromophore, stabilised by an external electrostatic binding of the positive charged amino sugar residue with negative phosphate group of DNA.
The intercalated drug molecules appear to prevent the changes in conformation of the helix, which are necessary as a preliminary to initiation of nucleic acid synthesis. The major lethal effect of doxorubicin is inhibition of nucleic acid synthesis. As consequence the drug is more active against dividing cells and the greatest effect is in the S stage of the cell cycle (Brown J. R., Adriamycin and related anthracycline antibiotics in: Progress in Medicinal Chemistry edited by G. P. Ellis and G. B. West, Elsevier/North-Holland Biomedical Press v.15, pp. 125-164, 1978).
Some observations are consistent with the formation complex of electrostatic nature between the positive amino group of doxorubicin and negative phosphate group of phospholipids such as cardiolipin, phosphatidyl serine, phosphatidyl inositol and phosphatidic acid. Cardiolipin is an almost characteristic component of the inner membrane of mitochondria, which are abundant in the cardiac muscle. The pathogenesis of the mitochondrial lesions is one of the major and more specific sub-cellular changes characterizing doxorubicin cardiotoxicity. The rather selective toxicity doxorubicin for mitochondria may be due to the high concentrations of cardiolipin in the mitochondria of the cardiac muscle (Duarte-Karim M., et al. Biochem. Biophys. Res. Comm., v.71, N.2, pp. 658-663, 1976).
The interaction between doxorubicin and lipids has been studied using large unilamellar vesicles (LUVET) composed of mixtures of anionic phospholipids and various zwitterionic phospholipids. Dilution of anionic lipids with zwitterionic lipids leads to decreased membrane association of the drug because electrostatic forces are very important in doxorubicin-membrane interaction. However, binding of doxorubicin to LUVET composed of anionic phospholipids combined with phosphatidylethanolamine (PE) is much higher than binding to LUVET made of anionic lipids plus a range of other zwitterionic lipids such as phosphatidylcholine and the N-methyethanolamine and N,N-dimethylethanolamine derivatives of PE (Speelmans G, et al., Biochemistry, v.36, N.28, pp. 8657-8662, 1997).
The interaction of adriamycin with human erythrocytes was investigated in order to determine the membrane binding sites and the resultant structural perturbation. Electron microscopy revealed that red blood cells incubated with the therapeutic concentration of the drug in human plasma changed their discoid shape to both stomatocytes and echinocytes. The drug was incubated with molecular models. One of them consisted of dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine multilayers, representatives of phospholipid classes located in the outer and inner leaflets of the erythrocyte membrane, respectively. X-ray diffraction showed that adriamycin interaction perturbed the polar head and acyl chain regions of both lipids. It is concluded that adriamycin incorporates into both erythrocyte leaflets affecting its membrane structure (Suwalsky M., Z Naturforsch [C] v.54, N3-4, pp. 271-277, 1999).
The different physicochemical properties of dipalmitoylphosphatidylcholine liposomes with soybean-derived sterols have been studied. Liposomal doxorubicin increased the pharmacological effect compared with free drug, suggesting a decrease of side effect and long circulation (Maitani Y., Yakugaku Zasshi, v.116, N.12, pp. 901-910, 1996).
Liposomes containing polyethylene glycol-derivatised phospholipids are able to evade the reticulo-endothelial system and thereby remain in circulation for prolonged periods. The doxorubicin encapsulated in these sterically stabilised liposomes suppresses the growth of established human lung tumour xenografts in severe combined immunodeficient mice and inhibits the spontaneous metastases of these tumours (Sakakibara T., et al., Cancer Res., v.56, N. 16, pp. 3743-3746, 1996).
A liposome encapsulation can protect surrounding tissue from the cytotoxic effects of the drugs after subcutaneous (s.c.) administration. Liposomes composed of "fluid-state" phospholipids only delayed the damaging effects of doxorubicin when injected s.c. Liposomes with a more rigid nature were much more effective in preventing local tissue damage over a longer period of time when administered s.c. (Oussoren C., et al., Biochim. Biophys. Acta, v.1369, N.1, pp. 159-172, 1998).
Exogenous polyunsaturated fatty acids modulate the cytotoxic activity of anti-cancer drugs in the human breast cancer cell line MDA-MB-231. Among all polyunsaturated fatty acids tested, docosahexaenoic acid was the most potent in increasing doxorubicin cytotoxicity (E. Germain, et al., Int. J. Cancer, v.75, pp. 578-583, 1998).
There remains a need for novel compounds and methods for the treatment of cancer. The present invention aims i.a. to increase the pharmacological activity of presently used anti-cancer drugs, such as doxorubicin, and to introduce novel approaches to the treatment of cancer.


An arrangement to provide an electronic enclosure joint that reduces both electromagnetic and radio frequency radiation between walls of an enclosure of an electronics product has a corrugated metal strip serving as a gasket. The walls of the enclosure have inner conductive surfaces which contact the apices of the corrugated strip. The walls form a channel for the corrugated strip, with the inner conductive surfaces being kept a pre-determined distance apart. The force exerted by the corrugated strip provides electrical continuity between the inner conductive surfaces, while plastic deformation of the strip is avoided by maintenance of the pre-determined distance between the inner conductive surfaces. Because of the relatively low force needed to ensure electrical continuity, creep-prone materials such as plastic can be used for the walls, without the need for an excessive amount of fasteners to hold the walls together against the force exerted by the corrugated strip.

It is well known that certain electronic products, such as computers, are sources of electromagnetic interference (EMI) and radio frequency interference (RFI). This troublesome interference can disturb the operation of nearby electronic equipment such as radios, televisions and sensitive analog circuitry. As a result, there are strict federal and international standards imposed on the amount of conducted and radiated EMI and RFI that is permitted in commercial products. There is therefore a need to provide enclosures for electronics products that prevent EMI and RFI from being conducted or radiated outside of the enclosure.
It has been found that no matter how mechanically tight a joint is made between two surfaces of an enclosure, EMI and RFI can take place unless there is electrical continuity between the two surfaces. In order to provide the required electrical continuity in the joint, conductive elastomer gaskets, flexible metal strips and the like are frequently used. The gaskets or strips are sandwiched between the two surfaces and provide electrical continuity between the surfaces of the enclosure. A Faraday cage surrounding the electronics product is thereby formed by the enclosure, preventing EMI and RFI outside of the enclosure.
When installed properly, elastomer gaskets and the like perform well and satisfy stringent military requirements. A problem with these gaskets, however, is that they cause the force needed to assemble the enclosure, (the closure force), to be relatively very high. This high closure force necessitates the use of a relatively large number of fasteners to hold the two surfaces of the joint together. The assembly cost and time needed to enclose a product increases greatly with the use of a large number of mechanical fasteners. Furthermore, the cost of these gaskets themselves is relatively very high.
The high closure force of the conductive elastomer gaskets and the like also makes these gaskets unsuitable for use with creep-prone materials, such as plastic. Instead, they are better suited for use with metal enclosures. With certain plastic materials, however, which are now being used for computer enclosures more frequently, the surfaces tend to move and thus in time to creep apart when a force is applied against the surface of the plastic. Electrical continuity in time can therefore no longer be assured between the surfaces of certain plastic enclosures.
A need exists for an arrangement to provide an EMI and RFI-tight joint between surfaces of an enclosure that requires a relatively low closure force. This would allow the enclosure to be made of plastic and other creep-prone materials and reduce the assembly costs of the enclosure.

Corrugated strip gasket for an electronic enclosure joint to reduce both electromagnetic and radio frequency radiation


A load drive control device is provided, which includes a pulse generator for generating pulse signals with a duty ratio to drive an inductive load, a feedback setting section for setting the duty ratio for feedback, a detection setting section for setting the duty ratio for detection of a natural vibration frequency of the inductive load, a natural vibration frequency setting section for setting the natural vibration frequency of the inductive load based on an actual current value detected at setting the duty ratio for detection, and a selection section for selecting the feedback setting section as a duty ratio setting section at a normal time and for selecting the detection setting section as the duty ratio setting section when a condition for detecting the natural vibration frequency is satisfied.

A known load drive control device controls driving of an inductive load by generating pulse signals with a predetermined duty ratio at a predetermined drive frequency.
In the inductive load driven at the predetermined drive frequency, resonance is generated when the drive frequency coincides substantially with a natural vibration frequency of the inductive load, or is substantially equal to the integral multiple of the natural vibration frequency of the inductive load. In order to prevent the resonance, it is necessary to determine a drive frequency based on the natural vibration frequency. However, when the natural vibration frequency changes due to an external factor, it is difficult to store the drive frequency in advance so that no resonance is generated.
When an inductive load is, for example, a solenoid of a hydraulic valve for controlling oil pressure applied to an automatic transmission, it is preferable to prevent the resonance because the resonance causes, for example, oil pressure pulsation of a valve body. However, because the viscosity of oil varies with, for example, temperature, it is difficult to store the drive frequency in advance so that no resonance is generated.
In this relation, JP-A-2003-167604 describes a control device of hydraulic equipment. In the control device, a stroke sensor detects the position of a spool linked to a plunger of a solenoid serving as an inductive load.
The stroke sensor makes it possible to switch the drive frequency based on a detected amplitude.
As described above, a known load drive control device may switch the drive frequency based on the amplitude detected by the stroke sensor. Consequently, the load drive control device may detect a resonant condition from the amplitude and switch the frequency to a drive frequency that causes no resonance generation.
The above load drive control device requires the stroke sensor in order to suppress the resonance. The stroke sensor is very expensive, and a man-hour for mounting the stroke sensor also arises.


A drain for a pressure vessel includes a valve, a knob, a tube, a passageway, and a drain cup. The valve is coupled between an interior surface and an exterior surface of a tank. The knob is coupled to the valve for opening and closing the valve. The tube has a top end and a bottom end and is coupled to the valve at an interior surface of the tank at the top end and extends into a bottom of the tank at the bottom end. The passageway extends through the valve and has an opening coupled to the tube at a first end and an exit at a second end. The passageway is openable and closeable by the knob. The drain cup is associated with the exit of the passageway and is positioned on an exterior surface of the tank for collecting condensation from the interior of the tank. The valve is positioned at a height that is vertically higher than the bottom end of the tube.

Air compressors, pressure vessels and tanks may collect moisture, condensation, or other fluids. The presence of such fluids inside a tank can cause corrosion. It is desirable to drain the fluid from a tank in order to avoid any adverse side effects caused by the accumulated condensation. It is also desirable to provide a vessel for storing the condensate once it has been removed from the tank until it may be disposed of in an appropriate manner. For example, if working inside away from a sink, it is appropriate to store the condensate in a cup until the user can properly dispose of the condensate in a sink or outside.


An electronically-controlled air injection system implemented in three different embodiments with respect to each cylinder. A first embodiment includes a T-adapter, an air solenoid, a fuel injector, and a control unit. The T-adapter receives pressurized fuel and pressurized air from an air solenoid, and outputs these to the fuel injector. The air solenoid controls the flow of air to the fuel injector via the control unit. The second embodiment includes a modified fuel injector, an air solenoid, and a control unit. The fuel injector is modified by forming therein an air passage and a communicating sac, wherein the sac communicates with the fuel valve. Compressed air is supplied through an air solenoid to the air passage. The third embodiment includes a modified cylinder head, an air solenoid, and a control unit. Compressed air is supplied through an air solenoid to at least one combustion chamber cylinder port in the cylinder head.

The present invention relates generally to reducing emissions from diesel engines and more specifically to electronically-controlled air injection to achieve simultaneous reduction of NOX and particulates emissions from a diesel engine.
Despite the numerous advantages and widespread usage of diesel engines, particulates (including soot and hydrocarbons) and oxides of nitrogen emissions from these engines are pollutants which engine manufacturers seek to minimize. Oxides of nitrogen, NO and NO2, commonly referred to as NOX, are formed by the reaction of nitrogen and oxygen from the combustion of the air-fuel mixture at high temperatures during the diesel combustion stroke. The high-temperature combustion of the diesel engine which is responsible for its high efficiency is also the cause of its NOx emissions. Particulates are conglomerates formed during combustion that may consist of large aromatic molecules with very high carbon-to-hydrogen ratios, inorganic species originating in the lube oil, sulfates from the oxidation of fuel sulfur, unburned fuel or lube oil, and products from the partial combustion of fuel or lube oil. It is difficult to control both particulates and NOx emissions simultaneously and cost-effectively without imposing significant penalties in fuel economy and/or power on diesel engines because of their inherent trade-off characteristics.
The diesel engine combustion process consists of an initial premixed stage in which chemical kinetics are rate controlling, followed by a diffusion stage in which mixing is rate controlling. Both NOX and particulate formation rates are generally high in the premixed stage because of higher energy release rates. The diffusion stage of the combustion process is generally associated with lower energy release rates than those of the premixed stage. The energy release at this stage is controlled by the mixing rate since, during this period, the characteristic time of combustion is much shorter than the characteristic time of fuel-air mixing. The mixing process is very important in determining the particulates oxidation rates. By enhancing turbulent mixing during the diffusion stage of the combustion cycle (where particulates oxidation is more pronounced) without disturbing the region of NOX formation, a reduction in visible smoke, hydrocarbons, and particulates in general can be achieved.
Previous analytical studies have shown that many factors will influence the effectiveness of late-cycle air injection. These include beginning of air injection, duration of air injection, air injection pressure, temperature, air composition, nozzle geometry (orifice diameter, number of holes, orifice aspect ratio), orifice orientation with respect to cylinder axis, location of the injector, beginning of fuel injection timing, fuel injection pressure, duration of fuel injection, fuel injection rate and shape, and composition of combustion air. Conceivably, the impact of late-cycle air injection would be significant if an air jet follows the fuel spray, or the combusting fuel spray plume. However, there is no practical (commercially available) system to perform direct combustion chamber air injection in diesel engines. Direct air injection through an additional injector might increase the system complexity and cost, and, hence, it is not preferable.
Accordingly, there is a clearly-felt need in the art for achieving simultaneous reduction of NOX and particulates in a diesel engine without reducing power output or fuel economy.
The present invention is an electronically-controlled late cycle injection of supplemental air to achieve simultaneous reduction of NOX and particulates emissions from a diesel engine without sacrificing its power output or fuel economy, wherein minimal modifications are required to the power assembly and fuel injection equipment, which modifications may be in the form of original engine manufacture or retrofit.
According to the present invention, a high-pressure jet of supplemental air is introduced into the cylinder (specifically, the combustion chamber thereof) late in the diesel cycle which serves to reduce particulate emissions over a broad range of engine operating conditions. When the supplemental air injection is coupled with NOX reducing methods, such as retarded fuel injection timing, multiple injections, or exhaust gas recirculation, simultaneous reduction of both NOX and particulate emissions is realized.
Controlled quantities of supplemental air, at relatively higher pressure than the combustion chamber combustion pressure, are introduced directly into the combustion chamber during the combustion (also referred to as the expansion) stroke or during the combustion and exhaust strokes of the diesel cycle. The mass of injected supplemental air is relatively small (about 2% to 10% of the total airflow) compared to the main intake airflow. The jet momentum of the supplemental air serves to augment turbulent mixing and also increases the partial pressure of oxygen in the gases surrounding the burning fuel droplets. These changes in mixing and chemical kinetics help to enhance the particulates (soot and hydrocarbon) oxidation and gas-phase hydrocarbon combustion reactions without adversely affecting NOX formation due to the supplemental air promoting a higher oxygen concentration and average lower temperature in the combustion zone. As a result of these enhanced oxidation reactions, visible smoke, unburned hydrocarbons, and total particulate emissions will be significantly reduced. The decreasing temperature, due to expansion and mixing of high-temperature gas with the supplemental air or cooler burned gas, freezes the oxides of nitrogen chemistry. This chemistry freezing effect occurs more rapidly in diesel engines and much less decomposition of the oxides of nitrogen occurs. The timing and delivery parameters for injection of diesel fuel, as well as the supplemental air, are electronically controlled so that NOX formation can still be reduced during the premixed and early diffusion stages of the diesel combustion cycle. The addition of supplemental air directly into the combustion chamber of a diesel engine has the potential to reduce both NOX and particulate emissions simultaneously, and lessens the trade-off between them.
These emissions reductions are achieved with the following major components:
a) a source of supplemental air in the form of a small portion of the engine""s intake air diverted from the intake manifold (filtered air at intake boost conditions);
b) a high-pressure compressor and/or a pump (piston, diaphragm or rotary type) to pressurize the supplemental air (for example, to pressures ranging up to 5,000 psi), wherein the pressure should generally be greater than the combustion chamber combustion pressure;
c) an accumulator or rail to hold the pressurized supplemental air and supply lines to the individual injectors;
d) an electronically-controlled solenoid valve to actuate the supply of the supplemental air into each injector, respectively;
e) an injector mounted on the cylinder head with one of more orifices to inject the supplemental air with a desired spray pattern directly into the respective combustion chamber; and
f) an electronic control system to control injection timing and delivery characteristics of the supplemental air during the combustion stroke or during the combustion and exhaust strokes of each cylinder, respectively, of a diesel cycle, wherein the beginning of supplemental air injection with respect to piston position in the cylinder, injection pressure, and duration of injection are all electronically controlled.
The electronically-controlled supplemental air injection system according to the present invention may be implemented in any of three different embodiments.
A first embodiment of an electronically-controlled supplemental air injection system includes a T-adapter, an air solenoid, a control unit, and a fuel injector. The T-adapter receives pressurized fuel from a fuel pump through a fuel check valve and pressurized air from a source of compressed air through an air solenoid and then an air check valve. The pressurized fuel and supplemental air are output from the T-adapter through the fuel injector, wherein the air solenoid controls the flow of supplemental air to the fuel injector. The air check valve prevents fuel from entering the air line and the fuel check valve prevents air from entering the fuel line. A computer control device dynamically controls the opening and closing of the air solenoid according to timing appropriate to a predetermined specific cycle of a diesel engine and the operating conditions of the engine.
A second embodiment of an electronically-controlled supplemental air injection system includes a modified fuel injector, an air solenoid, and a control unit. The fuel injector is modified by forming an air passage through an outside perimeter to a sac thereof. The sac is located below a needle of the fuel injector. Compressed supplemental air is supplied through an air solenoid to an input of the air passage on the outside perimeter of the fuel injector. The supplemental air is supplied to the sac when the control unit opens the air solenoid. The supplemental air flows from the sac through an orifice in a tip of the fuel injector. A computer control device dynamically controls the opening and closing of the air solenoid according to timing appropriate to a predetermined specific cycle of a diesel engine and the operating conditions of the engine.
A third embodiment of an electronically-controlled supplemental air injection system includes a cylinder head with at least one air passage, at least one cylinder passage valve, an air solenoid, and a control unit. The cylinder head will not have to be modified if it already contains cylinder relief passages, as for example for the purpose of testing and safety procedures. A cylinder head not having cylinder relief passages is modified by adding at least one air passage per cylinder. The cylinder relief valves are replaced with cylinder passage valves or added to the air passages in the modified cylinder head. Compressed supplemental air is supplied through the air solenoid to each cylinder air passage. The supplemental air passes into a particular combustion chamber when the control unit opens the air solenoid and the combustion chamber""s respective cylinder passage valve. A computer control device dynamically controls the opening and closing of the air solenoid according to timing appropriate to a predetermined specific cycle of a diesel engine and the operating conditions of the engine.
With regard to the aforementioned timing, the supplemental air is injected into a combustion chamber during, preferably, one of two specific time periods during the diesel cycle. In a first specific time period example, supplemental air is injected into the combustion chamber when the piston is at top dead center (TDC) at the start of the combustion stroke and continues until the exhaust valve is opened. In a second specific time period example, supplemental air is injected into the combustion chamber when the piston is at TDC at the start of the combustion stroke and continues until the piston is at TDC at the end of the exhaust stroke.
Accordingly, it is an object of the present invention to provide electronically-controlled supplemental air injection to achieve simultaneous reduction of NOX and particulates emissions from a diesel engine without reducing power output or fuel economy thereof.
This and additional objects, features and advantages of the present invention will become clearer from the following specification of a preferred embodiment.

Electronically-controlled late cycle air injection to achieve simultaneous reduction of NOx and particulates emissions from a diesel engine


The router is used to relay a packet to be transmitted from one node to another in an integrated circuit that has distributed buses according to a packet exchange method. The router includes: a plurality of buffers, each of which configured to store packets with information indicating their transmission node; a classifying section configured to classify the buffers that store the packets into a number of groups according to the transmission nodes of the packets; a selecting section configured to select at least one of the buffers of each group; and an output port configured to sequentially output the packets that are stored in the selected buffer.

1. Technical Field
The present application relates to a technology for arranging a transmission schedule for a plurality of traffic flows that run through multiple routers, which are connected together through distributed buses, in a semiconductor integrated circuit including such a bus. More particularly, the present application relates to a technique for controlling the transmission of packets which are constituent units that form multiple different traffic flows and which are stored and distributed in a plurality of buffers.
2. Description of the Related Art
Portion (A) of FIG. 1 illustrates an example of a centralized bus control. In a traditional integrated circuit that performs such a centralized bus control, a number of bus masters and a memory are connected together with a single bus, and accesses to the memory by the respective bus masters are arbitrated by an arbiter. However, as the functionality of an integrated circuit has been further improved and as the number of cores in an integrated circuit has been further increased these days, the scale of the circuit has become even larger and the traffic flows running through the bus has gotten even more complicated. As a result, it has become increasingly difficult to design an integrated circuit by such a centralized bus control.
Meanwhile, semiconductor integrated circuits with distributed buses have been developed one after another lately by introducing parallel computerized connection technologies and network control technologies such as ATM (asynchronous transfer mode). Portion (B) of FIG. 1 illustrates an example of a distributed bus control. In a semiconductor integrated circuit with distributed buses, a number of routers are connected together with multiple buses. Recently, people have been working on a so-called "Network on Chip (NoC)" in which the traffic flows in a large-scale integrated circuit are transmitted through a number of buses by adopting the distributed buses such as the one shown in portion (B) of FIG. 1.
FIG. 2 illustrates generally a basic configuration for a router for use in the NoC, parallel computers, ATM network, and so on. In such a router, traffic data is divided into a number of small units such as packets or cells, each of which is transmitted to its destination node. The data that has been sent to the router is temporarily retained in buffers.
Also, in order to transmit a number of different packets in parallel with each other through each input port, a virtual channel (which is sometimes called a "VC"), in which multiple buffers are connected in parallel with each other, is provided for each input port. That is to say, each virtual channel substantively consists of multiple buffer memories for a router. In this case, a number of buffers may actually be physically arranged for and with respect to each input port. Alternatively, a virtual channel may also be provided even by managing the data on a single buffer memory as if there were multiple buffers there.
In addition, a crossbar switch is further arranged in order to determine an exclusive connection between each input port and its associated output port. The exclusive connection between an input port and its associated output port via the crossbar switch is also determined by an arbiter.
By getting the crossbar switch turned by the arbiter in this manner, the router relays the data that is retained in the buffers to a destination.
Next, it will be described how to change the connection between an input port of a router and its associated output port. Each input port of a router and its associated output port are connected exclusively with each other via the crossbar switch. In this description, the "exclusive connection" refers to a situation where when multiple input ports and multiple output ports need to be connected at a time, not more than one input port is connected to one output port.
Next, the data structure of data to be transmitted by a NoC router will be described.
FIG. 3 illustrates an exemplary transmission format for a packet 300 and how the packet 300 may be divided into multiple flits.
Unlike a router to be generally used in parallel computers and ATM networks, a NoC router transmits a packet which has been generated at a transmission node after having divided the packet into multiple units called "flits" of a size that is small enough to send it in one cycle through a bus.
The packet 300 includes a header field 301, a data field 302, and a control code field 303.
In the header field 301, described are the receiving end's (i.e., reception node's) address, the transmitting end's (i.e., transmission node's) address, information about the deadline by which a packet transmitted should arrive at the reception node (which will be referred to herein as "time information"), for example. The time information may be described in any form as long as the amount of time that has passed since one packet was transmitted or the deadline by which the packet should arrive at the destination can be compared to another packet's.
In the data field 302, on the other hand, video data or audio data may be described, for example. In the control code field 303, the end code of a predetermined packet 300 may be described, for example.
The processing of relaying the packet 300 and the processing of receiving the packet 300 at the receiving end are performed based on the reception node's address and the transmission node's address among the data stored in the header field 301.
Each node on the transmitting end transmits the packet 300 after having divided it into smaller data units called "flits". In this case, one flit is data that can be transmitted through the bus in one cycle and its size is determined by the width of the bus. Among those flits obtained by dividing one packet 300, the flit to be transmitted first is called a "header flit" 304, to which flag information indicating that this flit is located at the beginning of a packet and information about the reception node's address of the packet are added.
It should be noted that the address information indicating the location of the reception node is not stored in any of the flits that follow the header flit 304. This is because those flits that follow the header flit 304 are supposed to be sent to the same destination as the header flit 304. When the destination is determined by the header flit 304 and when an output buffer to which the flits in that traffic are output is determined, the flits that follow the header flit 304 are transmitted to the destination indicated by the header flit 304 by using the same output buffer as what is used by the header flit 304.
On the other hand, the last flit of one packet is called a "tail flit" 306, to which added is flag information indicating that this is the last one of the flits that form one packet. Meanwhile, the flits other than the header flit 304 and the tail flit 306 are mainly used to transmit data and are called "data flits" 305.
On detecting the end code that is described in the control code field 303, the node on the receiving end restores those flits transmitted into the original packet based on that end code.
For example, one packet may have a size of 128 bytes, and one flit may have a size of 64 bits. In that case, one packet is transmitted after having been divided into 16 flits. It should be noted, however, that these sizes are just an example because one packet size and one flit size may vary according to the application or the bus width. Optionally, the length of a flit may be determined by a length that can describe control data using the reception node's address and the transmission node's address, for example.
FIG. 4A is a flowchart showing a series of processing operations to be performed by each router in a NoC in order to transmit a packet that has been received by the router to either an adjacent router or a reception node.
On the other hand, FIG. 4B illustrates a configuration for virtual channels which contribute to transmitting the flits as shown in FIG. 4A. In the example illustrated in FIG. 4B, each router has two input ports and two output ports, and each input port is provided with two virtual channels (VCs) to store flits.
One of the virtual channels of each input port gets connected to the output port by turning a crossbar switch SW, thereby transmitting the flits in the virtual channel through the output port. In FIG. 4B, the virtual channels VC1 and VC2 of only Input Port 0 are illustrated and the virtual channels of input port 1 are not illustrated for the sake of simplicity.
FIG. 4C shows the cycle-by-cycle state transitions of respective flits since a packet has been received at a router and until the packet is transmitted to either the next router or a reception node.
In order to relay a packet that has been divided into multiple flits to its destination, a router in a NoC carries out, on the flits received, all or part of routing computation (RC) processing, virtual channel allocation (VA) processing, switch allocation (SA) processing, and switch traversal (ST) processing (see, for example, W. Dally and B. Towles, "Principles and Practices of Interconnection Networks", Morgan Kaufmann Publishers).
Hereinafter, the basic operation of a router in a NoC will be described with reference to the flowchart shown in FIG. 4A and the block diagram shown in FIG. 4B first. In the following description, the upstream router will be referred to herein as "Router A" and the downstream router will be referred to herein as "Router B" as shown in FIG. 4B.
First, in Step 401 shown in FIG. 4A, Router A determines whether or not there is any virtual channel VC with flits. If the answer is YES, the processing performed by Router A advances to the next processing step 402. Otherwise, this processing step 401 will be performed over and over again until the decision is made that there is a virtual channel with flits.
If there is any virtual channel VC with flits, Router A determines, in the next processing step 402, whether or not the first one of the flits of that virtual channel VC is a header flit. If the answer is YES, the processing performed by Router A advances to the next processing step 403. Otherwise, the processing performed by Router A jumps to a processing step 405.
In the example illustrated in FIG. 4B, Router A has one virtual channel with a header flit. Thus, the processing performed by Router A advances to the next processing step 403.
If the first flit of the virtual channel has turned out to be a header flit, Router A carries out routing computation (RC) processing in this processing step 403 by reference to the destination information that is described in that header flit. By performing the routing computation processing, Router A selects one output port that leads to the destination of the packet.
In the example illustrated in FIG. 4B, Router A selects Output Port 0, which is connected to Router B that leads to the destination, by performing the routing computation processing.
After the output port has been selected by performing the routing computation processing, the processing advances to the next processing step 404, in which it is determined in which virtual channel of the adjacent Router B the packet to be transmitted from Router A needs be stored.
In a NoC, a packet is relayed after having been divided into multiple flits. Also, the basic information that is required to perform the routing control is described in only the header flit. That is why if flits of two or more different packets were mixed in the same virtual channel, those flits could not be delivered to the correct destination or the flits that have been delivered to the destination could not be restored into the original packet in some cases.
Thus, to avoid such an unwanted situation, each router in the NoC gets each single virtual channel occupied by a particular packet since the header flit of that packet has passed through the virtual channel and until the tail flit of that packet passes through the virtual channel and prohibits flits of any other packet from passing through that virtual channel occupied.
For example, Router A shown in FIG. 4B allocates one unused virtual channel in Router B, to which the flits are going to be transmitted, to the virtual channel VC1 that stores the header flit, thereby performing the virtual channel allocation (VA) processing.
When the virtual channel allocation (VA) processing is done, the processing by Router A advances to the next processing step 405.
However, if there are no unused virtual channels in the adjacent Router B, then Router A retries this processing step 404 over and over again until any of the virtual channels of Router B becomes available to allow Router A to complete the virtual channel allocation (VA) processing.
In the example illustrated in FIG. 4B, Router A selects the virtual channel VC1 of Router B as a buffer to store the flits and allocates the virtual channel VC1 to its own virtual channel VC1 that stores the header flit.
When the routing computation (RC) processing and the allocation of the virtual channel to store the flits in the adjacent router (i.e., the VA processing) are finished, the processing by Router A advances to the next processing step 405, in which Router A waits until the flits stored are transmitted.
In the processing step 405, in order to transmit the flits from the virtual channel, Router A turns the crossbar switch to allocate its own virtual channel VC1 to its output port (this is the switch allocation (SA) processing).
If multiple virtual channels are requesting to transmit flits through a single output port, then switch allocation (SA) processing is carried out in order to determine, on an output port basis, which virtual channel is allowed to transmit flits through a given output port.
Optionally, in this switch allocation processing, a router of the NoC may adjust, by reference to various kinds of information including the type of a given packet (such as a delay guaranteed type or a best effort type), the priority, the time of transmission, and the deadline for arrival, how long a virtual channel that stores the packet may be connected to an output port. Then, the schedule for transmitting packets from multiple different transmission nodes can be arranged.
When an output port is allocated and connected to the virtual channel that is waiting until the flits are ready to be transmitted as a result of the switch allocation (SA) processing step 405, the processing by Router A advances to the next processing step 406, in which Router A transmits the flits in the virtual channel connected through the output port selected (this is the switch traversal (ST) processing).
By performing this series of processing steps 401 through 406 on each virtual channel in this manner, the router transmits the flits received to the destination.
Hereinafter, it will be described with reference to FIG. 4C exactly how Router A shown in FIG. 4B relays a single packet. In the following example, it will be described how the flits are processed at respective points in time on the supposition that each packet is comprised of four flits.
First of all, when a header flit arrives at Router A at a time 1, Router A carries out routing computation (RC) processing by reference to the destination information included in the header flit, thereby selecting an output port through which flits will be transmitted next.
Next, at a time 2, Router A carries out virtual channel allocation (VA) processing, thereby determining to which virtual channel of Router B, to which the output port that has been selected through the routing computation processing (RC) is connected, the virtual channel that stores the header flit should be connected.
Meanwhile, at this point in time 2, Data Flit 1 arrives at Router A. However, as the header flit is already present at the top of the virtual channel, no processing is carried out on Data Flit 1.
Next, at a time 3, Router A carries out switch allocation (SA) processing, thereby determining which output port is allocated to the virtual channel that stores the header flit at the top.
Meanwhile, at this point in time 3, Data Flit 2 also arrives at Router A. However, as the header flit is already present at the top of the virtual channel, no processing is carried out on Data Flits 1 and 2.
Next, at a time 4, Router A transmits the header flit (which is the switch traversal (ST) processing). However, even after the header flit has been transmitted, the switch allocation (SA) processing is carried on to keep the same virtual channel-output port pair connected continuously.
Meanwhile, at this point in time 4, Tail Flit also arrives at Router A. However, as Data Flit 1 is already present at the top of the virtual channel, no processing is carried out on Data Flit 2 and Tail Flit.
Next, at a time 5, Router A transmits Data Flit 1 (which is the switch traversal (ST) processing). However, even after Data Flit 1 has been transmitted, the switch allocation (SA) processing is carried on to keep the same virtual channel-output port pair connected continuously. As Data Flit 1 is already present at the top of the virtual channel, no processing is carried out on Data Flit 2 and Tail Flit.
Next, at a time 6, Router A transmits Data Flit 2 (which is the switch traversal (ST) processing). However, even after Data Flit 2 has been transmitted, the switch allocation (SA) processing is carried on to keep the same virtual channel-output port pair connected continuously.
Finally, at a time 7, Router A transmits Tail Flit (which is the switch traversal (ST) processing). In this manner, one packet can be relayed completely.
This series of processing steps to be carried out to relay a single packet as shown in FIG. 4C is an example in which each processing step is supposed to be finished in one cycle. However, if it has turned out as a result of the virtual channel allocation (VA) processing that there is no virtual channel available from Router B to which a flit is going to be output, the virtual channel allocation (VA) cannot be completed until there is any virtual channel available. As a result, this routing processing should wait until this and following flits are ready to be transmitted.
The same can be said about the switch allocation (SA) processing. That is to say, if multiple virtual channels request to transmit flits through the same output port, then the transmission schedule needs to be arranged so that the output port is allocated to those virtual channels one by one. As a result, transmission of those flits should wait in such a situation.
Generally speaking, a larger number of transmission buffers (or virtual channels) can be secured for a packet of the same size in a router for use in a parallel computer or ATM than in a router for use in a NoC. That is why the influence of such a delay in the virtual channel allocation (VA) processing due to the shortage of virtual channels is less significant in the former type of router than in the latter. Meanwhile, it is far more important for the router of the former type to optimize the transmission schedule in order to transmit the respective flits in the transmission buffer (virtual channel) as efficiently as possible. That is why as for a router for use in a parallel computer or an ATM, a "wavefront allocator" which searches for the best possible combination of a transmission buffer (virtual channel) and an output port, "parallel iterative machining" which chooses the best combinations iteratively on the input port and output port sides of a router, and other techniques have been adopted (see W. Daily and B. Towles, "Principles and Practices of Interconnection Networks", Morgan Kaufmann Publishers, for example).
On the other hand, in some situation, multiple virtual channels may request to be connected to the same output port at the same time. To cope with such a situation, a so-called "age-based" method has been proposed in U.S. Pat. No. 6,674,720, for example. According to that method, a value called "age" is defined based on the length of the time that passed since a packet was transmitted and the number of hops that the packet has made in order to maintain the order in which a number of packets have been transmitted and to minimize an increase in time delay between the packets or their difference. And according to the "age-based" method, a packet with the maximum (or minimum) age is supposed to be transmitted first.

Panasonic Intellectual Property Management Co., Ltd.


A method for assembling a drug delivery device that includes mounting a cartridge with a bung, the mechanism, the plunger and the spring within a housing such that a spring biases a plunger in a dispensing direction and that a drum and/or the release member is attached to the plunger attaching a tool with torque measurement capability to the drum or a release member of a dose mechanism in a state where at least one housing part is detached from further housing part; setting a dose by rotating the dose setting member in a first direction, activating a trigger and monitoring the torque applied to the drum or the release member; releasing the trigger upon detection of a predetermined change in the torque measured by the tool; and releasing the tool and closing the housing.

Drug delivery devices have application where regular injection by persons without formal medical training occurs. This may be increasingly common among patients having diabetes where self-treatment enables such patients to conduct effective management of their disease. In practice, such a drug delivery device allows a user to individually select and dispense a number of user variable doses of a medicament.
There are basically two types of drug delivery devices: resettable devices (i.e., reusable) and non-resettable (i.e., disposable). For example, disposable drug delivery devices are supplied as self-contained devices. Such self-contained devices do not have removable pre-filled cartridges. Rather, the pre-filled cartridges may not be removed and replaced from these devices without destroying the device itself. Consequently, such disposable devices need not have a resettable dose setting mechanism. The present disclosure is in general applicable for both types of devices, i.e. for disposable devices as well as for reusable devices.
A further differentiation of drug delivery device types refers to the drive mechanism: There are devices which are manually driven, e.g. by a user applying a force to an injection button, devices which are driven by a spring or the like and devices which combine these two concepts, i.e. spring assisted devices which still require a user to exert an injection force. The spring-type devices involve springs which are preloaded and springs which are loaded by the user during dose selecting. Some stored-energy devices use a combination of spring preload and additional energy provided by the user, for example during dose setting. Further types of energy storage may comprise compressed fluids or electrically driven devices with a battery or the like. Although many aspects of the present disclosure are applicable for all of these types of devices, i.e. for devices with or without a drive spring or the like energy storage, the preferred embodiments require some kind of energy storage.
These types of delivery devices generally comprise of three primary elements: a cartridge section that includes a cartridge often contained within a housing or holder; a needle assembly connected to one end of the cartridge section; and a dosing section connected to the other end of the cartridge section. A cartridge (often referred to as an ampoule) typically includes a reservoir that is filled with a medication (e.g., insulin), a movable rubber type bung or stopper located at one end of the cartridge reservoir, and a top having a pierceable rubber seal located at the other, often necked-down, end. A crimped annular metal band is typically used to hold the rubber seal in place. While the cartridge housing may be typically made of plastic, cartridge reservoirs have historically been made of glass.
The needle assembly is typically a replaceable double-ended needle assembly. Before an injection, a replaceable double-ended needle assembly is attached to one end of the cartridge assembly, a dose is set, and then the set dose is administered. Such removable needle assemblies may be threaded onto, or pushed (i.e., snapped) onto the pierceable seal end of the cartridge assembly.
The dosing section or dose setting mechanism is typically the portion of the device that is used to set (select) a dose. During an injection, a plunger, spindle or piston rod contained within the dose setting mechanism presses against the bung or stopper of the cartridge. This force causes the medication contained within the cartridge to be injected through an attached needle assembly. After an injection, as generally recommended by most drug delivery device and/or needle assembly manufacturers and suppliers, the needle assembly is removed and discarded.
In known drug delivery devices, there may be an internal gap between parts of the drug delivery device after assembly which have to contact each other to ensure the delivery of the correct amount of the dose. The gap may be located between parts of the drive mechanism or between a part of the drive mechanism and e.g. the cartridge. This gap is a consequence of the tolerances associated with all the assembled parts and the requirement not to apply an undesirably high preload on the bung axially in the assembled drug delivery device, because too much preload would pressurize the drug in the cartridge and may cause it to leak, or may cause creep damage to plastic parts if they are loaded for significant periods of time during storage.
In a conventional drug delivery device, a priming operation is performed to ensure that the parts of the driving mechanism are moved to their predetermined position with respect to the other parts. Typically, the priming step has to be performed prior to the first use of the device to close a possible gap between the cartridge bung and the plunger and to overcome tolerances within the device. For the priming step, a user has to set a small dose and to dispense this dose while monitoring whether e.g. fluid leaves the device. This action has to be repeated until e.g. fluid actually leaves the device.
There is a risk of an underdose at least during the first use of the device if a user does not perform this priming step. Users who are unfamiliar with such drug delivery devices may fail to correctly prime their drug delivery device before dispensing the first dose. If this occurs, the correct volume of the drug may not be delivered in the first dose, as part of the dialed dose is needed to close up any gaps between parts in the mechanism.
EP 2 482 899 B1 discloses a manually operated drug delivery device with an assembly which can be adjusted during assembly of the device, preferably during final assembly after fitting the cartridge, to bring a piston rod in contact with a cartridge bung. This removes tolerance gaps from the assembly and eliminates the need for a priming operation which is undertaken by the user prior to delivery the first dose of drug. The assembly of this known device requires using a tool to move a first drive member with respect to a second drive member, thereby moving a piston rod towards a bung during an assembly action, and thereafter coupling the first drive member with the second drive member so that the movement of the first drive member with respect to the second drive member is prevented during a dose setting and delivery action.
WO 2014/036239 A2, WO 2010/112377 A1 and WO 2008/142394 A1 each disclose a drug delivery device comprising a spring loaded piston which is attached to a belt or tether retaining the piston against the force of the spring. One end of the belt is attached to a spool on a gear wheel which is in engagement with a worm gear driven by an electric motor. Actuation of the motor allows unwinding of the belt which in turn allows displacement of the piston by the spring. In addition, WO 2014/036239 A2 mentions a control unit with a sensor detecting slack in the belt or tether. Further a sensor and an encoder may be used to provide positional feedback, end-of-dose signal and error indication.
WO 2014/139918 A1 and WO 2011/039229 A1 each describe an assembly method for a drug delivery device, wherein the device comprises a threaded piston rod engaging a threaded drive sleeve. During assembly the drive sleeve is rotated thereby advancing the piston rod. The torque required for rotating the piston rod is measured to detect a sudden increase in torque when the piston rod contacts a bung in a cartridge. WO 2014/029682 A2 proposes a method for detecting snap engagement of a piston rod and a bung by a sudden change in force or torque required for piston rod displacement.

Method for assembling a drug delivery device and drug delivery device


Pharmaceutical formulations containing a salt of (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one, represented by Formula I, which are suitable for forming into a tablet dosage form, as well as tablet dosage forms are disclosed. Disclosed also are methods of treatment utilizing such dosage forms.

Identification of any publication, patent, or patent application in this section or any section of this application is not an admission that such publication is prior art to the present invention.
Certain diazaspirodecan-2-ones, for example, 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one, for example, (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one (the compound of Formula I) are useful antagonists of neuropeptide neurokinin-1 receptors (the "NK-1" receptor antagonists) in the treatment of certain medical conditions, for example, two of the most debilitating side effects of cytotoxic chemotherapy, delayed-phase nausea and vomiting (chemically-induced nausea and emesis, CINE). In therapy utilizing cytotoxic chemotherapy, delayed-phase CINE manifests from between 2 days and 5 days post chemotherapy administration. Acute-phase CINE has been managed by administering a 5HT3 receptor antagonists (e.g., ondansetron), often in combination with a corticosteroid, for example, dexamethasone. This treatment has not been effective in managing delayed-phase CINE. It is believed that acute-phase CINE and delayed-phase CINE arise from different physiological phenomena. It is believed that administration of the NK-1 receptor antagonist of Formula I, or a salt thereof, for example, one or more salts of (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro-[4.5]decan-2-one, either alone or in combination with one or more of a corticosteroid, for example, dexamethasone and/or a 5HT3 receptor antagonist, for example, ondensetron, granisetron, palonosetron, dolasetron, or tropisetron will provide a therapy effective in treatment of CINE in humans.

Synthesis of the compound of Formula I is described in U.S. Pat. No. 7,049,320, issued May 23, 2006 (the '320 patent), U.S. provisional application No. 60/919,666, filed Mar. 22, 2007, and in an international application co-filed in the U.S. receiving office with the present application under Attorney's docket no. CD06628L01US on Mar. 20, 2008, each of which are incorporated herein by reference in their entirety.
Compounds having therapeutic activity must be provided to a patient in a suitable formulation to take advantage of their therapeutic properties. In general, dosage forms suitable for oral administration are preferred. Oral formulations are easy to administer using a non-invasive procedure. Oral dosage forms provide the medicament in a form that is robust in the environment in which it is handled, administered, and stored. Moreover, tablet oral dosage forms conveniently offer the medicament in a variety of discrete dosage sizes and can provide the active pharmaceutical ingredient in a minimum volume per dosage unit. In addition, a tablet can be prepared in fewer unit operations than capsule dosage forms, and tablets, through the provision of tablet "scores", offer the potential of providing user-selectable multiple dosage strengths using a single dosage unit. Such convenience is unavailable in a capsule dosage form. On the other hand, in many instances, the active pharmaceutical ingredients used in pharmaceutical formulations (API, also termed herein, "drug substance"), especially those having a crystalline form, are not by themselves suitable for forming into a tablet, especially a tablet formed using direct compression techniques. To enable formation of a tablet which can be handled and stored without breakage or loss of material from the tablet (that is, a tablet having low percentage friability), the drug substance must be combined with excipients in a formulation that enables formation of a tablet that is sufficiently robust to withstand handling and storage until the point of use. Moreover, once formed into a tablet, the tableted formulation must be capable of readily releasing the API at a desired point within the gastrointestinal tract when administered to an end user.

Tablet formulations containing 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diaza-spiro[4.5]decan-2-one salts and tablets made therefrom