The present invention relates to substituted triazolopyridine compounds of general formula (I): in which R1, R2, R3, R4, and R5 are as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease of uncontrolled cell growth, proliferation and/or survival as well as to the use of intermediate compounds for the preparation of said compounds.

The present invention relates to chemical compounds that inhibit Mps-1 (Monopolar Spindle 1) kinase (also known as Tyrosine Threonine Kinase, TTK). Mps-1 is a dual specificity Ser/Thr kinase which plays a key role in the activation of the mitotic checkpoint (also known as spindle checkpoint, spindle assembly checkpoint) thereby ensuring proper chromosome segregation during mitosis [Abrieu A et al., Cell, 2001, 106, 83-93]. Every dividing cell has to ensure equal separation of the replicated chromosomes into the two daughter cells. Upon entry into mitosis, chromosomes are attached at their kinetochores to the microtubules of the spindle apparatus. The mitotic checkpoint is a surveillance mechanism that is active as long as unattached kinetochores are present and prevents mitotic cells from entering anaphase and thereby completing cell division with unattached chromosomes [Suijkerbuijk S J and Kops G J, Biochemica et Biophysica Acta, 2008, 1786, 24-31; Musacchio A and Salmon E D, Nat Rev Mol Cell Biol., 2007, 8, 379-93]. Once all kinetochores are attached in a correct amphitelic, i.e. bipolar, fashion with the mitotic spindle, the checkpoint is satisfied and the cell enters anaphase and proceeds through mitosis. The mitotic checkpoint consists of complex network of a number of essential proteins, including members of the MAD (mitotic arrest deficient, MAD 1-3) and Bub (Budding uninhibited by benzimidazole, Bub 1-3) families, the motor protein CENP-E, Mps-1 kinase as well as other components, many of these being over-expressed in proliferating cells (e.g. cancer cells) and tissues [Yuan B et al., Clinical Cancer Research, 2006, 12, 405-10]. The essential role of Mps-1 kinase activity in mitotic checkpoint signalling has been shown by shRNA-silencing, chemical genetics as well as chemical inhibitors of Mps-1 kinase [Jelluma N et al., PLos ONE, 2008, 3, e2415; Jones M H et al., Current Biology, 2005, 15, 160-65; Dorer R K et al., Current Biology, 2005, 15, 1070-76; Schmidt M et al., EMBO Reports, 2005, 6, 866-72].
There is ample evidence linking reduced but incomplete mitotic checkpoint function with aneuploidy and tumorigenesis [Weaver B A and Cleveland D W, Cancer Research, 2007, 67, 10103-5; King R W, Biochimica et Biophysica Acta, 2008, 1786, 4-14]. In contrast, complete inhibition of the mitotic checkpoint has been recognised to result in severe chromosome missegregation and induction of apoptosis in tumour cells [Kops G J et al., Nature Reviews Cancer, 2005, 5, 773-85; Schmidt M and Medema R H, Cell Cycle, 2006, 5, 159-63; Schmidt M and Bastians H, Drug Resistance Updates, 2007, 10, 162-81]. Therefore, mitotic checkpoint abrogation through pharmacological inhibition of Mps-1 kinase or other components of the mitotic checkpoint represents a new approach for the treatment of proliferative disorders including solid tumours such as carcinomas and sarcomas and leukaemias and lymphoid malignancies or other disorders associated with uncontrolled cellular proliferation.
Different compounds have been disclosed in prior art which show an inhibitory effect on Mps-1 kinase:
WO 2009/024824 A1 discloses 2-Anilinopurin-8-ones as inhibitors of Mps-1 for the treatment of proliferate disorders. WO 2010/124826 A1 discloses substituted imidazoquinoxaline compounds as inhibitors of Mps-1 kinase or TTK. WO 2011/026579 A1 discloses substituted aminoquinoxalines as Mps-1 inhibitors.
Substituted triazolopyridine compounds have been disclosed for the treatment or prophylaxis of different diseases:
WO 2008/025821 A1 (Cellzome (UK) Ltd) relates to triazole derivatives as kinase inhibitors, especially inhibitors of ITK or PI3K, for the treatment or prophylaxis of immunological, inflammatory or allergic disorders. Said triazole derivatives are exemplified as possessing an amide, urea or aliphatic amine substituent in position 2.
WO 2009/047514 A1 (Cancer Research Technology Limited) relates to [,2]-triazolo-[1,5-a]-pyridine and [,2]-triazolo-[1,5-c]-pyrimidine compounds which inhibit AXL receptor tyrosine kinase function, and to the treatment of diseases and conditions that are mediated by AXL receptor tyrosine kinase, that are ameliorated by the inhibition of AXL receptor tyrosine kinase function etc., including proliferative conditions such as cancer, etc. Said compounds are exemplified as possessing a substituent in the 5-position of said compounds and a substituent in the 2-position.
WO 2009/010530 A1 discloses bicyclic heterorayl compounds and their use as phosphatidylinositol (PI) 3-kinase. Among other compounds also substituted triazolopyridines are mentioned.
WO 2009/027283 A1 discloses triazolopyridine compounds and their use as ASK (apoptosis signal-regulating kinase) inhibitors for the treatment of autoimmune diseases and neurodegenerative diseases.
WO 2010/092041 A1 (Fovea Pharmaceuticals SA) relates to [,2]-triazolo-[1,5-a]-pyridines, which are useful as selective kinase inhibitors, to methods for producing such compounds and methods for treating or ameliorating kinase-mediated disorder.
However, the state of the art described above does not describe the substituted triazolopyridine compounds of general formula (I) of the present invention, or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same, as described and defined herein, and as hereinafter referred to as "compounds of the present invention", or their pharmacological activity. It has now been found, and this constitutes the basis of the present invention, that said compounds of the present invention have surprising and advantageous properties.
In particular, said compounds of the present invention have surprisingly been found to effectively inhibit Mps-1 kinase and may therefore be used for the treatment or prophylaxis of diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses or diseases which are accompanied with uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses, particularly in which the uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses is mediated by Mps-1 kinase, such as, for example, haemotological tumours, solid tumours, and/or metastases thereof, e.g. leukaemias and myelodysplastic syndrome, malignant lymphomas, head and neck tumours including brain tumours and brain metastases, tumours of the thorax including non-small cell and small cell lung tumours, gastrointestinal tumours, endocrine tumours, mammary and other gynaecological tumours, urological tumours including renal, bladder and prostate tumours, skin tumours, and sarcomas, and/or metastases thereof.


A monitor camera (1) has a front glass (13) and a glass hold-down plate for holding the front glass (13). The glass hold-down plate has an outer surface in a region continues to the front glass (13), and the outer surface is flush with or stepped back from an outer surface of the front glass (13). Further, the glass hold-down plate has a hold-down portion vertical to the direction of the thickness of the front glass (13), the hold-down portion presses the held-down portion stepped back from the outer surface of the front glass (13). The above structure prevents the field of vision of the monitor camera (1) from being hindered by natural substances including snow lying on the front glass and enhances waterproof property of the monitor camera.

A monitor camera is installed at a monitoring place for shooting an object to be monitored. The place to install the monitor camera may be an outdoor. FIG. 8 is a perspective view of an example of the monitor camera in the related art. A monitor camera 30 includes a camera case 31 and a front glass 32. The front glass 32 is formed of a transparent glass plate and, in an example shown in the drawing, has a square shape. The camera case 31 has a substantially square tubular shape in cross section, and includes an imaging device including a lens, an imaging element, and a processing circuit stored therein. The monitor camera 30 picks up an image of an object of shooting, which is an object to be monitored through the front glass 32 and shoots the object of shooting.
The camera case 31 holds a periphery of the front glass 32. An end of the camera case 31 is bent inwardly to form a front wall and the front glass 32 is held from the side of an outer surface thereof at an opening of the front wall.
FIG. 9 is an enlarged cross-sectional view showing a holding position at which the camera case 31 holds the front glass 32. The front glass 32 is pressed from a rear side thereof by a glass holding plate 33 against an inner surface of the front wall of the camera case 31 and fixed thereto. The glass holding plate 33 is fixed to the camera case 31 with screws. An O-ring 34 is provided at a portion where the front glass 32 and the camera case 31 come into abutment so that the waterproof property of the camera case 31 is secured.
As described above, in the monitor camera 30, the camera case 31 presses the front glass 32 from the side of the outer surface to hold the front glass 32. Accordingly, as shown in FIG. 8 and FIG. 9, the outer surface of the front glass 32 is stepped back inwardly in comparison with an outer surface of the camera case 31, and hence a step is formed. When the monitor camera 30 is installed in outdoor, natural substances such as snow or dust may be accumulated on the step. When snow is accumulated on the step, a field of view through the front glass 32 of the monitor camera 30 is hindered, and hence part of the image of the object to be monitored cannot be obtained.
In view of such points, for example, a camera case having a configuration as shown below is disclosed in JP-A-2002-156702 (pp. 2-3, FIG. 3). FIG. 10 shows a front view of the camera case. A front glass 42 is fitted to a front panel 43 of a camera case 41. A defroster glass 44 for removing water drops or fogging up is provided in front of the front glass 42. The defroster glass 44 is pressed against the front glass 42 from the side by a glass presser 45. Then, an annular packing groove 46 is provided at a part where the front panel 43 supports the front glass 42, and a packing 47 is fitted to the packing groove 46. The defroster glass 44 comes into tight contact with the packing 47 by being pressed by the glass presser 45. Accordingly, the waterproof property in the camera case 41 is secured.
As shown in FIG. 10, the defroster glass 44 has a tapered shape having an inclined portion 441 inclined so as to increase the diameter toward a surface of the front glass 42. The glass presser 45 has a tapered shape provided with an inclined portion 451 corresponding to the inclination of the inclined portion 441 of the defroster glass 44. The height of a surface of the glass presser 45 is set to be the same as or the lower than the height of the defroster glass 44 in a state in which the inclined portion 441 of the defroster glass 44 is held down by the inclined portion 451 of the glass presser 45. In this arrangement, the step caused by the glass presser 45 being higher than the defroster glass 44 is eliminated from the camera case 41, so that the field of view of the monitor camera is prevented from being hindered by snow accumulated on an outer surface of the defroster glass 44.
However, with the camera case 41, the inclined portion 441 of the defroster glass 44 is pressed by the inclined portion 451 of the glass presser 45, so that the defroster glass 44 is fixed. Therefore, when a tolerance of the defroster glass 44 is large and the dimensional accuracy is low, there is a case in which the defroster glass 44 does not come into tight contact with the packing 47 sufficiently in a state in which the glass presser 45 is fixed to the camera case 41. In this case, the waterproof property of the camera case 41 is lowered.

Matsushita Electric Industrial Co., Ltd.


A method and apparatus for setting a guard interval in an OFDM communication. The method includes attaching a part of a first valid symbol to the first valid symbol as a guard interval and attaching a part of a second valid symbol requiring higher channel quality than the first valid symbol, to the second valid symbol as a guard interval, and providing the guard interval of the second valid symbol at a length greater than the guard interval of the first valid symbol.

1. Field of the Invention
The present invention relates to a transmission/reception apparatus used for digital mobile communications using an orthogonal frequency division multiplexing (hereinafter referred to as "OFDM") system.
2. Description of the Related Art
A Conventional OFDM transmission/reception apparatus is explained using FIG. 1 and FIG. 2. FIG. 1 is a block diagram showing an outlined configuration of a transmission system of a conventional OFDM transmission/reception apparatus. FIG. 2 is a block diagram showing an outlined configuration of a reception system of the conventional OFDM transmission/reception apparatus.
In FIG. 1, serial-parallel converter (hereinafter referred to as "S/P converter") 11 converts a serial input signal to a plurality of parallel signals. IDFT circuit 12 performs inverse discrete Fourier transform (hereinafter referred to as "IDFT") on the input signals. Guard interval inserter 13 inserts a guard interval for every valid symbol. D/A converter 14 performs D/A conversion on the signal with guard interval inserted.
In FIG. 2, A/D converter 15 performs A/D conversion on a reception signal. Delayer 16 delays the input signal by a valid symbol length. Correlator 17 despreads the input signal. Timing generator 18 detects the timing of the reception signal at which the correlation result becomes largest. Guard interval eliminator 19 eliminates a guard interval inserted for every symbol. DFT circuit 20 performs discrete Fourier transform (hereinafter referred to as "DFT") on the input signal. Coherent detectors 21 to 24 perform coherent detection on the input signal. Deciders 25 to 28 judge the input signal. Parallel-serial converter (hereinafter referred to as "P/S converter") 29 converts a plurality of parallel signals to a serial signal.
Then, the operation of the conventional OFDM transmission/reception apparatus is explained. Here, suppose the number of carriers is 4, for example.
First, the operation of the transmission system is explained using FIG. 1. A modulated signal input to the transmission system is S/P-converted by S/P converter 11. This results in four modulated signals, which are transmitted by a first, second, third and fourth carriers, respectively.
Then, the 4 modulated signals are IDFT-processed by IDFT circuit 12.
A general OFDM transmission/reception apparatus has a frame format as shown in the frame format schematic diagram in FIG. 3. That is, in a frame format used for a general OFDM transmission/reception apparatus, a signal with the same waveform as that of the last part of a valid symbol is added at the start of the valid symbol as a guard interval. The OFDM transmission/reception apparatus can eliminate a delayed signal with a shorter delay time than this guard interval through DFT processing of the reception system.
Guard interval inserter 13 inserts a guard interval into the IDFT-processed signal. The signal with the guard interval inserted is converted to an analog signal by D/A converter 14. In this way, a transmission signal is obtained.
Then, the operation of the reception system is explained using FIG. 2. The reception signal input to the reception system is converted to a digital signal by A/D converter 15.
Generally, the OFDM transmission/reception apparatus finds a correlation between a pre-DFT signal and the pre-DFT signal delayed by a valid symbol length. Then, the OFDM transmission/reception apparatus detects a DFT integration interval by detecting the timing at which the correlation result becomes largest. To be more specific, delayer 16 delays the reception signal by a valid symbol length, then correlator 17 finds a correlation and timing generator 18 detects the timing at which the correlation result becomes largest. Guard interval eliminator 19 eliminates the guard interval from the reception signal according to this detection result.
The reception signal stripped of the guard interval is DFT-processed by DFT circuit 20. This results in 4 baseband signals, which are carried by 4 carrier. The 4 baseband signals are each subjected to coherent detection by coherent detectors 21 to 24. In this way, coherent detected signals are obtained.
Here, coherent detectors 21 to 24 are explained using FIG. 4. FIG. 4 is a block diagram showing an outlined configuration of the coherent detector of the OFDM transmission/reception apparatus. Digital multipliers 41 and 42 multiply the DFT-processed signals by pilot symbols. Conjugate complex number generator 43 generates a conjugate complex number for the input signal.
In a general frame format, a pilot symbol, a known reference signal, is added before a message interval. In a general coherent detection method, a fading variation is detected using a pilot symbol.
In (nT) which is a DFT-processed input signal in a pilot symbol interval is expressed as In (nT)=P (nT) A (nT)·exp (jΘ(nT)), where P (nT) is a pilot symbol, A (nT) is an amplitude variation due to fading and exp (jΘ(nT)) is a phase variation due to fading.
F (nT), which represents a variation due to fading, is expressed as follows:
                                                                        F                                                                                (                  nT                  )                                            =                                                          In                                                                                (                    nT                    )                                    ·                  P                                                                                (                  nT                  )                                                                                =                                                                                {                                              P                                                                                (                            nT                            )                                                    ·                          A                                                                                (                            nT                            )                                                    ·                          exp                                                                                (                                                      j                                                                                Θ                                                                                (                                nT                                )                                                                                )                                                                    }                                        ·                    P                                                                                (                    nT                    )                                                                                =                                                          P                                                                                (                      nT                      )                                        2                                    ·                  A                                                                                (                    nT                    )                                    ·                  exp                                                                                (                                      j                                                                                Θ                                                                    (                        nT                        )                                                                              )                                                                                1                ◯            Here, in a modulation system such as a QPSK modulation system in which the amplitude is constant and only the phase contains information, P (nT)2=1. Therefore, expression {circle around (1)} is expressed as follows:F(nT)=A(nT)·exp (jΘ(nT))Then, digital multiplier 41 obtains signal F (nT) that represents a variation due to fading by multiplying DFT-processed input signal (baseband signal) In (nT) by pilot symbol P (nT) in a pilot symbol interval.
Then, conjugate complex number generator 43 generates a conjugate complex number about F (nT), a signal representing a variation due to fading. In this way, conjugate complex number F (nT)* of F (nT) signal expressing a variation due to fading is obtained. Conjugate complex number generator 43 inverts the polarity of the Q component of the input signal and generates a conjugate complex number. Therefore, conjugate complex number F (nT)* is expressed in the following expression:F(nT)*=A(nT)·exp (−jΘ(nT))
Then, digital multiplier 42 multiplies the DFT-processed input signal (baseband signal) by the conjugate complex number of the signal representing a variation due to fading. In this way, a coherent detected signal is obtained.
Here, suppose the fading variation is sufficiently slow compared to the interval of pilot symbols and the fading variation is constant between pilot symbols. Based on this supposition, coherent detected signal Dout (nT) is expressed in the following expression:
                                                                                D                  out                                                                                (                  nT                  )                                            =                                                                            D                  in                                                                                (                    nT                    )                                    ·                  A                                                                                (                    nT                    )                                    ·                  exp                                                                                (                                          jΘ                                                                    (                        nT                        )                                                              )                                    ·                                                                                A                                                                                (                    nT                    )                                    ·                  exp                                                                                (                                      -                                          jΘ                                                                    (                        nT                        )                                                                              )                                                                                =                                                                            D                  in                                                                                (                    nT                    )                                    ·                  A                                                                                (                    nT                    )                                    2                                                                                2                ◯
In expression {circle around (2)}, A (nT)2 is the component with a constant phase and variable amplitude. Therefore, the phase variation of coherent detected signal Dout (nT) is only dependent on Din (nT). Therefore, the phase of the reception signal is demodulated by digital multiplier 42 multiplying the DFT-processed input signal (baseband signal) by a conjugate complex number of the signal indicating a variation due to fading. The QPSK modulation system is a modulation system with a constant amplitude and variable phase. Therefore, the OFDM transmission/reception apparatus performs coherent detection by demodulating the phase of the reception signal.
Furthermore, the OFDM transmission/reception apparatus can also eliminate any phase difference between transmission and reception carriers and phase variation by frequency offset as well as fading variation.
In a modulation system such as a 16QAM modulation system with a variable phase and variable amplitude, the OFDM transmission/reception apparatus detects a fading variation by dividing an input signal in the pilot symbol interval by a pilot symbol. The OFDM transmission/reception apparatus then performs coherent detection by dividing the input signal by a signal indicating a fading variation.
The OFDM transmission/reception apparatus can also use a delay detection system as the demodulation system.
The coherent signals detected by coherent detectors 21 to 24 are judged by Deciders 25 to 28. After judgment, the 4 signals are converted to a single signal by P/S converter 29. In this way, a demodulated signal is obtained.
As shown above, the conventional OFDM transmission/reception apparatus adds a signal with the same waveform as that of the last part of a valid symbol at the start of the valid symbol as a guard interval. By providing the guard interval, the OFDM transmission/reception apparatus can eliminate a delayed signal whose delay time is shorter than the guard interval through DFT processing of the reception system.
The explanation above referred to a case where the number of carriers is 4, but the same apparatus configuration can also be used when the number of carriers is increased to 8, 16, 32, 64, and so on.
However, the conventional OFDM transmission/reception apparatus adds a guard interval with a fixed length for every valid symbol independently of the channel quality. Therefore, in the case that the channel quality is good and the delay time of the delayed signal is short, a guard interval 2 that is longer than necessary is added, which deteriorates the transmission efficiency.

Method and apparatus for setting a guard interval in an OFDM communication


A method for controlling wear level operations in solid state memory. The method includes receiving a request to write to a memory location identified by a write address of the solid state memory, and making a first determination that the writing to the memory location results in a duplicate write to the memory location. The method further includes, based on the first determination, making a second determination that a number of encountered duplicate writes has reached an adaptively controlled maximum number of duplicate writes, and based on the second determination, performing a wear level operation.

Solid state memory storage devices may be used to store data. Such solid state storage devices may be based on solid state memory such as, for example, Phase Change Memory (PCM) and Spin Torque Magnetic Random Access memory, that degrades as data are written to the memory. Only a limited number of writes to solid state memory may thus be permissible before the solid state memory loses its ability to reliably retain data. Repeated writes to the same memory location may prematurely wear out the memory location, while other memory locations of the solid state memory may still be intact.

Method and system for adaptive wear leveling in solid state memory


An image processing apparatus in which, when a multi-tone image is printed by using an error diffusion technique, error data to be diffused is modified so that the tone level of the image data as printed varies linearly with variation of an input image data. A printed dot of a pixel has a larger area than that of the theoretical pixel so that the dot juts out into adjacent pixels. The error data to be diffused is modified in consideration of jut-out dot areas of adjacent pixels, so as to obtain a linear variation of the tone-level with variation of the input image data.

1. Field of the Invention
This invention relates to an image processing apparatus which expresses an image according to generation and non-generation of dots and more particularly to an image processing apparatus which expresses an image approximately in tones by controlling generation of dots based on a multi-tone image signal.
2. Description of the Prior Art
There is widely used a technique of image expression in which an input image signal is converted into a binary signal and dots are generated in accordance with the binary signal. In this case, intermediate tones are expressed by degree of density of generated (shaded) dots. Regarding a method of binary-coding the image signal for the reproduction of intermediate tones of the input image, attention is recently drawn to the error diffusion technique, as disclosed in Japanese Patent unexamined Publications JP-A-62-242473, JP-A-63-288567, JP-A-63-217768, JP-A-63-214073, JP-A-1-97066, and JP-A-1-115272.
The error diffusion technique is intended to calculate the difference of concentration between the input image and output image on a pixel-by-pixel basis, and the resulting error component is diffused with specific weights to adjacent pixels.
In a case that a pixel of the input image, which is generally square, needs to be expressed by a dot of other shape (e.g. for example, circle), the dot is generally dimensioned to include the corresponding pixel completely. In consequence, when such a dot is generated for a certain pixel, the dot should overlap with an adjacent pixel.
The overlap of dots affects the density of the output image. For example, when a white dot (actually no dot) is printed next to a black dot, the white dot has its area reduced due to the jut-out area of the black dot, resulting in a blackish tone of this portion. Similarly, when a black dot is printed next to a white dot, the black dot juts out into the white dot area, resulting in a blackish tone of this portion. The binary-coding process based on the conventional error diffusion technique is incapable of correcting the influence of dot overlap on the density of the output image.

Image processing apparatus with correction of diffusion errors of overlapping dots


A diverse set of tubulin binding agents have been discovered which are structurally characterized, in a general sense, by a semi-rigid molecular framework capable of maintaining aryl-aryl, pseudo pi stacking distances appropriate for molecular recognition of tubulin. In phenolic or amino form, these ligands may be further functionalized to prepare phosphate esters, phosphate salts, phosphoramidates, and other prodrugs capable of demonstrating selective targeting and destruction of tumor cell vasculature.

The cytoskeletal protein tubulin is among the most attractive therapeutic drug targets for the treatment of solid tumors. A particularly successful class of chemotherapeutics mediates its anti-tumor effect through a direct binding interaction with tubulin. This clinically-promising class of therapeutics, called Tubulin Binding Agents, exhibit potent tumor cell cytotoxicity by efficiently inhibiting the polymerization of αβ-tubulin heterodimers into the microtubule structures that are required for facilitation of mitosis or cell division (Hamel, Medicinal Research Reviews, 1996).
Currently, the most recognized and clinically useful antitumor agents are Vinca Alkaloids, such as Vinblastine and Vincristine (Owellen et al, Cancer Res., 1976; Lavielle et al, J. Med. Chem., 1991) along with Taxanes such Taxol (Kingston, J. Nat. Prod., 1990; Schiff et al, Nature, 1979; Swindell et al, J. Cell Biol., 1981). Additionally, natural products such as Rhizoxin (Nakada et al, Tetrahedron Lett., 1993; Boger et al, J. Org. Chem., 1992; Rao, et al, Tetrahedron Lett., 1992; Kobayashi et al, Pure Appl. Chem., 1992; Kobayashi et al, Indian J. Chem., 1993; Rao et al, Tetrahedron Lett., 1993), the Combretastatins (Lin et al, Biochemistry, 1989; Pettit et al, J. Nat. Prod., 1987; Pettit et al, J. Org. Chem., 1985; Pettit et al, Can. J. Chem., 1982; Dorr et al, Invest. New Drugs, 1996), Curacin A (Gerwick et al, J. Org. Chem., 59:1243, 1994), Podophyllotoxin (Hammonds et al, J. Med. Microbiol, 1996; Coretese et al, J. Biol. Chem., 1977), Epothilones A and B (Nicolau et al., Nature, 1997), Dolastatin-10 (Pettit et al, J. Am. Chem. Soc., 1987; Pettit et al, Anti-Cancer Drug Des., 1998), and Welwistatin (Zhang et al, Molecular Pharmacology, 1996), as well as certain synthetic analogues including Phenstatin (Pettit G R et al., J. Med. Chem., 1998), 2-styrylquinazolin-4(3H)-ones ("SQOs", Jiang et al, J. Med. Chem., 1990), and highly oxygenated derivatives of cis- and trans-stilbene and dihydrostilbene (Cushman et al, J. Med. Chem., 1991) are all known to mediate their tumor cytotoxic activity through tubulin binding and subsequent inhibition of mitosis.
Normally, during the metaphase of cell mitosis, the nuclear membrane has broken down and tubulin is able to form centrosomes (also called microtubule organizing centers) which facilitate the formation of a microtubule spindle apparatus to which the dividing chromosomes become attached. Subsequent polymerization and depolymerization of the spindle apparatus mitigates the separation of the daughter chromosomes during anaphase such that each daughter cell contains a full complement of chromosomes. As antiproliferatives or antimitotic agents, Tubulin Binding Agents exploit the relatively rapid mitosis that occurs in proliferating tumor cells. By binding to tubulin and inhibiting the formation of the spindle apparatus in a tumor cell, the Tubulin Binding Agent can cause significant tumor cell cytotoxicity with relatively minor effects on the slowly-dividing normal cells of the patient.
The exact nature of tubulin binding site interactions remain largely unknown, and they definitely vary between each class of Tubulin Binding Agent. Photoaffinity labeling and other binding site elucidation techniques have identified three key binding sites on tubulin: 1) the Colchicine site (Floyd et al, Biochemistry, 1989; Staretz et al, J. Org. Chem., 1993; Williams et al, J. Biol. Chem., 1985; Wolff et al, Proc. Natl. Acad. Sci. U.S.A., 1991),2) the Vinca Alkaloid site (Safa et al, Biochemistry, 1987), and 3) a site on the polymerized microtubule to which taxol binds (Rao et al, J. Natl. Cancer Inst., 1992; Lin et al, Biochemistry, 1989; Sawada et al, Bioconjugate Chem, 1993; Sawada et al, Biochem. Biophys. Res. Commun., 1991; Sawada et al, Biochem. Pharmacol., 1993). An important aspect of this work requires a detailed understanding, at the molecular level, of the "small molecule" binding domain of both the α and β subunits of tubulin. The tertiary structure of the α,β tubulin heterodimer was reported in 1998 by Downing and co-workers at a resolution of 3.7 Å using a technique known as electron crystallography (Nogales et al, Nature, 1998). This brilliant accomplishment culminates decades of work directed toward the elucidation of this structure and should facilitate the identification of small molecule binding sites, such as the colchicine site, using techniques such as photoaffinity and chemical affinity labeling (Chavan et al, Bioconjugate Chem., 1993; Hahn et al, Photochem. Photobiol., 1992).
An aggressive chemotherapeutic strategy for the treatment and maintenance of solid tumor cancers continues to rely on the development of architecturally new and biologically more potent Tubulin Binding Agents which mediate their effect through a direct binding interaction with tubulin. The present invention addresses this urgent need by providing a structurally novel class of Tubulin Binding Agent compositions with potent antiproliferative activity and tumor cell cytotoxicity. In addition, the present invention provides the important discovery that corresponding prodrug constructs of these agents have selective effects on the tumor vasculature which are independent of its primary antimitotic effects on the tumor itself. These agents are capable of selectively shutting down the flow of blood to a tumor and causing secondary tumor cell death. Thus the present compositions have expanded clinical utility over known tubulin binding agents.

Tubulin binding ligands and corresponding prodrug constructs


The invention provides methods for facilitating a cooperative purchasing service. One method includes: providing a conditional purchase opportunity including a purchase threshold, providing information associated with the a conditional purchase opportunity to at least one display node, receiving a contingent purchase input from a user having a social network user profile, and associating the conditional purchase opportunity with the user profile. A further method includes: requesting cooperative purchase feed formatted content associated with a social network user account, receiving cooperative purchase feed formatted content including a cooperative purchase offer in response to the request, and providing the a cooperative purchase offer including a social network identifier, at a social network user interface. A further method includes: providing a feed formatted cooperative purchasing opportunity, receiving a request to send the cooperative purchasing opportunity to a associate, and Indexing the cooperative purchasing opportunity to an associate feed based on the request.

The networked world, particularly the Internet and World Wide Web (WWW), has provided numerous communication formats and commerce opportunities. Two of the most ubiquitous communication formats include email and HTML web pages. Over the past several years, there has been an increased adoption and development of feed formatted content as a method of communication. Commerce formats have included direct business to consumer set price purchasing, consumer to consumer set price purchasing, as well as auction and bulk pricing.
FIG. 1 shows representative feed formatted content 100. Feed formatted content is structured data, such as for example Electronic Data Interchange (EDI), Extensible Markup Language (XML), or a subset of a general format such as RSS (Rich Site Summary or Really Simple Syndication), a hybrid or extension of some such standard, or the like. Feed formatted content 100 may be accessed through a feed, stored in a local file, or the like. A feed is the data returned when a request for feed formatted content is made. Feed formatted content may include a feed header 101. In one embodiment, feed header 101 includes a header labeling feed formatted content 100 as XML data, and further provides two element wrappers: rss and channel. Feed formatted content 100 often represents multiple items, as is that displayed in FIG. 1. Each feed item 106 may represent one or more news headlines, events, search results, items for sale or any other data. Feed item 106 may contain any number of elements. For example, it may include a title element 107, link element 108, and a description element 109. The term feed formatted content may describe an entire feed, a portion of a feed, a feed item, or a portion of a feed item.
A category of WWW site, commonly referred to as social networking sites, have been developed and grown in popularity in recent years. Site users establish accounts and then create relationships with other user accounts, connecting the users in a social network. While these have drawn large numbers of users, the introduction of commerce on these sites that take advantage of their capabilities has been limited.
It would be useful to provide a method for establishing commerce that may be provided on social network sites.

Method and system for providing cooperative purchasing over social networks


A novel process for producing hindered and unhindered primary amines represented by the formula RNH.sub.2 and R*NH.sub.2 in high yields from novel intermediates RBMe.sub.2 or R*BMe.sub.2 wherein R is an organo group, R* is a chiral organo group. attached to boron, B is boron and Me is methyl.

A. Technical Field
This invention relates to the synthesis of primary amines including optically active primary amines, and more particularly to improved processes for producing such primary amines from olefins and boronic esters, and to novel intermediates useful therein.
Optically active primary amines are of major biological and synthetic importance. For example, (R)-(-)-sec-butylamine is present in pharmacologically active species such as .beta.-blockers and CNS analgesics.
In the typical synthesis of primary amines, RNH.sub.2 from organoboranes, one organic group is typically lost as boronic acid which results in a maximum yield of 67% for less hindered R groups and 50% for more hindered R groups. Accordingly, there has been a long-standing need for methods which provide a more efficient transfer of organyl groups from boron to nitrogen. The present invention provides such intermediates and methodologies.
B. Prior Art
Organoboranes have been used to synthesize amines by reaction with appropriate aminating reagents such as NH.sub.2 Cl and NH.sub.2 OSO.sub.3 H (H. C. Brown, W. R. Heydkamp, E. Breuer, W. S. Murphy, J. Am. Chem, Soc, 1964, 86, 3365]; NH.sub.3 +NaOCl [G. W. Kabalka, K. A. Sastry, G. W. McCollum, H. Yoshioka, J. Org, Chem. 1981, 46, 4296); chloramine-T [V. B. Jigajinni, A. Pelter, K. Smith, Tetrahedron Letters 1978, 181] and Q-mesitylenesulfonylhydroxylamine (Y. Tamura, J. Minamikawa, S. Fujii, M. Ikeda, Synthesis 1973, 196].
As mentioned above, yields achieved in these prior art processes were, at most, 67% for less hindered R groups and 50% for more hindered R groups.
The reaction of trialkylboranes with freshly prepared chloramine proceeds in the presence of aqueous sodium hydroxide. However, only two of the three groups in R.sub.3 B were utilized. ##STR1## Consequently the maximum possible yield for R.sub.3 B is only 67%. H. C. Brown, W. R. Heydkamp, E. Breur and W. S. Murphy, J. Am. Chem, Soc., 86, 3365 (1964).
More hindered alkenes undergo hydroboration only to the dialkylborane stage, readily converted into the corresponding dialkylborinic acids or esters. These derivatives also react with preformed chloramine to form the primary amines. But in this case, only one of the two groups could be made to react. ##STR2## Consequently, in such cases, the maximum yield is only 50%. Moreover, the reaction of the more hindered dialkylborane derivatives is very sluggish with decreased yields. H. C. Brown, G. W. Kramer, A. B. Levy and M. M. Midland, "Organic Synthesis via Boranes", Wiley-Interscience, New York, 1975.
The preparation of optically active primary amines of very high enantiomeric purities from boronic esters of essentially 100% optical purity and LiMe was described by Herbert C. Brown et al, J. Am. Chem, Soc, 1986, 108, 6761-6764. This procedure produced optically pure primary amines in yields of between 72-83%. While improved yields were obtained on a laboratory scale, methyllithium is a relatively expensive reagent, and is too expensive to be used for large scale commercial production of amines. Thus a need remains for a process for economically producing primary amines in high yields as well as for economically producing optically active amines of high optical purity in improved yields.
The present invention provides a process which enables synthesis of both hindered and unhindered primary amines in excellent yields of up to 95%, and in all cases, in higher yields than those achieved by prior art methods.

Method of producing primary amines in high yields


A carabiner multi-tool includes a first generally C-shaped portion, a central extended portion, and a second generally C-shaped portion with the central extended portion joining the first and second C-shaped portions into a continuous body. Second ends of the first and the second C-shaped portions form first and second body ends positioned in spaced apart substantially opposed relationship. A shaft has one end pivotally attached to the first body end and a free end pivotally movable into a closed orientation with the second body end and an open orientation with the second body end. An engagement member is mounted on either the free end of the shaft or the second body end for engaging the free end of the shaft and the second body end in a closed orientation. Multiple tools are formed in the first and the second generally C-shaped portions.

In many fields, especially many modern sports, such as skateboarding and the like, the equipment serves best if care and maintenance are practiced regularly. While skateboards and the like are used herein for a convenient example, it will be understood that the tools referred to might be used with virtually any activity where such tools are kept handy for quick and multiple use. Skateboarding is referred to specifically as an example of equipment which, because of the complexity of much of the equipment adjustments, tightening, and other factors may need constant attention. To perform this care and maintenance in many instances requires special tools that can be cumbersome and inconvenient to carry along during performance or use of the equipment.
It would be highly advantageous, therefore, to remedy the foregoing and other deficiencies inherent in the prior art.
Accordingly, it is an object of the present invention to provide a new and improved carabiner multi-tool.
It is another object of the present invention to provide a new and improved carabiner multi-tool including a carabiner-type arrangement for easy and convenient carrying.
Another object of the invention is to provide a new and improved carabiner multi-tool including multiple tools and multiple types of tools in a single carabiner-type unit.


A method for reducing aqueous phase separation of an emulsion comprising ethanol-based fuel and a lubricating oil comprising molybdenum ester amide complex, comprising the step of adding to the lubricating oil a dispersant polyalkyl (meth) acrylate (DPMA) in an amount from about 0.01 to about 0.5% by weight of the lubricating oil, such that the weight ratio of molybdenum to DPMA is about 2.05 or less.

This invention relates to the method of reducing aqueous phase separation and improving emulsion retention capacity of an emulsion composition comprising a lubricant base oil containing molybdenum ester/amide and its combination with alcohol-based fuel, such as E85 fuel and water. E85 is an abbreviation for an ethanol fuel blend of 85% denatured ethanol fuel and 15% gasoline or other hydrocarbon by volume, although the exact ratio of fuel ethanol to hydrocarbon can vary considerably while still carrying the E85 label. The ethanol content is adjusted according to the local climate to maximize engine performance. ASTM D5798 specifies the allowable fuel ethanol content in E85 as ranging from 51% to 83%.
In recent years, use of alternative fuel has resonated with the consumers concerned about U.S. dependence on imported oil as well as the ever increasing price of gasoline. As an alternative fuel to gasoline, use of ethanol produced from biomass has increased in recent years for the internal combustion engine. With the introduction of ethanol in gasoline came the concern of water-phase separation. Water in gasoline can have different effects on an engine, depending on whether it is in solution or forms a separate water phase. While a separate water phase in a fuel can be damaging to an engine, a small amount of water in solution with gasoline should have no adverse effects on engine components.
Although ethanol will readily dissolve water, water will separate from blends of gasoline and ethanol when the solubility limit in ethanol is reached. The amount of water required for this phase separation varies with temperature. When phase separation occurs in an ethanol blended gasoline, the water will actually begin to remove the ethanol from the gasoline. Therefore, the second phase which can occur in ethanol blends contains both ethanol and water. In the case of four stroke engines, the water-ethanol phase may combust in the engine. This combustion can be damaging to the engine because the water ethanol phase creates a leaner combustion mixture. Leaner mixtures tend to combust at highest temperature and can damage engines and also results in reduced fuel economy. In addition, this water-ethanol phase will compete with the blended oil for bonding to the metal engine parts. Therefore, the engine will not have enough lubrication, and engine damage may result. Hence, maintaining emulsion stability of alcohol-gasoline mixed fuel with lubricating oil compositions is a primary concern. Inability to maintain stable emulsions, especially in the cold climate and small infrequent short distance driving cycles, leads to separation of an aqueous layer which results in corrosion of fuel tanks, fuel delivery systems and other critical components of the engine. Hence, any method to reduce aqueous phase separation will be useful.
A particularly useful friction modifier additive used in engine oils is a molybdenum ester amide, available as MOLYAN® 855 from Vanderbilt Chemicals, LLC, of Norwalk, Conn. While this molybdenum compound provides excellent friction modifier properties, it suffers from a drawback when used in engines running alcohol-based fuels, such as E85. In particular, the molybdenum ester amide compound used in such an engine may lead to unwanted aqueous phase separation in the fuel mixture. Accordingly, there is a desire to overcome this problem by formulating a lubricating composition which contains a molybdenum ester amide, but which avoids aqueous phase separation when used with E85 or other alcohol based fuels.
U.S. Pat. Application No. 20120108478 to Lam et al. discloses a lubricant composition suitable for use in engines fueled by gasoline or bio-renewable fuels, or both, comprising an oil of lubricating viscosity and a dispersant system to reduce aqueous separation in an emulsion composition. A dispersant system suitable for use herein can comprise at least one dispersant. Useful dispersants include, but are not limited to, basic nitrogen-containing ashless dispersants, such as hydrocarbyl succinimides; hydrocarbyl succinamides; mixed ester/amides of hydrocarbyl-substituted succinic acids, Mannich condensation products of hydrocarbyl-substituted phenols, formaldehyde and polyamines; and amine dispersants formed by reacting high molecular weight aliphatic or alicyclic halides with amines, such as polyalkylene polyamines. Mixtures of such dispersants can also be used.
Research paper published to Patel et al. (SAE Int. J. Fuels Lubr. 3(2):938-945, 2010) discusses the effect of viscosity index modifier on ethanol/gasoline/water emulsions formed in E25 and E85 fuels in passenger car motor oil. This study includes viscosity index modifiers such as olefin co-polymer (OCP), styrene-isoprene polymer (SI) and poly (alkyl methacrylate) polymer (PMA) at treat rate of 8.9 wt. %, 7.2 wt. % and 5.8 wt. % respectively. This study reported that none of the emulsion exhibited a separate water phase, regardless of the types of viscosity index modifier.
WO 2013/182581 relates to an engine oil additive for increasing fuel economy. The additive comprises a molybdenum compound, such as molybdenum ester amide (MOLYVAN® 855) in an amount which provides 1-1000 ppm (0.0001-0.1 wt. % Mo); a polyalkyl (meth) acrylate at 1-15 wt. %, preferably 2-8 wt. %; a phosphorus compound; and an antioxidant system. It is noted that the invention is specifically directed towards new fuel economy requirements for gasoline and/or diesel engines. There is no mention of E85 ethanol-based fuels, or their attendant emulsion problems.

Method of reducing aqueous separation in an emulsion composition suitable for engine fueled by E85 fuel


A light emitting device comprising a base, a rod-shaped heat sink element extending from the base along a longitudinal axis of the light emitting device, the rod-shaped heat sink element comprising N sides. The N sides comprise at least one top side which in an assembled condition of the light emitting device faces away from an exit window of the light emitting device, at least one bottom side which in an assembled condition of the light emitting device faces towards an exit window of the light emitting device, and at least two mutually opposite sides extending between said at least one top side and said at least one bottom side. The N sides comprise M LED arrays, each comprising a plurality of LEDs, each LED of the plurality of LEDs comprising a respective light output surface arranged facing in a main direction. The at least one first LED array comprises a plurality of side emitting LEDs, the at least one second LED array comprises a plurality of top emitting LEDs and the at least one third LED array and the at least one fourth LED array each comprises a plurality of either side or top emitting LEDs.

High Pressure Sodium (HPS) lamps, such as SON-T, are used for road and residential lighting, decorative floodlighting, commercial and industrial applications, and recreational sports facilities indoor and outdoor. Such lamps comprise a bright arc which emits light omnidirectional and is placed in the optical center of a reflector of a luminaire which collects and redirects the light to, for example, a road.
Various LED configurations have been proposed to replace these high brightness—high lumen output lamps. For instance, a light emitting device which comprises a base which has a longitudinal axis and an elongated rod-shaped heat sink which is configured to remove heat from 6 LED arrays which are placed on different sides of the elongated rod-shaped heat sink has been proposed. Two further heat sinks may be arranged in thermal contact with and on both sides of the elongated rod-shaped heat sink.
One such possible solution is disclosed in KR 968270 B1, which describes a lamp with a rod shaped heat sink comprising a hexagonal cross section and with LED arrays mounted on all six surfaces of the rod shaped heat sink. All LED arrays are of identical configuration, i.e. of identical number of LEDs and arrangement of the LEDs in the array. Also, the lamp comprises a reflector for each array of LEDs.
However, the further heat sinks of the LED light emitting device are rather bulky in order to provide sufficient cooling. As a result, they block part of the direct light from the LED sources and part of the light which is being reflected by the reflector. The luminaire socket may also block the light which is being reflected by the reflector.


Method and apparatus for wrapping a signature bundle by moving a wrapping sheet into the path of movement of a bundle, said sheet being maintained in self-supporting fashion by imparting a bend thereto as it is fed to the wrapping station. The bundle "crashes" into the sheet causing it to collapse and wrap itself about the bundle. When the wrapping operation is completed, the wrapping sheet is wrapped around three contiguous surfaces of the bundle. The sheet is automatically cut and a new wrapping operation is initiated. The wrapping sheet may be printed upon by an ink jet printing characters "on the fly". The characters are printed backwards and "bleed through" the wrapping sheet to appear in normal manner.

Signatures, such as newspapers, are typically produced at high production rates of 80,000 or more newspapers per hour. Signatures are delivered from the press, in overlapping fashion and are delivered to stackers which count and stack the newspapers forming bundles of either compensated or non-compensated type, said bundles comprising typically from as few as ten or fifteen newspapers to the order of one hundred newspapers per bundle. When a bundle is completed, it is typically provided with a protective wrap sheet which is wrapped about several surfaces (typically a bottom surface and two contiguous side surfaces) of the bundle whereupon the bundle is then tied with the wrap sheet in place.
Previous techniques employed to wrap a bundle typically utilize an articulated mechanical arm equipped with either suction heads or grippers for grabbing the wrapping paper off of the surface of the conveyor belts carrying the bundles and lifting the wrapping paper above the conveyor belt to form a "wall" of wrapping paper which lies in the path of movement of the approaching bundle. The mechanical arm moves at very high speed between the elevated and withdrawn positions subjecting the mechanical arm to severe wearing. In addition, the movement of the arm creates an extremely hazardous condition to personnel.
It is, therefore, extremely advantageous to provide apparatus for wrapping bundles of signatures, such as newspapers, in a high speed and yet safe manner and through the use of apparatus which does not present a hazard to operating personnel and does not require high speed movement of large mechanical arms.

Method and apparatus for wrapping signatures and the like


Provided is a gas barrier pressure-sensitive adhesive sheet having at least one gas barrier layer and at least one pressure-sensitive adhesive layer, the at least one pressure-sensitive adhesive layer having a storage modulus at 23° C. of 1.5×104 to 1.0×107 Pa, and the gas barrier pressure-sensitive adhesive sheet not including a base layer. Also, provided is the following: a gas barrier pressure-sensitive adhesive sheet that makes it possible to easily provide the adherend with a gas barrier capability without significantly increasing the thickness of the gas barrier pressure-sensitive adhesive sheet, does not show delamination (separation) at the interface between the pressure-sensitive adhesive layer and another layer even when subjected to high-temperature/high-humidity conditions, and exhibits excellent bendability, a method for producing the same, an electronic member that includes the gas barrier pressure-sensitive adhesive sheet, and an optical member that includes the gas barrier pressure-sensitive adhesive sheet.

Use of a transparent plastic film as a substrate of a display (e.g., liquid crystal display or electroluminescence (EL) display) has been studied in order to implement a display that has a reduced thickness, reduced weight, and flexibility.
However, since a plastic film generally allows water vapor, oxygen, and the like to pass through as compared with a glass substrate, the elements provided in a display may easily deteriorate when a transparent plastic film is used as a substrate of a display.
In order to solve the above problem, Patent Document 1 proposes a flexible display substrate in which a transparent gas barrier layer formed of a metal oxide is stacked on the surface of a transparent plastic film using a deposition method, an ion plating method, a sputtering method, or the like.
However, since excessive heat is applied to the plastic substrate when using the method disclosed in Patent Document 1, the optical properties of the plastic substrate may be adversely affected, and a deterioration in transparency may occur.
The above problem may be solved using a transfer laminate that includes a gas barrier layer. For example, Patent Document 2 discloses a method that includes forming a hard coat layer on a heat-resistant support, forming a gas barrier layer on the hard coat layer to obtain a transfer laminate, bonding a base formed of a polymer material to the gas barrier layer of the transfer laminate through an adhesive, and removing the heat-resistant support to obtain a liquid crystal display plastic substrate in which the gas barrier layer and the hard coat layer are stacked on the base formed of a polymer material.
Patent Document 3 discloses a plastic liquid crystal panel transfer foil in which at least one of a hard coat layer and a gas barrier layer and an adhesive layer are sequentially formed on a base film either directly or through a release layer. Patent Document 3 also discloses a method that produces a plastic liquid crystal panel by transferring the transfer foil to a plastic substrate using a heat transfer method.
However, the transfer laminates disclosed in Patent Documents 2 and 3 have a problem in that the gas barrier layer may be removed from the adhesive layer, or blisters or lifting may occur between the gas barrier layer and the adhesive layer when the transfer laminate is rolled (curved) or bent. Moreover, lifting may occur at the interface between the adhesive layer and the adherend (e.g., plastic substrate), and the transfer laminate may be removed from the adherend when the transfer laminate is bonded to the adherend, and subjected to high-temperature/high-humidity conditions.

Gas barrier adhesive sheet, method for producing same, electronic member, and optical member


A biocompatible material which is the product of graft-copolymerization of a water-soluble vinyl and/or an acrylate monomer with a sorption complex of polysilicic acid and collagen that has been rid of pigments, glycoproteins and proteoglycans, or a product obtained by virtue of chemical destruction, with the aid of hydrofluoric acid, of the afore-mentioned product of graft-copolymerization, containing up to 25 mass percent of polysilicic acid (in terms of SiO.sub.2), up to 12 mass percent of protein, and maximum 1 10.sup.-6 mole/g of an anion of hydrofluoric and hydrofluoric acids, methods of making the same and products produced thereby.

A number of diverse biocompatible materials are known to use in ophthalmological practice, which are based on collagen, i.e., fibrous protein. Collagen serves as a kind of framework performing a supporting function for other proteins, as well as for cells; it is present in all body tissues, in the skin, tendons, and bones.
A variety of techniques of collagen isolation from raw materials are widely known, by its dissolution in acids, alkalis, salts, or with the aid of enzymes, as well as its isolation in a solid undissolved fibrous state by exposing the disintegrated raw material to the effect of salts. The isolated collagen is cleaned from pigments, glycoproteins, and proteoglycans, using the commonly known methods.
One state-of-the-art biocompatible collagen-based material is known to use for making contact lenses (U.S. Pat. No. 4,268,131), said material being in fact a gel based on fibrous collagen or a mixture of fibrous collagen with collagen in a dissolved state.
In order to produce said material diverse methods are used for collagen extraction from raw stock (such as hides, tendons, skin, and others) by means of its dissolution in acids (acetic or citric) or in alkalis, followed by centrifugation of the resultant solution, washing it with water, dehydration, drying, redissolution, filtration, precipitation, and recentrifugation. To produce a lens, a 4- to 10-percent gel is prepared on the basis of collagen in an aqueous acid medium having the pH value of from 2 to 4. Resort is also made to enzymic extraction in the presence of proteolytic enzymes, such as pepsin, trypsin, protease, and others.
However, the aforesaid material cannot be used for making long-lived transplants and those having preset porosity of the material, and hence its gas permeability, since used for producing said material is a protein that features a statistical average mass of from 120 to 130 thousand D (the porosity of the material depends on the geometric dimensions of a molecule and the physicochemical characteristics of collagen by which said material is constituted).
Moreover, the material in question is not resistant to the effect of enzymes as being completely constituted by protein molecules, which are liable to undergo lysis. Thus, low porosity of the material and its low resistance to the effect of enzymes result in reduced biocompatibility of the material with the eve tissues.
Another prior-art collagen-based biological material containing ethylene-unsaturated compounds is known to use for making contact lenses (U.S. Pat. No. 4,388,428).
The material under consideration is in effect a polymerized hydrophilic composition liable to swell in water and consisting of soluble collagen and an ethylene-unsaturated monomer featured by the presence of a polymerizable double carbon-carbon bond.
The material discussed herein is produced by extracting fibrous collagen from animal's hide by enzymic extraction with the aid of pepsin. The thus-extracted and purified collagen is mixed with an aqueous solution of an ethylene-unsaturated monomer, and in the resultant mixture collagen is dissolved by acidifying said mixture with 1.0M HCl till the pH value of 3. The resultant solution is filtered, drawn in a syringe, wherein the solution is degassed, centrifugated and filled into lens moulds.
However, the material dealt with in the form of a hydrogel is featured by inadequate gas permeability and porosity accounted for by geometric dimensions of collagen molecules and of molecules of the monomer used, as well as by a low protein content, low shelf- and service life.

Biocompatible polymer material and a process for producing same

ulitsa Oktyabrskaya, 60, korpus 2, kv. 25


A drive unit of a robotic vehicle including a top surface having a mounting interface to interchangeably couple with multiple different modular payload structures configured to transport items in a facility, workspace or inventory management environment. The mounting interface is configured to securely engage with a mounting portion of the variety of different payload structures to enable a versatile exchange of the payload structure for different conveyance applications. The drive unit includes an electrical interface to communicatively couple with the modular payload structures. The drive unit is configured to use data communicated via the electrical coupling and interface to identify a type of modular payload structure that is mechanically coupled to the mounting interface and implement a motion profile (e.g., speed and acceleration parameters) associated with the identified modular payload structure.

Ground vehicles can operate in an environment to perform certain tasks, including the conveying of materials from one point to another. The environment may require the ground vehicles to transport many different types of materials to accommodate a variety of different applications. For example, the materials being transported can have a range of different shapes, sizes, weights, dimensions, etc. Since the environment may include other physical objects (e.g., workers, other ground vehicles, walls, equipment, etc.), safe conveyance and disposition of the variety of different materials is objects is desired.

Drive unit with interface to mount and identify multiple different payload structures


Techniques for processing each of multiple threads that share a core processor include receiving an intra-thread register address from the core processor. This address contains C bits for accessing each of 2c registers for each thread. A thread ID is received from a thread scheduler external to the core processor. The Thread ID contains T bits for indicating a particular thread for up to 2T threads. A particular register is accessed in a register bank that has 2(C+T) registers using an inter-thread address that includes both the intra-thread register address and the thread ID. The particular register holds contents for the intra-thread register address for a thread having the thread ID. Consequently, register contents of all registers of all threads reside in the register bank. Thread switching is accomplished rapidly by simply accessing different slices in the register bank, without swapping contents between a set of registers and memory.

1. Field of the Invention
The present invention relates to using hardware to assist in multi-threaded processing and, in particular, to using hardware to select a sliding window in a register bank and data random access memory (RAM) when switching between threads in fewer clock cycles than in conventional thread switching mechanisms.
2. Description of the Related Art
Many processors are designed to reduce idle time by swapping multiple processing threads. A thread is a set of data contents for processor registers and memory and a sequence of instructions to operate on those contents that can be executed independently of other threads. Some instructions involve sending a request or command to another component of the device or system, such as input/output devices or one or more high valued, high-latency components that take many processor clock cycles to respond. Rather than waiting idly for the other component to respond, the processor stores the contents of the registers and the current command or commands of the current thread to local memory, thus "swapping" the thread out, also described as "switching" threads and causing the thread to "sleep." Then the contents and commands of a different sleeping thread are taken on board, so called "swapped" or "switched" onto the processor, also described as "awakening" the thread. The woken thread is then processed until another wait condition occurs. A thread-scheduler is responsible for swapping threads on or off the processor, or both, from and to local memory. Threads are widely known and used commercially, for example in operating systems for most computers.
Some thread wait conditions result from use of a high-value, long-latency shared resource, such as expensive static random access memory (SRAM), quad data rate (QDR) SRAM, content access memory (CAM) and ternary CAM (TCAM), all components well known in the art of digital processing. For example, in a router used as an intermediate network node to facilitate the passage of data packets among end nodes, a TCAM and QDR SRAM are shared by multiple processors to parse data packets and classify them as a certain type using a certain protocol or belonging to a particular stream of data packets with the same source and destination. Processing for each packet typically involves from five to seven long-latency memory operations invoking the TCAM or QDR or both. These long-latency memory operations can take about 125 clock cycles or more of a 500 MegaHertz clock (MHz, 1 MHz=106 cycles per second) that paces processor operations. The parse and classify software programs typically execute twenty to fifty instructions between issuing a request for a long-latency memory operation. A typical instruction is executed in one or two clock cycles.
A desirable goal of a router is to achieve line rate processing. In line rate processing, the router processes and forwards data packets at the same rate that those data packets arrive on the router's communications links. Assuming a minimum-sized packet, a Gigabit Ethernet link line rate yields about 1.49 million data packets per second, and a 10 Gigabit Ethernet link line rate yields about 14.9 million data packets per second. A router typically includes multiple links. To achieve line rate processing, routers are configured with multiple processors. The idle time introduced by the frequent long-latency memory accesses increases the number of processors needed to support line rate processing.
In one approach, commercially available multi-threaded processors are used. While suitable for many purposes, the commercially available multi-threaded processors suffer some disadvantages. One disadvantage is that thread switching involves many clock cycles as all the contents of multiple registers used by the processor as operands and results of instructions are swapped, i.e., moved off the processor to a more spacious memory (that is often off the chip and requires use of a shared bus) and replaced by contents of registers for a different thread in another portion of that memory. These multi-threaded processors also consume clock cycles to swap instructions and data in local caches to other more spacious memory, such as off-chip memory. These extra cycles reduce the effectiveness of each multi-threaded processor and requires the deployment of more such processors to achieve line rate processing in a router
Another disadvantage is that some multi-threaded processors use a thread scheduler process that forces a thread switch at arbitrary times, such as after a certain number of clock cycles unrelated to when the thread issues a long-latency memory operation. Such processors incur the cost of thread switching without the benefit of reduced idle time on the processor.
In another approach, a processor could be designed to switch threads when long-latency commands are issued using larger on-chip memories to reduce clock cycles in swapping information with more distant larger capacity memories when threads are switched, and also provide an option to avoid swapping instruction sets. However, the design and development of a new processor is an extremely costly effort that takes many years. Such effort is typically justified only for a mass market. Thus, there is little likelihood that such an effort can or will be undertaken soon.
Based on the foregoing, there is a clear need for techniques for thread-switching that do not suffer some or all the deficiencies of the conventional approaches in multi-threaded processors.
The approaches described in this section could be pursued, but are not necessarily approaches that have been previously conceived or pursued. Therefore, unless otherwise indicated herein, the approaches described in this section are not to be considered prior art to the claims in this application merely due to the presence of these approaches in this background section.

Techniques for hardware-assisted multi-threaded processing


From tungsten or molybdenum powders, a tungsten or molybdenum compact is pressurized and molded into the same dimensions as or slightly larger than the end product and sintered into tungsten or molybdenum skeleton. After copper infiltration, chemical copper etching is applied to remove excess surface copper. A machining allowance with an absolute value >0-≦0.1 mm may be applied for the machining of uneven surfaces resulting from the chemical process of copper removal.

1. Field of the Invention
The present invention relates to a new process for making copper/tungsten and copper molybdenum composite packaging materials, and more specifically, to a chemical copper removal process that improves manufacturing and material utilization efficiency tremendously.
2. Description of the Prior Art
Copper/tungsten and copper molybdenum composites, preserving tungsten and molybdenum's characteristic of low thermal expansion and copper's high thermal conductivity, have been widely used in the packaging of microwave devices, optoelectronic components, integrated circuits, and many other electronic packaging applications. Their measures of thermal expansion coefficient, thermal conductivity, and electrical conductivity can easily be controlled by varying copper/tungsten and copper/molybdenum ratios. They can also be matched with semiconductor silicon, arsenic, gallium arsenide, aluminum oxide and beryllium oxide, etc.
Since tungsten, molybdenum and copper have considerably different melting points, it is impossible to melt W and Cu into each other at high temperatures. In other words, no eutectic will be formed. Therefore, copper/tungsten and copper/molybdenum composite material can only be fabricated through powder metallurgy. At present, there are three major techniques: infiltration, high-temperature liquid phase sintering, and activated liquid phase sintering.
Infiltration
In this technique, tungsten and molybdenum powder are mixed with a small amount of binders, pressurized and molded into a tungsten or molybdenum compact, and then sintered into a tungsten and molybdenum skeleton. Designed excess copper is thereafter attached to the surfaces of the tungsten and molybdenum skeleton and infused into the tungsten and molybdenum skeleton at temperature higher than the melting point of copper (typically 1350° C.). Precision machining will then be performed to get the desired dimensions.
An example can be found in U.S. Pat. No. 2,179,960, issued in 1939. Internationally, an example can be found in Chinese patent CN1995438, the disclosure of a process for making copper/tungsten and copper/molybdenum composites through sintering tungsten and molybdenum powder into a skeleton which is then infiltrated with molten copper.
An advantage of this technique is that during the process of infiltrating copper into the tungsten and molybdenum skeleton, most of the voids and interstices between the sintered tungsten or molybdenum particles can be filled by copper and hardly any eutectic develops. Therefore, critical measures such as hermeticity and thermal conductivity are ideal, especially the thermal conductivity, which can reach 180-200 W/mK.
The disadvantage associated with this method is that, for each and every piece of copper/tungsten and copper/molybdenum composite, thickness of the copper infiltration overflow is unpredictable and inconsistent. To facilitate precision machining, the tungsten or molybdenum skeleton needs to be at least 0.8 mm extra in thickness than the finished product. Machining allowance has to be even bigger when machining parts with mounting holes, steps, pedestals, slot and other 3D features to their desired shapes. The result is a decrease in efficiency and vast waste of tungsten or molybdenum, which sometimes accounts for 80% of the final composite and is a few times more expensive than copper. Compared to high temperature liquid phase sintering and activated liquid phase sintering, this method causes 10-45% more waste of materials. It is the most expensive technique of all considering the material and manufacturing costs, especially for irregular shaped products.
High-Temperature Liquid Phase Sintering
First, tungsten or molybdenum powders and copper powders are mixed to the designed proportion. The mixture is then pressurized and molded into compacts 0.2-0.3 mm larger in every dimension than the final product, after which it is sintered at temperature higher than 2000° C. To obtain the desired product dimensions, precise machining is performed to remove the excess copper.
An example can be found in U.S. Pat. No. 5,686,676, in which the sinterability of a copper/tungsten green compact is improved by using copper oxide, tungsten oxide or both as the copper and/or tungsten source. Sinterability is further enhanced by including steam in the sintering atmosphere.
Another example can be found in U.S. Pat. No. 6,589,310, in which the sinterability is further improved using phosphorous as sintering aid.
An advantage of this method is the efficient use of expensive tungsten, since the machining allowance will be much smaller than required by the infiltration method. It has its drawbacks, too. First, sintering temperature is high, which makes this process costly.
Sintering cost takes up the biggest proportion of total cost after material cost. Second, high temperature sintering leads to the formation of eutectic, which reduce the hermeticity and thermal conductivity of copper/tungsten and copper/molybdenum composites, the two properties that affect the reliability of integrated circuits. Thermal conductivity of final product attained by this method is only 180-190 W/mK. Finally, precise machining surface by surface and piece by piece increases complexity of manufacture and cost. It is especially the case for the fabrication of irregular shaped packaging materials.
Activated Liquid Phase Sintering:
This technique is developed to lower the temperature requirements by high-temperature liquid phase sintering. Chemical activators such as nickel, cobalt and copper oxide are included in the liquid phase sintering process. This action makes eutectic form at a lower temperature, thus reducing the temperature requirements for sintering.
Although activated liquid phase sintering lowers the sintering temperature to around 1600° C., the decrease is not significantly different from what is required by high temperature liquid phase sintering technique. Not only does it not eliminate disadvantages associated with the other manufacturing techniques, but the use of sintering activators increases the quantity of eutectics that may cause micro pores on some parts. Thus, parts produced by this technique have even lower hermeticity and thermal conductivity than those produced by high temperature liquid phase sintering. The thermal conductivity attained by this technique is only 50-170 W/mK.
Additional prior art related to this invention can be found in U.S. Pat. Nos. 343,875, 3,440,043, 3,969,754, 4,153,755, 4,158,719, 4,168,719, 4,196,442, 4,430,124, 4,451,540, 4,500,904, 4,672,417, 4,680,618, 4,736,883, 4,752,334, 4,788,627, 4,988,386, 5,009,310, 5,039,335, 5,049,184, 5,086,333, 5,099,310, 5,379,172, 5,379,191, 5,380,956, 5,386,143, 5,386,339, 5,387,815, 5,409,864, 5,413,751, 5,439,638, 6,589,310, 6,914,032, 7,063,815, 7,122,069 and 7,172,725.
All of the above techniques for manufacturing copper-tungsten composite packaging materials have their drawbacks. Extensive machining is the only way adopted by existing technologies to remove the excess copper. The amount of copper infiltration, molding shrinkage, and machinery process may cause 0.2-0.8 mm loss in size for the final product. In summary, the manufacturing efficiency has been low and the share of processing cost high, especially when fabricating products with mounting, holes, slots, pedestals and other irregular shapes.
Accordingly, there is a need for a new process for making copper/tungsten and copper molybdenum composite electronic packaging materials that reduces the complexity and cost of manufacture.

Process for making copper tungsten and copper molybdenum composite electronic packaging materials


The invention features an electrode array (7) in which pairs of electrodes (1) are geometrically arranged so that the broadest faces of the exposed electrodes are not directly opposing to each other. Rather, the broadest facing surfaces of the electrodes in the array are parallel, adjacent, or offset at an angle. The electrode geometry of an electrode array of the invention permits electrodes to be in close proximity, thereby lowering series resistance, while minimizing the possibility for short circuits that can cause electrical leakage. An electrode array of the invention can be used in an electrochemical cell, such as a battery, e.g., a lithium battery, a capacitor, a flow-through capacitor, or a fuel cell.

In electrochemical cells, such as capacitors, batteries, fuel cells, and flow-through capacitors, it is desirable to reduce series resistance and electrical leakage, which waste energy. Normally, to reduce series resistance, it would be desirable place the electrodes close together. However, proximity is difficult to achieve with purely opposing electrodes. In order to place the electrodes close together, for example, closer than 0.03 inches (˜760 μm), the dielectric between them must be thin, but this geometry has the undesirable effect of increasing the electrical leakage. Moreover, where the electrochemical cell is a flow-through capacitor, thin dielectric spacers lead to a drop in pressure. Therefore, it is desirable to provide for a new and improved electrochemical cell with minimal series resistance and with low electrical leakage.

Electrode array for use in electrochemical cells


A first conductor array (24, FIG. 5) of an electronic device (21) such as an integrated circuit is interconnected to a second conductor array (25) of a first substrate (22) by, first, using photolithographic masking and etching to make an array of substantially uniformly spaced apertures (15, FIG. 2) in a mask (11). The mask is located over a second substrate (12), and the apertures are used to form an array of substantially uniformly spaced metal particles (19). The metal particles are joined with insulative material (11) to form a layer of anisotropic conductive material (20), and the anisotropic conductive material layer is removed from the second substrate. The conductors (24) in the first conductor array of the electronic device are registered with conductors (25) of the second conductor array of the first substrate (22), and the layer of anisotropic conductive materials is compressed between the first and second conductor arrays. This causes individual particles of the layer of anisotropic conductive material to make simultaneous contact with conductors of the first (24) and second (25) conductor arrays so as to interconnect the electronic device to the conductors of the first substrate. The insulative material (11) may be an adhesive, in which case it permanently bonds the device (21) to the substrate (22), or alternatively, the anisotropic conductive material (20) may only temporarily interconnect the electronic device with the first substrate as is required for testing of the device.

Considerable work has been expended in improving techniques for bonding semiconductor integrated circuit chips to conductive circuit patterns of a substrate. One such method uses an anisotropically conductive adhesive between bonding pads on the substrate and matching bonding pads of the integrated circuit chip. The adhesive may typically be an insulative polymer containing conductive particles that simultaneously contact a pad of the chip and a matching pad of the substrate to provide interconnection. The conductive particles do not conduct in the lateral or horizontal direction; since they transmit current only in the vertical direction between the substrate and device bonding pads, the conduction is referred to as "anisotropic." The polymer is cured after mounting the chip on the substrate which thereafter provides a permanent structural bond in addition to a conductive interconnection. The replacement of solder bond connections by anisotropic conductive adhesives can often reduce assembly costs, can accommodate relatively high densities of conductive interconnections, and can make devices more amenable to repair and recycling.
A class of anisotropic conductors that provides a temporary interconnection between a device and a substrate is known as elastomeric conductive polymer interconnection (ECPI) material. This material is useful for interconnecting an electronic device to a test fixture so that current can be appropriately directed through the chip for testing purposes, with the device thereafter being removed from the test fixture. Whether the use is as an ECPI material or an adhesive, anisotropic conductive materials that are used for interconnections to integrated circuit chips must have an appropriately small separation, or pitch, between adjacent conductors so that one can assure that each of the tiny conductor pads of the device will be contacted, and yet the adjacent conductors cannot be so close as to provide lateral conduction or to permit any electrical breakdown within the insulative material. Accordingly, there is a continuing need for anisotropic conductive materials that have a sufficiently small pitch that they can dependably be used to make contact with tiny conductors of an integrated circuit chip and yet are dependable in providing insulation between adjacent conductors of an integrated circuit chip. There is a need for such anisotropic conductors, both for permanently bonding integrated circuit chips to substrates, and for permitting temporary interconnection as is required for device testing.


A distance sensor detects a distance to an object in front of a vehicle. An ECU executes pre-crash control when the detected distance becomes equal to or smaller than a prescribed value. A regeneration level selector selects a regeneration level of a motor in accordance with driver's operation. A motor makes regenerative braking force at the time of turning off an accelerator larger when the selected regeneration level is high than when the selected regeneration level is low. The ECU makes the prescribed value larger when the selected regeneration level is low than when the selected regeneration level is high.

1. Field of the Invention
The present invention relates to a vehicle, and particularly to a vehicle including a regeneration level selector for a motor and executing pre-crash control when a distance to an object in front becomes short.
2. Description of the Background Art
There has been conventionally known a vehicle in which pre-crash control such as issuance of an alarm is executed when a distance between the vehicle and a vehicle in front becomes equal to or smaller than a prescribed value. For example, a traveling control device for a vehicle described in Japanese Patent Laying-Open No. 2007-245834 changes the aforementioned prescribed value depending on the vehicle speed, thereby issuing an alarm when the distance between the vehicles corresponding to the vehicle speed is reached.

Vehicle including regeneration level selector for motor


An artificial airway device to facilitate a patient's lung ventilation comprises an airway tube and a laryngeal mask at one end of the tube. The mask is of generally elliptical configuration, with an inflatable peripheral cuff of flexible material around the edges of the mask, for sealed support of the mask around the inlet to the patient's larynx. The mask has an aperture through which the airway tube opens into the interior of the mask. The mask also comprises a longitudinally directed bar, extending across the mask aperture, from the central upper edge or rim of the mask aperture, to which it has effectively a hinged attachment, to the posterior rim of the mask aperture, at which the bar is free. The hinged mounting of this bar is so positioned at longitudinal offset from the distal end of the mask (which locates in the upper sphincter or oesophageal inlet) that the introduction of an inserted endotracheal tube will automatically engage and swing the bar backward into camming engagement with the epiglottis, thus easily folding the epiglottis backward against the wall of the laryngeal inlet and permitting undeflected insertional passage of the endotracheal tube to and through the laryngeal inlet, and permitting undeflected insertional passage of the endotracheal tube to and through the laryngeal inlet.

This invention relates to an endotracheal-guidance system, such as an artificial airway device, or laryngeal-mask airway (LMA) device, of the type that finds use in anaesthetic procedures.
Patent No. GB 2,205,499 describes a miniature mask attached to a tube designed to fit into the lower throat as a means of securing the airway of an unconscious patient during anaesthesia. Such devices have met with quite remarkable success and are currently used in some 50 percent of general anaesthetic procedures in the United Kingdom. The use of such masks continues to spread throughout the world. The principal advantages associated with the use of such a mask are the simplicity of its installation and uses, the freeing of the anaesthetist's hands, and the lack of trauma to airway structures, as compared with the conventional and more traditional endotracheal tube (ET).
An important limiting factor in the use of the LMA device is its failure to adequately protect the lungs of an unconscious patient when regurgitation of stomach contents unexpectedly occurs. An endotracheal tube (ET), once placed in the windpipe, is still considered to be the definitive solution to this problem in patients at risk. However, it is sometimes difficult or even impossible to correctly position an ET owing to anatomical factors which may be unpredictable, and there is therefore always a risk that intubation of the windpipe will fail. This has resulted in death or brain damage of previously completely healthy people. While the LMA device can prevent this disaster, if there is also a risk of stomach contents entering and damaging the lungs (for example, in the case of anaesthesia for Caesarian Section), then most practitioners will want to subsequently achieve insertion of an ET even if disaster has been averted by supplying oxygen to the lungs via an LMA device.
This requirement has led to the design of a special LMA device (see, for example, U.S. Pat. No. 5,303,697) adapted to serve as guidance means to allow insertion of the appropriate size of ET. Indeed, the standard LMA device will permit insertion of a rather small-size ET, although the technique is not always successful, and it may subsequently be necessary to exchange the small ET for a larger one; such an exchange is a somewhat complicated and often difficult procedure, which is not without risk to the patient. The reason why it is not always possible to pass an ET through an LMA device into the windpipe (trachea) can only be understood by reference to an anatomical structure known as the epiglottis, which is in effect a cartilaginous shield attached to the upper border of the opening into the larynx (the glottis).
The epiglottis has an important function in directing the flow of food or drink when swallowed so that the flow does not accidentally spill into the windpipe or trachea via the glottic opening. The epiglottis is a hinged structure which swings down somewhat like a visor over the glottis during the action of swallowing. When the LMA device is placed in the lower throat (hypopharynx), the epiglottis is pushed forward, and its rim is held away from the LMA mask aperture by two bars, the mask-aperture bars (MABs). The MABs prevent the flap-like epiglottis from folding down to obstruct the passage of gas through the mask aperture, and in practice they fulfil this function reliably without traumatising the epiglottis. However, in order to pass an ET through the mask aperture of the LMA and into the glottis and trachea, it is sometimes necessary for the epiglottis to be lifted further upwards (swung further out of the way of the aperture) than can be achieved with the current design of MABs. Indeed, the MABs are not designed to force the epiglottis away from its normal anatomical neutral position in the airstream, and it is therefore not surprising that it may be difficult to pass a tube under the epiglottis to get it into the glottic opening even though gas may be passing freely through the LMA into the patient's lungs.
Normally, this problem can be solved by use of a fibrescope, which is a bendable light source and telescope which permits the anaesthetist to directly view the structures described and then thread an ET over the fibrescope and into the trachea. However, such direct-viewing equipment is expensive, and the procedure may be time-consuming. In matters pertaining to management of the airway of unconscious patients, time is of the essence, in that four minutes without oxygen is enough to cause brain damage.
MABs of current design consist of twin parallel bars of soft silicone material which (1) are sufficiently pliable to readily deflect and thus to allow passage of an object up to the diameter of the mask aperture itself, but which (2) are firm enough to resist penetration of the aperture by the epiglottis, which is caught up against them, rather like a fish caught in a net. Two bars have been used rather than some other number such as three or one, so that any tube passing through will not encounter a central bar and will thus not be deviated to one side (of a central bar), while a greater number than three bars would unnecessarily increase resistance to gas flow.

Endotracheal-tube guidance system with epiglottis-elevating feature

Sandford House Fan Court Gardens, Longcross Road