An apparatus for producing round brushes, which have bristles twisted in between two portions of a folded wire. The apparatus has a bristle feeding device and a rotary gripper for twisting two portions of wire with bristles located therebetween, a deflecting device with two deflecting rollers spaced apart in the longitudinal direction of the wire. The rotary gripper is linearly displaceable transversely in relation to the longitudinal direction of the wire, for gripping the folded region of the wire that is formed by force being applied by an application element that is adjustable between the deflecting rollers transversely in relation to the longitudinal direction of the wire. A bristle feeding device, for feeding bristles to the bent-around portions of wire, is provided in the region of the deflecting rollers. In the region of the unfolded portions of wire there is provided a device for slowing the advancement of the wire.

The invention relates to an apparatus and a method for producing round brushes, which have bristles twisted in between two portions of wire of a folded wire, the apparatus having a bristle feeding device and a rotary gripper for twisting two portions of wire with bristles located between them.
Such apparatuses along with associated production methods are known in various forms. For example, EP 1 917 886 B1 discloses a method and an apparatus in which bristles are fed between two portions of wire of a previously folded wire, the portions of wire are twisted at a first winding station to the extent that the bristles are held between the portions of wire and the brush prefabricated in this way is fully twisted, to a desired degree of winding, at a second winding station. However, this is very complex due to the large number of working stations. Moreover, such an apparatus is only suitable for relatively small brushes such as mascara brushes, since in the case of larger brushes with longer bristles the covering material may be flung away by the centrifugal forces acting during the twisting. In order to minimize this effect, it has previously been the practice in the production of larger brushes for the covering material to be held by an operator until the covering material is clamped between the portions of wire. This requires considerable expertise and experience on the part of the operator and presents a hazard for the operator, since he must have his hands in the danger area of the apparatus during the twisting. Moreover, this production method does not represent a safe process and is only possible for brush dimensions that can be handled by an operator.
Although, for example, DE 10 2005 045 827 A1 or U.S. Pat. No. 3,791,421 A disclose apparatuses with which bristle material can be twisted automatically in between two portions of wire, these apparatuses require feeding of two separate portions of wire. As a result, both ends of the brushes must be worked after the twisting in of the covering material and a certain distance is necessary between the head end of the brush and the beginning of the bristle covering.

Apparatus and method for producing round brushes


There is provided an information processing apparatus including a determination unit configured to determine, for each window, whether time decided by a certain method has elapsed since a last operation performed on a window in a display screen, and a control unit configured to shut down an application of a window for which the determination unit has determined that the time has elapsed.

The present disclosure relates to an information processing apparatus, an information processing method, and a storage medium.
Recently, it has become common to adopt, as a function of a operating system (OS) or the like, a multi-window function by which a plurality of windows are simultaneously displayed on a screen. However, when windows are launched, visibility of the screen sometimes becomes worse. With regard to the above issue, JP H09-190329A discloses an invention that performs minimization or the like on a window that is not focused on for a certain period of time. In addition, JP H06-202838A discloses an invention that performs minimization or the like on a window that is not in a specific state such as waiting for key input from a user.

Control of application based on user operation on information processing apparatus


A basic rotary vane mechanical power system, suitable for engines, pumps, compressors and the like, having an enclosed chamber housing a rotating hub plate, with the hub plate assembly supporting a plurality of spaced apart rotary vanes rotating on their own separate shafts and carried in a circular path by the hub plate assembly. The rotation of the hub plate assembly imparts rotation of the plurality of vanes within the enclosed, tight-fitting chamber, the angular rotation of the vanes being one-half of the angular velocity at which the hub plate and power shaft are rotating and transmitting power, or some other suitable ratio. During rotation of the vanes, the volume between the vanes increases and decreases, so that the volume of fluid within that space is contracted or expanded to drive the system or provide a source of power to the system or the working fluid. The volume of fluid between the vanes is determined principally by the thickness of the vane on one side of this circular path and also determined by the width of the vane where the chamber reaches its maximum width.

1. Field of the Invention
The system of the present invention relates to orbital rotary piston power systems, and to rotary vane mechanisms. More particularly the present invention relates to a power system for internal combustion engines, steam engines, fluid power units, fluid motors, pumps, compressors, turbochargers and the like, utilizing orbiting rotary vanes or rotary pistons confined within a close-fitting enclosure to provide expanding and contracting chambers that transmit power when coupled to input or output drive shafts.
2. General Background
In the general field of powered pumps or engines, rotary piston pumps and rotary piston engines have been designed in many variations. Rotary piston pumps are exemplified by the following U.S. patents: U.S. Pat. No. 4,373,484 issued to Boehling in 1983; U.S. Pat. Nos. 2,006,298 and 2,084,846 both issued to Hutchinson in 1935 and 1937 respectively; and earlier patents, U.S. Pat. No. 1,241,513 issued to Hicks in 1917, and U.S. Pat. No. 996,984 issued to Ginrod in 1911. In each of these designs elliptical or elongated pistons rotate on shafts whose positions are fixed within a confined space. The systems include rocker valves or ports positioned to admit fluids into an expanding chamber at its minimum volume or into a contracting chamber at or near its maximum volume, depending on whether expansion, pumping or compression was the desired power transmission effect. Other such systems will also be referred to in the list of art that is included in applicant's art statement accompanying this application.
For example, the '484 patent to Boehling teaches an improved rotary piston mechanism including stationary components, and rotor components housed within the stator components. The axles of the rotary components rotate within fixed positions in holes (or bearings) in the two stationary (stator) flat walls.
Another prior art engine is the famous "Wankel" engine, which is a rotary engine, having a somewhat triangular, thickened piston travelling back and forth between two somewhat cylindrical chambers undergoing intake, compression, power and exhaust strokes, said piston coupled by an internal gear to a drive shaft.
Neither of these examples, nor any of the other prior art patents, teach the concept of the present invention. The present invention, as will be described further, may share the same classification, rotary engine, but the present invention teaches a completely different concept of rotary mechanical power systems.
Other objects of the invention will become obvious to those skilled in the art from the following description of the invention.

Rotary vane mechanical power system utilizing positive displacement


This invention relates to the use of compounds capable of inhibiting the activity of a proton-gated cation channel in the treatment of alleviation of diseases or disorders associated with, or mediated by a drop in extra cellular pH.

This invention relates to the use of compounds capable of inhibiting the activity of a proton-gated cation channel in the treatment or alleviation of diseases or disorders associated with, or mediated by a drop in extracellular pH.
For almost 20 years, proton-gated cation channels have been known to exist in membranes of sensory neurons, where they are assumed to participate in nociception. Recently, several Acid Sensing Ion Channels (ASIC) have been cloned, and while some of these like ASIC3 (DRASIC) and ASIC-xcex2 are selectively expressed in sensory ganglia and/or the spinal cord, others, like ASIC1 and ASIC2, are expressed also in the brain [see e.g. Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M: A proton-gated cation channel involved in acid-sensing; Nature 1997 386 (6621)173-177; Lingueglia E, De Weille J R, Bassilana F, Heurteaux C, Sakai H, Waldmann R, Lazdunski M: A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells; J. Biol. Chem. 1997 272 (47) 29778-29783; Bassilana F, Champigny G, Waldmann R, De Weille J R, Heurteaux C, Lazdunski M: The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties; J. Biol. Chem. 1997 272 (46) 28819-28822; Olson T H, Riedl M S, Vulchanova L, Ortiz-Gonzalez X R, Elde R: An acid sensing ion channel (ASIC) localizes to small primary afferent neurons in rats; NeuroReport 1998 9 (6) 1109-1113; Chen C -C, England S, Akopian A N, Wood J N: A sensory neuron-specific, proton-gated ion channel; Proc. Natl. Acad. Sci. USA 1998 95 (17) 10240-10245; and Coscoy S, de Weille J R, Lingueglia E, Lazdunski M: The pre-transmembrane 1 domain of acidxe2x80x94sensing ion channels participates in the ion pore; J. Biol. Chem. 1997 274 (15) 10129-101321].
The proton-gated channels cloned all belong to the amiloride-sensitive Na-channel/degenerin family of ion channels, and like for ionotropic purinergic receptors, the topology presumably is two transmembrane domains flanking a long extracellular loop.
Compounds inhibiting the proton-gated cation channels have been suggested useful for the treatment of pain.
WO 98/35034 discloses mammal neuronal acid sensing cationic channels, which are considered useful for screening for analgesic drugs and for the treatment of degeneration of periferic neurons
Since the demonstration that the level of extracellular glutamate in the brain is greatly elevated under ischaemia, much pharmaceutical research has been focused on design of glutamate receptor antagonists. There has, however, been discrepancy between in vitro and in vivo studies: especially with respect to the effect of antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. In vitro, neuro degeneration due to oxygen/glucose deprivation is blocked by the NMDA receptor antagonist MK-801, but not by xcex1-amino-3-hydoxy-5-methyl4-isoxazolepropionic acid (AMPA) receptor antagonists. Strikingly, the case is opposite in in vivo models of global cerebral ischaemia: AMPA receptor antagonists reduces infarct volume, while NMDA receptor antagonists are ineffective.
Isatin derivatives like those described herein, for use as AMPA antagonists have been disclosed in e.g. WO 94/26747, WO 96/08494 and WO 96/08495. However, the use of these isatin derivatives as ASIC antagonising compounds have never been disclosed.
The present work shows the presence of ASIC in cultured mouse cortical neurons, a preparation widely used for studying native ion channels and in vitro models of neuro degeneration after ischaemia.
The presence of ASIC in central neurons is of particular interest because tissue acidosis is a well established feature of cerebral ischaemia. While the acidic pH in general has been regarded as neuro-protective due to proton inhibition of NMDA receptors, it may also have adverse effects by reason of activation of acid sensing ion channels contributing to membrane depolarisation, subsequent Ca2+ accumulation and neuro-degeneration.
Therefore, in a first aspect, the invention relates to the use of a compound capable of inhibiting a mammalian proton-gated cation channel for the manufacture of a medicament for the treatment, prevention or alleviation of a disease, disorder or condition associated with, or mediated by a drop in extracellular pH.
In another aspect the invention provides a method for the treatment, prevention or alleviation of a disease, disorder or condition in a subject, including a human, which disease, disorder or condition is associated with, or mediated by a drop in extracellular pH, said method comprising administering to the subject a pharmaceutically effective amount of a compound capable of inhibiting a mammalian proton-gated cation channel.
Other objects of the invention will be apparent to the person skilled in the art from the following detailed description and the examples.
ASIC Antagonising Compounds
In its first aspect the invention relates to the use of compounds capable of inhibiting a mammalian proton-gated cation channels for the manufacture of medicaments for the treatment, prevention or alleviation of a disease, disorder or condition associated with, or mediated by a drop in extracellular pH.
In the context of this invention compounds capable of inhibiting a mammalian proton-gated cation channel is also designated ASIC antagonising compounds.
Method of Screening
The ASIC antagonising compounds of the invention may be identified using the following screening method, which method comprises the subsequent steps of
(i) subjecting a proton-gated cation channel containing cell to the action of protons by adjustment of the pH to an acidic level;
(ii) subjecting a proton-gated cation channel containing cell to the action of the chemical compound; and
(iii) monitoring the change in membrane potential or the current induced by protons on the proton-gated cation channel containing cell.
In a preferred embodiment, the proton-gated cation channel is ASIC1 (also known as human brain sodium channel channel 2 (hBNaC2)), ASIC1A, ASIC1B, ASIC2 (also known as human brain sodium channel channel 1 (hBNaC1), or MDEG1), ASIC2A, ASIC2B, ASIC3 (also known as DRASIC), or ASIC-xcex2.
The proton-gated cation channel may or may not be endogenous to the cell in question, i.e. be a channel naturally occurring in the cell.
Cells for use in the method of the invention, in which proton-gated cation channel are naturally present includes cortical neuronal cells, in particular mouse or rat cortical neuronal cells, and human embryonic kidney (HEK) cells, in particular HEK 293 cells.
Alternatively the proton-gated cation channel may be exogenous to the cell in question, and may in particular be introduced by recombinant DNA technology, such as transfection or infection. Such cells include Chinese hamster ovary (CHO) cells, Xenopus laevis oocytes, or any other cell lines capable to express proton-gated cation channels.
The proton-gated cation channel containing cells may be subjected to the action of protons by adjustment of the pH to an acidic level using any convenient acid or buffer, including organic acids such as formic acid, acetic acid, citric acid, ascorbic acid and lactic acid, and inorganic acids such as hydrochloric acid, hydrobromic acid and nitric acid, perchloric acid and phosphoric acid.
In the method of the invention, the current flux induced by protons over the membrane of the proton-gated cation channel containing cell may be monitored by patch clamp techniques.
Alternatively, the change in membrane potential induced by protons of the proton-gated cation channel containing cells may be monitored using fluorescence methods. When using fluorescence methods, the proton-gated cation channel containing cells are incubated with a membrane potential indicating agent, that allow for a determination of changes in the membrane potential of the cells, caused by the added protons. Such membrane potential indicating agents include fluorescent indicators, preferably DIBAC4(3), DiOC5(3), and DiOC2(3).
In a preferred embodiment, the change in membrane potential induced by protons on the proton-gated cation channel containing cells are monitored by spectroscopic methods, e.g. using a FLIPR assay (Fluorescence Image Plate Reader; available from Molecular Devices).
The ASIC antagonising compounds of the invention show activity in concentrations below 100 xcexcM, preferably below 10 xcexcM, more preferred below 1 xcexcm. In its most preferred embodiment the ASIC antagonising compounds show activity in low micromolar and the nanomolar range.
Preferred ASIC Antagonising Compounds
In a preferred embodiment the compound for use according to the present invention is an isatin derivative represented by the general Formula I
or a pharmaceutically acceptable salt thereof, wherein
R1 represents hydrogen, alkyl, phenyl or benzyl; and
X represents oxygen, or a group of the formula NOR2 (i.e. an oxim), wherein R2 represents hydrogen, alkyl, acyl, phenyl or benzyl; and
Y represents a group of the formula Nxe2x80x94R4, wherein R4 represents hydrogen, hydroxy or alkyl; and
n is 0 or 1; and
R6 represents phenyl, naphthyl, thienyl, or pyridyl, all of which groups may be substituted one or more times with halogen, CF3, nitro, amino, cyano, hydroxy alkyl, alkoxy or phenyl, or a group of the formula xe2x80x94SO2NRxe2x80x2Rxe2x80x3, wherein NRxe2x80x2 and Rxe2x80x3 independently of each another represents hydrogen or alkyl; and
xe2x80x9cAxe2x80x9d represents a ring holding of from five to seven atoms, which ring is fused to the benzo-ring at the positions marked xe2x80x9caxe2x80x9d and xe2x80x9cbxe2x80x9d, and formed by one or the following bivalent radicals:
(a) xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94 (b),
(a) xe2x80x94NR12xe2x80x94CH2xe2x80x94CH2xe2x80x94 (b),
(a) xe2x80x94CH2xe2x80x94NR12xe2x80x94CH2xe2x80x94 (b),
(a) xe2x80x94CH2xe2x80x94CH2xe2x80x94NR12xe2x80x94 (b),
(a) xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94 (b),
(a) xe2x80x94NR12xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94 (b),
(a) xe2x80x94CH2xe2x80x94NR12xe2x80x94CH2xe2x80x94CH2xe2x80x94 (b),
(a) xe2x80x94CH2xe2x80x94CH2xe2x80x94NR12xe2x80x94CH2xe2x80x94 (b),
(a) xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94NR12xe2x80x94 (b),
(a) xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94 (b),
(a) xe2x80x94NR12xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94 (b),
(a) xe2x80x94CH2xe2x80x94NR12xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94 (b),
(a) xe2x80x94CH2xe2x80x94CH2xe2x80x94NR12xe2x80x94CH2xe2x80x94CH2xe2x80x94 (b),
(a) xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94NR12xe2x80x94CH2xe2x80x94 (b), or
(a) xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94NR12xe2x80x94 (b),
wherein R12 represents hydrogen, alkyl, alkyl substituted with hydroxy, alkoxy-alkyl, alkoxy-carbonyl-alkyl, alkyl-carbonyl-oxy-alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, alkynyl, phenyl or benzyl, which phenyl or benzyl group is optionally substituted with halogen, CF3, nitro, amino, cyano, hydroxy alkyl, alkoxy, or a group of the formula xe2x80x94SO2NRxe2x80x2Rxe2x80x3, wherein Rxe2x80x2 and Rxe2x80x3 independently of each another represents hydrogen or alkyl.
In another preferred embodiment, the compound for use according to the present invention is represented by the general Formula II
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, R12, X, Y and n have the meanings set forth above.
In a third preferred embodiment, the compound for use according to the present invention is represented by the general Formula III
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, R12 and X have the meanings set forth above.
In a more preferred embodiment, the compound represented by Formula III is
8-ethyl-5-phenyl-6-7-8-9-tetrahydro-1H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-oxim;
8-methyl-5-phenyl-6-7-8-9-tetrahydro-1H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-oxim;
8-methyl-5-phenyl-6-7-8-9-tetrahydro-1H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-methyloxim;
5-phenyl-6-7-8-9-tetrahydro-1H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-oxim;
5-(4-chlorophenyl)-8-methyl-6-7-8-9-tetrahydro-1-H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-oxim;
5-(2-naphthyl)-8-methyl-6-7-8-9-tetrahydro-1-H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-oxim;
8-methyl-5-phenyl-6,7,8,9-tetrahydro-1H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-acetyloxim;
8-methyl-5-(4-(N,N-dimethylsulfamoyl)-phenyl)-6,7,8,9-tetrahydro-1H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-oxime;
8-benzyl-5-Phenyl-6-7-8-9-tetrahydro-1H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-oxim;
8-methoxycarbonylmethyl-5-phenyl-6,7,8,9-tetrahydro-1H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-oxime;
8-(2-propynyl)-5-phenyl-6,7,8,9-tetrahydro-1H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-oxime; or
8-cyclopropylmethyl-5-phenyl-6,7,8,9-tetrahydro-1H-pyrrolo-[3,2-h]-isoquinoline-2,3-dione-3-oxime;
or a pharmaceutically acceptable salt thereof.
In a fourth preferred embodiment, the compound for use according to the present invention is represented by the general Formula IV
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, R12, X, Y and n have the meanings set forth above.
In a fifth preferred embodiment, the compound for use according to the present invention is represented by the general Formula V
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, R12 and X have the meanings set forth above.
In a sixth preferred embodiment, the compound for use according to the present invention is represented by the general Formula VI
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, R12, X, Y and n have the meanings set forth above.
In a seventh preferred embodiment, the compound for use according to the present invention is represented by the general Formula VII
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, R12 and X have the meanings set forth above.
In a more preferred embodiment, the compound represented by Formula VII is
7-ethyl-5-phenyl-6,7,8,9-tetrahydro-1H-pyrrolo-[3,2-f]-isoquinoline-2,3-dione-3-oxim; or
5-phenyl-7-methyl-6-7-8-9-tetrahydro-1-methyl-pyrrolo-[3,2-f]-isoquinoline-2,3-dione-3-oxim;
or a pharmaceutically acceptable salt thereof.
In an eight preferred embodiment, the compound for use according to the present invention is represented by the general Formula VIII
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, R12, X, Y and n have the meanings set forth above.
In a ninth preferred embodiment, the compound for use according to the present invention is represented by the general Formula IX
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, R12 and X have the meanings set forth above.
In a more preferred embodiment, the compound represented by Formula IX is
7-methyl-5-phenyl-1-6-7-8-tetrahydrobenzo-[2,1-b:3,4-c]-dipyrrole-2,3-dione-3-oxime;
7-methyl-5-(1-naphthyl)-1-6-7-8-tetrahydrobenzo-[2,1-b:3,4-c]-dipyrrole-2,3-dione-3-oxime; or
7-ethyl-5-phenyl-1-6-7-8-tetrahydrobenzo-[2,1-b:3,4-c]-dipyrrole-2,3-dione-3-oxime;
or a pharmaceutically acceptable salt thereof.
In a tenth preferred embodiment, the compound for use according to the present invention is represented by the general Formula X
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, X, Y and n have the meanings set forth above.
In an eleventh preferred embodiment, the compound for use according to the present invention is represented by the general Formula XI
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, and X have the meanings set forth above.
In a more preferred embodiment, the compound represented by Formula XI is
5-phenyl-6-7-8-9-tetrahydro-1-H-pyrrolo-[3,2-h]-naphthalene-2,3-dione-3-oxim; or
5-(4-chlorophenyl)-6-7-8-9-tetrahydro-1-H-pyrrolo-[3,2-h]-naphthalene-2,3-dione-3-oxim;
or a pharmaceutically acceptable salt thereof.
In a twelfth preferred embodiment, the compound for use according to the present invention is represented by the general Formula XII
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, X, Y and n have the meanings set forth above.
In a thirteenth preferred embodiment, the compound for use according to the present invention is represented by the general Formula XIII
or a pharmaceutically acceptable salt thereof,
wherein R1, R6, and X have the meanings set forth above.
In a fourteenth preferred embodiment, the compound for use according to the present invention is
N-amidino-3,5-diamino-6-chloropyrazine-2-carboxamide (Amiloride).
Definition of Substituents
In the context of this invention halogen represents a fluorine, a chlorine, a bromine or an iodine atom. Thus, a trihalogenmethyl group represents e.g. a trifluoromethyl group and a trichloromethyl group.
In the context of this invention an alkyl group designates a univalent saturated, straight or branched hydrocarbon chain. The hydrocarbon chain preferably contain of from one to eighteen carbon atoms (C1-18-alkyl), more preferred of from one to six carbon atoms (C1-6-alkyl; lower alkyl), including pentyl, isopentyl, neopentyl, tertiary pentyl, hexyl and isohexyl. In a preferred embodiment alkyl represents a C1-4-alkyl group, including butyl, isobutyl, secondary butyl, and tertiary butyl. In another preferred embodiment of this invention alkyl represents a C1-3-alkyl group, which may in particular be methyl, ethyl, propyl or isopropyl.
In the context of this invention an alkenyl group designates a carbon chain containing one or more double bonds, including di-enes, tri-enes and poly-enes. In a preferred embodiment the alkenyl group of the invention comprises of from two to eight carbon atoms (C2-8-alkenyl), more preferred of from two to six carbon atoms (C2-6-alkenyl), including at least one double bond. In a most preferred embodiment the alkenyl group of the invention is ethenyl; 1- or 2-propenyl; 1-, 2- or 3-butenyl, or 1,3-butenyl; 1-, 2-, 3-, 4- or 5-hexenyl, or 1,3-hexenyl, or 1,3,5-hexenyl; 1-, 2-, 3-, 4-, 5-, 6-, or 7-octenyl, or 1,3-octenyl, or 1,3,5-octenyl, or 1,3,5,7-octenyl.
In the context of this invention an alkynyl group designates a carbon chain containing one or more triple bonds, including di-ynes, tri-ynes and poly-ynes. In a preferred embodiment the alkynyl group of the invention comprises of from two to eight carbon atoms (C2-8-alkynyl), more preferred of from two to six carbon atoms (C2-6-alkynyl), including at least one triple bond. In its most preferred embodiment the alkynyl group of the invention is ethynyl; 1-, or 2-propynyl; 1-, 2-, or 3-butynyl, or 1,3-butynyl; 1-, 2-, 3-, 4-pentynyl, or 1,3-pentynyl; 1-, 2-, 3-, 4-, or 5-henynyl, or 1,3,5-hexynyl or 1,3,5-hexynyl; 1-, 2-, 3-, 4-, 5- or 6-heptynyl, or 1,3-heptynyl, or 1,3,5-heptynyl; 1-, 2-, 3-, 4-, 5-, 6- or 7-octynyl, or 1,3-octynyl, or 1,3,5-octynyl, or 1,3,5,7-octynyl.
In the context of this invention a cycloalkyl group designates a cyclic alkyl group, preferably containing of from three to seven carbon atoms (C3-7-cycloalkyl), including cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
In the context of this invention a cycloalkyl-alkyl group designates a cycloalkyl group as defined above, which cycloalkyl group is substituted on an alkyl group as also defined above. Examples of preferred cycloalkyl-alkyl groups of the invention include cyclopropylmethyl and cyclopropylethyl.
In the context of this invention an alkoxy group designates an xe2x80x9calkyl-Oxe2x80x94xe2x80x9d group, wherein alkyl is as defined above.
In the context of this invention an alkoxy-alkyl group designates an xe2x80x9calkyl-O-alkyl-xe2x80x9d group, wherein alkyl is as defined above.
In the context of this invention an acyl group designates a carboxy group (xe2x80x94COOH) or an alkyl-carbonyl group (alkyl-COxe2x80x94), wherein alkyl is as defined above. Examples of preferred acyl groups of the invention include carboxy, acetyl, and propionyl.
In the context of this invention an alkoxy-carbonyl-alkyl group designates an xe2x80x9calkyl-Oxe2x80x94CO-alkylxe2x80x9d group, wherein alkyl is as defined above.
In the context of this invention an alkyl-carbonyl-oxy-alkyl group designates an xe2x80x9calkyl-COxe2x80x94O-alkyl-xe2x80x9d group, wherein alkyl is as defined above.
In the context of this invention an amino group may be a primary (xe2x80x94NH2), secondary (xe2x80x94NH-alkyl), or tertiary (xe2x80x94N(alkyl)2) amino group, i.e. it may be substituted once or twice with an alkyl group as defined above.
Pharmaceutically Acceptable Salts
The chemical compound of the invention may be provided in any form suitable for the intended administration. Suitable forms include pharmaceutically (i.e. physiologically) acceptable salts, and pre- or prodrug forms of the chemical compound of the invention.
Examples of pharmaceutically acceptable addition salts include, without limitation, the non-toxic inorganic and organic acid addition salts such as the hydrochloride derived from hydrochloric acid, the hydrobromide derived from hydrobromic acid, the nitrate derived from nitric acid, the perchlorate derived from perchloric acid, the phosphate derived from phosphoric acid, the sulphate derived from sulphuric acid, the formate derived from formic acid, the acetate derived from acetic acid, the aconate derived from aconitic acid, the ascorbate derived from ascorbic acid, the benzenesulphonate derived from benzensulphonic acid, the benzoate derived from benzoic acid, the cinnamate derived from cinnamic acid, the citrate derived from citric acid, the embonate derived from embonic acid, the enantate derived from enanthic acid, the fumarate derived from fumaric acid, the glutamate derived from glutamic acid, the glycolate derived from glycolic acid, the lactate derived from lactic acid, the maleate derived from maleic acid, the malonate derived from malonic acid, the mandelate derived from mandelic acid, the methanesulphonate derived from methane sulphonic acid, the naphthalene-2-sulphonate derived from naphtalene-2-sulphonic acid, the phthalate derived from phthalic acid, the salicylate derived from salicylic acid, the sorbate derived from sorbic acid, the stearate derived from stearic acid, the succinate derived from succinic acid, the tartrate derived from tartaric acid, the toluene-p-sulphonate derived from p-toluene sulphonic acid, and the like. Such salts may be formed by procedures well known and described in the art.
Other acids such as oxalic acid, which may not be considered pharmaceutically acceptable, may be useful in the preparation of salts useful as intermediates in obtaining a chemical compound of the invention and its pharmaceutically acceptable acid addition salt.
Metal salts of a chemical compound of the invention includes alkali metal salts, such as the sodium salt of a chemical compound of the invention containing a carboxy group.
In the context of this invention the xe2x80x9conium saltsxe2x80x9d of N-containing compounds are also contemplated as pharmaceutically acceptable salts. Preferred xe2x80x9conium saltsxe2x80x9d include the alkyl-onium salts, the cycloalkyl-onium salts, and the cycloalkylalkyl-onium salts.
The chemical compound of the invention may be provided in dissoluble or indissoluble forms together with a pharmaceutically acceptable solvents such as water, ethanol, and the like. Dissoluble forms may also include hydrated forms such as the monohydrate, the dihydrate, the hemihydrate, the trihydrate, the tetrahydrate, and the like. In general, the dissoluble forms are considered equivalent to indissoluble forms for the purposes of this invention.
Steric Isomers
The chemical compounds of the present invention may exist in (+) and (xe2x88x92) forms as well as in racemic forms. The racemates of these isomers and the individual isomers themselves are within the scope of the present invention.
Racemic forms can be resolved into the optical antipodes by known methods and techniques. One way of separating the diastereomeric salts is by use of an optically active acid, and liberating the optically active amine compound by treatment with a base. Another method for resolving racemates into the optical antipodes is based upon chromatography on an optical active matrix. Racemic compounds of the present invention can thus be resolved into their optical antipodes, e.g., by fractional crystallisation of d- or I-(tartrates, mandelates, or camphorsulphonate) salts for example.
The chemical compounds of the present invention may also be resolved by the formation of diastereomeric amides by reaction of the chemical compounds of the present invention with an optically active activated carboxylic acid such as that derived from (+) or (xe2x88x92) phenylalanine, (+) or (xe2x88x92) phenylglycine, (+) or (xe2x88x92) camphanic acid or by the formation of diastereomeric carbamates by reaction of the chemical compound of the present invention with an optically active chloroformate or the like.
Additional methods for the resolving the optical isomers are known in the art. Such methods include those described by Jaques J, Collet A, and Wilen S in xe2x80x9cEnantiomers, Racemates, and Resolutionsxe2x80x9d, John Wiley and Sons, New York (1981).
Optical active compounds can also be prepared from optical active starting materials.
Moreover, some of the chemical compounds of the invention being oximes, may thus exist in two forms, syn- and anti-form (Z- and E-form), depending on the arrangement of the substituents around the xe2x80x94Cxe2x95x90Nxe2x80x94 double bond. A chemical compound of the present invention may thus be the syn- or the anti-form (Z- and E-form), or it may be a mixture hereof.
Methods of Preparation
The chemical compounds of the invention may be prepared by conventional methods for chemical synthesis, e.g. those described in WO 94/26747, WO 96108494 and WO 96108495, and in the working examples. The starting materials for the processes described in the present application are known or may readily be prepared by conventional methods from commercially available chemicals.
Also one compound of the invention can be converted to another compound of the invention using conventional methods.
The end products of the reactions described herein may be isolated by conventional techniques, e.g. by extraction, crystallisation, distillation, chromatography, etc.
Biological Activity
The presence of ASIC in central neurons is of particular interest because tissue acidosis is a well established feature of cerebral ischaemia. While the acidic pH in general has been regarded as neuro-protective, due to proton inhibition of NMDA receptors, it may also have adverse effects by reason of activation of acid sensing ion channels contributing to membrane depolarisation, subsequent Ca2+ accumulation and neuro-degeneration. In this respect it seems justified that the administration of ASIC antagonising compounds provide protection to individuals against injury arising from a drop in extracellular pH.
Diseases and disorders contemplated according to the present invention include in particular diseases of the central nervous system (CNS). In particular, the invention relates to combating diseases associated with reduced blood flow to the brain and other CNS tissue and with instances of a temporary break in blood supply to the brain or to other CNS tissue. Examples include ischaemic diseases, anoxic episodes, and injury to the brain and other parts of the CNS caused by trauma or other injury, for example a blow to the head, or spinal injury. In such reduced blood flow episodes, or episodes where there is a temporary break in blood supply, oxygen supply to the brain is reduced or interrupted.
Diseases and disorders contemplated according to the present invention also include cerebrovascular disorders such as cerebral ischaemia or cerebral infarction resulting from a range of conditions, such as tromboembolic or haemorrhagic stroke, cerebral vasospasm, hypoglycaemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from near-drowning, pulmonary surgery and cerebral trauma as well as lathyrism, Alzheimer""s disease, and Huntington""s disease. The method can be used in the treatment or prevention of traumatic brain injury, in particular ischaemic, hypoxic or anoxic brain damage, spinal cord injury, tissue ischaemia and reperfusion injury in a mammal at risk for such damage.
The brain damage may follow cerebral ischaemia, either global or focal, or be caused by cardiac arrest, or may follow high risk surgery such as cardiac surgery. It may also follow or be caused by stroke, neonatal hypoxia, hypoxia caused by compromised lung function, neonatal anoxia, anoxia caused by compromised lung function, cerebral trauma, secondary regional ischaemia induced by brain oedema, increased intercranial pressure, open brain surgery, endarterectomy, surgical interventions involving temporary, artificially sustained arrest of cardiopulmonary functions resulting in impairment of cerebral blood flow, and emergency treatment involving cardiopulmonary resuscitation (CPR).
As used herein, reperfusion injury refers to the cellular changes and tissue damage seen after a period of total ischaemia followed by reperfusion. Extremity re-plantation, organ transplantation, free flap tissue reconstruction and even myocardial infarction and stroke are all clinical examples of interval tissue ischaemia which can lead to tissue loss due to reperfusion injury after blood flow is re-established. Tissue reperfusion injury, seen in its full clinical extent as the no-reflow phenomenon, appears as inflammatory response to reperfusion resulting in the ultimate death of the tissue.
Thus the chemical compounds of the invention are found to be particularly useful in acute treatment of ischaemic stroke, in treatment of brain damage following global cerebral ischaemia, or for prevention of brain damage following high risk surgery.
In many instances of brain ischaemia, treatment is not available to the patient for several, e.g. up to 6 hours, in stroke patients typically 3 to 6 hours, after the ischaemic injury. Such a delay places great demands on any therapeutic regime designed to mitigate ischaemic brain injury.
When administered post-ischaemically it is advisable that the chemical compounds of the invention be administered within one day of the ischaemic insult. Although the neuro-protective agent used in the invention may be administered as late as 14 hours after brain reperfusion, the treatment should preferably be carried out within 12 hours of ischaemic alleviation or reperfusion. Preferably, the treatment should occur within 6 hours of alleviation of ischaemia. Yet more preferred is the administration of the chemical compounds used in the invention within 3 hours of alleviation of ischaemia.
Pharmaceutical Compositions
Thus viewed from one aspect, the invention provides ASIC antagonising compounds for use in the manufacture of a pharmaceutical composition for treatment or alleviation of diseases and disorders associated with or mediated by a drop in extracellular pH.
In a preferred embodiment of this aspect, pharmaceutical compositions for treatment or alleviation of diseases and disorders associated with or mediated by a drop in extracellular pH, which pharmaceutical compositions comprise a pharmaceutically effective amount of an ASIC antagonising compound together with a pharmaceutically effective amount of an AMPA receptor antagonising compound.
While a chemical compound of the invention for use in therapy may be administered in the form of the raw chemical compound, it is preferred to introduce the active ingredient, optionally in the form of a physiologically acceptable salt, in a pharmaceutical composition together with one or more adjuvants, excipients, carriers, buffers, diluents, and/or other customary pharmaceutical auxiliaries.
In a preferred embodiment, the invention provides pharmaceutical compositions comprising an ASIC antagonising compound or a pharmaceutically acceptable salt or derivative thereof, together with one or more pharmaceutically acceptable carriers therefor, and, optionally, other therapeutic and/or prophylactic ingredients, know and used in the art. The carrier(s) must be xe2x80x9cacceptablexe2x80x9d in the sense of being compatible with the other ingredients of the formulation and not harmful to the recipient thereof.
The pharmaceutical composition of the invention may be administered by any convenient route which suite the desired therapy. Preferred routes of administration include oral administration, in particular in tablet, in capsule, in drage, in powder, or in liquid form, and parenteral administration, in particular cutaneous, subcutaneous, intramuscular, or intravenous injection. The pharmaceutical composition may be prepared by the skilled person using standard and conventional techniques appropriate to the desired formulation. When desired, compositions adapted to give sustained release of the active ingredient may be employed.
Further details on techniques for formulation and administration may be found in the latest edition of Remington""s Pharmaceutical Sciences (Maack Publishing Co., Easton, Pa.).
The actual dosage depend on the nature and severity of the disease being treated, and is within the discretion of the physician, and may be varied by titration of the dosage to the particular circumstances of this invention to produce the desired therapeutic effect. However, it is presently contemplated that pharmaceutical compositions containing of from about 0.1 to about 500 mg of active ingredient per individual dose, preferably of from about 1 to about 100 mg, most preferred of from about 1 to about 10 mg, are suitable for therapeutic treatments.
The active ingredient may be administered in one or several doses per day. A satisfactory result can, in certain instances, be obtained at a dosage as low as 0.1 xcexcg/kg i.v. and 1 xcexcg/kg p.o. The upper limit of the dosage range is presently considered to be about 10 mg/kg i.v. and 100 mg/kg p.o. Preferred ranges are from about 0.1 xcexcg/kg to about 10 mg/kg/day i.v., and from about 1 xcexcg/kg to about 100 mg/kg/day p.o.
Viewed from another aspect, the invention provides a method for treatment, prevention or alleviation of a disease or a disorder or a condition of a living animal body, including a human, which disease or a disorder or a condition is associated with, or mediated by a drop in extracellular pH, said method comprising administering to a subject a pharmaceutically effective amount of a proton-gated cation channel inhibiting compound.
In a preferred embodiment, the disease, disorder or condition is associated with reduced blood flow to the brain and other CNS tissue, or associated with instances of a temporary break in blood supply to the brain or to other CNS tissue.
In another preferred embodiment, the disease, disorder or condition is an ischaemic disease, an anoxic episode, an injury to the brain and other parts of the CNS caused by trauma or other injury, a blow to the head, or a spinal injury, a tromboembolic or haemorrhagic stroke, a cerebral vasospasm, hypoglycaemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia, cerebral trauma, lathyrism, Alzheimer""s disease, and Huntington""s disease, cerebral ischaemia or cerebral infarction, ischaemic, hypoxic or anoxic brain damage, spinal cord injury, tissue ischaemia and reperfusion injury in a mammal at risk for such damage.
In a third preferred embodiment of this aspect, the method of the invention comprises co-administration of an ASIC antagonising compound and a pharmaceutically effective amount of an AMPA receptor antagonising compound.
In a more preferred embodiment, the AMPA receptor antagonising compound is 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo-(f)-quinoxaline (NBQX), 6,7-dinitroquinoxaline-2,3-dione, or 6-cyano-7-nitroquinoxaline-2,3-dione, or a pharmaceutically acceptable salt thereof.
It is at present contemplated that suitable dosage ranges are 0.1 to 1000 milligrams daily, 10-500 milligrams daily, and especially 30-100 milligrams daily, dependent as usual upon the exact mode of administration, form in which administered, the indication toward which the administration is directed, the subject involved and the body weight of the subject involved, and further the preference and experience of the physician or veterinarian in charge.
AMPA receptor antagonising compounds are well known and described in the literature.
Preferred examples of AMPA receptor antagonising compounds include those described in e.g. EP 451626, EP 432648, EP 503349, EP 522494, WO 93/05043, EP 633262, WO 94/26747, EP 629615, EP 667340, WO 96/08494, WO 96/08495, WO 96/08494 and WO 98/14447, and the quinoxaline- or quinoxalinedione derivatives, in particular 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo-(f)-quinoxaline (NBQX), and 6,7-dinitroquinoxaline-2,3-dione or 6-cyano-7-nitroquinoxaline-2,3-dione.
The actual dosage depend on the nature and severity of the disease being treated, and is within the discretion of the physician, and may be varied by titration of the dosage to the particular circumstances of this invention to produce the desired therapeutic effect. However, it is presently contemplated that pharmaceutical compositions containing of from about 0.1 to about 500 mg of active ingredient per individual dose, preferably of from about 1 to about 100 mg, most preferred of from about 1 to about 100 mg, are suitable for therapeutic treatments.
The active ingredient may be administered in one or several doses per day. A satisfactory result can, in certain instances, be obtained at a dosage as low as 0.1 xcexcg/kg i.v. and 1 xcexcg/kg p.o. The upper limit of the dosage range is presently considered to be about 10 mg/kg i.v. and 100 mg/kg p.o. Preferred ranges are from about 0.1 xcexcg/kg to about 10 mg/kg/day i.v., and from about 1 xcexcg/kg to about 100 mg/kg/day p.o.

Inhibitors of proton-gated cation channels and their use in the treatment of ischaemic disorders


Disclosure is a wavelength division multiplexed-passive optical network having a bus structure capable of connecting one central office to a plurality of remote nodes through one optical fiber. The wavelength division multiplexed-passive optical network (WDM-PON) having a bus structure includes a central office for downwardly transferring downstream optical signals having different wavelengths through a feeder fiber and for receiving upstream optical signals upwardly transferred through the feeder fiber; a plurality of remote nodes including at least a first remote node connected to the central office through the feeder fiber and a second remote node connected to the first remote node through the feeder fiber, dropping optical signals having corresponding wavelengths from among downwardly-transferred optical signals from the central office to at least one subscriber unit connected to each of the remote nodes, and adding the upstream optical signals, which are upwardly transferred from each subscriber unit, so as to upwardly transfer the upstream optical signals to the central office; and at least one subscriber unit for receiving the optical signals having the corresponding wavelengths dropped from each of the remote nodes and for upwardly transferring the upstream optical signals having different wavelengths through each of the remote nodes.

1. Field of the Invention
The present invention relates to a wavelength division multiplexed-passive optical network, and more particularly to a wavelength division multiplexed-passive optical network having a bus structure capable of connecting one central office to a plurality of remote nodes via a single optical fiber.
2. Description of the Related Art
In general, a wavelength division multiplexed-passive optical network (WDM-PON) provides specific wavelengths to subscribers in order to ensure communication security and enhance communication services required by the subscribers. In addition, the WDM-PON can easily adapt new subscribers by simply increasing the number of dedicated wavelengths dedicated to the new subscribers.
Referring to FIG. 1, a conventional WDM-PON 100 has a star structure including a central office (CO) 10 connected to a remote node (RN) 20 through a feeder fiber 1 and the remote node 20 connected to a plurality of subscriber units 30 through distribution fibers by using a multiplexer/demultiplexer 21. In this regard, the multiplexer/demultiplexer 21 mainly uses an array waveguide grating (AWG) for the subscriber units.
As shown in FIG. 1, downstream signals multiplexed by a multiplexer/demultiplexer 11 of the central office are transferred to the remote node 20 through the feeder fiber 1 and demultiplexed by the multiplexer/demultiplexer 21 positioned at the remote node 20. Then, the downstream signals are transferred to each of subscriber units 31 and 32 through corresponding distribution fibers 2. Upstream signals outputted from the subscriber units 31 and 32 are transferred to the remote node 20. The upstream signals of subscribers, which are inputted to the multiplexer/demultiplexer 21 positioned at the remote node 20, are multiplexed so as to be transferred to the central office 10.
The conventional WDM-PON 100 mainly employs an expensive array waveguide grating as the multiplexer/demultiplexer 21, and a passive optical network (PON) having the structure described above is suitable for a plurality of subscribers in major cities. However, the PON having such a structure is not economical in areas outside the major cities, which have a smaller number of subscribers.

Mae Tan-Dong, Yeongtong-Gu, Suwon-Si, Gyeonggi-Do, Korea


A storage and charging station for storing and charging a plurality of mobile electronic devices communicable with a remote electronic device. The station comprises a storage assembly and an electrical system coupled to the storage assembly. The storage assembly comprises a frame and a plurality of storage bays supported by the frame. The plurality of storage bays is to receive the plurality of mobile electronic devices. The electrical system comprises a power component, a communication component, a logic component, a memory component, and a plurality of ports electrically coupled to the power component and the communication component. When a first mobile electronic device connects with a first port, the power component powers the first mobile electronic device via the first port, and the station communicates with the remote electronic device via the first port and the first mobile electronic device.

Mobile electronic devices have become common place in personal and professional endeavors, including educational and business settings. Mobile electronic devices may also be referred to as "mobile computer devices," "handheld electronic devices," and "handheld computer devices." Desktop computers initially paved the way for common personal and business use of computers for word processing, data entry, planning, general and technical information-transfer, business management, remote communication, self-education, and other uses. Improving mobile electronic devices, including laptop computers, tablets, and cell phones, rapidly increased individual electronics use within organizations, including educational and business organizations, which now may centrally purchase quantities of generally uniform selected mobile electronic devices for use by students, employees, or other users served by such organizations.
As the number of mobile electronic devices increases, storage, charging, and deployment becomes more difficult. Therefore, holders and stations for these devices are known, such as disclosed in U.S. Pat. No. 10,084,327 and its related patents and applications, which may be understood to provide background information for this disclosure. An improved solution is desired.

Storage and charging station for storing and charging a plurality of mobile electronic devices, system including the station, and method of communication among the same


The invention relates to a multi-layer structure used in an optical communication field and its manufacturing method in which the capacitance effect between the metal patterns of a Silicon Optical Bench (SiOB) is significantly reduced. The multi-layer structure includes a dielectric layer and conductive patterns on a semiconductor substrate, such that the conductive patterns are separated from each other, wherein the dielectric layer and upper portions of the semiconductor substrate between the conductive patterns are etched out to a predetermined thickness to effectively reduce the capacitance without changing the area or structure of the metal patterns.

This application makes reference to and claims all benefits accruing under 35 U.S.C. Section 119 from an application entitled, xe2x80x9cMULTI-LAYER STRUCTURE FOR REDUCTION OF CAPACITANCE AND METHOD FOR MANUFACTURING THE SAME,xe2x80x9d filed in the Korean Intellectual Property Office on Mar. 5, 2002 and there duly assigned Serial No. 2002-11495.
1. Field of the Invention
The present invention relates to a multi-layer structure for reducing capacitance and a manufacturing method thereof, in particular, for reducing capacitance between metal patterns of a Silicon Optical Bench (SiOB), which is used in optical communication applications.
2. Description of the Related Art
As one skilled in the art can appreciate, a laser-diode chip and a photo-diode chip are used as a Transceiver (Tx) and a Receiver (Rx) of optical subscriber elements, respectively, in which a Silicon Optical Bench (SiOB) is deployed to connect these chips as a single module. In manufacturing this type of SiOB, the magnitude of capacitance plays an important role as the capacitance is enlarged and the frequency performance is degraded, thereby preventing the module from performing at high speed.
FIG. 1 is a sectional view illustrating a bench structure used for manufacturing an optical bench, such as SiOB, in which a SiN or SiO2 dielectric film 2, and metal patterns 4 and 4xe2x80x2 are formed on a silicon substrate 1. FIG. 2 illustrates a circuit diagram equivalent to FIG. 1, in which a section marked by a circle, i.e., a capacitance CS, an inductance LS, or a resistance RS, between the metal patterns 4 and 4xe2x80x2, represents similar components served by the dielectric film and the silicon substrate between the metal patterns. Note that this type of structure increases the capacitance.
In order to reduce the capacitance between the metal patterns 4 and 4xe2x80x2 in the above conventional structure, the resistance of silicon is raised, the thickness of the dielectric film is increased, and the area of the metal patterns is reduced.
However, the first method of raising the resistance of silicon requires cost increase due to delicate techniques in a silicon-wafer fabricating process. In the second method of thickening the dielectric film, the desired thickness of deposition is hard to obtain due to the limited Chemical Vapor Deposition (CVD), such as Plasma Enhanced Chemical Vapor Deposition (PECVD) or Low Pressure Chemical Vapor Deposition (LPCVD). Although the thickness can be increased if the thermal-oxidation deposition technique is employed in the second method, the deposition time is undesirably long. Lastly, the third method of reducing the area of the metal patterns has drawbacks with a limit on how much to decrease the metal pattern area due to physical and structural constraints.
Accordingly, the present invention overcomes the above-described problems and provides additional advantages, by providing a manufacturing method and a multi-layer structure for reducing capacitance, in which the capacitance can be effectively reduced without changing the area or structure of metal patterns.
According to one aspect of the invention, the multi-layer structure includes a dielectric layer and conductive patterns on a semiconductor substrate, wherein the conductive patterns are separated from each other, and wherein the dielectric layer and upper portions of the semiconductor substrate between the conductive patterns are etched out to a predetermined thickness.
Preferably, the etched-out portions of the silicon substrate between the conductive patterns have a thickness of 0.5-2 xcexcm.
Preferably, the dielectric layer is a SiO2 layer.
According to another aspect of the invention, a method of manufacturing a multi-layer structure is provided, as well as a method comprising the following steps: (a) forming a dielectric layer on a silicon substrate; (b) forming metal patterns separate from each other on the dielectric layer to expose portions of the dielectric layer underlying the metal patterns; and, (c) etching the exposed portions of the dielectric layer and upper portions of the underlying silicon substrate between the metal patterns to a predetermined thickness.
Preferably, the (b) step of forming a dielectric layer on a silicon substrate comprises the steps of carrying out lift-off photolithography to form lift-off photo-sensitive patterns on the dielectric layer except for areas for forming the metal patterns; depositing metal over the entire structure; and, removing the photosensitive patterns and metal deposited on the photosensitive patterns via a lift-off process to form metal patterns.
Preferably, the (c) step of etching the exposed portions of the dielectric layer and upper portions of the underlying silicon substrate between the metal patterns for a certain thickness comprises the step of dry-etching the exposed underlying dielectric layer and subsequently over-etching to remove the upper portions of the underlying silicon substrate by using the metal patterns as an etching mask.

Multi-layer structure for reducing capacitance and manufacturing method thereof


A hat holding device has a generally circular ring adapted to encircle a hat. The ring is pivotally mounted on lateral supports of a hanger member. The ends of the lateral supports have loops that project downwardly and terminate in a generally horizontal U-shaped body. The U-shaped body extends into the interior of the hat to support the hat and retain the hat inside of the ring. The mid-portion of the hanger member has a downwardly turned hook adapted to be placed on a support to remove the hat from the risk of damage.

Commonly, hats are placed on a table, counter top, or floor thereby subjecting the hats to possible damage. The hats can be crushed, spilt on or otherwise defiled. Hats placed out in the open increases the clutter and messiness of a household, establishment, or office. Prior hat holding devices have been used to support hats. These devices use rings connected to a hanger for accommodating a hat. The prior hat holders do not provide support to the interior of the hat whereby the crown of the hat may be damaged.


An electrical connector assembly includes a first connector. The first connector has a main body. The main body has a first end wall and a second end wall opposite to each other. Multiple first terminals are provided on the main body. The first connector is used to be mated with a circuit board. The circuit board has multiple first conductive portions, multiple second conductive portions and multiple first wires electrically connecting the first conductive portions and the second conductive portions correspondingly. The second conductive portion is correspondingly electrically connected to the first terminal. The first end wall is located closer to the first conductive portion relative to the second end wall. A top surface of the first end wall is lower than a corresponding first conductive portion adjacent to the first end wall.

The background description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present disclosure.
An existing electrical connector assembly includes a circuit board, a first connector and a second connector. The circuit board is provided with a plurality of first conductive portions and a plurality of second conductive portions, and a plurality of wires correspondingly connect the first conductive portions and the second conductive portions. The first connector has a plurality of first terminals correspondingly electrically connected with the second conductive portions on the circuit board, and the second connector has a plurality of second terminals correspondingly electrically connected with the first conductive portions on the circuit board. The first connector has a main body. The main body has a first end wall and a second end wall provided opposite to each other, and heights of the first end wall and the second end wall are equal.
Since the heights of the first end wall and the second end wall are equal, and the top surface of the first end wall is higher than the first conductive portion adjacent to the first end wall, when the first terminals are correspondingly electrically connected to the second conductive portions, there is a need to provide a notch having a higher bottom surface at one side of the circuit board close to the first end wall to accommodate the first end wall. Further, the top surface of the first end wall is higher than the first conductive portion adjacent to the first end wall, and the bottom surface of the notch is correspondingly higher than the first conductive portion adjacent to the first end wall. Thus, the wires from the first conductive portions to the second conductive portions need to get around the notch with the higher bottom surface, which results in the wires to have more bending, thus increasing the average length of the wires, easily causing the signal loss and crosstalk, and affecting the high frequency characteristics of the electrical connector assembly.
Therefore, a heretofore unaddressed need to design a novel electrical connector exists in the art to address the aforementioned deficiencies and inadequacies.


An image processing apparatus includes an image reading unit configured to read information as image data, a character recognition unit configured to recognize individual characters included in the image data, a grouping unit configured to group the individual characters recognized into one or more character string based on character information indicating a format of the character, a character extraction unit configured to extract a character string for which a link is to be created based on an importance of the character string obtained by the grouping, a character search unit configured to search the image data in which the characters have been recognized for the character string having the same character base among the character strings extracted, and a link setting unit configured to link the character strings having the same character base that are retrieved to each other based on the importance.

I. Technical Field
The present disclosure relates to an image processing apparatus that generates hyperlink structure data from image data read by a scanner.
Unless otherwise indicated herein, the description in this background section is not prior art to the claims in this application and is not admitted to be prior art by inclusion in this section.
II. Description of the Related Art
One method of generating hyperlink structure data involves generating a hyperlink based on data in a table of contents and an index page. A page number to which reference is made by a term mentioned in the table of contents or the index page and a page number of a normal page in which the term is mentioned are linked to each other. A user who views image data is allowed to move a page directly from the table of contents and the index page to the normal page to which the reference is made.
However, in the above-described technology, only the page numbers shown in the table of contents (index page) and the normal page are linked to each other. Therefore, it is not possible to create a link to a term that is not mentioned in the table of contents or the index page, an arbitrary term selected by the user, or other such term.

Image processing apparatus that generates hyperlink structure data


A stacking device for forming stacks of articles of predetermined count, using a stacking wheel having a multiplicty of uniformly spaced peripheral slots. The slots are adapted to receive articles sequentially at a loading station and carry them to an unloading station having a plurality of stacking sites. The slots are divided into two or more sets, the slots in each set being equal to number to the predetermined count and adapted to deliver the articles therein to the unloading station with the leading edges of the articles at a predetermined radial offset from the axis of the stacking wheel. Each set of slots is associated with the stacking of articles at a specific stacking site and the slots of a set associated with one stacking site provide a different radial offset than those of a set associated with another stacking site. The stacking sites are arranged, in the downstream direction, in order of diminishing radial offset of their associated sets of slots. Separation of the stacks is effected by having stripping fingers for each stacking site act at the appropriate radial offset.

During the course of manufacturing articles such as facial tissues, sanitary napkins, diapers, and other such objects, it is often required that serially fed articles be taken from a conveyor, accumulated in stacks of predetermined count and the stacks advanced for further processing and/or packaging. This has been done both manually and by various mechanisms throughout the years. In connection with machinery adapted to perform such functions, these frequently include slotted wheels to carry the articles from the conveyor to a discharge station at which the articles could be stacked, shingled, or the like. For example, Leuthold U.S. Pat. No. 4,522,387, which issued on June 11, 1985 discloses a device for stacking sheets which comprises several disks arranged adjacent one another on a shaft. The disks have spiral slots formed in them which extend from the periphery towards their centers. Corresponding slots overlap in an axial direction and form pockets, each of which is adapted to receive a sheet. The spiral slots of adjacent disks are staggered to exert frictional force on the incoming sheets to dissipate their kinetic energy. As the disks rotate, the sheets are removed from the slots by a pick-off arranged between the disks and stacked on a tray. Presumably, they are manually removed from the tray on which they are accumulated.
Similarly, Rabinow et al, U.S. Pat. No. 3,531,108, issued Sept. 29, 1970, concerns a document stacker and/or sorter employing a number of stacking wheels having curved slots for document pockets. As the stacking wheels rotate, a stripping device operatively associated with each removes the documents from the respective pockets and stacks them neatly in a tray. No means is shown to remove the stacks, so presumably this is also accomplished manually.
In Hertel U.S. Pat. No. 4,736,936, issued on Apr. 12, 1988, apparatus is described for stacking and removing articles of predetermined count. The articles are fed sequentially into slots in a rotating wheel. As the articles follow their circular path, they are stripped and stacked on buckets carried by a conveyor moving along an intersecting path. When the stack of articles on one bucket is completed, the bucket progresses from a stripping position and the next subsequent bucket is rapidly moved into stripping position. Ultimately, each loaded bucket is aligned with another conveyor and its stack withdrawn and carried by the other conveyor to an accumulation station. Thereafter, the empty buckets return in sequence to the stripping position. This interaction between moving machine parts involves timing, position and clearance problems which will hamper efforts to move in the direction of high speed operation.
The sheet stacking apparatus disclosed in Nakamura, U.S. Pat. No. 4,595,193, issued June 17, 1986, involves a blade wheel having slots wherein sheets are inserted and carried to a stripping/stacking station, at which they are removed and separated into units of predetermined number. The apparatus uses a separator rotably mounted about the same axis as the blade wheel and intermittently operated in unison therewith to position itself between the last sheet of one stack and the first sheet of the next. The separator is then held stationary while the completed stack is removed. During the removal process, subsequent sheets accumulate on the separator. Thereafter, these sheets are transferred to the stacking means as the separator is rotated to its standby position adjacent the sheet infeed means. It will be apparent that this apparatus, too, could be difficult to operate at high production rates because it involves synchronous coordination of dynamic machine elements.
Other teachings relative to shingling, sorting and stacking of articles are found in Kobler et al U.S. Pat. No. 4,434,979, issued on Mar. 6, 1984; Hoffman U.S. Pat. No. 3,744,790, issued on July 10, 1973; and Campbell U.S. Pat. No. 4,523,671, issued June 18, 1985.


An upright surface cleaning apparatus comprises a surface cleaning head a cleaning unit moveably mounted to the surface cleaning head between a generally upright position and a rearwardly inclined in use position, a push handle and an above floor cleaning assembly. The above floor cleaning assembly comprises a flexible conduit having an inlet end and an outlet end, wherein in a floor cleaning mode the above floor cleaning assembly is positioned between a front transverse plane that extends transverse to the central longitudinal axis of the surface cleaning head and is located at the front side of the cleaning unit and a rear transverse plane that extends transverse to the central longitudinal axis and is located at the rear side of the cleaning unit.

The following is not an admission that anything discussed below is part of the prior art or part of the common general knowledge of a person skilled in the art.
Various types of surface cleaning apparatus are known including upright vacuum cleaners and extractors. Typically, an upright vacuum cleaner includes an upper section, including an air treatment member such as one or more cyclones and/or filters, drivingly mounted to a surface cleaning head. An up flow conduit is typically provided between the surface cleaning head and the upper section. In some such vacuum cleaners, a spine, casing or backbone extends between the surface cleaning head and the upper section for supporting the air treatment member. The suction motor may be provided in the upper section.
U.S. Pat. No. 7,188,388 (Best) discloses a multi-use vacuum cleaner with a detachable cyclonic vacuum module. The vacuum cleaner may be used as an upright vacuum cleaner when the detachable vacuum module is mounted to the base or the detachable vacuum module may be detached and used by itself. The detachable vacuum module includes a vacuum motor, a motor driven fan, a cyclonic dirt separator and a hose.
US patent publication No. US 2015/0096143 (Conrad) discloses an upright vacuum cleaner with a removable hand vacuum cleaner. The upright vacuum cleaner may be used in different cleaning modes including use as an upright vacuum cleaner when the hand vacuum cleaner is mounted to the handle.


An apparatus for holding a rubber or elastic cover covering a bulb exchange opening of a lamp assembly of a vehicle, comprises a holder defining the bulb exchange opening and having a plurality of outer engagement claws formed at predetermined intervals in the circumferential direction of the holder, and a cap retaining the cover together with the holder. The cap has a plurality of hooks engaging the claws when the cap is rotated for engaging the holder. At least one cap abutment is provided on the holder at a circumferential position of the holder between adjacent two claws, which provides interference in the direction of engagement between the cap and the cap abutment when the cap is mounted on the holder, so that a sensible physical response is given to an operator for confirming the correct right engagement of the cover, the cap and the holder, to reliably enhance the holding function.

1. Field of the Invention
This invention relates to an apparatus for holding a cover of a lamp assembly of a vehicle, and more particularly to an apparatus for holding a rubber or elastic cover which is removably mounted on a holder of a lamp assembly of a vehicle and covers a bulb exchange opening from rain or water.
2. Background Art
FIG. 3 shows a prior-art apparatus for holding a rubber cover 80 on a hollow cylindrical holder 91 of a lamp assembly 90 of a vehicle. The holder 91 defines a bulb exchange opening and has outer engagement claws 91a formed at its plural (e.g. three) circumferential positions. The lamp assembly 90 comprises a separate cap 92 having hooks 92a engageable with the outer engagement claws 91a. In mounting, an outwardly extending flange 80a of the cover 80 is in contact with the top edge surface of the holder 91, the cap 92 is then placed over the holder 91 to sandwich the flange 80a of the cover 80 with the top edge surface of the holder 91, and the cap 92 is then rotated for engaging the hooks 92a with the outer engagement claws 91a of the holder 91.
Each of the hooks 92a has a tapered portion 92b and a concavely stepped portion 92c so that the cap 92 forcibly presses the flange 80a between the cap 92 and the holder 91 as an operator rotates the cap 92. Thereby the apparatus secures a tight seal of the interior of the lamp assembly against rain or water. Further, when the outer engagement claws 91a reach the concavely stepped portions 92c, fingers of the operator feel a physical response by which he or she realizes that the cap 92 has been set in place. The concavely stepped portions 92c also prevent the cap 92 from rotating in the reverse direction in service of the lamp assembly 90 to increase reliability of the function of the cap 92 of retaining the cover 80 on the holder 91.
In the prior-art apparatus, the retention of the cap 92 on the holder 91 and the physical response of the operator are attributed to elasticity of the flange 80a of the rubber cover 80. Therefore, if the cover 80 loses elasticity due to aging, then the operator feels no physical response in mounting the cover 80 on the holder 91, and the cap 92 cannot securely retain the cover 80 on the holder 91. Thus, reliability of the holder 91 and the cap 92 in retaining the cover 80 in a rain-tight manner decreases. The solution of such problem therefore has been desired.

Apparatus of holding cover of lamp assembly of vehicle


A corrosion detection apparatus for permanently and integrally monitoring a state of corrosion of a component is provided. The corrosion detection apparatus makes it possible to use the change in electrical conductivity to detect corrosion of a component to be monitored. A corrosion-sensitive bridging element that establishes an electrical connection between a first electrical line section and a second electrical line section of a sensor circuit is used to change certain electrical properties of the sensor circuit. On account of the corrosion-sensitive property of the bridging element, the latter changes its electrical conductivity when corrosion starts. This makes it possible to use the sensor circuit to detect corrosion of the bridging element and thus of the component to be monitored.

Due to extended vehicle operating times, which can be, for example, up to 30 years in the case of aircraft, the protection of metal structural components against occasional corrosion is of special importance. A majority of the materials that are used in the aviation industry involve aluminum alloys. Locations that evade direct visual inspection altogether or that are only accessible with considerable effort and known to be potentially exposed to more extensive exposure to water and electrolytes, should be monitored for corrosion at regular intervals.
Civil aircraft and military transporters operate more or less regularly inside climate zones of high air humidity and high ambient temperatures such as, for example, in maritime atmospheres, which are conducive to the formation of condensation.
The prior art specifies moisture sensors that are provided with a water-sensitive layer for detecting instantaneous moisture. These sensors are typically configured as thin-layer systems and operate reversibly, depending on the respectively occurring outer instantaneous partial pressure of H2O. Any reversible take-up of water in the sensitive layer on or into the condenser causes a change of the capacitance, whereby this change constitutes the measured value in these sensors. However, sensors of this type are not able to detect an integral take-up of H2O or electrolytes directly.

Corrosion detection apparatus for monitoring a state of corrosion


Disclosed are methods and techniques for providing favorable fabrication characteristics for optical elements. One method includes providing a desired integrated computational element (ICE) design comprising a plurality of layers, each layer having a design thickness, randomizing the design thickness of each layer of the desired ICE design to simulate a fabrication error in each layer, thereby generating a plurality of randomized ICE designs, calculating a standard error of calibration between each randomized ICE design and the desired ICE design, correlating the standard error of calibration between a given layer of the desired ICE design and the fabrication error of each corresponding layer of each randomized ICE design, and ranking the plurality of layers of the desired ICE design based on the sensitivity to changes in the standard error of calibration.

The present invention relates to optical computing devices and, more particularly, to optical design techniques that provide favorable fabrication characteristics for optical elements used in optical computing devices.
Optical computing devices, also commonly referred to as "opticoanalytical devices," can be used to analyze and monitor a substance in real time. Such optical computing devices will often employ a processing element that optically interacts with the substance to determine quantitative and/or qualitative values of one or more physical or chemical properties of the substance. The processing element may be, for example, an integrated computational element (ICE), also known as a multivariate optical element (MOE), which is essentially an optical interference filter that can be designed to operate over a continuum of wavelengths in the electromagnetic spectrum from the UV to mid-infrared (MIR) ranges, or any sub-set of that region. Electromagnetic radiation that optically interacts with the ICE is changed so as to be readable by a detector, such that an output of the detector can be correlated to the physical or chemical property of the substance being analyzed.
One exemplary type of ICE includes a plurality of layers consisting of various materials whose index of refraction and size (e.g., thickness) may vary between each layer. An ICE design refers to the number and thickness of the respective layers of the ICE component. The layers may be strategically deposited and sized so as to selectively pass predetermined fractions of electromagnetic radiation at different wavelengths configured to substantially mimic a regression vector corresponding to a particular physical or chemical property of interest. Accordingly, an ICE design will exhibit a transmission function that is weighted with respect to wavelength. After the electromagnetic radiation from a light source interacts with a sample and ICE, the output light is conveyed to an optical transducer or detector. The total intensity measured by the detector is related to the physical or chemical property of interest for the substance.
It has been found, however, that the resulting transmission function for some ICE designs may change or shift based on errors in fabricating the individual ICE components. For example, during fabrication of an ICE component, slight errors may be made while depositing one or more of its layers. While some errors in a particular layer might cause a large shift in the transmission spectra of the ICE component as a whole, such errors may not be detrimental to the prediction performance of the ICE component. On the other hand, errors on another layer may cause only a slight spectral shift in the transmission profile, but this small shift may be significant with respect to prediction performance. It may be advantageous to determine which ICE designs may have hypersensitive layers for which extra care should be taken during the fabrication process to ensure minimal layer error.

Optical design techniques for providing favorable fabrication characteristics


The present invention relates to binding molecules such as antibodies that specifically bind plasma coagulation factor XI and that inhibit factor XI activation and/or activity. The factor XI-binding molecules of the invention may used in methods for preventing or treating diseases, disorders and/or conditions that are mediated by factor XI activation and/or wherein inhibition of factor XI has a beneficial effect.

Coagulation consists of a humoral and a cellular response. The former leads to the conversion of soluble fibrinogen into insoluble fibrin, the latter consists of activation of platelets leading to a platelet plug. Platelet plugs, fibrin threads and included red blood cells together constitute a blood clot. A key molecule in clot formation is thrombin. This protease converts soluble fibrinogen into the insoluble fibrin, it activates platelets, and converts a number of other factors including factors XI, VIII and V, into active species.
Pathological thrombosis refers to clot formation that is not part of a normal hemostatic process and that may result in disease symptoms. For example, thrombosis on an atherosclerotic plaque in a coronary artery may result in acute myocardial infarction and can be considered as a type of pathological thrombosis. Deep venous thrombosis and thrombosis on vascular grafts are other examples of pathological thrombosis.
Current anticoagulant drugs inhibit the basal pathway of coagulation: heparin (via antithrombin III) hits thrombin, factors Xa and IXa, coumarins inhibit the synthesis of prothrombin, factors VII, IX and X, whereas LMW heparin mainly inhibits factor Xa. The therapeutic window of these drugs is narrow, requiring careful monitoring of patients. Some of the newer anticoagulant drugs under development target at the FVIII/FIX amplification loop.
Considering the severe bleeding tendency resulting from a complete deficiency of factor VIII or IX, in hemophilia A or B, respectively, targeting at this level likely will also require careful monitoring to prevent the risk of bleeding side effects, particularly at overdosing.
Factor XI is not a target for current anticoagulants. This is mainly due to the fact that factor XI deficiency, in contrast to a deficiency of factor VIII or IX, does not result in a severe bleeding tendency. As a matter of fact many factor XI deficient persons never experience a severe bleeding episode. Only two studies have been performed with antibodies, in both cases polyclonal, against factor XI that inhibit the function of factor XI in vivo, either by inhibiting the activity of the molecule or by preventing its activation. In a first study (Minnema et al., 1998, J Clin Invest. 101:10-14) polyclonal antibodies against rabbit factor XI were used to evaluate the effect of factor XI blockade on clot formation in vivo in an experimental thrombosis model in rabbits. Incorporation of anti-factor XI antibodies in jugular vein thrombi resulted in an almost twofold increase in endogenous thrombolysis compared with a control antibody. A similar effect was observed when the anti-factor XI antibody was administered systemically.
The effect of administration of neutralizing polyclonal goat anti-factor XI-antibodies on the accumulation of platelets and fibrin on arterio-venous grafts in baboons was topic of another study to evaluate factor XI as target for antithrombotic therapy (Gruber and Hanson, 2003, Blood 102:953-955). In that study the role of factor XI-dependent thrombus propagation under arterial flow conditions was investigated. Under the conditions used rapid thrombus growth was produced on the grafts of Dacron or Teflon deployed into arteriovenous shunts in baboons treated with anti-human factor XI antibody. Administration of the polyclonal antibodies against factor XI markedly reduced intraluminal thrombus growth on both surfaces. The antithrombotic effect of the polyclonal antibodies against factor XI was found to be comparable with that of heparin at doses that significantly prolonged the partial thromboplastin time, prothrombin time, and bleeding time, whereas anti-FXI antibodies only affected the partial thromboplastin time but not prothrombin time and bleeding time.
There is however still a need in the art for anti-coagulant therapies based on antigen binding molecules that target factor XI.

Use of anti-factor XI antibodies for prevention of thrombus formation


A calibration assembly for a spectrometer is provided. The assembly includes a spectrometer having n detector elements, where each detector element is assigned a predetermined wavelength value. A first source emitting first radiation is used to calibrate the spectrometer. A device is placed in the path of the first radiation to split the first radiation into a first beam and a second beam. The assembly is configured so that one of the first and second beams travels a path-difference distance longer than the other of the first and second beams. An output signal is generated by the spectrometer when the first and second beams enter the spectrometer. The assembly includes a controller operable for processing the output signal and adapted to calculate correction factors for the respective predetermined wavelength values assigned to each detector element.

A typical spectrometer includes a plurality of detector elements. When the spectrometer is illuminated with radiation having multiple wavelengths, each detector element records an intensity factor for a particular wavelength. The wavelength assignment of each detector element should be the value of the particular wavelength that reaches that detector after passing through the spectrometer optics. In order to determine the wavelength assignment of each detector element, the spectrometer is calibrated using a source that emits radiation at a few known wavelength points in the spectrum. The spectrometer receives the radiation and records an intensity value for the known wavelength points. In order to determine the wavelength assigned to each detector element, a functional fit or polynomial fit is performed to interpolate points within the spectrum and extrapolate points outside the spectrum. However, the wavelength assignments obtained by this method of calibration are typically accurate only to approximately one nanometer.

Method and apparatus for accurately calibrating a spectrometer

The United States of America as Represented by the Administrator of the National Aeronautics and Space Administration


System and computer-implemented method for determining optimal combinations of elements having multiple dimensions, including determining the optimal number of destination servers for server consolidation, wherein existing servers are evaluated across multiple dimensions.

With the increasing adoption of Service-oriented Architecture (SOA) and cloud computing technologies where Information Technology, including infrastructure, platforms and applications are delivered as services, there is an increasing use of the shared resource model. In such a model, computing and IT resources are shared across multiple applications. Accordingly, there is an increasing need for solutions that optimize the resource allocation. Power, cooling and real estate costs represent a significant portion of the overall cost in operating a cloud computing platform, service or datacenter. The reduction or optimization of resources associated with such costs creates a net benefit in total operating cost, reduces the need for expensive infrastructure and provides an opportunity to expand the platform. The challenge in consolidating such workloads is to minimize the number of physical servers while taking into consideration the resource needs across multiple dimensions. In this space, the dimensions include, but are not limited to, CPU, memory, data storage, I/O, networking bandwidth, network topology, and router utilizations—which are all subject to change in real-time dependent upon user needs and workloads.
Server consolidation methods aim to provide an efficient usage of computer server resources in order to reduce the total number of servers required for a particular software implementation, or a collection of software implementations. That is, server consolidation functions to address the problem of "server sprawl". Server sprawl is understood in the art to refer to multiple under-utilized servers consuming more resources than is necessary to provide the functionality required by the software packages loaded thereupon.
Server consolidation may generally be classified into three stages: centralization, physical consolidation and data and application integration. Centralization involves moving servers to a common location. Physical consolidation involves moving a large number of existing servers to a small number of high-performance servers. Storage consolidation is also a kind of physical consolidation where disparate or related data and applications are integrated into a common database and common application. These classifications operate to reduce server under-utilization—typical levels of under-utilization in a non-consolidated environment may range from 15-20% of individual physical server capacity being unused.
A technique for physical consolidation, which is well known in the art, is the use of server virtualization technology. Virtualization enables multiple existing servers to be moved to share the resources of a single computer, or a dynamically selected grouping of computers. That is, software is used to divide one physical server into multiple isolated virtual environments or instances. Multiple methods of virtualization are known to those skilled in the art, e.g., hardware emulation, para-virtualization, OS-level virtualization, application level virtualization, etc. Regardless of the particular virtualization implementation method, the goal is to minimize the number of physical servers. This goal, minimizing the number of physical servers, competes directly with the twin goal of ensuring that sufficient resources are made available to avoid performance degradation. Put another way, sufficient resources are required to avoid degradation in performance, wherein the sum of resource utilization for virtual machines on a physical server (destination server) does not exceed the threshold limits prescribed for that particular destination server, while the number of destination servers is as small as possible to provide a cost benefit to the server consolidation process.
The optimization of destination servers may be viewed as a bin or vector packing problem. That is, items of different sizes must be packed into a minimum number of bins with a defined capacity. The basic bin packing problem is as follows: given N objects, each with a value vi, i=1, . . . , N, these objects must be packed in as few bins as possible such that Σνt of objects packed in the same bin does not exceed the bin's capacity. The bin packing problem may be understood in the server consolidation context as follows: objects for server consolidation are existing servers, object sizes are resource utilizations, bins are destination servers, and the bin capacity is the utilization threshold of the destination servers. Resource utilizations may include existing server CPU, disk and memory requirements. Where multiple resources (CPU, disk, memory, etc.) are being considered, the resources form multiple dimensions in the packing problem. The solutions to bin and vector packing problems are the same in the one-dimensional case. However, in multi-dimensional cases, the problem is considered as a vector packing problem.
A two-dimensional server packing problem may be formally understood as follows: Let ρci and ρdi be the CPU and disk utilization of an existing server si (i=1, . . . n), Xj be a set of existing servers consolidated into a destination server s′j (j=1, . . . , m), and Rc and Rd be the thresholds of CPU and disk utilizations prescribed for the destination servers. Thus n existing servers are all consolidated into m destination servers. The problem is then to minimize n under the constraints that Σsiεxjρci≦RC and Σsiεxjρdi≦Rd. Note, however, that the performance characteristics (CPU, disk, etc.) of a destination server may be higher than that of an existing server. In such an instance, if the performance of a destination server is h times higher than that of an existing server, CPU utilization ρmeasured on the existing server is converted into ρ/h on the destination server. Further, the virtualization overhead increases the utilizations of servers running on virtual machines and the threshold values for destination servers must be modified accordingly.
There are several methods well known in the art to solve such multi-dimensional vector packing problems, for example, the First Fit Decreasing (FFD) algorithm. The FFD algorithm may be understood by the following pseudo code.
sort existing servers to {s1, ..., sn} in descending order;m← 1; X1 ← { };for i ← 1 to n do for j ← 1 to m do  if packable (Xj, si) then   Xj ←Xj ∪{si};   break  fi end for; if j = m + 1 then/* if fail to pack si, */  m ← m + 1;/* a new server is added */  Xm ← {si}/* to have si */ fiend for
The FFD algorithm addresses the server packing problem by first receiving n existing servers and sorting them in descending order of utilizations of a certain resource. After the algorithm is executed, it produces server accommodations Xj (j=1, . . . , m), where m is the number of destination servers. The function packable (Xj, si) returns true if packing existing server si into destination server s′j satisfies the constraints (i.e., the utilization of s′j does not exceed a threshold for any resource); otherwise it returns false. FFD sequentially checks if all existing servers s1, . . . , sn can be packed into one of m current destination servers. FFD then packs si into a destination server first found to be able to accommodate it. If si cannot be packed into any current destination server, the (m+1)-th destination server is added to accommodate it. The complexity of this FFD algorithm is O(n2) because m is almost proportional to n.
A second algorithm for vector packing known in the art is the Least Loaded algorithm (LL). The LL algorithm may be understood by the following pseudo code.
sort existing servers to {s1, ..., sn} in descending order;m←LB ({s1, ..., sn });while true do for j ← 1 to m do  Xj←{ }   /* initialization */ end for; for i←1 to n do  sort destination servers to {X1, ..., Xm} in ascending order;  for j←1 to m do   if packable (Xj, si) then     Xj←Xj∪{si};     break   fi  end for;  if j= m + 1 then  /* If fail to pack si, a new server is added */   m ←m + 1;   break  fi end for; if i = n + 1 then      /* all packed */  break fiend while
The LL algorithm attempts to balance the load between servers by assigning incoming jobs to the least-loaded server. In server packing, an existing server with a high utilization is packed into a server with low utilization. The function LB({s1, . . . , sn}) returns the theoretical lower bound for the number of destination servers that accommodate existing servers {s1, . . . , sn}. The lower bound is the smallest integer of numbers larger than the sum of the utilizations divided by a threshold. The lower bound for the CPU is
            LB      c        =                                  ∑                      i            =            1                    n                                              ρ                          c              i                                /                      R            c                                      ,while that for the disk is
      LB    d    =                                    ∑                      i            =            1                    n                                              ρ                          d              i                                /                      R            d                                      .  Function LB({s1, . . . , sn}) returns the larger integer of the two lower bounds.
There are two differences between LL and FFD. First, LL starts repacking after a new destination server is added when it has failed to pack an existing server into current m destination servers. This is aimed at balancing the load between a newly added destination server and the others. In contrast, FFD packs the existing server in question into a new destination server and continues to pack the remaining existing servers. LL initializes m to the lower bound to save time, even though we can also start with m=1. Second, LL sorts destination servers (which accommodate X1, . . . , Xm) in ascending order of utilizations each time before packing an existing server to pack it into a less-loaded destination server. The complexity of LL is O(d·n2 log n) where d is the difference between the lower bound and the final number m of destination servers.
The LL and FFD algorithms are limited in that only a single dimension is optimized at a time, i.e., neither LL nor FFD optimize multiple resources in a simultaneous manner. Further, because each dimension must first be considered independent of other dimensions, there is an inherent performance (time) cost to the optimization process.

System and method for fast server consolidation