Disclosed is a process for the recovery of a phytolipid composition from a vegetable oil by-product. The phytolipid composition produced comprises squalene, phytosterols, mixed tocopherols and tocotrieneols, and vegetable wax and is useful as an emollient. The phytochemical composition may be applied directly to the skin to provide emolliency. Alternatively, the phytolipid composition may be formulated in various aqueous or anhydrous cosmetic compositions such as creams, lotions, gels, ointments, lip balms, sticks, or pencils for treatment of the skin and lips. The phytolipid composition also may be incorporated into foods, beverages, and nutraceuticals to provide health benefits.

U.S. Pat. No. 5,660,691 describes a process for the production of tocotrienol/tocopherol blend concentrates from vegetable oil by-products such as deodorizer distillates, steam refining distillates, acidulated soapstock and other vegetable oil by-products rich in tocotrienol. U.S. Pat. No. 6,224,717 discloses solvent/water mixtures in connection with the separation of tocotrienol from tocol-containing mixtures. According to U.S. Pat. No. 6,224,717, DE 3615029 discloses the purification of tocopherols by contacting a tocopherol containing substance with neat methanol to form two layers, separating the methanol layer, cooling the methanol layer to produce a methanol phase and a raffinate layer, and recovering the tocopherols from the methanol layer. A disadvantage of this method is that a considerable amount of tocopherols are lost to the raffinate, thereby reducing the overall recoverable yield. U.S. Pat No. 4,550,183 discloses extracting a tocopherol containing material with caustic methanol to produce a two-phase system. The methanol layer is removed and neutralized with acid. A disadvantage of this method is that an additional step is required to neutralize the basic methanol layer. JP 03127730 A discloses extracting an unsaturated oil or fat with a neat extraction solvent composed of neat butanol, ethylene glycol, methyl ethyl ketone, acetone, benzene, or cyclohexane followed by a series of distillation steps.
Published U.S. Patent Application No. 20020142083 entitled Process for the Production of Tocotrienols uses "solvent wintering" as a process step in the preparation of tocotrienols. Wintering is the cooling of oil, with or without added solvent, to effect the crystallization of sterols and sterol like materials.
The prior art pertaining to processes for separating or recovering components of vegetable oil sources includes U.S. Pat. No. 6,552,208; WO 200151596, Isolation of Non-Saponifiables from Vegetable Oils; EP 1097985 (Chemical Abstracts 2325224), Chromatographic Isolation for Non-Glyceride Components; Chang, Chiehming J. et al., Supercritical Carbon Dioxide Extraction of High-Value Substances from Soybean Oil Deodorizer Distillate, Industrial & Engineering Chemistry Research (2000), 39 (12), 4521-4525; Binder, Thomas P., ADM Research, Processing Deodorizer Distillate for Value-Added Products, Abstracts of Papers, 225th ACS National Meeting, New Orleans, La. Mar. 23-27, 2003, AGFD-113, American Chemical Society.
The outer-most layer of human skin, the stratum corneum, provides the barrier function of the skin, preventing dehydration of underlying tissues and preventing absorption of various undesirable substances into the body. The stratum corneum consists of dead cells that are surrounded by proteins and lipids. It is primarily the lipid layer that provides the barrier function of the skin. Both squalene and sterols (predominately cholesterol) are natural components of the stratum corneum lipid layer. See, for example, De Paepe, Kristien, Cosmetic Lipids and the Skin Barrier, Foerster, Thomas, Ed. Marcel Dekker: New York, 2002; pages 152-153). Squalene is a major component of sebum secreted by the sebaceous glands (Moller, Hinrich, Cosmetic Lipids and the Skin Barrier, p 5). The benefits of lipids in cosmetics are discussed in detail by Lanzendorfer, Ghita in Cosmetic Lipids and the Skin Barrier, pages 271-290).
Several patents cite the use of the various components of lipid compositions, individually and in combinations with one another, to provide benefits to the skin, including the lips, or to the personal care product itself. U.S. Pat. No. 6,306,898 (WO 9632933) describes four aspects of preparations for treating dermatoses. The third aspect comprises a nonsteroidal anti-inflammatory agent, vitamin E, and squalane and/or squalene. The fourth aspect comprises an antihistaminic agent, vitamin E, and squalane and/or squalene. The vitamin E in combination with squalane or squalene is described as having a synergistic therapeutic effect in cooperation with the nonsteroidal anti-inflammatory agent or antihistaminic agent, respectively.
U.S. Pat. No. 5,494,657 describes the use of compositions comprising petrolatum, squalene or hydrogenated polybutene, non-hydrogenated polybutene, a fatty acid or fatty acid ester, and an antioxidant for moisturizing skin. The antioxidant is described as comprising a natural or synthetic alpha-tocopherol. One object of U.S. Pat. No. 5,494,657 is to provide skin care compositions similar to natural sebum. This patent teaches that the combination of polybutenes, the fatty acid or fatty acid ester, and anti-oxidant provides a balanced formulation which protects the skin while allowing controlled oxygen permeability. U.S. Pat. No. 5,378,461 describes a composition for topical treatment of damaged skin comprising a carrier solution consisting of squalene or squalane, a ubiquinone (coenzyme Q), and vitamins E, A, and D. Squalane and squalene have been shown to be a very effective transport medium for the other ingredients. U.S. Pat. No. 5,378,461 teaches that squalene is a natural emollient since it is synthesized in the sebaceous glands and Vitamin E is known to serve as an antioxidant—reducing or eliminating lipid peroxidation.
U.S. Pat. No. 4,454,159 describes preparations for the treatment of irritated, pruritic, and dry skin conditions that contain glycerol trioleate, a glyceride oil, hydrogenated glyceride oil, lecithin, tocopherol, a humectant, isopropyl palmitate, squalene or squalane, and a collagen product. The lipids used in the preparations should be rich in tocopherol. The compositions of U.S. Pat. No. 4,454,159 were found to exhibit unusual skin therapy in their ability to relieve skin irritation and itching. WO 2002026207 describes a cosmetic formulation that is characterized by a lipid composition comprising squalene which approximates human sebum. The compositions also contain natural vitamin E acetate. JP 09169638 describes a composition for treating dermatological diseases containing astringent (0.9-50%), vitamin E (0.1-99%), and squalane and/or squalene (0.1-99%). The astringent is preferably tannic acid, zinc oxide, or potassium aluminum sulphate. Patents that mention both squalene and vitamin E (or tocopherol) as ingredients in skin care formulations, refer to them as optional ingredients or include them in long lists of optional components. The prior art does not attribute any particular benefit to the combination of squalene and tocopherol in skin care formulations.
The following publications pertain to the use of sterols or phytosterols in skin care applications. U.S. Pat. No. 6,534,074 describes a composition applied to "a body facing material" that enhances skin barrier properties. The composition comprises natural fats or oils, sterols or sterol derivatives, a surfactant, a humectant, an emollient, a wax, and an oil soluble or dispersible viscosity enhancer. The specific benefit of including sterols or sterol derivatives in the formulation is not discussed. Rice bran wax is not included in the list of waxes that can be used as the wax component.
U.S. Pat. No. 6,284,802 describes a method for regulating the condition of mammalian keratinous tissue by applying a composition comprising farnesol, other skin care actives, and a carrier. Antioxidant and anti-inflammatory agent are listed as possible skin care actives. The antioxidant is selected from a group that includes tocopherol; and the anti-inflammatory agent is selected from a group that includes phytosterol. U.S. Pat. No. 6,153,209 describes an article for applying a skin care composition to the skin. The skin care composition is further described as comprising an emollient, a permeability agent, and an immobilizing agent. Sterols and sterol esters are included in the list of possible emollients; squalene is included in the list of possible permeability agents; and wax is included in the list of immobilizing agents. Rice bran wax is not included in the list of waxes that are specifically mentioned as possible waxes. The skin care composition can further comprise an antioxidant selected from a group that includes tocopherols and mixed tocopherols.
U.S. Pat. No. 5,882,660 describes a personal care composition in the form of an aqueous liquid comprising a lipid composition, a surface-active agent, and a cationic polymer. The lipid composition comprises two components, one of which is selected from a group that includes 3-beta-sterol and squalene. Examples of 3-beta-sterols include cholesterol, sitosterol, stigmasterol and ergosterol. This patent discloses that cholesterol is a vital component of the natural skin lipids that constitute the moisture barrier in the stratum corneum. U.S. Pat. No. 5,733,572 (WO 9109629) describes a gas filled lipid-containing microsphere comprising a therapeutic agent or cosmetic for topical application. Among the many components that can make up the composition are vitamins, including vitamin E; ointment bases including squalene; and a biocompatible lipid, including cholesterols, tocopherols, and non-ionic lipids.
U.S. Pat. No. 5,688,752 describes an aqueous liquid personal care cleansing composition comprising three components. One of the components is selected from a group that includes 3-beta-sterol and squalene. EP 467218 describes a lipid composition for cosmetics comprising fatty acids and/or their tocopheryl esters (0-95%), n-alkanes (0-65%), squalene (0-30%), cholesterol and/or lanolin alcohol (0-50%), triglycerides (0-80%), and/or wax esters (0-60%), where at least 2 of these components must be present. Also described is a skin oil containing the above lipid composition (10%).
Both U.S. Pat. No. 4,218,334 and U.S. Pat. No. 6,087,353 discuss the problem of solubilizing or dispersing phytosterols in emulsions and other formulations. U.S. Pat. No. 4,218,334 proposes that this problem may be solved by making a blend of phytosterol with free fatty acids or saturated free fatty alcohols. U.S. Pat. No. 6,087,353 proposes a solution to the problem which includes esterifying, then hydrogenating, the phytosterol. U.S. Pat. No. 6,087,353 also discusses the need to enhance the stability of phytosterol compositions.
The following publications pertain to the use of lipid compositions in food, nutritional, and pharmaceutical applications. U.S. Pat. Nos. 5,952,393 and 6,197,832 describe compositions and method for reducing serum cholesterol in humans and animals. The method comprises administering phytosterol and policosanol which together produce a synergistic effect in lowering serum cholesterol levels. Preferably, the administered composition includes about 3.2:1 parts by weight of phytosterol and policosanol. U.S. Pat. No. 6,025,348, U.S. Pat. No. 6,139,897 and U.S. Pat. No. 6,326,050 describe oil or fat compositions comprising 15 or more weight percent of a diacylglycerol and 1.2 to 20 weight percent phytosterol dissolved or dispersed in the fat and oil. U.S. Pat. No. 6,087,353 provides an esterified and subsequently hydrogenated phytosterol composition for use alone or for incorporation into foods, beverages, pharmaceuticals, nutraceuticals, and the like. The composition has the advantage of enhanced solubility/dispersibility, increased molar potency and enhanced stability over naturally isolated phytosterol compositions. Methods for the esterification and subsequent hydrogenation of the phytosterols are also provided.
U.S. Pat. No. 6,204,290 pertains to novel tocotrienols and tocotrienol-like compounds that exhibit biological activity. This patent discloses that the tocotrienols and tocotrienol-like compounds may be conveniently obtained from biological sources or by chemical synthesis and may be used in pharmaceutical compositions, foodstuffs and dietary supplements. U.S. Pat. No. 6,204,290 also discloses the use of tocotrienols, tocotrienol-like compounds, and mixtures thereof, as hypocholesterolemic, antithrombotic, antioxidizing, antiatherogenic, antiinflammatory and immunoregulatory agents, or as agents useful to decrease lipoprotein (a) concentration in the blood or to increase feed conversion efficiency.
U.S. Pat. No. 6,277,431 describes an edible oil that decreases the synthesis, absorption and blood level of cholesterol by a human patient, increases the excretion of cholesterol from the human patient, curtails accumulation of peroxidized material in the blood of the human patient, and also increases the blood level of vitamin E in said human patient. The edible oil is comprised of about 10 to 30% tocopherols, tocotrienols or combinations thereof; about 2 to 20% free sterols; about 2 to 20% sterol esters; about 0.1 to 1.0% of cycloartenols; and; about 7 to 19% of saturated fats, wherein all percentages are weight/weight.
Sterols are naturally occurring triterpenoids that perform many critical cellular functions, and so phytosterols have received a great deal of attention due to their ability to decrease serum cholesterol levels when fed to a number of mammalian species, including humans. Phytosterols such as campesterol, stigmasterol and beta-sitosterol in plants, ergosterol in fungi and cholesterol in animals are each primary components of cellular and sub-cellular membranes in their respective cell types. The dietary source of phytosterols in humans comes from plant materials i.e. vegetables and plant oils. The estimated daily phytosterol content in the conventional western-type diet is approximately 60-80 milligrams in contrast to a vegetarian diet that provides about 500 milligrams per day.
Plant constituents have been proven useful in the prevention and treatment of a wide variety of diseases and conditions. Recent studies have indicated that tocotrienols may be biologically active. For example, U.S. Pat. No. 4,603,142 identifies d-alpha-tocotrienol, isolated from barley extracts, as an inhibitor of cholesterol biosynthesis. See also A. A. Qureshi et al. (1986), supra. Various human and animal studies have confirmed the impact of pure tocotrienols, isolated from barley, oats and palm oil, on cholesterol biosynthesis, specifically LDL-cholesterol (A. A. Qureshi et al., Dietary Tocotrienols Reduce Concentrations of Plasma Cholesterol, Apolipoprotein B, Thromboxane B. sub.2 and Platelet Factor 4 In Pigs With Inherited Hyperlipidemias, Am. J. Clin. Nutr., pp. 1042S-46S (1991); A. A. Qureshi et al., Lowering Of Serum Cholesterol In Hypercholesterolemic Humans By Tocotrienols (Palmvitee), Am. J. Clin. Nutr., 53, pp. 1021S-26S (1991); D. T. S. Tan et al., The Effect Of Palm Oil Vitamin E Concentrate On The Serum And Lipoprotein Lipids In Humans, Am. J. Clin. Nutr., 53, pp. 1027S-30S (1991)).
Other chromanols, the tocopherols, including d-α-tocopherol (vitamin E), have been extensively studied. As a result of these studies, certain biological activities have been attributed to the tocopherols. Such activities include platelet aggregation and antioxidant functions—see, for example, E. Niki et al., Inhibition of Oxidation of Biomembranes By Tocopherol, Annals of the New York Academy of Sciences, 570, pages 23-31 (1989) and K. Fukuzawa et al., Increased Platelet-Activating Factor (PAF) Synthesis in Polymorphonuclear Leukocytes of Vitamin E-Deficient Rats, Annals of the New York Academy of Sciences, 570, pages 449-453 (1989)). Although the exact structure-function relationship is not known, several experiments have highlighted the importance of the phytyl side chain in the biological activity of tocopherols. See W. A. Skinner et al., Antioxidant Properties of .alpha.-Tocopherol Derivatives and Relationships of Antioxidant Activity to Biological Activity, Lipids, 5(2), pp. 184-186 (1969) and A. T. Diplock, Relationship of Tocopherol Structure to Biological Activity, Tissue Uptake, and Prostaglandin Biosynthesis, Annals of the New York Academy of Sciences, 570, pp. 73-84 (1989)).

Process for the recovery of a phytolipid composition


A method and a network node (110, 120, 140) for enabling configuration of at least two patterns for a cell (C0) are provided. The patterns are transmission patterns or measurement patterns. The network node (110, 120, 140) obtains (402) the at least two patterns. Each of the at least two patterns is associated with information about a respective restricted area (A1, A2) such that each pattern is used when a user equipment (130) served by the cell (C0) is located in the respective restricted area. Each respective restricted area (A1, A2) is smaller than an entire area of the cell (C0). Moreover, a method and a user equipment (130) for configuring measurements are provided. The user equipment (130) is served by a cell (C0, C1, C2) of a radio base station (110, 120, 140). The user equipment (130) receives at feast two measurement patterns from the radio base station. Each measurement pattern is associated with a respective restricted area. Each respective restricted area is smaller than an entire area of the cell. The user equipment (130) obtains information about the respective restricted area.

The interest in deploying low-power nodes, such as pico base stations, home radio base stations (home eNodeBs), relays, remote radio heads and the like, in a network has constantly increased over the last few years. When a network employs low-power nodes in addition to regular base stations, the network is usually referred to as a heterogeneous network. The regular base stations are often referred to as a macro layer and the low-power nodes are often referred to as a pico layer. A purpose of employing low-power nodes is to enhance performance of the macro layer in terms of network coverage, capacity and service experience of individual users.
At the same time as interest for love-power nodes has grown, it has been realized that there is a need for enhanced interference management techniques to address the arising interference issues caused by, for example, a significant transmit power variation among different cells. Cell association techniques are also needed for more uniform networks.
In the Third Generation Partnership Project (3GPP), heterogeneous network deployments have been defined as deployments where low-power nodes of different transmit powers are placed throughout a macro-cell layout, implying non-uniform traffic distribution. Such deployments are, for example, effective for capacity extension in certain areas. These areas may include so-called traffic hotspots, i.e. small geographical areas with higher user density and/or higher traffic intensity. Installation of low-power nodes, such as pico nodes, in these areas can enhance performance. Heterogeneous deployments may also be viewed as a way of densifying, or concentrating, networks to adopt for the traffic needs and the environment. However, heterogeneous deployments also bring challenges for which the network has to be prepared in order to ensure efficient network operation and superior user experience. Therefore, different interference management techniques, or interference management procedures, have been proposed.
One example of such interference management procedure relates to interference management for heterogeneous deployments. To ensure reliable and high-bitrate transmissions as well as robust control channel performance, maintaining a good signal quality is a must in wireless networks. The signal quality is determined by the received signal strength and its relation to the total interference and noise received by the receiver. A good network plan, e.g. good cell planning, is a prerequisite for successful network operation, but the cell planning is static. For more efficient radio resource utilization, the network plan has to be complemented by semi-static and dynamic radio resource management mechanisms. These mechanisms are intended to facilitate interference management and deploy more advanced antenna technologies and algorithms.
One way to handle interference is to utilize more advanced transceiver technologies, e.g. by implementing interference cancellation mechanisms in terminals, or user equipments (UEs). Another way, which can be complementary to the former, is to design efficient interference coordination algorithms, such as inter-cell interference coordination (ICIC) and transmission schemes in the network.
Inter-cell interference coordination (ICIC) methods for coordinating data transmissions between cells have been specified in Long Term Evolution (LTE) release 8. In LTE release 8, the exchange of ICIC information between cells in LTE is carried out via an X2 interface by means of the X2-Application Protocol (X2-AP protocol). The X2 interface and the X2-AP are known from 3GPP terminology. Based on this information, the network can dynamically coordinate data transmissions in different cells in the time-frequency domain and also by means of power control so that the negative impact of inter-cell interference is minimized. With such coordination, base stations may optimize their resource allocation by cells either autonomously or via another network node ensuring centralized or semi-centralized resource coordination in the network. With the current 3GPP specification, such coordination is typically transparent to user equipments.
Two examples of coordinating interference on data channels are illustrated in FIG. 1a and FIG. 1b. In FIGS. 1a-e, subcarriers, i.e. different frequencies, are vertically arranged along a vertical axis and time is expressed along the horizontal direction. Exemplifying data channels are denoted D1, D2, D3 and D4. In the example of FIG. 1a, data transmissions, such as D1, D2, D3 and D4, in two cells are separated in frequency, i.e. the no-data regions D1, D4 do not overlap in the vertical direction. The two cells, such as the pico and the macro, belong to different layers, i.e. macro and pico layers. By contrast, in the example of FIG. 1b, low-interference subframes are created at some time instances, such as at a center subframe of the three subframes shown for the macro, for data transmissions in pico cells by suppressing macro-cell transmissions in these time instances. This may, for example, enhance performance of user equipments which would otherwise experience strong interference from macro cells. For example, this applies to user equipments which are closely located to macro cells, or macro radio base stations. Such coordination mechanisms are possible already with the current specification.
Unlike for data transmission, current specifications limit ICIC possibilities for control channels. For instance, the mechanisms illustrated in FIG. 1a-b are not possible for control channels and are not possible for reference signals measured for mobility.
FIGS. 1c-e illustrate three approaches (1) (2), (3) of enhanced ICIC to handle the interference on control channels.
(1) as in FIG. 1c illustrates use of low-interference subframes in time.
In FIG. 1c, the vertical stripes indicate reduced interference to the control channels in the control region.
(2) as in FIG. 1d illustrates use of time shifts. It is noted that (2) has some limitations for Time Division Duplex (TDD) and is not possible with synchronous network deployments. Moreover, (2) is not efficient at high traffic loads. From the legacy terminal point of view, Cell-Specific Reference Signals (CRS) still need to be transmitted in all subframes, so there will still be inter-cell interference from CRS.
(3) as in FIG. 1e illustrates use of in-band control channel in combination with frequency re-use. In FIG. 1e, the grids indicate reduced interference to the enhanced control channels in the data region.
(1) and (3) require standardization changes whilst (2) is possible with the current standard.
Interference coordination techniques, as illustrated in FIGS. 1a-e, reduce the interference from a strong interferer, e.g. a macro cell, during other-cell, e.g. pico, transmissions. In doing so, the techniques assume that second cells, such as pico cells, are aware about the time-frequency resources with low-interference conditions and thus can prioritize scheduling of transmissions in those subframes for users which potentially may strongly suffer from the interference caused by the strong interferers.
As mentioned above, the possibilities to efficiently mitigate inter-cell interference to and from control channels are limited with the current standard. However, even less flexibility exists for dealing with interference to/from physical signals which typically have a pre-defined static resource allocation in the time-frequency space. In the following, some known techniques for interference cancellation are described.
In signal cancellation techniques, the channel is measured and used to restore the signal from a limited number of strongest interferers. This technique impacts receiver implementation and its complexity. Furthermore, in practice, channel estimation puts a limit on how much signal energy can be subtracted.
In symbol-level time shifting techniques, there is no impact on the standard, but it is not relevant for TDD networks or networks providing the MBMS service. This technique is applicable when a macro base station and a home base station are time-synchronized. This approach uses time shifting of transmission from the home base station relative to downlink frame timing of macro base station and uses power reduction, or muting, by the home base station and/or the macro base station, on the portion of a symbol(s) that overlap the control region of the macro or home base station.
A further technique completely mutes a signal in a subframe. In this technique, CRS are not transmitted at all in some subframes for energy efficiency reasons. This technique was proposed earlier in 3GPP. The technique is not backward compatible to Release 8 and/or 9 user equipments, which expect CRS to be transmitted at least on antenna part 0.
Given a very limited set of possibilities for interference cancellation listed above, there is a strong need for simple but yet efficient new techniques to resolve the CRS interference issue. A similar issue exists, for example, for synchronization and broadcast channels, where time shifts may be utilized to address the issue.
The need for enhanced ICIC techniques is particularly crucial when the cell assignment rule diverges from the Reference Signal Received Power (RSRP) based approach, e.g. towards a pathloss- or a 'path gain'-based approach. This is sometimes also referred to as the cell range expansion when adopted for cells with a transmit power lower than neighbor cells. An idea of the cell range expansion is illustrated in FIG. 2, where the cell range expansion of a pico cell is implemented by means of a delta-parameter, aka bias or cell selection offset. The cell range expansion approach is also known as biased cell selection.
As discussed above, different interference coordination techniques, also referred to as enhanced ICIC (eICIC), have been discussed in the context of heterogeneous network deployments.
Now returning to the X2 interface, information to be signaled between radio base stations and from radio base stations, such as eNodeB, to a user equipment (UE) is described. It has been proposed that the signaling shall comprise the following:                one bitmap pattern to indicate an Almost Blank Subframe (ABS) pattern of Macro cell to Pico cell,        a second bitmap to indicate a subset of the subframes indicated by the first bitmap, which are recommended to the receiving node for configuration of restricted Radio Link Monitoring (RLM) and/or Radio Resource Management (RM) measurements, and        the pattern length and periodicity: Frequency Division Duplex (FDD)—40 ms: TDD—20 ms for downlink and/or uplink (DL/UL) configuration 1˜5, 70 ms for DL/UL configuration 0, 60 ms for DL/UL configuration 6.
It is also proposed that the requested Radio Resource Control (RRC) signaling comprises RRC signaling for resource specific RLM/RRM measurements and Channel State Information (CSI) measurements, where the resources that can be used for measurements are indicated by patterns, such as an ABS pattern or a pattern for RRM/RLM. A definition of ABS subframes is described in the following. For an ABS subframe, user equipments may assume the following:                All ABS subframes carry CRS;        If Primary Synchronization Signal (PSS), Secondary Synchronization Signal (SSS), Physical Broadcast Channel (PBCH), System Information Block 1 (SIB1), Paging and/or Positioning Reference Signals (PRS) coincide with an ABS, they are transmitted in the ABS (with associated PDCCH when SIB1/Paging is transmitted);        Needed for legacy support;        CSI reference signals (CSI-RS) transmission on ABS is not determined yet;        No other signals are transmitted in ABSs;        If ABS coincides with Multicast Broadcast Single Frequency Network (MBSFN) subframe not carrying any signal in data region, CRS is not present in data region;        MBSFN subframe carrying signal in data region shall not be configured as ABS.
According to the current state of the art, a measurement pattern per cell is to be decided. The measurement pattern is determined by a bitmap which is signaled to the user equipment, and it does not have to be the seine as the transmission pattern.
In a scenario, where load varies significantly among cells, it Is expected that different ABS patterns are configured in different cells. When determining the measurement pattern, the different ABS patterns Will need to be taken into account. Thus, only a small set of resources may be available for measurements. As a result, measurement quality may degrade and measurement time may increase.
Moreover, according to the current state of the art, a transmission pattern, or a ABS pattern, may be signaled to a neighbor radio node. The transmission pattern is determined by another bitmap.
With reference to the above mentioned scenario, the ABS pattern puts limitation on the network performance, in particular in terms what measurement pattern can be used.
In 3GPP DRAFT: R2-106449, to ALCATEL-LUCENT, titled "Signalling support for Almost Blank Subframe patterns", made available on 9 Nov. 2010 (2010-11-09), XP050467151, RAN WG2, Jacksonville, USA, there is disclosed signaling for enhancing Inter-cell interference coordination. For example, X2 and RRC signaling is described. In one example, with a UE specific RRC signaling, a Pica eNB is able to indicate an appropriate ABS pattern to the UE based on its location (based on the strongest interferer). Alternatively, it is also possible to provide the UEs with two sets of ABS patterns (corresponding to a first Macro eNB and a second Macro eNB.
WO2009/129261 discloses systems and methodologies that facilitate resource management in a wireless communication system. a network cell in a wireless communication system (e.g., a macro cell) is configured to mitigate the effects of Interference on other surrounding network cells (e.g. femto cells embedded within the coverage of the macro cell). For example, a network cell can allocate control resources that overlap control resources of a nearby cell and assign resources within the region of overlap only to users that will not cause substantial interference to the nearby cell. As another example, a network cell can utilize a control channelization that partially coincides with a control and/or random access channelization of a nearby cell. The network cell can subsequently elect not to use the control resources in the coinciding region in order to enable the nearby cell to control the effects of interference though data scheduling.

Methods and network nodes for configuring almost blank subframe transmission patterns and corresponding measurement patterns for reducing intercell interference in an heterogeneous cellular radio communication system


A valve (100) includes a valve body (300), a spool assembly (600), and a pendulum assembly (700). The valve body (300) is adapted for fixed attachment to a mounting surface (260) having an orientation corresponding to the incline of a supporting surface (210. The spool assembly (600) comprises a spool (610) pivotally mounted within the valve body (300), and the pendulum assembly (700) pivots the spool (610) in gravitational response to the orientation of the valve body (300). The valve body (300), the spool assembly (600), and/or the pendulum assembly (700) include one or more elements for adjusting flow symmetry between the LIO flowpaths and the GIO flowpaths.

Agricultural, construction, utility-repair, military and other types of equipment are often required to travel over inclined supporting surfaces oriented at an incline. This equipment sometimes comprises a structure that preferably (or perhaps necessarily) should be compensated for the non-levelness of the supporting surface. This compensation can be accomplished by, for example, an actuator and valve that supplies control fluid to the actuator in response to the incline of the supporting surface (i.e., an incline-responsive valve).
An incline-responsive valve can comprise a valve body, a spool assembly, and a pendulum assembly. The valve body is fixed to a mounting surface having an orientation corresponding to the incline of the supporting surface and the spool assembly includes a spool pivotally mounted within the valve body. A pendulum assembly pivots the spool in gravitational response to the orientation of the valve body to thereby situate the spool relative to the valve body among an IO (intended optimum) position, sequential LIO (less than intended optimum) positions that define enlarging LIO flowpaths, and sequential GIO (greater than intended optimum) positions that define enlarging GIO flowpaths.


The present invention provides for recombinant Endo-D and selected mutants that exhibit reduced hydrolysis activity and increased transglycosylation activity for the synthesis of glycoproteins wherein a desired sugar chain is added to a core fucosylated or nonfucosylated GlcNAc-protein acceptor by transglycosylation. Such recombinant Endo-D and selected mutants are useful for efficient glycosylation remodeling of IgG1-Fc domain.

1. Field of the Invention
The invention relates to glycoprotein synthesis, and more particularly, to the use of a recombinant Endo D, an Endo-β-N-acetylglucosaminidase, that possesses transglycosylation activity with sugar oxazoline with limited hydrolyzing activity thereby providing for efficient glycosylation remodeling of IgG1-Fc domain.
2. Description of the Related Art
Endo-β-N-acetylglucosaminidases (ENGases) are a class of glycoside hydrolases that hydrolyze the β-1,4-glycosidic bond in the N,N′-diacetylchitobiose core of N-glycans. The deglycosylation property of ENGases has been frequently used for structural and functional studies of glycoproteins. ENGases are classified into two classes of the glycoside hydrolase (GH) families in the CAZY database, GH18 and GH85. The commonly used bacterial endo-β-N-acetylglucosaminidases, such as Endo-H from Streptomyces plicatus (1) and Endo-F1, Endo-F2, and Endo-F3 from Flavobacterium meningosepticum (2,3), belong to the GH18 family. In contrast, the GH85 family includes ENGases from both prokaryotes and eukaryotes, including Endo-M from Mucor hiemalis (4,5), Endo-A from Arthrobacter protophormiae (6), Endo-D from Streptococcus pneumoniae (7), and Endo-CE from Caenorhabditis elegans (8). In addition to the hydrolytic activity, some of the ENGases have been shown to possess transglycosylation activity, capable of transferring the released N-glycan to an alcoholic acceptor such as an N-acetylglucosamine (GlcNAc) moiety to reconstitute the natural β-1,4-glycosidic linkage. The transglycosylation activity of ENGases has attracted much attention in recent years for chemoenzymatic synthesis of oligosaccharides, glycopeptides, and glycoproteins (9, 10).
Structural and mechanistic studies on Endo-H (11), Endo-F1 (12), Endo-F3 (13), Endo-A (14, 15), and Endo-D (16) suggest that the ENGase-catalyzed N-glycan hydrolysis follows a substrate-assisted mechanism. In this mechanism, a general acid/base residue (Asp or Glu) first acts as a general acid to protonate the glycosidic oxygen. Upon activation, the 2-acetamide group of the (−1)GlcNAc in the substrate acts as a nucleophile to attack the anomeric center, resulting in the breakdown of the glycosidic bond with simultaneous formation of an oxazolinium ion intermediate. The oxazolinium intermediate then undergoes hydrolysis or transglycosylation via its reaction with a water molecule or an alcoholic acceptor activated by the general acid/base residue. These structural studies also identified another important residue, which is located at 1 or 2 amino acid residues upstream from the general acid/base catalytic residue. This key residue was shown to be an Asp residue for the GH18 ENGases (Endo-H, Endo-F1, and Endo-F3) or an Asn residue for the GH85 ENGases (Endo-A, Endo-M, and Endo-D), which was required for the proper orientation of the acetamide group to promote the oxazolinium ion formation. The essential role of this residue for hydrolysis was confirmed by the fact that mutation of this residue abolished the hydrolytic activity of ENGases (11-16).
These mechanistic and mutagenesis studies laid the basis for exploring synthetic sugar oxazolines as donor substrates for transglycosylation, which resulted in significant enhancement of the transglycosylation efficiency for glycopeptide and glycoprotein synthesis (17-22). Moreover, it was further demonstrated that novel glycosynthases could be generated by site-directed mutation at the critical Asn residue that promotes oxazolinium intermediate formation in hydrolysis (Asn-175 in Endo-M and Asn-171 in Endo-A). The resulting mutants such as EndoM-N175Q and EndoA-N171A were able to take the activated sugar oxazolines for transglycosylation with marginal or abolished hydrolytic activity on the transglycosylation product (23-29). These discoveries open a new avenue to glycoprotein synthesis and glycosylation remodeling and specifically, immunoglobulin G (IgG) antibodies.
A typical IgG antibody is composed of two light and two heavy chains that are associated with each other to form three major domains connected through a flexible hinge region: the two identical antigen-binding (Fab) regions and the constant (Fc) region. It is noted that there are heterogeneous glycosylation states of the human IgG when expressed in mammalian cell lines (e.g., CHO cell lines), and isolation of human IgG having a particular glycosylation state from this mixture is extremely difficult. Small amounts of impurities of a highly active species can dramatically interfere with the results and data interpretation. Generation of high-affinity mAbs to Fc receptors, such as the Fc γIIIa receptor, may overcome the problem of polymorphism of the Fcγ receptor variants, thus enhancing the clinical efficacy of therapeutic mAbs.
Endo-D from S. pneumoniae belongs to the glycoside hydrolase family 85 (GH85). However, in contrast to Endo-A and Endo-M that belong to the same family, Endo-D is able to hydrolyze fucosylated N-glycan core. Fairbanks and co-workers (30) first reported that Endo-D possessed transglycosylation activity, capable of using Man3GlcNAc oxazoline as donor substrate to glycosylate a GlcNAc acceptor, but the transglycosylation efficiency was very low.
In light of the above known activities of Endo D, it would be advantageous to provide a mutant Endo-D that exhibits reduced hydrolyzing activity with increased transglycosylating activity.

Transglycosylation activity of glycosynthase mutants of an endo-beta-N-acetylglucosaminidase (endo-D) from streptococcus pneumoniae


The present invention provides a method of purifying a vinyl polymer to be used as a component of a composition capable of undergoing hydrosilylation.

The hydrosilylation reaction is utilized in functional group conversion, crosslinking and other reactions and is one of very useful reactions from the industrial viewpoint. It is known, for example, that a polymer having an alkenyl group as a functional group at a molecular chain terminus can be crosslinked and cured to give cured products excellent in heat stability, durability and the like properties when a hydrosilyl group-containing compound is used as a curing agent, and that when an alkenyl group-terminated polymer is reacted with a a hydrosilyl group-containing compound having a crosslinkable silyl group, a crosslinkable silyl group-terminated polymer is produced. These hydrosilylation reactions proceed upon heating, and a hydrosilylation catalyst is added for causing the reactions to proceed more rapidly. Such hydrosilylation catalyst includes radical initiators, such as organic peroxides and azo compounds, and transition metal catalysts. In particular, it is known that when a transition metal catalyst is used in a catalytic amount, the hydrosilylation can be allowed to proceed rapidly.
On the other hand, living polymerization is generally known as a precise method of polymer synthesis. A feature of living polymerization is that not only the molecular weight and molecular weight distribution can be controlled but also polymers definite in terminal structure can be obtained. Therefore, living polymerization may be mentioned as one of effective methods of functional group introduction at a polymer terminus or termini. In radical polymerization as well, polymerization systems in which living polymerization is possible have recently been found and, thus, advanced studies on living radical polymerization are underway. In particular, when atom transfer radical polymerization is utilized, polymers narrow in molecular weight distribution can be obtained. As examples of atom transfer radical polymerization systems, there may be mentioned polymerization systems using, as an initiator, an organic halide or halogenated sulfonyl compound and, as a catalyst, a metal complex with a central atom selected from among elements of the group 8, 9, 10, and 11 of the periodic table of the elements. (For example, see Matyjaszewski et al., J. Am. Chem. Soc., 1995, 117, 5614, Macromolecules, 1995, 28, 7901, Science, 1996, 272, 866, or Sawamoto et al., Macromolecules, 1995, 28, 1721).
However, the transition metal complex, namely the polymerization catalyst, remains in the vinyl polymers produced by atom transfer radical polymerization, producing such problems as coloration of the polymers, influences on the physical properties thereof, and environmental safety problems. For example, in the case of alkenyl group-terminated vinyl polymers produced by utilizing the atom transfer radical polymerization technique, the residual catalyst and the like serve as catalyst poisons in the hydrosilylation reaction and, thus, the hydrosilylation reaction is inhibited, producing a problem in that the expensive transition metal catalyst is required in larger amounts.
The present inventors previously found that the hydrosilylation activity of vinyl polymers obtainable by atom transfer radical polymerization can be improved by purifying the polymers by bringing them into contact with an adsorbent such as aluminum silicate (Japanese Kokai Publication Hei-11-193307). On that occasion, however, the adsorbent is required in large amounts, causing such problems as an environmental impact by the waste and an adsorbent-related increase in purification cost. It is an object of the present invention to solve these problems and provide an economical and efficient method of purifying vinyl polymers as well as a polymer and a composition capable of reacting in the manner of hydrosilylation.

This patent is subject to a terminal disclaimer.

Abstract: The present invention provides a vinyl polymers obtainable by atom transfer radical polymerization can be purified economically and efficiently by adsorption treatment using an acidic adsorbent and a basic adsorbent combinedly, with the result that the reactivity in hydrosilylation thereof is improved. Thus, the polymers can be used as components in hydrosilylation reaction-susceptible compositions.


A camera system and associated method for aligning a component with a footprint on a PCB including: a housing having a first side and a second side opposite to the first side; a first image sensor positioned on the first side of the housing and pointing to a first direction away from the housing to capture an image of the component and generating a first image signal, wherein the first image sensor includes a first lens assembly without a prism; a second image sensor positioned on the second side of the housing and aligned with the first image sensor pointing to a second direction opposite to the first direction to capture an image of the footprint on the PCB and generating a second image signal, wherein the second image sensor includes a second lens assembly without a prism; a mixing circuit for mixing the first image signal with the second image signal and generating a mixed image signal; and a processor for processing the mixed image signal and displaying a superimposed image of the component and the footprint on a display monitor.

With the greater variety of components used on PCBs, smaller passive components and larger IC's with finer ball pitch dimensions, the demands on vision systems to aid PCB assembly (PCBA) rework have increased.
In electronic assembly industry, it is common to use one camera with an optical prism to view the PCB and component simultaneously. All these cameras use prism type optics. In ball grid array (BGA) rework applications, a large field of view (FOV), a high magnification and a high image quality is required during the alignment process, since the component footprints and their pitches are increasingly smaller. Traditionally, an expensive charge coupled device (CCD) camera is used with an expensive and bulky optical zoom lens and a split prism for viewing multiple surfaces at the same time. This increases the cost and complexity of such systems.
As a result, a high definition image, without the imperfections that result from the use of an external optical system, is now required to facilitate the placement of today's components.

Camera system for aligning components of a PCB


In a wireless communication apparatus, data transmitted from at least one wireless transmitter is received by direct wireless communication, and its wireless reception condition is detected. Relation reference information setting two or more relations between the wireless reception condition on a reception of transmitted data and location information of the transmitter is stored. Relative distance information of a relative distance between the transmitter and the apparatus is measured. Relation information indicating a relation between the wireless reception conditions and the relative distance information is generated. A relation between the location information and the relative distance information is determined by comparing the relation reference information and the relation information. A current location of the apparatus is determined on the basis of the relation between the location information and the relative distance information and a current wireless reception condition.

1. Technical Field
The present invention relates to a wireless communication apparatus and a wireless positioning system, which perform positioning through wireless communication.
2. Related Art
GPS (global positioning system) is well known as a wide-area position information service. However, GPS suffers from a problem that, within buildings or behind doors, position information services are not available. Further, GPS, which relies on GPS satellite infrastructure, also suffers from a problem that infrastructure failure or service outage will disable use of the position information services.
Wireless LAN (local area network) positioning technique has been used for some time, which enables positioning not relying on a GPS satellite but using electrical measurement information of widespread wireless LAN. However, in the wireless LAN positioning technique, the positioning accuracy depends on the number of base stations that can receive signals and specify positions. Therefore, the wireless LAN positioning technique suffers from a problem of the cost of building the base stations involved in spreading the technique in a wide area.
In order to solve the problems as set forth above, infrastructure that makes it possible to provide wide-area position information services not relying on a GPS satellite has started to build (see, for example, JP-A-2008-104029). In this infrastructure, the information of detecting wireless LAN stations that are used for communication is aggregated in the cloud for cloud computing using computing resources provided as a service over a network. Then, the LAN stations can be used as base stations for position detection, thereby reducing the cost of building base stations. Thus, wide-area position information services not relying on a GPS satellite becomes available.
However, the technique of aggregating in cloud the information of detecting wireless LAN base stations as disclosed in JP-A-2008-104029 also suffers from a problem that the positioning accuracy greatly depends on the density of the registered base stations.

Wireless communication apparatus and wireless positioning system


A variable gain analog amplifier is described that uses pulse-density modulation in the form of a sigma-delta modulator (SDM) to produce a gain by modulating the selection of a switch that selects the amount of resistance in a negative feedback loop of the amplifier. The output of the SDM is dithered to increase the gain resolution of the analog amplifier, wherein the increased resolution produces a quiet, inaudible transition between changes in gain setting at an output of the variable gain amplifier and in addition produces a quiet, inaudible mixing and merging of audio signals.

1. Field of Invention
The present invention is related to audio amplifiers and in particular to increasing gain resolution of output stages of audio amplifiers.
2. Description of Related Art
Present day audio systems and integrated audio devices can have a plurality of sources that play into a plurality of different types of outputs, for example, an auxiliary input may be reproduced in an earphone amplifier or a DAC output may be played into an earpiece amplifier. In home high fidelity systems the selection is made by a switching device where the transition between sources is controlled so as not to introduce auditable effects of switching between input and output devices. In integrated audio devices a large number of distinct paths can be configured through summing amplifiers that perform a mixing operation. Unwanted sounds, e.g. pops and clicks, may be audible when the different source signals are at a different level when switched into the summing amplifier. A solution to the unwanted sounds could be to effectively mute the output, perform the required switching and then raise output amplitude back to where it was before muting.
The gain accuracy of audio amplifiers is usually determined by fixed value resistance in the feedback of the amplifier where the step size is dependent upon the number of elements in the feedback network and the intended range of the amplifier gain. If the gain is changed with a step size that is too large, for instance >0.01 dB for a 60 dB range, a zipping noise will be introduced. The large number of resistors needed to produce such an effect would make the amplifier device expensive and noncompetitive. Unwanted audio effects can often be eliminated by using discrete components on a PCB, but the cost of components can be in the order of magnitude of the integrated audio device itself.
US 2010/0166084 A1 (Galton et al.) is directed a successive re-quantizer that replaces a delta sigma modulator in a fractional-N PPL or DAC, which avoids spurious tone problems in non-linear analog circuitry. US 2006/0092059 A1 (Guimaraes) is directed to an automatic gain control using a sigma delta ADC. An amplifier is within a sigma delta time continuous loop prior to quantization and an attenuator in the feedback prior to summation with incoming signals. U.S. Pat. No. 7,821,341 B2 (Kim et al.) discloses a gain device with an amplifier that uses the gain device, which uses a linearly variable resistance to control the gain of the amplifier. In U.S. Pat. No. 7,583,213 B2 (Wang et al.) a signal processing system that is directed to changing the level of an input signal to produce an output signal, which includes a shifter, a sigma delta modulator and a level adjuster. U.S. Pat. No. 7,148,829 B2 (Inukai) is directed to a sigma delta modulation circuit having a gain control function, wherein a control unit controls the gain of a variable gain amplifier using a sigma delta modulator and a filter that operates on the output of the sigma delta modulator. In U.S. Pat. No. 7,102,441 B2 (Lee et al.) a variable gain amplifier circuit is directed to a use of a resistor ladder for obtaining a precise gain.
U.S. Pat. No. 6,404,367 B1 (Van der Zwan et al.) is directed to a sigma delta modulator that is used to interchange (chop) the input network and the feedback network to average out the differences in the two gain stages and produce a more accurate gain. U.S. Pat. No. 6,127,893 (Llewellyn et al.) is directed to a control circuit for controlling a level of an audio signal, wherein the control circuit is based on a R-2R resistive network having a plurality of resistor nodes and a plurality of switches to connect the resistors to a low impedance node. An article by Kevin. J Wang, "Spurious Tone Suppression Techniques Applied to a Wide-Bandwidth 2.4 GHZ Fractional-N PPL", IEEE Journal of Solid State Circuits, Vol. 43, No. 12, December 2008, is directed to spurious tones in the output of a fractional-N PLL that are reduced by replacing a sigma delta modulator with a digital quantizer with a charge pump offset and a sampled loop filter. An article by James A. Kaehler, "Periodic-Switched Filter Networks—A means of Amplifying and Varying Transfer Functions", IEEE Journal of Solid State Circuits, vol. sc-4, no. 4, August 1969, is directed to a technique of periodically switching filter networks to allows continuously variable filter parameters.
FIG. 1 shows a variable gain analog amplifier of prior art. An operational amplifier 10 is connected between an input signal, Vin, and an output signal, Vout, created by the operational amplifier. Switches S1 and S2 select the amount of negative feedback resistance connected between the output of the amplifier 10 and the negative input (summing junction) of the operational amplifier 10. The positive input terminal of the amplifier is connected to Vref, which is often ground potential. Selection of either switch S1 or S2 determines the amount of resistance between the input signal Vin and the negative input of the operational amplifier 10. Assuming that Rin=R1=R2, then the gain of the amplifier 10 is G1=−(R1+R2)/Rin=−2 when switch S1 is selected, and when switch S2 is selected the gain G2=−(R2)/(R1+Rin)=−½.
If the two switches S1 and S2 are toggled (turned on and off) at a relatively rapid rate with a fifty percent duty cycle, an average gain of Gavg=−(2+½)/2=−1.25 as shown in FIG. 2 where the two switches are opened and closed out of phase with each other. When Vin 20 applied to the amplifier is a ramp over a span of time t, Vout becomes a ramp 21 interrupted by the two different gains resulting from G1=−2 and G2=−½. The effective, or average output voltage 22 is twenty five percent higher than the input voltage Vin.
A portion of the control signal that drives the switches S1 and S2 can appear at the output of the amplifier, but this can be attenuated by the ratio of the switched resistance to the total resistance, or Rmod=Rsw/Rtot where Rmod is the control signal attenuation, Rsw is the switched resistance and Rtot=Rin+R1+R2. Also some of the high frequency switch control signal can be coupled to the output of the amplifier through parasitic capacitance of the circuitry. The higher the modulating frequency compared to the amplifier gain bandwidth (Fmod=fclk/fbw, where Fmod is the modulating frequency, fclk is the clock rate and fbw is the frequency bandwidth of the amplifier) and the lower Rmod, the lower the amplitude of the control signal that will appear at the output of the amplifier Vout.

Sigma-delta modulator approach to increased volume resolution in audio output stages


Polyethylene glycol ethers of alkyl alcohols having the general formula CH3(CH2)xCH2(OCH2CH2)nOH wherein x is 8 to 20 (of which ceteareth-20, steareth-20 and steareth-100 are preferred), poloxamer 185, poloxamer 407, N,N-dimethyl dodecylamine N-oxide, and mixtures thereof, are employed to increase follicular delivery and/or follicular residence time of certain water soluble ornithine decarboxylase inhibitors of which 2(difluoromethyl)-2,5-diamino pentanoic acid and its pharmaceutically acceptable salts, hydrates, optical enantiomers and racemic mixture are preferred.

ODC inhibitors, particularly, DFMO and its pharmaceutically acceptable salts and hydrates, are known to be topically useful in regulating hair growth in mammals, particularly humans (see U.S. Pat. No. 4,720,489 and P.D.R., 55 Edition, 2001, pages 1031-1033).
PCT WO 98/25603 discloses an isomeric pharmaceutical formulation containing DFMO. Examples 7 and 8 respectively teach preparation of a [−]-DFMO containing lotion and topical solution. Patentees teach that the lotion formulation is useful for the treatment or prevention of skin melanoma. The solution is disclosed to be suitable for topical treatment or prevention of proliferative skin disorders. The treatment of such conditions does not require delivery of drug to the hair follicles. More importantly, there is no appreciation whatsoever of enhancement of delivery of DFMO to the skin, much less to the hair follicle. Although Example 7 employs Poloxamer 235, there is no disclosure whatsoever of any advantage for it other than its known use as a co-emulsifier.
U.S. Pat. No. 5,851,537 discloses the topical application of alpha-DFMO monochloride monohydrate for preventing skin cancer. The drug, carried in a hydrophilic cream base, is applied to actinic keratoses. Hydrophilic cream contains 0.025% methyl paraben, 0.015% propyl paraben, 1% sodium lauryl sulfate, 12% propylene glycol, 25% stearyl alcohol, 25% petrolatum and 37% water. There is no disclosure whatsoever of a follicular delivery enhancing component or the desirability of including it. In point of fact, patentees state that the compositions of their invention contain no absorption enhancer.
U.S. Pat. No. 4,720,489 discloses a process for reducing the rate and altering the character of human hair growth. The process comprises applying to the skin a composition containing an ODC inhibitor. Patentees, however, fail to disclose or even appreciate the desirability of targeting the ODC inhibitor to the hair follicle or the need to use a follicular delivery enhancer for such purpose.
U.S. Pat. No. 5,648,394 discloses a topical composition for inhibiting mammalian hair growth. The composition comprises about 1 to 20 parts by weight of a water-soluble, hair-growth-inhibiting drug dispersed in about 99 to 80 parts by weight of an oil-in-water emulsion based vehicle. In parts by weight, the vehicle is comprised of water 78 to 87; glyceryl stearate 2.8 to 4.8; PEG-100 stearate 2.7 to 4.7; cetearyl alcohol 1.9 to 3.3; ceteareth-20 1.6 to 2.7; mineral oil 1.7 to 2.7; stearyl alcohol 1.0 to 2.0; and dimethicone 0.3 to 1.0. Patentees contend that compositions of the invention are superior in efficacy to a water-ethanol composition containing penetration enhancers. They state that this suggests that the compositions of the invention achieve either enhanced skin penetration of the active or increased residence time of the active at the treated site. Patentees, however, fail to teach or even suggest which composition ingredient, or combination of ingredients, accounts for the enhanced skin penetration or increased residence time. Thus, one skilled in the art would attribute it to the entire composition as opposed to any particular composition component or combination of components.
Patentees prepared the vehicles of Examples I and II (see Col. 2 of U.S. Pat. No. 5,648,394). Test compositions containing 2.5, 5, 10, and 15 percent DFMO were then prepared using the two vehicles. A composition containing 10 percent DFMO in water-ethanol was also prepared. The compositions were then tested for hair growth inhibition using the hamster flank model (see Example, Col. 3 of U.S. Pat. No. 5,648,394). The test results (set forth in the table in Column 3 of U.S. Pat. No. 5,648,394) demonstrate that, in each case, the DFMO composition prepared using the vehicle of Example II had a higher percentage of inhibition than the respective DFMO composition prepared using the vehicle of Example I. Consequently, even if one skilled in the art were to select, for example, ceteareth-20, out of the ten ingredients that make up the vehicle, he or she would be led away from the present invention. Although the vehicle of Example II contained less ceteareth-20 than the vehicle of Example I, patentees test results show that the percentage of inhibition obtained with the use of the vehicle of Example II was higher. Thus, if one skilled in the art wishing to increase the percentage of inhibition is led to ceteareth-20, he or she would be led by the teaching of this patent to reduce the amount of ceteareth-20 contained in the composition. The skilled artisan would not increase the amount of ceteareth-20 or, for that matter, the amount of any other ingredient(s) of the vehicle.
The prior art, typified by U.S. Pat. No. 5,648,394, demonstrates the effectiveness of ODC inhibitors for inhibiting hair growth by measuring changes in flank organ hair mass in adult male hamsters treated with ethanol solutions of the ODC inhibitors. The standard hamster flank organ mass study is described in, for example, U.S. Pat. Nos. 4,720,489, 5,095,007, 5,096,911 and 5,132,293.
Prior art topical DFMO compositions generally show relatively low efficacy in humans. Possibly the presumed levels of DFMO achievable in human follicles through use of prior art topical DFMO compositions are insufficient to cause sustained and effective inhibition of target enzyme ornithine decarboxylase ("ODC").
Complicating matters is the fact that with hair mass analysis, it is very difficult to differentiate the efficacy of different DFMO formulations. This is in part due to physical effects of lotion-based formulations on hamster hair.
The present inventors hypothesized that hair follicle atrophy could represent a surrogate end point for DFMO efficacy.
Clinical studies that were later carried out confirmed that hair follicle atrophy is indeed a valid marker for DFMO efficacy.
The half-life of ODC in the hair follicle is about thirty minutes. In order to block ODC enzyme when it is present in the hair follicle, the ODC inhibitor must be present in the follicle in sufficient amount and for a prolonged duration.
Thus, an aim of the present invention was to identify excipients that would target a high concentration of an ODC inhibitor, preferably DFMO and its pharmaceutically acceptable salts, hydrates, optical enantiomers and racemic mixtures, more preferably Eflornithine, to the hair follicle and, ideally, keep it there for a prolonged duration.
In order to determine differences in the efficacy of DFMO in lotion-based formulations, as well as the onset of action of DFMO, independent of hair growth, the present inventors had to develop a method of analysis of human hair follicle bulbs.
Another goal of the present invention was to develop a formulation that would enhance the delivery of an ODC inhibitor, particularly DFMO and its pharmaceutically acceptable salts, hydrates, optical enantiomers and racemic mixture, to the pilosebaceous unit target site (consisting of the hair follicle, hair shaft and sebaceous gland) and maintain its concentration over a prolonged period of time. Since ornithine decarboxylase has a fifteen-minute to one-hour half-life it is highly desirable that the ODC inhibitor be present in the hair follicle for as long a time as is possible.

Topical composition for follicular delivery of an ornithine decarboxylase inhibitor


The embodiments of the application provide a backlight module and a displaying device, relating to the technical field of display. The backlight module comprises a first support structure, an optical film material and a buffer structure; the first support structure is arranged on a side away from a light-outgoing side of the optical film material, and the first support structure and the optical film material have a through-hole; the buffer structure comprises a first buffer portion arranged in the through-hole, and a rigidity of the first buffer portion is less than a rigidity of the first support structure. The backlight module is internally provided with the buffer structure, and the first buffer portion in the buffer structure is arranged in the through-hole that penetrates through the first support structure and the optical film material.

To ensure that a displaying device has a narrow frame, the shape of the displaying device becomes diversified. A full screen, a blind-hole screen, a water-drop screen, etc. have emerged. Among them, the blind-hole screen is able to extremely the minimize the frame of the displaying device.
At present, in the displaying device with a blind-hole screen, an optical film material of a backlight module is provided with a performative through-hole. The through-hole is internally provided with a rigid support structure which enhances the strength of the backlight module. The rigid support structure is arranged along a side wall of the through-hole.

Backlight module including buffer structure and display device including the same

Beijing BOE OptoelectronicsTechnology Co., Ltd.


A method and system for performing device identification is disclosed. A source signal may be directed from an energy source towards the surface of a device for reflection therefrom. An interference pattern may be detected from the surface of the device, such as by a sensor. A determination as to whether a match exists between the representation of the interference pattern and a stored representation of an interference pattern may be performed. If a match exists, the device may be identified based on the stored representation of the interference pattern. Otherwise, a representation of the interference pattern may be stored and a unique identifier may be assigned to the stored representation of the interference pattern.

1. Technical Field
The disclosed embodiments pertain to methods and systems for identifying devices. The disclosed embodiments particularly pertain to methods and systems for identifying devices using speckle patterns.
2. Background
Implantable medical devices can be used to perform a variety of functions for patients needing medical care. Such devices include relatively large devices, such as implantable defibrillators, and relatively small devices, such as bone screws and stents.
In order to provide an appropriate level of patient safety, all implanted devices, and many non-implanted devices, must be serialized to enable tracking if a part defect, product recall, concerns about counterfeit parts or other reliability issue arises. While a relatively large medical device is typically identified by a serial number that is written, engraved or otherwise labeled on the device, a smaller device is conventionally identified only on its packaging by a serial number or a lot number because such devices are too small to be directly labeled by conventional means. As such, when a small, unlabeled medical device is explanted and/or returned to a supplier without its packaging, it can be impractical or impossible to identify the manufacturing lot from which the device came and/or the serial number assigned to the device.
Adequately identifying small devices can also be problematic in other fields as well. For example, a small semiconductor device might not be sufficiently large to identify the part number, the lot number, the manufacturer and the like.
What is needed is a method and system for uniquely identifying a device, particularly a device that is difficult to directly label with a serial number.
A further need exists for a simple and inexpensive process for performing such identification for medical and non-medical devices.
The present embodiments are directed to solving one or more of the aforementioned problems.

Method and system for device identification


An implant configured to be placed in a living body to be expansively deformed and contractively deformed comprises a first layer that forms a filling unit that is configured to be filled with a filling material to maintain an expanded state of the implant, the first layer comprising a porous membrane; a second layer that covers the first layer, the second layer comprising at least one of (i) a fluid-impermeable membrane, and (ii) a gas-permeable porous membrane that is impermeable by liquids or gels; and an introduction port that communicates with the filling unit and is configured to introduce the filling material into the filling unit. An introduction region is formed between the first layer and the second layer, the introduction region being configured to receive a fluid permeating the first layer when the filling material is introduced into the filling unit.

1. Technical Field
The disclosure relates to an implant that is placed into a living body, and an implant assembly that includes the implant.
2. Background Art
In the medical field, techniques relating to implants that are placed into living bodies and various techniques relating to methods for placing the implants into the living bodies are known. For example, International Publication No. WO 2009/006258 discloses an implant that is placed between spinous processes of the living body to treat lumbar spinal canal stenosis.
In the related art, an expansively deformable balloon is injected with a filling material and the balloon is used as an implant for spacing between the spinous processes. The balloon injected with the filling material causes the distance between the adjacent spinous processes to be expanded and maintained with a predetermined gap. The balloon functions as a spacer which is placed in the living body over a long period of time. A relatively rigid material is sometimes used as the filling material so as to maintain an expanded state of the balloon over a long period of time. However, when the rigidity of the filling material is high, a load on the spinous processes and living body tissue present around the spinous processes increases, and thus, this type of implant is not suitable to be placed in the living body over a long period of time.
U.S. Patent Publication No. 2010/0249841 discloses an implant for spinous processes that includes an inner side container forming a space to hold the filling material and an outer side container which is arranged in an overlapping manner so as to cover a part of an outer circumferential surface of the inner side container. This implant is capable of addressing the problem of WO 2009/006258 described above by filling the inner side container with the filling material and filling the outer side container with a relatively flexible material. However, in order to allow the inner side container to be filled with the filling material and additionally allow the relatively flexible material to be introduced into the outer side container, a plurality of introduction paths (catheters and the like) must be used to communicate with the respective containers. When the plurality of introduction paths are used, a larger wound hole must be formed in the living body during the introduction of the implant into the living body, which is problematic in that the introduction of the implant cannot be performed in a minimally invasive manner.
Therefore, there is a need for an implant which can be introduced into the living body in a minimally invasive manner and can reduce the load on the living body while in use regardless of the type of the filling material used to maintain the expanded state, and an implant assembly including the implant.


A processing system includes: a first statistical operator configured to divide data output from each sensor of a target apparatus according to each processing division of a processing performed by the target apparatus, and perform a statistical operation for each processing division; a second statistical operator configured to divide data output from each sensor of a comparative apparatus according to each processing division of the processing performed by the comparative apparatus, and perform a statistical operation for each processing division; a calculator configured to calculate a difference value between a result of the statistical operation performed by the first statistical operator and a result of the statistical operation performed by the second statistical operator, for each processing division; and a display controller configured to display the difference value for each processing division in a graph.

In the related art, in various processing apparatuses such as, for example, a substrate processing apparatus, an operation of a target apparatus is verified in the manner that a "data checking task" for checking data output from a sensor in the apparatus is performed by executing a processing according to a general method at the time of booting the apparatus.
Meanwhile, for a processing apparatus such as, for example, a substrate processing apparatus where a large number of sensors (e.g., 1,500 sensors) exist, and a period of data sampling is short (e.g., a period of 0.1 second), the number of data points becomes enormous when the processing according to the general method is executed. See, for example, Japanese Patent Laid-Open Publication No. 2010-505209.

Processing system and method for comparatively analyzing data


Disclosed are methods for treating wells to form a permeable barrier around the well for consolidating unconsolidated mineral particles such as sand in a subterranean petroleum formation penetrated by a well, or for forming an impermeable barrier for fluid entry control, or for plugging the well for abandonment. A fluid containing a polymerizable resin such as furfuryl alcohol, a polar organic diluent such as butyl acetate and an oil soluble acid catalyst to cause polymerization of the resin at formation temperatures is prepared. The acid should have a pK in the range of 0.4 to 6.0. The acid and acid concentration are selected to cause the polymerization reaction to be essentially complete in from 0.75 to 4.0 hours and preferably 1.0-2.0 hours at the formation temperature. Usually the selected acid concentration will be in the range of from 0.2 to 5.0 percent. This fluid is injected into the formation to saturate at least a portion of the formation adjacent to the well. In one embodiment, when it is desired to form a permeable treated zone for sand control, an aqueous fluid comprising water which is from 70 to 100% saturated with inorganic salts including sodium chloride is injected into the same portion of the formation contacted by the resin containing fluid. The injected resin-containing fluid is allowed to remain in the formations for at least four hours to accomplish at least partial polymerization of the resin, forming a permeable or impermeable mass around the wellbore.

Formation treating for purposes of sand consolidation, water exclusion or well plugging for abandonment are well known terms applying to procedures routinely practiced in the commercial production of petroleum. When wells are completed in petroleum-containing which also contain unconsolidated granular mineral material such as sand or gravel, production of fluids from the formation causes the flow of the particulate matter, e.g. sand, into the wellbore, which often leads to any of several difficult and expensive problems. Sometimes a well will "sand up", meaning the lower portion of the production well becomes filled with sand, after which further production of fluid from the formation becomes difficult or impossible. In other instances, sand production along with the fluid results in passage of granular mineral material into the pump and associated hardware of the producing well, which causes accelerated wear of the mechanical components of the producing oil well. Sustained production of sand sometimes forms a cavity in the formation which collapses and destroys the well. All of these problems are known to exist and many methods have been disclosed in the prior art and applied in oil fields in order to reduce or eliminate production of unconsolidated sand from a petroleum formation during the course of oil production.
Another problem encountered in oil production to which the present process offers an attractive solution is encountered when a well is in fluid communication with a section that includes one or more oil producing intervals and one or more water producing intervals. Production from such a zone results in production of some oil and some water. Since the viscosity of water is less than the viscosity of oil, a much larger volume of water than oil is frequently produced.
In yet another embodiment, the resin-catalyst mixture can be used to completely plug a well which is to be abandoned. This embodiment requires a slightly greater volume of resin-catalyst mixture to be used, since the best results for this embodiment require that the interior of the well casing and/or tubing be filled completely with the resin for all or a substantial amount of its length. The long term durability of the material used to plug wells for abandonment is of high current interest because of the danger that salt water or petroleum might enter and contaminate fresh water-containing 15 intervals.
The above-described sand control problems and potential solutions to the problems have been the subject of extensive research by the petroleum industry in the hope of developing techniques which minimize or eliminate the production of sand particles into the producing well and associated equipment during the course of producing fluids from the formation. One general approach suggested in the prior art for consolidating sand to form a fluid permeable zone around the well involves consolidating the porous but unconsolidated sand structure around the wellbore in order to cement the loose sand grains together, thereby forming a permeable mass which will allow production of fluids from the formation into the well but which will restrain the movement of sand particles into the wellbore when used for fluid exclusion, into an impermeable mass if the desired result is water exclusion. Another approach involves removing a portion of the formation around the well and packing specially prepared granular material into the formation around the wellbore which is subsequently caused to be cemented together in a manner which maintains fluid permeability.
It is a primary objective of any successful sand consolidation method that a barrier be formed around the wellbore which restrains the movement of sand particles into the well while offering little or no restriction to the flow of fluids, particularly oil, from the formation into the wellbore where it can be pumped to the surface of the earth. Consolidation only needs to extend into the formation to a depth of 6 to 12 inches around the periphery of the perforations or other openings in the outer casing of the production well.
The objective of a water exclusion of fluid entry control process is to form an impermeable barrier around the well to prevent the flow of sand and formation fluids into the well. A process similar to that used to control sand problems can be used for plugging formation for water exclusion, provided the process is modified to cause creation of an impermeable barrier rather than a permeable barrier.
A very important quality of a satisfactory sand consolidation method, plugging or water exclusion method is durability of the permeable or impermeable barrier formed around the wellbore. Once a permeable barrier is formed and the well is placed on production, there will be a continuing flow of fluids through the flow channels within the permeable barrier, and it is important that the barrier last for a significant period of time, e.g. several months and preferably years, without excessive abrasive wear or other deterioration of the consolidation matrix which would cause the particulate matter to flow once again into the wellbore.
It is also important that the material injected into the formation for all of our formation treating methods described above should be essentially unreactive during the period it is inside the wellbore, i.e. while it is being pumped down the well and positioned where it is desired adjacent to the perforations of the production casing. It is this desire to delay the polymerization reaction that has lead prior art methods to employ multi-step procedures in which first a catalyst is injected into the formation, after which the polymerizable resin-containing fluid is injected. While this reduces the propensity for the fluid to polymerize in the wellbore, it does give rise to several problems which constitute inherent weaknesses in many prior art methods for accomplishing sand consolidation. First, each separate injection step increases the time and cost associated with the well treatment by which sand consolidation, water shut off or well plugging is accomplished. Second, injection of catalyst into the formation in advance of the polymerizable fluid does not accomplish uniform mixing of catalyst with all of the polymerizable fluid which is needed to ensure optimum polymerization of the resin, which is essential for strength and durability of the consolidated mass. Use of aqueous fluids to inject catalyst often gives rise to the need for yet additional steps to clean the sand to remove formation petroleum so the catalyst will be absorbed by the sand and later mix with the subsequently injected resin containing fluid.


Thin films of isotropically conductive material are formed from Sr.sub.1-x Ca.sub.x RuO.sub.3. This material is easily deposited as a thin film by methods such as 90.degree. off-axis sputtering and laser ablation. The materials are epitaxially deposited on a wide variety of substrates and allow overlying epitaxial growth of an equally large number of significant oxides such as superconducting oxides, dielectric, and ferroelectric materials.

1. Field of the Invention
This invention relates to devices containing epitaxial oxide thin films, and in particular, devices having electrically conductive oxides.
2. Art Background
Many electrical and optical devices rely on deposited thin oxide films. For example, thin films of superconducting oxides such as YBa.sub.2 Cu.sub.3 O.sub.7 have been proposed for electronic devices such as SNS (superconductor-normal metal-superconductor) Josephson junctions and regions of normal metallic conductivity in an integrated superconducting device. Similarly, ferroelectric oxide materials such as Pb(Zr.sub.0.52 Ti.sub.0.48)O.sub.3 (PZT) have been proposed for use in ferroelectric memory devices.
In forming thin film devices, a series of layers are deposited on a single crystal substrate. Typically, a thin film device has, in addition to the active region, (e.g. an optically, electrically, or magnetically active area) regions having dielectric properties and regions having relatively high electrical conductivity. (Relatively high electrical conductivity in the context of this invention is a resistivity less than 1000 .mu..OMEGA.-cm.) The conductive regions are generally employed to form contact to and interconnections between active regions while the dielectric regions are required to provide electrical isolation between different conductive and/or active regions. As shown in FIG. 1 to produce electrical conductivity between active regions 12 and 14, it is necessary to have equally high conductivity throughout the conductive material forming interconnect region 15 and contact regions 10. Thus, for many electrically conductive regions such as contact regions, it is quite desirable or even necessary that the conductivity be isotropic, i.e., the conductivity along the z-axis (an axis perpendicular to the major surface of the thin film), as well as two other mutually perpendicular axes have a mean deviation of less than 300% over the operating temperature range.
The characteristics of the device, however, rely on more than just the chemical composition of the constituent layers. To obtain the desired properties such as electrical properties, these layers, (e.g., the oxide materials, such as the ferroelectric oxide material or the superconducting oxide material) must be epitaxially deposited. (Epitaxial growth in the context of this invention is defined as there being no more than three discrete crystallographic orientations of one layer with respect to the adjoining material upon which it is deposited.) Generally grain boundaries, crystal defects, and interface defects between the layers resulting from non-epitaxial growth are undesirable. For example, non-epitaxial growth leads to high angle grain boundaries in materials such as PbZr.sub.0.52 Ti.sub.0.48 O.sub.3, which in turn, result in device degradation through aging and fatigue induced by charge segregation and decay at the grain boundaries. Similarly, lack of epitaxial growth in the deposition of copper oxide based superconductor materials leads to significantly decreased critical current densities and degraded device properties. Interfaces between conductive layers and active layers should also be free of objectionable defects and exhibit coherent crystal structure. The presence of contamination or incoherency at an interface with, for example, copper oxide based superconductors leads to high interfacial resistance and an additional insulating interfacial region. Interfacial problems in ferroelectric devices often lead to degraded performance characteristics.
Thus, it is quite desirable to have an isotropically conductive oxide material that 1) grows epitaxially on substrates and/or other oxides, 2) allows epitaxial growth of other oxides deposited upon it, and 3) does not adversely undergo chemical reactions with these other oxides. Conductive oxide materials proposed for device applications include Sr.sub.2 RuO.sub.4 Lichtenberg, F., et al., Applied Physics Letters, 60, 1138 (1992), PrBa.sub.2 Cu.sub.3 O.sub.7, and isotropic perovskites such as Nb-doped SrTiO.sub.3. However, the first has never been grown as a film, and is a layered, highly anistropic material; the second is semiconductive and anistropic; and the third is also extremely difficult to grow reproducibly while being incompatible with oxidizing conditions used to form oxides such as YBa.sub.2 Cu.sub.3 O.sub.7. Therefore, an improved oxide having isotropic electrical characteristics is still not available.


In the laser printer for performing image formation through an electrophotography process, the agitator 32 is rotated to agitate toner in the toner cartridge 30 to supply toner through the toner exhaust port 206 to the process unit 7. To rotate the agitator 32, the engagement member 302 and the flange 304 are inserted in the end port 230 of the toner cartridge 30. The sealing member 306 is attached in close contact with the engagement member 302 and the flange 304. The washer member 308 is disposed between the sealing member 306 and the flange 304. The grooved portion 305 is provided on the contact surface of the flange 304 in contact with the washer member 308.

1. Field of the Invention
The present invention relates to a toner cartridge for use in a developing device and the developing device for an image forming apparatus for performing an image formation by an electrophotography process using toner that is supplied through a toner supply port from a toner cartridge by rotation of an agitator attached to a rotating shaft provided in the toner cartridge. In particular, the invention relates to a developing device for an image forming apparatus capable of preventing leakage of toner from a toner cartridge.
2. Description of Related Art
Heretofore, there have been proposed various types of developing devices for an image forming apparatus, e.g., a laser printer and the like. Many of the developing devices are constituted as a unit capable of being detachably mounted on a laser printer and also are provided with an exchangeable toner cartridge serving as a toner storing portion.
An embodied example of such the developing device is described referring to FIG. 17. FIG. 17 is an explanatory view of schematically showing a main part of the conventional developing device.
In FIG. 17, the developing device has a toner cartridge 100 which accommodates therein toner. The toner cartridge 100 is provided with a toner exhaust port 101 and an agitator 103 for agitating toner. In a frame F of a process unit supporting the toner cartridge 100, a toner introduction port F0 is formed corresponding to the toner exhaust port 101 of the toner cartridge 100. The frame F includes an upper frame F1 and a lower frame F2 which form a closed developing chamber 102. In the developing chamber 102, a toner supply roller 104 is rotatably disposed and a developing roller 105 is arranged adjacent to the supply roller 104. Thus, toner is supplied due to rotation of the agitator 103 from the atoner cartridge 100 through the toner exhaust port 101 and the toner introduction port F0 into the developing chamber 102. Rotation of the toner supply roller 104 then causes supply of the toner onto the developing roller 105.
A blade 107 is secured on an inner wall of the upper frame F1, above the developing roller 105, by a fixing member 106. This blade 107 serves to regulate the thickness of a toner layer formed on a circumferential outer surface of the developing roller 105. The developing roller 105 is disposed so as to be in contact with a photosensitive drum 108. An electrostatic latent image can be formed on a circumferential outer surface of the photosensitive drum 108 by a light exposure unit (not shown) which scans the surface of the drum 108 with laser light in accordance with image data. The developing roller 105 then performs toner development by supplying toner on the electrostatic latent image formed on the surface of the photosensitive drum 108. The developed image is transferred onto a paper sheet fed from a paper supply unit (not shown) to form the visual image thereon.
In the toner cartridge 100 of the conventional developing device, rotation of the agitator 103 in the toner cartridge 100 is caused by the driving power of motors disposed outside the toner cartridge 100. Therefore, a power transmitting member for causing rotation of the agitator is inserted in a port formed in the toner cartridge 100. A sponge member is firmly attached to the power transmitting member so as to be compressed toward the port by a pressing member of the power transmitting member, thereby closing the port.
When a rotation speed of the agitator 103 becomes higher, the sponge member tends to rotate along with the agitator owing to a large frictional power generated between the sponge member and the pressing member of the power transmitting member, which may cause leakage of toner through gaps between the sponge member and the port of the toner cartridge 100 to the outside. The leaked toner may stick to other portions in the image forming apparatus, for example, the outer surface of the toner cartridge 100, which may make operator's hands dirty in an exchanging operation of the toner cartridge 100. The leakage of toner is desired to be perfectly prevented from occurring.
To prevent the rotation of the sponge member, it is conceivable that, for example, a double-sided adhesive tape is provided on the sponge member whereby the sponge member is secured on the inner surface of the toner cartridge 100. At the time of assembling of the agitator 103 in the toner cartridge 100, however, a removing operation to remove releasable paper from the double-sided adhesive tape is troublesome and the adhesive surface of the tape may stick to unwanted portions except a predetermined portion in the toner cartridge 100, causing a long time for assembling them. Additionally, toner leakage may caused if the sponge member is adhered through the double-sided adhesive tape to a position displaced from a predetermined position in the toner cartridge 100.

Developing device for image forming apparatus and toner cartridge for use in the developing device


The lactic acidCH.sub.3 CH(OH)CO.sub.2 H! addition salt of the compound of formula I ##STR1## wherein the molar ratio of lactic acid, preferably L-lactic acid, to the compound of formula I is preferably about 1:1, pharmaceutical compositions of the lactic acid addition salt in an aqueous lactic acid carrier suitable for intravenous administration, and methods of using either of them to treat and/or prevent susceptible fungal infections in a host such as a mammal are disclosed.

This invention relates to a water soluble lactic acid addition salt of (-)-(2R)- cis!-4-4-4-4--5-(2,4-difluorophenyl)-tetrahydro-5-(1 H-1 ,2,4-triazol-1 -ylmethyl)-3-furanyl!methoxy!phenyl!-1 -piperazinyl!phenyl!-2,4-dihydro-2-1 (S)-ethyl-2(S)-hydroxpropyl!-3H-1,2,4-triazol-3-one, pharmaceutical compositions containing the lactic acid addition salt in pharmaceutically acceptable carrier such as aqueous lactic acid as well as methods of treating and/or preventing susceptible fungal infections in a host including mammals especially humans with said lactic acid addition salt.
Systemic fungal infections are becoming a serious and potentially fatal problem in immunocompromised patients. Such patients have a compromised or suppressed immune system due to immunosuppression therapy following organ transplant, use of cytotoxic drugs for treatment of cancer or HIV infections. Injectable antifungal agents such as Amphotericin B are active against a wide variety of fungi but exhibit significant toxic side effects. The azole antifungals fluconazole, itraconazole and ketoconazole can be administered orally or via injection but have more limited antifungal activity th an Amphotericin B. In addition, prolonged exposure to antifungals agents has resulted in increased fungal resistance to some of these agents.
Thus, there is a need for a broad spectrum antifungal agent having activity against fungi such as Aspergillus and Candida krusei resistant to existing anti- fungal agents and which is capable of being administered intravenously.
International Publication No. PCT/EP/00174, published 27 Jul. 1995 discloses azole tetrahydrofuran and dioxolane antifungals, but not the lactic acid addition salt of this invention.
International Publication No. WO 95/17407 published 29 Jun. 1995 discloses various (2 R-cis)-4-4-4-4--5-(2,4-difluorophenyl)-tetrahydro-5-(1 H-1,2,4-triazol-1 -ylmethyl)-3-furanyl!methoxy!phenyl!-1 -piperazinyl!phenyl!2,4-dihydro-2-mono- or dihydroxy(C.sub.3 -C.sub.8) alkyl!-3 H-1,2,4-triazol-3-one substituted antifungals, esters, ethers and salts thereof. The hydrochloride salt of the glycine ester of (-)-(2 R)-cis!-4-4-4-4--5-(2,4-difluorophenyl)-tetrahydro-5-(1 H-1,2,4-triazol-1 -ylmethyl)-3-furanyl!methoxy!phenyl!-1 -piperazinyl!phenyl!-2,4-dihydro-2-1 (S)-ethyl-2(S)-hydroxypropyl!-3 H-1,2,4-triazol-3-one is disclosed in U.S. Pat. No. 5,714,490. There is no disclosure in the above-listed patent or patent applications of the specific monolactic acid addition salt or the specific pharmaceutical compositions of the present invention.