The present invention features colony-forming unit cells derived from the chorion of human placenta and describes compositions and methods for the uses of chorionic cells and their products for therapeutic purposes based upon production and release of multiple growth factors and cytokines by these cells stimulating tissue regeneration independent of engraftment, as well as differentiation into a specific cell type.

Derivation, characterization and therapeutic use of stem cells is among the most rapidly-developing fields of modern biology and medicine. Ability of stem cells differentiate into many lineages, as well as significantly influence processes of tissue regeneration paves the way for wide use of stem cell-based therapies in many medical applications. Multiple types of stem cells, embryonic and adult, are currently investigated. Though embryonic and induced pluripotent stem cells may be differentiated into any other cell types, their ability to form teratomas currently precludes their use in medical practice. Adult stem cells are currently used in humans, though only hematopoietic stem cells have been proven to provide therapeutic effect. One of the main problems is the difficulty in obtaining sufficient amount of stem cells, maintaining their "stemness" potential while in culture. Therefore, supply of stem cells is very limited, and novel sources are in high demand.
Human embryonic stem cells are derived from the pre-implantation or peri-implantation embryo and are characterized by the following major features: prolonged undifferentiated proliferation and stable developmental potential to form all the three of germ layers even after prolonged culture. Prolonged undifferentiated proliferation of human ECS is achieved by growing these cells on mouse embryonic fibroblast feeder layers in special ECS medium. Other specific features of human ESC, including: 1) high levels of telomerase activity; 2) formation of embryonic bodies; 3) expression of specific cellular markers Oct-4, Nanog, Sox-2 and surface markers CD117, SSEA-3, SSEA-4, TRA-1-60, TRA-1-81 and alkaline phosphatase activity; and 4) formation of teratomas in immuno-compromised animals, are used to confirm derivation of pluripotent stem cell lines, similar to ECS.
Mesenchymal stem cells (MSC) are derived from adult body. Currently the most widely used and well characterized source of MSC is bone marrow. The basic features of adult mesenchymal stem cells (MSC) are: 1) proliferation potential; 2) the ability to differentiate; 3) plasticity; and 4) the ability to adhere to plastic, promoting the basic procedure for the MSC isolation, storage and usage. The MSC are characterized by expression of many common molecules required for adherence to solid surface and cell to cell interactions (Dominici et al., 2005). MSC possess a rich differential potential allowing them to differentiate into almost all possible mesenchymal lineages except hematopoietic cells. Several technical difficulties exist in practical approaches for obtaining stem cell populations from different organs of adult tissue due to very low occurrence of stem cells (fractions of a percent) and clear ethical problems associated with embryos or fetuses. Harvesting stem cells from adult sources such as bone marrow is labor-intensive and expensive. Harvesting stem cells from an adult donor, which is a current practice for obtaining hematopoietic cells and stromal cells of bone marrow possesses certain threats to donor, is expensive, labor-intensive and effective transplantation requires immunological match between donor and recipient.
Placenta, as a discarded material after birth, represents a unique opportunity for harvest of autologous or allogeneic populations of stem cells. Stem cells derived from feto-placental complex have been previously described. Stem cells of amniotic fluid have been described in many studies (Alviano et al, 2007; in't Anker et al, 2004). Stem cells isolated from human-term amniotic fluid may be cultured over 50 population doublings (in'tAnker et al, 2004). Phenotype of these cells was close to phenotype of MSC from bone marrow by expression of CD90, CD105, CD166, CD49, SH3, SH4 and negative for CD31, CD34, CD45, HLA-DR. However, at third trimester of pregnancy the viability of these cells decreases substantially and only in 20% it was possible to obtain viable stem cells from amniotic fluid. Embryonic-like stem cells in amniotic fluid are identified by expression of Oct-4, stem cell factor (SCF), high telomerase activity. Report by DeCoppi et al (2007) describes stem cell lines isolated from amniotic fluid following enrichment of c-kit positive cells. These cells expand without feeders up to 250 population doublings, are not tumorigenic, and can be differentiated into cell types representing cells of all the germ layers.
Yet another source of MSC is human placenta itself (Fukuchi Y et al, 2004; Matikainen T, Laine J. 2005). Previous studies (Linjuy Yen et al, 2005) demonstrated that multipotent, multilineage cells were present in the human term placenta. Although the initial cell culture consisted of both fibroblastoid and non-fibroblastoid cell types, only the fibroblastoid population remained after enzymatic digestion and passaging. MSC markers such as CD105/endoglin/SH-2 and SH-3, SH-4, integrins and matrix receptors displayed by placental stem cells, suggesting that these cells resemble MSC from the bone marrow. This is further supported by their fibroblastoid morphology, plastic-adherence nature, and mesodermal differentiation capabilities. In addition to MSC markers, cell surface markers SSEA-4, TRA-1-60, and TRA-1-81 were present on placenta-derived cells, which were previously found only in embryonic stem and germ cells.
First International Workshop on placenta-derived stem cells (Parolini et al, 2007) suggested the following nomenclature for cells derived from fetal placenta: Amniotic Epithelial Cells (hAEC), Amniotic mesenchymal Stromal cells (hAMSC), Chorionic Mesenchymal Stromal Cells (hCMSC), and Chorionic Trophoblastic Cells (hCTC) and suggested that cells isolated from fetal membranes should be termed mesenchymal stromal cells. Minimal criteria for defining these cells were adherence to plastic, formation of colonies, specific pattern of surface antigen expression and differentiation potential. hAEC were extensively studied by the group of S. Strom, (Miki et al, 2005, 2007). Cells obtained from amniotic membrane are phenotypically heterogeneous, could proliferate up to 5-10 passages and express very low levels of HLA-A,B,C. These cells express markers of pluripotent cells such as SSEA-3 and -4, TRA-1-60 and TRA-1-81, Oct-4, SOX-2 and Nanog. Such hAMC are capable to differentiate into the cells of all three germ layers (Tamagawa et al, 2004, Ilancheran et al, 2007). According to reports (Chien et al, 2006; Miki et al 2005; Sakuragawa et al, 2000), hAMC can be differentiated into hepatic-like cells. Differentiation of hAEC into neuronal-like (Sukuragawa, 2004) was reported. Functional genomic studies by Ming-Song Tsaia et al (2007) revealed that core gene expression profiles were preserved in those four kinds of MSC from amniotic fluid, amniotic membrane, cord blood and bone marrow. The core signature transcriptomes of all MSCs, in comparison with those of fetal organs, included genes involved in the regulation of extracellular matrix and adhesion, transforming growth factor-β receptor signaling, and the Wnt signaling pathways.
Mesenchymal stem cells of placenta: hAMSC and hCMSC are likely to originate from extraembryonic mesoderm. hAMSC were characterized in several publications (Surakagawa et al, 2004; int'Anker et al, 2004; Portmann-Lanz et al, 2006; Wolbank et al, 2007), though descriptions of hCMSC are very limited (Zhang et al, 2006). Profile of surface marker expression on hAMSC and hCMSc is close to bone marrow-derived MSC as both are positive for CD90 and CD105, but do not express markers of hematopoietic of leukocyte markers (Portmann-Lanz et al, 2006; Alviano et al, 2007; Zhao et al, 2005). Differentiation of hAMSC and hCMSC was demonstrated towards mesodermal lineages, while hAMSC could be induced to differentiate into neural (ectoderm) and pancreatic cells (endoderm) (Parolini et al, 2007). However, as hAMSC and hCMSC described in the above cited publications were derived by plastic-adherence techniques, they represent mixed populations and clones of multiple different stem and progenitor cells. Since these cells are not clonally-derived, their pluri- or multipotency remains unproven. Qualitative evidence of engraftment of chorionic and amniotic cells in newborn rat and swine was detected only by RT-PCR, without morphological evidence of engraftment and/or differentiation in tissues (Bailo et al, 2004).
Thus, though amniotic epithelial and amniotic mesenchymal stem cells have been studied in several reports over the past decade, information on chorionic mesenchymal and/or other stem cells has been not presented yet. Clonal-derived stem cell lines have not been described. Cell lines so far isolated from mesenchyme of placenta, have been characterized by limited capability of proliferation (only 5-10 passages). Mesenchymal cells from chorion have not been characterized by their ability to differentiate into cells of all three germ layers, nor have they been reported for their ability to engraft tissues of animals, differentiate in tissues, or form tumors. Further, placental tissue has not been yet reported for the presence of primitive pluripotent cells, different from mesenchymal stomal plastic-adherent cells.
The subject matter of this invention are novel stem cell populations originating from chorion of human placenta, termed chorionic colony-forming unit cells (CCFUC) which are uniquely characterized by expression of novel acetyl-coenzyme A binding protein (ACBD6) described in placental chorionic stromal stem cells by us (Soupene et al, 2008) and references therein.
Human mesenchymal stem cells of different origin have been a subject of multiple patents. Most of patents describe cells, capable of differentiation in connective tissue type, obtained from bone marrow, adhere to plastic, positive for surface markers SH2, SH3, SH4 (Caplan, U.S. Pat. No. 5,486,359 "Human mesenchymal stem cells"). Methods of directed differentiation of such stem cells ex vivo are further described (Bruder et al., U.S. Pat. No. 5,942,225 "Lineage-directed induction of human mesenchymal stem cell differentiation"). Methods and systems are described for selective expansion of target cell populations, and methods of treating patients with cell populations and products (Krauss et al., U.S. Pat. No. 6,338,942 "Selective expansion of target cell populations"), as well as methods of using non-autologous mesenchymal stem cells comprising treating a recipient (Bruder et al., U.S. Pat. No. 7,029,666 "Uses for non-autologous mesenchymal stem cells"). Simmons et al., describes mesenchymal precursor cells based upon expression of STRO-1 (U.S. Pat. No. 7,399,632 "Mesenchymal precursor cell").
Placenta and its parts as a source of stem cells and physiologically active substances has been a subject of patents. Sanders (U.S. Pat. No. 3,862,002 "production of physiologically active placental substances") teaches a system, in which viable placental tissue is placed in circulating culture medium and processed culture medium is then removed from tissue and desired substances are withdrawn. Limitations of this technique are based upon the fact that such method does not teach isolation of stem cell population. Also, such technique provides very low yield of cells as cells remain attached to tissue matrix.
Tseng (U.S. Pat. No. 6,326,019 "Grafts made from amniotic membrane") teaches a method for making surgical grafts from amniotic membrane. As amnion represents only a very small fraction of placental tissue—less than 5%, yield of viable colony-forming unit cells from this specific source is very low. Low yield of primary cells requires multiple steps of cell passaging in order to obtain amount of cells required for therapeutic use in humans (about 100 million cells). Multiple passages in turn significantly increase the risk of chromosomal aberrations in cultured cells, making it highly risky for therapeutic use. Amniotic epithelial cells form teratomas and, therefore, can not be readily used in humans.
Cells isolated from umbilical cord—anatomical structure which connects a baby with placenta—have been described in several patents. Messina et al., (U.S. Pat. No. 7,524,489 "Regeneration and repair of neuronal tissue using postpartum-derived cells"), teaches method of treatment patients with cells derived from umbilical cord which do not express CD117 while expressing oxidized LDL receptort interleukin 8 or reticulon 1. Mistry et al., (U.S. Pat. No. 7,510,873 "Postpartum cells isolated from umbilical cord tissue, and methods of making and using the same") teaches method of isolation of a cell from umbilical cord by enzymatic digestion that does not express CD117, CD31, CD34, CD141 or CD45 and express CD10, CD13, CD44, CD73, CD90, PDGFr-alpha or HLA-A, and further teaches use of these cells for treatment of retinitis (Mistry et al., U.S. Pat. No. 7,413,734 "Treatment of retinitis pigmentosa with human umbilical cord cells"). Harmon et al. (U.S. Pat. No. 7,560,276 "Soft tissue repair and regeneration, using postpartum-derived cells") teaches use of these cells from umbilical cord and their products for soft tissue repair. Davies et al., U.S. Pat. No. 7,547,546 "Progenitor cells from Wharton's jelly of human umbilical cord" teaches obtaining cells from umbilical cord and their use in tissue repair. Use of proteolytic enzymes required for all the above described methods, first, dramatically reduces cell viability and yield of colony-forming unit cells, and, second, eliminates expression of many stem cell markers on cell surface, thus not allowing using sorting techniques for isolation of stem cells. The above described methods to obtain cells from umbilical cord feature same problems as obtaining stem cells from other low volume sources—yield of viable colony-forming unit cells from this source is very low. Low yield of primary cells requires multiple steps of cell passaging in order to obtain amount of cells required for therapeutic use in humans, while passaging increases the risk of chromosomal aberrations and tumor formation. Such risk of tumor formation from human fetal cells is more than real, and clinical cases of brain tumor development in patient from transplanted cells following administration of fetal cells were reported. It is, therefore, a subject matter of this invention to disclose novel techniques, methods and stem cell populations which could be obtained from the largest (95% of tissue mass of placenta) portion of placenta which allows to obtain very large yield of primary cells (several billion primary stem cells) without the use of proteolytic enzymes. Chen et al., (U.S. Pat. No. 7,534,606 "Placental stem cells and methods thereof") claims a method of neurogenic differentiation of human placental stem cells, comprising culturing of placental stem cells in medium comprising an effective amount of 1-methyl-3-isobytylxantine.
Hariri (U.S. Pat. No. 7,045,148) reports that the first collection of blood from the perfused placenta, referred to as cord blood, contains populations of hematopoietic progenitor cells which are CD34 positive and CD38 positive or CD34 positive and CD38 negative or CD34 negative and CD38 positive. Subsequent perfusions of the placenta were reported to yield embryonic-like stem cells that are SSEA-3 negative, SSEA-4 negative, Oct-4 positive, ABC-p positive, CD10 positive, CD38 negative, CD29 positive, CD34 negative, CD44 positive, CD45 negative, CD54 positive, CD90 positive, SH2 positive, SH3 positive and SH4 positive. Hariri (U.S. Pat. No. 7,311,905 "Embryonic-like stem cells derived from post-partum mammalian placenta, and uses and methods of treatment using said cells") describes a composition of human stem or progenitor cells that are positive for SH2, SH3, SH4 and Oct-4, while negative for CD34, CD45, SSEA3 and SSEA4, and obtained from placenta that has been drained from cord blood. Cells could express at least one of the following markers: CD10, CD29, CD44, CD54, CD90. Hariri (U.S. Pat. No. 7,468,276 "Placental stem cells") describes the same placental stem cell population, adherent to plastic. Hariri (U.S. Pat. No. 7,255,879 "Post partum mammalian placenta, its use and placental stem cell populations") teaches method to obtain the above described placental stem cell population by perfusing placenta via circulation with a perfusion solution containing an anticoagulant, growth factor or cytokine selected from a group consisting of a colony stimulating factor, interferon, erythropoietin, stem cell factor, thrombopoietin, an interleukin, granulocyte colony-stimulating factor, and any combination thereof, and collection of cells from perfusate. Methods of directed differentiation of these cells are described by Hariri (U.S. Pat. No. 7,498,171 "Modulation of stem and progenitor cell differentiation, assays and uses thereof"). The main disadvantage of methods described by Hariri in the above cited patents is in the fact that long-term perfusion of placenta is required to obtained claimed cells. It is know to those skilled in arts that in most cases of placentas obtained by Caesarian section and in all cases of placentas collected following natural birth, placentas are ruptured. This precludes the possibility of the long-term perfusion, as perfusate is rapidly lost via ruptures of chorion; therefore, long-term perfusion becomes unworkable. In most cases, arteries of umbilical cord rapidly completely constrict, and as thrombosis develops in placental vessels perfusion of placenta by techniques claimed by Haririr's patents (U.S. Pat. No. 7,045,148; U.S. Pat. No. 7,255,879; U.S. Pat. No. 7,311,905; U.S. Pat. No. 7,468,276) becomes practically impossible. Most importantly, perfusion of placenta via natural circulation does not allow collecting populations of stem cells which are located in stroma, interstitial tissue or non-perfused regions of placental circulation. Therefore, placental perfusion and cells claimed by Hariri's patents (U.S. Pat. No. 7,045,148; U.S. Pat. No. 7,311,905; U.S. Pat. No. 7,468,276; U.S. Pat. No. 7,498,171) allow obtaining very restricted and limited cell populations present in placenta, which belong to pool located inside the circulatory space. It is, therefore, a subject matter of this invention to disclose novel techniques, methods and stem cell populations which could be obtained without placental perfusion and collection of perfusate, as well as without the use of proteolytic enzymes. Placental stem cell populations and compositions of placental stem cells described by Hariri (U.S. Pat. No. 7,045,148; U.S. Pat. No. 7,311,905; U.S. Pat. No. 7,468,276) are characterized only by expression of several classical surface antigens (CD34, CD45, SSEA, SH-2, SH3, SH4, CD38, CD10, CD29, CD44, CD54, CD90). Moreover, Hariri wrongfully claims that cells described in these patents bear Oct-4 as surface marker (for example U.S. Pat. No. 7,311,905, claim 15), while Oct-4 is cytosolic/nuclear protein which is not expressed on surface of any cell, including embryonic stem cells. Placental cells claimed by Hariri (U.S. Pat. No. 7,045,148; U.S. Pat. No. 7,311,905; U.S. Pat. No. 7,468,276) are not characterized by their ability to form colonies, produce clones, differentiate into lineages of any of germ layers, form or not form teratomas, engraft immuno-compromised animals of humans, therefore differentiation potential and "sternness" of claimed cells is unknown. It is, therefore, a subject matter of this invention to disclose novel techniques, methods and stem cell populations from placenta which demonstrate specific phenotype and ability to form clones, differentiate into lineages of all 3 germ layers and engraft immunocompromized animals without formation of teratomas.
Naugtington et al. (U.S. Pat. No. 5,962,325) claims a method of making a composition comprising culturing fibroblast cells in 3-dimensional conditions. Naugtington et al. (U.S. Pat. No. 7,118,746 "Conditioned cell culture medium compositions and methods of use") claims methods to obtain and use conditioned medium obtained from culture of human mesenchymal cells. The drawbacks of claimed methods is its limitations to secreted factors produced by mesenchymal cells, while stem cells produce different compositions of secreted factors which are more potent in tissue regeneration. Uchida (Uchida et al., 2000) described neurotrophic function of conditioned medium from human amniotic cells.

Colony-forming unit cell of human chorion and method to obtain and use thereof


An overlay optimizer can enhance the functionality of a write filter using an auxiliary overlay. An overlay optimizer can be loaded above a write filter. Based on the configuration of the write filter's overlay, the overlay optimizer can be configured to implement a volatile or persistent auxiliary overlay and then use the auxiliary overlay to selectively cache artifacts. To minimize the likelihood that the consumption of the write filter's overlay will exceed a critical threshold, the overly optimizer can be provided a list of monitored artifacts. The overlay optimizer can employ the list to selectively move monitored artifacts from the write filter's overlay to the auxiliary overlay when the overlay's consumption reaches a threshold. The overlay optimizer may also selectively allow I/O requests generated by particular applications while redirecting I/O requests generated by other applications.

Operating systems, such as Windows, provide functionality for preventing the content of a storage medium from being changed. In a typical example, it may be desirable to prevent the operating system image, which may be stored on a particular disk partition or on flash media, from being changed at runtime. For example, Windows 10 provides the Unified Write Filter (UWF) which can be used to redirect all writes that target the operating system image to a RAM or disk cache called an overlay. This overlay stores changes made to the operating system at runtime but is removed when the user device is restarted thereby restoring the user device to its original state.
FIG. 1A illustrates how a write filter 110a can be employed to prevent the contents of a protected volume on disk 100 from being modified. Disk 100 is intended to generally represent any type of physical storage medium (or volume). In accordance with the Windows architecture, a driver stack consisting of file system driver 111, volume manager 112, and disk driver 113 sit atop disk 100, and I/O manager 120 manages the flow of I/O requests through the driver stack. An application can employ file/directory management APIs 160 to invoke a service of system services 130 (e.g., by calling ReadFile, WriteFile, CreateFile, etc. on a particular file) which will result in I/O manager 120 creating an IRP for the request. This IRP will then be passed down through the driver stack.
As depicted in FIG. 1, write filter 110a is positioned at the top of the driver stack and will therefore be able to process an IRP prior to the IRP being passed down to the lower level drivers. Write filter 110a can be configured to detect writes targeting a protected volume and redirect (or reparse) them to overlay 140 rather than allowing them to be passed down the driver stack unchanged. Accordingly, the driver stack can be referred to as a protected volume stack.
As represented by the dashed line, when write filter 110a detects a write to the protected volume, it will cause the content to be written in overlay 140 rather than to disk 100. Write filter 110a can be further configured to detect reads that target content that was previously redirected to overlay 140 and redirect these reads to overlay 140. In this way, even though it will appear to the application that the content of disk 100 is being updated, the updates are actually being temporarily maintained in overlay 140. The contents of overlay 140 can be maintained until the operating system is restarted or until an explicit command is received to discard the contents of the overlay.
Write filter 110a is an example of a file-system filter driver (e.g., uwf.sys). However, in Windows implementations, the write filter will also include a registry filter driver (e.g., uwfreg.sys) so that the write filter can also prevent the content of the registry from being modified. FIG. 1B represents this architecture. As shown, write filter 110b is registered with configuration manager 120a as a registry filter driver. Therefore, when applications use registry management APIs 160a to perform registry operations, configuration manager 120a will pass the registry operations to write filter 110b to allow it to handle the registry operations before they are completed. As with write filter 110a, write filter 110b can redirect registry operations to overlay 140 to prevent the content (or in the case, the registry hives 101) on the protected volume from being modified. Given that write filter 110a and write filter 110b function in the same general manner, in the remainder of the specification, a general reference to write filter 110 will be used and may be construed as encompassing only write filter 110a in some embodiments (e.g., when write filter 110 is used on user devices running non-Windows operating systems) and both write filter 110a and 110b in other embodiments (e.g., when write filter 110 is used on user devices running Windows operating systems).
As mentioned above, write filter 110 can be configured so that the contents of overlay 140 are discarded at reboot. In other words, overlay 140 may be a volatile overlay. However, in some cases, if may be desirable to maintain the content of overlay 140 across reboots—i.e., to make overlay 140 persistent. For this reason, certain versions of write filter 110 (e.g., the UWF available for Windows 10 RS4) enable an administrator to configure overlay 140 to be either volatile or persistent.
Various issues exist when overlay 140 is volatile as well as when it is persistent. For example, in both cases, the consumption of overlay 140 may reach a critical threshold (e.g., 90%) at which point write filter 110 will block further writes to overlay 140 (i.e., writes that would cause consumption to exceed the critical threshold) and will typically force a reboot. If overlay 140 is volatile, the content of overlay 140 will be discarded including any critical files that may be stored therein such as updates to the operating system, antivirus updates, system configurations, etc.
In contrast, if overlay 140 is persistent, the content of overlay 140 will not be discarded and, as a result, after reboot the consumption of overlay 140 will quickly or immediately exceed the critical threshold. This may cause indefinite reboots. In this scenario, an administrator will need to manually discard overlay 140 by disabling write filter 110 and resetting the cache. However, given that the persistent overlay is already "full," even after a reboot, another reboot may be initiated before the administrator even has the opportunity to disable write filter 110. For this reason, when employing a persistent overlay, the administrator must typically identify files/folders that are consuming a large portion of overlay 140 and exclude them from write filter protection so that during a subsequent reboot, the administrator will have sufficient time to disable the write filter. However, even in this scenario, the disabling of write filter 110, along with the resulting discarding of overlay 140, defeats the purpose of employing a persistent overlay. In particular, a persistent overlay is typically intended to preserve updates to certain files, but these updates will still be discarded as if a volatile overlay had been used.
Versions of write filter 110 provide a feature called Hibernate Once, Resume Many (HORM). When this feature is enabled, a hibernation file (e.g., hiberfil.sys) is created to define a preconfigured state for the system and then this hibernation file is used at each subsequent reboot to resume the system in the preconfigured state.
To employ the HORM feature, write filter 110 must be configured with various limitations. For example, write filter 110 must protect all volumes that are mounted on the system. Because of this limitation, the HORM feature is not available on Unified Extensible Firmware Interface (UEFI) user devices unless they are running the latest version of the Windows operating system since prior versions of Windows employed an installation procedure for UEFI that created a hidden system partition (i.e., a volume that UWF could not protect). This limitation also prevents HORM from being used on systems that need to exclude a volume from write filter 110's protection (e.g., systems that employ an overlay optimizer to enhance the functionality of write filter 110).
Additionally, when the HORM feature is used, there must not be any file, folder or registry exclusions configured with write filter 110. However, to properly function, some applications, such as antivirus software, management agents, setup services, browsers, etc., need to register exclusions so that their writes will be maintained across reboots. Therefore, when the HORM feature is enabled, such applications cannot be used, or at a minimum, the performance of such applications will suffer.
The inability to register exclusions also causes the consumption of overlay 140 to reach the critical threshold more quickly. In particular, when files, folders, registry entries, etc. are excluded, writes to these excluded artifacts will be directed to disk rather than to overlay 140 and will therefore not consume overlay 140. Enabling the HORM feature forces these writes to be made to overlay 140 which may lead to the indefinite reboot problem described above.

Enhancing write filter features using an auxiliary overlay


Apparatus for sealing bearing assemblies includes a first bearing with a first inner race, a second bearing with a second inner race, a shaft, the first and second inner races being juxtaposed on the shaft with their inner surfaces facing the shaft, thus forming a gap between opposing edges of the races, the opposing edges of the first and second inner races are beveled to form a deformation. The apparatus has an annular ring including a positioning member having an inwardly projecting edge for axially positioning the annular ring on the first and second inner races, and a seal for sealing the annular ring against the first and second inner races. The inwardly projecting edge of the positioning member engages the beveled opposing edges of the first and second inner races so that oil supplied between the shaft and the inner surfaces of the races is prevented from flowing through the gap.

In connection with motor vehicles, different types of bearings may be utilized for supporting the wheels on their respective wheel axles. Where, for instance, heavier commercial vehicles are concerned, the rear wheels may be carried on bearings on the rear axle of the vehicle by means of two roller bearings mounted next to each other. According to the prior art, these roller bearings are typically arranged side by side so that they bear on each other. The roller bearings are kept together in an unmounted condition by means of a bearing ring, which is substantially annular, and which is mounted on the rear axle.
Within the internal surfaces of the inner races of the bearings, i.e. on the surfaces which constitute the inside of the inner races and the outside of the rear axle itself, a thin layer of oil must be supplied for the purpose of protecting the bearings and the rear axle from corrosion. This oil is successively supplied through the interior of the rear axle and is conducted in between the peripheral surface of the rear axle and the inner side of each respective roller bearing.
Furthermore, according to the prior art, the roller bearings themselves are lubricated by bearing grease. This bearing grease is applied when assembling the roller bearings and is retained on the bearing rollers and bearing races by means of seals.
A problem which occurs in connection with these previously known rear axle assemblies is related to the fact that a small gap or interval is formed between the inner races of the two roller bearings. This, in turn, creates the risk that the oil layer between the insides of the roller bearings and the rear axle can penetrate through this gap during operation of the vehicle. This may occur as a result of the small movements which always arise in the rear axle during operation of the vehicle, in which case the gap between the inner races cannot be kept completely sealed.
The fact that oil leaks out in a radial direction through the gap between the two bearings entails certain disadvantages. On the one hand, the oil is harmful to the bearing grease of the roller bearings. On the other hand, the oil may contain impurities in the form of small particles which may be deposited on the bearings, something which naturally is a disadvantage. A further disadvantage with such leakage is that the surf ace of the rear axle and the internal surfaces of the inner races risk running dry, which in turn creates a risk of contact corrosion between the bearings and the rear axle. This means, for instance, that wheel changes are rendered considerably more difficult.
In light of the above-mentioned problems, there is a need for seals, which can seal the gap between the inner races. However, this presents further difficulties, among other things resulting from the fact that the area around the gap becomes inaccessible once the bearings have been pressed into position. This results in difficulties when mounting the bearings and seals for such bearings.

Sealing device for bearing arrangements and arrangement for sealing of a bearing device


Disclosed is an oven which provides convenient removal of a rack, achieving enhanced usability. The oven includes a cabinet having a chamber, a door to open or close the cabinet, a rack assembly including an operating member to support a cooking object seated thereon, the operating member being removable from the chamber, and a support member fixed inside the chamber to support the operating member, and a spring device including a first fixing piece located at the operating member, a second fixing piece located at the support member, and an elastic member having one side connected to the first fixing piece and the other side connected to the second fixing piece and located in a vertical gap between the operating member and the support member so as to be elastically restored by a distance between the first and second fixing pieces to remove the operating member from the chamber.

Field of the Invention
The present invention relates to ovens and, more particularly, to ovens that may allow a user to conveniently remove a rack on which an object to be cooked is seated, thereby achieving enhanced usability.
Discussion of the Related Art
Ovens may be referred to as home appliances that cook an object by applying heat thereto. Such an oven generally includes a cabinet defining an external appearance of the oven and a chamber defined in the cabinet to receive an object to be cooked (hereinafter referred to as cooking object).
The interior space of the chamber may be heated to an extremely high temperature. The cooking object within the chamber is cooked using the high temperature. There are a variety of ovens including ovens that use fossil fuel, ovens that use electricity, ovens that use steam, and the like. Of course, these heat sources may be used in combination.
The cabinet may be provided with a rotatable door. The door serves to open or close the chamber. More specifically, the door closes the chamber to isolate the interior space of the chamber from the outside during cooking and then, upon completion of cooking, opens the chamber to communicate the interior space of the chamber with the outside.
In many cases, a rack on which the cooking object is seated may be placed within the chamber. The rack may function to assist the cooking object in being positioned in the interior space of the chamber such that high temperature atmosphere within the chamber is transferred to the cooking object. That is, the rack may function to cause the cooking object to be indirectly cooked via the high temperature atmosphere without direct contact between the cooking object and the heat source.
To cook the cooking object, a user will first open the door and seat the cooking object on the rack placed within the chamber. In this case, the user must extend their hand deep into the chamber. Since the cooking object is generally placed on the rack after the interior of the chamber is preheated to a high temperature, the user has to wear oven mitts when placing the cooking object. Of course, removing the cooking object immediately after completion of cooking or removing the cooking object during cooking to check progress of cooking may inconvenience the user. That is, the user may suffer from great inconvenience when placing or removing the cooking object in or from the high temperature chamber. In particular, a process of placing or removing a heavy cooking object in or from the chamber by hand may be troublesome to the user and cause strain to the user's body. These problems may be further worsened when the rack is fixed in the chamber so as not to be removed outward.
To solve the aforementioned problems, as exemplarily shown in FIGS. 1 and 2, there are provided ovens in which a rack may be removed out of a chamber.
Referring to FIG. 1, the oven, designated by reference numeral 10, includes a cabinet 20, a chamber 25 defined in the cabinet 20 to receive a cooking object, and a door 30 pivotally rotatably connected to the cabinet 20. When a user, designated by reference character "a", grips a handle 40 of the door 30 and opens the door 30, the chamber 25 may communicate with the outside. The door 30 is generally a pull-down type door that is opened as the user grips the handle 40 installed near an upper end of the door 30 and pivotally rotates the door 30 downward.
FIG. 2 shows the interior of the chamber 25 in a completely opened state of the door 20 provided in the oven 10 shown in FIG. 1. Generally, the door 20 may be rotated 90 degrees to be opened.
As exemplarily shown in FIG. 2, a rack 50 is slidably supported by rack supporters 60.
The rack 50 is a component on which a cooking object c is seated. Cooking may be performed after the cooking object c is seated on the rack 50. Of course, the cooking object c may be seated on the rack 50 while being placed on or received in a cooking utensil b.
FIG. 2 shows a configuration in which the rack 50 may be removed from the chamber 25 as the user pulls the rack 25 and the rack 50 may be introduced into the chamber 25 as the user pushes the rack 25. However, in the case of the oven having the above-described configuration, the user has to directly grip and operate the rack 50. In addition, this operation must be continued until the rack 50 is completely removed or introduced by a predetermined distance. Therefore, the rack 50 is inconvenient to use and removal and introduction of the rack 50 may not be smoothly performed due to friction between the rack 50 and the rack supporters 60. Of course, the slidable rack 50 inevitably causes the user's hand to be exposed to a high temperature environment for a long time, in the same manner as in use of a fixed rack.
Referring to FIG. 2, the cabinet 20 is provided with a chamber opening 26 and a gasket 70 mounted around the chamber opening 26. When the door 30 is closed, an inner surface of the door 30 comes into close contact with the gasket 70, thus allowing the interior of the chamber 25 to be sealed.
FIG. 3 shows an oven having an improved configuration as compared to the oven shown in FIG. 2. More particularly, the oven is configured to achieve smoother removal and introduction of the rack 50 via sliding rails 80.
In this configuration, each sliding rail 80 is interposed between a support bracket 60 fixed inside the chamber 25 and a rack bracket 51 fixed to the rack 50. That is, the rack bracket 51 is movable relative to the support bracket 60 via the sliding rail 80.
However, the sliding rack structure basically causes the same problems as the oven shown in FIG. 1, although it provides smoother removal and introduction of the rack 50. For example, the user may still have to grip and operate the high temperature rack until removal or introduction of the rack is completed.
For this reason, there is a need to provide an oven that may provide easy removal and introduction of a rack and allow a user to operate the rack with minimum motion and time. In addition, there is a need to provide an oven that may minimize the frequency and time of the user's hand being exposed to a high temperature environment and to allow a user to operate a rack from the outside of a chamber.


A trolley for transporting objects hanging from an I-beam normally securely grips or latches to the I-beam via a pair of brake pads that are urged upward against the bottom of the beam by a torsion spring. The torsion spring is released by pulling a lever downward. Applying lateral force to the trolley, preferably by applying a lateral force to the same lever, pulls the trolley along the I-beam as the wheels engaging the upper portion of the I-beam can rotate freely once the brake pads are released. Releasing the lever after the trolling is pulled to the desired location causes the brakes to again firmly grip the I-beam.

The present invention relates to a system and apparatus for transporting objects along an overhead beam or track, and in particular to a transport mechanism having a braking means particular suitable for the transport of punching or kick bags in a gymnasium or Dojo.
Prior methods of using an overhead transport system are well known. Typically, a rolling trolley is suspended from an overhead rail or track. The trolley includes wheel that engage the track and a brake mechanism for locking the wheels or otherwise preventing the movement of the trolley after the objected suspended therefrom has been moved to the desired location on the rail.
Such trolleys have been developed and are used for transporting industrial equipment. Other uses suggested in the literature are for transporting patients and food. It should be appreciated that while there are many ways to configure such a trolley and braking system, the development of this art has only evolved to the point to meet the needs of the particular industry and application. In particular, such a system would be expected to take into account the weight and size of the object being transported, whether machinery is used to power the trolley, the need for automation.
The current invention addresses the recently discovered and unmet need for a trolley and system adopted to the transport kick/punching bags that are used in a gymnasium or dojo.
Such kick/punching bags are suspended from above so that the can swing freely when punched or kicked. Typically, a gymnasium is used for multiple purposes. As such, it would be convenient to be able to store the kick/punching bags when not needed, but have them available with a means for rapid deployment throughout the facility, spacing them apart to safely accommodate a large number of athletes.
Overhead rail transport systems are generally capable of supporting such bags in a clustered arrangement for storage, and generally transporting them to the dispersed location for use. It has been discovered by the inventor that the state of the art such trolley and their brake and release mechanism are not suitable to support kick/punching bags that are used in a gymnasium or dojo.
In particular, there is a need for the rapid deployment and return of the bags, it is desirable that the Athletes themselves can deploy them. However, such deployment must be done safely, taking into account that the age and skill of the athletes can vary considerably, as it is unlikely that they will receive or recall the type of safety training that would be given in industrial or commercial establishments. Given that such bags frequently weight more than an adult and are going to subject to repeated impact from the athletes it is of parameter important that they do not move or slip once they are moved to the desired location.
Accordingly, there is a need for a system for conveying and supporting kick/punching bags that is particularly adapted to disperse then from a clustered arrangement for storage in a gym or Karate dojo to a different arrangement where they are accessible to the athletes.
It is therefore a first object of the present invention to provide such a transport system wherein the kick/punching bags is readily released from a locked position on the rail.
It is a further object of the invention to provide such a system wherein it is relatively easy to transport the bag along the rail.
It is still another object of the invention to provide a system where the bag will not move or come loose once it is moved.


A circuit board assembly is provided, comprising a first circuit board and a ball-grid array jumper. The ball-grid array jumper comprises a second circuit board smaller in size than the first printed circuit board and has at least one layer of conductive traces and at least two solder ball connectors. The ball grid array jumper is mounted to the first printed circuit board via the solder ball connectors.

The invention relates generally to electronic printed circuit boards, and more specifically to high-density jumper connection via a ball grid array.
Electronic components are typically assembled into complex circuits by mounting them on printed circuit boards. These printed circuit boards are usually flat nonconductive boards with one or more layers of a conductive material such as copper fixed on or in the printed circuit board. The layers of copper are etched or otherwise formed to specific shapes and patterns in the manufacturing process, such that the remaining conductive copper traces are routed to connect electrical components to be attached to the printed circuit board.
It is not uncommon for printed circuit boards such as these to have copper layers on both a top and bottom side of the circuit board, but also several layers of copper traces or patterns sandwiched at various depths within the circuit board itself. These traces allow greater flexibility in circuit routing, and usually allow designing a more compact circuit board for a particular circuit than would otherwise be possible. The various layers are sometimes dedicated to particular purposes, such as a ground layer that only serves to distribute ground or signal return connections to various components.
Multiple layers that serve to connect components to other components often must be connected to components attached to a different layer (top or bottom) or the layers must be attached to each other at selected points, requiring use of what are commonly known as vias. These vias typically are essentially small conductive plated-through hole elements oriented perpendicular to the top and bottom surfaces of a circuit board that extend through at least two conductive layers of the circuit board, and that electrically connect circuit traces on at least two of the conductive layers to each other.
But, each layer of a printed circuit board adds a significant amount of cost to the board, making use of as few layers as are practical to achieve the desired performance and configuration economically desirable. For example, it is estimated that for a printed circuit board of standard ATX personal computer motherboard size, the difference in board cost alone between a four-layer printed circuit board and a six-layer circuit board is approximately seven dollars. Unfortunately, the increasingly dense components used in modem electronic systems and the relatively complex power requirements of such systems can make designing a four-layer circuit board virtually impossible. As an example, a modem personal computer has hundreds of connections between the processor, chipset, memory, and attached bus, in addition to the required power distribution that may include 12 v, 5 v, 3.3 v, and other voltages at increasingly high current levels as transistor counts and clock speeds continue to increase.
The dilemma that is then faced by motherboard designers is how to create a densely routed motherboard that is cost-effective and has as few layers as is practical to achieve. What is desired is a way of enabling printed circuit board designers to design circuit boards with as few layers as is practical while enabling the high routing densities that sometimes require a greater number of circuit board layers.


A method, computer program product, and computing system for associating a time indicator with a message. The time indicator may be indicative of an urgency of a particular task associated with the message. The message having the time indicator may be displayed at a computing device. Numerous other variations and embodiments are also included within the scope of the present disclosure.

Today, email and instant messaging are some of the most common forms of communication. These messaging techniques have led to an explosion of messaging in which many people communicate and share content. Messages of particular importance may be marked as such, and identified using a "high importance" identifier.
In a work environment many important messages are received everyday, and although some email messages may be labeled as "high importance" these messages may still be mistakenly overlooked. In some cases, the number of high importance emails received may be overwhelming and may also diminish the relative importance of any one particular email message.
One of the biggest issues concerning email transmission presently is the continuing obstacle of time criticality. As such, emails that may require immediate attention may not be distinguishable from all of the other email messages in a user's inbox.

System and method for distinguishing messages

International Business Machines Corporation


The invention provides a prefabricated volumetric construction module having connection mechanism for securing to other similar modules. A prefabricated volumetric construction module includes a self-supporting structure and pairs of corner castings arranged at least at the corners of the structure. During building construction, the modules are assembled and secured together using connection rods and interlocking plates to provide vertical securement between vertically adjoining modules and horizontal securement between horizontally adjoining modules.

In sharp contrast to rapid development of technology in many other fields, construction technology has proceeded at a relatively slow pace over the last half century. Construction industry remains labour-intensive and of a handcraft nature and, as a result, housing and building costs have remained very high.
Prefabrication has been cited as a potential solution, but many prefabrication proposals to date have not proven to be commercially successful and relatively few prefabrication techniques have been adopted by the industry. Prefabrication techniques fall under two major categories, namely, steel structure module construction and pre-cast volumetric concrete modules.
These prefabrication systems tend to be costly, requiring expensive prefabrication factories and relatively expensive handling and erection equipment and techniques. To be viable such concepts usually require a very high degree of repetition.
One common problem which remains largely unsolved is that the existing prefabricated systems provide only limited architectural and space flexibility.

Connection system and method for prefabricated volumetric construction modules


Embodiments of embedded MEMS sensors and related methods are described herein. Other embodiments and related methods are also disclosed herein.

In the electronics industry, flexible substrates are quickly becoming popular as a base for electronic circuits. Flexible substrates can include a wide variety of materials including, for example, any of a myriad of plastics. Once a desired electronic component, circuit, or circuits are formed over a surface of the flexible substrate, the flexible substrate can be attached to a final product or incorporated into a further structure. As an example, recent developments have fabricated display matrices on flexible substrates.
MEMS (microelectromechanical system) devices have also gained in popularity in the electronics industry. Many types of MEMS devices have been developed for a myriad of applications, including MEMS sensors configured to measure pressure variations. Due to manufacturing constraints, however, the fabrication of MEMS devices has been relegated thus far to standard substrates such as silicon substrates. Integration of MEMS devices with displays and/or other devices fabricated on flexible substrates has thus been constrained.
Shockwave-induced trauma, including closed-head brain trauma, can be difficult to diagnose and treat both in the field where quick decisions are required, as well as in a hospital environment where early decisions can impact the long-term prognosis for recovery and rehabilitation. Field decisions are crucial since appropriate immediate action for treatment can have a large effect on the long-term prognosis. Moreover, knowledge of the type and severity of traumatic brain injury sustained is critically important in developing and prescribing the appropriate longer term rehabilitation strategies. Not to be ignored is the psychological importance of being able to provide realistic expectations to the patient and his or her family and caregivers.
Therefore, a need exists in the art to develop MEMS devices compatible with flexible substrates and methods to integrate the fabrication of such MEMS devices along with other devices on flexible substrates for applications such as the detection and measurement of peak shockwave exposure and/or blast dosimetry for affected personnel.
For simplicity and clarity of illustration, the drawing figures illustrate the general manner of construction, and descriptions and details of well-known features and techniques may be omitted to avoid unnecessarily obscuring the invention. Additionally, elements in the drawing figures are not necessarily drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help improve understanding of embodiments of the present invention. The same reference numerals in different figures denote the same elements.
The terms "first," "second," "third," "fourth," and the like in the description and in the claims, if any, are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances such that the embodiments described herein are, for example, capable of operation in sequences other than those illustrated or otherwise described herein. Furthermore, the terms "include," and "have," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, device, or apparatus that comprises a list of elements is not necessarily limited to those elements, but may include other elements not expressly listed or inherent to such process, method, system, article, device, or apparatus.
The terms "left," "right," "front," "hack," "top," "bottom," "over," "under," and the like in the description and in the claims, if any, are used for descriptive purposes and not necessarily for describing permanent relative positions. It is to be understood that the terms so used are interchangeable under appropriate circumstances such that the embodiments of the invention described herein are, for example, capable of operation in other orientations than those illustrated or otherwise described herein.
The terms "couple," "coupled," "couples," "coupling," and the like should be broadly understood and refer to connecting two or more elements or signals, electrically, mechanically or otherwise. Two or more electrical elements may be electrically coupled, but not mechanically or otherwise coupled; two or more mechanical elements may be mechanically coupled, but not electrically or otherwise coupled; two or more electrical elements may be mechanically coupled, but not electrically or otherwise coupled. Coupling (whether mechanical, electrical, or otherwise) may be for any length of time, e.g., permanent or semi-permanent or only for an instant.
"Electrical coupling" and the like should be broadly understood and include coupling involving any electrical signal, whether a power signal, a data signal, and/or other types or combinations of electrical signals. "Mechanical coupling" and the like should be broadly understood and include mechanical coupling of all types. The absence of the word "removably," "removable," and the like near the word "coupled," and the like does not mean that the coupling, etc. in question is or is not removable.

Embedded MEMS sensors and related methods

Arizona Board of Regents, a body corporate of the State of Arizona, Acting for and on behalf of Arizona State University


The mobile carrier for an augmentative communication device of the present invention encompasses an apparatus enabling the carried augmentative communication device and carrier to be pushed or pulled to accommodate users preference for walking and their disability. The handle of the carrier is adjustable, to accommodate different people of different heights, as well as to adapt to individual needs of users depending upon the severity of their handicap, and the carrier is foldable to a cane configuration for instances where there is insufficient space to allow the carrier to be used in its rolling configuration.

Communication is believed to be the essence of human life. In our society the ability to achieve is often dependent on the ability to communicate. For those of us not born with the ability to communicate, or whose ability to communicate has been impaired, life is often hard and uncontrollable. However, with new technology and the imagination of people who wanted to help, the Augmentative Communication device was conceived and brought to the market.
Market availability of these devices granted people who lack the ability to communicate an opportunity to do so. It allows a special group of individuals who were thought never to have the capability of achieving, to grow and create bright futures for themselves and continually moving towards the goal of independence.
There are a variety of Augmentative Communication Devices available to the public. The devices vary in size, shape, weight and complexity but all have some form of computerized voice and a selection of letters, words or complete thoughts the user may choose from. Some of these devices portray by pictures the thoughts to be transmitted. All which the user may change and enhance as their intelligence progresses.
There are currently several Augmentative Communication Devices commercially available. One company, known as Prentke Romich, has a line of products including the LIBERATOR.SM., the TOUCH TALKER.SM., and the INTRO TALKER.SM.. Another company, Sentient Systems Technology Inc. has a model known as the DYNAVOX.SM.. A company known as Zygo produces models known as MACAW.SM., SECRETARY.SM., and PARROT.SM.. The A.C.S. Technologies company produces a product known as the REAL VOICE.SM.. There may be other devices produced and they are intended to perform a similar function to the devices outlined above, and include any other device which is meant to be transported by the person using it.
Augmentative Communication devices have created greater freedom for non-oral people. For non-ambulatory people, the unit is held by a specially designed mounting bracket for wheelchairs. This allows the wheelchair occupant to use their communication unit whenever and wherever they want. Nothing, however has been proposed for semi-ambulant people, who due to their disabilities are only capable of moving themselves about and usually have very limited control in carrying anything of significant size or weight. Augmentative Communication Devices are evolving constantly with greater capabilities and lighter weight. However, those currently on the market have a weight, with their battery power supply, ranging from about seven pounds to about seventy pounds. This weight, with respect to individuals who are semi-ambulatory, is tremendous. The weight, even if attempted will eventually prove too difficult and dangerous. For if the person were to fall while carrying the device and injure themselves and the unit this could be a major set back in their progress towards independence, and a productive life.
The inability to carry the Augmentative Communication devices creates a high level of frustration in the user. They are in possession of an apparatus which enables them to communicate with the world for the first time, but they are limited as to where and when they can use it. This severe limitation slows down their learning processes as well as creates immense limitations for Augmentative Communication devices which were designed to allow the user to interact freely with their environment.
Having others carry the Augmentative Communication Device is unsatisfactory both due to the excess time of another person which is occupied for a purely mechanical task, as well as the human dependency which is engendered undesirably, rather than diminished. Further, when the Augmentative Communication Device is carried, there is always the possibility that it will be inadvertently dropped. This risk of being dropped is increased when the Augmentative Communication Device is carried by a semi-ambulatory person. Further, the Augmentative Communication Devices are quite expensive, ranging in price from several thousand dollars up to about fifteen thousand dollars. A damaged unit can result in an expensive repair bill and significant down time.
What is therefore needed is a device to help semi-ambulatory, non-oral people over come the challenges accompanying the Augmentative Communication Device both in terms of its weight and mobility. Such a device would free them to face and tackle other challenges, which in turn would permit and encourage them to strive for a fuller life.

Mobile carrier for augmentative communication


The present invention relates to a method of capturing and stabilising volatile thiol malodour generated on the human skin, comprising steps of: i) contacting the human skin with a substrate, ii) absorbing said thiol into the substrate, and iii) reacting said thiol with a thiol-capture agent. The invention also relates to a method of quantifying said thiol, a method of assessing the deodorizing performance of a cosmetic composition on the human skin.

Malodour generated on human skin, especially in the underarm area, is a well-known problem. Such malodour arises from a combination of thiols, volatile fatty acids and steroids. Thiols are particularly smelly. They are perceptible by the human nose at concentrations as low as 1-3 pg L−1 (Natsch et al, Chem Biodivers 2004; 1, 1058-72). Current techniques employed to determine and analyze the malodour are inconvenient and problematic. The main technique is based around a group of trained 'sniffers' who smell people's underarms to determine how foul the odour is. This is only a snapshot of odour development during the day and this method is a type of non-contact sampling. The aforementioned thiols are highly volatile and with the non-contact sampling method, their true amounts and types within perspiration are not fully known. The technique is apparent not a good basis for evaluating the performance of a deodorant product. It is also difficult to map the scent profile for individuals despite suspicion that quantities and types of these volatile thiols might be different between different groups, e.g. 20-24 year males vs. 50-54 year females. In addition, 'sniffing underarm' is inconvenient and uncomfortable for both the panellists and 'sniffers'.
U.S. Pat. No. 3,843,781 describes a method for deodorizing and sweetening the smell of odoriferous materials and objects having mercaptans and hydrogen sulfide as a bad-smelling component. The method comprises applying to said material or object a series of maleimide derivatives. The maleimides are applied in an amount sufficient to substantially reduce the mercaptan and hydrogen sulfide content of the odoriferous material or object.
U.S. Pat. No. 4,680,272 describes a staining method for detecting protein molecules having amine or thiol groups, comprising halogenated maleimides and derivatives thereof. By applying the stain to a substrate suspected of containing amine or thiol groups, and applying an ultraviolet light source thereto, any fluorescence, indicative of the presence of amines or thiols, can be detected.
J. AM. CHEM. SOC. 2010, 132, 1960-65 highlights the potential for a new class of maleimide in protein modification. The report focuses on the use of mono- and dibromomaleimides for reversible cysteine modification and illustrate this on the SH2 domain of the Grb2 adaptor protein (L111C). The resultant protein-maleimide products can be cleaved to regenerate the unmodified protein by addition of a phosphine or a large excess of a thiol.
Despite all the prior art, there is no technique or method that allows the capture, stabilization and precise quantification of the volatile thiols generated on human skin. There also remains a need to assess the performance of deodorant products by evaluating how thiols are affected after the application of said products.
The present invention addresses those problems.

This patent is subject to a terminal disclaimer.

Method of capturing and stabilising thiols


Down-time at switching of systems is reduced in a communication system that implements functional safety communication. Provided are a first preparation part 1222 that, when a functional safety communication initialization sequence is started between a slave and a control-system master, executes a first sequence group consisting of some sequences of the functional safety communication initialization sequence together with the slave; a second preparation part 1223 that executes a second sequence group being a sequence of the functional safety communication initialization sequence other than the first sequence group together with the slave when a failure of the control-system master is detected after execution of the first sequence group is completed; and a control communication control part 110 that starts control communication with the slave after execution of the second sequence group is completed.

There is a network system that employs a master-slave method for the field of instrumentation. FIG. 1 is a diagram illustrating an example of the configuration of the network system that employs the master-slave method (system-switching system 500).
The network system illustrated in FIG. 1 is composed of two masters 100 (control-system master 100a, standby-system master 100b) and a plurality of slaves 200 (slave 1 (2001), . . . , slave n (200n)) in order to maintain availability. Maintaining availability means to shorten the time during which the system is halted as much as possible.
By providing the duplicated masters 100 as described above, the standby-system master 100b can take over the role even if a malfunction occurs in the control-system master 100a, and availability can be maintained.
In order to maintain availability, it is necessary not only to provide the duplicated masters 100 but also to reduce down-time which occurs when the role of the control-system master 100a and the role of the standby-system master 100b are switched.
The down-time is the time during which a system or service is halted, and refers herein to the time from when a malfunction occurs in the control-system master 100a to when communication is resumed between the standby-system master 100b and the slave 200.
As an example of a technique for reducing the down-time, Patent Literature 1 is presented. Patent Literature 1 reduces the start-up time of an execution on-line system of a standby computing machine when a failure occurs in an execution computing machine. A system of Patent Literature 1 is composed of one execution computing machine and one standby computing machine. An execution on-line system is incorporated in the execution computing machine. A dummy on-line system is incorporated in the standby computing machine. A switching monitor program is incorporated in each of the execution computing machine and the standby computing machine.
The operation of the system of Patent Literature 1 is as described below. First, the execution computing machine operates at normal times. At this time, the dummy on-line system that is identical with the on-line system of the execution computing machine is launched on a memory in the standby computing machine. Thereafter, the dummy on-line system is executed on the standby computing machine until switching of the systems occurs.
When a failure occurs in the execution computing machine, switching of the systems occurs and the processing of the execution computing machine is taken over by the standby computing machine. In the standby computing machine, the identical dummy on-line system has already been started, so that the processing can be continued without initializing the memory, and the down-time can be reduced.

Communication system, standby device, communication method, and standby program


A tube holder (105) for use with a peristaltic pump includes a housing having a recess (165) for receipt of a pump rotor and a tube race around the recess. The tube race has a first race part and a second race part, a first tube inlet (167a) into the first race part and a first tube outlet (167b) from the first race part, a second tube inlet (167c) into the second race part and a second tube outlet (167d) from the second race part. The tube is insertable in the tube race by movement in a substantially orthogonal direction relative to the tube race so that it extends in through the first tube inlet (167a), around the first race part, out through the first tube outlet (167b), in through the second tube inlet (167c), around the second race part, and out through the second tube outlet (167d).

A large number of applications require the pumping of fluids. Standard pumps result in the fluid coming into contact with the pumping apparatus, thereby risking contamination of the fluid. Peristaltic pumps operate by occluding a tube containing the fluid, so that the fluid only comes into contact with the interior of the tube, and not the pumping head or other pumping components.
One problem faced with conventional peristaltic pumps is maintaining the tube in a desired position within the tube race, as if the tube moves with movement of the pumping head, the fluid will not be pumped efficiently.
Another issue with conventional peristaltic pumps is maintaining correct alignment between the pump head and the tube in the raceway, and maintaining the desired pressure on the tube for consistent fluid pumping.
It is an object of at least a preferred embodiment of the present invention to provide a peristaltic pump head and/or tube holder which address at least one of the issues outlined above and/or which at least provides the public with a useful choice.


In a user-interactive display-based telephone terminal, a user of the telephone terminal is provided easy access at the terminal to both local features and network-based features from a telecommunication switch. The user of the terminal reconfigures the terminal to a state wherein network based information is obtained by simply actuating any of the associated network-based keys. Similarly, the user of the telephone terminal reconfigures the terminal to a state wherein local information stored in the terminal is obtained by simply actuating an associated local key. The information selected, local or network-based, is displayed in the same location in an associated display on the terminal. The user of the terminal is therefore not provided with nor is he or she required to have knowledge of the location of a particular feature.

1. Technical Field
This invention is directed to interactive display arrangements and more particularly to an apparatus and a method for enabling a user to easily access both local and network-based features through an interactive display arrangement.
2. Description of the Prior Art
Telephone terminals that contain user interactive displays and enable a user to access local and network-based features and also to execute local and network-based commands at the telephone terminal are now becoming popular. In these terminals, the number of features or commands available on a display for selection by the user is limited, at any given time, by the finite size of the display.
Most high function telephone terminals provide buttons and indicators for access to network-based features available from a telecommunication switch. Many of these telephone terminals also provide a display which further describes the feature or other available network-based information. Some telephone terminals also provide local features wherein access to a personal directory on a display or a repertory dialer may be provided, for example. When telephone terminals provide access to both local and network-based features, however, the operation of selecting from one or the other set of displayable features may be confusing to a user. This confusion occurs since often a user is not able to readily determine the particular state (local or network-based) that the telephone terminal is in and then reconfigure the terminal to the other state for accessing its features or to execute a command in this other state.
To minimize the confusing aspects of the display operation, some telephone terminals available in the art are constructed with the display separated into two separate areas. For these terminals, the buttons and a first part of the display are assigned to accessible network-based or switched features while other buttons and a second pan of the display are assigned to accessible local features. Other telephone terminals are constructed with completely separate displays and buttons for accessing the local and network-based features or require the user to consciously switch the display between the local state and the network-based state before being able to access a feature in the switched to state. It is desirable, therefore, that a telephone terminal providing access to both local and network-based features allows a user to be able to easily gain access to and use either of these features without undue confusion.

Apparatus and method for accessing both local and network-based features at a telephone terminal


A main cartridge attachable and detachable to and from an apparatus body of an image forming apparatus for forming an image on a recording medium is provided. The main cartridge include a process device configured to act on a photosensitive member, a grip portion configured to be held by a user, and an attachment unit to attach a sub cartridge containing developer along the longitudinal direction of the main cartridge. In the longitudinal direction, the center position of the grip portion is disposed at the upstream side in the attachment direction of the sub cartridge from the center position of the main cartridge.

1. Field of the Invention
The present invention relates to a main cartridge attachable and detachable to and from an electrophotographic image forming apparatus, and a process cartridge. The present invention also relates to an image forming apparatus having the process cartridge.
The electrophotographic image forming apparatuses form an image on a recording medium using an electrophotographic image forming process. The electrophotographic image forming apparatuses include, for example, electrophotographic copying machines, electrophotographic printers (for example, laser beam printers and light-emitting diode (LED) printers), electrophotographic facsimile apparatuses, and electrophotographic word processors.
The recording media on which an image is formed by an electrophotographic image forming apparatus include, for example, paper and overhead projector (OHP) sheets.
The process cartridge is detachably attached to the main body of an electrophotographic image forming apparatus. The process cartridge is provided with at least one process device used in an image forming process for forming an image on a recording medium. The process cartridge and the process device are integrated as a cartridge. The electrophotographic process devices include charging devices, development devices, and cleaning devices.
2. Description of the Related Art
The above-described cartridge is replaced by the user when the user attaches the cartridge to the apparatus main body or when the cartridge reaches its end of life. In the replacement of the cartridge by the user, a grip portion can be provided for the user to surely hold the cartridge. For example, Japanese Patent Application Laid-Open No. 2003-208074 discussed this type of a grip. In Japanese Patent Application Laid-Open No. 2003-208074, in attaching the cartridge to the apparatus body, the user holds the grip portion protruding from a frame body of the cartridge, and inserts the cartridge into the apparatus along a guiding portion of the apparatus body. When the user removes the cartridge from the apparatus body, the user holds the grip portion with hands, and takes it out of the apparatus. The grip portion provided in the cartridge enables the user to easily attach and detach the cartridge to and from the apparatus body.
Further, in a technique discussed in Japanese Patent Application Laid-Open No. 2002-311709, the attachment and detachment directions of a cartridge containing toner is orthogonal to the attachment and detachment directions of a developing unit. In contrast to a mechanism in which the attachment and detachment directions of the toner unit and the development unit are the same, the fixation releasing mechanism of the development unit can be omitted.
The cartridge may be further separated into a plurality of cartridges, and in such cartridges, one cartridge is referred to as a main cartridge and the other cartridge detachably provided to the main cartridge is referred to as a sub cartridge. In Japanese Patent Application Laid-Open No. 2002-311709, the development unit (development cartridge) is the main cartridge, and the toner unit (toner cartridge) is the sub cartridge. Among mechanisms attaching and detaching the sub cartridge in the longitudinal direction of the main cartridge, a case that the grip portion is provided in the whole longitudinal direction of the main cartridge as discussed in Japanese Patent Application Laid-Open No. 2002-311709 is described.
In the case where the grip portion is provided in the whole longitudinal direction of the main cartridge, the portions held by the user vary. Depending on the portions in the grip portion held by the user, the balance in the longitudinal direction can be lost, which makes it hard to grip. Moreover, if the grip portion is provided at a central portion of the main cartridge in the longitudinal direction, when the user attaches the sub cartridge, the distance between the position of the grip portion of the main cartridge and the position of the sub cartridge held by the user increases. As a result, especially in a case of a large cartridge, the attachment and detachment operation of the main cartridge and the sub cartridge can become difficult.

Main cartridge, process cartridge, and image forming apparatus


The column for distillation of charge products which form a heavier liquid phase and a lighter liquid phase and connected sump circulating boiler are provided with a liquid impermeable collecting bottom plate located in a lower part of the column. The bottom plate has a discharge passage and the column is provided with a liquid withdrawal outlet arranged closely underneath the collecting bottom plate but above the lower end of the discharge passage so that the heavier phase can be prevented from reaching the liquid withdrawal outlet by gravity. One pipe connects the sump circulating boiler with the liquid withdrawal outlet to provide a free flow of liquid from the column to the sump circulating boiler for heating and another pipe connects the column with the sump circulating boiler above the collecting bottom plate so that the reheated liquid can flow from the sump circulating boiler to the column without a circulating pump. The column also has a column sump arranged so that the lower part of the column opens into the column sump, which has a cross-section which is smaller than the cross-section of the remaining portion of the column; and a separating layer regulator for regulating a separating layer between the lighter and the heavier phase of the charge product and connected with the column sump having the smaller cross-section for greater sensitivity and reliability.

The present invention relates to a column for distillation of charge products which have a tendency to form two-phases in a sump of the column.
Particularly, it relates to such a column for distillation of charge products having the above tendency, which is heated by a sump circulating boiler.
Columns of the above-mentioned general type are known in the art. During operation of such columns which are heated by a sump circulating boiler, as a rule difficulties occur when the charge product to be distilled has tendency to two-phase formation in the sump of the column. The heavy phase produced in this case can bring to stoppage the circulation of liquid between the column sump and the boiler required for the column heating, or at least considerably affect the same.
For eliminating these difficulties it has been proposed to provide a forced circulation between the column sump and a separate separating container by means of a pump. Thereby the heavy phase in the separating container is separated by gravity force separation, and only a light phase is pumped back into the column sump. The separating layer between the light and heavy phases is maintained constant by a separating layer regulator. This method is not free of disadvantages, since the installation of a pump for the forced circulation as well as a separate separating container cause additional installation and operational costs. Moreover, the use of the pump leads to the fact that the liquid is mixed by the pump before the entrance in the separator. The heavy phase is therefore produced only in the form of very small droplets, which naturally affect its subsequent separation.

Column for distillation of charge products having a tendency for two-phase formation in sump


A highly-reflective liquid crystal on silicon (LCOS) panel includes pixel electrodes on a substrate, each pixel electrode having a top surface with a first reflectivity. A continuous reflective coating covers the pixel electrodes and substrate surfaces therebetween, forming a plurality of coated pixel electrodes having an enhanced reflectivity that exceeds the first reflectivity. A method for increasing pixel reflectivity in a LCOS panel includes depositing a continuous reflective coating covering both (1) a plurality of pixel electrodes on a substrate and (2) a plurality of inter-pixel substrate surfaces, and depositing a layer on the continuous reflective coating.

This invention relates to the manufacture of liquid-crystal-on-silicon (LCOS) displays, and particularly, LCOS displays with enhanced reflectivity.
LCOS displays are used in consumer electronics, such as hand-held projectors and near-eye displays, and also have applications in optical communications technologies. LCOS displays include a reflective LCOS panel that contains a pixel array formed on a semiconductor wafer.

Highly-reflective liquid crystal on silicon panel comprising a continuous reflective coating covering pixel electrodes and an inter-pixel coating


A quick-release capo for a dulcimer musical instrument is presented. The capo body is an inverted U-shaped design having a fixed top and perpendicular side. A second perpendicular movable side is provided. Outside the movable side is a quick-release mechanism. The movable side and quick-release mechanism is adjusted to snugly fit across the dulcimer fret board by means of a thumbscrew and adjusting shaft. As the quick-release piece is adjusted inwardly by the thumbscrew, it compresses the movable side until the capo is snugly fit on the fret board. An L-shaped lever moves a non-concentric cam to alternately tighten or loosen the movable side. This L-shaped lever allows the user of the capo to quickly release and/or re-attach the capo to the dulcimer fret board.

This invention relates to a capo for a mountain dulcimer or other dulcimer. More particularly, it relates to a capo which may be quickly attached or detached from the fret board of a dulcimer musical instrument.
Many stringed instruments such as the guitar or dulcimer require the player of the instrument to change chords. Changing cords is accomplished by depressing the strings on the fret board at various lengths along the strings. This procedure is sometimes accomplished by hand, although it may also be conveniently accomplished by use of a capo.
Guitar capos are commonly known in the musical instrument industry. One such guitar capo is shown in the 1982 patent issued to Wilkerson, U.S. Pat. No. 4,324,165. This particular capo, and other capos found in the guitar industry, utilize an essentially L-shaped device which is attached to the string board to depress the strings at various lengths along the string board. Some of these capos are quick-release type of aids. However, the guitar capos are all distinct from a dulcimer capo due to the nature of a guitar as opposed to a dulcimer.
A guitar has a lower body and an extended and narrow neck or string board. This narrow string board allows the guitar capo to be attached around the entire string board. In the dulcimer application, the construction of the dulcimer makes it impossible to place the capo around a narrow extended string board since there is no extended string board about which to attach the capo.
A dulcimer is made of a body which has on its top, running along the length of the body, a raised fret board. The entire length of the fret board is attached to the lower dulcimer body thus making it impossible to attach a capo underneath the fret board. This feature renders the use of a guitar capo on a dulcimer impossible. Additionally, since dulcimers often utilize fewer strings than a guitar, it is common when playing the dulcimer to be required to change chords frequently and rapidly. Although known dulcimer capos have provided the capability for changing chords on the dulcimer, none of the prior art provides a dulcimer capo capable of quick-release and re-attachment.
It is an object of this invention to provide a capo which is capable of being attached to a dulcimer fret board. It is a further object of this invention to provide a dulcimer capo which may be quickly and easily attached and re-attached to a dulcimer fret board by means of a quick-attach lever. It is a still further object of this invention to provide a reliable and quickly removable dulcimer capo for use with a dulcimer stringed instrument.
Further and other objects of this invention will become apparent upon reading the below Specification.


A method for shortening image delay includes, but is not limited to refreshing a current frame image from a frame buffer area to the display screen from top to bottom, and notifying an application to draw next frame image when the current frame image is refreshed to a predetermined row. The method further includes updating content in predetermined rows from top of next frame image drawn by the application to the frame buffer area of the system, and replacing content in the predetermined rows of the current frame image that have already been displayed The method further includes updating the content in the remaining rows of next frame image drawn by the application to the frame buffer area, and replacing content in the remaining rows of the current frame image that have already been displayed.

In recent years, as virtual reality (abbreviated as VR) technology gradually becomes mature, various virtual reality apparatus arise gradually. Due to Android open source property and sound ecological system, many virtual reality apparatuses are developed based on Android system.
A display procedure of current Android application generally includes two portions: application-side drawing and system-side rendering. For example, Android application invokes SurfaceFlinger service to render, to a display screen, Surface which has passed through measurement, layout and drawing. Generally, when an image is drawn, a so-called "dual buffer" technology is employed. Dual buffer means that two buffer areas (SharedBufferStack) are used: one is called FrontBuffer, and the other is called Backbuffer. A display end processes the FrontBuffer, while a Central Processing Unit (CPU) and a Graphics Processing Unit (GPU) process the BackBuffer. Based on a display refresh mechanism, the image is always drawn in the BackBuffer first, then exchanged with the FrontBuffer, and rendered on the display screen.
In a virtual reality system, there is very crucial index, namely, delay from movement to display, for example, namely, a time period required from a moment when the user's head position changes to a moment when the application draws a corresponding image according to the change and finally displays the image on the display screen. To obtain an optimal user experience, the time period must be very short, preferably so short that the user by no means feels it. If the delay is too long, the user will feel the image shaking and feels dizzy, and the user's experience is undesirable. However, since Android system is not designed for a virtual reality apparatus, the current image display of Android causes the image of the virtual reality apparatus to experience a longer delay from rendering to display, and the user's experience is undesirable.
In addition, other objects, desirable features and characteristics will become apparent from the subsequent summary and detailed description, and the appended claims, taken in conjunction with the accompanying drawings and this background.

Method and apparatus for shortening image delay, and virtual reality apparatus


The present disclosure provides a single-degree-of-freedom (SDOF) magnetic damping shock absorber based on an eddy current effect, comprising a lower plate, a ring-shaped magnet a, a ring-shaped magnet b, an aluminum cylinder, a bottom copper sheet, a copper sheet, a top copper sheet, a bearing seat, a linear bearing, a bearing end cap, a load, a piston shaft, a stepped shaft, a fixed collar, a coil spring, a lower clamping shaft, and fixing screws. When the shock absorber is working, the ring-shaped magnet a keeps stationary at the lower end and the ring-shaped magnet b reciprocates in the vertical direction. Both magnets are arranged in a mutual attraction manner. Under the action of a time-varying electromagnetic field generated by the relative movement of the ring-shaped magnet b, the copper sheet arranged between the two ring-shaped magnets generates eddy current damping. The movement of the ring-shaped magnet b is inhibited.

Vibration is a common phenomenon in engineering technologies and also usually occurs in daily life. The vibration is also an important factor in affecting the processing accuracy and working accuracy of devices in some complex environments. People have paid much attention to vibration reduction and developed various vibration reduction devices by which the processing accuracy and production efficiency are extremely improved.
A traditional passive shock absorber is composed of a mass, a spring, and a damping element that have set parameters. With a simple and reliable structure, the traditional passive shock absorber can meet the production requirements in common industrial occasions. However, it cannot satisfy people's demands on precision devices due to its shortcomings of poor effects of low frequency isolation and ultra-low frequency vibration. Therefore, semi-active vibration reduction and active vibration reduction are mainly researched. At present, shock absorbers are controlled in three modes: passive control, active control, and semi-active control. Due to the simple structure and low cost, shock absorbers based on the passive control mode are widely used and usually designed for use according to specific engineering requirements. According to the information of controlled objects that is acquired by sensors in real time, shock absorbers based on the active control mode can directly provide a force to balance the force generated by vibration. This extremely improves the system performance. Since they require the supply of external power to provide rapid response, the cost is higher and they are not frequently used in actual production. Shock absorbers based on the semi-active control mode can change inherent frequency according to the information of controlled objects that is acquired by sensors in real time. In this way, they can achieve an excellent vibration reduction effect, without consuming much energy. In spite of this, there are also some limitations in use.

Single-degree-of-freedom magnetic damping shock absorber based on eddy current effect


A data entry pad is described herein comprising a plurality of keys with each corresponding to a predefined sequence of characters indicative of at least one of a geographic size and geographic location related to land or mineral interests. A data entry pad is also described herein comprising a plurality of distinct and non-overlapping regions with at least one region of the plurality of distinct and non-overlapping regions encompassing a plurality of keys with each key corresponding to a predefined sequence of characters indicative of at least one of a geographic size and geographic location related to land or mineral interests.

Data entry pads, otherwise referred to herein as "keypads" or "keyboards," are used in conjunction with numerous electronic devices. Common examples of data entry pads are: (i) physical keypads that can be externally or internally connected to one or more devices, (ii) virtual keypads on, e.g., touch screen devices, and (iii) virtual laser keypads—all of which act as input devices in one way or another. Not all data entry pads, however, convey the same information in the same way. For example, the majority of computer keyboards have both a numeric keypad and an alphabetic (e.g., "QWERTY") keypad capable of conveying information in a variety of ways. As such, many variations of keypads and keyboards have been developed over the years—each one modified in order to increase its functionality and/or efficiency for a particular use, setting, and/or device with which it is to be used. See, e.g., U.S. Pat. Nos. 8,627,224 and 7,439,959, and U.S. Patent Publication Nos. 2008/0205960, 2010/0333011, and 2008/0284744, all of which are hereby incorporated by reference herein in their entirety.
One particular use of data entry pads is for entering information related to land and/or mineral interests (e.g., oil, natural gas, and precious metals) into electronic devices using, for example, computer executable code interfaces. Until the presently disclosed and/or claimed inventive concept(s), users (e.g., landmen, title attorneys, county clerks, and county assessors) had to enter such land and/or mineral-related information into electronic devices by pressing multiple keys on a keypad in order to produce terms or abbreviations repeatedly used in the field. For example, each letter of terms like "section," "township," "range," "mineral," "degrees," "rods," and "chains" had to be entered by pressing numerous keys on a keypad in a particular order and in succession to form the desired word. Additionally, each letter, number, and punctuation mark likewise had to be entered by pressing numerous keys on a keypad in a particular order and in succession to form desired abbreviations like "N/2," "S/2," "E/2," and "W/2," all of which can be used over and over again when entering information related to land and/or mineral interests.
As such, there is a need for a data entry pad comprising a plurality of geographic indication keys with each key corresponding to a predefined sequence of characters corresponding to terms and/or abbreviations indicative of geographic sizes and/or geographic locations related to land and/or mineral interests in order to decrease the number of keystrokes needed to enter a single term and/or abbreviation related to land and/or mineral interests into an electronic device using, e.g., computer executable code interfaces.

Data entry pad for entering information related to land and mineral interests and/or geographic locations