Provided is a method of combination therapy for prevention or treatment of c-Met-induced or angiogenesis factor-induced diseases including co-administering an angiogenesis inhibitor and an anti-c-Met antibody or an antigen-binding fragment thereof to a patient.

1. Field
A method of combination therapy for prevention and/or treatment of c-Met and/or angiogenesis factor induced diseases including co-administering an angiogenesis inhibitor and an anti-c-Met antibody or an antigen-binding fragment thereof to a patient in need thereof is provided.
2. Description of the Related Art
c-Met, a typical receptor tyrosine kinase (RTK) present at the surface of cells, binds to its ligand, hepatocyte growth factor (HGF) to promote intracellular signal transduction thereby not only promoting the growth of cells but also being over-expressed in cancer cells so that it is widely implicated in cancer incidence, cancer metastasis, cancer cell migration, cancer cell penetration, angiogenesis, etc. c-Met is over-expressed in many kinds of cancers and in particular, most of the patients with over-expressed c-Met tend to have poor prognosis.
Angiogenesis inhibitors refer to any drugs designed to suppress the growth of cancer by blocking blood supply into cancer cells, and typical examples thereof may include a vascular endothelial cell growth factor (VEGF) antagonist (inhibitor). The vascular endothelial cell growth factor (VEGF) is also present in normal cells and in particular, it is secreted from cancer cells and binds to its receptor, VEGFR to induce angiogenesis, through which the cancer cells are provided with nutrients necessary for their growth.
Therefore, both of c-Met and VEGF related to angiogenesis are of great importance as a target in developing anticancer drugs.
Up to now, however, there haven't been suggested any technologies of treating cancer by concurrently administering a medicine having c-Met as its target and a medicine having angiogenesis factors (e.g., VEGF) as its target.

Method of combination therapy for prevention or treatment of c-Met or angiogenesis factor induced diseases


A method for manufacturing multi-layer package substrates is shown. A substrate with a first side and a second side is first provided, and a layer of release film is formed on the first side and second side of the substrate. After drilling a plurality of through holes on the substrate bonded to the release film and plugging the through holes with a conductive material, the release film is removed. A first copper film is formed on the first and second side of the substrate. First, circuit layer patterns are formed on the first and second side of the substrate through photolithography and etching processes. After coating an build-up layer on the first and second side of the substrate and drilling the build-up layers with a laser to form counter vias on the first side and second side of the substrate, a copper seed layer is formed on the inner surfaces of the counter vias. Second circuit layer patterns are formed on the first side and second side of the substrate. Finally, contact pads are formed on the first side and second side of the substrate.

The invention relates to a method for manufacturing multi-layer package substrates and particularly to a method for producing package soft substrates through Roll to Roll, Reel to Reel, or Panel to Panel approaches.
Printed circuit boards are composite material substrates coated with single layer or multi-layer circuits. Their main function is to provide support and connections between electronic circuit components such as capacitors, resistors and the like, which are built and assembled on a first layer to construct components for selected functions. Printed circuit boards, depending on the number of circuit layers, can be classified as single-sided, double-sided and multi-sided printed circuit boards. Classified by structural materials, they may be divided into hard substrates and soft substrates. As integrated circuit designs and manufacturing techniques have evolved to encompass deep sub-micron engineering, and computers and other electronic devices have followed a trend towards miniaturization, conventional hard substrates used in integrated circuit packages have become obsolete. They have been replaced by soft substrate PACKAGES in Roll to Roll, Reel to Reel, or Panel to Panel methods.
The soft substrates have flexible characteristics. According to the structural characteristics of conductive line circuits, the soft substrates can be categorized as single-sided, double-sided, single-access, double-access, rigid-flex, and rigidized types.
As previously discussed, the soft substrates made through Roll to Roll or Reel to Reel methods have only one or two layers of circuit layer patterns for use as conductive layers. Although they can meet the requirements of high density and fine line circuits (such as line width and line interval down to 25 microns and output end/input end ranging from 400 to 800 microns), for applications in encased chip packages and high performance output/input, it is necessary to allocate a ground conductive element to avoid high frequency interference and noise. As a result, the effective area for circuit configurations is greatly reduced. Taking into account electric characteristics, the difficulty of circuit configuration for conductive layers that use conventional double-sided circuit layer patterns increases significantly. Hence, the use of multi-layer circuit patterns for conductive layers on soft substrates becomes an unavoidable trend in the development of encased chip packaging.
The primary object of the invention is to provide a method for the manufacturing of multi-layer package substrates.
Another object of the invention is to provide a method for producing package soft substrates using Roll to Roll, Reel to Reel, or Panel to Panel approaches.
The method for manufacturing multi-layer package substrates according to the invention first provides a substrate having a first side and a second side that are respectively bonded to a release layer. Then the substrate bonded to the release layers is drilled to form a plurality of through holes. Then the through holes are plugged with conductive materials. The release layers are then removed, and a first copper film is formed respectively on the first side and second side of the substrate. After this process, the first copper films are processed through photolithography and etching operations to form first circuit layer patterns on the first and second side of the substrate. Thereafter, the first side and second side of the substrate are respectively coated with an build-up layer, and the build-up layers are drilled by means of a laser to form counter vias on the first side and second side of the substrate. A copper film is formed on the inner surface of the counter vias, and second circuit layer patterns are formed on the first side and second side of the substrate. Finally, a contact pad is formed on the first and second side of the substrate.
In a first embodiment of the invention, the method for forming the second circuit layer patterns is: first, plate the first and second side of the substrate to form a copper layer. Then form a photo resistant layer on the first side and second side of the substrate, and form photo resistant patterns through photolithography processes. Then, plate the first and second layer of the substrate to form a second copper film among the photo resistant patterns, and fill the counter vias. Then, remove the photo resistant patterns, and etch the second copper film to form the second circuit layer pattern.
In a second embodiment of the invention, the method for forming the second circuit layer patterns is: first, plate the first and second side of the substrate to form a second copper film. Then, form a photo resistant layer on the first side and second side of the substrate, and form photo resistant patterns through photolithography processes. Then, etch the second copper film to form the second circuit layer pattern. Finally, the photo resistant patterns are removed.
In a third embodiment of the invention, the method for forming the second circuit layer patterns is: first, form a conductive bonding layer on the first side and second side of the substrate to fill the counter vias. Then, remove bulged objects on the conductive bonding layer by grinding. Then, remove the second release film. Then, plate the first side and second side of the substrate to form a second copper film. Then, form photo resistant patterns through photolithography processes. The second circuit layer patterns are formed through etching processes. Finally, remove the photo resistant patterns.
The foregoing, as well as additional objects, features and advantages of the invention will be more readily apparent from the following detailed description, which is explained with reference to the accompanying drawings.

Method for manufacturing multi-layer package substrates


The present invention, SMASH (Short Multiply Aggregated Sequence Homologies), is a technique designed to pack multiple independent mappings into every read. Specifically, the invention relates to a composition comprising a first mixture of different chimeric genomic nucleic acid fragments, wherein each different fragment in the mixture comprises randomly ligated DNA segments, wherein each DNA segment in the fragment is a nucleic acid molecule at least 27 base pairs in length resulting from random fragmentation of a single genome. The invention also relates to methods for generating said composition and use of said composition to obtain genomic information, for example, copy number variation.

Analysis of copy number variants (CNVs) on a genomic scale is useful for assessing cancer progression and identifying congenital genetic abnormalities. CNVs are typically identified by microarray hybridization, but can also be detected by next-generation sequencing (NGS) (Alkan et al., 2009; Sudmant et al., 2010). This is generally done using algorithms that measure the number of sequence reads mapping to specific regions. Consequently, the resolution of sequence-based copy number methods depends largely on the number of independent mappings.
The current trend in next generation sequencing technologies is to increase the number of bases read per unit cost. This is accomplished by increasing the total number of sequence reads per lane of a flow cell, as well as increasing the number of bases within each read. Because the accuracy of copy number determination methods is driven by the quantity of independent reads, increased length of sequence reads does not improve the resolution of copy number analysis. Most of the genome is mapped well by short reads, on the order of 25-30 base pairs (bp). At the moment, high throughput sequencers are generating read lengths of ˜150 bp, well in excess of what would suffice for unique mapping.

Genetic copy number determination using high throughput multiplex sequencing of smashed nucleotides


A screen to be presented to a customer administrator is generated according to the license status. Also, as a license status, a processing progress status is provided in which the customer administrator is prohibited to perform operations during asynchronous license status change processing.

1. Field of the Invention
The present invention relates to a cloud system and a license management method for cloud services, and more particularly to a license management method for performing access control for various cloud services based on, for example, user license information.
2. Description of the Related Art
In recent years, various cloud services are provided over the Internet. For these services, an authentication system is generally provided as a security measure that performs, for example, maintenance and management of IDs and passwords as well as access control. Accordingly, users generally purchase licenses for each service that they want before they use the service. Japanese Patent Laid-Open No. 2002-333928 discloses a service operation method that performs authentication and license management for various services. According to this service operation method, access control is performed based on license information managed for each service, and control is performed for each service so as to decide whether or not the service is available.
With the conventional technique, however, because the access control based on the license information is performed centrally by a cloud server, it is difficult for an administrator user or a customer licensed for a service to further assign access rights to general users or customers who use the service, based on the license. For example, an administrator user or a customer who has been granted a trial license for testing a service by the server enables general users to use the trial license. The general users can thereby enforce access rights assigned to the trial license. However, even if, for example, the administrator user wants to assign different access rights to different general users, it is difficult to control rights included in the granted license on a user-by-user basis.
The increase in the types of licenses requires the server to carry out various types of processing such as license switch processing for switching from a trial license to a permanent license. At this time, the access rights assigned to individual users need to be sequentially updated in the license switch processing. Such processing, however, requires a very long time in a system used by a large number of users such as a cloud service. Accordingly, it has been difficult to update access rights assigned to individual users in synchronization with the license switch processing. Also, for the same reason, it has been difficult to update the access rights of individual users in synchronization with the changes in the license status such as termination and recovery of license.

Cloud system, license management method for cloud service


A resin-seal type semiconductor device includes a main substrate divided into first and second surfaces on which first and second insulating substrates are respectively provided. Circuit wiring patterns and first end portions of outer leads are provided on the first and second insulating substrates. Semiconductor elements are soldered onto the wiring patterns and coated with a surface protection material. The main substrate is then folded over so that the first and second surfaces oppose one another and the device acquires a U-shaped cross-section. A space formed between the first and second surfaces inside the U-shape is sealed with a resin such that second end portions of the outer leads are exposed from the resin.

1. Field of the Invention
The present invention relates to a resin-seal type semiconductor device containing an insulating circuit substrate on which a semiconductor element is mounted.
2. Description of the Related Art
FIG. 9 is a cross-sectional view showing a conventional SIP (Single-In-Line-Package) type resin-sealed semiconductor device.
A semiconductor element 2 is fixed on a metal lead frame 1 by means of solder 3. The semiconductor element is electrically connected to a first end portion of an outer lead 5 by a metal wire 4. The metal lead frame 1, semiconductor element 2 and the first end portion of the outer lead 5 are sealed with a resin 6 by a transfer molding process. A second end portion of the outer lead projects from the resin 6.
FIG. 10 is a cross-sectional view showing a conventional DIP (Dual-In-Line-Package) type resin-sealed semiconductor device. The parts common to those shown in FIG. 9 are denoted by like reference numerals, and only different parts will be described.
Second end portions of outer leads 5, which are opposite to the first end portions thereof sealed with resin 6, are projected in two directions.
The SIP- and DIP-type resin-sealed semiconductor devices can be manufactured at low material cost in simple assembly steps, and these devices are suitable for mass-production.
In the above semiconductor devices, a radiation part situated under the metal lead frame 1 is also sealed with resin. Thus, compared to a semiconductor device having a radiation part formed of a ceramic material, the saturation heat resistance Rth (.degree.C/W) of the above devices is higher. Consequently, in the conventional resin-seal type semiconductor devices, the power loss Pc(W) allowable to the resin or a casing is low.
In addition, in the case where two or more semiconductor elements are mounted in the conventional resin-seal type semiconductor device, it is very difficult to form wiring patterns connecting the semiconductor elements, since the lead frame cannot be made finer or thinner. Thus, two or more semiconductor elements cannot be mounted in the conventional resin-seal type semiconductor device. Consequently, the density of mounted semiconductor elements is not satisfactorily high in this semiconductor device.


A roller body receives a tape at a cylindrical surface. First and second flange members are located adjacent one and the other ends of the roller body for movement in the axial direction of the roller body, respectively. If one edge of the tape creases, the movement of the first flange member is restrained, so that a reference position can be set for the other edge of the tape in the first flange member. If the other edge of the tape creases, the movement of the second flange member is restrained, so that a reference position can be set for the one edge of the tape in the second flange member. In either case, the centerline can be prevented from shifting. Employment of the guide roller of this type in a tape drive allows a head to reliably follow a servo track on the tape.

1. Field of the Invention
The present invention relates to a tape drive such as a magnetic recording tape drive. In particular, the present invention relates to a guide roller utilized to guide a tape.
2. Description of the Prior Art
A pair of guide rollers is often incorporated in a magnetic recording tape drive, for example. The guide roller includes a roller body supported on a support shaft. The guide roller is designed to receive a magnetic recording tape at an outer cylindrical surface. A lower flange member is located adjacent the lower end of the roller body. An upper flange member is located adjacent the upper end of the roller body. The upper flange member is allowed to move in the axial direction of the roller body. The lower and upper flange members are designed to extend farther than the roller body in the radial direction from the longitudinal axis of the roller body. The lower flange member serves to define a reference position for the lower edge of the magnetic recording tape. The upper flange member is coupled to a restraint member fixed to the upper end of the support shaft, for example. An elastic member such as a coil spring is located between the upper flange member and the restraint member, for example.
When the magnetic tape is driven in the magnetic recording tape drive, the elasticity of the coil spring forces the upper flange member to urge the magnetic recording tape against the lower flange member in the aforementioned guide roller. The magnetic recording tape is thus allowed to travel along the reference position on the lower flange member. In this case, if the lower edge of the magnetic recording tape creases, the width of the magnetic recording tape narrows. The upper flange member forces the creasing lower edge of the magnetic recording tape to align with the reference position of the lower flange member. As a result, the servo track deviates from a predetermined reference position on the magnetic recording tape. A so-called off-track occurs. A magnetic head cannot follow the servo track on the magnetic recording tape. A tracking control cannot be realized.

Guide roller in tape drive and method of controlling the same


An energy absorbing system that is adapted for absorbing energy of an object in a vehicle in a crash situation by decreasing acceleration and force acting on the object in the crash situation, the energy absorbing system comprising at least one plastically deformable energy absorber that is plastically deformable in the crash situation. A mass-dependent self-adjusting mechanism is provided, the mass-dependent self-adjusting mechanism being adapted for adjusting, on the basis of an underlying mass of the object, a required compensation force that is to be provided by the energy absorbing system in the crash situation for plastically deforming the at least one plastically deformable energy absorber in order to decrease the acceleration and force acting on the object.

(1) Field of the Invention
The invention is related to an energy absorbing system that is adapted for absorbing energy of an object in a vehicle in a crash situation by decreasing acceleration and force acting on said object in said crash situation. The invention is further related to a vehicle seat and to a vehicle having a seat provided with such an energy absorbing system.
(2) Description of Related Art
An Energy Absorbing System (EAS), which may also be referred to as an Energy Absorption/Attenuation System, is usually provided in a crashworthy seat of a vehicle, such as an aircraft, for protecting an occupant of the crashworthy seat e.g. in a crash situation of the vehicle by reducing an occurring body load. Currently, complex EAS exist that are automatically electronically adjustable, for instance by using magneto-rheological fluids. Furthermore, fixed-force EAS with multiple different functioning principles exist, which are generally cheaper and easier to manufacture.
The document US2002/0079725 describes an exemplary fixed-force EAS for absorbing energy of a vehicle or component of a vehicle or occupant of the vehicle in a crash situation so as to allow relatively gradual deceleration of the vehicle, component or occupant. This fixed-force EAS includes a first part, a second part and an elongate deformable member secured to the first part and extending through a deforming arrangement carried by the second part. The elongate deformable member normally acts as a tie or strut between the first and second parts, but the arrangement is such that, when the force acting between these first and second parts exceeds a predetermined amount in a predetermined direction, the elongate deformable member is forced progressively through the deforming arrangement as the distance between the first and second parts changes and the deformable member is thereby forced to undergo plastic deformation, whereby energy is absorbed. The deforming arrangement is such as to effect such plastic deformation substantially without changing the material cross sectional area of the deformable member.
More specifically, the fixed-force EAS according to the document US2002/0079725 is implemented as a roller-tube assembly, wherein the deforming arrangement is provided by means of a roller arrangement having rollers with fixed, i.e. predefined, distances relative to each other, and the deformable member is provided by means of a plastically deformable attenuation tube. In other words, energy absorption/attenuation is performed by deformation of the attenuation tube by means of the rollers with the predefined distances relative to each other.
However, by fixing the distances between the rollers of the roller arrangement to such predefined distances, the rollers may only transmit a predetermined compression force to the plastically deformable attenuation tube for plastically deforming the latter. Consequently, this system can only be manually and stepwise adjusted by adding and connecting additional roller-tube assemblies.
The document US2002/0079725 further describes that manual or automatic adjustment of the energy absorbing characteristics of the described roller-tube assembly can be achieved in a number of ways, including:
(1) Adjustment of wall thickness by rotating, about its longitudinal axis, an attenuation tube having a circular cross-section exterior and a non-circular internal cross-section, to various positions within the roller arrangement, so as to vary the force required to flatten or deform the attenuation tube and hence to alter the attenuation characteristics.
(2) Partially pre-deforming, e. g. flattening, the attenuation tube varying amounts:                (2.1) Rotation of an attenuation tube having a noncircular form of constant or varying wall thickness such that different parts of the periphery of the attenuation tube are presented to the rollers of the roller arrangement so that different forces are needed to deform the attenuation tube, thus providing adjustment for different occupants.        (2.2) Varying a predefined gap between the rollers of the roller arrangement or equivalent parts of the respective deforming arrangement, thereby increasing or decreasing the force required to flatten/deform the attenuation tube.
(3) Varying the roller diameter via tapered cones. In a similar fashion to (2.2) above, the gap that the attenuation tube is required to pass through may be either increased or decreased by moving the rollers of the roller arrangement or other corresponding fixed members as appropriate to present the desired diameter to the attenuation tube, thus, changing the attenuation properties.
However, while the document US2002/0079725 describes that the energy absorbing characteristics of the described roller-tube assembly can be adjusted manually or automatically and further enumerates a number of ways how this can be achieved, it remains silent on concrete realizations. For instance, one described way consists in varying a predefined gap between the rollers of the roller arrangement for increasing or decreasing the force required to flatten/deform the attenuation tube. Nevertheless, it is not described how this variation is performed, whether it is performed manually or automatically, whether it is performed between different discrete predefined gap values and so on.
The document US2009/326765 describes load limiting on a seat belt buckle by providing an adjustable energy absorbing device mounting the seat belt buckle. Vehicle and occupant conditions are electronically sensed to determine the optimal adjustment of the adjustable energy absorbing device. The adjustable energy absorbing device is an extendable strut having an end connected to the buckle and an end connected to the vehicle. The strut has metal deforming elements to be deformed upon the load reaching a certain magnitude by ball shaped plow shoes.
The document US2009/322066 describes a load limiting device for mounting a seat belt buckle that also includes a plow shoe attached to one of the buckle and a pair of opposed plates attached to the other of the buckle and the vehicle. The plow shoe travels between the plates and absorbs energy by deforming at least one of the plates. An electronic adjuster mechanism adjusts the distance between the opposed plates to selectively increase or decrease the energy absorbing capacity of the load limiting device.
The document U.S. Pat. No. 5,273,240 describes an impact energy absorption system for aircraft seats. A seat is movable between a first unloaded position and a second crash induced position. A deforming die and an additional set of die jaws are connected to a seat mounting and defines an aperture of variable size. A deformable rod has a shoulder connecting the seat to the mounting the rod passing through the deforming die and the variable die jaws. During crash induced movement of the seat, the rod is pulled through the deforming die.

Energy absorbing system for absorbing energy of an object in a vehicle in a crash situation


A proximity sensor module used in an electronic device includes a combination sensing element and antenna, and a detecting circuit electrically connected to the combination sensing element and antenna. The combination sensing element and antenna is used to detect whether an external object is in vicinity of the combination sensing element and antenna according to capacitance changes of the combination sensing element and antenna in presence or absence of an external object in the vicinity, the detecting circuit detects the capacitance changes, and generates a signal associated with the changes to decrease or increase transmission power transmitted to the combination sensing element and antenna.

1. Technical Field
The disclosure generally relates to proximity sensor modules, particularly to a capacitive proximity sensor module and an electronic device using the capacitive proximity sensor module.
2. Description of Related Art
Proximity sensors are built into many electronic devices (e.g., tablet computers) to detect when an external object, such as a human body part, comes within a given distance of the electronic device. When the presence of an external object in a vicinity of the electronic device is detected, a transmit power of an antenna of the electronic device may be reduced to ensure that radiation transmission levels are sufficiently low to meet regulatory limits for specific absorption rate (SAR). When the external object is no longer present, transmit power of the antenna may be increased. Generally, a typical capacitive proximity sensor includes a detecting circuit and a sensing element which can be a sensing capacitor or a group of sensing capacitors. Capacitance of the sensing element changes according to the presence or absence of the conductive or the dielectric object in the vicinity of the sensing element. The detecting circuit detects capacitance changes of the conductive or the dielectric object, and transmits signals accordingly.
A typical sensing element of the capacitive proximity sensor is made of copper and formed on a printed circuit board (PCB) of the electronic device. However, the sensing element occupies area of the PCB which causes an increase in overall volume of the electronic device.
Therefore, there is room for improvement within the art.

Proximity sensor module and electronic device using same


A catalyst for producing styrene-based polymers having mainly syndiotactic configuration which comprises (A) a titanium compound and (B) a contact product of a methyl group-containing organoaluminum compound and water, wherein the contact product (B) has a high magnetic field component of not more than 50% in the methyl proton signal region due to an aluminum-methyl group (Al-CH.sub.3) bond as determined by the proton nuclear magnetic resonance absorption method.

1. Field of the Invention
The present invention relates to a process for producing styrene-based polymers and catalysts for use therein. More particularly, it is concerned with a process for efficiently producing styrene-based polymers having mainly syndiotactic configuration and catalysts for used therein.
2. Description of the Related Art
Styrene-based polymers having a syndiotactic configuration, particularly those with high syndiotactic configuration, have not been known although those having an atactic or isotactic configuration are known.
The present inventors' group has succeeded in developing styrene-based polymers having stereostructure that is mainly syndiotactic (Japanese Patent Application Laid-Open Nos. 104818/1987 and 187708/1987).
The catalysts to be used in production of the above styrene-based polymers having mainly syndiotactic configuration are not only expensive but also have insufficient activity.
Thus the present inventors made expensive investigations to develop a process whereby styrene-based polymers having syndiotactic configuration can be produced more efficiently.

Catalyst for producing syndiotactic configuration styrene-based polymers


The present invention relates to a method of making a header or housing for connection to a semi-conductor device including the step of trimming a single terminal frame molded into the header while the header or housing is in the molding cavity. To accomplish this, the present invention utilizes a single terminal frame including a plurality of substantially parallel electrical connection fingers held together at one end by a tie-bar. The terminal frame has a "V-notch" in each of the electrical connection fingers at a location adjacent the tie-bar. The terminal frame is placed in a mold having an upper and lower mold shell each having cavities formed therein which together define the header or housing to be molded. The upper and lower mold shells come together and grasp the terminal frame at a position adjacent the notch and so that the tie-bar extends outwardly from the upper and lower mold shells. The molding apparatus includes a trim punch positioned to advance towards the tie-bar so that the terminal frame bends at the location of the notch and the tie-bar is eventually torn away from the electrical connection fingers. The tie-bar may be trimmed from the terminal frame either before or after the plastic material is injected into the molding cavity and solidified to form the plastic header or housing.

It is quite common for semi-conductor devices, such as a hybrid circuit formed on a ceramic substrate, to be enclosed in a plastic molded housing. The housing includes a header portion having electrical connection pins made from a terminal frame molded therein. Wirebonds are connected from one end of the electrical connection pins to contact pads or electrical leads of a hybrid circuit. The other end of the electrical connection pins extend out of the housing and header for connection to an external source in a manner known to those skilled in the art.
Heretofore, the header has been formed using a single-piece terminal frame including a plurality of parallel electrical connection fingers connected together along one end by a tie-bar. In such an operation, the single-piece terminal frame is placed in the mold cavity and directly molded into the header for the housing of the semi-conductor device. When the frame is placed in the mold, the tie-bar and a portion of each of the electrical connection fingers are positioned so that they will not be surrounded by the plastic of the header or housing. Once the header is molded around a portion of the electrical connection fingers, the housing is removed from the mold. Thereafter, the tie-bar portion of the terminal frame is punched and removed. After removing the tie-bar, the header then has a plurality of individual electrical connection pins available for connection to an external source. Thus, under this method of making the semi-conductor housing and header, additional tooling and additional steps are required to punch the terminal frame and remove the tie-bar. Further, punching the terminal frame to remove the tie-bar results in substantial wear to the punch tooling which must be frequently replaced.
Thus, heretofore there has been a need for a simple method of making a housing or header for connection to a semi-conductor device including trimming the terminal frame molded into the housing header.

Method of making a header or housing for electrical connection to a hybrid circuit including an in-cavity trim of a terminal frame


Anti-TIM-3 antibodies and antigen-binding fragments thereof are described. Also described are nucleic acids encoding the antibodies, compositions comprising the antibodies, and methods of producing the antibodies and using the antibodies for treating or preventing diseases such as cancer, an inflammatory disease, an autoimmune disease, a metabolic disease, and/or infectious diseases.

T-cell immunoglobulin and mucin-domain containing molecule 3 (TIM-3) is a receptor expressed on myeloid cells, including dendritic cells (DCs), macrophages and NK cells, and a subset of lymphoid cells, such as T cells. The documented ligands for TIM-3 include galectin-9 (Gal-9), phosphatidylserine (PtdSer), and high mobility group protein B1 (HMGB1). The ligations of Gal-9 and PtdSer are mediated by the variable immunoglobulin domain (IgV) of TIM-3. The glycosylation of IgV is required for Gal-9 binding but not for PtdSer binding. By interacting with these ligands, TIM-3 modulates both innate and adaptive immunities. HMGB1 also plays an important role in chronic inflammation of the adipose tissue in obesity, suggesting that TIM-3 function could be involved in inflammation-related metabolic changes.
On the surface of myeloid cells, high expression of TIM-3 inhibits the production of cytokines from macrophages and DCs. The inhibition can be reversed by stimulus from T cells and similarly by blocking monoclonal antibodies. In tumors, the cancer protective and promoting M2 macrophages are associated with high level of TIM-3 expression, whereas the cancer fighting M1 macrophages are associated with low level of TIM-3 expression. It remains to be demonstrated whether blocking TIM-3 by a monoclonal antibody can convert M2 to cancer engulfing M1 macrophages.
On the surface of T cells, TIM-3 modulates adaptive immunity by interacting with the ligand Gal-9. TIM-3 is expressed on CD4+ helper (Th1 and Th17), regulatory (Treg) and CD8+ cytotoxic 1 (Tc1) T cells. Chronic ligation of TIM-3 to Gal-9 induces apoptosis of Th1 cells, downregulating immune response and duration. The surface expression, or possibly the function, of TIM-3 depends on the binding to CEACAM1 in both cis and trans. Remarkably, TIM-3 is usually found on CD8+ T cells expressing immune-repressing PD-1. It has been proposed that TIM-3 and PD-1 are co-suppressors leading to dysfunctional intratumoral T cells. This makes a TIM-3 antagonist antibody a potentially great therapeutic alone and in combination with a PD-1/PDL-1 and/or other immuno-oncology therapy.
In addition to modulating immune cells, TIM-3 is also highly expressed on the leukemic stem cells (LSCs) in acute myeloid leukemia (AML). On LSCs, TIM-3 and Gal-9 form an autocrine stimulatory loop to drive self-renewal pathways of cancerous LSCs and leukemic progression. Interestingly, TIM-3 is not present on the surface of hematopoietic stem cells (HSCs), providing an opportunity to treat AML and other myeloid leukemia disorders using a blocking/depleting/cytotoxic therapeutic TIM-3 antibody.
TIM-3 modulates the activities of both innate and adaptive immune cells. A TIM-3 blocking monoclonal antibody has the potential to unleash the immune system via unique mechanisms to eliminate cancer cells.


Apparatus and associated methods relate to selection of an operating baud rate for a building automation system that communicates over a Master-Slave Token-Passing (MS/TP) BACnet. A server (or router or gateway) connected to the MS/TP BACnet is programmed to iteratively select operating baud rates from a series of available operating baud rates. Each iteration, the server broadcasts a frame indicating baud rate selection to a plurality of building automation devices connected to a MS/TP BACnet. Each of the plurality of building automation devices connected to the MS/TP BACnet then iteratively sets its baud rate so as to match the baud rate selected by the server. The server monitors communications conducted over the MS/TP BACnet so as to determine reliability or unreliability of the communications conducted over the MS/TP BACnet using the baud rates iteratively selected. A highest reliable baud rate is then used by the building automation system.

Building Automation and Control network (BACnet) was developed by the American Society of Heating Refrigerating, and Air-Conditioning Engineers (ASHRAE) for the purpose of providing a standard data communication protocol to permit various venders of building automation system components to communicate with each other. Such building automation system components includes Heating Ventilation and Air Conditioning (HVAC) control, fire detection and alarm, lighting control, security, "smart" elevators, utility company interface, and various other control and automation.
BACnet communications can be performed over various network protocols, such as, for example, ARCNET, Ethernet, LonTalk, Master-Slave Token-Passing (MS/TP), Point-To-Point (PTP), etc. The present application is directed to BACnet communications using MS/TP protocols. MS/TP types of communications can be performed over various physical network protocols, such as, for example, RS485, ZigBee, and LonTalk. An MS/TP network can have a series of master components and a series of slave components. Master components can initiate communication with other master and slave components, while slaves can only respond to communications directed to them. Control of a MS/TP network is passed from master to master by a token in a cyclic fashion. Each master is assigned a MAC (Media Access Control) address between 0 and 127, for example. The token is sequentially passed in ascending order and then from the master component with the highest MAC address again to the master component with the lowest MAC address.
Such communications can facilitate control an operation of these various building automation system components. A series of related building automation system components can be in communication with one another on a shared BACnet. Control or operation of these related building automation system components can be performed by a server or router or gateway connected to the shared BACnet. Control of a building environment can be controlled, for example, at a server connected to a BACnet that is also connected to various HVAC system components (or any other type of system). The server is simply one of the master components on the BACnet, and thus shares control of the BACnet communications. The server, however, can be the only device connected to the BACnet with a program configured to coordinate the system made up of the related building automation components. The server can receive data from and/or send instructions to the various HVAC system components and can control such data flow when the server has the token.
The various building automation system components can communicate over a BACnet at various baud rates, such as, for example, 9600, 14400, 19200, 38400, 57600, 76,800, 115200, etc. Every device on a shared BACnet, however, must communicate with one another using the same baud rate. Selection of baud rate at which all devices on a shared BACnet operate is not automated. An engineer must manually set the baud rate and then monitor the communications of the various building automation components connected thereto. If one of more of the connected building automation components has difficulty communicating, as indicated by flickering of communications, the engineer must lower the baud rate and again monitor the communications. The engineer must check the baud rate assigned to the building automation components experiencing difficulty communicating, so as to ensure that it is attempting to communicate at the proper baud rate. Some devices require a reboot when changing their baud rates, and so such baud rate changes can be time consuming. If, however, none of the connected building automation components has difficulty communicating, then the engineer must increase the baud rate and again monitor the communications. Such a process can be time consuming and expensive. An automated method of selecting a baud rate for a series of building automation components connected to a shared BACnet is desired.

BACnet MSTP optimal baud-rate selection using auto baud feature


The present invention provides new methods for the in vitro preparation of bioartificial tissue equivalents and their enhanced integration after implantation in vivo. These methods include submitting a tissue construct to a biomimetic electrical stimulation during cultivation in vitro to improve its structural and functional properties, and/or in vivo, after implantation of the construct, to enhance its integration with host tissue and increase cell survival and functionality. The inventive methods are particularly useful for the production of bioartificial equivalents and/or the repair and replacement of native tissues that contain electrically excitable cells and are subject to electrical stimulation in vivo, such as, for example, cardiac muscle tissue, striated skeletal muscle tissue, smooth muscle tissue, bone, vasculature, and nerve tissue.

Cardiovascular diseases are responsible for a preponderance of health problems in the majority of the developed countries as well as in many developing countries. Heart disease and stroke, the principal components of cardiovascular disease, are the first and third leading cause of mortality in the U.S., accounting for nearly 40% of all deaths (Heart and Stroke Statistical Update, American Heart Association 2002). Cardiovascular diseases also include congenital heart defects, which occur in about 1% of live births (R. F. Gillum, Am. Heart J. 1994, 127: 919-927) and are the main cause of mortality in the first year of life (J. L. Hoffman, Pediatr. Cardiol. 1995, 16: 103-113 and 115-165). When they do not lead to death, cardiovascular diseases may alternatively result in substantial disability and loss of productivity. About 61 million Americans (almost one-fourth of the population) live with cardiovascular disorders, such as coronary heart disease, congenital cardiovascular defects, and congestive heart failure. In 2001, 298.2 billion dollars were spent in the treatment of these clinical conditions, and the economic impact of cardiovascular disease on the U.S. health care system is expected to grow as the population ages.
Over the past 30 years, advances in the treatment and prevention of cardiac diseases have led to constantly declining morbidity and mortality rates. Treatments for both congenital heart defects and cardiomyopathies have become more sophisticated. However, when these treatments fail, organ or tissue replacement remains the only other possible option. Different surgical procedures may be performed to treat heart failure and cardiac deficiency. These procedures include transplantation of organs from one individual to another, reconstructive surgery, and implantation of mechanical devices such as mechanical heart valves.
Cardiac transplantation is so common that the primary limitation on patient outcome is not the surgical technique, but the declining availability of donor organs. In 2000, 2,500 heart transplants were performed in the U.S. while it was estimated that between 20,000 and 40,000 patients could have benefited from such a medical operation. To circumvent the problem of donor organ scarcity, one can resort to surgical reconstruction, whereby damaged or defective tissue at one site of the patient is replaced by healthy tissue from another part of the patient's body. These autografts include blood vessel grafts for heart bypass surgeries. The disadvantages of using autografts are their limited durability (E. Braunwald, Heart Disease 4th Edition, E. Braunwald (Ed.), W. B. Saunders: Philadelphia, Pa., 1992, pp. 1007-1077) and a loss of function at the donor site. In addition, reconstructive surgery often involves using the body's tissues for purposes not originally intended, which can result in long-term complications. Mechanical heart valve prostheses have proved to effectively improve patient's quality of life. However, they are also subject to mechanical failure and rejection, can induce inflammation and/or infection, and require long-term drug intervention to prevent blood-clotting. Furthermore, since these mechanical valve substitutes are nonviable, they have no potential to grow, to repair or to remodel; therefore their durability is limited, especially in growing children (J. E. Mayer Jr., Semin. Thorac. Cardiovasc. Surg. 1995, 7: 130-132). Since currently available treatments (with the exception of cardiac transplantation) are only palliative, new drugs and procedures for treating cardiovascular diseases, especially approaches allowing the recovery of diminished cardiac function, are highly desirable.
Tissue engineering is emerging as a significant potential alternative or complementary solution. In tissue engineering, tissue or organ failure is addressed by implanting natural, synthetic, or semi-synthetic tissue and organ mimics that are fully functional from the start or that grow into the required functionality to replace, repair, maintain and/or enhance organ/tissue function. Although efforts to generate bioartificial tissues and organs for human therapies go back at least thirty years, such efforts have come closer to clinical success only in the last ten years. In addition to developing improved bioartificial tissue equivalents for therapeutic purposes as well as for in vitro research and drug development, tissue engineering also aims at providing measures to enhance survival and integration of engineered grafts following implantation in vivo.
One of the major strategies adopted for the creation of engineered tissues is the in vitro growth of isolated cells on three-dimensional templates or scaffolds under conditions that coax the cells to develop into a functional tissue. The scaffolds, which can be fashioned from synthetic polymers or from natural materials such as collagen, temporarily provide the biomechanical support needed by the cells. As the cells grow and differentiate on the scaffold, they produce their own extracellular matrix. When implanted, the bioartificial tissue should become structurally and functionally integrated into the body.
The feasibility of engineered functional cardiac muscle has been demonstrated (T. Eschenhagen et al., FASEB J. 1997, 11: 683-694; L. E. Freed and G. Vunjak-Novakovic, In Vitro Cell Dev. Biol. 1997, 33: 381-385; R. Akins et al., Tissue Eng. 1999, 5: 103-118; N. Bursac et al., Am. J. Physiol. Heart Circ. Physiol. 1999, 277: H433-H444; R. L. Carrier et al., Biotechnol. Bioeng. 1999, 64: 580-589). Eschenhagen and co-workers (T. Eschenhagen et al., FASEB J. 1997, 11: 683-694) showed that embryonic chick cardiac myocytes cultured in collagen gels displayed characteristic physiological responses to physical and pharmacological stimuli; and Akins et al. (R. Akins et al., Tissue Eng. 1999, 5: 103-118) demonstrated that rat ventricular cardiomyocytes cultured on polystyrene microcarrier beads in bioreactors formed three-dimensional spontaneously contractile aggregates. Cultivation of neonatal rat cardiac myocytes on polyglycolic scaffolds in bioreactors has been shown to result in contractile three-dimensional tissues (L. E. Freed and G. Vunjak-Novakovic, In Vitro Cell Dev. Biol. 1997, 33: 381-385) with ultrastructural features of cardiac muscle (N. Bursac et al., Am. J. Physiol. Heart Circ. Physiol. 1999, 277: H433-H444). These studies also provided evidence that variations in initial cell density and cultivation conditions affect the structure of the engineered cardiac tissue produced (R. L. Carrier et al., Biotechnol. Bioeng. 1999, 64: 580-589; M. Papadaki et al., Am. J. Physiol. Heart Circ. Physiol. 2001, 280: H168-H178).
One of the major difficulties in engineering a functional cardiac tissue starting from isolated cells is the heart's complex structure and function at different spatial scales. The complex structure of the heart stems from the elongation and spatial alignment of cardiac myocytes, from the distribution of intercellular connections, and from the formation of cardiac muscle fibers and bundles that rotate transmurally inside the heart wall. This unique architecture of cardiac tissue enables an orderly sequence of electrical and mechanical activity and efficient pumping of blood from the heart. Unsurprisingly, the intricate arrangement and geometrical order of different cell types in living cardiac muscle tissue is difficult to reproduce in vitro; and standard tissue engineering culture of cardiac muscle cells seldom yields tissue of such complex structure.
Indeed, most tissue engineering techniques used so far have led to cardiac muscle constructs with a number of shortcomings that limit their usefulness for both in vitro and in vivo applications. Most often, unlike native cardiac muscle that consists of fibers with a defined orientation, the cells in engineered constructs exhibit random orientation and a poor degree of differentiation. Furthermore, the constructs often present a non-uniform spatial cell distribution with, for example, a good tissue formation at the periphery and a loose network of disoriented cells at the center of the construct. Since only a minor fraction of the three-dimensional structure consists of cardiac tissue, its usefulness as a medical implant for replacement therapy is limited. Furthermore, it is generally recognized that structural and functional integration of engineered grafts remains unsolved. Even if high-fidelity engineered tissue equivalents become available, the process of integration will need to be enhanced for the tissue graft to survive implantation and remain functional.
Therefore, a need continues to exist for new strategies that offer novel and satisfactory platforms for in vitro research and the eventual development of compact, thick and functional transplantable heart muscle. In particular, methods for the production of three-dimensional bioartificial constructs with properties resembling those of native cardiac tissue are highly desirable, as are methods allowing their enhanced integration and functionality in vivo.

Application of electrical stimulation for functional tissue engineering in vitro and in vivo


The present disclosure teaches a power management device for providing one or more voltages and prohibiting the operation until the IC is initialized and voltage stability is achieved. The power management device includes a power regulator block and a masking block. The power regulator block includes one or more of the following elements:- a regulator, a bandgap reference generator, a low voltage detector LVDD, a low voltage detector LVDM, and a plurality of logic gates. In one embodiment, the masking block includes one or more level shifters, a plurality of logic gates, a D flip-flop, and a power on reset circuit (PoR).

In semiconductor technology, rapidly shrinking integrated circuit (IC) dimensions drive the requirement of reduced device geometries resulting in the need for multiple voltages to retain compliance with operational constraints. This necessitates the use of on-chip power regulators. In typical applications, the on-chip power regulator derives the supply voltage for the digital core from the input/output (IO) supply voltage. For example, an on-chip regulator generates the 1.2 V supply (for the digital core) from the 3.3 V supply (of the IOs) to save an extra off-chip supply and also to reduce the bill of material (BOM) cost.
In order to facilitate testing, the on-chip regulator is often enabled/disabled by a control signal. This control signal can either be given directly from the IO pad (on the IO ring) or can be driven by the digital core logic itself. However, providing the control signal from the IO ring increases the required number of IO pads resulting in increased cost of packaging.
FIG. 1 illustrates an on-chip control mechanism 100 for on-chip power regulators. The on-chip regulator is controlled by signals which are generated by the digital core. However, since the digital core itself is operating on the Vdd supply generated by the regulator, this may result in unreliable system operation. Further, this approach does not allow the testing of the various sub blocks of the power management unit (PMU).


An optical disk storage tray having a plurality of storage locations, each of which is supplied with a separate optical head and drive mechanism and with common electronics for controlling the optical heads and drive mechanisms and for interfacing them to a host device.

Optical disks are an increasingly popular medium for digitally storing information. Information is stored in binary format, with binary zeros represented by non-reflective pits stamped into a plastic disk and binary ones represented by reflective high points on the disk. The data is retrieved by an optical head which directs a laser source onto the surface of the disk and which utilizes a light sensitive photo diode to detect light reflecting from the disk surface. The binary information is converted to electrical signals and decoded into audio and/or video output.
In present large-scale optical disk storage and retrieval systems each disk is installed in a separate cartridge having a separate drive. Each drive is comprised of an enclosed casing which includes the disk and all of the components, including the interface, loading and unloading mechanics, drive mechanics, optical head, and all of electronics which are necessary for retrieving the data from the disk and delivering the data to the host computer. The drives installed in the storage system are multiplexed to the central processing unit.
These extensive storage systems are highly desirable because of their large capacity and because they provide immediate access to data stored on any of the installed disks. However, these storage systems require considerable amounts of bulky hardware and therefore are extremely costly and highly consumptive of space and power. This makes them impractical for use in schools, small libraries and other small businesses.

Optical disk storage tray having multiple storage sites and corresponding drive components


A preform 20 comprises a neck portion 22 having an opening 21, a cylindrical barrel portion 23, and a bottom portion 24 larger in diameter than the barrel portion 23, and has a corner portion 25 at a boundary between the barrel portion 23 and the bottom portion 24.

Containers made of glass have been used by preference as containers accommodating toilet lotions, milky lotions, etc. (may hereinafter be referred to as cosmetic containers). This is because cosmetic containers made of glass have aesthetic appearances such as a massive feeling and a luxurious feel, and tend to increase consumers' appetite for buying.
In recent years, the aesthetic appearances of resinous containers have also improved. Because of this improvement, coupled with the advantage that resinous containers are lightweight and minimally break compared with glass containers, the resinous containers have been put to use as cosmetic containers. Currently, however, it is difficult to form the resinous containers with an aesthetic appearance comparable to that of cosmetic containers made of glass.
Many glass cosmetic containers are formed with thick walls, for example, for stressing their luxurious feel or massive feeling. The shape of the container is changed, as appropriate, in accordance with the contents of the container. Generally, however, the bottom surface section of the container is considerably thick-walled, whereas the barrel of the container has a small and uniform wall thickness in comparison with the bottom surface section. In imitation of the shape of the cosmetic container made of glass as mentioned above, the resinous container also has the bottom surface section thick-walled and the barrel uniformly thin-walled. By so doing, an improvement in the aesthetic appearance of the resinous container can be expected.
Such a resinous container is produced, for example, by injection-molding a bottomed cylindrical preform with the use of a starting resin material such as polyethylene terephthalate (PET), and blow-molding the preform. On this occasion, a bottom portion of the preform (parison) is formed in a larger wall thickness than its barrel portion, whereby the bottom surface section of the resulting container is rendered larger in wall thickness than its barrel. Various methods have been proposed in this connection (see, for example, Patent Document 1).

Preform and method for producing container


A piggy-back package for holding a basketball backboard and rim with positioning tabs on the package of the basketball backboard, which tabs position and hold a rim package on the backboard package. The rim package is off-set and at one end of the backboard to allow for tight stacking of two piggy-back packages (one upside down and rotated 180.degree. from the other).

The invention is directed to a stackable carton for separately packaging a basketball backboard and a basketball rim into a single carton which can also be used to package the basketball backboard by itself.
In the past basketball backboards and their rims were each separately packaged and shipped to retailers as two separate items. First time consumers buying a rim and backboard prefer a single package or unit. This is also a desirable and effective marketing technique for the retailers.
Additionally, it has been known to ship basketball backboards, rims and supports in a single carton, see U.S. Pat. No. 4,653,646 to Allen, et al. issued Mar. 31, 1987. This Allen, et al. package has the disadvantage that it takes up a considerable amount of storage space and requires internal spacers to keep the rims from sliding around in the package and is especially wasting of space when only a backboard is shipped. Therefor normally a different box is used for the three-in-one construction than when the backboard alone is shipped.
The instant invention relates to a carton which can handle a single backboard by itself in a compact manner and without spacers, or alternatively can contain both a basketball backboard and its rim in a single unitary package. The carton has a stacking feature which allows two combined packages (each containing a backboard and rim) to be stacked in a manner to take up approximately the same amount of space as one package of the above-mentioned Allen, et al. type. Thus the instant invention is not only saving of space, but is cheaper to use since it requires inventorying one shipping carton or package and can be used without spacers to ship a backboard by itself.
This double purpose use limits the different number of cartons a manufacturer has to stock, since the same carton is used whether or not a basketball rim is shipped with a backboard.
The compact piggy-back stacking arrangement is obtained by mounting the rim package on one side of the basketball backboard carton such that the rim package is located between an end of the backboard carton and its midpoint. In this manner two cartons can be piggy-backed one on top of the other by rotating one package 180.degree. horizontally and placing it atop the other package in an inverted manner so as to create a sandwich structure with the two backboard portions acting as the bread and the two rim packages acting as the sandwich filler, located side by side.
The carton has location means on one side for securing the rim package. This location means comprises tabs which are scored into a carton blank and which can be lifted up to securely position and hold the rim package. There are two scorings to create the tabs.
Each scoring is preferably, but not necessarily located along two opposing edges of the carton blank when it is flat and is "Y" shaped. The stem of the "Y" abuts an edge of the carton and the "V" portion of the "Y" opens toward the center of the carton. The type of scoring allows for some overlapping of the edges of the carton blank when it is folded about a backboard so as to accommodate different sized backboards in the same package and to compensate for variations in the centering of the fold that encases the backboard. Here the stem portions of the "Y" would overlap when the blank is folded. If the score lines are not located at an edge of the blank, then additional score lines will be necessary. For example six score lines to create a box divided into four quarters could produce four tabs. Here, the score lines would be in the form of a swastika. Alternatively an "X" score could produce four tabs.
Fold lines can also be impressed into the carton blank. The tabs can be long enough so that they will be first upwardly rotated 90.degree. from the plane of the carton after the carton is folded around the backboard. The rim package is then placed between the folded out tabs and tip portions of the tabs can then be folded 90.degree. to face one another as well as being parallel to the backboard. These tip portions would then extend over the rim package. Stapling, gluing or taping of the tips to the top of the rim package would secure it to the carton in a fixed position. The two "Y" scores produce six tabs. Two have delta configurations and correspond to the "V" portion of the "Y" score. The other four tabs are four sided and have two parallel sides joined by one right angle side formed by the edge of the carton and an acutely angled side formed by one leg of the "V" portion of the "Y" score.
It is not necessary that the tip portions of the tabs be folded over from the tab itself. Instead the once folded upright tabs could be attached to the sides of the rim basket package without folding of the tip portions.
Alternatively, only some of the tabs can be rotated 90.degree. and the others could remain flat to provide a cushion between the rim package and the backboard if such is desired. Where glass backboards are used, this non-folding of some tabs may be advantageously used to keep the rim package from damaging the backboard, which it might do if it rested directly on the glass surface. Also with fan-shaped (curved edged) backboards, retaining one or more of the flaps flat, might help fill in a void area of the backboard package to hold the rim package horizontal for the purpose of preventing an edge thereof from gouging into the backboard. Some cutting of the tab may be necessary here. Preferably the tabs are an integral part of a paperboard (cardboard) blank that makes up the carton housing the backboard.
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.

Stackable piggy-back carton for basketball backboard and rim


A sensor dispensing instrument adapted to handle a sensor pack containing a plurality of sensors and to perform a test using one of the sensors. The sensor dispensing instrument includes an outer housing and a mechanical mechanism contained therein for rotating the sensor pack and ejecting one of the sensors from the sensor pack and through a sensor slot on the housing. The sensor dispensing instrument also includes a puller handle for operating the mechanical mechanism. The puller handle is adapted to be grasped between the thumb and finger of a user's hand, and is moveable between a testing position adjacent to the rear end of the outer housing and an extended position spaced outwardly from the rear end of the outer housing.

1. Field of the Invention
The present invention generally relates to a fluid monitoring system, and, more particularly, to a new and improved instrument for handling multiple sensors that are used in analyzing blood glucose or other analytes contained therein.
2. Description of the Prior Art
People suffering from various forms of diabetes routinely need to test their blood to determine the level of blood glucose. The results of such tests can be used to determine what, if any, insulin or other medication needs to be administered. In one type of blood glucose testing system, sensors are used to test a sample of blood.
Such a sensor may have a generally flat, rectangular shape with a front or testing end and a rear or contact end. The sensor contains biosensing or reagent material that will react with blood glucose. The testing end of the sensor is adapted to be placed into the fluid being tested, for example, blood that has accumulated on a person's finger after the finger has been pricked. The fluid is drawn into a capillary channel that extends in the sensor from the testing end to the reagent material by capillary action so that a sufficient amount of fluid to be tested is drawn into the sensor. The fluid then chemically reacts with the reagent material in the sensor with the result that an electrical signal indicative of the blood glucose level in the blood being tested is supplied to contact areas located near the rear or contact end of the sensor.
In order to couple the electrical signals produced at the sensor contacts to monitoring equipment, the sensors need to be inserted into sensor holders prior to the sensor end being placed into the fluid being tested. The holders have corresponding mating contact areas that become coupled to the contacts on the sensor when the sensor is inserted into the holder. Consequently, the holders act as an interface between the sensor and monitoring equipment that accumulates and/or analyzes the test results.
Prior to being used, the sensors need to be maintained at an appropriate humidity level so as to insure the integrity of the reagent materials in the sensor. Sensors can be packaged individually in tear-away packages so that they can be maintained at the proper humidity level. For instance, blister type packaging methods could be used. In this connection, the packages can include desiccant material to maintain the proper humidity in the package. In order for a person to use an individual sensor for testing blood glucose, the package must be opened by tearing the seal. Alternatively, some packages require the user to exert force against one side of the package resulting in the sensor bursting or rupturing the foil on the other side. As can be appreciated, the opening of these packages can be difficult. Moreover, once the package is opened, the user needs to be sure that the sensor is not damaged or contaminated as it is being placed into the sensor holder and used to test the blood sample.
U.S. Pat. No. 5,610,986, issued on May 20, 1997, and entitled Dispensing Instrument For Fluid Monitoring Sensors (referred to hereinafter as "the '986 patent"), discloses a type of sensor pack with multiple sensors and a testing blood glucose and dispensing instrument for handling the sensors contained in such a sensor pack. In particular, the sensor dispensing instrument disclosed in the '986 patent is adapted to receive a sensor pack containing a plurality of blood glucose sensors. The sensor pack includes a circular base having a plurality of sensor retaining cavities, each of which hold an individual sensor. Each of the sensors has a generally flat, rectangular shape with a front testing end through which fluid is drawn so as to react with a reagent material in the sensor and an opposite rear, contact end.
The sensor instrument disclosed in the '986 patent includes an outer housing having an upper and a lower case that are pivotable with respect to each other so that the sensor pack can be positioned in the housing on an indexing disk disposed in the housing. With the sensor pack loaded in the housing, a slide latch on a slide actuator disposed on the upper case of the housing controls whether the movement of the slide actuator places the instrument in a display mode or in a testing mode. The instrument is placed into its display mode when the slide latch is moved laterally and the slide actuator is pushed away from its standby position. When in the display mode, a person using the instrument can view data displayed on a display unit in the upper case and/or input data into the instrument.
The instrument is in its testing mode when the slide latch is in its normal position and the slide actuator is pushed towards its testing position. As the slide actuator is moved towards its actuated position, the driver with the knife blade thereon moves toward the testing position of the feed mechanism and the disk drive arm travels in a straight, radially extending groove in the indexing disk such that the disk is not rotated as the feeding mechanism is moving towards its testing position. The knife blade is moved towards one of the sensor cavities in the sensor pack and pierces the foil covering the sensor cavity so as to engage the sensor disposed in the cavity. As the slide actuator and the driver are pushed toward the actuated position of the actuator, the knife blade ejects the sensor out from the sensor cavity and into a testing position near the testing end of the sensor housing.
Once the blood analyzing test is completed, the slide actuator is moved in the opposite direction towards its standby position so that the sensor can be removed from the dispensing instrument. The continued retraction of the driver causes the indexing disk drive arm to travel along a curvilinearly extending groove in the indexing disk, resulting in the rotation of the indexing disk. The rotation of the indexing disk results in the sensor pack being rotated so that the next sensor is positioned in alignment with the knife blade for the next blood glucose test that is to be performed.
Although the sensor instrument disclosed in the '986 patent overcomes many of the problems discussed above in connection with the use of individual sensors, some users have experienced difficulties in the operation and/or manipulation of the disclosed sensor instrument. For example, users with limited dexterity may find the manipulation of the slide latch difficult. As explained above, the slide latch is designed to be manipulated by the user's thumb, and requires the application of a downward pressure that is sufficient to prevent the thumb from sliding on the slide latch while simultaneously applying a lateral pressure sufficient to move the slide latch in back-and-forth direction. In addition, a transverse pressure must be applied to move the slide latch sideways to select between the display mode and the testing mode. Many users, particularly elderly users suffering from diabetes, lack the dexterity or strength in their fingers necessary to manipulate the slide latch.
Similarly, some users may find the operation of the disclosed device complicated or confusing. The device requires the user to select between a testing mode and a display mode. The selection of these modes, however, is not intuitive to the user. To the contrary, the user must read an operating manual supplied with the device, or otherwise receive instructions for the device, to learn how to properly operate the device. Some users, elderly users in particular, may forget how to operate the device. It would then be necessary for these users to review the operating manual or receive additional instructions. Moreover, the complexity of the design may lead to errors in the use of the device.

This patent is subject to a terminal disclaimer.

Sensor dispensing instrument having an activation mechanism and methods of using the same


The invention is an apparatus and method for on-line sorting of waste matter, at the entrance to a waste processing plant, according to the level of specific chemicals, typically chlorine detected therein. The apparatus comprises a waste matter inlet that provides waste matter to a weighing module, preferably until a preset limit is reached. Then, this control volume of waste is introduced into a pulsed neutron material analyzer that is optimized for the determination of the content of the specific chemical in the control volume. A control means such as a computer then decides whether the level of the chemical in the waste control volume is above or below a preset threshold, and accordingly channels the waste into one or another of two channels. One of these channels accepts waste with low content of the given chemical, for introduction into the waste processing chamber. The other channel stores the waste until, for example, it may be mixed with other waste having a sufficient low content such that the overall amount of the chemical is still below the threshold value.

The processing of waste including municipal waste, medical waste, toxic and radioactive waste by means of plasma-torch based waste processing plants is well known.
One problem commonly encountered in the operation of such plants is that of minimizing the production and emission of chlorine containing compounds resulting from the plasma treatment of the waste. Waste, particularly municipal solid waste (MSW), typically comprises a mixture of solid waste which often contains unpredictable levels of chlorine containing materials, for example, PVC pipes, plastic containers, etc. If too large an amount of such materials is processed at any one time in the processing plant, then the level of emission of pollutants containing chlorine may exceed safety and/or legal limits, requiring the plant to be shut down temporarily or alternatively upgrading the gas cleaning system, thus increasing the cost of operation and/or investment of the plant. Further, high levels of chlorine-containing materials may also cause harm to the equipment of the plant, requiring more frequent maintenance operations and may also interfere with the chemical processes that take place during the processing procedure.
Accordingly, it would be advantageous in such plants to monitor the composition of the waste before it is fed into the plant, and to remove from processing, at least temporarily, batches of waste having excessively high chlorine content.
U.S. Pat. No. 3,794,843 relates to a gauge for determining the percentage by weight of moisture contained in a bulk material. U.S. Pat. No. 4,028,267 is directed to an apparatus and method for measuring the concentration of iron in iron ore, by exposing the material to a neutron source. JP 10258428, JP 2002137224, JP 2000126649 and JP 06210632 describe various means for separating or sorting plastics from other material, none of which means makes use of a neutron generator. U.S. Pat. No. 4,702,379 and U.S. Pat. No. 4,830,193, relate to a plant specifically for sorting discrete pieces of gold ore which is irradiated while descending through rotating cylinders in a continuous process.
However, none of these references provides a solution to or in fact even addresses the problems relating to determining the content of chorine-containing materials in waste, particularly for the purpose of removing such waste from subsequent processing in a plasma-torch based processing plant if the amount of chlorine exceeds a predetermined value.
It is therefore an aim of the present invention to provide an apparatus for determining the level of chlorine-containing materials in batches of waste prior to feeding them into a plasma waste converting plant, and a system for separating and processing waste that contains a quantity of chorine-containing material that exceeds a predetermined threshold value.
It is another aim of the present invention to provide such an apparatus and system that may be incorporated into a municipal solid waste processing apparatus.
It is another aim of the present invention to provide such an apparatus and system that is relatively simple mechanically and thus economic to incorporate into a processing plant design.
It is another aim of the present invention to provide such an apparatus and system that is incorporated as an integral part of a plasma-torch based type waste converter.
It is also an aim of the present invention to provide such an apparatus and system that is readily retrofittable with respect to at least some existing plasma-torch based waste converters and other systems for thermal treatment of waste such as incinerators.
Further purposes and advantages of this invention will appear as the description proceeds.

System for controlling the level of potential pollutants in a waste treatment plant

E.E.R. Environmental Energy Resources (Israel) Ltd.


A system and method for carpeting trench headers, including a cover plate having a support flange on the bottom of one lateral edge with a notch therein and an aligned notch in the other lateral edge, a "L" bracket on the longitudinal edges and the lateral edge where the flange is located, carpet on the cover within the "L" brackets, and a tool adapted to the inserted through the slots of adjacent covers to engage the bottom of one cover and lift the cover without disturbing the carpet.

This invention relates to a method of covering utility trenches and in particular, relates to the commercial installation of carpet over a floor which is provided with utility trenches to which access is had for repair or replacement of utility lines. Conventionally, the carpet over such trenches is cut so a flap can be raised to provide access to the trench cover. Because workmen may be careless, this often results in damage to the carpet over the trench and requires frequent replacement of the carpet with attendant costs and mismatches in carpet appearance.
It is a principal object of the present invention to provide a method of carpet installation over utility trenches that results in easy access to the trench and eliminates damage to the carpet over the trench. These and other objects and advantages will become apparent hereinafter.

Carpet system for utility trench and method


A tapered roller bearing assembly includes a one-piece inner ring that has two outer raceways oriented at angles relative to a longitudinal axis and a first outer ring with a first inner raceway and a second outer ring having a second inner raceway. The bearing assembly includes a spacer ring that has an axial width and is positioned around the inner ring and between the first and outer rings. A plurality of rolling elements is in rolling engagement with the first outer raceway and the first inner raceway. A plurality of rolling elements is in rolling engagement with the second outer raceway and the second inner raceway. The axial width is selectively established to obtain a predetermined axial clearance between the inner ring and the first outer ring and the second outer ring.

As shown in FIG. 3, typical spherical roller bearings 100 include an inner ring member 112 have a cylindrical inside diameter surface extending through and an exterior surface consisting of two spherical shaped bearing surfaces 114A and 114B, positioned inside a one piece outer ring 116 having an inside diameter surface of two spherical shaped bearing surfaces 118A and 118B and a cylindrical outside diameter surface. Affixed between the inner ring 112 and the outer ring 116 are two rows of a plurality of spherically shaped rollers 120A and 120B equally spaced and guided by a centrally located cage member 122. It is difficult in some mechanical applications utilizing such prior art spherical roller bearings, to precisely control the axial looseness between the inner ring 112 the outer ring 116 and the plurality of rollers 120A and 120B. Thus operating efficiency cannot be precisely optimized.
In the bearing industry, the geometry of the Tapered Roller Bearings is standardized by American Bearing Manufacturers Association (AMBA) standard.
Based on the foregoing, there is a need to provide a bearing that has the capability of more precisely establishing axial clearance therein.

Double row tapered roller bearing assembly having a two-piece outer ring


An image forming apparatus forms an image on an image forming medium and can form a specific hidden pattern for specifying a body of an apparatus at a predetermined position of the medium. A hidden pattern addition mechanism uses both a software control signal which is generated by software and a hardware control signal which is generated by hardware and must be used for forming the image on the medium as control signals for adding the specific hidden pattern when the specific hidden pattern is added to a specific position of the medium to form the image.

The present invention relates to a color image forming apparatus such as a plain paper copy machine (which will be abbreviated as PPC—Plain Paper Copy machine—hereinafter) or a printer which prints and records on an image forming medium such as plain paper or a transparency (such as an OHP—OverHead Projector—) sheet image data supplied from an image information supplying apparatus such as a personal computer (which will be abbreviated as PC—Personal Computer—hereinafter) or a digital camera or image data read by an image input apparatus. More particularly, the present invention relates to a color image forming apparatus which adds a specific hidden pattern when a color image is formed on the image forming medium.
Here, the specific hidden pattern means a pattern inherent to a color image forming apparatus, with which the color image forming apparatus which has printed using a specific color that is hard to be identified by the naked eye, for example, a color material of yellow can be specified with respect to not only an image that must not be reproduced but all the reproduced images in order to specify a color image reproducing apparatus from the reproduced images printed on a medium even if a specific original which must not be essentially printed (reproduced), e.g., bank bills or marketable securities is printed.
Conventionally, in the image forming apparatus for adding a specific hidden pattern, a hidden pattern must be added in case of inputting a usual original to output an image. In case of outputting a test pattern in a test mode and the like used for, e.g., adjusting the image forming apparatus, however, a problem occurs during adjustment if a hidden pattern using a color material of, e.g., yellow is added. Adding no specific hidden pattern may be convenient in terms of adjustment in some cases. Therefore, when a test pattern is outputted from the image forming apparatus, control is carried out so as not to add a specific hidden pattern.
FIG. 1 is a block diagram showing a structure of a conventional hidden pattern addition mechanism in a color image forming apparatus. In FIG. 1, the conventional hidden pattern addition mechanism is constituted by a specific pattern generation portion 1 for generating a specific pattern; a first register 2 for generating a signal "0x00" (hexadecimal) as an addition prohibition signal directing to inhibit printing a specific hidden pattern on an output image; a second register 3 for generating by software a specific pattern addition signal as a control signal for adding a specific pattern; a selector 4 for respectively inputting the specific pattern signal as an input X, the signal "0x00" as an input Y and the specific pattern addition signal as a selective control input S to supply a specific hidden pattern from an output Q; and an adder 5 for receiving yellow image data as an input A and the output Q of the selector 4 as an input B.
In the conventional hidden pattern addition mechanism shown in FIG. 1, the specific pattern generation portion 1 generates a specific hidden pattern; the register 2 generates by software the signal "0x00" as the addition prohibition signal directing to prohibit printing of a specific hidden pattern on an output image; and the register 3 generates by software the specific pattern addition signal as a control signal. These signals are respectively supplied to the selector 4. The selector 4 selects a signal level of the inputs X and Y based on a signal level of the selected signal and outputs the selected signal to the adder 5. The adder 5 adds, e.g., a yellow signal of the inputted image data as the input A and the output of the selector as the input B to output "A+B" to a printer engine. If a specific pattern for printing a specific hidden pattern is included in the input B, the hidden pattern is printed on the image forming medium at a predetermined position.
In this manner, in the conventional mode by which a hidden pattern is not added only when a test pattern is outputted from an apparatus for adding a specific hidden pattern, a control signal which is set by, e.g., the second register 3 and generated by software is used as a control signal indicating whether a specific hidden pattern is added.
With such a control signal generated by software, however, a problem is necessarily generated even if verification of the software is performed in detail. A specific hidden pattern cannot be added due to this problem when usual printing is made, and an image alone may be possibly printed and outputted.
In such a situation, the image forming operation is an erroneous operation. Further, when a color image forming apparatus is used for precise forgery of bank bills or marketable securities, the image forming medium on which an image having no hidden pattern added thereto is formed getting into circulation is not preferable in the social system and the legal system despite the fact that addition of a hidden pattern is obligate in order to specify an apparatus.


A method and an apparatus for imaging a sample structure (34) with a light microscope are described. The sample structure (34) is prepared with markers and an active marker subset is generated in that a part of the markers is brought into a state in which they can be imaged. When a predetermined activation state is present, the sample structure (34) is imaged onto an arrangement (40) of sensor elements which each generate an image signal, these image signals resulting in a single frame of the sample structure (34). The presence of a predetermined activation state is checked in that at least two test single frames are generated at an interval, and the respective change of the image signal between the two test single frames is detected. The presence of the predetermined activation state is determined when the detected changes of the image signals in their entirety exceed a quantity.

In the recent past, light microscopic imaging methods have been developed with which, based on a sequential, stochastic localization of individual markers, in particular fluorescence molecules, sample structures can be imaged that are smaller than the diffraction-dependent resolution limit of conventional light microscopes. Such methods are, for example, described in WO 2006/127692 A2; DE 10 2006 021 317 B3; WO 2007/128434 A1, U.S. 2009/0134342 A1; DE 10 2008 024 568 A1; "Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM)", Nature Methods 3, 793-796 (2006), M. J. Rust, M. Bates, X. Zhuang; "Resolution of Lambda/10 in fluorescence microscopy using fast single molecule photo-switching", Geisler C. et al, Appl. Phys. A, 88, 223-226 (2007). This new branch of microscopy is also referred to as localization microscopy. The applied methods are known in the literature, for example, under the designations (F)PALM ((Fluorescence) Photoactivation Localization Microscopy), PALMIRA (PALM with Independently Running Acquisition), GSD(IM) (Ground State Depletion Individual Molecule return) Microscopy) or (F)STORM ((Fluorescence) Stochastic Optical Reconstruction Microscopy).
The new methods have in common that the sample structures to be imaged are prepared with markers that have two distinguishable states, namely a "bright" state and a "dark" state. When, for example, fluorescent dyes are used as markers, then the bright state is a state in which they are able to fluoresce and the dark state is a state in which they are not able to fluoresce. For imaging sample structures with a resolution that is higher than the conventional resolution limit of the imaging optical system, a small subset of the markers is repeatedly brought into the bright state. In the following, this subset is referred to as active subset. In this connection, the density of the markers forming the "active" subset is to be chosen such that the average distance of adjacent markers in the bright state and thus in the state in which they can be imaged by a light microscope is greater than the resolution limit of the imaging optical system. The markers forming the active subset are imaged onto a spatially resolving arrangement of sensor elements so that of each marker a light distribution in the form of a light spot is detected whose size is determined by the resolution limit of the optical system.
The present invention relates generally to microscopic imaging. When the density of the markers contained in the active subset is so low that the average distance of the markers, as explained above, exceeds a minimum distance predetermined by the resolution limit of the light microscopic imaging, then a desired activation state is present. This activation state guarantees that each light spot detected by the sensor element arrangement originates from exactly one activated marker.
The above-explained method is illustrated in FIG. 1. In the left-hand side of FIG. 1, a sequence of raw data single frames is illustrated, which are numbered with 1, . . . , N. Each of the light spots imaged in these raw data single frames originates from an active marker subset that is in the desired activation state, i.e. its marker density is so low that it is guaranteed that the average distance of the markers is greater than the minimum distance predetermined by the resolution limit of the light microscopic imaging.
In the upper right-hand part of FIG. 1, a total image is illustrated which results from the superimposition of raw data single frames 1, . . . , N. This total image has a spread-out, spatially non-resolved light distribution which does not reproduce the sample structure to be imaged in detail.
In the lower right-hand part of FIG. 1, a total image is illustrated which results from the superimposition of centroids of the light distributions determined from the raw data single frames. This total image has a much higher resolution so that the sample structure can be well identified in detail—in the present example with its three concentric circular rings.
For quantifying the localization precision which is to be achieved in the above-explained method, reference is made to FIG. 2 in which the situation shown in FIG. 1 is again illustrated merely schematically. In the upper part of FIG. 2, a sequence of raw data single frames is shown. The sample structure to be imaged, which is comprised of concentric circular rings, is illustrated in broken lines in FIG. 2 and is identified with the reference sign 2.
The individual markers of the active subset generate light distributions 4 whose size is determined by the resolution capability of the imaging optical system and is identified with ΔxAbb in FIG. 2. As schematically illustrated in FIG. 2, the markers have an average distance to one another that is smaller than the size ΔxAbb so that the light distributions 4 do not overlap.
In the lower part of FIG. 2, light distributions 6 are shown which result from the light distributions 4 obtained by the centroid determination. The achievable localization precision is given by the size ΔxSP of the light distributions 6. For the localization precision ΔxSP the following applies:
  Δ                  x    SP      α              Δ                                              x        Abb                    n
wherein n denotes the number of photons detected per light distribution 4. The localization precision ΔxSP is typically in a range of about 10 to 50 nm.
Prior to the capturing of a raw data single frame, the above-explained activation state is to be established. From which initial state this activation state is to be established, differs from method to method. Basically, two methods have to be distinguished, namely a method referred to as "bottom-up" method and a method referred to as "top-down" method. In the bottom-up method, at first all markers are in their dark state. The generation of the active marker subset as required for the high-resolution localization is achieved by an appropriate activation, e.g. by irradiation of activation light. This is for example the case for the (F)PALM method. In contrast thereto, in the top-down method at first all markers are in their bright state, i.e. their state in which they can be imaged by a light microscope. For generating the active marker subset, then most of the markers are brought into their dark state, again for example by irradiation of light. Here, the markers can be so-called "switchable" markers, e.g. switchable proteins. Likewise, these markers can, for example, be specific conventional fluorescent dyes which change into long-lived dark states, e.g. triplet states, when irradiated with excitation light (and thus are non-switchable markers in the true sense). For example, the GSD(IM) methods make use thereof.
Both in the bottom-up method and in the top-down method, it is relatively difficult to reproducibly establish the predetermined activation state which only makes the high resolution localization of the individual markers possible. In particular, it is not possible up to now to determine in an easy manner whether this predetermined activation state is present or not. Thus, it often occurs that too many of the markers are in their bright state so that the light distributions generated by the markers are not spatially separated from one another in the raw data single frames. This makes the light microscopic imaging of the sample structure more difficult, in particular the decision when the actual measuring can be started, i.e. when actually only so few markers are still in their bright state that the light distributions generated by the markers have, with a sufficiently high probability, a spatial distribution which makes a separate detection of the light distributions possible.

Method and apparatus for the microscopic imaging of a sample structure


Aspects of the disclosure provide a method of beam failure handling. The method can include performing beam quality measurement of one or more beams transmitted from a base station (BS) at a user equipment (UE) in a beamformed wireless communication system, determining a beam failure occurs based on the beam quality measurement, and performing a beam recovery process that includes at least one of a contention-free beam recovery process or a contention-based beam recovery process. The one or more beams are used for transmitting physical downlink control channels (PDCCHs).

The background description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent the work is described in this background section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present disclosure.
High frequency bands (e.g., above 6 GHz) is used in 5th Generation (5G) wireless communication systems to increase system capacity. Beamforming schemes can be employed to focus transmitted and/or received signal in a desired direction to compensate for unfavorable path loss of high frequency signals. For example, a base station may employ multiple beams to cover a serving area in a 5G system. Accordingly, a user equipment (UE) within the serving area may communicate with the base station using a first set of serving beams while monitoring signal qualities of a second set of candidate beams. When signal qualities of the serving beams fall below a threshold, the UE may switch to qualified candidate beams.

Methods and apparatus supporting beam failure recovery in system with multiple-beam operation