The subject of the invention is a composition comprising (i) from 10% to 25% by weight of 1,1,1,3,3-pentafluorobutane, preferably 16% to 24% by weight of 1,1,1,3,3-pentafluorobutane; (ii) from 62% to 70% by weight of trans-dichloroethylene, preferably from 63% to 68% by weight of trans-dichloroethylene, (iii) from 10% to 21% by weight of nonafluoromethoxybutane, preferably from 11% to 17% by weight of nonafluoromethoxybutane; and; (iv) from 1% to 4% by weight of nonafluoroethoxybutane, preferably from 2% to 4% by weight of nonafluoroethoxybutane. The subject matter of the invention is also to the use of said composition as a cleaning, solvent, degreasing, defluxing or drying agent.

1,1,2-Trichloro-1,2,2-trifluoroethane (F113) has been widely used in industry for cleaning and degreasing highly-varied solid surfaces (metal components, glasses, plastics, composites) for which the absence or at the very least the lowest possible residual content of impurities, in particular of organic origin, is required. F113 was particularly suitable for this use owing to its nonaggressive nature with regard to the materials used. This product was used in particular in the field of the fabrication of printed circuits, for removing the residues of the substances used to improve the quality of the soldered joints (denoted by the term solder flux). This removal operation is denoted in the trade by the term "defluxing".
Mention may also be made of the applications of F113 in the degreasing of heavy metal components and in the cleaning of mechanical components of high quality and of great accuracy, such as, for example, gyroscopes and military, aerospace or medical equipment. In its various applications, F113 is most commonly used in combination with other organic solvents (for example methanol), in order to improve its cleaning capacity.
F113 is also used in fields, in particular in optics, where it is required to have surfaces which are devoid of water, i.e. surfaces where water is only present in trace amounts undetectable by the measurement method (Karl Fisher method). F113 is, for this purpose, used in operations for drying (or dewetting) said surfaces, in combination with hydrophobic surfactants.
However, the use of F113-based compositions is now prohibited since F113 is one of the chlorofluorocarbons (CFCs) suspected of attacking or damaging stratospheric ozone.
Various solutions have been proposed for providing a replacement for F113, but which does not have the problems of destroying the ozone layer or of increasing the greenhouse effect. The greenhouse effect of a given product is quantified by its GWP (global warming potential) which takes into account the intrinsic effect of absorption of radiation by the molecule, but also the lifetime of the molecule in the atmosphere (or what amounts to its concentration for a considered period of time, most commonly one century). This GWP is given with respect to CO2, taken as reference gas.
Document U.S. Pat. No. 6,770,614 describes compositions to replace F113, comprising in particular 1,1,1,3,3-pentafluoro-butane (365mfc), trans-dichloroethylene (tDCE), an ether such as nonafluoromethoxybutane (HFE7100) or nonafluoroethoxybutane (HFE7200), and also methylal and an alcohol. The amount of pentafluorobutane is described as being from 20% to 55, preferably from 25% to 50% by weight. The amount of trans-dichloroethylene is described as being from 40% to 70%, preferably from 53% to 62% by weight. The amount of ether is described as being less than 20%, preferably from 5% to 15% by weight. The minimum amount of methylal and/or of alcohol is not expressly mentioned, but the examples give an amount of approximately 1% by weight for methylal and approximately 1% by weight for the alcohol (isopropanol). The compositions according to that document have the drawback of being inflammable.
Document WO-A-00/36046 describes quite generally mixtures of pentafluoropentane and fluorinated ether, with optionally an organic solvent. Chlorinated solvents, such as trans-dichloroethylene, can be used as organic solvent.
Application WO-A-0056833 is directed toward cleaning compositions. This application describes mixtures of pentafluorobutane, trans-dichloroethylene and nona-fluoromethoxybutane. The amounts proposed (as % by weight) are in particular 1-98/1-64/1-75. Among the examples of such compositions, a mixture containing, as % by weight, 35% of pentafluorobutane, 64% of trans-dichloroethylene and 1% of nonafluoromethoxybutane is indicated. Application US20050267006, which is a continuation of the previous application, specifically claims quaternary mixtures of pentafluorobutane, trans-dichloroethylene, nonafluoromethoxybutane and isopropanol.
There is still a need for a cleaning composition as a replacement for F113, which is preferably more effective than the prior art compositions, in particular with regard to the precision cleaning and/or degreasing of metal components, and which is preferably non-inflammable and advantageously which remains non-inflammable when used in machines.


A process for producing a tube suitable for microfluidic devices. The process uses first and second wafers, each having a substantially uniform doping level. The first wafer has a first portion into which a channel is etched partially therethrough between second and third portions of the first wafer. The first wafer is then bonded to the second wafer so that a first portion of the second wafer overlies the first portion of the first wafer and encloses the channel to define a passage. The second wafer is then thinned so that the first portion thereof defines a thinned wall of the passage. Second and third portions of the second wafer and part of the second and third portions of the first wafer are then removed, and the thinned wall defined by the second wafer is bonded to a substrate such that the passage projects over a recess in the substrate surface. The second and third portions of the first wafer are then removed to define a tube with a freestanding portion.

The present invention generally relates to micromachining processes and devices formed thereby. More particularly, this invention relates to a process of forming a micromachined tube suitable for a microfluidic device.
Processes for fabricating resonant mass flow and density sensors using silicon micromachining techniques are disclosed in commonly-assigned U.S. Pat. Nos. 6,477,901 and 6,647,778. As used herein, micromachining is a technique for forming very small elements by bulk etching a substrate (e.g., a silicon wafer), and/or by surface thin-film etching, the latter of which generally involves depositing a thin film (e.g., polysilicon or metal) on a sacrificial layer (e.g., oxide layer) on a substrate surface and then selectively removing portions of the sacrificial layer to free the deposited thin film. In the processes disclosed in U.S. Pat. Nos. 6,477,901 and 6,647,778, wafer bonding and etching techniques are used to produce a micromachined tube supported above a surface of a substrate. The tube can be vibrated at resonance, by which the flow rate, density, and/or other properties or parameters of a fluid flowing through the tube can be measured.
According to one embodiment of U.S. Pat. No. 6,477,901, a tube is formed using p-type doped layers and selective etching techniques. The doped layers form the walls of the tube, and therefore determine and limit the size of the tube walls as well as the cross-sectional dimensions of the tube. According to another embodiment of U.S. Pat. No. 6,477,901, a tube is formed with the use of a silicon-on-insulator (SOI) wafer. The buried oxide layer of the SOI wafer is used as an etch stop in a manner that determines and can limit the thickness of the tube. Another consideration of this embodiment is the higher cost of SOI silicon wafers as compared to standard silicon wafers. In co-pending U.S. patent application Ser. No. 11/161,901, a process is disclosed by which an epitaxial wafer can be employed to avoid the cost of using a SOI wafer. Though of considerably lower cost than SOI silicon wafers, epitaxial silicon wafers are significantly more expensive than standard silicon wafers.
In view of the above, while well suited for producing micromachined tubes for microfluidic devices, it would be advantageous if other micromachining processes were available that avoid the size restraints of previous processes, as well as potentially simplify processing and reduce cost and processing time.

Process of making a microtube and microfluidic devices formed therewith


A computer-implemented method for recording behavioral information of an unverified component is described. Interactions between a first process and an unverified component loaded in the first process are monitored. A fault is detected from the monitored interactions. Information associated with an event is sent to a proxy module loaded in a second process. The execution of the event in the second process is verified. Information associated with the behavior of the unverified component during the execution of the event is recorded.

The use of computer systems and computer-related technologies continues to increase at a rapid pace. This increased use of computer systems has influenced the advances made to computer-related technologies. Indeed, computer systems have increasingly become an integral part of the business world and the activities of individual consumers. Computer systems are used to carry out several business, industry, and academic endeavors.
A user of a computer system typically interacts with computer software running on the system via a user interface on a screen. Computer software may interact with additional software programs. For example, a host computer program may interact with a computer plug-in application. A plug-in may provide a certain function to the host application on demand. In some instances, the host application provides services which the plug-in can use. For example, the host application may provide a way for plug-ins to register themselves with the host application as well as a protocol for the exchange of data with the plug-ins.
Plug-ins and other components interacting with computer software depend on the services provided by the host application. Open application programming interfaces (APIs) typically provide a standard interface, allowing third parties to create plug-ins that interact with the host application. However, third parties may create malicious plug-ins and other components that impede the performance of the computer software, extract sensitive information about the user of the computer software (e.g., financial information, identification, etc.), and engage in other malicious activities. As such, benefits may be realized by providing improved systems and methods for monitoring and recording the behavior of unknown components (such as plug-ins) as they execute an event. The monitored and recorded behavior may then allow a determination to be made as to whether the plug-in or other unknown component is a malicious or non-malicious component.

Systems and methods for recording behavioral information of an unverified component


In one embodiment, a system includes a network having one or more devices interconnected therebetween, the network including a first device having a first port and logic integrated with and/or executable by a first processor, the logic being adapted to exchange credit exchange (CE) capabilities between the first port and a second port of a second device in the network, receive a credit grant packet from the second port, the credit grant packet indicating credits granted to the first port, and send one or more packets of data from the first port to the second port, the one or more packets corresponding with the granted credits. Other systems and methods for providing credit-based flow control are described according to more embodiments.

The present invention relates to data center infrastructure, and more particularly, this invention relates to credit-based link level flow control and credit exchange using Data Center Bridging eXchange (DCBX).
Ethernet port-based flow control is based on a reactive stop-and-go (on-off) mechanism, called PAUSE, as defined in Institute of Electrical and Electronics Engineers (IEEE) standard 802.3x, which is used only after a receiver's buffer backlog exceeds a certain high watermark, sending a PAUSE (i.e., stop) signal to the sender, and sending an UNPAUSE (i.e., go) signal when the receiver's buffer backdrop drops below a low watermark. To ensure that no frame drops caused by buffer overflow(s) occur, the receiver's high watermark must be set at least one bandwidth-delay product (BDP) below the receiver's buffer capacity, thus increasing buffer size requirements. Moreover, for a given threshold setting, an increase in BDP, e.g., due to installing a longer cable between the sender and the receiver, or due to delayed processing of a PAUSE frame, may lead to unwanted frame drops. These issues are exacerbated by continuously increasing line rates (from the original 10 Mb/s per port up to 100 Gb/s and faster) which leads to increasing BDP. Accordingly, it would be beneficial for Ethernet to adopt proactive reservation-based flow control and frame acceptance schemes with a mechanism to guarantee buffer space at the receiver to ensure absence of frame drops independent of BDP.
Interaction between peer ports before data exchange brings in more certainty and better resource utilization. Ethernet does not have such a mechanism for the purpose of catering to specific applications and convergence of Infiniband over Ethernet.
Therefore, Ethernet installations would benefit greatly from a credit-based flow control mechanism to bring in more certainty for transmission.

Credit-based link level flow control and credit exchange using DCBX

International Business Machines Corporation


Via a tunnel configured on a Virtual eXtensible Local Area Network (VXLAN) Tunnel End Point (VTEP), a notification message is received from a peer VTEP over the tunnel. The received notification message contains VXLAN Network Identifiers (VNIs) of VXLANs currently configured on the peer VTEP. For each of VXLANs currently configured on the VTEP, when the same VXLAN as the VXLAN configured on the VTEP exists in the VXLANs indicated by the VNIs contained in the received notification message and when the VXLAN configured on the VTEP has not been associated with the tunnel, the VXLAN configured on the VTEP is associated with the tunnel.

Virtual eXtensible Local Area Network (VXLAN) is an overlay network technology, in which a message is encapsulated according to a Media Access Control (MAC) in User Datagram Protocol (UDP) method. For example, an initial message may be encapsulated into a UDP message.
A VXLAN Tunnel End Point (VTEP) is an edge device of a VXLAN, and may be implemented by a physical switch or a virtual switch. Any two VTEPs may be connected across a layer 3 network and communicate with each other through establishing a tunnel between them. A VXLAN is identified by a VXLAN Network Identifier (VNI). The length of the VNI may be 24 bits. The VXLAN is implemented through a tunnel. Accordingly, after the VXLAN and the tunnel are configured on the VTEP respectively, the VXLAN should be associated or bundled with the tunnel.

Hewlett Packard Enterprise Development LP


Canceling interference in a multi-input multi-output (MIMO) system is accomplished with a plurality of interference cancellers. Each interference canceller outputs an interference-cancelled received version of its corresponding transmitted signal. An estimate of the transmitted signals from all transmitting antennae is used in each interference canceller. Each estimate is multiplied by a channel coefficient matrix, which can be derived from the communication of known pilot symbols, and the resulting products of each estimate and the channel coefficient matrix are subtracted from the received signals, resulting in a corresponding difference. Each corresponding difference may be multiplied by a filter weight vector. The received signal is decoded based upon the resulting products If a predetermined interrupt criteria is not met, then the decoded signal is used in the preparation of the estimate for a subsequent interference cancellation iteration. The method can be iteratively performed until the predetermined interrupt criteria is met.

1. Field of Invention
The invention relates to the field of telecommunications and more specifically to an iterative soft interference canceller (I-SIC) for use on the receiving side of a multi-input multi-output (MIMO) telecommunications system.
2. Description of Related Art
Widespread use of the Internet motivates the design of more reliable, comfortable and efficient communication systems, especially in the mobile environment due to its portability and convenience. So-called the third generation (3G) systems are being introduced to support several hundred kbps data services in addition to high quality voice message transmissions, and its upgraded version, high-speed downlink packet access (HSDPA), is also under discussion and standardization at the third generation partnership project (3GPP) to offer higher bit rate services. However, achievable bit rate is still limited up to 10 Mbps even when HSDPA utilizes automatic repeat request (ARQ) and adaptive modulation and coding scheme (AMCS). However, user demand for data rate requires approximately 100 Mbps to enjoy streaming video, high-speed Internet connection and so forth, even in a mobile situation.
One known strategy to realize high-speed transmission in the physical layer is the expansion of bandwidth. Atarashi, et al., proposed variable spreading factor orthogonal frequency and code division multiplexing (VSF-OFCDM) which assumes 130 MHz bandwidth to achieve 100 Mbps in outdoor environments. However, this approach requires very high speed digital-to-analog and analog-to-digital converter due to its very high sampling rate. Hence, the power consumption, especially in the user equipment, would become a problem. Another problem is that such a wide bandwidth induces excessive multi-path delay, which makes such a suitable receiver difficult to design and operate.
An alternative approach to increasing the spectral efficiency is to adopt higher-order modulation schemes. In fact, IEEE 802.11a employs 64QAM to realize 54 Mbps with 20 MHz bandwidth for indoor wireless local area network (LAN) systems. However, when we consider application of this scheme in the mobile environment, 64QAM would be no longer efficient because it is less tolerant to interference than QPSK. Moreover, greatly increased transmission power would be required to compensate for its poor error rate performance.
On the other hand, spatial multiplexing techniques, for example, the so-called multi-input multi-output (MIMO) system, have gained much attention recently. Information theory results indicate that the capacity of a MIMO system increases linearly with the minimum of the number of transmit antennas and the receive antennas. In MIMO systems, the most serious problem would be interference from other transmit antennas. Foschini, et al., proposed the Bell Laboratories Layered Space-Time (BLAST) architecture to achieve high-speed wireless transmission and the corresponding detection algorithms that employ interference cancellation and suppression. However, this scheme would not be efficient when combined with error correction coding since processing in the detector and the decoder are separately performed. On the other hand, although the maximum a posteriori (MAP) algorithm is known as optimum when jointly operated for detector and decoder, the computational complexity becomes prohibitive.

Iterative soft interference cancellation and filtering for spectrally efficient high-speed transmission in MIMO systems


Methods for testing the operation of an aircraft braking system utilize the steps of applying a predetermined electrical energy level to an electromechanical actuator attached to a brake assembly, followed by discontinuing electrical energy to the electromechanical actuator. In some test methods, an actuation level of the electromechanical actuator is determined and used to evaluate braking performance. In other tests, a voltage generated by an electric motor in an actuator is measured and used to evaluate braking performance.

Aircraft typically utilize landing gear including one or more wheel assemblies. These wheel assemblies include braking systems which apply braking force to the wheels to assist in decelerating and/or steering the plane during landing or rejected take off (RTO) events. Failure of such braking systems may result in accidents, including runway excursions and collisions with objects, including ground equipment and other aircraft. Undesired and/or uncommanded braking may also result in other aircraft malfunctions.


Method and device for transmitting information between electronic devices, which are able to send and to receive information as well as be in wireless communication connection with each other. In the method an active communication connection is identified and in case the communication connection is active following phases are carried out: the first earlier mentioned electronic device sends automatically the information the user of the earlier mentioned device has chosen as a response to the identified communication connection and the earlier mentioned information is automatically presented by the other electronic device to the user of the other electronic device as a response to the identified communication connection.

Nowadays it is possible to send and receive information, such as text messages during a voice connection with telecommunication devices, such as mobile telecommunication devices operating in GSM-system. Sending text messages during a voice connection is difficult to realize by the user and through text messages there can be given no such additional information that could not be sent as spoken information.
In the future apart from text messages it is also possible to send multimedia with a mobile phone, such as voice and moving pictures. While operation possibilities and various kinds of information transmitting possibilities, for example, are increasing it is important that the use of a telecommunication device is even then easy and simple. This is advantageous especially in case two users of telecommunication devices are in connection with each other and want to share also other information during this communication connection.

Method and device for speeding up and simplifying information transfer between electronic devices


A semiconductor device that can be readily manufactured, can include a large number of pads, and can be thin, and a method for manufacturing the same are provided. The semiconductor device is characterized in that the semiconductor device includes an LSI chip, an insulating layer provided on the LSI chip and made of a nonphotosensitive resin, the insulating layer including a via hole in the position corresponding to an externally connected pad, and a wiring layer extending along the insulating layer through the via hole to the externally connected pad, and at least part of the via hole is formed by irradiating the insulating layer with laser light.

Recently, attention has paid to a semiconductor device called a "substrate with a built-in chip" in which a individually divided LSI chip and the like are buried in a substrate made of resin and the like and a semiconductor device in which an insulating resin layer and a wiring layer are formed on an LSI chip. In semiconductor devices such as a substrate with a built-in chip, it is necessary to bury a chip in a substrate made of resin and the like, then laminate an insulating layer over the substrate, and further form a via hole through the insulating layer to electrically connect an electrode pad on the chip to an external electric terminal and the like.
An example of a method for forming a via hole through an insulating layer includes a method for forming an insulating layer made of a photosensitive resin on a substrate with a built-in chip, exposing the photosensitive resin to light, and developing the photosensitive resin to form a via hole. The mechanical strength of a photosensitive resin is, however, typically so low that the device is often disadvantageously unreliable. Further, many sheet-shaped resin materials used to form the insulating layer are nonphotosensitive resins. Since photosensitive resins are not produced in volume, the use of a photosensitive resin disadvantageously increases the cost.
On the other hand, nonphotosensitive resins are frequently used as sheet-shaped insulating materials used in printed wiring boards and the like. Nonphotosensitive resins are therefore produced in volume, and the use of a nonphotosensitive resin can reduce the cost. When a nonphotosensitive resin is used to form an insulating layer in a semiconductor device with a built-in chip, however, there is a problem of how to form a via hole.
That is, when a nonphotosensitive resin is used, a via hole is typically formed by using a laser beam. In this case, a laser beam passes through the insulating layer made of a nonphotosensitive resin, and an electrode pad located under the insulating layer and made of Al and the like is flied apart by irradiation of the laser beam. As a result, the device including a semiconductor chip is disadvantageously damaged.
To solve such a problem, in the printed wiring technology disclosed in Japanese Patent Laid-Open No. 2003-7896 (FIG. 6), transition layer (A) is provided as a laser stopper layer. The transition layer is comprised of at least two metal layers (33, 36, and 37) and larger than die pad (24) of IC chip (20), which is a semiconductor element. The technology described in Japanese Patent Laid-Open No. 2003-7896 thus allows a laser beam to form a via hole without damage to the die pad (paragraph number (0009)).
On the other hand, in the printed wiring technology described in Japanese Patent Laid-Open No. 2005-332887, stud bump 105 is formed on electrode pad 104 on chip 101, and insulating layer 109 made of epoxy and the like is laminated over the stud bump. A laser machining is then performed to form via hole 110 that reaches the stud bump (FIG. 7).
In this technology, since stud bump 105 serves as a stopper layer in the laser machining, electrode pad 104 will not be directly irradiated with the laser beam. Therefore, the electrode pad is not flied apart by the laser beam, or the device including a semiconductor chip is not damaged (paragraph numbers (0022) and (0062)).

Semiconductor device including an LSI chip and a method for manufacturing the same


The invention relates to an adapter base for receiving electronic test objects (DLTT) comprising an outer group (array) of contact pins (26) that pass through the base from the upper side to the lower side, as well as an inner matrix (38) that consists of contacts (36) that protrude only on the lower side corresponding to an area (28) on the upper side which presents no contacts. Each contact pin (26) is connected to a series connection (30) embodied in the adaptor (24) and constituted by a switching transistor (32), as well as at least one capacitor (34) that via a control signal can be connected and disconnected by means of the gate (G) of the switching transistor (32), the gate being connected to a corresponding contact (36) on the lower side.

1. Field of the Invention
The invention relates to an adapter base for receiving electronic test objects (DUT=device under test), which has an outer group (array) of contact pins led through from its top side to the underside, and also an inner matrix of contacts which are led out only on the underside and to which a region free of circuitry corresponds on the top side.
2. Discussion of the Prior Art
In order to test objects, in particular compact electronic components having a multiplicity of terminals, it is known to clamp these fixedly on a zero insertion force base (ZIF=Zero Insertion Force) which is fixedly connected to a board by its contacts projecting on the underside. The difficulty is that the configuration of the object to be tested varies within a series or from manufacturer to manufacturer, so that only by expending effort and devoting a great deal of time is it possible for the integrated circuit that is to be tested to be connected up in accordance with the requirements. only with the aid of an individually produced transition circuit is it possible for electrical signals and supply voltages to be allocated correctly to the individual contacts.
The invention is based on the object of remedying this and providing an adapter base for receiving electronic test objects which, within an extremely short time, for all the contact pins simultaneously ascertains the electrical contact of the integrated circuit to be tested and performs automatic switching at the contact pins in accordance with the object to be tested, to be precise depending on whether the contact pins are intended to transmit electronic signals or serve as supply contacts.
In the case of an adapter base of the design explained in the introduction, this object is achieved according to the invention by virtue of the fact that each contact pin is connected to a series circuit which is formed in the adapter and comprises a switching transistor and at least one capacitor which, by means of a control signal, can be connected in and disconnected by the gate of the switching transistor, said gate being connected to an assigned contact on the underside.
The fact that each contact pin is connected to additional electronic components (switching transistor and capacitor) affords the possibility, depending on the required operating mode of the contact pin, of transmitting signals or connecting the contact pin to operating voltage or ground. By means of a control signal supplied by a control unit, e.g. computer or PC, the gate of the switching transistor is opened or closed, so that the capacitor is connected in as required.
It is advantageous if two capacitors having different capacitances are provided.
In another embodiment of the invention, the contact pins are designed as spring pins, which ensure a reliable connection between the soldering lands of the board accommodating the components to be tested and the contacts of the adapter base.
If the adapter base has a multilayer hybrid structure, a highly compact design is possible which allows a multiplicity of components to be accommodated in the base. Thus, it is possible for instance to accommodate 225 transistors and 500 capacitors, for example, in a plurality of layers.

Adapter base for receiving electronic test objects


A memory unit with one field line; at least two thermally-assisted switching magnetic tunnel junction-based magnetic random access memory cells, each cell comprising a magnetic tunnel junction having an insulating layer disposed between a magnetic storage layer and a magnetic reference layer; wherein a selection transistor is connected to the magnetic tunnel junction; the one field line is used for passing a field current for switching a magnetization of the storage layer of the magnetic tunnel junctions of the cells. A magnetic memory device can be formed by assembling an array of the memory units, wherein at least two adjacent magnetic tunnel junctions of the cells can be addressed simultaneously by the field line. The memory unit and magnetic memory device have a reduced surface area. Magnetic memory devices with an increased density of memory units can be fabricated resulting in lower die fabrication cost and lower power consumption.

Thermally-assisted switching magnetic tunnel junction (TAS-MTJ) based magnetic random access memory (MRAM) cells have been described in U.S. Pat. No. 6,950,335 and U.S. Patent Application Publication No. US 2006/0291276 A1 while single-line (SL) TAS-MTJ-based MRAM cells have been described in the co-pending U.S. patent application "SYSTEM AND METHOD FOR WRITING DATA TO MAGNETORESISTIVE RANDOM ACCESS MEMORY CELLS," Ser. No. 12/418,747, filed Apr. 6, 2009, which is assigned to the assignee of the present application and the disclosure of which is hereby incorporated herein by reference in its entirety and for all purposes. These typical implementations use one dedicated conductor field line per bit line or per word line.
FIG. 1a shows an implementation of a conventional TAS-MTJ based MRAM cell 1. As illustrated in FIG. 1a, the cell 1 comprises a magnetic tunnel junction 2 formed from an insulating layer 22 disposed between a reference layer 23, having a fixed magnetization, and a storage layer 21, having a magnetization which direction is adjustable at a threshold temperature. The magnetic tunnel junction 2 is placed between a selection CMOS transistor 3 and a bit line 4, represented parallel to the page and connecting the magnetic tunnel junction 2. Also orthogonal with the bit line 4, a field line 5 is placed underneath the magnetic tunnel junction 2. This configuration includes a strap 7 between the bottom of the magnetic tunnel junction 2 and the selection transistor 3.
The writing of the TAS-MTJ-based MRAM cell 1 is performed by heating the magnetic tunnel junction 2 with a heating current 31 that passes through the magnetic tunnel junction 2 via the bit line 4. This is achieved when the transistor 3 is in a conducting mode (ON). Simultaneously (or after a short time delay) and once the magnetic tunnel junction 2 has reached the suitable temperature threshold, a field current 51 is passed through the field line 5, producing a magnetic field 52 capable of addressing the magnetic tunnel junction 2 by switching the magnetization of the storage layer 21, into the appropriate direction. The heating current 31 then is turned off by setting the selection transistor 3 in a cutoff mode (OFF) or by removing the transistor's source-drain bias. The field current 51 is maintained during the cooling of the magnetic tunnel junction 2 and switched off when the magnetic tunnel junction 2 has reached a predetermined temperature, wherein the magnetization of the storage layer is frozen in the written state.
FIG. 1b illustrates a SL-TAS-MTJ-based MRAM cell 10, where the magnetic tunnel junction 2 is disposed between the selection transistor 3 and the field line 5. The field line 5 is shown as being electrically connected to the magnetic tunnel junction 2 on the side of the storage layer (not shown in FIG. 1b). A control current line (not shown) can be used to control the opening and the closing of the transistor 3 in order to address the SL-TAS-MTJ-based MRAM cell 10 individually. The field line 5 of the SL-TAS-MTJ-based MRAM cell 10 can fulfill several MRAM operational functions. First, the field line 5 can fulfill a function of a bit line by passing the heating current 31. The field line 5 likewise can fulfill a function of a field line by passing the field current 51 to produce the magnetic field 52 capable of switching the magnetization of the storage layer in the magnetic tunnel junction 2.
FIG. 2a represents two adjacent TAS-MTJ-based MRAM cells 1 and FIG. 2b represents two adjacent SL-TAS-MTJ-based MRAM cells 10. As shown in FIGS. 2a and 2b, each adjacent TAS-MTJ-based MRAM or SL-TAS-MTJ-based MRAM cell are addressed by a separate field line 5.
A magnetic memory device (not shown) can be formed by assembling an array comprising a plurality of the TAS-MTJ-based MRAM cell 1 or SL-TAS-MTJ-based MRAM cell 10. The array of cells 1, 10 can be disposed within a device package (not shown). When forming the magnetic memory device, the magnetic tunnel junction 2 can be connected on the side of the storage layer 21 to the bit line 4 and on the opposite side to the field line 5, in the case of the TAS-MTJ-based MRAM cell 1. The magnetic tunnel junction 2 is connected on the side of the storage layer 21 to the field line 5, in the case of the SL-TAS-MTJ-based MRAM cell 10. In the case of the TAS-MTJ-based MRAM cell 1, the field line 5 is preferably placed perpendicularly with reference to the bit line 4.
The magnetic memory device usually comprises a current driver (not represented) placed at each extremities of the field line 5 to control the direction of the field current 51. The current driver comprises two or more control transistors (not shown) depending on their configuration. In order to generate a magnetic field 52 able to switch the magnetization of the storage layer 21 in all the magnetic tunnel junctions 2 along the field line 5, the intensity of the field current 51 must be in the order of 10 mA or more. Consequently, current drivers having a large size must be used increasing the surface area of the memory cell array. Since the thickness of the field line 5 cannot be easily increased due to fabrication process limitations, the width of the field line 5 is restricted by the time-to-failure limit of the metallic field line 5 due to electromigration. Moreover, the use of a narrow field line 5 with a high sheet resistance may cause the intensity of the magnetic field 52 to decrease along the field line 5 due to ohmic drop, limiting the number of memory cells 1, 10 being adequately addressed along the field line 5.
In order to minimize the ohmic drop effect along the field line 5, the magnetic memory device can be segmented in sub-arrays (not shown), each sub-array comprising a smaller number of memory cell. This configuration, however, requires an additional driver transistor for every additional field line 5 to drive the current to the appropriate field line 5 for each sub-array. This results in an increased magnetic memory device size and circuit complexity.

Shared line magnetic random access memory cells


Novel amides and imides are inhibitors of tumor necrosis factor.alpha. and phosphodiesterase and can be used to combat cachexia, endotoxic shock, retrovirus replication, asthma, and inflammatory conditions. Typical embodiments include 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-cyclopentyloxy-4-methoxyphenyl)pro pionamide and 3-(1,3-dioxo-4-azaisoindol-2-yl)-3-(3,4-dimethoxyphenyl)-propionarnide.

This invention relates to a method of reducing the level of cytokines and their precursors in mammals and to compounds and compositions useful therein.
In particular, the invention pertains to a class of compounds which inhibit the action of phosphodiesterases, particularly PDE III and PDE IV, and the formation of TNF.alpha. and NF.sub..kappa. B. In a first embodiment, the compounds of the present invention can be diagrammatically represented by the formula: ##STR1## in which: R.sup.5 is:
(i) the divalent residue of pyridine, pyrrolidine, imidizole, naphthalene, or thiophene, wherein the two bonds of the divalent residue are on vicinal ring carbon atoms; PA2 (ii) a divalent cycloalkyl of 4 to 10 carbon atoms, unsubstituted or substituted with one or more substituents each selected independently of the other from the group consisting of nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, substituted amino, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, phenyl or halo; PA2 (iii) di-substituted vinylene, substituted with nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, carbamoyl substituted with and alkyl of 1 to 3 carbon atoms, acetoxy, carboxy, hydroxy, amino, amino substituted with an alkyl of 1 to 3 carbon atoms, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or halo; or PA2 (iv) ethylene, unsubstituted or substituted with 1 to 2 substituents each selected independently from nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, carbamoyl substituted with and alkyl of 1 to 3 carbon atoms, acetoxy, carboxy, hydroxy, amino, amino, substituted with an alkyl of 1 to 3 carbon atoms, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or halo; PA2 (i) cyclic or bicyclic alkyl of 4 to 12 carbon atoms; PA2 (ii) pyridyl; PA2 (iii) phenyl substituted with one or more substituents each selected independently of the other from nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, straight or branched alkyl of 1 to 10 carbon atoms, straight or branched alkoxy of 1 to 10 carbon atoms, or halo; PA2 (iv) benzyl substituted with one to three substituents each selected independently from the group consisting of nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 10 carbon atoms, or halo; PA2 (v) naphthyl; or PA2 (vi) benzyloxy; PA2 (i) the vicinally divalent residue of pyridine, pyrrolidine, imidizole, naphthalene, or thiophene, wherein the two bonds of the divalent residue are on vicinal ring carbon atoms; PA2 (ii) a vicinally divalent cycloalkyl of 4-10 carbon atoms, unsubstituted or substituted with 1 to 3 substituents each selected independently from the group consisting of nitro, cyano, halo, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, substituted amino, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, phenyl; PA2 (iii) di-substituted vinylene, substituted with nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, carbamoyl substituted with and alkyl of 1 to 3 carbon atoms, acetoxy, carboxy, hydroxy, amino, amino substituted with an alkyl of 1 to 3 carbon atoms, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or halo; or PA2 (iv) ethylene, unsubstituted or substituted with 1 to 2 substituents each selected independently from nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, carbamoyl substituted with and alkyl of 1 to 3 carbon atoms, acetoxy, carboxy, hydroxy, amino, amino substituted with an alkyl of 1 to 3 carbon atoms, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or halo;
R.sup.6 is --CO--, --CH.sub.2 --, --CH.sub.2 CO--, or --SO.sub.2 --; PA1 R.sup.7 is PA1 Y is --COX, --C.tbd.N, --OR.sup.8, alkyl of 1 to 5 carbon atoms, or aryl; PA1 X is --NH.sub.2, --OH, --NHR, --R.sup.9, --OR.sup.9, or alkyl of 1 to 5 carbon atoms; PA1 R.sup.8 is hydrogen or lower alkyl; PA1 R.sup.9 is alkyl or benzyl; and, PA1 n has a value of 0, 1, 2, or 3. PA1 R.sup.3 is monocycloalkyl of up to 10 carbon atoms, polycycloalkyl of up to 10 carbon atoms, or benzocyclic alkyl of up to 10 carbon atoms; PA1 X is --CH.sub.2 -- or --O--; PA1 R.sup.5 is: PA1 R.sup.6 is --CO--, --CH.sub.2 --, or --CH.sub.2 CO--; PA1 Y is --COX, --C.tbd.N, --OR.sup.8, alkyl of 1 to 5 carbon atoms, or aryl; PA1 X is --NH.sub.2, --OH, --NHR, --R.sup.9, --OR.sup.9, or alkyl of 1 to 5 carbon atoms; PA1 R.sup.8 is hydrogen or lower alkyl; PA1 R.sup.9 is alkyl or benzyl; and, PA1 n has a value of 0, 1, 2, or 3.
Within this group, Y is preferably --C.tbd.N or --CO(CH.sub.2).sub.m CH.sub.3 in which m has a value of 0, 1, 2, or 3; and
In a second embodiment, the compounds of the present invention can be diagrammatically represented by the formula: ##STR2## in which: one of R.sup.1 and R.sup.2 is R.sup.3 --X-- and the other is hydrogen, nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, lower alkyl, lower alkoxy, halo, or R.sup.3 --X--;
The term alkyl as used herein denotes a univalent saturated branched or straight hydrocarbon chain. Unless otherwise stated, such chains can contain from 1 to 18 carbon atoms. Representative of such alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, and the like. When qualified by "lower", the alkyl group will contain from 1 to 6 carbon atoms. The same carbon content applies to the parent term "alkane" and to derivative terms such as "alkoxy".
The term cycloalkyl as used herein denotes a univalent saturated cyclic hydrocarbon chain. Unless otherwise stated, such chains can contain up to 18 carbon atoms. Monocyclicalkyl refers to groups having a single ring group. Polycycloalkyl denotes hydrocarbon systems containing two or more ring systems with two or more ring carbon atoms in common. Benzocycloalkyl signifies a monocyclicalkyl group fused to a benzo group.
Representative of monocycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, cyclotridecyl, cyclotetradecyl, cyclopentadecyl, cyclohexadecyl, cycloheptadecyl, and cyclooctadecyl. Representative of polycycloalkyl include bicyclo[2.2.1]heptyl, bicyclo[3.2.1]octyl, and bicyclo[2.2.2]octyl. Benzocycloalkyl is typified by tetrahydronaphthyl, indanyl, and 1.2-benzocycloheptanyl.
Tumor necrosis factor .alpha., or TNF.alpha., is a cytokine which is released primarily by mono nuclear phagocytes in response to a number immunostimulators. When administered to animals or humans, it causes inflammation, fever, cardiovascular effects, hemorrhage, coagulation, and acute phase responses similar to those seen during acute infections and shock states. Excessive or unregulated TNF.alpha. production thus has been implicated in a number of disease conditions. These include endotoxemia and/or toxic shock syndrome {Tracey et al., Nature 330, 662-664 (1987) and Hinshaw et al., Circ. Shock 30, 279-292 (1990)}; cachexia {Dezube et al., Lancet, 335 (8690), 662 (1990)} and Adult Respiratory Distress Syndrome where TNF.alpha. concentration in excess of 12,000 pg/mL have been detected in pulmonary aspirates from ARDS patients {Millar et al., Lancet 2(8665), 712-714 (1989)}. Systemic infusion of recombinant TNF.alpha. also resulted in changes typically seen in ARDS {Ferrai-Baliviera et al., Arch. Surg. 124(12), 1400-1405 (1989)}.
TNF.alpha. appears to be involved in bone resorption diseases, including arthritis. When activated, leukocytes will produce bone-resorption, an activity to which the data suggest TNF.alpha. contributes. {Bertolini et al., Nature 319, 516-518 (1986) and Johnson et al, Endocrinology 124(3), 1424-1427 (1989).} TNF.alpha. also has been shown to stimulate bone resorption and inhibit bone formation in vitro and in vivo through stimulation of osteoclast formation and activation combined with inhibition of osteoblast function. Although TNF.alpha. may be involved in many bone resorption diseases, including arthritis, the most compelling link with disease is the association between production of TNF.alpha. by tumor or host tissues and malignancy associated hypercalcemia {Calci. Tissue Int. (US) 46(Suppl.), S3-10 (1990)}. In Graft versus Host Reaction, increased serum TNF.alpha. levels have been associated with major complication following acute allogenic bone marrow transplants {Holler et al, Blood, 75(4), 1011-1016(1990)}.
Cerebral malaria is a lethal hyperacute neurological syndrome associated with high blood levels of TNF.alpha. and the most severe complication occurring in malaria patients. Levels of serum TNF.alpha. correlated directly with the severity of disease and the prognosis in patients with acute malaria attacks {Grau et al., N. Engl. J Med. 320(24), 1586-1591 (1989)}.
Macrophage-induced angiogenesis TNF.alpha. is known to be mediated by TNF.alpha.. Leibovich et al. {Nature, 329, 630-632 (1987)} showed TNF.alpha. induces in vivo capillary blood vessel formation in the rat cornea and the developing chick chorioallantoic membranes at very low doses and suggest TNF.alpha. is a candidate for inducing angiogenesis in inflammation, wound repair, and tumor growth. TNF.alpha. production also has been associated with cancerous conditions, particularly induced tumors {Ching et al., Brit. J. Cancer, (1955) 72, 339-343, and Koch, Progress in Medicinal Chemistry, 22, 166-242 (1985)}.
TNF.alpha. also plays a role in the area of chronic pulmonary inflammatory diseases. The deposition of silica particles leads to silicosis, a disease of progressive respiratory failure caused by a fibrotic reaction. Antibody to TNF.alpha. completely blocked the silica-induced lung fibrosis in mice {Pignet et al, Nature, 344, 245-247 (1990)}. High levels of TNF.alpha. production (in the serum and in isolated macrophages) have been demonstrated in animal models of silica and asbestos induced fibrosis {Bissonnette et al., Inflammation 13(3), 329-339 (1989)}. Alveolar macrophages from pulmonary sarcoidosis patients have also been found to spontaneously release massive quantities of TNF.alpha. as compared with macrophages from normal donors {Baughman et al, J. Lab. Clin. Med. 115(1), 36-42 (1990)}.
TNF.alpha. is also implicated in the inflammatory response which follows reperfusion, called reperfusion injury, and is a major cause of tissue damage after loss of blood flow {Vedder et al., PNAS 87, 2643-2646 (1990)}. TNF.alpha. also alters the properties of endothelial cells and has various procoagulant activities, such as producing an increase in tissue factor pro-coagulant activity and suppression of the anticoagulant protein C pathway as well as down-regulating the expression of thrombomodulin {Sherry et al., J. Cell Biol. 107, 1269-1277 (1988)}. TNF.alpha. has pro-inflammatory activities which together with its early production (during the initial stage of an inflammatory event) make it a likely mediator of tissue injury in several important disorders including but not limited to, myocardial infarction, stroke and circulatory shock. Of specific importance may be TNF.alpha.-induced expression of adhesion molecules, such as intercellular adhesion molecule (ICAM) or endothelial leukocyte adhesion molecule (ELAM) on endothelial cells {Munro et al., Am. J. Path. 135(1), 121-132 (1989)}.
TNF.alpha. blockage with monoclonal anti-TNF.alpha. antibodies has been shown to be beneficial in rheumatoid arthritis {Elliot et al., Int. J. Pharmac. 1995 17(2), 141-145}. High levels of TNF.alpha. are associated with Crohn's disease {von Dullemen et al., Gastroenterology, 1995 109(1), 129-135} and clinical benefit has been achieved with TNF.alpha. antibody treatment.
Moreover, it now is known that TNF.alpha. is a potent activator of retrovirus replication including activation of HIV-1. {Duh et al., Proc. Nat. Acad. Sci. 86, 5974-5978 (1989); Poll et al., Proc. Nat. Acad. Sci. 87, 782-785 (1990); Monto et al., Blood 79, 2670 (1990); Clouse et al., J. Immunol. 142, 431-438 (1989); Poll et al., AIDS Res. Hum. Retrovirus, 191-197 (1992)}. AIDS results from the infection of T lymphocytes with Human Immunodeficiency Virus (HIV). At least three types or strains of HIV have been identified, i.e., HIV-1, HIV-2 and HIV-3. As a consequence of HIV infection, T-cell mediated immunity is impaired and infected individuals manifest severe opportunistic infections and/or unusual neoplasms. HIV entry into the T lymphocyte requires T lymphocyte activation. Other viruses, such as HIV-1, HIV-2 infect T lymphocytes after T cell activation and such virus protein expression and/or replication is mediated or maintained by such T cell activation. Once an activated T lymphocyte is infected with HIV, the T lymphocyte must continue to be maintained in an activated state to permit HIV gene expression and/or HIV replication. Cytokines, specifically TNF.alpha., are implicated in activated T-cell mediated HIV protein expression and/or virus replication by playing a role in maintaining T lymphocyte activation. Therefore, interference with cytokine activity such as by prevention or inhibition of cytokine production, notably TNF.alpha., in an HIV-infected individual assists in limiting the maintenance of T lymphocyte caused by HIV infection.
Monocytes, macrophages, and related cells, such as kupffer and glial cells, also have been implicated in maintenance of the HIV infection. These cells, like T cells, are targets for viral replication and the level of viral replication is dependent upon the activation state of the cells. {Rosenberg et al., The Immunopathogenesis of HIV Infection, Advances in Immunology, 57 (1989)}. Cytokines, such as TNF.alpha., have been shown to activate HIV replication in monocytes and/or macrophages {Poli et al., Proc. Natl. Acad. Sci., 87, 782-784 (1990)}, therefore, prevention or inhibition of cytokine production or activity aids in limiting HIV progression for T cells. Additional studies have identified TNF.alpha. as a common factor in the activation of HIV in vitro and has provided a clear mechanism of action via a nuclear regulatory protein found in the cytoplasm of cells (Osborn, et al., PNAS 86 2336-2340). This evidence suggests that a reduction of TNF.alpha. synthesis may have an antiviral effect in HIV infections, by reducing the transcription and thus virus production.
AIDS viral replication of latent HIV in T cell and macrophage lines can be induced by TNF.alpha. {Folks et al., PNAS 86, 2365-2368 (1989)}. A molecular mechanism for the virus inducing activity is suggested by TNF.alpha.'s ability to activate a gene regulatory protein (NF.kappa.B) found in the cytoplasm of cells, which promotes HIV replication through binding to a viral regulatory gene sequence (LTR) {Osborn et al., PNAS 86, 2336-2340 (1989)}. TNF.alpha. in AIDS associated cachexia is suggested by elevated serum TNF.alpha. and high levels of spontaneous TNF.alpha. production in peripheral blood monocytes from patients {Wright et al., J. Immunol. 141(1), 99-104 (1988)}. TNF.alpha. has been implicated in various roles with other viral infections, such as the cytomegalia virus (CMV), influenza virus, adenovirus, and the herpes family of viruses for similar reasons as those noted.
The nuclear factor .kappa.B (NF.kappa.B) is a pleiotropic transcriptional activator (Lenardo, et al., Cell 1989, 58, 227-29). NF.kappa.B has been implicated as a transcriptional activator in a variety of disease and inflammatory states and is thought to regulate cytokine levels including but not limited to TNF.alpha. and also to be an activator of HIV transcription (Dbaibo, et al., J. Biol. Chem. 1993, 17762-66; Duh et al., Proc. Natl. Acad. Sci. 1989, 86, 5974-78; Bachelerie et al., Nature 1991, 350, 709-12; Boswas et al., J. Acquired Immune Deficiency Syndrome 1993, 6, 778-786; Suzuki et al., Biochem. And Biophys. Res. Comm. 1993, 193, 277-83; Suzuki et al., Biochem. And Biophys. Res Comm. 1992, 189, 1709-15; Suzuki et al., Biochem. Mol. Bio. Int. 1993, 31(4), 693-700; Shakhov et al., Proc. Natl. Acad. Sci. USA 1990, 171, 35-47; and Staal et al., Proc. Natl. Acad. Sci. USA 1990, 87, 9943-47). Thus, inhibition of NF.kappa.B binding can regulate transcription of cytokine gene(s) and through this modulation and other mechanisms be useful in the inhibition of a multitude of disease states. The compounds described herein can inhibit the action of NK.kappa.B in the nucleus and thus are useful in the treatment of a variety of diseases including but not limited to rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, other arthritic conditions, septic shock, septis, endotoxic shock, graft versus host disease, wasting, Crohn's disease, ulcerative colitis, multiple sclerosis, systemic lupus erythrematosis, ENL in leprosy, HIV, AIDS, and opportunistic infections in AIDS. TNF.alpha. and NK.kappa.B levels are influenced by a reciprocal feedback loop. As noted above, the compounds of the present invention affect the levels of both TNF.alpha. and NK.kappa.B.
Many cellular functions are mediated by levels of adenosine 3',5'-cyclic monophosphate (cAMP). Such cellular functions can contribute to inflammatory conditions and diseases including asthma, inflammation, and other conditions (Lowe and Cheng, Drugs of the Future, 17(9), 799-807, 1992). It has been shown that the elevation of cAMP in inflammatory leukocytes inhibits their activation and the subsequent release of inflammatory mediators, including TNF.alpha. and NK.kappa.B. Increased levels of cAMP also leads to the relaxation of airway smooth muscle. Phosphodiesterases control the level of cAMP through hydrolysis and inhibitors of phosphodiesterases have been shown to increase cAMP levels.
Decreasing TNF.alpha. levels and/or increasing cAMP levels thus constitutes a valuable therapeutic strategy for the treatment of many inflammatory, infectious, immunological or malignant diseases. These include but are not restricted to septic shock, sepsis, endotoxic shock, hemodynamic shock and sepsis syndrome, post ischemic reperfusion injury, malaria, mycobacterial infection, meningitis, psoriasis, congestive heart failure, fibrotic disease, cachexia, graft rejection, cancer, autoimmune disease, opportunistic infections in AIDS, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, other arthritic conditions, Crohn's disease, ulcerative colitis, multiple sclerosis, systemic lupus erythrematosis, ENL in leprosy, radiation damage, and hyperoxic alveolar injury. Prior efforts directed to the suppression of the effects of TNF.alpha. have ranged from the utilization of steroids such as dexamethasone and prednisolone to the use of both polyclonal and monoclonal antibodies {Beutler et al., Science 234, 470-474 (1985); WO 92/11383}.
The compounds claimed in this patent inhibit the action of NK.kappa.B in the nucleus and thus are useful in the treatment of a variety of diseases including but not limited to rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, other arthritic conditions, septic shock, septis, endotoxic shock, graft versus host disease, wasting, Crohn's disease, ulcerative colitis, multiple sclerosis, systemic lupus erythrematosis, ENL in leprosy, HIV, AIDS, and opportunistic infections in AIDS.
It is not known at this time, however, how the compounds of the present invention regulate the levels of TNF.alpha., NK.kappa.B, or both. As noted above, the compounds of the present invention affect the levels of both TNF.alpha. and NF.kappa.B.
The compounds can be used, under the supervision of qualified professionals, to inhibit the undesirable effects of TNF.alpha. or phosphodiesterase. The compounds can be administered orally, rectally, or parenterally, alone or in combination with other therapeutic agents including antibiotics, steroids, etc., to a mammal in need of treatment. Oral dosage forms include tablets, capsules, dragees, and similar shaped, compressed pharmaceutical forms. Isotonic saline solutions containing 20-100 milligrams/milliliter can be used for parenteral administration which includes intramuscular, intrathecal, intravenous and intra-arterial routes of administration. Rectal administration can be effected through the use of suppositories formulated from conventional carriers such as cocoa butter.
Dosage regimens must be titrated to the particular indication, the age, weight, and general physical condition of the patient, and the response desired but generally doses will be from about 1 to about 1000 milligrams/day as needed in single or multiple daily administration. In general, an initial treatment regimen can be copied from that known to be effective in interfering with TNF.alpha. activity for other TNF.alpha. mediated disease states by the compounds of the present invention. Treated individuals will be regularly checked for T cell numbers and T4/T8 ratios and/or measures of viremia such as levels of reverse transcriptase or viral proteins, and/or for progression of cytokine-mediated disease associated problems such as cachexia or muscle degeneration. If no effect is observed following the normal treatment regimen, then the amount of cytokine activity interfering agent administered is increased, e.g., by fifty percent a week.
The compounds of the present invention can also be used topically in the treatment or prophylaxis of topical disease states mediated or exacerbated by excessive TNF.alpha. production, such as viral infections, for example those caused by the herpes viruses or viral conjunctivitis, psoriasis, other skin disorders and diseases, etc.
The compounds can also be used in the veterinary treatment of mammals other than humans in need of prevention or inhibition of TNFA production. TNF.alpha. mediated diseases for treatment, therapeutically or prophylactically, in animals include disease states such as those noted above, but in particular viral infections. Examples include feline immunodeficiency virus, equine infectious anaemia virus, caprine arthritis virus, visna virus, and maedi virus, as well as other lentiviruses.
These compounds possess at least one center of chirality and thus will exist as optical isomers. Both the racemates of these isomers and the individual isomers themselves, as well as diastereoisomers when there are two or more chiral centers, are within the scope of the present invention. The racemates can be used as such or can be separated into their individual isomers mechanically as by chromatography using a chiral absorbent. Alternatively, the individual isomers can be prepared in chiral form or separated chemically from a mixture by forming salts with a chiral acid, such as the individual enantiomers of 10-camphorsulfonic acid, camphoric acid, alpha-bromocamphoric acid, methoxyacetic acid, tartaric acid, diacetyltartaric acid, malic acid, pyrrolidone-5-carboxylic acid, and the like, and then freeing one or both of the resolved bases, optionally repeating the process, so as to obtain either or both isomers substantially free of the other; i.e., in a form having an optical purity of >95%.
Prevention or inhibition of production of TNF.alpha. by these compounds can be conveniently assayed using methods known in the art. For example, TNF.alpha. Inhibition Assays can be performed as follows:
PBMC isolation: PBMC from normal donors were obtained by Ficoll-Hypaque density centrifugation. Cells were cultured in RPMI supplemented with 10% AB+ serum, 2 mM L-glutamine, 100 U/mL penicillin and 100 mg/mL streptomycin.
PBMC suspensions: Drugs were dissolved in DMSO (Sigma Chemical), further dilutions were done in supplemented RPMI. The final DMSO concentration in the presence or absence of drug in the PBMC suspensions was 0.25 wt %. Drugs were assayed at half-log dilutions starting at 50 mg/mL. Drugs were added to PBMC (10.sup.6 cells/mL) in 96 wells plates one hour before the addition of LPS.
Cell stimulation: PBMC (10.sup.6 cells/mL) in the presence or absence of drug were stimulated by treatment with 1 mg/nL of LPS from Salmonella minnesota R595 (List Biological Labs, Campbell, Calif.). Cells were then incubated at 37.degree. C. for 18-20 hours. Supernatants were then harvested and assayed immediately for TNF.alpha. levels or kept frozen at -70.degree. C. (for not more than 4 days) until assayed.
TNF.alpha. Determination: The concentration of TNF.alpha. in the supernatant was determined by human TNF.alpha. ELISA kits (ENDOGEN, Boston, Mass.) according to the manufacturer's directions.
Another assay procedure utilizes plates (Nunc Immunoplates, Roskilde, DK) which are treated with 5 mg/mL of purified rabbit anti-TNF.alpha. antibodies at 4.degree. C. for 12 to 14 hours. The plates then are blocked for 2 hours at 25.degree. C. with PBS/0.05% Tween containing 5 milligrams/millilter BSA. After washing, 100 mL of unknowns as well as controls are applied and the plates incubated at 4.degree. C. for 12 to 14 hours. The plates are washed and assayed with a conjugate of peroxidase (horseradish) and mouse anti-TNF.alpha. monoclonal antibodies, and the color developed with o-phenylenediamine in phosphate citrate buffer containing 0.012% hydrogen peroxide and read at 492 nm.
The compounds can be prepared using methods which are known per se. for example, a cyclic anhydride of lactone can be reacted with the appropriate amine: ##STR3## in which R.sup.5, R.sup.6, R.sup.7, Y, and n are as defined above. The reaction can be effected analogously to the methods described in U.K. Patent Specification No. 1,036,694, the disclosure of which is incorporated herein by reference. Optionally acetic acid, with or without sodium acetate, can be added.
In place of the acid anhydride or lactone, one can utilize an N-carbethoxy derivative of the formula: ##STR4##
In a further embodiment, compounds in which R.sup.6 is --CH.sub.2 -- can be formed through condensation of a dialdehyde with a disubstituted aromatic compound in the presence of refluxing acetic acid utilizing the method of Griggs et al., J.Chem. Soc. Chem. Comm., 1985, 1183-1184, the disclosure of which is incorporated herein by reference.
The disubstituted aromatic starting materials can be obtained through condensation of an appropriately substituted aldehyde and malonic acid, with intermediate formation of the amidine and subsequent decarboxylation.
The disubstituted aldehydes can be prepared utilizing classical methods for ether formation; e.g., reaction with the appropriate bromide in the presence of potassium carbonate. Numerous cycloalkyloxy benzaldehydes and procedures for preparing them are described in the literature. See, e.g., Ashton et al., J. Med. Chem., 1994, 37, 1696-1703; Saccomano et al., J. Med. Chem., 1994, 34,, 291-298; and Cheng et al., Org. and Med. Chem. Lett., 1995, 5(17), 1969-1972, the disclosures of which are incorporated herein by reference.
Typical compounds include 3-(1-oxobenzo[f]isoindol-2-yl)-3-(3-cyclopentyloxy-4-methoxyphenyl)propion ic acid, 3-(1-oxobenzo[f]isoindol-2-yl)-3-(3-ethoxy-4-cyclohexyloxyphenyl)propionic acid, 3-(1-oxobenzo[f]isoindol-2-yl)-3-(3-methoxy-4-ethoxyphenyl)propionic acid, 3-(1-oxobenzo[f]isoindol-2-yl)-3-(3, 4-dimethoxyphenyl)propionic acid, 3-(1-oxobenzo[f]isoindol-2-yl)-3-(3-ethoxy-4-cyclopentyloxyphenyl)propioni c acid, 3-(1-oxo-4-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propionic acid, 3-(1-oxo-5-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propionic acid, 3-(1-oxo-4-azaisoindol-2-yl)-3-(3-ethoxy-4-cyclopentyloxyphenyl)propionic acid, 3-(1-oxo-4-azaisoindol-2-yl)-3-(3-methoxy-4-ethoxyphenyl)propionic acid, 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-cyclopentyloxy-4-cyclohexyloxyphen yl)propionamide, 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-ethoxy-4-cyclohexyloxyphenyl)-prop ionamide, 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-methoxy-4-cyclobutyloxyphenyl)prop ionamide, 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)pro pionamide, 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)pro pionamide, 3-(1,3-dioxo-4-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propi onamide, 3-(1,3-dioxo-5-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propi onamide, 3-(1,3-dioxo-4-azaisoindol-2-yl)-3-(3-ethoxy-4-cyclopentyloxyphenyl)propio namide, 3-(1,3-dioxo-4-azaisoindol-2-yl)-3-(3-methoxy-4-cyclobutyloxyphenyl)propio namide, 3-(1-oxobenzo[f]isoindol-2-yl)-3-(3-cyclopentyloxy-4-cyclohexyloxyphenyl)p ropionic acid, 3-(1-oxobenzo[f]isoindol-2-yl)-3-(3-cyclopentyloxy-4-methoxyphenyl)propion amide, 3-(1-oxobenzo[f]isoindol-2-yl)-3-(3-ethoxy-4-cyclohexyloxyphenyl)propionam ide, 3-(1-oxobenzo[f]isoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyl)propionamide , 3-(1-oxobenzo[f]isoindol-2-yl)-3-(3,4-dicyclopentyloxyphenyl)propionamide , 3-(1-oxobenzo[f]isoindol-2-yl)-3-(3,4-dicyclohexyloxyphenyl)propionamide, 3-(1-oxo-4-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propionam ide, 3-(1-oxo-5-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propionam ide, 3-(1-oxo-4-azaisoindol-2-yl)-3-(3-ethoxy-4-cyclopentyloxyphenyl)propionami de, 3-(1-oxo-4-azaisoindol-2-yl)-3-(3-cyclohexyloxy-4-ethoxyphenyl)propionamid e,3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-cyclopentyloxy-4-methoxyphenyl)pr opionic acid, 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-ethoxy-4-cyclohexyloxyphenyl)-prop ionic acid, 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-methoxy-4-cyclohexyloxyphenyl)-pro pionic acid, 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3,4-dicyclohexyloxyphenyl)propionic acid, 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3, 4-dicyclopentyloxyphenyl)propionic acid, 3-(1,3-dioxo-4-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propi onic acid, 3-(1,3-dioxo-5-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propi onic acid, 3-(1,3-dioxo-4-azaisoindol-2-yl)-3-(3-ethoxy-4-cyclopentyloxyphenyl)propio nic acid, 3-(1,3-dioxo-4-azaisoindol-2-yl)-3-(3-ethoxy-4-cyclopentyloxyphenyl)propio nic acid, methyl 3-(1,3-dioxobenzo[flisoindol-2-yl)-3-(3-cyclopentyloxy-4-methoxyphenyl)pro pionate, methyl 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-ethoxy-4-cyclohexyloxyphenyl)propi onate, methyl 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-ethoxy-4-cyclopentyloxyphenyl)prop ionate, methyl 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3,4-dicyclopentyloxyphenyl)propionat e, methyl 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3,4-dicyclohexyloxyphenyl)propionate , methyl 3-(1,3-dioxo-4-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propi onate, methyl 3-(1,3-dioxo-5-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propi onate, methyl 3-(1,3-dioxo-4-azaisoindol-2-yl)-3-(3-ethoxy-4-cyclopentyloxyphenyl)propio nate, ethyl 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-cyclopentyloxy-4-methoxyphenyl)-pr opionate, ethyl 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-ethoxy-4-cyclohexyloxyphenyl)propi onate, ethyl 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3-methoxy-4-ethoxyphenyl)propionate, ethyl 3-(1,3-dioxobenzo[f]isoindol-2-yl)-3-(3, 4-dimethoxyphenyl)propionate, ethyl 3-(1,3-dioxo-4-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propi onate, ethyl 3-(1,3-dioxo-5-azaisoindol-2-yl)-3-(3-methoxy-4-cyclopentyloxyphenyl)propi onate, ethyl and 3-(1,3-dioxo-4-azaisoindol-2-yl)-3-(3-ethoxy-4-cyclopentyloxyphenyl)propio nate.
Representative aldehyde starting materials include 3-cyclopentyloxy4-methoxybenzaldehyde, 3-cyclopentyloxy-4-ethoxybenzaldehyde, 3-cyclohexyloxy-4-cyclohexyloxybenzaldehyde, 3-(exo-bicyclo[2.2.1]hept2-yloxy)-4-methoxybenzaldehyde, 3-(endo-bicyclo[2.2.1]hept-2-yloxy)-4-methoxybenzaldehyde, 3-(bicyclo[2.2.2]oct-2-yloxy)-4-methoxybenzaldehyde, 3-(bicyclo-[3.2.1]oct-2-yloxy)-4-methoxybenzaldehyde, 3-indan-2-yloxy-4-methoxybenzaldehyde, and 3-(endo-benzobicyclo(2.2.1]hept-2-yloxy)-4-methoxybenzaldehyde.


A network connected delivery box includes an input unit for inputting a user code. A communication unit communicates with a computer through the network so that an electrically controlled lock in the delivery box can be opened by a signal from the computer when the input user code matches a valid user code stored in the computer. Also provided is a method of managing purchase and delivery information associated with deliveries to a delivery box by storing, at a central computer, delivery information for each delivery by a delivery company. Aggregate and average delivery information is calculated and presented to a delivery box user to make an informed selection of a delivery company.

1. Field of the Invention
This invention relates to delivery boxes that are connected to a computer network, such as the Internet. These network connected delivery box allows users to receive shipment of items at any time and to a method for providing them. In particular, this invention relates to a network connected delivery box, which may be added or integrated to apartments, houses, offices or buildings and can be opened only with a valid access code. More specifically, this invention relates to a network connected delivery boxes that have a list of valid access codes which can be used to open the delivery box, wherein the delivery person is provided one of the valid access codes. Another feature of this invention relates to network connected delivery boxes that can communicate with a central computer over a network so that a valid user code can be generated and verified at the central computer. The central computer also stores and provides information related to purchase and deliveries of goods using the delivery box.
2. Description of the Related Art
Internet based or electronic commerce is growing dramatically, resulting in a dramatic increase in the delivery of products. For example, virtual grocery stores are satisfying customers' interest in having grocery items delivered to the consumers' home as a new convenience. The customer orders groceries on-line via the Internet or other wireless device or by phone, and a delivery company delivers the items to the consumers' home.
The conventional delivery method is to prearrange a delivery time between the delivery company and the customer and have the items delivered at that prearranged time. However, this conventional method requires the customer to be available in order for the delivery to be completed. Moreover, it causes extreme inefficiencies if the customer is not available at the prearranged time or if too many customers want to select the same delivery time. Therefore, there is a need for a delivery method that obviates the need for the customer to be available for the delivery to be completed.
Also, some items such as food, plants and flowers are perishable, and other items may be temperature-sensitive. Therefore, there is also a need for a delivery method that enables the delivery items to be kept at a desired temperature until the customer finally receives the items. Furthermore, there is a need to control the timing of the heating and cooling of a delivery box to ensure an optimum environment for the delivered goods as well as provide for efficient heating and cooling to optimize energy consumption.
Furthermore, certain items such as expensive goods or pharmaceuticals need to be stored in a secured manner until retrieved by the customer.
There is also a need for a user to access timely information about the quality of service of delivery companies so that a user or a goods provider can make an informed choice about which delivery service to use for a specific purpose.
There is also a need to store and track purchase and delivery information to improve service and customer relationship management related to the purchase and delivery of goods using a delivery box.

Network connected delivery box using access codes and methods for providing same


Provided are composite materials that include a polymeric material and one or more metal organic frameworks intermixed with the polymeric material. A polymeric material may be a block copolymer that is optionally polymerized prior to combination with the metal organic framework. The composite materials are useful for many applications including as sorbents for removal of a chemical, optionally a toxic chemical, from a surface where the surface is contracted with the composite material which reacts with or adsorbs the chemical and is then removed to remove the chemical from the surface.

Metal organic frameworks (MOFs) are a class of materials comprised of secondary building units (SBU), typically made from metal oxide clusters, connected by organic linkers. The resulting structures are an extended, 3-dimensional framework that is often highly porous. Due to the ability to change/tune both the SBU (e.g., changing metal type) and organic linker (e.g., putting functional groups on the linker, using larger/bulkier/longer linkers), an incredible range of structures is possible.
There are multiple sub-groups of MOFs, such as isoreticular MOFs (IRMOFs), UiO-MOFs, MIL MOFs, zeolitic imidazolate frameworks (ZIFs), among others. Typically these groups are based on structural similarities of the MOFs. For example, most of the IRMOFs contain zinc acetate SBUs, and changing the linker results in a wide range of porous structures. IRMOFs in particular are not stable to water, however.
UiO-66-type MOFs are structures originally synthesized at the University of Oslo. Comprised of zirconium based SBUs, this series of MOFs is particularly stable to water as well as acidic conditions. UiO-66 utilizes a terephthalic acid (aka benzene dicarboxylate) linker that can be functionalized with a variety of groups, such as an amine (aka amino) group (herein known as UiO-66-NH2).
Provided herein are new ways of utilizing MOFs as personal protection such as in filtration media or membranes or for detoxifying or decontaminating a surface or fluid including a chemical warfare agent, simulant, other toxic chemical, or other hazardous chemicals such as explosives.

Metal organic framework polymer composites

The United States of America as Represented by the Secretary of the Army


A method of controlling a state of charge of a battery in a vehicle includes receiving a request to enter an enhanced charging mode. A target for the state of charge is increased from a normal operating target to at least one enhanced mode target. The state of charge may be controlled to the at least one enhanced mode target during a drive charging cycle and during a park charging cycle.

Vehicles commonly have an engine and a battery for storing a charge used to start the engine. In hybrid electric vehicles, the battery may also be used to power one or more electric motors. Generally, an idle battery will lose its charge over time. This is generally not a concern for drivers who use their vehicle on a regular basis because almost all vehicles contain a battery charging system to recharge the battery while driving.
But it is possible for a battery to remain idle too long so that it reaches a charge level, known as a state of charge, that is too low to start the engine. For example, a battery in a vehicle parked for many weeks may reach a state of charge too low to start the vehicle. Likewise, a newly manufactured vehicle may be shipped a long distance, such as overseas, allowing the sate of charge of the battery to drop too low to start the vehicle at its destination. Therefore, it may be desirable to increase the time that a battery remains idle yet provides sufficient power to start the engine after that time.
Likewise, some vehicle operations, such as racing a hybrid electric vehicle or providing electrical power to on-board or off-board electrical equipment, require a level of electrical charge greater than that required for normal vehicle operation. Therefore, it may be desirable to increase the amount of power available from the battery for those operations.

Controlling state of charge of a vehicle battery


A device for connecting two drum pedals of a drum includes an outer tube, an inner rod and a resilient strip. The outer tube defines therein an axial hexagonal (tetragonal) hole. A first end of the outer tube forms a recess on a periphery thereof having a plurality of screw holes and a through hole defined from a circumference of the outer tube to the outer surface of the recess. The inner rod is received in the hexagonal hole of the outer tube and defines a cutout in an appropriate position of a circumference thereof. The resilient strip is received in the recess of the outer tube and abuts the inner rod. A first end of the resilient strip has a protrusion integrally extending from one end thereof to be received in the through hole of the outer tube and a second end of the resilient strip is retained by the cutout of the inner rod. With this arrangement, the device for connecting two drum pedals can prevent damage to the inner rod and separation from the outer tube.

1. Field of the Invention
The present invention relates to a device for connecting two drum pedals of a drum and, more particularly to a device for connecting two drum pedals of a drum which can prevent damage to an inner rod and separation from an outer tube thereof.
2. Description of Related Art
Drums have been popular musical instruments for thousands of years all over the world, and the bass drum has become particularly popular in modern music. A device for connecting two drum pedals of a drum is adopted to enable a performer to play the bass drum simultaneously with two feet, thereby leaving his/her hands free to play other drums. A conventional device for connecting two drum pedals of a bass drum generally has a structure as shown in FIG. 6 and FIG. 7. The connecting device includes an outer tube 60 and an inner rod 70. The outer tube 60 has a first end connected with one of two drum pedals via a linkage unit (not shown) which may be a cardan bearing. A second end of the outer tube 60 defines two radial screw holes 61. The outer tube 60 further defines an axial hexagonal (or tetragonal) hole 63 therein (see FIG. 7) for receiving inner rod 70 configured to mate therewith. A distal end of the inner rod 70 is mounted with a flexible sleeve 71 and defines a screw hole 73 therein. The flexible sleeve 71 also has a cardan bearing 72 disposed therein provided for connecting the inner rod 70 to the other of two drum pedals. In assembly, the inner rod 70 is inserted into the outer tube 60 from the second end thereof, leaving its distal end at an outside of the outer tube 60. Then two bolts 62 are respectively screwed into the two screw holes 61 of the outer tube 60 and abutted on a circumference of the inner rod 70, and a screw 74 is screwed into the screw hole 73 for securing the inner rod 70 to the other pedal.
Though this kind of device can connect two drum pedals of a drum, it has several disadvantages. Firstly, when the inner rod 70 is adjusted with respect to the outer tube 60, it may be separated from the outer tube 60 because there is no means for preventing the inner rod 70 from slipping away from the outer tube 60, and furthermore, it is difficult for the inner rod 70 to return to its original position during reassembly. Secondly, a tip portion of the bolt 62 abutting on the circumference of the inner rod 70 may result in damage to the inner rod 70.
The present invention provides an improved device connecting two drum pedals of a drum to mitigate and/or obviate the aforementioned problems.

Device for connecting two drum pedals of a drum


A mobile terminal is provided in the present disclosure. The mobile terminal includes a cover plate, a display screen, a middle frame, an edge frame, and a photosensitive device, where the cover plate is fixedly connected to the edge frame, the display screen is located between the cover plate and the middle frame, a first gap is provided between the display screen and the edge frame, a second gap is provided between the middle frame and the edge frame, and the first gap and the second gap are connected to form an optical channel for the photosensitive device.

With rapid development of mobile terminals, mobile terminals have become an indispensable tool in people's lives, and have brought great convenience to all aspects of users' lives. In the related art, there are some photosensitive devices, such as an infrared sensor or a photosensitive sensor, on a mobile terminal, and different photosensitive devices can implement different functions.
However, a photosensitive device of the mobile terminal in the related art is generally arranged on the front side of the mobile terminal, which limits a screen-to-body ratio of the whole terminal, resulting in a relatively low screen-to-body ratio of the mobile terminal.


Example described herein include a three-dimensional printer a threedimensional printing device that includes a fusible material applicator to apply a layer of fusible material, a inhibiting material applicator to apply a patterned layer of inhibiting material to establish exposed regions of the layer of fusible material and blocked regions of the layer of fusible material based on information corresponding to a three-dimensional model, and a photonic energy emitter to apply photonic energy to fuse the exposed regions of the layer of fusible material.

Three-dimensional printing, otherwise known as "3D printing", involves processes by which a machine transforms machine readable instructions into a three-dimensional physical object. The machine readable instructions often include an electronic or digital model that describes the dimensions and configuration of the physical object. The materials and the corresponding characteristics of the physical object can vary based on the particular process used in the three-dimensional printing process.

Hewlett-Packard Development Company, L.P.


A new and distinct variety of sweet cherry tree which produces large and firm fruit having rich, strong cherry flavor, crisp flesh and which contain large stones of round to round-conic shape. The fruit has exceptionally high levels of soluble solids at ripeness. A seeding of `NY1725`, the tree is particularly characterized as being self-unfertile, late coming into production, but which bears dark, sweet fruit that is resistant to water stress induced cracking. This vigorous tree is of upright branching habit, forms a tall pyramidal figure, and shows resistance to bacterial canker.

This invention is a new and distinct cultivar of sweet cherry `Royalton`, which we discovered in a test planting belonging to the New York State Agricultural Experiment Station, Cornell University, Geneva, Ontario County, N.Y. This discovery is a product of a cherry breeding research program of the New York State Agricultural Experiment Station ("Station").
In 1968 open-pollinated seed from unknown male parent source was gathered from a NY1725 cherry tree growing on `Station` property. This seed was given cold treatment to satisfy its stratification requirement along with other seeds derived from our research. It was planted in Research Field Number D-1 Row-19, Tree-161 on Station grounds. When the tree resulting from this seed bore fruit in 1975 we selected it because it had unique fruit. It was designated NY11390 and grafted in 1976 utilizing two different grafting techniques, topworking and nursery T-budding. One top-worked, grafted tree was constructed by grafting onto NY5389 which become the interstem. This tree was located in the Station research field designated as Lucey in Row 6, Tree 16 (abbreviated as LR6T16). Three grafted trees resulted from "T" budding onto "Mahaleb " rootstocks in the nursery. These were harvested in 1980 and stored in Station tree storage facilities until the spring of 1981 when they were planted in a Station research location designated as Crittenden Number 30, Row 7, Trees 25, 26, and 27 (abbreviated as C30R7T25, T26 and T27). The trees located at LR6T16 and C30R7T25 and T26 subsequently fruited and had research observations taken about their performance on a regular, annual basis, and were identical to one another in all horticultural respects that were noted by the various technicians and faculty scientists who took observations on them. The tree located at C30R7T27 died without providing any important evaluation records. C30R7T25 is still alive and in a sufficiently good state of health to afford useful performance evaluation records. Further trees were propagated by Station technicians in 1984 using plant parts taken from the NY 11390 trees located in LR6T16. These trees were planted in the spring of 1986 in a Station research field designated Lucey Number 50, Row 4, Trees 1 through 7. Other `Royalton` trees from our nursery propagation were distributed during the 1980s to private orchardist-cooperators for the purpose of testing using a restricted distribution test agreement. Trees of NY11390, including a few hundred trees asexually propagated by grafting, in evaluations prior to filing of the patent application herein were consistantly found to be true-to-type and stable in their horticultural traits. Since the patent application was submitted in 1991, vegetative buds of `Royalton` have been provided to commercial fruit tree nurseries, and a breeder-inventor herein has seen commercial orchards of `Royalton` and has seen no change in traits from those that were noted in evaluations prior to the patent application being submitted.


An apparatus and method for exercising whereby the user is supported by various mechanisms in such as way that the user's shoulder area is free to translate and rotate; the user's pelvic area is free to translate and rotate; or in any combination.

1. Field of Invention
This invention generally relates to an exercise device. This invention more particularly relates to an exercise device that closely simulates a free-weight squat movement.
2. Background
Many of a person's daily events require the use of the lower body involving multiple muscle groups across multiple joints. For example, walking, running, climbing stairs, sitting or standing, bending down to pick up a child or an object etc. all involve multiple joint movements. Since these activities mainly involve the lower body and because they all involve multiple muscle groups across multiple joints, the optimal exercise for maintaining or increasing strength for daily activities of living should involve multiple muscles across multiple joints. In addition, most of these activities require balance to prevent tripping and falling. The exercise that most closely mimics or involves all of the same muscle groups and joints while increasing the stability of the body is the squat exercise.
The free-weight squat exercise is an important exercise because it is a triple-extension movement that requires use of multiple major muscle groups (e.g., the quadriceps, hamstrings and hip musculature) over three different joints (e.g., hip, knee and ankle) to operate in unison to complete the movement. The free-weight squat is performed while standing in an upright posture with weight resting over the upper back and shoulders. The ability to move the hips backward is what allows the exercise to incorporate the hip and hamstring muscles. This same movement is what also allows the smaller stabilization muscles of the abdomen, lower back, hip rotators, and calf to be used. Incorporation of so many muscle groups over multiple joints allows a person to increase strength of the entire lower body and is considered the optimal method to strengthen the lower body. The squat exercise also requires the body to use the smaller musculature of the abdomen and back to stabilize the body at the trunk as well as the calf musculature to stabilize the knee and the ankle joints. The use of the smaller stabilization muscles allows an increase in balance creating a more stable base. The squat exercise is safe and effective as long as it is performed correctly. A drawback to the performance of this exercise is that in order to perform it correctly a person needs to be instructed by a knowledgeable professional who can train them on the proper technique for the performance of the exercise and carefully watch them over multiple sessions to ensure the technique is continually performed correctly. The squat movement also allows for large amounts of weight to be lifted while performing the exercise. If a person were to perform the exercise incorrectly or fall, the weight could cause injury to the person. Since this exercise requires so many muscle groups across three separate joints, there is a wide margin within which a person could perform the technique incorrectly resulting in injury, if not properly instructed or supervised.
Many different types of leg exercise devices have been developed for use in the field of strength training, physical therapy and rehabilitation, and the like. More particularly, many different types of leg exercise devices that attempt to simulate a free-weight squat movement have been developed. These different types of leg exercise devices may be organized into two primary groups. The first group of devices utilizes an immovable upper back and shoulder support sled guided along two support rails. See U.S. Pat. No. 4,535,985 to Mask, U.S. Pat. No. 5,263,913 by Boren, and U.S. Pat. No. 5,941,803 by Chamberlain, et. al. Generally, in these devices, the user will push his/her feet against a foot plate thereby moving the user's upper back and shoulders on a sled along a fixed longitudinal axis defined by the device's support rails. In these devices, the only degrees of freedom allowed are flexion and extension of the user's hips, knees, and ankles. These devices do not allow the pelvis to translate freely out of plane as in a classic free-weight squat movement. Since the user's shoulders and pelvis cannot move independently, the squat motion performed does not recruit the user's back musculature to stabilize the user's upper torso. The second group of devices utilize curved path defined by a track frame. See U.S. Pat. No. 4,176,836 to Coyle and U.S. Pat. No. 5,411,458 to Giust. There are two major constraints inherent in the second group of devices. The first major constraint is that the user's pelvis, back, and shoulders, are all supported by the same rigid sled. The user's pelvis cannot move independently from the user's shoulders and thus the user's back musculature is not recruited to stabilize the user's upper body. The second major constraint is that the rigid sled is required to move along a predefined path defined by the track system. As a result, the user's upper body and leg joints are prevented from assuming the user's natural positions and form, which are inherent in a free-standing squat movement in which the user's upper body is free to move to whatever positions achieves a natural balance with respect to the user's feet. Another constraint of these devices is that they do not provide a means whereby a resistive force can be applied along the line of action perpendicular to the plane defined by the foot plate. In other words, these devices do not show how a resistive force can be applied along the same line of action with respect to that body as would be the case with gravity acting on a weighted barbell, as in a free-standing squat movement.
The present invention seeks to provide an apparatus that supplies additional advantages over the prior art and takes into account the aforementioned considerations.

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


Liquid-dispensing systems that include integrated aeration systems to aerate a liquid while the liquid is being dispensed are described. Integrated aeration systems enable seamless aeration of a liquid during dispensing. In one aspect, a liquid-dispensing system includes a liquid-conditioning dispenser with an integrated aeration system composed of one or more channels that convey a fluid to mix with a liquid as the liquid is dispensed. The aeration system also includes an aeration switch used to open and close the channels and regulate the amount of the fluid that mixes with the liquid. The liquid-dispensing system also includes a pump and control system to apply pressure on a reservoir that contains the liquid. The pressure forces the liquid from the reservoir to the dispenser via a liquid supply line.

Aeration is a process by which air is circulated through, mixed with or dissolved in a liquid or substance. Various aeration techniques have been used to oxidize, reduce, evaporate or change certain compounds found in liquids. For example, tannins are the chemicals that make wine astringent. In older wines, tannins break down in the bottle as the wine ages, but in younger wines tannins can mask some of a wine's more delicate and sought after flavors. Aerating a younger wine for a period of time causes the tannins to break down and lessens the astringency. Although most wines improve with as little as 15-20 minutes of aeration time, young wines typically have high tannin levels and may need more time to aerate before enjoying. For example, a young cabernet sauvignon may need about an hour of aeration for flavor softening. Aeration can also be used to evaporate other volatile and undesirable compounds in a beverage while retaining desirable ones. In particular, there are a number of compounds that are reduced with aeration, such as sulfites, which are added to certain beverages to prevent oxidation and microbial activity but produce unpleasant smells.
Typical approaches to reduce aeration time include use of fountains, cascades, paddle-wheels or cones. However, these aeration devices are often inconvenient to use, require additional expense and clean-up time, and cannot be fine tuned to provide a desired level of aeration. For example, dispensing a boxed wine with a typical aerator requires one hand to hold a glass, another hand to press the dispensing button on a spigot, and a third hand to hold an aerator located between the glass and the spigot, which is inconvenient for practical use. As a result, beverage distributors and manufactures continue to seek systems that enable convenient beverage aeration, control over the amount of air a beverage is combined with and reduce the aeration time.

Liquid-dispensing systems with integrated aeration