An impeller (1) for an axial flow fan comprises a hub (2) supporting the blades (3). The hub (2) has bores (5) in its peripheral surface, whereby each bore (5) has a first radially inner section (10) with larger diameter than a second radially outer section (6). Each blade (3) has a substantially circular foot section (4) allowing adjustment of the blade pitch. Mach blade foot section (4) is mounted in a corresponding bore (5) by means of two connecting plates (8, 9) which in the first bore section (10) are spaced apart and face each other along substantially the entire diameter of the bore (5).

The present invention relates to an impeller for an axial flow fan comprising a hub supporting the blades, the hub having bores in its peripheral surface, whereby each bore has a first radially inner section with larger diameter than a second radially outer section, each blade having a substantially circular foot section allowing adjustment of the blade pitch, each blade foot section being mounted in a corresponding bore by means of connecting plates engaging with a shoulder between the two bore sections.
In conventional axial flow fans of this type the blade foot section is clamped against six connecting plates, each of which constitutes a segment of a circular disc, the segments being arranged in the bore in spaced relationship in order to permit mutual displacement by insertion and removal of the plates from the bore section. At the centre of the arrangement of the segments the borders of the segments jointly form a circular hole, in which a retaining ring is fitted in a groove at insertion of the segments in order to keep these in place while mounting the blade foot section and especially during subsequent rotation of the foot section in the bore for adjustment of the blade pitch. The connecting plates are pressed against the shoulder in the bore by means of a spring placed in the central hole. However, by the known fans, it is a disadvantage that the blade foot section in certain cases may have a tendency to lock in its corresponding bore in the hub, thereby impeding adjustment of the pitch.
The object of the invention is to provide an impeller of the type described in the introduction, whereby the above mentioned problem is remedied, and whereby at the same time a solid connection between the blade and the hub is obtained.
In view of this object, the impeller according to the invention is characterized in that each blade foot section is mounted by means of two connecting plates which in the first bore section are spaced apart and face each other along substantially the entire diameter of the bore.
By arranging two larger connecting plates in this way, instead of using six smaller in the conventional way, the connecting plates are far less inclined to tilt by rotation in the bore and thereby impede adjustment of the blade in relation to the hub. Furthermore, the larger plates provide sufficient space for the provision of more than one bolt in respect of each plate for clamping the blade foot section against the plate. This further reduces the tendency of the plates to tilt in the bore, thereby also facilitating the adjustment of the blade pitch. Moreover, the contact surface between the connecting plates and the shoulder in the bore may in this way be constituted by two relatively long continuous areas, as opposed to six discretely arranged small areas in the prior art impellers. The more uniform structure of the total contact area between the connecting plates and the shoulder provides less frictional force by rotation of the blade foot section. Furthermore, a much more uniform stress distribution may be obtained in the hub around the respective bores, as well as in the foot section of the blade, against which the connecting plates are clamped, this resulting in a considerably stronger connection between blade and hub.
In an advantageous embodiment very simple to manufacture the connecting plates have sections, the periphery of which extend substantially along a circle having a diameter larger than that of the second bore section in the hub, and the largest dimension of each plate is shorter than the diameter of said bore section. In this manner, a uniform, continuous contact surface is obtained between the connecting plate and the shoulder in the corresponding bore, thereby providing a further improved stress distribution, especially in the hub material surrounding the bore. In addition, the two connecting plates necessary for mounting one blade can be machined by turning one circular disc, cutting it through diametrically, thereby removing sufficient material for provision of the space necessary between the two plates in their mounted position, and eventually, if necessary, cutting off the extreme tips to allow the plates to enter through the second bore section.
In a further advantageous embodiment, a radial clearance is provided between the periphery of the connecting plates and the first bore section. In this manner, adjustment of the blade pitch may be further facilitated in that tilting of the connecting plates during rotation of the blade cannot cause engagement between the periphery of the connecting plates and the wall material of the first bore section.
A blade shaft projecting from the blade foot section may be clamped against an elastic member located in the bore under the connecting plates. By providing the elastic member under the connecting plates, the member does not take up any space between the plates, and no cutout or other reduction of the plate material, which would reduce its strength, is required.
The elastic member may have the form of one or more disc springs located in a hole in the bottom of the bore in the hub, which hole may have substantially the same diameter as the outer diameter of the springs. In this manner, the elastic member is kept in place when mounting the blade, possibly further by a retaining ring mounted in the hole.
The present invention also relates to a blade connecting means for mounting an impeller blade on a hub for an axial flow fan, the connecting means comprising connecting plates adapted to be clamped against a foot section of the blade and engage in a corresponding bore in the hub with a shoulder between a first radially inner bore section with larger diameter than a second radially outer bore section. According to the invention, the blade connecting means is characterized in that there is provided two connecting plates which are adapted to be mounted in the first bore section spaced apart and facing each other along substantially the entire diameter of the bore.
The invention further relates to a blade for an axial flow fan comprising the above described blade connecting means.
The invention also relates to a method of mounting a blade on a hub for an axial flow fan, whereby a blade foot section is clamped against connecting plates located in a corresponding bore in the peripheral surface of the hub, and the connecting plates are caused to engage with a shoulder between a first radially inner bore section with larger diameter than a second radially outer bore section. According to the invention, the method is characterized by clamping the blade foot section against two connecting plates which are spaced apart and face each other along substantially the entire diameter of the bore.
The connecting plates may be positioned in such a manner that the periphery of sections of the plates extend substantially along a circle having a diameter larger than that of the second bore section in the hub, and each of the plates utilized may have a maximum dimension that is shorter than the diameter of said bore section.
The connecting plates may be positioned in such a manner that a radial clearance is provided between the periphery of the connecting plates and the first bore section.

Impeller for an axial flow fan and a method of mounting a blade on a hub for such fan


A module includes a semiconductor chip having at least a first terminal contact surface and a second terminal contact surface. A first bond element made of a material on the basis of Cu is attached to the first terminal contact surface, and a second bond element is attached to the second terminal contact surface. The second bond element is made of a material different from the material of the first bond element or is made of a type of bond element different from the type of the first bond element.

Various techniques are available to electrically connect a semiconductor chip in a module to external terminals of the module. For example, clip-bonding, ribbon-bonding or wire-bonding are techniques known in the art. Further, various different materials have been used for the bond element, among them Al, Cu or Au. The selection of the bonding technique may have a significant impact on the overall manufacturing costs and performance of the module.


A membrane-based assay device, methods and kits for determining the presence or quantity of an analyte in a test sample are provided. The immunochromatographic device comprises a membrane having a capture antibody bound thereto at a test zone, wherein the capture antibody is capable of binding with an analyte, in particular a Z-AAT protein present in a sample from a PiZ gene carrier.

Various analytical procedures and devices are commonly employed in flow-through assays to determine the presence and/or concentration of analytes that may be present in a test sample. Lateral flow tests, also known as lateral flow immunochromatographic assays or lateral flow assays (LFAs), are commonly used in point-of-care (POC) devices for medical diagnostics, for example. Individual assay layouts are adapted to a particular application.
Alpha-1 Antitrypsin Deficiency (AATD) is a hereditary disease, which can be diagnosed by genetic testing. However, AATD is under-diagnosed and only 10-15% are identified. Unidentified patients are sometimes misdiagnosed as "usual" chronic obstructive pulmonary disease (COPD) and Asthma, respectively.
A need still exists for an effective lateral flow assay for determining the presence of an analyte, in particular a Z-AAT protein.

This patent is subject to a terminal disclaimer.

Immunochromatography devices, methods, and kits


A card and foldable currency carrying device is described. The device is made up of a substantially rectangular wallet assembly with a plurality of panels. The panels make up a compartment for holding one or more cards, including credit cards, debit cards, ATM cards, gift cards, driver's licenses, identification cards, library cards, and business cards, as well as foldable currency. The device also contains a strap member. The strap member is slidable along the wallet assembly between a first position and a second position.

The present invention is directed towards a slim wallet and card holder device for holding foldable currency, credit cards or identification cards in a convenient, easy to use arrangement.
Previously, money clips have been used to hold folded currency and are designed to be carried in a pants or jacket pocket or other area. These money clips are fashioned from a single piece of bent or formed metal stock generally in the form of a spring clip and are available in a variety of materials. The money clip is currently not as widely used as it has been in the past, possibly due to the widespread use of credit cards and the accompanying need to conveniently and securely carry credit cards as well ATM cards, bank cards, business cards, access cards, gift cards, multi-tools, driver's licenses and other identification cards. Most money clips do not adequately accommodate cards, and those that do hold cards often pose the disadvantage of added weight and bulk caused by the need for a heavy spring attachment to hold the cards in place. While money clips are a convenient way to carry folded money, they do not work very well in carrying credit cards, driver's licenses or the like because the items tend to fail out of money clips or are bent, scratched, broken or destroyed by the money clip while being carried or removed.
Wallets are also used for carrying credit cards and foldable currency and can be carried in the user's front or rear pocket. However, wallets can be bulky and in some instances uncomfortable when the wearer is driving long distances or sitting for long periods of time. Additionally, wallets can be clearly visible in the user's pocket and can be a target for a thief. Furthermore, over time, when contents are are added and removed from a wallet, the wallet material stretches but doesn't retract when contents are removed, resulting in the contents falling out.
Thus, there is a need for a device that can accommodate foldable currency as well as credit cards, ATM cards, bank cards, business cards, access cards, gift cards, multi-tools, identification, and similar sized items. It is also contemplated that the device can be sized to accommodate a passport. The device is capable of being carried in any pocket and also be capable of carrying several credit cards and a quantity of foldable currency. The present invention is directed towards a such a device for carrying a number of credit sized cards, identification cards and foldable currency in a convenient, easy manner in a user's pants pocket, shirt pocket or the like.


A flag, or marker for identifying the locations of a plurality of tissue cassettes containing mounted Formalin Fixed Paraffin Embedded (FFPE) tissue specimens once removed from a tissue cassette/block storage system. The invention comprises a rectangular cuboid body member having front, rear, left, right, top, and bottom surfaces which substantially approximates the shape of a predefined number of tissue cassette/blocks, with a recessed area with grooves to accept one tissue index marker card for recording the patient's case information, or other relevant information. When multiples of the present invention are used within a tissue cassette/block storage system, they point to locations where pluralities of tissue cassette/blocks should be returned, and provides a support structure for neighboring tissue cassette/blocks within the storage location from becoming askew or damaged within the tissue cassette/block storage system.

Within the field of Pathology, Formalin Fixed Paraffin Embedded (FFPE) tissue blocks or more commonly known as "tissue blocks", refers to the process of preserving human or animal medical tissue specimens by exposure to Formaldehyde solutions, followed by embedding the preserved tissue into a block of paraffin wax. FFPE tissue blocks are utilized far and wide in the diagnosis and treatment of diseases.
The method of producing FFPE tissue blocks, or "tissue blocks", from excised tissue samples is a complicated, and time consuming process, and is beyond the scope of this application; however a brief description is required for an understanding of the invention presented herein. Within the medical industry a human patient who undergoes a biopsy procedure has a sample of tissue excised, or removed from their personage. Biopsy samples are sent to Pathology laboratories where laboratory staff dissect these tissue samples in order to maximize the exposure of a particular abnormality, or point of interests in the tissue. The tissue samples are then cut down to fit within tissue cassettes. These cassettes are small plastic boxes with attached lids, and small holes incorporated into the body of the cassettes to allow chemicals to flow throughout the internal cavities, and bathe the tissue with specific chemicals. At some point the patient's data is written or "engraved" onto the plastic base cassette with all the relevant medical information for future reference. The tissue cassette lid is closed, and the cassette is immersed into Formaldehyde solution baths to inhibit putrefaction, or autolysis, and to maintain the proteins and structural integrity of the tissue. Groups of these tissue cassettes are placed into a "vacuum infiltration" processor (VIP) machines, that processes the tissue samples with heat, and vacuum, to dehydrate, and then re-hydrates the tissue by replacing water with molten paraffin wax inside the samples. This process can take several hours and these machines are often computer controlled, which does not require human intervention. When the tissue samples have been sufficiently re-hydrated they are removed from the VIP machines. The plastic cassettes are opened and the tissue sample is inserted into a metal mold, and orientated to maximize the exposure of the tissue's point of interest during the Microtomy procedure. The empty space within the mold is filled with additional molten paraffin to entomb the tissue sample inside a block of paraffin. This process is known as "embedding" the tissue sample. Lastly, the lids are removed from the plastic cassettes and discarded, the base cassette is inserted on top of the corresponding molded tissue, and additional paraffin is added to the cassette to lock the molded "block" onto the plastic base cassette. Once the tissue samples have been "embedded" the process continues to microtomy where microscope slides are created, and then stained to highlight the tissue's structural detail. These microscope slides are reviewed by medical personnel via microscopy procedures, at which point a determination is made to the course of treatment required for a particular patient.
By virtue of the patient's lives affected, and the uniqueness of each tissue biopsy, all are irreplaceable. Medical facilities are governed by rules and regulations, in which every single tissue block must be accounted for. Hence, complicated storage, filing, and tracking systems are implemented to account for every tissue block. By utilizing industry standards, or agreed upon classification systems, once a tissue block has been processed and a medical determination has been made to the patient's course of actions, the tissue blocks are filed into a tissue block storage system for long term storage, future reference, or referrals.
Within prior art the preferred method of storing tissue blocks for long term storage is laterally within drawers/cabinets or in box type containers providing vertical orientation, whereby the blocks are inserted standing on one end of the plastic cassette within the drawer or box. The tissue blocks are positioned front to back within rows, drawers, or containers. The vertical orientation provides quick viewing of specimen data printed on the plastic cassette and easy access and retrieval of the tissue blocks.
When tissue blocks are inserted into block storage systems the physical inclination of unsupported tissue blocks are to fall forward, or backwards, depending upon gravity, and other forces. A standard practice is to insert pieces of closed cell foam between, or behind, the tissue blocks to provide support, or prevent the tissue blocks from laying down flat, or reclining upon a neighboring tissue block. A multitude of tissue blocks are required to fill the entire drawer row.
As with all storage systems, medical librarians withdraw a plurality of tissue blocks from their respective locations to further process additional specimen for microscopy review, or as part of outside pathological consultation or review. The length of time that these tissue blocks remain withdrawn depends upon what action is being pursued in the course of care. Traditionally, when tissue blocks are removed from their storage system, the librarian transcribes the particular specimen information onto a block index marker card, and it is inserted into the area from whence the tissue blocks were removed. These block index marker cards are made from card stock paper or paper board, and may incorporate pre-printed lines for recording the particular patient's case information or the destination of the tissue blocks removed for future reference.
The plastic tissue cassettes detailed above are produced in multitudes of variations in size, form, and designs. All tissue cassettes have a base cassette with a corresponding lid either attached or separate. The standard tissue cassette measures 41×30×6 mm, or 1⅝″×1⅛″×¼″, and is offered in a plurality of color, and function. Standard tissue cassettes are used with the typical biopsy, or dissected tissue specimen, because of the number and size of the slots, which measure 1×5 mm per slot with a total of 128 slots within each base cassette. The lid also incorporates these same slots within its member. These slots are designed to allow the reagents to flow in and around the tissue specimen during the Vacuum Infiltration process. The slots also offer a lattice structure to support the specimen during the Microtomy process. Other cassettes offered are biopsy, and compartment cassettes each offering their own features used during the infiltration process. Mega-Cassettes are another cassette used within the medical industry. As the name implies, these cassettes are for much larger tissue specimens, and offer the same features as a standard tissue cassette. All cassettes are produced in myriads of colors to allow the laboratory technician to discern different specimens or processing procedures.

Tissue cassette/block file position flag and method related thereto


A system for supplementing a fixed fuel source for an engine includes a motor-generator set connected to a mechanical load device and a controller. The motor-generator set includes a motor and a generator. The engine is configured to provide a first torque from a fixed fuel source from an independent variable flow input. The fixed fuel source is independent of the engine and set external to the engine. The mechanical load device is driven by the engine and configured to require a second torque defined by an independent flow device. The controller is configured to compare the first torque and the second torque, provide a first control signal to the motor to provide power to the engine when the second torque exceeds the first torque and provide a second control signal to the generator to draw power from the engine when the first torque exceeds the second torque.

An engine combusts fuel to convert energy stored in the fuel to mechanical energy. The fuel is mixed with air to create a combustible mix. A throttle controls the air flow rate into the engine. The throttle may include a valve between the air intake filter of the engine and the manifold of the engine. As more air is provided to the engine, more fuel is mixed with the air to provide a consistent air-fuel ratio, and the engine provides more power.
Typically, the fuel is provided to the engine as needed. That is, the throttle regulates the amount of air and thus, by ratio, fuel entering the engine according to the demands placed on the engine or operation by the user. However, in some instances, the engine may be supplied with a source of fuel that cannot be regulated. The fuel is supplied to the engine by another source and the engine must combust all of the supplied fuel.
In order to combust all the supplied fuel, the engine power output must vary independently of the speed characteristics of the engine. One mechanism to accomplish this involves operating the engine in synchronous operation with a power grid, setting the speed of the engine and allowing for variable power. Challenges remain in operation of an engine under a fixed fuel source.

Motor generator control for fixed fuel source engine


An apparatus for simultaneously producing both high and low purity oxygen, which contains a double rectification column having therein a lower pressure fractionating column with two reboilers therein, and a higher pressure fractionating column, wherein an intermediate outlet is provided between the two reboilers of the lower pressure fractionating column for extracting a lower purity oxygen stream therefrom, and a high purity liquid oxygen stream from a bottom portion of the column simultaneously.

1. Field of the Invention
The present invention relates to a process for the mixed production of high or low purity oxygen using a double reboiler and double column arrangement.
2. Description of the Background
The double reboiler and double column process was developed to produce relatively low purity oxygen at purities below 97% oxygen content. This process is described in U.S. Pat. No. 3,113,854 and in the Electric Power Research Institute (ERPI) Study 3499. Additionally, U.S. Pat. No. 4,895,583 discloses a modification of an earlier process in order to improve the overall recovery of oxygen.
Another example of a conventional double column and double reboiler process for producing relatively low purity oxygen is that disclosed in U.S. Pat. No. 4,705,548. However, this process is disadvantageous as it requires the use of a compressor for nitrogen recycling.
Attempts to produce high oxygen purities, such as above 97% oxygen content, using the double reboiler and double column methodology have not been considered interesting due to the sharp reduction in process efficiency and loss of recovery which is entailed. These drawbacks occur because it is necessary to perform the very difficult argon/oxygen separation by cryogenic distillation for oxygen contents of higher than 97%.
At present, in order to obtain an oxygen content of greater than 97%, the single reboiler, double column process is usually used. Unfortunately, this process has a much higher specific power consumption than the double reboiler and double column process.
It would be extremely advantageous if a process were known for producing oxygen at both low and high purity. Frequently, an on-site oxygen facility may produce a gaseous oxygen product at 95% purity for a pipeline customer, yet local demand may require a liquid oxygen product having 99.6% oxygen content which is a normal standard grade for liquid oxygen.
Furthermore, in situations where significant liquid production is required a traditional single reboiler process is used whereby air, expanded through an expander, is injected into the high pressure column. This affords a good recovery of oxygen since the majority of the air is still being treated in the high pressure column and does not by-pass the first step of distillation.
However, this feature has a major drawback because of the relatively high discharge pressure of the expander which is the high pressure column pressure. The feed air pressure must, therefore, be maintained at a high pressure to achieve the required refrigeration. In such situations, high power consumption would be needed to produce the required liquid.
Thus, a need exists for a process for producing oxygen at both low and high purity, more precisely, low purity gaseous oxygen and high purity liquid oxygen, and which is not characterized by a prohibitively high specific power consumption.

Process for the mixed production of high and low purity oxygen


A fireplace including a burner disposed to combust a combustible gas and air mixture within a combustion chamber. An exposed panel defining an exposed surface. A touch portion of the exposed surface isolated from heat generated within the combustion chamber to reduce a temperature of the touch portion. A control circuit coupled to the touch portion. The control circuit monitoring the touch portion and driving a component of the fireplace in response to a change at the touch portion.

The present invention relates to fireplaces. More particularly, the invention relates to a touch switch system for a fireplace.
Fireplaces have become increasingly commonplace in homes, businesses, and other buildings. A fireplace provides benefits including the generation of heat as well as an aesthetically-pleasing arrangement of flames, sounds, and smells. A gas fireplace is typically mounted in a wall of a structure and includes a switch for starting the fireplace and generating flames. A gas fireplace is typically turned on and off by throwing the switch, which is located behind an access panel located at the bottom of the fireplace.
However, gaining access to the fireplace creates several problems. For example, a person accessing the switch has to bend over, raise the access panel, and then turn or flip the switch to the desired position. In addition, because the fireplace produces heat, it is possible for one or more exterior surfaces of the fireplace to become heated. These exterior surfaces of the fireplace also pose a risk of burns to individuals or damage to objects that come into contact with the surfaces during operation of the switch located at the bottom of the fireplace. Other current fireplace designs remotely locate a switch from the fireplace. This may make it difficult for a user to identify the switch that actually operates the fireplace. Yet, other fireplace designs include toggle or push button switches located on the fireplace that can get hot, are noticeable, and, often, not as visually appealing to a person viewing the fire. Current fireplace designs fail to provide an easy, safe, and appealing system or method for turning the fireplace on and off.
Thus, there is a need for a fireplace that allows for a safe and easy switching of the fireplace from off and on positions, or for controlling other features of the fireplace.
Generally, the present invention relates to fireplaces. More particularly, the invention relates to apparatus and method for switching fireplace components on and off, or altering that state of fireplace component.
In one aspect, the invention relates a gas fireplace including a burner disposed to combust a combustible gas and air mixture within a combustion chamber, an exposed panel, wherein the exposed panel defines an exposed surface, a touch portion of the exposed surface, wherein the touch portion is isolated from heat generated within the combustion chamber to reduce a temperature of the touch portion, a gas valve, and a control circuit coupled to the touch portion and gas valve, wherein the control circuit monitors the touch portion and controls the opening and closing of the gas valve in response to a change at the touch portion.
In another aspect, the invention relates to a method for turning a gas fireplace on and off including: providing a touch portion of an exposed surface of the fireplace; coupling the touch portion to a control circuit; monitoring the voltage at the touch portion; and turning the fireplace on or off in response to a voltage change at the touch surface.
In another aspect, the invention relates to a gas fireplace including a burner disposed to combust a combustible gas and air mixture within a combustion chamber, an exposed panel, wherein the exposed panel defines an exposed surface, a touch portion of the exposed surface, wherein the touch portion is isolated from heat generated within the combustion chamber to reduce a temperature of the touch portion, and a control circuit coupled to the touch portion, wherein the control circuit monitors the touch portion and drives a component of the fireplace in response to a change at the touch portion.
In yet another aspect, the invention relates to a combustion chamber enclosure defining a combustion chamber in which combustion occurs and heat is generated, an exposed panel positioned adjacent the combustion chamber, wherein the exposed panel is heated by the combustion within the combustion chamber, a touch portion defined as a portion of the exposed panel, wherein the touch portion is isolated from the heat generated within the combustion chamber to reduce a temperature of the touch portion, a gas valve, and a control circuit coupled to the touch portion and gas valve, wherein the control circuit monitors the touch portion and modulates the gas valve in response to a change measured at the touch portion.
The above summary of the present invention is not intended to describe each disclosed embodiment or every implementation of the present invention. Figures in the detailed description that follow more particularly exemplify embodiments of the invention. While certain embodiments will be illustrated and described, the invention is not limited to use in such embodiments.


The present invention further relates to a method of inhibiting MRP1 in a mammal which comprises administering to a mammal in need thereof an effective amount of a compound of formula (I).

Along with surgery and radiotherapy, chemotherapy continues to be an effective therapy for many cancers. In fact, several types of cancer, such as Hodgkin""s disease, large cell lymphoma, acute lymphocytic leukemia, testicular cancer and early stage breast cancer, are now considered to be curable by chemotherapy. Other cancers such as ovarian cancer, small cell lung and advanced breast cancer, while not yet curable, are exhibiting positive response to combination chemotherapy.
One of the most important unsolved problems in cancer treatment is drug resistance. After selection for resistance to a single cytotoxic drug, cells may become cross resistant to a whole range of drugs with different structures and cellular targets, e.g., alkylating agents, antimetabolites, hormones, platinum-containing drugs, and natural products. This phenomenon is known as multidrug resistance (MDR). In some types of cells, this resistance is inherent, while in others, such as small cell lung cancer, it is usually acquired.
Such resistance is known to be multifactorial and is conferred by at least two proteins: the 170 kDa P-glycoprotein (MDR1) and the more recently identified 190 kDa multidrug resistance protein (MRP1). Although both MDR1 and MRP1 belong to the ATP-binding cassette superfamily of transport proteins, they are structurally very different molecules and share less than 15% amino acid homology. Despite the structural divergence between the two proteins, by 1994 there were no known consistent differences in the resistance patterns of MDR1 and MRP1 cell lines. However, the association, or lack thereof, of MRP1 and resistance to particular oncolytics is known. See Cole, et. al., xe2x80x9cPharmacological Characterization of Multidrug Resistant MRP-transfected Human Tumor Cellsxe2x80x9d, Cancer Research, 54:5902-5910, 1994. Doxorubicin, daunorubicin, epirubicin, vincristine, paclitaxel, mitoxantrone, melphalan, and etoposide are substrates of MRP1, i.e., MRP1 can bind to these oncolytics and redistribute them away from their site of action, the nucleus, and out of the cell. Id. and Marquardt, D., and Center, M. S., Cancer Research, 52:3157, 1992.
Doxorubicin, daunorubicin, and epirubicin are members of the anthracycline class of oncolytics. They are isolates of various strains of Streptomyces and act by inhibiting nucleic acid synthesis. These agents are useful in treating neoplasms of the bone, ovaries, bladder, thyroid, and especially the breast. They are also useful in the treatment of acute lymphoblastic and myeloblastic leukemia, Wilm""s tumor, neuroblastoma, soft tissue sarcoma, Hodgkin""s and non-Hodgkin""s lymphomas, and bronchogenic carcinoma.
Vincristine, a member of the vinca alkaloid class of oncolytics, is an isolate of a common flowering herb, the periwinkle plant (Vinca rosea Linn). The mechanism of action of vincristine is still under investigation but has been related to the inhibition of microtubule formation in the mitotic spindle. Vincristine is useful in the treatment of acute leukemia, Hodgkin""s disease, non-Hodgkin""s malignant lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilm""s tumor.
Etoposide, a member of the epipodophyllotoxin class of oncolytics, is a semisynthetic derivative of podophyllotoxin. Etoposide acts as a topoisomerase inhibitor and is useful in the therapy of neoplasms of the testis, and lung.
It is presently unknown what determines whether a cell line will acquire resistance via a MDR1 or MRP1 mechanism. Due to the tissue specificity of these transporters and/or in the case where one mechanism predominates or is exclusive, it would be useful to have a selective inhibitor of that one over the other. Furthermore, when administering a drug or drugs that are substrates of either protein, it would be particularly advantageous to coadminister an agent that is a selective inhibitor of that protein. It is, therefore, desirable to provide compounds that are selective inhibitors of MDR1 or MRP1.
The present invention relates to a compound of formula:
where:
A is a C3-C8 cycloalkyl, optionally substituted 1-3 times with a C1-C4 alkyl;
het is a five (5) membered heterocyclic ring comprising N and a second heteroatom selected from N, O, or S;
wherein the non-fused carbon atom of the heteroaryl ring may be optionally substituted with Rb: C1-C6 alkyl, optionally substituted aryl, optionally substituted heterocycle, an amino acid ester, CH2OH, CH2O-heterocycle, halo, CH2N3, CH2SR1, CH2NR4R6, OR1, SR13, S(CH2)k-phenyl, or NR4R6; provided that when het is pyrazole or imidazole, the saturated nitrogen of the het ring may be optionally substituted with Ra: C1-C4 alkyl;
k is 0, 1, 2, 3, or 4;
n is 0, 1, or 2;
p is 0 or 1;
q is 0, 1, or 2;
r is 0, 1, or 2;
t is 0, 1, 2, 3, or 4;
u is 0, 1, 2, 3, or 4;
Y is xe2x80x94Exe2x80x94C(O)R3, xe2x80x94Exe2x80x94CHxe2x95x90CHR13, xe2x80x94Exe2x80x94C(OH)R13, xe2x80x94Exe2x80x94NR4R5, xe2x80x94Exe2x80x94OR2, xe2x80x94Exe2x80x94S(O)qR13, xe2x80x94Exe2x80x94SO2NR4R6, xe2x80x94C(R11)xe2x95x90NR6, or an optionally substituted heterocycle;
E is a bond or xe2x80x94C(R11)(R11)xe2x80x94;
R1 is independently at each occurrence hydrogen or C1-C6 alkyl;
R2 is independently at each occurrence hydrogen, C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, or optionally substituted heterocycle, C(O)-aryl, or (CH2)2NR4R5;
R3 is independently at each occurrence hydrogen, C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, optionally substituted heterocycle, OR13, or NR4R6;
R4 is independently at each occurrence hydrogen, C1-C6 alkyl, optionally substituted (C1-C6 alkyl)-aryl, optionally substituted aryl, or R4 and R5, R6, R6xe2x80x2 combine to form xe2x95x90CR1R14;
R5 is independently at each occurrence hydrogen, C1-C6 alkyl, C1-C4 alkoxy, optionally substituted heterocycle, optionally substituted C3-C8 cycloalkyl, optionally substituted C6-C10 bicycloalkyl; optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, optionally substituted (C1-C4 alkyl)-heterocycle, C(O)C(O)R13, C(O)R7, CH2R7, SO2R8, a moiety of the formula
or R4 and R5, together with the nitrogen to which they are attached, combine to form an optionally substituted N-heterocycle;
R6 is independently at each occurrence hydrogen, C1-C6 alkyl, C1-C4 alkoxy, optionally substituted C3-C8 cycloalkyl, optionally substituted C6-C10 bicycloalkyl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, optionally substituted (C1-C4 alkyl)-heterocycle, optionally substituted heterocycle, or R4 and R6, together with the nitrogen to which they are attached, combine to form an optionally substituted N-heterocycle;
R6xe2x80x2 is independently at each occurrence hydrogen, C1-C6 alkyl, C1-C4 alkoxy, optionally substituted C3-C8 cycloalkyl, optionally substituted C6-C10 bicycloalkyl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, optionally substituted (C1-C4 alkyl)-heterocycle, optionally substituted heterocycle, (C1-C4 alkyl)-OR13:
wherein the (C1-C4 alkyl) of the (C1-C4 alkyl)-OR13 may be optionally substituted from 1 to 2 times with C1-C4 alkyl, optionally substituted aryl, optionally substituted heterocycle;
or R4 and R6xe2x80x2, together with the nitrogen to which they are attached, combine to form an optionally substituted N-heterocycle;
R7 is independently at each occurrence optionally substituted C1-C6 alkyl, C1-C6 alkoxy, (C1-C4 alkoxy)-aryl, (C1-C4 alkoxy)-heterocycle, (C1-C4 alkoxy)-SiCH3, optionally substituted (C3-C8 cycloalkyl), optionally substituted (C1-C4 alkyl)-(C3-C8 cycloalkyl), optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, diphenylmethyl, optionally substituted (C1-C4 alkyl)-CO-aryl, optionally substituted CO-aryl, optionally substituted (C1-C4 alkyl)-heterocycle, optionally substituted CHxe2x95x90CH-heterocycle, optionally substituted phenoxy, optionally substituted heterocycle, optionally substituted (C1-C4 alkyl)-phenoxy, (CH2)tS(O)rR1, (CH2)tC(R12)(R9)N(R16)(R15), (CH2)tC(R12)(R9)O(R17), (CH2)tC(R12)(R9)S(R17), or NR4R6xe2x80x2;
R8 is independently at each occurrence optionally substituted C1-C6 alkyl, optionally substituted aryl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted (C1-C4 alkyl)-heterocycle, or optionally substituted heterocycle;
R9 is independently at each occurrence hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, optionally substituted heterocycle, (CH2)u-(C1-C6 alkoxy), optionally substituted (CH2)uxe2x80x94Oxe2x80x94(C3-C8 cycloalkyl), optionally substituted (CH2)u-(C1-C4 alkoxy)-aryl, optionally substituted (CH2)uxe2x80x94O-aryl, optionally substituted (CH2)uxe2x80x94O-heterocycle, (C1-C4 alkyl)-CO2-(C1-C6 alkyl), optionally substituted (C1-C4 alkyl)-CO2-(C3-C8 cycloalkyl), optionally substituted (C1-C4 alkyl)-CO2-(C1-C4 alkyl)-aryl, optionally substituted (C1-C4 alkyl)-CO2-aryl, optionally substituted (C1-C4 alkyl)-CO2-heterocycle, or R9 and R12 can combine to form a C3-C8 cycloalkyl;
R10 is 0 to 4 substituents from the aryl ring independently at each occurrence hydrogen, halo, C(O)R3, cyano, optionally substituted heterocycle, optionally substituted aryl, Cxe2x89xa1Cxe2x80x94R1, C1-C4 alkoxy, (C1-C4 alkyl)-phenyl, NR19R20, or C2-C6 alkenyl;
R11 is independently at each occurrence hydrogen, C1-C6 alkyl, optionally substituted heterocycle, optionally substituted (C1-C4 alkyl)-heterocycle, optionally substituted aryl, or optionally substituted (C1-C4 alkyl)-aryl;
R12 is independently at each occurrence hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, optionally substituted (C1-C4 alkyl)-heterocycle or optionally substituted heterocycle;
R13 is independently at each occurrence hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, CO2CH2CO2CH2CH3, or optionally substituted heterocycle;
R14 is independently at each occurrence C1-C6 alkyl or optionally substituted (C1-C4 alkyl)-aryl;
R15 is independently at each occurrence hydrogen, C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C6-C10 bicycloalkyl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, optionally substituted (C1-C4 alkyl)-heterocycle, optionally substituted heterocycle, C(O)OR13, SO2R8, C(O)R18, or a moiety of the formula
R16 is independently at each occurrence hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, optionally substituted heterocycle, SO2R8, or xe2x80x94COR8; or R16 and R15, together with the nitrogen to which they are attached, combine to form an optionally substituted N-heterocycle;
R17 is independently at each occurrence hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, COR18, optionally substituted heterocycle, optionally substituted (C1-C4 alkyl)-heterocycle, optionally substituted C1-C6 alkoxy, optionally substituted (C1-C4 alkoxy)-aryl, optionally substituted (C1-C4 alkoxy)-heterocycle, (C1-C4 alkyl)-N(R1)(R1), or an amino acid ester;
R18 is independently at each occurrence hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, optionally substituted heterocycle, (C1-C4 alkyl)-NHCO2-(C1-C4 alkyl), or optionally substituted (C1-C4 alkyl)-heterocycle;
R19 is independently at each occurrence hydrogen, or optionally substituted C1-C6 alkyl;
R20 is independently at each occurrence hydrogen, optionally substituted C1-C6 alkyl, CH2OH, COxe2x80x94(C1-C4 alkyl); or a pharmaceutical salt thereof.
The present invention further relates to a method of inhibiting MRP1 in a mammal which comprises administering to a mammal in need thereof an effective amount of a compound of formula I.
In another embodiment, the present invention relates to a method of inhibiting a resistant neoplasm, or a neoplasm susceptible to resistance in a mammal which comprises administering to a mammal in need thereof an effective amount of a compound of formula I in combination with an effective amount of an oncolytic agent.
The present invention also relates to a pharmaceutical formulation comprising a compound of formula I in combination with one or more oncolytics, pharmaceutical carriers, diluents, or excipients therefor.

Methods and compounds for inhibiting MRP1


A dispensing kit for medicine bottlecaps that includes a first bottlecap with a first preprogrammed timer programmed for a first time interval, a second bottlecap with a second preprogrammed timer programmed for a second time interval and a dispensing device for independently dispensing the first and second bottlecaps.

The effectiveness of a medication regime often depends on maintaining appropriate corporeal concentrations of the medication which, in turn, is affected by regular dose administration. In a supervised setting, where a medical practitioner is responsible for administering medicine, providing doses at appropriate times can be reliably achieved. Outside of such environments, even the most sophisticated and diligent patient may find it difficult to reliably self administer medications on schedule.
In light of this issue, a variety of medication timers have previously been proposed. For example, U.S. Pat. No. 4,662,537 describes a keyboard assembly which stores and dispenses pills and an electronic assembly which records data regarding key closures whenever a pill is dispensed.
U.S. Pat. No. 5,313,439 shows an ordinary medicine bottle with a cap modified so as to include a timer, a battery, a buzzer or display light and means for closing a circuit. When the cap is closed, the circuit is automatically closed through contact with a conducting material on the upper edge of the bottle.
U.S. Pat. No. 5,377,614 shows a reminder device with circular dials similar to the face of a clock for pill and medicine containers. The rotatable dials may be manually set to an indicator showing the weekday, date and time for taking a pill or other medicinal dose. The reminder device is disposable and maybe pin to the bottle top or other medicine container.
U.S. Pat. No. 6,324,123 describes a medication timer for tracking when medication is to be taken. The medication timer includes a bottle for housing the medication. The bottle has an open end which has a lip. The lip has threads formed thereon. A first cap for removably closing the bottle has a first portion and a second portion. The first and second portions are generally annular. The first and second portions each have an interior threaded surface. A timer for tracking medication use has a top wall, a bottom wall and a peripheral side wall extending therebetween. The peripheral side wall has threads thereon. The peripheral side wall has a plurality of bores therein. Control circuitry is fixedly mounted in an interior of the timer. The control circuitry is adapted for tracking elapsing time, and adapted for activation of an alarm. A display for displaying information from the control circuitry is mounted on the control circuitry. The display is operationally coupled to the control circuitry. A button for programming the control circuitry is in each one of the bores in the timer.
U.S. Pat. No. 7,081,807 describes an electronic pill reminder device. The reminder device can be retrofitted inside a conventional pill bottle cap between the bottle cap and the bottle container. When the user closes the pill bottle cap on the bottle container, the electronic timer, with factory predetermined time interval, is automatically activated. That activated timer will generate alert signals not only remind user last pill has taken but also to remind the user to take his/hers next dose at time-out. The reminder device and alert signals are automatically deactivated and reset when the user opens the pill bottle cap (to take contents from the bottle container).
Similarly, US published patent application number 2009/0052283 describes a disposable electronic timer in the form of a disk having a liquid crystal or similar display, adapted to be glued to a medication bottle cap. A lower major surface of the timer has an adhesive layer with a cover that can be peeled off to expose the adhesive so that the timer can be secured to the bottle cap. The upper major surface of the timer contains the timer display and a control button that in one mode starts the timer so that an alarm within the timer sounds after a preset time interval, and in another mode sets or resets the timer to a different preset time interval. Operating power is supplied by a battery within the timer.
Each of the above-noted documents is herewith incorporated by reference in its entirety.

System method and apparatus for medication scheduling


A welding carriage which is movable in two directions of travel opposite one another comprises at least one welding device possessing at least one welding nozzle for welding two overlapping webs of material and having at least one pressing device for applying pressure to the upper web of material after the welding operation. The welding carriage is operable in both directions of travel, wherein in each direction of travel the welding nozzle is arranged or arrangeable ahead of the pressing device.

The invention relates to a welding carriage for welding two overlapping webs of material.
Welding carriages are generally known and are preferably used for welding plastic films overlapping in the transverse direction for sealing roofs. The known welding carriages, however, are not limited to this special application. They are additionally suitable, for example, for welding lorry tarpaulins, tents, covers used in agriculture, swimming pool covers, awnings, boat tarpaulins, advertising awnings, floor coverings, etc. The essential thing is that the webs of material to be welded be arranged in overlapping manner so that a welding nozzle of a welding device arranged on the welding carriage can be positioned between the webs of material in order to heat up the overlapping sections of material on traversal of the welding carriage and hence to weld them. In known welding carriages a pressing device is usually arranged behind the welding nozzle in the welding direction to apply pressure to the upper web of material after the welding operation so that the upper web of material has pressure applied to it after heating on traversal of the welding carriage as a result of which an intimate bond is produced between the slightly fused webs of material. Such a welding carriage is disclosed, for example, in EP 1 371 474 B1. A disadvantage of the known welding carriage is that it can be operated in only one welding direction (operating direction).
When welding overlapping webs of material the procedure for doing so must be as shown in FIG. 11. In FIG. 11 two overlapping sections A and B extending in the longitudinal direction and spaced apart from one another in the transverse direction are shown, wherein in the overlapping section A a first web of material a overlaps a neighbouring second parallel web of material b in the transverse direction and in the overlapping section B the second web of material b overlaps a neighbouring third parallel web of material c. At position I the welding nozzle of a welding carriage is first of all positioned in the overlapping section A between the webs of material a and b and after this displaced along the dotted line up to position II in a first longitudinal direction. In the traversal of the welding carriage from position I to position II the fused weld tracks are pressed against one another by a pressing device arranged behind the welding nozzle in the first direction of travel. At position II the welding nozzle is moved out of the overlapping section A and after this the entire welding carriage is transported counter to the first direction of travel (only possible operating direction) into a second direction of travel that is also transverse thereto along the dotted line from position II to position III, wherein during this transport operation no welding ensues. Position III is located spaced apart in the transverse direction from the starting position I. At position III the welding nozzle is positioned in the overlapping section B between the webs of material b and c and the welding carriage is displaced in the first longitudinal direction again along the dotted line in the direction of the arrow to position IV, wherein in doing so the webs of material b and c are welded to one another. For welding further parallel webs of material to one another the welding carriage must now be transported once again counter to the welding direction (first longitudinal direction) and transverse thereto. Due to the sometimes very long transport step (II-III), especially in the case of large roofs, after the welding of two webs of material a considerable proportion of the available working time is not productively utilised since while traversing the long transport pathway no welding work can be carried out.
Other examples of known welding carriages are described in CH 4,65197, DE 3537244 A1, DE 423088 C2, DE 9110487 U1, DE 9110488 U1, DE 100 32 450 A1, DE 198 136 25 C1, EP 300 209 A2, EP 949 057 B1, EP 1464471 B1, U.S. Pat. No. 3,080,910, U.S. Pat. No. 4,440,588 and U.S. Pat. No. 5,865,942.
It is an object of the invention to propose a welding carriage by means of which a plurality of overlapping webs of material arranged alongside one another can be effectively and rapidly welded to one another. Furthermore, a method is to be proposed by means of which the neighbouring webs of material can be welded to one another in the shortest time using a welding carriage.


A function processing service may receive a request to execute source code. The source code may include instructions to perform a function. The function processing service may determine whether at least one hardware acceleration condition has been satisfied for the function. If at least one hardware acceleration condition has been satisfied, the instructions in the source code may be translated into hardware-specific code corresponding to a hardware circuit. The hardware circuit may be configured based on the hardware-specific code, and the hardware circuit may perform the function. The function processing service may then provide the result obtained from the hardware circuit to the requesting entity.

Cloud computing is the delivery of computing services (e.g., servers, storage, databases, networking, software, analytics) over the Internet. Broadly speaking, a cloud computing system includes two sections, a front end and a back end, that are in electronic communication with one another via the Internet. The front end includes the interface that users encounter through a client device. The back end includes the resources that deliver cloud-computing services, including processors, memory, storage, and networking hardware. The back end of a cloud computing system typically includes one or more data centers, which may be located in different geographical areas. Each data center typically includes a large number (e.g., hundreds or thousands) of computing devices, which may be referred to as host machines.
Many different types of services may be provided by a cloud computing system. A function processing service is a cloud computing service that allows users to execute source code without the complexity of building and maintaining the infrastructure that is typically associated with developing and launching an application. A function processing service automatically manages the computing resources that are required to execute the source code. Therefore, a function processing service makes it possible for software developers to execute source code without having to worry about provisioning or managing servers.
As the name "function processing" implies, a function processing service may be utilized to execute source code that includes instructions to perform one or more functions. Function processing is sometimes referred to as serverless computing or function as a service (FaaS).
As function processing services grow in popularity, the source code that is being executed is growing more complex and data intensive. For instance, machine learning or artificial intelligence applications can utilize data intensive scripts that process massive amounts of data. These data intensive scripts can greatly increase processing time and consume significant amounts of computing resources. Users, however, expect function processing services to run efficiently and quickly. Accordingly, benefits may be realized by techniques for enhancing the efficiency of a function processing service in a cloud computing system.

Hardware acceleration for function processing


According to one embodiment, a recording medium controller includes a recording medium, an input module, a reading module, and a writing module. The recording medium includes a write area and an escape area. The write area includes track groups. Each of the track groups is a unit for writing data and includes tracks. The input module receives a write command for data. The reading module reads data stored in the escape area and data from a first track group of the track groups. The writing module writes data received for the write command to the escape area, and writes merged data obtained by merging the data read from the escape area and the data read from the first track group to each track of a second track group of the track groups by using a shingle recording technique in which adjacent tracks are partly overlapped with each other.

A hard disk drive (HDD) comprising a magnetic disk has conventionally been used. The recent trend is to further increase the capacity of a hard disk. In order to increase the recording density for increasing the capacity, there has been disclosed a technique in which the track density is decreased by reducing track widths.
There has also been disclosed another technique for increasing the track density. In this technique, the track widths are decreased to an extent that data is written to adjacent tracks in a partly overlapping manner. Such a recording technique is often referred to as shingle recording. However, when this technique is applied, the data stored in the adjacent track in a partly overlapping manner is lost. Therefore, data writing must be performed per unit track group composed of a plurality of tracks (for example, see Japanese Patent Application Publication (KOKAI) No. 2006-338731).
However, employing the technique disclosed in Japanese Patent Application Publication (KOKAI) No. 2006-338731 takes long time to write data because the writing must be performed per unit track group.

Recording medium controller and method thereof


The distance between a discharge electrode and a counter electrode of a discharge device is set to not more than 10 mm such that a streamer discharge is caused between the electrodes. The frequency of sound made by the streamer discharge is raised to 6 kHz or higher to exceed the frequency range which is easily perceivable by human hearing.

(a) Field of the Invention
The present invention relates to a discharge device which performs streamer discharge and an air purifier. In particular, it relates to a technology for reducing noise of streamer discharge.
(b) Background Information
Air purifiers provided with discharge devices have conventionally been used as a means of decomposing and removing odorous components and hazardous components by using plasma generated by discharge. Among various discharge-based air purifiers, a streamer discharge-based air purifier is suitable for decomposition of the hazardous components and deodorization due to its high decomposition efficiency at a relatively low electric power.
FIG. 8 shows a schematic configuration of a discharge device in an air purifier. The discharge device (29) includes projecting discharge electrodes (30) for generating low temperature plasma and flat counter electrodes (31) opposed to the tips of the discharge electrodes (30). Discharge is caused between the electrodes (30) and (31) to generate the low temperature plasma, and then a target gas is introduced therebetween to allow hazardous components and odorous components contained in the target gas to contact active species (fast electrons, ions, radicals and other excited molecules) generated by the low temperature plasma. In this way, these components are decomposed and removed (for example, see Japanese Unexamined Patent Publication No. 2002-336689).
However, streamer discharge makes a relatively loud discharge sound due to electrical breakdown in the air. Since the frequency range of the discharge sound is significantly likely to be perceived by human hearing, the discharge sound caused by the operation of a streamer discharge-based air purifier may possibly be recognized as a noise. Therefore, the streamer discharge-based air purifier is regarded as unsuitable for places where certain silence is required such as living space and small stores. However, to put it the other way around, if the discharge sound made by streamer discharge can be reduced, streamer discharge will be applicable to compact air purifiers for consumer use. That is, it will be possible to make full use of the high decomposition efficiency of streamer discharge in a wide range of fields.


High-specificity antibodies can distinguish between modified (e.g, hIGF-1/Ea 3mut) and endogenous wild-type human IGF-1 proteins. These antibodies have little or no cross-reactivity with hIGF-1 or hIGF-2. They also have little or no cross-reactivity with rodent IGF-1 or IGF-2. The antibodies can be used in pharmacokinetic (PK)/pharamcodynamic (PD) assessments of IGF-1/E peptides that have been administered to humans or animals. A sandwich ELISA assay, using the antibody of the invention as a capture antibody, can quantify the mutant IGF-1/E proteins in samples.

Insulin-like growth factor 1 (IGF-1, somatomedin) is a small single-chain protein that induces muscle hypertrophy and blocks skeletal muscle atrophy. IGF-1 is initially synthesized in the human body as an IGF-1/E precursor, where E is an extension peptide at the C-terminus of the mature IGF-1 protein. The mature IGF-1 is initially encoded by one of three known splice variant mRNAs. The open reading frame of each mRNA encodes a precursor protein containing the 70 amino acid IGF-1 moiety and a particular extension (E) peptide at the C-terminus, which can be Ea, Eb or Ec, depending on the particular IGF-1 mRNA. The C-terminus E peptide is later cleaved as IGF-1 matures.
Modified recombinant human IGF-1/E proteins have been constructed and described in published PCT patent application WO2007/146689. These modified IGF-1/E peptides have longer half-life, increased stability, reduced affinity to inhibitory insulin-like growth factor binding proteins (IGFBPs), and increased efficacy compared to wild type IGF-1. An exemplary modified human IGF-1/E protein is hIGF-1/Ea 3mut (see FIG. 1). The "3mut" designation refers to a hIGF-1-E-peptide precursor having the following three sots of modifications: (1) deletion of G1, P2, and E3; (2) mutation of Arg 37 to Ala (R37A); and (3) deletion of R71 and S72. These hIGF-1/E 3mut peptides are proposed as being potential new drug for the treatment of skeletal muscle atrophy.
However, assessing the pharmacokinetics (PK) and pharacodynamics (PD) for this drug candidate is difficult, because the wild type and modified hIGF-1/E peptides differ with each other in only one or two amino acids at three separate positions over the length of the entire peptide chains (FIG. 1). No commercially available antibody recognizes the hIGF-1/Ea 3mut peptides without also detecting the endogenous hIGF-1.

Antibodies to modified human IGF-1/E peptides


A high temperature electrochemical system, such as a solid oxide fuel cell system, generates hydrogen and optionally electricity in a fuel cell mode. At least a part of the generated hydrogen is separated and stored or provided to a hydrogen using device. A solid oxide regenerative fuel cell system stores carbon dioxide in a fuel cell mode. The system generates a methane fuel in an electrolysis mode from the stored carbon dioxide and water by using a Sabatier subsystem. Alternatively, the system generates a hydrogen fuel in an electrolysis mode from water alone.

A solid oxide fuel cell (SOFC) is an electrochemical device that converts chemical energy directly into electrical energy. A solid oxide regenerative fuel cell (SORFC) is an electrochemical device that converts electrical energy directly into chemical energy and subsequently reconverts chemical energy back to electrical energy. This device differs significantly from rechargeable batteries in that the chemicals are stored outside of the SORFC converter. The SORFC system has many building electrical energy storage applications that cannot be satisfied by batteries. For example, a SORFC system for building power generation is discussed in the Proceedings of the 2001 DOE Hydrogen Program Review NREL/CP-570-30535. A SORFC system which generates hydrogen in the electrolysis mode and which generates electricity in the fuel cell mode is described in Proceedings of the 2002 DOE Hydrogen Program Review NREL/CP-610-32405. This SORFC system may contain a separate electrolyzer unit which operates in the electrolysis mode and which is operatively connected to the fuel cell stack to generate hydrogen. However, these SORFC systems have certain environmental and economic drawbacks.
The SOFC and SORFC are high temperature electrochemical systems. Another high temperature electrochemical system is a molten carbonate fuel cell. Fuel cells often use hydrogen as fuel. For example, fuel cell powered vehicles would require hydrogen refueling stations for operation. However, distribution of hydrogen from centralized hydrogen producing plants to refuel vehicles is not currently economical. Furthermore, hydrogen production is fairly expensive.

Co-production of hydrogen and electricity in a high temperature electrochemical system


A sphygmograph includes: a first signal processing unit and a second signal processing unit that process pulse waves obtained from a pulse sensor unit; a signal processing selection unit that determines whether or not to cause the second signal processing unit to also operate at the same time as the first signal processing unit; and a save data generation unit that saves, of the signal processing results from the first signal processing unit and the second signal processing unit, the signal processing result selected by the signal processing selection unit.

1. Technical Field
The present invention relates to sphygmographs and to signal processing methods used in such sphygmographs.
2. Related Art
Internal states of the human body can be discovered by using a photoelectric sensor that emits light at a specific wavelength and measures the reflected or transmitted light in order to analyze obtained waveforms. As one example, information related to the pulse, blood, and so on in a human body can be obtained by utilizing the light-absorbing characteristics of blood in areas of the living body in which blood is present.
For instance, if a pulse wave can be accurately captured, information regarding cardiac movement can be obtained. The pulse wave interval is sometimes used in the same manner as the RR interval of an electrocardiogram, and although the pulse wave interval is used in judging partial arrhythmia, it can also be used to derive an autonomic nerve index and determine sleep states by analyzing frequencies, if long-term data can be obtained; in addition, fluctuation in the RR interval is also sometimes used to analyze heart function.
JP-A-2008-253579 attempts to acquire a pulse peak interval that corresponds to an electrocardiogram RR interval by obtaining a sphygmograph using a photoelectric sensor. Furthermore, a noise removal process is carried out in order to remove reflected waves, notches, and so on that result in noise.
However, when, in the stated method, the signal processing, or in other words, the DC component of the photoelectric sensor output signal is unstable, such as when the measurement subject is not at rest, the noise removal is insufficient for the noise resulting from body movements; it is necessary to employ signal processing that can handle high-frequency noise, low-frequency noise, and changes in the DC component. As examples of such a signal processing method, an adaptive filter that extracts a spectrum unique to pulse waves (for example, see U.S. Pat. No. 4,955,379), applying independent component analysis (for example, see U.S. Pat. No. 6,701,170), and so on have been proposed.
However, in an integrated device (sphygmograph) that has limited processing capabilities and power performance, the signal processes described in U.S. Pat. No. 4,955,379 and U.S. Pat. No. 6,701,170 are complicated in the case where a pulse is to be measured continuously on a daily basis. Accordingly, these signal processes cannot be carried out to a sufficient degree in devices with low computational processing capabilities, such as such integrated devices.
With respect to this point, the signal processing disclosed in JP-A-2008-253579 is simple and can thus be implemented, but doing so is problematic in that sufficient processing for noise cannot be carried out, which makes the measurement results unreliable. It is therefore necessary to save a plurality of signal processing results that complement one another, but the storage capacity for saving such results is limited in integrated devices.

Sphygmograph and signal processing method


Methods and circuits for assigning pilot boosting factors and calculating traffic to pilot ratios in a wireless communication system. The data to be transmitted is first modulated to generate a plurality of data modulation symbols. The plurality of data modulation symbols and a plurality of reference signal symbols are mapped into transmission resources of each of a plurality of antennas in accordance with a transmit diversity scheme. The transmission resources of each of the antennas are divided into a plurality of subcarriers in a frequency domain and a plurality of time units in a time domain. Then, a power scaling factor are assigned for data modulation symbols on each of the antennas in dependence upon power levels of the reference signal symbols to maintain a fixed power level across the plurality of antennas in each time unit. Finally, the data modulation symbols and the reference signal symbols are transmitted via the plurality of antennas in accordance with the mapping scheme and the assigned scaling factors.

1. Field of the Invention
The present invention relates to methods and circuits for assigning pilot boosting factors and calculating traffic to pilot ratios in a wireless communication system.
2. Description of the Related Art
A typical cellular radio system includes a number of fixed base stations and a number of mobile stations. Each base station covers a geographical area, which is defined as a cell. Typically, a non-line-of-sight (NLOS) radio propagation path exists between a base station and a mobile station due to natural and man-made objects disposed between the base station and the mobile station. As a consequence, radio waves propagate while experiencing reflections, diffractions and scattering. The radio wave which arrives at the antenna of the mobile station in a downlink direction, or at the antenna of the base station in an uplink direction, experiences constructive and destructive additions because of different phases of individual waves generated due to the reflections, diffractions, scattering and out-of-phase recombination. This is due to the fact that, at high carrier frequencies typically used in a contemporary cellular wireless communication, small changes in differential propagation delays introduces large changes in the phases of the individual waves. If the mobile station is moving or there are changes in the scattering environment, then the spatial variations in the amplitude and phase of the composite received signal will manifest themselves as the time variations known as Rayleigh fading or fast fading attributable to multipath reception. The time-varying nature of the wireless channel require very high signal-to-noise ratio (SNR) in order to provide desired bit error or packet error reliability.
The scheme of diversity is widely used to combat the effect of fast fading by providing a receiver with multiple faded replicas of the same information-bearing signal.
The schemes of diversity in general fall into the following categories: space, angle, polarization, field, frequency, time and multipath diversity. Space diversity can be achieved by using multiple transmit or receive antennas. The spatial separation between the multiple antennas is chosen so that the diversity branches, i.e., the signals transmitted from the multiple antennas, experience fading with little or no correlation. Transmit diversity, which is one type of space diversity, uses multiple transmission antennas to provide the receiver with multiple uncorrelated replicas of the same signal. Transmission diversity schemes can further be divided into open loop transmit diversity and closed-loop transmission diversity schemes. In the open loop transmit diversity approach no feedback is required from the receiver. In one type of closed loop transmit diversity, a receiver knows an arrangement of transmission antennas, computes a phase and amplitude adjustment that should be applied at the transmitter antennas in order to maximize a power of the signal received at the receiver. In another arrangement of closed loop transmit diversity referred to as selection transmit diversity (STD), the receiver provides feedback information to the transmitter regarding which antenna(s) to be used for transmission.
It can be noted that the power available from each antenna port for subcarriers other than the reference signals, e.g., data subcarriers, vary from OFDM symbol to OFDM symbol. Keeping the power level the same across antennas on these subcarriers results in inefficient use of power because power level is limited to the minimum power level available from a given antenna port even though other ports may have extra power available. Likewise, keeping the power level the same across OFDM symbols on these subcarriers also results in inefficient use of power because power level is limited to the minimum power level available in one OFDM symbol although other OFDM symbols may have extra power available. Another solution could be to puncture some data subcarriers in OFDM symbols containing pilots to keep the power level the same across the symbols. This approach, however, may result in waste of subcarrier resources thus degrading system performance and capacity.

Pilot boosting and traffic to pilot ratio estimation in a wireless communication system


A turbine vane for a rotary turbomachine has a turbine blade delimited by a concave pressure-side wall and a convex suction-side wall which are connected in the region of a vane front edge which can be assigned to the turbine blade and enclose a cavity which extends in the longitudinal extent of the vane front edge and is delimited on the inner wall by the pressure-side wall and the suction-side wall in the region of the vane front edge and by an intermediate wall which extends in the longitudinal direction to the vane front edge and connects the suction-side wall and the pressure-side wall on the inner wall. The intermediate wall has a perforation at least in sections in the connecting region to the suction-side wall and/or pressure-side wall, in order to increase the elasticity of the intermediate wall.

Turbine blades of the abovementioned generic type are heat-resistant components which are used in particular in turbine stages of gas turbine arrangements and, in the form of guide blades or rotor blades, are exposed to the hot gases directly leaving the combustion chamber.
The heat resistance of such turbine blades comes, on one hand, from the use of heat-resistant materials and, on the other hand, from a highly efficient cooling of the turbine blades which are directly exposed to the hot gases and which, in order that a coolant, preferably cooling air, can continuously flow through and act on them, have corresponding cavities that are connected to a coolant supply system of the gas turbine arrangement, which coolant supply system provides cooling air for the purpose of cooling all of the gas turbine components which are exposed to heat, i.e. in particular the turbine blades, when the gas turbine is in operation.
Conventional turbine blades have a blade root to which the blade airfoil is connected directly or indirectly in the radial direction, which airfoil has a concave-shaped pressure side wall and a convex-shaped suction side wall which are integrally connected in the region of the blade leading edge and between which is bounded an interspace that, for cooling purposes, is supplied with cooling air from the direction of the blade root. In this context, the term "in the radial direction" signifies the turbine blade extent in the mounted state in the gas turbine arrangement, which is oriented radially with respect to the axis of rotation of the rotor unit. In order to undertake the supply and distribution of cooling air in the interspace enclosed between the suction side wall and the pressure side wall, for an optimized cooling of the turbine blade, the interspace is provided with intermediate walls which run in the radial direction and which in each case separate cavities that are oriented radially inside the blade airfoil, some of which have fluidic connections. At suitable positions along the cavities, throughflow openings are provided in the suction side wall or the pressure side wall, in the region of the turbine blade leading edge and/or trailing edge or at the turbine blade tip, such that the cooling air can escape outward into the hot gas duct of the turbine stage.
A gas turbine blade which has been optimized with respect to cooling purposes is known from EP 1 319 803 A2, which provides for a multiplicity of radially oriented cooling duct cavities inside the turbine blade airfoil which are in each case fluidically connected in meandrous fashion and through which more or less cooling air flows depending on the thermal load on the various blade airfoil regions. It is particularly expedient to provide particularly efficient cooling for the region of the blade leading edge, which experiences the greatest flow exposure and heat exposure to the hot gases. To that end, a cavity extends internally in the longitudinal direction with respect to the blade leading edge, which cavity is delimited by the suction side and pressure side which unite at the blade leading edge and by an intermediate wall which connects the suction side and pressure side with one another internally, this cavity being supplied with cooling air from the direction of the blade root. The cooling air flowing through the cavity usually leaves in the region of the blade airfoil tip. Furthermore, in order to improve the transfer of heat between the blade airfoil wall and the cooling air flowing through the cavity, structures that swirl the cooling air flow are provided along the wall regions which enclose the cavity.
A further preferred cooling of the blade leading edge region of a turbine blade is described in U.S. Pat. No. 5,688,104. Along the blade leading edge there runs a cavity which, on one hand, is bounded by the suction side wall and pressure side wall which unite at the blade leading edge, and by an intermediate wall which rigidly connects the suction side wall and pressure side wall to one another inside the blade airfoil. The cavity running along the blade leading edge is supplied with cooling air which enters the cavity only through cooling duct openings provided in the intermediate wall. The straight intermediate wall is provided, in its radial longitudinal extent, with a multiplicity of individual throughflow ducts through which cooling air from an adjacent radial cooling duct enters the aforementioned cavity along the blade airfoil, in the direction of the blade leading edge, in the manner of an impingement cooling. In order to evacuate the cooling air introduced into the cavity, film cooling openings are provided along the blade leading edge, respectively oriented toward the suction side outer wall and pressure side outer wall, through which openings the cooling air introduced into the cavity is expelled, forming a film cooling respectively on the pressure side outer wall and suction side outer wall.
In order to improve the cooling effect, especially of the blade leading edge of a turbine blade, it is appropriate with the known cooling techniques to, on one hand, increase the supply of cooling air and, on the other hand, optimize the cooling mechanisms of the impingement cooling.
Turbine blades which, for the purpose of an optimized heat resistance in particular in the region of the blade leading edge, have the abovementioned cooling measures nonetheless often exhibit, in the blade leading edge region along the pressure side wall and suction side wall, fatigue symptoms which, in the final stages, become apparent by the formation of cracks. The reason for such crack formation lies in the apparition of thermomechanical stresses, within the suction side wall and pressure side wall in the blade leading edge region, which stem from large temperature differences between the blade leading edge exposed to the hot gases and the inner wall regions of the blade airfoil which are acted upon by the cooling air. In particular in the case of transient operating states of the gas turbine arrangement, such as those which arise in the turbine stage during startup or changes in load, temperature differences of approximately 1000° C. may occur between the blade leading edge exposed to the hot gases and the intermediate wall and inner wall sections which are acted upon by the cooling air. It is obvious that such great temperature differences give rise, within the suction side wall and pressure side wall along the blade leading edge, to considerable thermomechanical stresses which lead to considerable material loads, as mentioned above.


Various embodiments include apparatus, systems, and methods having a conductive contact configured to couple to a resistor-capacitor (RC) network, a device unit coupled to the conductive contact, and a mode switching unit to change a characteristic of a signal at the conductive contact based at least in part on an RC time constant of the RC network. The mode switching unit may switch the device unit between a first operating mode and a second operating mode based on a signal level of the signal.

Integrated circuit (IC) devices are widely used in electronic products. An IC device usually includes many different components enclosed in an IC package (or IC chip). Different components of an IC may perform different activities. Some IC devices may operate at a lower power mode for some activities and operate at a higher power mode for other activities. Some of these IC devices may use a crystal oscillator as a timer to switch between different power modes. In some cases, a crystal oscillator may be unsuitable for switching function in some IC devices.


A long handled sock donning tool includes a handle portion adapted to be gripped by a user and an opposing sock engaging portion. The sock engagement portion includes first and second flanges spaced from an elongated support by first and second spacers. Each of the flanges include a sock engagement arm for retaining a sock thereon, and an opposing stabilizing arm for supporting the tool during the mounting of the sock onto the tool. First and second rubber sock gripping portions help retain the sock on the tool. Once an upper portion of a sock is folded over the sock gripping portions, a user's foot can be inserted into the sock comfortably without being forced into contact with a hard plastic wall of the tool. Additionally, the tool can be used as a shoe horn by fitting one of the first and second flanges into the heel of a shoe.

1. Field of the Invention
The present invention pertains to the art of medical aid devices, and more particularly to sock or hosiery donning tools.
2. Discussion of the Prior Art
People with back, knee and hip problems, people with decreased flexibility, pregnant women, or people who are overweight, have a hard time bending over far enough to put on their socks and hosiery.
In general, it is known in the art to have a long handled tool for aiding a user in putting on hosiery or socks, wherein the tool comprises flanges about which a user fits the top of a sock such that the top of the sock is held in an open position to receive the foot of a user, as demonstrated by at least U.S. Patent Application Publication No. 2011/0049201. However, such devices fail to provide an adequate gripping structure to maintain socks in place during insertion of a user's foot. Further, the manner in which such devices are utilized blocks the user's view of the foot as it is being inserted into hosiery. It is also known to fold the top of a stocking over a stocking holding portion of a device, and slide a foot into the open end of the stocking, as demonstrated by U.S. Pat. No. 7,070,074. However, the '074 device is large, and is not easily portable. Therefore, there exists a need in the art for an improved hand-held sock donning apparatus that is easily utilized, facilitates retention of socks during use, and allows easy disengagement of a donned sock and that can be utilized as a shoe horn.

Long handled sock donning tool and method of use


The invention enables server administrators (SAs) to improve their productivity and performance. With the methods and systems described herein, the prior art needed to search for appropriate tools for appropriate tasks is minimized and/or eliminated. Easier scripting and automation that does not require implementation across tools is provided. A consistent logical place is provided for all resources to be used. Standardization of tools enables improvements in service quality. Tools may be provided using one unambiguous authoritative data model, which eliminates data inconsistencies between sources. With the invention, updates to service delivery clients may be delivered more quickly. The invention also reduces costs for developing, deploying, and maintaining a tightly integrated service delivery client. Integration may be provided from the bottom up rather than after the fact. With the invention, common base objects are provided for events, problem and change records, and other system administration artifacts.

In the prior art, software developers utilize integrated development environments (IDEs) to develop and debug software. Prior to the current reliance on such IDEs, software developers needed to use separate and distinct tools for syntax checking their code, compiling, debugging, handling version control, and so forth. Modern software IDEs have the ability to merge all this functionality so that software developers don't see and aren't distracted by such separate and distinct tools.
One prior art IDE that is currently used by software developers is an open source platform know to those in the software arts as Eclipse, more information about which can be obtained from Eclipse Foundation, Inc. 102 Centrepointe Drive Ottawa, Ontario, Canada, K2G 6B1. Eclipse is an extension-rich platform that is based on the notion of plug-ins. Eclipse uses basic Java programmatic elements such as Package and Source File. Eclipse includes notions of perspectives and views. In Eclipse, different perspectives refer to different ways of looking at and working with the same underlying data. In Eclipse, views are windows focused on subsets of data within a given perspective.
The phrase "server administrator" (SA) refers generically to operating system-level administrators, database administrators, web administrators, network administrators, and the like. In the prior art, SAs have been limited by their use and interaction with underlying tools and processes, which have been based on little or no standardization and, as well, little or no integration. In order to perform their daily responsibilities, SAs often have had to create "glue code" to cobble together the outputs from one or more systems, services, tasks, tools, and processes with that of their own self-developed scripts. In the prior art, such "glue code" is typically created in a variety of languages and uses non standardized interfaces, "breaks" under the stress of enterprise usage, and as such is typically unsupported.
Referring to FIG. 8, there is seen a representation of server administrator (SA) 801 interacting with various tools, services, and/or processes 803 via a prior art System Administrator Desktop 802. In such prior art systems, one sees a variety of non-interacting stand-alone tools and systems with little or no standardization amongst them. For example, in FIG. 8 one sees IT monitoring tools (Tivoli ITM, TEC), problem/change/ticketing tools/systems (ManageNow), reporting tools (SRM, ESMRT), search interfaces to knowledge repositories (HelpNow), patch management tools (VSA) and collaboration tools (telephone handoffs, email, team rooms and chat), some of which are known to those skilled in the art and some of which are proprietary applications.
Referring to FIG. 9, and FIG. 8 as needed, there is seen a view of a prior art Server Administrator Desktop 902. In the prior art, although views/perspectives are visible, they are not provided in a manner that enables communication of information between tools 803; which may, for example, cause the SA 801 to lose focus and access the wrong information at the wrong time. In the prior art, different perspectives on the same data are provided by different tools or applications that do not share a common data model. In the prior art Server Administrator Desktop 902 example shown, one sees a so-called dashboard that depicts system vitals (i.e. consumption of system resources), pressing problems, change records, bar charts of resource consumption, and various collaboration tools. In the prior art, none of the tools 803 communicate or are integrated in more than a superficial way.
It would therefore be desirable to provide SAs with systems and methods that provide them with improved access to tools, services, and processes.

System and method for delivering an integrated server administration platform

International Business Machines Corporation


A digital content transfer appliance comprises a memory card reader, a memory, and a controller. The memory card reader is configured to removably receive at least one memory card and to read and write a digital content on the memory card wherein the digital content includes at least one of a digital image file and a digital audio file. The controller is configured for directing transfer of the digital content, independent of a personal computer, via a modem between the memory card and a digital content service provider. The memory is configured for storing the digital image file and the digital audio file.

The advance of technology into the digital age has transformed nearly every facet of our lives. For the consumer, perhaps nothing represents this shift better than entertainment media. We have progressed from analog audio recordings and playback devices, such as a record player and eighttrack cassettes, to digital recordings and playback devices, such as compact disc players. In photography, digital cameras and digital video recorders are now commonplace.
However, with these changes come new problems and new opportunities. For example, a consumer can have digital photos stored on a memory card processed the same way that a roll of film was previously processed at a film processing center. The consumer delivers the memory card to the photo processing center by hand or by mail, and then waits for the processing center to produce the requested photos. While taking the pictures is more convenient, the processing end of the pathway is still slow and requires much human involvement. A consumer also could purchase digital music by buying a compact disc or purchasing music on the internet for downloading onto a memory device such as computer hard drive. However, each of these steps typically requires the interaction of a personal computer.
Accordingly, although the digital age has brought some improvement in the quality of music and photography, most consumers are still burdened with using a personal computer and multiple accessory devices for photo processing of image data from a digital camera and/or downloading digital music files.

System and method for transferring digital content on a memory card

Hewlett-Packard Development Company, L.P.


Agricultural formulations of fluroxypyr that contain an ester of fluroxypyr that is liquid at ambient temperatures, such as the 1-butoxy-2-propyl ester or the 2-ethylhexyl ester, and that contain a reduced amount of organic solvent or no organic solvent are disclosed. The formulations have good physical properties and are highly effective herbicides.

Agricultural chemicals, such as herbicides, insecticides, and fungicides are typically combined with carriers and adjuvants to obtain a formulated product before sale to the ultimate user. The adjuvants and carriers employed add to the cost and, in some cases, make the products less desirable environmentally. On the other had, these ingredients often contribute positively to the efficacy of the formulated product. The organic solvents, especially hydrocarbon solvents, typically found in formulated agricultural products are examples of carriers that have these characteristics. The preparation of formulated agricultural products that contain very little or no organic solvent, and, especially, no petroleum hydrocarbon or chlorinated hydrocarbon solvents, but that are at least as effective as formulated products that do, is a desirable objective.
Fluroxypyr, which is ((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetic acid, is a commercially available herbicide that is presently sold as the 1-methylheptyl ester in the form of an emulsifiable concentrate formulation containing 180 grams of acid equivalent per liter of formulation. Emulsifiable concentrate formulations containing higher levels of this ester and common solvents were found to be unsuitable due to solubility limitations. U.S. Pat. No. 4,108,629 proposes that emulsifiable concentrate formulations containing from about 2 to about 50 percent of fluroxypyr esters can be prepared, but only discloses such formulations containing up to about 25 percent.
Wettable powder and water dispersible granule formulations containing fluroxypyr in the form of the 1-methyl-heptyl ester have not been commercialized because they are not as effective as liquid formulations. The efficacy of such formulations can be improved by the addition of a low-volatile organic solvent, but this is not desirable because, in addition to the previously mentioned disadvantages of such solvents, they reduce the amount of fluroxypyr ester that the product can contain and still maintain acceptable physical properties.

Agricultural formulations comprising fluroxypyr esters which are liquid at 25.degree. C.


Provided herein are small molecule inhibitors for the targeting or IRE1 protein family members. Binding may be direct or indirect. Further provided herein are methods of using IRE1 small molecule inhibitors for use in treating or ameliorating cancer in a subject. Moreover, IRE1 small molecule inhibitors described herein are for the treatment of cancer, where the cancer is a solid or hematologic cancer.

Aggressive tumors have evolved strategies that enable them to thrive under constant adverse conditions. For example, cancer cells respond to hypoxia, nutrient starvation, oxidative stress, and high metabolic demand by adjusting their protein folding capacity via the endoplasmic reticulum (ER) stress response pathway. There exists a need for improved methods and compositions to target cancer cells and counter their mechanisms of survival.