A hypodermic needle device for administration of anesthesia to a patient's epidural space comprising a hypodermic needle having a barrel portion with opposed distal and proximal ends, a hub assembly located at the proximal end of the barrel portion of the needle, through which instruments such as a rigid stylet, or a flexible catheter having a pre-affixed connector, may be introduced into the needle, and a slot formed axially along the length of the needle from the distal end through the hub at the proximal end of the needle. The slot has a minimum width dimension not greater than the outer diameter of a stylet or epidural catheter such that during location of the epidural space, and placement of a catheter in the epidural space, the stylet and catheter will not come out of the needle, yet the needle may be easily removed from the catheter once the catheter is in place, by pulling the catheter through the slot in the needle.

1. Field of the Invention
This invention most generally relates to anesthesia needles used to administer regional anesthesia to a patient. More particularly the invention relates to a regional anesthesia needle used to apply anesthesia to the epidural space of a patient. Most particularly the invention relates to an epidural anesthesia needle having a slot running the length of the needle from the distal end through a hub at the proximal end. The slot allows the use of a catheter with a permanently pre-affixed connector at its proximal end for administration of anesthesia to a patient. The slot is formed with a dimension that is smaller than the outer diameter of a stylet and catheter. The smaller diameter prevents the stylet and catheter from inadvertently coming out of the needle during the procedure. Once the catheter is in place in the epidural space of a patient and secured, the needle is withdrawn and can be removed by pulling the flexible catheter out of the slot in the needle, thus allowing the use of a catheter with a permanently pre-affixed connector at its proximal end.
2. Description of the Prior Art
Regional anesthesia is performed to bring about anesthesia in a specific region of the body. The patient remains conscious of his surroundings and may retain complete mobility of the area anesthetized. When successfully performed, regional anesthesia provides complete analgesia in the specific area to which it was directed and requires only a small amount of local anesthetic. The regional anesthesia relevant to the present invention relates specifically to spinal anesthesia delivered to the epidural space, as related to the cervical, thoracic, lumbar, or caudal regions of the spine, but more specifically to the regional anesthesia performed in the lumbar or thoracic regions.
There are many preparative steps before administration of the anesthesia. The general technique of administering epidural anesthesia involves injecting a local anesthetic solution into the epidural space, from which it defuses to the immediate vertebral spaces around the injection site and around the outer layers of the spinal cord, surrounding spinal nerves, producing anesthesia. The technique is most commonly performed at the lumbar level of the spine and is applicable in the diagnosis and treatment of chronic pain, for example in cancer patients, as well as providing surgical and obstetric anesthesia.
The epidural space extends from the base of the skull to the tip of the caudal vertebrae, and lies between the dura which surrounds the spinal cord and the ligaments which join the vertebrae. The epidural space is not considered a true space, because unless separated, it is practically invisible.
Before administering the anesthesia to the epidural space, the space must first be located, and care taken not to penetrate to the spinal cord. There are two different techniques which can be used to determine when the tip of the needle has entered the epidural space; the "hanging drop", and "loss of resistance" techniques. An epidural needle is first inserted until a marked resistance is felt, indicating entry into the interspinous ligament, and up to but not through, the ligamentum flavum. At this point, in the "loss of resistance" technique, the epidural needle is advanced into the ligamentum flavum, and the stylet is removed. A syringe with an easily moving plunger is filled with air or normal saline and attached to the needle. When the needle tip is in the ligamentum flavum, air or saline can not be ejected from the syringe when pressure is applied to the plunger. Constant pressure is exerted on the plunger by one hand as the needle is slowly advanced. When the tip of the needle enters the epidural space, there is a sudden release of air or saline into the epidural space, thus the loss of resistance. Once the epidural space is located, the syringe is removed and a catheter is placed onto the needle hub, and then inserted through the epidural needle, between about 2 cm to about 4 cm past the end of the needle, into the epidural space. When the catheter is in place, the needle is then withdrawn over the catheter taking care not to move the catheter. Once the catheter is advanced past the tip of the needle the catheter cannot be withdrawn because it might be sheared by the sharp tip of the needle. If readjustment is needed, both needle and catheter must be removed together. An epidural catheter connector is then attached to the catheter to allow syringe attachment for administration of anesthesia through the catheter. The catheter is then taped in place on the patient's back.
With the above procedure in which the needle is removed by being slid over the catheter, the catheter can not have a connector "built in" or preaffixed to its proximal end because the needle would not fit over the connector. The typical connector is placed on the catheter after the needle is removed. The connector is comprised of three parts, two that are threaded together sandwiching the third part, an elastomeric tube. The catheter is slid into the connector going through the elastomeric tube. When the two threaded parts are tightened together the elastomeric tube is compressed, so its inside diameter (ID) squeezes the catheter outside diameter (OD). The problems with attaching a connector to the catheter at the time of treatment are that the connector can be over-tightened, crushing the catheter or it can be under-tightened creating a leak path or leading to the connector falling off the catheter potentially exposing the patient to extrinsic contamination. The procedure is cumbersome and the person performing the treatment may drop the connector during installation. A solution would be to have a catheter with a connector permanently or preaffixed to its proximal end by the manufacturer or at least prior to insertion of the catheter into the needle. However, the typical needle cannot be removed over a permanently or preaffixed connector.
One solution was advanced by Mohiuddin in U.S. Pat. Nos. 5,322,512 (the '512 patent) and 5,425,717 (the '717 patent). Mohiuddin's solution was to have a needle which was splittable and could break away from the catheter. The needle is removed from the catheter by breaking the needle in half along its length. Both the '512 and the '717 patents address this issue. The '512 patent deals with protecting the splittable needle, and the second includes with the splittable needle a catheter with a fixed connector. This needle can be used with a catheter having a permanently affixed connector, but presents its own problems. These problems include; the needle not splitting all the way, preventing its removal from the catheter as intended, and the needle splitting prematurely while still in the patient during placement, preventing catheter placement until the split needle is removed and another needle placed. The present invention solves the problems of the prior art by providing an epidural anesthesia needle which may be more efficiently and safely used with a catheter having a permanently affixed connector.


Compounds of Formula I, including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth:

Acquired immunodeficiency syndrome (AIDS) is the result of infection by HIV. HIV continues to be a major global public health issue. In 2015, an estimated 36.7 million people were living with HIV (including 1.8 million children)—a global HIV prevalence of 0.8%. The vast majority of this number live in low- and middle-income countries. In the same year, 1.1 million people died of AIDS-related illnesses.
Current therapy for HIV-infected individuals consists of a combination of approved anti-retroviral agents. Close to four dozen drugs are currently approved for HIV infection, either as single agents, fixed dose combinations or single tablet regimens; the latter two containing 2-4 approved agents. These agents belong to a number of different classes, targeting either a viral enzyme or the function of a viral protein during the virus replication cycle. Thus, agents are classified as either nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), or entry inhibitors (one, maraviroc, targets the host CCR5 protein, while the other, enfuvirtide, is a peptide that targets the gp41 region of the viral gp160 protein). In addition, a pharmacokinetic enhancer (cobicistat or ritonavir) can be used in combinations with antiretroviral agents (ARVs) that require boosting.
Despite the armamentarium of agents and drug combinations, there remains a medical need for new anti-retroviral agents. High viral heterogeneity, drug-associated toxicity, tolerability problems, and poor adherence can all lead to treatment failure and may result in the selection of viruses with mutations that confer resistance to one or more antiretroviral agents or even multiple drugs from an entire class (Beyrer, C., Pozniak A. HIV drug resistance—an emerging threat to epidemic control. N. Engl. J. Med. 2017, 377, 1605-1607; Gupta, R. K., Gregson J., et al. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis. Lancet Infect. Dis. 2017, 18, 346-355; Zazzi, M., Hu, H., Prosperi, M. The global burden of HIV-1 drug resistance in the past 20 years. PeerJ. 2018, DOI 10.7717/peerj.4848). As a result, new drugs are needed that are easier to take, have high genetic barriers to the development of resistance and have improved safety over current agents. In this panoply of choices, novel mechanisms of action (MOAs) that can be used as part of the preferred antiretroviral therapy (ART) can still have a major role to play since they should be effective against viruses resistant to current agents.
Certain potentially therapeutic compounds have now been described in the art and set forth in Blair, Wade S. et. al. Antimicrobial Agents and Chemotherapy (2009), 53(12), 5080-5087, Blair, Wade S. et al. PLoS Pathogens (2010), 6(12), e1001220, Thenin-Houssier, Suzie; Valente, Susana T. Current HIV Research, 2016, 14, 270-282, and PCT Patent applications with the following numbers: WO 2012065062, WO 2013006738, WO 2013006792, WO 2014110296, WO 2014110297, WO 2014110298, WO 2014134566, WO 2015130964, WO2015130966, WO 2016033243, WO2018035359, WO2018203235, WO 2019161017, and WO 2019161280.
What is now needed in the art are additional compounds which are novel and useful in the treatment of HIV. Additionally, these compounds should provide advantages for pharmaceutical uses, for example, with regard to one or more of their mechanisms of action, binding, inhibition efficacy, target selectivity, solubility, safety profiles, bioavailability or reduced frequency of dosing. Also needed are new formulations and methods of treatment which utilize these compounds.

Inhibitors of human immunodeficiency virus replication


A new method for processing search radar data is revealed using the mathematics of random matrix theory. During the time that the radar receiver is listening for return target echoes, the raw data stream is fed to an analog to digital converter to create a sample voltage file. This sample voltage file is processed by a digital signal processor that computes the eigenvalues of a sample covariance matrix generated for each pulse duration interval. The ratio of the largest to smallest eigenvalue is determined and compared to the system noise eigenvalue ratio. The sensitivity for detecting targets over the present state of the art is expected to be an approximate enhancement factor of one thousand, due to the detection of coherent energy instead of a transmitted waveform. The increase of detection distance for same radar cross section is expected to be an approximate 5.6 enhancement factor.

Search radars transmit energy packets and receive energy echoes from targets. In order to discover a target, the signal to noise power ratio (SNR), where signal power here is the returned radar echo power, and noise power is the system power for no target, must be equal to or greater than a threshold (Kossiakoff U.S. Pat. No. 4,005,415). In operational uses, this threshold is 10. As an example of search radars, in FIG. 1, a nominal SNR curve as a function of target distance is given for the Russian P37 'Bar Lock' search radar (www.radartutorial.eu), for a 10 m2 target. Such a target is a typical third generation fighter radar cross section for centimetric radiation. From FIG. 1, the 'Bar Lock' has a nominal detection range of approximately 220 km (SNR≅10) for this particular target. We wish to increase the detection range to approximately 1200 km for this same target radar cross section, by doing a new method of radar processing. The reader should appreciate that a detection of any target at 1200 km, yet alone a target of 10 m2 cross section, is so far outside our example of a conventional P37 search radar envelope that the original Russian radar design engineers would consider it fantasyland.

Method for search radar processing using random matrix theory


A hybrid vehicle includes an electric motor with a rotatable rotor. A centrifugally-actuated clutch has a first rotatable member, a second rotatable member, and at least one actuator member attached to the first rotatable member. One of the first rotatable member and the second rotatable member is operatively connected to the wheels. The other of the first rotatable member and the second rotatable member is operatively connected to the rotor. The actuator member is configured to transfer torque between the first rotatable member and the second rotatable member by an amount that decreases due to centrifugal force acting on the actuator member as a rotational speed of the first rotatable member increases. A method of control is also provided.

Electric drive modules for hybrid vehicles include an electric motor that is connected to a drive axle of the vehicle through a gearing arrangement. The electric motor provides propulsion assistance in certain vehicle operating modes. A higher gear ratio of the gearing arrangement allows the motor to have a relatively low maximum torque, as the torque provided by the motor is multiplied by the gear ratio. An electric drive module may be limited in gear ratio by a number of factors, especially by the top speed of the motor. That is, at high axle speeds, the speed of the electric motor will be even greater with a high gear ratio, so the gear ratio must be kept below that which would cause the motor to exceed its maximum speed.

Hybrid powertrain with centrifugally-actuated motor disconnect clutch and method of control


Described in example embodiments herein are techniques for implementing power savings in a wireless local area network (WLAN). In accordance with an example embodiment, a centralized controller can be employed to gather data about network activity and select access points to switch to power save mode. Optionally, the controller may designate certain access points to remain active so as to monitor for clients attempting to access the WLAN. An aspect of an example embodiment is that it allows the controller to configure and manage power consumption based on demands on the overall system. In an example embodiment, techniques for implementing power savings within individual hardware components, such as access points, are disclosed. An aspect of a technique described in an example embodiment is that it provides flexibility to balance power savings and performance.

Wireless networks may operate twenty-four hours a day, seven days a week. Most wireless network environments, however, do not need the entire network to be powered up at all times. For example, a typical workplace may have very low use requirements during evening and weekend hours. During low use periods, it is desirable to power down unneeded devices in order to save energy and, consequently, costs. Traditionally, the components of a network, such as an access point (AP) and controller, contain facilities to disable subsections so as to limit power consumption. A challenge to the system designer is to determine when to enter and exit power saving modes.

Multiple density configurations and algorithms for intelligent power savings infrastructure in wireless LANs


A molded safety pin having an elongated base portion with extensions at both ends is described. At the first extension a hinged connection provides the means for biasing the pin portion at the juncture of the means for anchoring the pin and the base portion. At the second extension a detent structure provides the means for holding the pin portion securely when the safety pin is in a closed position while permitting convenient manual release of the pin when required.. Additionally a simplified injection mold for fabricating the safety pin is described.

This invention relates to safety pins of the positive locking type, wherein the piercing end of the biased pin shaft is manually depressed from its open position and moved into a restraining or locking detent, and wherein the pin can be subsequently released only by a joint manipulation of the pin shaft and locking detent. Safety pins of this character are disclosed in my U.S. Pat. Nos. 2,546,669, 2,760,247, 3,018,533, 3,883,930, and 4,071,927. The instant invention is concerned with improvements on my patents, and is particularly directed to an improved safety pin of inexpensive molded construction.
It is therefore a principal object of the invention to provide a molded safety pin of the character described above that can be mass produced inexpensively.
A further object of this invention is to provide a safety pin of the character described above that can be molded in a simplified plastic injection mold.
Another object of the invention is to provide a safety pin of the character described above wherein a hinged section provided the means for biasing the pin shaft.
Still another object of this invention is to provide a safety pin of the character described above having additional convenience in both pin insertion and pin release.
An additional object of this invention is to provide a safety pin of the character described wherein the pin shaft can be fabricated in either plastic or metal.


A method for a prediction correlation between a first group of branch instructions in a bunch of instructions and a second group of branch instructions in a bunch of instructions is disclosed. The method includes indicating a direction of a plurality of branch instructions in a bunch of instructions. More particularly, the method includes building an address composed of an instruction fetch address and bits in a history register. The method accesses a bunch of instructions using the fetch address and accesses a prediction bits set from a branch history table using the composed address. The accessed bunch of instructions are processed. Further, the history register and the branch history table are updated to correlate a first group of a branch instructions in the accessed bunch of instructions to a second group of branch instructions in a next group of branch instructions in the bunch of instructions.

Conventional microprocessors which do not use a superscalar or multipipelined architecture accept instructions from a serial instruction stream, and process those instructions sequentially, in a logical order allowing jumps and branches. When a conditional branch instruction is encountered, the microprocessor tests certain flags which have been set by instructions previously executed by the microprocessor, and either resumes executing at the instruction which followed the conditional branch instruction in the serial instruction stream, or resumes execution at an instruction stored at a location described by the conditional branch instruction.
Superscalar microprocessors can accept a serial instruction stream, and produce the same results as a non superscalar microprocessor. However, superscalar microprocessors may internally process multiple instructions simultaneously, which may cause instructions to be executed out of their logical order, the order intended by the original creator of the instructions.
Referring now to FIG. 1, a conventional superscalar microprocessor 102 and memory 104 is shown. Fetch circuitry 106 directs memory 104 to transfer blocks of instructions 110, 112 starting with the memory address contained in the fetch program counter 108 a block at a time into memory area 114, for simultaneous processing by execution units 116, 118, 120. Although the size of the blocks 110, 112 and memory area 114 shown in FIG. 1 are four words, and the number of execution units 116, 118, 120 shown in FIG. 1 is three, conventional superscalar microprocessors may have blocks 110, 112 and storage areas 114 of any size, and any number of execution units 116, 118, 120.
Producing results in a superscalar microprocessor which are identical to the results which would be produced by a conventional non-superscalar microprocessor poses certain problems for a superscalar microprocessor. One problem posed by a superscalar microprocessor design arises in the processing of a conditional branch instruction. Because the instructions which set the flags in a superscalar microprocessor may not have been processed at the time the branch instruction is ready for execution by the superscalar microprocessor, it is impossible to determine with certainty which instruction the non-superscalar microprocessor would have executed after the execution of the conditional branch instruction without waiting for all instructions which logically precede the conditional branch instruction to execute. Waiting for all such preceding instructions to execute would introduce undesirable delays.
One approach to avoid these delays has been to attempt to predict the result of the conditional branch instruction without waiting for the logically preceding instructions to execute, and continue processing instructions as if the prediction was accurate. When the instructions which logically precede the conditional branch have all completed execution, the prediction may be tested for accuracy. If the result of the branch prediction is indeed accurate, processing continues and the undesirable delays are avoided. If the result of the branch prediction is inaccurate, processing stops, and resumes at the instruction which should have been executed after the conditional branch, with the delay no greater than if processing had suspended waiting for execution of the instructions which logically preceded the conditional branch instruction.
Various conventional ideas exist for predicting which branch direction to take. One approach is to always predict the branch described in the branch instruction will be taken. Such a prediction can often be correct more than fifty percent of the time, as many programs contain loop instructions that result in the branch described in the branch instruction being taken more often than not. For example, the PASCAL instructions:
______________________________________ For i:=1 to 100 do begin . . . end; ______________________________________
cause the branch described in the branch instruction to be taken 99 percent of the time. Of course, other instructions, such as if..then, while..do, and repeat..until may not yield the same prediction accuracy, but the scheme is relatively simple to implement, saving valuable area in a superscalar microprocessor 102.
When an instruction described in the conditional branch instruction is executed following the conditional branch instruction, the action is described as "taking the branch" and thus, the branch or "direction" of the branch is "taken". When the instruction which physically follows the branch instruction is executed because the conditions of the conditional branch instruction were not true, the action is described as "not taking the branch" and the branch or "direction" of the branch is described as "not taken."
One idea which can improve the accuracy of branch prediction is known as "bimodal" branch prediction and involves the use of a two-bit saturating counter as a prediction indicator to indicate whether a branch should be taken. A two bit saturating counter makes use of the assumption that branches should be taken in groups, and so the whether a branch or group of branches should be taken may be predicted by reference to whether the last branch or branches were taken. Referring now to FIGS. 2A and 2B, an illustration of a state table of a two-bit saturating counter is shown. State 210 represents a strong indication that the branch should not be taken. State 212 represents a weak indication that the branch should not be taken. State 214 represents a weak indication that the branch should be taken. State 216 represents a strong indication that the branch should be taken. The state of the prediction may be initialized to any state 210, 212, 214, 216. The branch is predicted taken if the most significant bit of the current prediction state has a value of "1", such as states 214, 216, and the branch is not taken if the most significant bit in the current prediction state has a value of "0", such as states 210, 212. When the prediction is tested after the instructions logically preceding the branch have been executed, the state of the prediction is changed according to table 218. Column 220 represents the current state, column 222 represents the new state, and column 224 represents the actual branch action: taken, meaning the branch was actually taken, or not taken, meaning the branch was not actually taken. From a strong indication, two actual branches opposite the indication are required before a change is made to the branch prediction. Other arrangements of counters, including those with more than two bits, may be utilized to vary the number of actual branches opposite the strong indication required to change the prediction.
The states of FIG. 2A may also have the values opposite those shown: strong taken, weak taken, weak not taken and strong not taken for states 210, 212, 214, 216, respectively. In this case, the most significant bit having a value of "1" indicates the branch should be predicted not taken, "0" indicates the branch should be predicted taken. Table 218 of FIG. 2B is used as described above, with the opposite actual actions in column 224.
The accuracy of bimodal branch prediction may be enhanced through the use of a history register, which records the history of the actual branch action taken. The use of a history register assumes that conditional branches are taken according to repeating patterns. For example, in the following PASCAL program:
______________________________________ For i:= 1 to 100 do For j:= 1 to 3 do begin . . . end; ______________________________________
The inner branch will be taken two times, but not the third, followed by the outer branch taking its branch, behavior which will be repeated ninety-eight times due to the outer branch. Knowledge of the behavior of the last four branches of both the inner and outer branch can predict the behavior of the next branch with higher accuracy than bimodal branch prediction. A shift register may be used as a history register to keep track of the behavior of the branches by shifting bits one position in a single direction (right or left) for each branch encountered, shifting in a "1" for each branch that is actually taken, and shifting in a "0" for each branch that is not actually taken. For example, a left shift register would read 1101 after the outer branch was taken, with the zero in the second least significant position showing that the end of the inner loop had been reached. The next branch should be predicted taken, as it will be the first branch in the next iteration of the inner loop.
The history register is used with a history table and the two-bit saturating counters of bimodal branch prediction to complete the prediction. Referring now to FIG. 3, the contents of a history register 308 as described above are used as an index to a history table 312. The pointer 316 having the same index 314 as that of history register 308 points to a two-bit saturating counter 318, 320, 322, 324, 326 having a state table as described above with reference to FIG. 2A which is used to determine the branch prediction as described above. The entire history register 308 may be used as an index to the table 312, or a certain number of bits including and adjacent to the bit most recently shifted in to the history register 308 may be used as an index to the table 312.
Another method is similar to the history table method described above, except that the address of all, or a certain number of the least significant bits, of the address of the conditional branch instruction are used in place of the history register 308 as the index to the table 312.
Still other methods combine the low order bits of the address of the conditional branch instruction and some or all of the branch history, for example by concatenation or exclusive-OR-ing, to create an index to the table 312, in place of the history register 308 alone.
Referring again to FIG. 1, if the address of the conditional branch instruction is used to create the index, the address must be computed from the fetch program counter register 108 and the position of the conditional branch instruction in the memory 114, causing added complexity of the microprocessor 102 and computational delay. If the history is used to create the index, it must be updated for each conditional branch instruction executed, resulting in additional complexity in the design of the microprocessor 102.

Branch prediction based on correlation between sets of bunches of branch instructions


Ring deuterated gaboxadol is provided. The ring deuterated gaboxadol is useful in the treatment of psychiatric disorders and is more effective than non-deuterated gaboxadol in such treatments. Deuterated gaboxadol is useful in combinations with other compounds to provide additive and synergistic effects for patient therapies. In a specific embodiment, the deuterated gaboxadol is d6-gaboxadol.

According to the World Health Organization, depression is the leading cause of disability and ill health in the world affecting more than 300 million people worldwide and costing the global economy an estimated $1 trillion in lost productivity each year. The Centers for Disease Control (CDC) estimate that in the U.S. alone, 20-25% of all adults aged 18 and older and 10.9% of young adults aged 18-25 experience at least one episode of major depression each year. Left untreated, mental diseases, like major depression, are a major contributor to suicide in the U.S which takes the lives of more than 47,000 Americans every year or one death by suicide every 11 minutes (Shepard et al., Suicide Life Threat Behav. (2016) 46(3):352-62.). There is one suicide for every estimated 25 suicide attempts which means each year there are an estimated quarter million people who become suicide survivors. Hence, there is a critical unmet need for medications for the treatment of psychiatric disorders such as suicidal ideation and treatment-resistant depression (TRD).
Psychiatric disorders are common in across the world and in the United States, with nearly one in five U.S. adults estimated to experience a mental illness (over 50 million in 2019), with the highest prevalence of mental illness seen among females and young adults aged 18-25 years, including (alphabetically) Agoraphobia, Anorexia Nervosa, Any Anxiety Disorder, Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Binge Eating Disorder, Bipolar Disorder, Borderline Personality Disorder, Bulimia Nervosa, Dementia, Eating Disorders, Generalized Anxiety Disorder, Major Depression, Obsessive-Compulsive Disorder (OCD), Panic Disorder, Persistent Depressive Disorder (Dysthymic Disorder), Personality Disorders, Post-Traumatic Stress Disorder (PTSD), Postpartum Depression, Schizophrenia, Social Anxiety Disorder, Social and other Specific Phobias and Treatment-resistant Depression (TRD). It is widely observed that psychopharmacological agents used to treat psychiatric disorders have only modest efficacy and considerable side-effects. Hence, there is a critical unmet need for medications for the treatment of psychiatric disorders.
Gaboxadol, also called gaboxadolum, or THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c) pyridin-3-ol; C6H8N2O2; Cas Number: 64603-91-4; PubChem CID: 3448) is a selective GABAA receptor agonist with a preference for δ-subunit containing GABAA receptors. In the early 1980s gaboxadol was the subject of a series of pilot studies that tested its efficacy as an analgesic and anxiolytic, as well as a treatment for tardive dyskinesia, Huntington's disease, Alzheimer's disease (Mohr, Bruno et al. Clin Neuropharmacol. 1986; 9(3):257-63) and spasticity. In the 1990s gaboxadol moved into late stage development for the treatment of insomnia. The development was discontinued after the compound failed to show significant effects in sleep onset and sleep maintenance in a three-month efficacy study (ClinicalTrials.gov Identifier: NCT00209963). Methods of treating depression with gaboxadol are disclosed in WO2004112786, which is incorporated by reference herein in its entirety.
A clinical trial has been undertaken to investigate the efficacy of gaboxadol in the treatment of symptoms of Angelman Syndrome (a developmental disorder) (ClinicalTrials.gov Identifier: NCT02996305) (Cogram, Deacon et al. 2019). Patent applications on related subject matter include U.S. Pat. No. 9,744,159, published US Patent Application No. 2017/348232 and WIPO International Patent Application WO2017015049, the contents of which are incorporated herein by reference in their entireties.
A clinical trial by Lundbeck reported at ClinicalTrials.gov Identifier: NCT00807248 treated 490 patients with daily oral doses of escitalopram (20 mg) and gaboxadol (5 mg or 10 mg). The trial found that oral gaboxadol at this amount provided no additional benefit relative to escitalopram alone in the treatment of patients with severe major depressive disorder. A report on this trial is found at Kasper et al (2012) Int J Neuropsychopharmacol. 2012 July; 15(6):715-25. The trial did not test the effect of gaboxadol alone.
Gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol) (THIP)) is also described in EP Patent No. 0000338 EP 0840601, EP1641456, U.S. Pat. Nos. 4,278,676, 4,362,731, 4,353,910, and WO 2005/094820, the contents of which are hereby incorporated by reference herein in their entireties.
Effects of deuteration are described in (Harbeson and Tung, 2014; Perrin and Dong, 2007; Perrin et al., 2005; Turowski et al., 2003). Binding isotope effects can contribute positively or negatively to a measured deuterium kinetic isotope effect (DIE) (Schramm, 2007; Schwartz and Schramm, 2009). These DIE changes are primarily due to the increase in energy required for the cleavage of the carbon-deuterium (C-D) covalent bond than the energy required to cleave the carbon-hydrogen (C—H) bond. The primary DIE can be expressed as kH/kD, the ratio of the rate of C—H vs. C-D bond-cleavage (Harbeson and Tung, 2014). Such DIE effect can be expected for example in drug metabolism by cytochrome P450s (CYPs) (Meunier et al., 2004). Gaboxadol is not metabolized by CYPs and the majority (84-93%) of the drug is excreted in the form of unchanged, unmetabolized drug and a glucuronic acid conjugate in urine (Schultz et al., 1981).
Citation of a reference, including publications, patents, and patent applications, herein shall not be construed as an admission that such reference is prior art to the present invention.

Ring deuterated gaboxadol and its use for the treatment of psychiatric disorders


A sample changer for precise positioning of a selected sample from a plurality of samples stored on a removable annular sample file. The samples comprising a rectangular dimensioned object is radially removed from the annular cassette and precisely positioned at a predetermined location for testing. Upon completion of the desired testing, the sample is replaced into the cassette which is repositioned and a subsequently selected sample is accordingly extracted and positioned for testing. Furthermore, the present invention includes a combination of elements which act together to detect and dislodge samples which may become temporarily stuck or jammed in the mechanism, reducing the need for operator intervention. Furthermore, the annular cassette is removable from the sample changing mechanism and includes a concentric locking ring which selectively retains all samples within the cassette or permits the removal of all samples. The sample changer mechanism includes a stationary arcuate slide retainer wherein the slides released by the annular locking ring are retained within the cassette mechanism until selectively positioned and lowered into the mechanism for testing.

In complex manufacturing processes, it is frequently necessary to monitor the chemical, mechanical, metallurgical or other characteristics during the process. In particular, chemical composition manufacturing processes monitored by x-ray spectroscopy require the sampled material to be positioned to reflect or refract a beam of x-ray to a measuring detector, wherein position deviations by a few parts of a mil cause significant variations in analysis readings.
In a typical sample changer, samples, comprising rectangular samples of compressed material approximately 3.times.4 cm., are arranged in a linearly spaced tray of approximately 35 cm. in length and are retained within the sample tray by forces provided by spring elements. The sample tray is received by and moveable in a generally u-shaped channel piece of approximately twice the length of the sample tray, at about the center of which is a mechanism for which mechanically forces a selected sample through the bottom of the tray into a position defined on one surface by fixed, rigid members, and retained by spring members. The positioning and sample retaining spring members become fatigued and deformed over time and use, causing the apparatus to jam or otherwise improperly function. Furthermore, the spring retention typically used is relatively intolerant of accumulated residual particulate matter from the samples, causing wearing or displacement of the samples from the desired position. Moreover, so critical is the position of the sample x-ray spectroscopy that s significant sample displacement is dependent on the position of the sample tray within its channel. In particular, when the bulk of the sample tray is at either extreme, that is forward or rearward, sufficient bending of the support mechanism causes a variation in the x-ray spectroscopy reading of the sample.
Moreover, prior art sample changers have required the operator to place the samples in a particular sequence and in order, making it virtually difficult or inconvenient to operate or to attempt to adjust the weight of the sample tray by positioning the samples therein. Thus, the existing changers provide marginal reliability and problematic operation.


A capacitive load driving circuit which includes an operational amplifier, a pulse width modulator, a digital power amplifier, a first filter, a first feedback circuit and a second feedback circuit. The operational amplifier outputs a differential signal between a signal fed back to the inverting input terminal and an input signal inputted to the non-inverting input terminal. The pulse width modulator pulse width-modulates output from the operational amplifier and outputs a digital signal. The digital power amplifier amplifies power of the digital signal. The first filter smooths output of the digital power amplifier and inputs the smoothed signal to the capacitive load as the driving signal. The first feedback circuit feeds back the driving signal outputted from the first filter to the inverting input terminal of the operational amplifier. The second feedback circuit feeds back a signal outputted from the digital power amplifier, which signal includes a phase which is advanced relative to the driving signal, to the inverting input terminal of the operational amplifier.

1. Field of the Invention
The present invention relates to a capacitive load driving circuit, a droplet ejection device, a droplet ejection unit and an inkjet head driving circuit, and more particularly relates to a capacitive load driving circuit, droplet ejection device, droplet ejection unit and inkjet head driving circuit for driving capacitive loads.
2. Description of the Related Art
Heretofore, inkjet head driving circuits have caused ink droplets to be ejected from nozzles of inkjet heads, which nozzles are provided in correspondence with piezoelectric actuators, by outputting analog driving signals to the piezoelectric actuators so as to discharge the ink droplets from the nozzles. In such an inkjet head driving circuit, an analog amplification circuit is employed, and an analog driving signal which has been power-amplified by the analog amplification circuit is outputted to the piezoelectric actuators. However, analog amplification circuits have a drawback in that power supply efficiency is poor and they tend to generate heat during power amplification. Consequently, when a number of piezoelectric actuators are driven at the same time, a lot of heat is generated and there is a risk of heat damage to the driving circuit itself.
Further, it has been necessary to additionally mount radiators at inkjet head driving circuits in order to dissipate the heat generated by the analog amplification circuits.
Further yet, because piezoelectric actuators are capacitive elements, there is a problem in that when the number of piezoelectric actuators that are being driven at the same time is large, the waveform of a driving signal being inputted to the piezoelectric actuators is degraded, and when the number of piezoelectric actuators being driven at the same time is small, there is a lot of ringing in the waveform of the driving signal.
As a technology for solving these problems, a technique of correcting a voltage of a driving signal at an inkjet head driving circuit in accordance with an environmental temperature of an inkjet printer has been disclosed (see, for example, Japanese Patent Application Laid-Open (JP-A) No. 11-20203). According to the technology of JP-A No. 11-20203, the voltage of an analog driving signal outputted from a driving circuit is corrected such that the voltage is lower when the environmental temperature is higher and the voltage is higher when the environmental temperature is lower. In addition, a structure thereof employs a thermistor which has a characteristic of resistance falling when environmental temperature rises, so as to prevent thermal runaway of the driving circuit. As a result, a danger of thermal damage to the driving circuit can be avoided.
Further, in a technology of JP-A No. 2000-117980 relating to inkjet head analog amplification circuits, rather than bipolar transistors, MOSFETs are used as transistors included in the analog amplification circuits. Thus, the danger of thermal damage to the driving circuits due to heat generation is avoided.
JP-A No. 2000-117980 also discloses a technique for generating analog driving signals to drive piezoelectric actuators with large load capacitances without malfunctioning. In this technology of JP-A No. 2000-117980, negative feedback is applied to terminal voltages of the piezoelectric actuators in order to maintain terminal voltages of the piezoelectric actuator at a predetermined bias voltage. As a result, it is possible to compensate for degradation of the waveform of the analog driving signal that is inputted to the piezoelectric actuators.
With the conventional technologies described above, it is possible to avoid the risk of thermal damage to a driving circuit and to compensate for degradation of a waveform of an analog driving signal. However, none of the related technologies described above suppresses heating of the driving circuit itself. Therefore, it is still necessary to mount a radiator in order to dissipate heat generated in an analog amplification circuit.
Now, D-class amplification circuits which use pulse width modulation are known as amplification circuits in which power supply efficiency is good and heat generation temperatures are low. Whereas analog amplification circuits are of types which utilize linear amplification operations of transistors and the like, D-class amplification circuits are circuits which perform amplification by using digital techniques, meaning switching operations, utilizing variations in average output provided by ratios of on and off states of power sources. More specifically, at a D-class amplification circuit, input signals are pulse width-modulated to digital signals, power amplification is performed on the digital signals, the digital signals are demodulated back to analog driving signals after power amplification, and the analog driving signals are outputted. Thus, it is possible to perform amplification more efficiently than with an analog amplification circuit, and power consumption and heat generation are lower. Hence, in recent years, D-class amplification circuits have been particularly employed in audio circuits.
Employing such a D-class amplification circuit in place of an analog amplification circuit in an inkjet printer driving circuit has been considered as a method for suppressing the generation of heat in the driving circuit. However, there are a number of problems with employing D-class amplification circuits in inkjet head driving circuits, and this has not yet been realized.
To be specific, the load of an audio circuit is a speaker, so the load can be regarded as a substantially resistive load, and there is little load variation. In contrast, a piezoelectric actuator is a capacitive load, and the load varies in accordance with the number of actuators being used at the same time, which is problematic.
Furthermore, because a D-class amplification circuit performs power amplification after an input signal has been converted to a digital signal, a low-pass filter (LPF) is provided in order to return the power-amplified signal to an analog signal. The low-pass filter is structured with an inductor and a capacitor. Therefore, when capacitive elements such as piezoelectric actuators are being driven, a cutoff frequency of the LPF will vary in accordance with load variations due to variations in the number of piezoelectric actuators being driven at one time, which is problematic.
Moreover, for audio signals, signals in a frequency range of up to 10 kHz, possibly 20 kHz, are used. However, the range of driving signals of piezoelectric actuators is 100s of kHz. Accordingly, a sampling frequency of 5 MHz to 10 MHz is necessary for application of a D-class amplification circuit to an inkjet head driving circuit, but it is difficult to perform rapid switching operations at these frequencies in a D-class amplification circuit.
Because of these problems, it has been difficult to apply D-class amplification circuits to inkjet head driving circuits.

Capacitive load driving circuit, droplet ejection device, droplet ejection unit and inkjet head driving circuit


In accordance with an exemplary embodiment of the invention, a friction plate assembly is provided. The assembly includes a locking member having a toothed portion, a bolt extending through the locking member, and a friction plate configured for frictional engagement with the locking member. The friction plate receives the bolt therethrough and includes at least one biasing member configured to bias the bolt and the locking member in a first direction. When a predetermined force acts on the at least one biasing member, the friction plate is configured to force the locking member toothed portion into engagement with an object to facilitate preventing movement of the bolt in a second direction.

Conventional adjustment assemblies, for example, adjustment assemblies which allow for adjustment of a steering column in a vehicle, include a lever that is rotatable between two positions to lock and unlock the adjustment assembly. For example, with a lever in a first position, the adjustment assembly may lock a steering column in a desired position, thereby fixing the steering column against adjustment. The lever may be rotated to a second position, thereby unlocking the adjustment assembly and allowing the steering column to be adjusted.
Some known steering column assemblies may include one or more friction locks arranged along the raking and telescoping ranges of motion of the steering column. Such locks may facilitate fixing a position of the steering column assembly or enabling adjustments in both the telescoping and raking directions. For example, a steering column lock may include friction plates to create additional friction surfaces between friction plate sets to achieve higher holding loads. As more plates are added to the set, more friction is achieved. However, some known locks may not provide a frictional force sufficient to prevent movement of the steering column assembly during high load events such as a crash event.
Accordingly, it is desirable to provide a system and method for selectively fixing and adjusting a position of a steering column with improved resistance to high loads.

Steering Solutions IP Holding Corporation


Various aspects provide for genetically modifying photosynthetic cells. In some cases, an integrated light harvesting efficiency of photosynthetic cells may be increased by reducing the amount of incident light that is absorbed but not used for photosynthesis. In some cases, an increased transparency may be associated with an increased light harvesting efficiency when absorption due to non-photosynthetic processes is reduced. A reduced capacity of various light-harvesting antenna apparatus may increase transparency. In some cases, a capacity of an organism to adapt to varying light levels may be reduced, and in certain cases, a modified organism may have a reduced ability to acclimate to a low light irradiance.

1. Technical Field
The present invention relates to improving the efficiency with which photosynthetic organisms use light.
2. Description of Related Art
Photosynthetic organisms use energy from light to form chemical bonds. Energy embodied within the chemical bonds may be used at a later date. As such, chemical bonds provide a storage mechanism for the energy associated with incident light.
A supply of light is often finite in a given period of time. For a given fluence of incident light, photosynthetic organisms may use some of the light to perform photosynthesis. Some of the light may not be used for photosynthesis. Some light may be converted to heat. Some light may be absorbed and reemitted (e.g., fluoresced). Some light may damage the organism. Light that is not used for photosynthesis may not be converted into stored chemical energy within the organism, and so the energy associated with this unconverted light may not be available for subsequent use. Improving the conversion of incident light to biomass (e.g., increasing the percentage of incident energy converted to chemical bonds) may increase the efficiency of biomass production, which may increase the amount of incident solar energy available for subsequent use.


A heat exchanger of the type for directing air across a core thereof for heat transfer with fluid flowing within the core includes a pair of tubes connected in parallel between an inlet and an outlet. The tubes form a plurality of passes across the face of the heat exchanger with tube bends at the ends of each pass defining a serpentine path. A header channel extends over the bends of the passes. The header channel includes a zinc alloy coating on the interior surface thereof in contact with the bends. The zinc alloy coating provides sacrificial corrosion that prevents corrosion of the bends.

Heat exchangers have been used in vehicles as either radiators or condensers. Such heat exchangers may be of the serpentine flow tube type. Representative of this type of heat exchanger is the condenser disclosed in U.S. Pat. No. 4,901,791 issued Feb. 20, 1990 in the name of Kadle, and assigned to the assignee of the subject invention. The patent discloses a serpentine condenser having unequal flow paths communicating between an inlet and an outlet. The heat exchanger includes a header channel forming a mounting bracket for supporting the flow tubes and for allowing mounting of the condenser in the vehicle.
During testing of long life alloys for serpentine tube and center condensers, it has been determined that the cores almost always fail on a tube bend. In the tube bend area there are no centers contacting the tube. In the core face, the zinc within the air centers helps protect the tubes by sacrificially corroding itself over a broad, but shallow area thereby preventing deep pits through the tube. Currently, brackets or header channels are fitted over the ends of the core in the area of the tube bends to mimic the mounting arrangement for a headered tube and fin style condenser. A layer of protective zinc may be placed on the steel by hot dip galvanizing. Currently, the header channels are then painted on both sides with epoxy paint. However, the paint acts as a barrier to the zinc.
The benefit of using corrosion resistant materials in a radiator is disclosed in U.S. Pat. No. 4,209,059 issued Jun. 24, 1980 Anthony et al and U.S. Pat. No. 4,473,110 issued Sep. 25, 1984 in the name of Zawierucha. The '059 patent discloses a corrosion resistant material between the header and tank, and the Zawierucha patent discloses a corrosion resistant header in a plate and fin type heat exchanger.

Sacrificial brackets for aluminum heat exchanger


A sliding sleeve for a disengagement mechanism for clutch actuation in motor vehicles has at least two pairs of cams with convexities of different heights from an actuation level on the sliding sleeve that is connectable to the clutch. Each of the pairs of cams selectively fits into a window of an oscillating link or clutch release fork, whereby the oscillating window and sliding sleeve have contours that fix the sliding sleeve at one position. By selecting which of the pair of cams engages the oscillating link or clutch release lever, different mounting heights of the actuation level on the sliding sleeve from the oscillating link or the clutch release fork may be realized.

1. Field of the Invention
The invention relates to a disengagement mechanism for clutch actuation in motor vehicles.
2. Description of the Related Art
A prior art disengagement system known from reference DE 38 10 369 A1 includes a clutch release fork having one end that is pivotally supported on a casing part and another end that is connected to an operating mechanism. An area lying between these two ends has an opening that is penetrated by a gear shaft and partially penetrated by a release bearing, whereby two brackets located opposite each other on a sliding sleeve 8 of the clutch release bearing are provided for fastening the clutch bearing to the clutch release fork. A radial flange located on the sliding sleeve has two convexities whose crown line interacts with a surface of the clutch release fork. The convexities on the radial flange are limited toward the middle of the sliding sleeve by a boundary edge that interacts with a guide edge in the clutch release fork to assume a position relative to the clutch release fork that is secured against torsion.

Disengagement mechanism for clutch actuation in motor vehicles


A method and system of customizing a portable voice-based control user interface for multiple types of appliances are disclosed. The method performed at a user device includes establishing a data communication connection with a voice control apparatus; detecting a first user request to update a NLP module of the voice control apparatus; establishing a connection to a NLP model server; displaying a listing of appliance types and a respective listing of appliance functions for each appliance type, in a graphical user interface of the user device; receiving user selection of a first set of appliance functions for a first appliance type and a second set of appliance functions for a second appliance type; downloading, from the NLP model server, a first NLP model for the first set of appliance functions for the first appliance type, and a second NLP model for the second set of appliance functions for the second appliance type; and integrating the first NLP model and second NLP model into the NLP module of the voice control apparatus.

Recently, voice-based digital assistants, such as Apple's SIRI, Amazon's Echo, Google's Google Assistant, and Microsoft's Cortana, have been introduced into the marketplace to handle various tasks such as home appliance controls, web search, calendaring, reminders, etc. One advantage of such voice-based digital assistants is that users can interact with an appliance in a hands-free manner without handling or even looking at the appliance. Conventionally, to initiate the voice-based digital assistant, users speak a trigger phase (e.g., a predefined wake-up word or command) to the voice-based digital assistant, or interacts with a user device (e.g., by opening an application on a smartphone and pressing virtual buttons on the user interface) that is coupled to control the voice-based digital assistant. The voice-based digital assistant interprets the voice command it receives after it has been activated, and performs an action (e.g., providing an informational answer and/or sending an encoded instruction to control a peripheral device, such as an appliance in a smart home environment).
Conventional voice-based digital assistants interpret a wide range of user's voice command, and perform actions accordingly, such as providing an informational answer, and/or sending an encoded instruction to control a peripheral device (e.g., an appliance in a smart home environment). Conventional digital assistant utilizes a comprehensive natural language processing model to interpret a user's intent and disambiguate the user's voice command based on various contextual factors, such as the user's location, the user's past behavior, the user's calendar, etc. However, the accuracy of the recognition is low, and the user is frequently frustrated with non-responsive answers or erroneous commands being generated based on incorrectly derived user intent.
It would be beneficial to provide portable NLP interface to improve the way that multiple appliances are controlled.

System and method for customizing portable natural language processing interface for appliances


A method includes configuring a first plurality of beamsplitters in a network of interconnected beamsplitters of an optical circuit into a transmissive state. The optical circuit is configured to perform a linear transformation of N input optical modes, where N is a positive integer. The first plurality of beamsplitters is located along a beam path within the optical circuit and traversing a target location. The method also includes configuring a second plurality of beamsplitters in the network of interconnected beamsplitters of the optical circuit into a reflective state to reconfigure the optical circuit into a reconfigured optical circuit. The reconfigured optical circuit is configured to perform a linear transformation on M input optical modes, where M is a positive integer less than N. The second plurality of beamsplitters is located along at least one edge of the optical circuit.

Scaling up linear optics (e.g., linear optical interferometers) to a large number of optical modes is a promising approach towards obtaining a quantum advantage in simulation, computation, communication, and metrology. For example, interferometers acting on thousands of optical modes can outperform classical computers in processing boson sampling tasks. Scaling up linear optics, however, also increases the number of optical components in the resulting optical circuits and accordingly the probability of having one or more imperfections in the optical circuit.
An optical circuit can have at least two types of imperfections. The first type of imperfection includes lossy modes and unresponsive optical components (e.g., a reconfigurable beamsplitter unresponsive to external control). Known methods to address this type of imperfection usually include fabricating multiple copies of the same optical circuits for quality inspection, discarding the defective ones, and choosing optical circuits that are free of defect. This approach may be feasible for small scale optical circuits. As the number of optical modes increases, however, the number of copies to be fabricated also increases (e.g., by two to four orders of magnitude), thereby incurring significant costs.
The second type of imperfections in an optical circuit includes compromised parameter ranges of an optical component. For example, the extinction ratio of a beamsplitter may be specified as from 0:100 to 100:0, but the actual dynamic range of this beamsplitter may be between 5:95 and 95:5. Known methods of addressing this type of imperfection include nonlinear optimization and self-reconfiguring optics, but nonlinear optimization does not guarantee the existence of any solution and self-reconfiguring optics typically increases the footprint of the resulting optical circuit (e.g., at least by a factor of two).

Methods and apparatus for mitigating imperfections in optical circuits


A process for determining coordinate values of touchdown sites of a needle for forming sewing patterns with an electronically controlled sewing machine, which is equipped with a feed dog performing only relatively small amounts of displacement and with a needle pivotable in one direction of displacement of the feed dog. The coordinate values for a straight seam section, the consecutive touchdown points of the needle, are determined when the maximum amount of feed of the feed dog in the X coordinate direction and/or the sum of the maximum amount of the lateral movement of the needle which is possible at a given needle position and the maximum amount of feed of the feed dog in the Y coordinate direction is exceeded. The seam section is subdivided by equidistant intermediate touchdown sites, the distances between which in the direction of movement of the needle are composed of a constant percentage of the lateral movement of the needle and of a constant feed percentage of the feed dog.

An electronically controlled household sewing machine, which is able to prepare sewing patterns whose width exceeds the normal width of the patterns stored, has become known from German Offenlegungsschrift DE-OS 40,27,364. These pattern combinations are prepared by a combination of individual sewing patterns with individual stitches, at least some of which can be prepared at right angles to the direction of sewing of the individual pattern. Even though freely programmable individual patterns can be prepared with this machine, the coordinates of every individual stitch must be entered by hand into the program memory during programming.
In the area of industrial machines, embroidery machines have been combined with personal computers. Various programming devices have been developed here in order to develop the coordinate values of the touchdown sites of an embroidery pattern. In these programming devices, the coordinate values, which form the desired sequence of touchdown sites of the needle in a workpiece, are entered by the operator by hand directly into a memory device for each stitch position, and entry is possible via a screen display unit.
To simplify entry, a device (West German Offenlegungsschrift No. DE-OS 32,32,842 corresponding to U.S. Pat. No. 4,444,135), in which only the coordinates of the two end points of a straight line or of an arc section are to be entered, rather than having to enter every individual pair of coordinate values by hand, has become known as well. The control device will subsequently automatically compute the coordinates of the missing touchdown points of the needle, and insert these between the end points of the curve section.
The said programming device is used in a sewing machine which is equipped with a fabric frame that is freely movable in the direction of the X and Y coordinates. The fabric frame is driven by stepping motors during the time during which the needle has been withdrawn from the fabric. Even though the duration of movement of the fabric frame is consequently limited, the magnitude of the movement in the two coordinate directions can be freely selected, insofar as this is permitted by the free mobility of the frame during the predetermined time.
It is not possible to apply the prior-art measure to a sewing machine, in which the fabric to be sewn is transported by a feed dog extending through slots in a needle plate, because only rather minimal fabric feed movements of the feed dog in the two coordinate directions can be performed by stitch formation cycles due to the dimensions of the slots being limited because of the sewing technology.
For this reason, satisfactory programming of the intermediate stitches is not possible with the prior-art solution in the case of a straight seam. Entering the consecutive stitches manually is also almost impossible because of the complicated relationships to be taken into account.

Process for determining the coordinate values for sewing patterns


Example wellbore telemetry systems and methods for transmitting signals between a surface unit and a downhole tool are disclosed. One example method transmits data between a downhole location in a wellbore and a surface location associated with the wellbore by measuring downhole data via at least one downhole component and generating a data frame containing at least a portion of the downhole data. The example method varies a telemetry bandwidth allocated to the at least one downhole component in response to the at least some of the downhole data corresponding to a special event and transmits the at least some of the downhole data to the surface location via the telemetry bandwidth allocated to the at least one downhole component.

Wellbores may be drilled to locate and produce hydrocarbons, minerals, or water. The drill string and the downhole tool are typically composed of a series of pipes threadably connected together to form a long tube with a drill bit at the lower end thereof. As the drilling tool is advanced, drilling mud is pumped from a surface mud pit through a passage or passages in the drilling tool and out the drill bit. The mud exiting the drill bit flows back to the surface to be returned to the mud pit and may be re-circulated through the drilling tool. In this manner, the drilling mud cools the drilling tool, carries cuttings and other debris away from the drilling tool, and deposits the cuttings and other debris in the mud pit. As is known, in addition to the cooling and cleaning operations performed by the mud pumped into the wellbore, the mud forms a mudcake that lines the wellbore which, among other functions, reduces friction between the drill string and subterranean formations.
During drilling operations, communications between the bottom hole assembly (which may include a plurality of components) and a surface-based processing unit and/or other surface devices may be performed using a telemetry system. In general, such telemetry systems enable the conveyance of power, data, commands, and/or any other signals or information between the bottom hole assembly and the surface devices. Thus, the telemetry systems enable, for example, data related to the conditions of the wellbore and/or the bottom hole assembly to be conveyed to the surface devices for further processing, display, etc. and also enable the operations of the bottom hole assembly to be controlled via commands and/or other information sent from the surface device(s) to the bottom hole assembly.
Various wellbore telemetry systems may be used to establish the desired communications capabilities. Examples of such systems may include a mud pulse telemetry system as described in U.S. Pat. No. 5,517,464, a wired drill pipe wellbore telemetry system as described in U.S. Pat. No. 6,641,434, an electromagnetic wellbore telemetry system as described in U.S. Pat. No. 5,624,051, an acoustic wellbore telemetry system as described in PCT Patent Application No. WO2004085796, all of which are incorporated by reference herein in their entireties. Further examples using data conveyance or communication devices (e.g., transceivers coupled to sensors) have also been used to convey power and/or data between a bottom hole assembly and a surface unit.
Telemetry systems typically involve transmitting data captured by a bottom hole assembly (e.g., one or more components composing a bottom hole assembly) to a surface system or unit. With these systems, data is typically collected and organized in packets, which may be referred to as frames, containing one data point or multiple data points. The data is typically transmitted uphole in a constant or continuous data stream. For example, a set of data collected from individual components is gathered into frames and conveyed to the surface. Data from a frame is continuously sent to the surface until all of the data from that frame has been sent. A series of frames containing interleaved data from various components is typically sent uphole to the surface. The above-described process is repeated for a given set of frames and/or may be repeated continuously (e.g., until power is turned off). Telemetry components or systems typically have practical limitations (e.g., bandwidth) that restrict the data rate and/or the amount of data that can be transmitted uphole in a given time period. As a result, there are often delays sending data from the bottom hole assembly to the surface and/or receiving data at the surface. Additionally, repeated data often consumes the limited available telemetry bandwidth, thereby slowing or preventing the transmission of data relating to key information and/or important events.

Downhole data transmission apparatus and methods


A link mechanism, such as a panhard rod or the like, has a rod section and a collar section at each of its two ends. One collar section is supported on the case side bracket through a bushing. The other collar section is supported on the body side bracket through a bushing. A mass is provided at each collar section for limiting vibrations. Each mass is configured so that its principal inertia axis coincides with the principal elastic axis of its bushing in at least one direction of the bending vibration mode of the rod section so that the nodes of the bending vibration mode of the panhard rod also coincide with the principal inertia axis of the mass and thus the principal elastic axis of the bushing. This significantly dampens the vibrations imparted to the link mechanism.

The present invention relates to a link mechanism utilized for a panhard rod (a lateral rod) and so forth in five-link-type rear suspension for an automobile.
Conventionally, this kind of link for example, as a panhard rod, which is used for a rear suspension is shown in FIG. 1 (referring to "New Version Structure of chassis 1!" published by K. K. Sankaido, Mar. 25, 1995, pages 200 to 201). The rear suspension is a five-link-type suspension, in which an axle case 1 is suspended from a car body, the rear suspension includes lower links 3 at right and left thereof, upper links 5 at right and left thereof (only illustrated right side portion of the body width lateral direction), shock absorbers 7 at right and left thereof, and coil sprigs 9 at right and left thereof, and further includes a panhard rod 11 as a link. The right end of the body width lateral direction of the panhard rod 11 is supported on the case side bracket (not illustrated), which is mounted on the axle case 1, while the left end thereof is supported being body side bracket (not illustrated), which is mounted on the portion of the car body side. Further, the case side bracket which transmits the vibration from the differential device to the panhard rod 11 through the axle case 1, becomes an exciting side portion, while the body side bracket becomes a receiving side portion.
Such panhard rod 11 is constituted as shown in FIG. 2. Namely, the panhard rod 11 has collar sections 17a, 17b on both ends of a hollow rod section 15. A mass 19 for limiting vibration is fixed to the collar section 17b. One collar section 17a is supported on the body side bracket being receiving side portion through a bushing of an elastic body not illustrated. The other collar section 17b is supported being case side bracket 13 on the exciting side portion through a bushing of an elastic body not illustrated. Consequently, the lateral force input from the wheel toward the axle shaft 1 is capable of being supported by the panhard rod 11 to the car body side.
Now, if the panhard rod 11 is supported as described above, the vibration (different whine) at for example approximately 400 Hz caused by engagement of differential device supported on the inside of the axle case 1 is imputed to the panhard rod 11 through the axle case 1 and the case side bracket. Furthermore, this vibration is imputed to the car body through the body side bracket, so there is fear that the vibration causes the room noise of the car body. This is attributed to the fact that the panhard rod 11 bending-vibrates with the mode such as representation of the chain line of FIG. 3 by the diff noise. Further, although only FIG. 3 shows the primary vibration and the secondary vibration, other multiple vibration exist. Namely, the nodes 21 of the bending vibration mode exist on the rod section 15 of the panhard rod 11, while the nodes 21 do not exist on the principal inertia axis of the bushings on the inside of the collar sections 17a, 17b, the collar sections 17a, 17b vibrate in the direction of up and down such as the arrows N, so that the diff noise is transmitted to the car body.
For this reason, conventionally, the mass 19 is provided thereto, and the vibration of the collar section 17b is suppressed by weight of the mass 19, with the result that transmission of the vibration to the car body is regulated. Further, in order to suppress the vibration of the collar sections 17a, 17b by the mass 19, it causes the weight thereof to increase as large as possible.
However, the mass 19 is regulated in the supported condition in such a way that the mass 19 does not enter into the portion 23 indicated by hatching of FIG. 2, in relation to the case side bracket 13 which supports the collar section 17b or another parts. Consequently, the mass 19 is incapable of being enlarged unlimitedly so that there are limits of vibration-suppressing function by weight thereof. Furthermore, if the mass 19 is enlarged as large as possible, a periphery of the bracket 13 is susceptible to be large-sized. That would be disadvantageous since the space is very crowded with a plurality of parts.


An electronically controlled lock with a single throw acting as a passage lock and also as a deadbolt lock is provided by the invention. The lock is equipped with an electronic activation device on its exterior housing and a door lever on its internal housing. A user unlocks the door from outside by touching an electronic key against the electronic activation device. After the door is unlocked, the throw acts as a passage lock. The door can be locked internally by moving the door lever from a horizontal position upwardly to a vertical position.

1. Field of the Invention
The present invention generally relates to locks, and more specifically, relates to single bolt lock with both a passage and deadbolt state and an electronic control of locking.
2. Description of the Related Art
Locks are well known and used by every household. Generally speaking, there are two types of locks commonly used as door locks, passage lock and deadbolt lock. The passage lock typically includes a bolt mounted on a door frame along with a door knob and other connecting mechanism. The bolt usually has a surface slanted in relation to a longitudinal direction to which the bolt moves. The bolt that can slide, along the longitudinal direction, in and out of a receiving hole on a door frame with turn of the door knob. The bolt can be fixed on its extended position when a button on the door knob is pressed, thus locking the door. The deadbolt lock, on the other hand, typically includes a bolt that has a longer body and a surface that is perpendicular in relation to the longitudinal direction. The bolt can slide in and out of a receiving hole on the door frame with movement of a key inserted into the deadbolt lock. When a user wants an added security to his house, he usually installs a deadbolt lock in addition to the passage lock.
Electronic door locks are also well known and commonly used in the hotel industry. An electronic door lock generally includes an electronic control mechanism and a locking mechanism. The locking mechanism generally includes a deadbolt lock and a passage lock, each separated from the other. The electronic control mechanism typically unlocks the deadbolt and engages the passage lock. From inside, the deadbolt lock is usually activated by a turn knob placed above the door handle, putting the lock in passage mode. These electronic door locks are widely used by hotels, but they are not easily retrofitted into older doors where there is only one opening on the door frame for the passage lock. For hotel operators and residential home owners who like to have security of a deadbolt lock, they have to go through the job of modifying both the door and the door frame before a deadbolt lock can be installed.
Therefore, it is desirous to have an apparatus that can easily replace a passage lock and provide added security of a deadbolt without needing to modify the door frame. It is to such apparatus and method the present invention is primarily directed.

Electronic deadbolt lock with a leverage handle


This invention provides a semiconductor laser that enables to oscillate at a wavelength defined by a Bragg grating formed therein in a wide temperature range without any temperature-controlling. The semiconductor laser comprises an active region and the Bragg grating formed with the active region. A light-emitting surface and a light-reflecting surface are formed so as to sandwiches the active region. The light-emitting surface has an anti-reflective coating, the reflectivity of which is so adjusted that the minimum thereof is at the wavelength where the gain attributed to the FP modes is the maximum and is smaller than 0.3%.

1. Field of the Invention
The present invention relates to a semiconductor laser, especially relates to a semiconductor laser with a grating.
2. Related Prior Art
In the optical fiber communication, particularly in the long reach and high-speed field, semiconductor lasers with a grating has been used. Such semiconductor lasers are a distributed feedback laser (DFB laser), a distributed Bragg reflector laser (DBR laser) and a laser with an external cavity
A configuration and mechanism of the DFB laser are well known to various articles, such as a specification of Japanese Patent laid open 10-051072. The DFB laser provides a light-reflecting surface and a light-emitting surface with relatively low reflectivity to the light-reflective surface. A Bragg grating is disposed between the light-reflecting surface and the light-emitting surface. A relatively high reflective coating on the light-reflecting surface and an anti-reflective coating on the light-emitting surface are disclosed in Japanese Patent laid open 10-190139 and also Japanese Patent laid open 09-326531, respectively.
An optical module including the DFB laser generally provides a thermo-electric element, such as Peltier element, to keep the temperature of the DFB laser constant. In such optical module with the Peltier element, even the ambient temperature change, the practical temperature of the DIB laser may be kept constant through the Peltier element, thereby enabling to output light in single mode.
On the other hand, to install the Peltier element within the optical module results in raising cost of the module due to the increase of parts and assembly process. Similarly, power consumption of the module increases due to current supplied to the Peltier element. The conventional DFB lasers without any Peltier element oscillate in numerous Fabry-Perot mode at low temperatures around −40° C. because the gain attributed to the Fabry-Perot mode superiors to that of the DFB mode at low temperature.

DFB laser with ar coating selected to provide wide temperature range of operation


Biotin-binding modified avidin-type molecules are provided in which the essential tyrosine residue in the biotin-binding site is modified in such a way that its pKa is decreased in comparison to the pKa of the unmodified tyrosine residue in the corresponding unmodified avidin-type molecule. The avidin-type molecules include: (i) native egg-white avidin; (ii) recombinant avidin; (iii) deglycosylated forms of avidin; (iv) bacterial streptavidin; (v) recombinant streptavidin; (vi) truncated streptavidin; and (vii) derivatives of (i)-(vi) which are modified at sites other than the essential tyrosine residue. The modification is achieved by substitution at one or both ortho positions to the hydroxy radical of the tyrosine residue by radicals such as nitro, halogen, azo and amino. The modified avidin-type molecules can be used in all applications of the avidin-biotin technology.

The present invention relates to an avidin-type molecule which is modified at the binding-site tyrosine residue, known to be critical to the binding of biotin. The modified avidin is still capable of binding biotin or a biotinylated ligand under specific conditions, but upon altering these conditions, for example, high pH or competition with biotin, the bound biotin moiety or biotinylated ligand is removed. The invention thus provides a reversible form of avidin for use in avidin-biotin technology, thus "correcting" one of the major disadvantages of the avidin molecule for various applicative purposes, i.e., the extreme denaturing conditions required to disrupt the avidin-biotin complex. These drastic conditions necessary to dissociate the avidin-biotin complex usually inactivate irreversibly the biological activity of the biotinylated component, thus rendering it unsuitable for subsequent use.
Avidin (from egg-white) and streptavidin (from Streptomyces avidinii) are two related proteins that bind biotin with similar dissociation constants of about 10.sup.-15 M (Green, 1975). In addition to the binding of biotin, many of their physical properties are quite similar. Both, for example, are constructed of four non-covalently attached identical subunits, each of which bears a single biotin-binding site. The subunit M.sub.r values are also very similar. Moreover, several short stretches in the sequences of the two proteins are preserved, particularly to Trp-Lys stretches that occur at approximately similar positions (Argarana et al., 1986). We have previously shown (Gitlin et al., 1987, 1988a) that certain lysine and tryptophan residues are involved in the biotin binding in both proteins (Gitlin et al., 1988b). More recently, it was shown that both avidin and streptavidin exhibit the same three dimensional fold, and the most of the binding site residues are identical or similar (Weber et al., 1989). The binding site geometry and bonds formed between both proteins with the biotin molecule are indeed very similar.
Despite these similarities, several differences exist between the two proteins. Avidin is a disulphide-bridged glycoprotein containing two methionine residues, whereas streptavidin is not glycosylated and is devoid of sulphur-containing amino acid side chains. Another significant difference is in the tyrosine content. Avidin has only one tyrosine residue (Tyr-33), whereas streptavidin has six tyrosine residues at positions 22, 43, 54, 60, 83 and 96. Interestingly, the single tyrosine residue of a avidin is located in a region which contains a sequence identical with that of one of the streptavidin tyrosine residues (Tyr-43 in the stretch Thr-Gly-Thr-Tyr). This tyrosine residue occupies a prominent position in the biotin-binding site and the chemical modification of the tyrosine hydroxyl group leads to irreversible inactivation of the avidin molecule (Gitlin et. al., 1990).
Each avidin monomer binds one molecule of biotin. The unique feature of this binding, of course, is the strength and specificity of formation of the avidin-biotin complex. The resultant affinity constant, estimated at 1.6.times.10.sup.15 M.sup.-1 for avidin and 2.5.times.10.sup.13 M.sup.-1 for streptavidin (Green, 1990), is the highest known for a protein and an organic ligand. It is so strong that biotin cannot be released from the binding site, even when subjected to a variety of drastic conditions such as high concentrations of denaturing agents at room temperature, e.g., 6M guanidinium hydrochloride, 3M guanidinium thiocyanate, 8M urea, 10% .beta.-mercaptoethanol or 10% sodium dodecyl sulfate. Under combined treatment with guanidinium hydrochloride at low pH (1.5) or upon heating (>70.degree. C.) in the presence of denaturing agents or detergents, the protein is denatured, and biotin is dislodged from the disrupted binding site.
Avidin recognizes biotin mainly at the ureido (urea-like) ring of the molecule. The interaction between the binding site of avidin with the sulfur-containing ring of the valeric acid side chain of the vitamin is of much lower strength. The relatively weak interaction between the carboxy-containing side chain of biotin and avidin means that the former can be modified chemically and attached to a wide variety of biologically active material; the biotin moiety of the resultant derivative or conjugate is still available for interaction with avidin. In turn, the avidin can be derivatized with many other molecules, notably "probes" or reporter groups of different types.
This is the crux of avidin-biotin technology (Wilchek and Bayer, 1990). Thus, a biologically active target molecule in an experimental system can be "labeled" with its biotinylated counterpart (a binder), and the product can then be subjected to interaction with avidin, either derivatized or conjugated with an appropriate probe.
The use of the egg-white avidin in the avidin-biotin technology is sometimes restricted due to the high basicity (pI.about.10.5) and presence of sugar moieties on the avidin molecule, which may lead to nonspecific or otherwise undesired reactions. In recent years, the bacterial protein streptavidin, has largely replaced egg-white avidin for most applications in avidin-biotin technology. However, the problems with streptavidin (high cost and biotin-independent cell binding) has prompted renewed interest in egg-white avidin as the standard for avidin-biotin technology. For this purpose, modified avidins exhibiting improved molecular characteristics both over the native protein (and previous derivatives thereof) as well as over streptavidin, have been prepared, such as N-acyl avidins, e.g., N-formyl, N-acetyl and N-succinyl avidins. These derivatives of avidin reduce the charge of the protein, but they are all prepared via covalent attachment to the available lysines of avidin, and the consequent blocking of the free amino groups hinders subsequent preparation of other types of conjugates (notably protein-protein conjugates such as avidin-labeled enzymes) which are often prepared by crosslinking via lysine residues using bifunctional reagents (e.g., glutaraldehyde).
A more useful and effective alternative to lysine modification is the modification via arginines. In this case, the pI of the protein is efficiently reduced and the lysines are still available for subsequent interaction. Two different derivatives of avidin which are modified in this manner are commercially available. One, ExtrAvidin.RTM., can be obtained in various functionally derivatized or conjugated forms from Sigma Chemical Company (St. Louis, Mo.). A second, NeutraLite Avidin.TM. (a product of Belovo Chemicals, Gastogne, Belgium) is additionally modified and can be purchased in bulk quantities.
Although the reduction of the pI of egg-white avidin solves one of the problems, the presence of the oligosaccharide residue remains a serious source of nonspecific (biotin-independent) interaction which restricts its application. The return of egg-white avidin as the standard for avidin-biotin technology has been contingent upon the removal of its sugars.
The possibilities for removing a sugar from a glycoprotein are quite limited; it is possible to do so either chemically or enzymatically. The chemical methods currently available, e.g., using HF or periodate oxidation, are either destructive or inefficient. The well known enzymatic method, which employs N-glycanase (Tarentino et al., 1984), is usually very expensive and not very effective for avidin when conventional methodology is used. Eventually, a viable procedure for deglycosylation was established and the resultant product was subsequently modified chemically via the arginines and is known under the trade mark NeutraLite Avidin.TM. (Belovo Chemicals).
In spite of these improvements, one of the main problems in the several applications of the avidin-biotin technology is the lack of reversibility of the binding and the difficulty of separating the avidin and the biotin moieties at the end of the process, without denaturation of the avidin or damaging or inactivating the biological material which had been attached via the biotin bridge. Alternatively, it would be advantageous (particularly for industrial use) to remove damaged or inactivated material from an avidin column, thus reconstituting the column for attachment of the new sample of biotinylated component.
It is an object of the present invention to provide modified avidins which are still biotin-binding and can be advantageously used in methods employing the avidin-biotin technology in which reversibility of the method is desired or is an advantage.
Nitration of tyrosine residues in model peptides and proteins using tetranitromethane has been described (Riordan et al., 1966; Sokolovsky et al., 1967). In a previous work of the present inventors (Gitlin et al., 1989), a nitrotyrosine derivative of avidin was prepared by nitration of egg-white avidin dissolved in 9M-urea with tetranitromethane (TNM). The resultant nitro-avidin preparation was inactive, i.e. it failed to bind biotin, because the nitration was carried out on a denatured form of avidin (in the presence of urea). The nitro-avidin thus prepared is entirely inadequate for use in avidin-biotin technology.
.sup.125 I-labelled avidin and streptavidin have been prepared for analytical purposes. The single tyrosine residue of each avidin subunit is not readily accessible to iodination. Avidin is rendered susceptible to iodination (chloramine T method) by the introduction of 3-(p-hydroxyphenyl)propionyl groups and thus .sup.125 I-labelled avidin containing said groups was prepared. .sup.125 I-labelled Bolton-hunter reagent can also be employed to label avidin (Finn and Hofmann, 1985). .sup.125 I-streptavidin was produced by iodination of streptavidin with Na.sup.125 I using the iodogen method (Suter et al., 1988). Unlabelled iodinated avidin and streptavidin have not been described heretofore.
Azotization and amination of tyrosine residues in model peptides and proteins, e.g. ribonuclease A, has been previously described (Gorecki et al., 1971; Sokolovsky et al, 1967).

Modified avidin and streptavidin molecules and use thereof


In order to solve the problem that sufficient center brightness is not always obtained in a conventional liquid crystal TV and a liquid crystal monitor, a backlight module of the invention includes a plurality of cold cathode fluorescent lamps (CFL) and a diffusing reflector below, the distance between the respective CFLs is arranged so that a central portion is narrow and an end portion is wide, and the backlight module includes a triangular sectional projection structure on at the diffusing reflector only between the CFLs between which the distance is the widest, in the end portion. According to the invention, enhancement of the center brightness without increasing consumption power, reduction in the number of CFLs, and cost reduction accompanying it are achieved.

1. Field of the Invention
The present invention relates to a backlight module for a liquid crystal television and a liquid crystal monitor, and a liquid crystal display using the same.
2. Description of Related Art
Conventionally, JP-A-6-75216 discloses a liquid crystal display in which a backlight is disposed under a liquid crystal display panel, and the brightness of the backlight in a central portion of a screen of the liquid crystal display panel is made the highest and gradually reduced in a direction toward an end portion. In this liquid crystal display, there is disclosed a method of providing a bright liquid crystal display by narrowing the distance between cold-cathode fluorescent lamps (hereinafter, referred to as CFL) constituting the backlight in the central portion, and widening the distance in the end portion to enhance the center brightness without increasing power consumption while reducing the weight by decreasing the number of CFLs constituting the backlight.

Backlight module and liquid crystal display using the same