Power supply for a networking device may be provided. The networking device may comprise a first plurality of switch bars each comprising a first switch type arranged parallel to one another and a second plurality of switch bars each comprising a second switch type arranged parallel to one another. The first plurality of switch bars and the second plurality of switch bars may be arranged orthogonally. A first plurality of power supplies may be fed by a first source. A second plurality of power supplies may be fed by a second source. Respective ones of a first portion of the first plurality of power supplies feed first respective pairs of the first plurality of switch bars and respective ones of a first portion of the second plurality of power supplies feed second respective pairs of the first plurality of switch bars. The first respective pairs of the first plurality of switch bars may be different from the second respective pairs of the first plurality of switch bars.

Cloud computing is a model that allows access to a shared pool of configurable computing resources. Cloud computing and storage solutions provide users and enterprises with various capabilities to store and process their data in third-party data centers. It shares resources to achieve coherence and economies of scale.
Cloud computing also focuses on maximizing the effectiveness of the shared resources. Cloud resources are usually not only shared by multiple users, but are also dynamically reallocated per demand. This can work for allocating resources to users. For example, a cloud computer facility that serves European users during European business hours with a specific application (e.g., e-mail) may reallocate the same resources to serve North American users during North American business hours with a different application (e.g., a web server). This approach helps maximize computing power use while reducing the overall resources cost by using, for example, less power, less air conditioning, and less rack space, to provide the required functions. With cloud computing, like other client-server architectures, multiple users can access a single server to retrieve and update their data without purchasing licenses for different applications.
Interconnecting these shared resources is an important challenge. In conventional data centers, several layers of IP switches, and large numbers of cabled Ethernet connections complete the interconnect between servers, storage engines, networking devices, appliances, and other endpoints to enable the cloud to perform its required application services. In large data centers, these switches and interconnects can be difficult to install and configure, consume large physical volumes, energy and cooling resources, and are expensive. Multiple layers of switches including spine, leaf and top of rack, and techniques such as fat trees, which may consist of layers of richly interconnected switches, are often employed to address these challenges.

Power supply for a networking device with orthogonal switch bars


The present invention relates to a semiconductor device having an integrated metal shield. The shield, created as part of a MOSFET, is formed about a gate electrode of the MOSFET to effectively reduce drain-to-gate capacitance and increase breakdown voltage. The shield consists of a metallic shield contact via and a source contact extension. The metallic shield contact via, formed between the gate electrode and a drain region of the MOSFET, may be either a series of closely spaced vias or a wide continuous via. The metallic shield contact via is isolated from the surface of a semiconductor wafer by a shield isolation layer at one end. The metallic shield contact via is electrically coupled to the source contact extension at the other end. The source contact extension is metallic, and may be formed from the same metal used to create a source contact and a drain contact for the MOSFET.

With reference to FIG. 1, a typical metal oxide semiconductor field effect transistor (MOSFET) 10 is illustrated. The MOSFET 10 is formed by creating a source region 12 and a drain region 14 in a semiconductor wafer 16 and placing a gate electrode 18 over the surface of the semiconductor wafer 16 between the source region 12 and the drain region 14. The source region 12 and the drain region 14 are heavily doped with N-type material. The gate electrode 18 is isolated from the surface of the semiconductor wafer 16 by an appropriate gate dielectric layer 20. In the illustrated embodiment, a lightly doped drain region 22 in the semiconductor wafer 16 extends from the drain region 14 to the gate electrode 18. Also, a body region 24 may be formed in the semiconductor wafer 16 adjacent to the source region 12 wherein the source region 12 is between the body region 24 and the gate electrode 18.
Electrical contacts to the body region 24, source region 12, and drain region 14 may be established through conductive vias. As illustrated, a body contact via 26 and a source contact via 28 extend from the respective body region 24 and source region 12 to a source contact 30. A drain contact via 32 extends from the drain region 14 to a drain contact 34. The electrical contact to the gate electrode 18 is not shown.
MOSFETs 10 are used in numerous electrical applications, including those that are required to operate at high frequencies and over wide operating voltage ranges. Designers are constantly faced with the challenge of creating MOSFETs 10 that operate at higher frequencies and higher operating voltage ranges. The inherent drain-to-gate capacitance of the MOSFET 10 is a significant obstacle in achieving higher operating frequencies. The breakdown voltage of the MOSFET 10 is a significant obstacle in achieving wider operating voltage ranges.
Reference is now made to FIG. 2. In an effort to reduce drain-to-gate capacitance and increase breakdown voltage, a shield 36 was formed over the gate electrode 18 and lightly doped drain region 22. The shield 36 effectively reduces drain-to-gate capacitance. FIGS. 1 and 2 provide electrostatic potential contour lines throughout the semiconductor wafer 16 at the breakdown voltage of the respective MOSFET 10. As illustrated, the breakdown voltage is significantly increased when the shield 36 is employed.
The shield 36 is isolated from the gate electrode 18 and the surface of the semiconductor wafer 16 by extending a gate electrode spacer 38 from the gate electrode 18 toward the drain region 14. Notably, the shield 36 is formed by depositing an additional polysilicon layer over the extended gate electrode spacer 38. Unfortunately, formation of the additional polysilicon layer requires an additional polysilicon process step, which is not part of a common MOSFET manufacturing process. Further, the widely varying topology of the MOSFET 10 makes the etching process for creating the shield 36 from the additional polysilicon layer complex.
Accordingly, there is a need to create a shield that reduces drain-to-gate capacitance and increases breakdown voltage of a MOSFET 10 in a more efficient and effective manner. In particular, there is a need to create a shield that does not require adding an additional polysilicon layer to the normal manufacturing process or require etching over a complex topology.

Integrated metal shield for a field effect transistor


Methods are disclosed for gas-cluster ion-beam deposition of thin films on silicon wafers rendered free of native oxides by termination of the surface bonds and subsequent reactive deposition. Hydrogen termination of the surface of silicon renders it inert to reoxidation from oxygen-containing environmental gasses, even those found as residue in vacuum systems, such as those used to deposit films. Nitrogen termination improves the interface with overlying metal-oxide thin films. The film is formed in intimate contact with the silicon crystal surface forming a nearly ideal interface.

This invention relates generally to the formation of thin films, and, more particularly to the formation of thin dielectric films by gas-cluster ion-beam (GCIB) on surfaces rendered free of native oxides to assure high quality interfacial layers and films.
The use of a GCIB for etching, cleaning, and smoothing of the surfaces of various materials is known in the art (See for example, U.S. Pat. No. 5,814,194, Deguchi, et al., xe2x80x9cSubstrate Surface Treatment Methodxe2x80x9d, 1998). Means for creation of and acceleration of such GCIBs are also described in the Deguchi reference. It is also known (U.S. Pat. No. 5,459,326, Yamada, xe2x80x9cMethod for Surface Treatment with Extra-Low-Speed Ion Beamxe2x80x9d, 1995) that atoms in a cluster ion are not individually energetic enough (on the order of a few electron volts) to significantly penetrate a surface to cause the residual sub-surface damage typically associated with the other types of ion beam processing in which individual ions may have energies on the order of thousands of electron volts. Nevertheless, the cluster ions themselves can be made sufficiently energetic (some thousands of electron volts), to effectively etch, smooth or clean surfaces as shown by Yamada and Matsuo (in xe2x80x9cCluster ion beam processingxe2x80x9d, Matl. Science in Semiconductor Processing I, (1998) pp 27-41).
The heart of high-density memory and microprocessor chips is a very thin film of an electrically insulating material formed on the surface of a silicon crystal wafer. This insulator, referred to as the gate dielectric, must sustain very high electric fields and serve efficiently as the key component in the storage of electrical charge. A conductor film, not necessarily a true metal, must then be formed on top of the dielectric. Two basic types of microelectronic devices are fabricated from these so-called metal/insulator/silicon (MIS) layered structures, namely bit storage or xe2x80x9cmemoryxe2x80x9d, and logic transistors. An assembly of many bit-storage units on a single silicon wafer is used to fabricate dynamic random-access memory (DRAM) integrated circuits, while an assembly of many logic transistors is used to fabricate microprocessors. As the chip industry moves toward smaller circuit elements packed more tightly on the chip, it is required that the area devoted to each charge-storage circuit on the chip be not only smaller but also store at least the same amount of charge. Two approaches are possible, first the thickness of the gate dielectric film can be reduced and second the intrinsic storage ability of that insulator, called its dielectric constant, can be increased by choice of a new kind of material. Up until the present time, the chip industry has used silicon oxide (nominally SiO2, referred to as silica or just xe2x80x9coxidexe2x80x9d) as the dielectric and has succeeded in making each chip generation with thinner oxide films. When the insulator is this oxide, then the structures consisting of a conductor (metal or polysilicon) film, on an oxide film, in turn on silicon, is the metal/oxide/silicon (MOS) structure employed as the basic building block unit of the vast majority of the semiconductor industry product. But the trend of continuing to reduce the thickness of the oxide film in the MOS is projected to run out of potential as it reaches basic physical limits.
Silicon oxide thin films have been the basis for gate dielectrics in silicon-based very large scale integration (VLSI) complementary metal-oxide semiconductors (CMOS) for several decades now. As the industry moves toward more advanced devices, the gate dielectric thickness is reduced with each design generation but will soon reach what is believed to be an ultimate limit. When the physical thickness of any dielectric material is less than about 5 to 15 xc3x85, direct quantum tunneling across this dielectric barrier results in sufficient current (leakage) as to cause the CMOS transistors to malfunction. CMOS now being developed for production manufacture and marketing in the near future, will utilize oxide films at about this critical thickness. Thinner films of oxide cannot be used in future generations of CMOS technology, no matter what their composition or state of matter. The physical thickness of the film must be kept greater than this approximate amount.
Research into new materials has suggested that a compound known as silicon nitride (nominally Si3N4) may be used for a gate dielectric with a higher dielectric constant. In a CMOS structure when the dielectric is other than silicon oxide, the layer stack of gate/dielectric/silicon is referred to as metal/insulator/silicon or MIS. The dielectric constant (xcexa) for Si3N4 is about 4.2 compared with about 2.13 for SiO2, at low frequencies. Considerable effort has already been expended on developing apparatus and methods to fabricate thin silicon nitride films. While material quality has improved, it appears that heretofore it has not been possible to avoid having the quality of this material compromised by either poor atomic structure, unsatisfactory stoichiometry (ratio of number of silicon atoms to those of nitrogen), or unwanted impurities such as oxygen or hydrogen. This has delayed the introduction of such films and now it is less clear that the modest increase in physical thickness will result in the necessary advantage for CMOS device performance in future generations.
Metal-oxide compounds of many kinds, mainly those utilizing transition metals, have potentially useful dielectric properties as well as compatibility with silicon wafers and the fabrication processes required to construct VLSI CMOS devices. There are a wide variety of materials being evaluated at present for this application, which can be grouped according to the approximate magnitude of their dielectric constant. So-called medium-xcexa materials include: Ta2O5, CeO2, TiO2, ZrO2, HfO2, and (Al,Zr)O2. (Al,Zr)O2 can be formed with many ratios of Al to Zr content (as in a metal alloy). For these, the xcexa ranges from xcx9c10 to 50, with 28 for ZrO2 and HfO2 being typical. These latter are known to provide films that at physical thickness of 50 xc3x85 function in thin-film MIS capacitors with effective (oxide-like) thickness of about 10 xc3x85. Other metal-oxide compounds are dielectrics with much larger xcexa, the so-called high-xcexa materials. Among these BaTiO3, SrTiO3, PbTiO3, ZrTiO3 and the alloys (Ba,Sr)TiO3 and (Pb,Zr)TiO3 are known to have xcexa in excess of 100 and in single crystals in excess of 1000. Film deposition and processing difficulties presently limit the introduction of these dielectrics into CMOS technology.
Oxide dielectric films on silicon of the best quality are grown at elevated temperature by reaction of environmental oxygen or oxygen-containing gasses with the silicon surface, i.e., so-called thermal oxidation. All of the dielectrics with larger xcexa must be deposited and this introduces several difficulties. One of these difficulties is that the metal-oxide compounds that compose these dielectrics will themselves react with the silicon forming a compound of metal, silicon, and oxygen in a thin layer at the interface (H. Ono and K.-I. Koyanagi in xe2x80x9cFormation of Silicon-Oxide Layers at the Interface Between Tantalum Oxide and Silicon Substratexe2x80x9d, Applied Physics Letters, Vol. 75, pp. 3521-3523 (1999)). These interfacial layers often are poor quality dielectrics with either reduced xcexa, are somewhat conducting or have a high density of charge trapping sites. Also, any appreciable thickness of this layer will then reduce the overall effective dielectric effect of the capacitor in the CMOS device and hence the deposited film must be reduced in thickness to achieve the required capacitance, and this in turn counters the intent of using the higher-xcexa film material.
One nearly ideal construction for metal-oxide dielectric films on silicon is to have a single atomic layer (i.e., a monolayer) of some suitable element terminating the silicon at the interface. Hydrogen and nitrogen are two known suitable elements for silicon termination. Silicon wafers, prior to coverage with a film, are known to be extremely reactive with oxygen containing gasses, even in trace amounts. This reaction forms a very thin oxide film, often called a native oxide on the silicon surface, but it is of poor dielectric quality. Methods are known to use aqueous solutions with HF that etch off oxides from silicon and leave behind a monolayer of hydrogen, so-called hydrogen termination (H-termination) of the surface. Connell et al (U.S. Pat. No. 5,173,474, Silicon Substrate Having an Epitaxial Superconducting Layer Thereon and Method of Making Same, (1992)) have described such a method that can be incorporated into the process for thin film deposition by the methods of physical-vapor deposition (PVD) including pulsed-laser deposition (PLD). Heating the silicon wafer to well above 400xc2x0 C. in the deposition system just prior to initiation of the flux of material to be deposited, causes the hydrogen to desorb from the silicon and to move into the chamber vacuum. Thus, hydrogen is not present on the surface during the film deposition, and consequently, upon completion of the deposition, no hydrogen remains as an interfacial layer. Yttria-stabilized zirconia (YSZ) films deposited by this method were found to form dielectrics useful in MIS capacitors (see E. Ajimine, et al. in xe2x80x9cElectrical Characterization of Metal-Insulator Semiconductor Diodes Fabricated from Laser-Ablated YBa2Cu3O7xe2x88x92xcex4/Yttria-Stabilized Zirconia Films on Si Substratesxe2x80x9d, Applied Physics Letters, Vol. 59, pp. 2889-2891 (1991); and J. Qiao, et al. in xe2x80x9cThermally Activated Reversible Threshold Shifts in YBa2Cu3O7xe2x88x92xcex4/Yttria-Stabilized Zirconia/Si Capacitorsxe2x80x9d, Applied Physics Letters, Vol. 61, pp. 3184-3186 (1992); and J. Qiao, et al. in xe2x80x9cDetermination of the Density of Trap States at Y2O3-Stabilized ZrO2/Si Interface of YBa2Cu3O7xe2x88x92xcex4/Y2O3-Stabilized ZrO2/Si Capacitorsxe2x80x9d, Applied Physics Letters, Vol. 64, pp. 1732-1734 (1994)).
It is known that nitrogen annealing has an improving effect on the dielectric quality of many types of grown oxide dielectrics on silicon (see H. Yang and G. Lucovsky, xe2x80x9cIntegration of Ultrathin (1.6xcx9c2.0 nm) RPECVD Oxynitride Gate Dielectrics into Dual Poly-Si Gate Submicron CMOSFETsxe2x80x9d IEDM Technical Digest, pp. 245-248 (IEEE, 1999)). Nitridation of the silicon surface prior to growth by exposure to NO or NH3 gas results in a very thin interfacial layer after deposition of metal-oxide dielectric films (see H. F. Luan, et al., xe2x80x9cHigh Quality Ta2O5 Gate Dielectrics with Tox,eq less than 10 xc3x85xe2x80x9d, IEDM Technical Digest, pp. 141-144 (IEEE, 1999)). The nitrogen-termination layer reduces the charge-trapping defects and acts as a diffusion barrier to prevent the oxygen of the overlying metal-oxide film from migrating down to the silicon where it would otherwise form a silicon oxide.
Methods of hydrogen termination of silicon that render improved interfaces with subsequently deposited thin, metal films have been described by I. Kondo et al. (in xe2x80x9cEffects of Different Pretreatments on the Surface Structure of Silicon and the Adhesion of Metal Filmsxe2x80x9d, Journal of Vacuum Science and Technology, Vol. A10, p. 3166-3170 (1992); in xe2x80x9cInterface Structure and Adhesion of Sputtered Metal Films on Silicon: The Influence of Si Surface Conditionxe2x80x9d, Journal of Vacuum Science and Technology, Vol. A11, p. 319-324 (1993)); by B. G. Demczyk et al. (in xe2x80x9cGrowth of Cu Films on Hydrogen Terminated Si(100) and Si(111) Surfacesxe2x80x9d, Journal of Applied Physics, Vol. 75, p. 1956-1961 (1994)); by E. T. Krastev et al. (in xe2x80x9cSurface Morphology and Electric Conductivity of Epitaxial Cu(100) Films Grown on H-Terminated Si(100)xe2x80x9d, Journal of Applied Physics, Vol. 79, p. 6865-6871 (1996) ); and by H. Gong et al (in xe2x80x9cHighly Oriented NiFe Soft Magnetic Films on Si Substratesxe2x80x9d, Journal of Applied Physics, Vol. 85, p. 5750-5752(1999)).
It is highly desirable to effectively form thin dielectric films which overcome the past problems associated with such thin film deposition.
It is therefore an object of this invention to provide improved methods for deposition of an improved thin dielectric film on silicon wafers.
It is a further object of this invention to improve control of the interface and interfacial layer between a semiconductor and a thin dielectric film on the semiconductor.
The objects set forth above as well as further and other objects and advantages of the present invention are achieved by the various embodiments of the invention described hereinbelow. Methods are disclosed for gas-cluster ion-beam deposition of thin films on silicon wafers rendered free of native oxides by termination of the surface bonds. The present invention controls the interface between deposited thin films and monocrystalline silicon, which is critical to the film properties, and hence enhances the usefulness of such films in microelectronic and photonic applications. Hydrogen termination of the surface of silicon renders it inert to reoxidation from oxygen-containing environmental gasses, even those found as residue in vacuum systems, such as those used to deposit films. Nitrogen termination improves the interface with overlying metal-oxide thin films. The present invention describes both ex-situ and in-situ methods for termination.
Upon initiation of the film-deposition flux, much of the hydrogen is displaced from the surface and the film is formed in intimate contact with the silicon crystal surface forming a nearly ideal interface. Ion beams composed of nanoparticles or clusters of condensed gasses may be used to deposit thin films with advantages derived from the nanoparticle impact energy but without the known effects of ion mixing, implantation and roughening which occur with atomic and molecular ion-beam deposition. Advantages of this combination of deposition and initial substrate surface processing are described in detail hereinbelow. In particular, this invention is especially effective for, but not limited to, formation of metal-oxide compounds such as Ta2O5, CeO2, HfO2, TiO2, ZrO2 and AlxZr1xe2x88x92xO2 with higher dielectric constant than silicon dioxide films.
For a better understanding of the present invention, together with other and further objects thereof, reference is made to the accompanying drawings and detailed description and its scope will be pointed out in the appended claims.

Interface control for film deposition by gas-cluster ion-beam processing


The present invention describes novel pharmaceutical compositions and methods for treatment of diseases, disorders, or conditions characterized by recurrent seizures, particularly, epilepsy. According to the invention, compounds which inhibit the activity or expression of non-receptor Fyn tyrosine kinase can prevent activation epileptic pathophysiology and provide protection from and treatment of epilepsy. Particularly preferred is the class of small molecule Fyn kinase inhibitors such as sacaratinib and its prodrugs, derivatives, analogs and the like.

Epilepsy is the most common neurological disorder, affecting about 1% of the population worldwide. Epilepsy describes a condition in which a person has recurrent seizures due to a chronic, underlying process. Epilepsy refers to a clinical phenomenon rather than a single disease entity, since there are many forms and causes of epilepsy. Using a definition of epilepsy as two or more unprovoked seizures, the incidence of epilepsy is estimated at 5 to 10 people per 1000. An essential step in the diagnosis and treatment of a patient with a seizure is to determine the type of seizure that has occurred. The main characteristic that distinguishes the different categories of seizure is whether the seizure activity is partial or generalized or unclassified.
For the general population there are approximately 20-70 new cases per 100,000 diagnosed each year with a 3-5% lifetime probability of developing the disease. The older established antiepileptic drugs (AEDs) phenytoin, carbamazepine, clonazepam, ethosuximide, valproic acid and barbiturates are widely prescribed but suffer from a range of side effects. Furthermore, there is a significant group of patients (20-30%) that are resistant to the currently available therapeutic agents. Since 1989 several new drugs have been launched, including felbamate, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, vigabartrin, zonisamide and levetiracetam. While many of new AEDs show improved efficacies and side-effect profiles, about 30% of patients with epilepsy remain untreated. Additionally, new antiepileptic drugs based on their action on the ion-channels have started to be developed (Bialer and White, 2010; Rogawaski and Loscher, 2004; Schmidt, 2009). However, the majority of the current AEDs (including 47 failed drugs in human trials) are less effective, or do not cure the disease, and some even require lifelong administration with some potential side-effects (Kwan et al., 2011; Varvel et al., 2015). This suggests the need for development of more effective drugs that target alternative pathways to prevent/treat epilepsy. There is clearly a need for improved medication.
Neuroinflammation is emerging as a new mechanistic target for drug development, and it also serves as a biomarker for neuroimaging in various neurodegenerative diseases (Abi-Dargham and Horga, 2016; Albrecht et al., 2016; French 2016; Gershen et al., 2015). The microglia are considered as resident macrophages and they mediate neuroinflammation and hyperexcitability in neurons (Block, 2014; Davis and Carson, 2012; Devinsky et al., 2013). The reactive glia are known to produce proinflammatory cytokines, reactive oxygen and nitrogen species (ROS/RNS), lipid peroxidation, hippocampal neurodegeneration, reorganization of neural circuits, and hyper-synchronicity (Bertram 2013; Goldberg and Coulter, 2013; Ryan et al., 2014; Scharfman and Binder, 2013; Vezzani et al., 2011 and 2013). The microglia become reactive in response to SE insult (Avignone et al., 2008; Puttachary et al., 2016a and b). Increased levels of proinflammatory cytokines and nitro-oxidative stress molecules are known to cause neurodegeneration (Glass et al., 2010; Vezzani et al., 2011 and 2013), altered synaptic plasticity, and decreased seizure threshold in epilepsy models (Bozzi et al., 2011; Reddy and Kuruba, 2013). However, the mechanism of microglial activation following seizures is largely unknown. Therefore, understanding the mechanism of activation of microglia will reveal its impact on epileptogenesis.
There are nine members of Src family of intracellular non-receptor tyrosine kinases (SFK). Five of them (Src, Fyn, Lck, Lyn, and Yes) are expressed in the central nervous system, but Src and Fyn are most highly expressed in the brain. Fyn activity, like that of other Src family kinases, is regulated by intramolecular interactions that depend on an equilibrium between tyrosine phosphorylation and dephosphorylation (Thomas et al., 1997, Ann. Rev. Cell & Dev. Biol. 13:513-609). In the basal state, catalytic activity is constrained by intramolecular interactions, such as engagement of the SH2 domain by a phosphorylated C-terminal Tyr 527. Disruption of these interactions by phosphorylation at Tyr 416 in the activation loop of the kinase domain and/or by dephosphorylation of Tyr 527 results in Fyn activation (Hunter, 1987, Cell, 49: 1-4).
The Fyn is associated with both excitatory and inhibitory ion channels, and its role in pathophysiology of synaptic transmission, plasticity, neurodevelopment, and brain injury are well known (Knox and Jiang, 2015; Kojima et al., 1998; Lu et al., 1999; Nygaard et al., 2014; Salter and Kalia, 2004). The neuronal Fyn has been known to modulate both NMDA and GABAA receptors (Kojima et al., 1998; Lu et al., 1999), and the role of Fyn in normal amygdala kindling (Cain et al., 1995) suggests its potential association with acute seizure onset. However, its role in chronic seizures are not well known. Likewise, the roles of Fyn kinase and one of its downstream targets, the protein kinase C delta (PKCδ), in microglia that mediate neuroinflammation and epileptogenesis are also not well known. Their role in microglia in experimental disease models is however beginning to emerge as has been described in Parkinson's disease (PD) models (Nygaard et al., 2015; Panicker et al., 2015). Therefore, the Fyn-PKCδ signaling pathway may also mediate microglial activation in seizures, and disabling the Fyn kinase will suppress epileptiform activity and seizures by dampening neuroinflammation and neurodegeneration.
In a cell culture and animal model of Parkinson's disease (PD), it has been shown that phosphorylated Fyn activates PKCd in microglia, which in turn translocates to the nucleus (Saminathan et al., 2011) and initiates transcription of proinflammatory cytokines either directly or in association with c-Abl or NF-κB signaling components (Buj or et al., 2011; Gordon et al., 2016). It was shown that shRNA-mediated knockdown or genetic ablation of PKCd in primary microglia abolished inflammogens-induced proinflammatory response in microglia, and also suppressed ROS and RNS production, and proinflammatory cytokines release (Gordon et al., 2016). Phosphorylated PKCd also activates cytoplasmic subunit of the NOX2, which forms a functional complex with the membrane associated gp91phox to activate NOX2 signaling pathway and drives ROS and RNS production (Bedard and Krause, 2007; Fontayne et al., 2002; Gordon et al., 2016).
Inhibitors of SFK, such as dasatinib, bosutinib, saracatinib or ponatinib, are used in the treatment of cancer, in particular lung cancer. Approximately 85% of all lung cancer incidences are non-small cell lung cancer (NSCLC) (Jemal, Siegel et al., 2008). Non-small cell lung cancer (NSCLC) is one of the two main types of lung carcinoma, non-small cell (80.4%) and small-cell (16.8%) lung carcinoma, the classification being based on histological criteria. The non-small cell lung carcinomas have a similar prognosis and similar management and comprise three sub-types: squamous cell lung carcinoma, adenocarcinoma and large cell lung carcinoma. Squamous cell lung carcinoma (31.1% of lung cancers) often starts near a central bronchus and commonly shows cavitation and necrosis within the center of the cancer. Adenocarcinoma (29.4% of lung cancers) mostly originates in peripheral lung tissue and is usually associated with smoking. Large cell lung carcinoma (10.7% of lung cancers) is a fast-growing form that develops near the surface of the lung. Common treatments of NSCLC include surgery, chemotherapy, and radiation therapy. In particular, NSCLC is treated with adjuvant chemotherapy (i.e. chemotherapy after surgery). Wu (2009) describes phosphorylation patterns in lung cancer (see Wu (2009) PloS ONE 4 (11) e7994).
Previous studies have shown that SFK inhibitor, PP2 reduces frequency of epileptiform discharges in the hippocampal in vitro model (Salter and Kalia, 2004; Sanna et al., 2000). Saracatinib is more potent than other SFK inhibitors, and has been in clinical trials for Alzheimer's disease (AD) (Nygaard et al., 2015) and breast cancer (Gucalp et al., 2011). Saracatinib is an anilinoquinazoline compound which has high specificity for the tyrosine kinase domains of SFK (Hennequin et al., 2006). In these enzymes, an adenine moiety of ATP is bound to Src kinase domains through hydrogen bond networks. This allows chlorobenzodioxide moiety of quinazoline compounds to sit deep inside the hydrophobic pocket of SFK making number of hydrophobic contacts forming stronger inhibitor-enzyme complex. Moreover, the presence of C5 position on the quinazoline ring, which fits well into enzyme's ribose pocket, makes them even more selective for SFKs thereby increasing their binding affinity and potency (Ballard et al., 2005; Gibson et al., 2002; Hennequin et al., 2006). Furthermore, the SFKs has some enzyme residues present at the entrance of their pocket site, also known as gatekeepers, is another potential feature for the selectivity of quinazolines as inhibitors of SFKs. In contrast to SFKs, the ribose pocket in other kinases is open to wide range of compounds that makes them less selective in nature (Hennequin et al., 2006).

Tyrosine kinase inhibition as a treatment for epilepsy

Iowa State University Research Foundation, Inc.


A method and apparatus are provided for communicating information and carrying out other interactions between a browser and an application program. A hyperaction protocol is defined that enables a browser to directly call functions of an application program executed by a separate server over a public network. In one embodiment, in the course of parsing and displaying an HTML document or other HTML source text, a browser encounters or receives a hyperaction request of the form “hyperaction://<ApplicationAction>#<Payload>.” In response, the browser identifies a function or other action of a separate application. The browser calls that function of the application over the network and provides the payload. When a response is received, the browser extracts data values or function results provided by the application. As a result, a browser can directly interact with an application without using scripts or other awkward mechanisms of existing protocols.

Specialized computer programs called browsers are now widely used in networked computer systems for the purpose of retrieving and interacting with information stored in servers. A browser is a computer program specifically designed to help users view and navigate hypertext, on-line documentation, or a database. The term "browser" most often refers to a computer program designed to permit a user to view and interact with hypertext information, such as pages and programs written in the Hypertext Markup Language (HTML) that is communicated using the Hypertext Transfer Protocol (HTTP).
FIG. 1 is a block diagram showing a client-server system, in which client 100 communicates over a network 104 with server 106. Client 100 executes a browser 102. Server 106 executes application 108, which has access to one or more stored electronic documents 110.
In this configuration, browser 102 may establish a connection through network 104 to application 108. For example, browser 102 opens an HTTP connection through network 104 to an HTTP server running on server 106, or an HTTP daemon of application 108. Under control of client 100, browser 102 issues a request that specifies one or more of the documents 110 using a document identifier, such as a Universal Resource Locator (URL). Server 106 receives the request, parses it, retrieves the specified document from among documents 110, and sends a copy of the document in a response to browser 102. Browser 102 receives the document, parses coded instructions within the document, e.g., HTML source code, and displays the contents of the document at client 100 according to the coded instructions contained in the document.
Browsers can be configured as stand-alone computer programs or as processes that can be called from within another application program. Examples of stand-alone browsers are NCSA Mosaic, Netscape Communicator®, and Microsoft Internet Explorer®. Netscape Communicator and Microsoft Internet Explorer also are available in the form of executables that can be called from within an application program.
Browsers also have numerous graphical user interface display capabilities, communications functions, and security functions. For example, the HTML 3.0 standard defines various graphical user interface elements ("widgets") that a browser can automatically create and display when an HTML source document contains a particular type of command. However, there is presently no way for a separate application program, at the client or at a separate server, to selectively invoke such capabilities and functions without sending an HTML document to the browser for standard processing. There is a need for a mechanism whereby an application can invoke a particular function of the browser, and the browser can obtain data values from the application that are needed for proper or successful execution of the function that is invoked.
In conventional approaches, a browser is invoked from within an application program in order to load a page based on a standard protocol such as HTTP, file transfer protocol (FTP), etc. In the current approach, the application can pass output to the browser only by creating and passing a URL to the browser that defines a particular static page on a particular server, or a script and parameters for use by the script. An HTTP server or an application that is addressed by the browser then generates an output page and instructs the browser to load it. However, this approach has many disadvantages and drawbacks.
For example, HTTP and FTP are cumbersome to use for certain kinds of interactions between an application and a browser. CGI scripts or other mechanisms have to be used in order to request application functions and pass variable values or references using HTTP. The lists of parameters and values that appear in the scripts are complicated and must be carefully constructed and concatenated to assure proper operation.
The HTTP approaches require, to at least some extent, the HTTP protocol to carry out functions for which it was not designed. The scripts and other parameter passing mechanisms are grafted onto HTTP and are functional, but they are not elegant and have definite limitations. There is a need for a new protocol or an improved protocol that is intended for and designed from the ground up to handle communications between a browser and an application or server.
Moreover, using the traditional protocols, the browser cannot easily obtain information that it may need from the application while the application is running. There is no convenient way to obtain, for example, the value of a single variable that is maintained by a Web application.
Based on the foregoing, there is a clear need in this field for a mechanism that enables a browser to directly access functions and data that are maintained by an application executed remotely or separately from the browser.
Other needs and objects will become apparent from the following description.

This patent is subject to a terminal disclaimer.

Method and apparatus for communicating information between a browser and an application program


A sail having at least three tops and three corresponding edges opposite the tops and comprising a plurality of panels each of which in turn comprises two outer covering layers, between which a plurality of reinforcement elements are positioned which define, in their entirety, a multi-directional main reinforcement structure. The plurality of reinforcement elements are disposed in a pre-determined manner with respect to three generatrix lines, which have in common a determinate reference point, disposed in a substantially central position of the sail and each one passing through, or near, one of the three tops.

It is known to produce a sail of the laminated type of a triangular shape having three tops defining respectively three corners, that is, tack corner, head corner and clew corner, and three sides, respectively the foot or base of the sail, between the tack corner and the clew corner, the fore leech or reef, between the tack corner and the head corner, and the after leech, between the clew corner and the head corner.
The sail comprises a plurality of sailcloths joined together by means of stitching or gluing, each of which comprises in turn two outer covering layers, made of plastic material, between which reinforcement elements are positioned, made of carbon fiber. The latter are disposed following the force lines generated on the sail by the state of stress to which it is subjected during use. All together, the reinforcement elements achieve a main reinforcement structure for the sail.
It is also known to insert auxiliary reinforcement elements between the two outer covering layers of all the sailcloths, in order to achieve auxiliary reinforcement structures, for example with regular pre-formed grids or nets, or with bundles of threads angled with respect to the reinforcement threads disposed according to the aforesaid force lines and forming the main reinforcement structure, in order to support secondary forces, always present on the sail, and responsible for considerable deformations of the outer covering layer.
The state of stress acting on the sail is the sum of the stresses of an aerodynamic nature generated by the action of the wind on the surface of the sail, consisting of a field of pressures that varies from point to point, and of stresses imposed by the action of the crew on the sail in order to perform maneuvers, stresses that are transmitted to the sail at the points where the sail is constrained to the boat.
This state of stress is in itself very complex, as it is a function of the structure of the sail itself, and to determine it entails the need to solve what is commonly defined in the state of the art as an aero-elastic problem.
Making sails of a laminated type, where the force lines represent a kind of guide direction according to which the reinforcement elements are disposed, has the disadvantage, however, that the reciprocal position and orientation of the force lines vary continuously as the conditions of the wind vary and as the control lines or current maneuvers are adjusted (for example sheets, halyards, flying shrouds or other) by the crew, making it necessary, in practice, to choose one or more design points when designing the sail, and to distribute the reinforcement elements in a way which represents a compromise and is not the best possible solution.
Another disadvantage of sails made in this way is the increase in the number of auxiliary reinforcement elements, which therefore entails a considerable increase in the material used to make the sail, and hence of the weight of the sail.
The solution is also known of making a sail using reinforcement elements that are not disposed on the force lines.
According to this conventional solution, however, large size curved molds are used, which make the method to construct large size sails very inefficient from the economic point of view, and very laborious and complex.
It is also known to make sails by putting a large quantity of reinforcement elements at the points where the sail is constrained to the boat, neglecting the central zone of the sail, which on the contrary is fundamental in order to maintain its shape during use.
It is also known to make sails relying on curves having the same level of stress value, known as iso-stress curves. However, this approach also has the disadvantage that one force condition from among the infinite possibilities is chosen, and since, between one iso-stress curve and the next, the stress is not constant but continuously varies, a structure like the one proposed would in fact only be iso-stress if one were to have recourse to infinite iso-stress elements, something which is impossible in practice.
One purpose of the present invention is to achieve an apparatus and perfect a method to make a sail wherein the reinforcement elements are dependent directly on the state of stress to which the sail is subject, and not on the force lines acting on the sail, which are a consequence of said state of stress, with the purpose of guaranteeing a better maintenance and control of the shape, a greater strength and duration given the same weight with respect to other sails of the laminated type.
The Applicant has devised, tested and embodied the present invention to overcome the shortcomings of the state of the art and to obtain these and other purposes and advantages.

Apparatus and method to make a sail and relative sail made


A lens system (100,200,300,400,500) that employs one or more liquids (130,230,340,350) to participate in correcting chromatic aberration. The liquids (130,230,340,350) are natural or having manually adjusted physical properties. The liquids (130,230,340,350) are filled in a chamber (430,540,550) formed by a frame and a lid (150,250,370,450,570) on a top surface of the frame, and a base (140,240,360,440,560) on a bottom surface of the frame.

A common physical problem or phenomenon associated with optical systems is chromatic aberration. Chromatic aberration is a physical phenomenon resulting from dispersion in which a lens fails to focus all colors or different wavelength of light, to the same convergence point. It occurs because lenses have different refractive indices for different wavelengths of light. A lens system that corrects chromatic aberration is said to be a "color-corrected" or achromatic lens system. An achromatic lens system brings light rays with different color or wavelength to a common focus on the optical axis of the system. Therefore it can improve the resulting image quality of the optical system.
At present almost all achromatic lens systems use expensive special characteristic optical glasses or crystals. Lenses made of glasses or crystals, however, are costly and hard to manufacture and may require individual special grinding and polishing processes.
A better, both in performance and in production process point of view, optical system for correcting chromatic aberration would be desired.

Achromatic optical system with liquid lens


An improved internal combustion engine with rotary valves. The engine includes a cylinder head above each cylinder and there is a single opening located in the cylinder head above each piston for use as an intake and as an exhaust port. A rotary valve member is in the form of a hollow cylinder, the outer surface of which abuts the outer surface of the single opening, the rotary valve has an intake port formed through the wall thereof and an exhaust port also formed through the sidewall, the cylinder includes an inner wall dividing the interior of the rotary valve cylinder into an exhaust compartment and an intake compartment. The rotary member has an opening at one end which comprises the intake port and an opening at an opposite end which comprises the exhaust port. Means are provided for rotating the rotary valve in a timed manner so that as the piston moves downwardly in an intake stroke, the intake port is passing over the single opening permitting an air fuel mixture to be drawn through the intake end the rotary valve and into the cylinder. As the piston begins to move upwardly in a compression stroke, the cylindrical sidewall of the rotary valve is passing over the single opening which is also the case as the piston is moving downwardly in a power stroke. Then as the piston begins moving up in an exhaust stroke, the exhaust port passes over the single opening causing the exhaust gases to flow out of the exhaust end of the rotary valve member.

The field of the invention is internal combustion engines and the invention relates more particularly to four cycle internal combustion engines of the type utilized in automobiles and other motor vehicles.
Rotary valves have been used in an internal combustion engines at least in the patent literature. The Tischler U.S. Pat. No. 3,993,036 shows an internal combustion engine with two rotary valves about each cylinder. The Lyons et al U.S. Pat. No. 4,473,041 similarly has a pair of rotary valves about each cylinder.
Lyons, et al U.S. Pat. No. 4,545,337 shows another construction of a dual rotary valve engine with two rotary valves above each cylinder.
Lastly, the Hansard U.S. Pat. No. 5,003,942 shows a rotary vaned valve has an intake valve and a second exhaust valve above each cylinder.
It is not believed that any of the rotary valve engines set forth above have become practical and yet the concept of having a valve opening which provides a much larger port for the intake of air fuel mixture and the expelling of exhaust gases can provide a more efficient engine, as compared to the conventional poppet valves. Conventional valves provide a substantial amount of resistance to gas flow as they are only opened around the annular edges thereof.

Internal combustion engine with rotary valves


Phosphor screens are disclosed that exhibit decreased Coulombic aging and/or lower threshold voltages. The phosphor compositions and electrochemical methods for making those screens are also disclosed.

The use of cathodoluminescent materials (phosphors), substances that transform energy into light, has become ubiquitous in consumer electronic displays, including the wrist watch, electronic equipment status displays, and lap-top computers. Phosphor films are also important in defense applications, ranging from high definition table top map displays to helmet-mounted and "headsup" displays.
One of the most common uses for phosphor films is in computer screens. A major limitation in the use of phosphor films is that their luminescence degrades over time. The mechanism(s) for this degradation is poorly understood, but the degree of degradation is related to the "Coulombic aging" of the phosphor. "Coulombic aging" is the current multiplied by time and expressed as Coulombs of charge per unit area.
The most widely used phosphors in the manufacture of computer screens are zinc sulfides because their quantum efficiency is known to be the highest, about 22%, compared to some other oxysulfides or silicate phosphors which have a quantum efficiency of about 2-12%. A major problem with the zinc sulfide phosphors, however, is their Coulombic aging which leads to a loss of efficiency and brightness with use. Zinc sulfide phosphors lose about half of their brightness, or 50% of their initial efficiency, after only 30-50 Coulombs/cm.sup.2 charge loading. Since 1 Coulomb/cm.sup.2 corresponds to about 250 hours of cathode ray tube (CRT) phosphor screen use, the life expectancy of a zinc sulfide phosphor screen typically does not exceed 12,500 hours of operational life. Zinc sulfides, being the standard cathodoluminescent material used in phosphor screens, have dictated the commercial requirement that CRTs have an operational life span of 10,000 hours.
The Coulombic aging of phosphors has become increasingly critical for the computer industry with the development of the Flat Panel Display (FPD), which operates at higher current densities than CRTs and therefore has an even shorter life span than CRTs. For example, the operational voltage for FPDs range from 100 V to 1,000 V and require higher current densities to achieve the same power loading. Under these operational conditions, the phosphors (especially the more efficient sulfide and oxysulfide phosphors) quickly degrade due to Coulombic aging and saturation. Thus, extending the life span of the FPDs, which could lead to the commercial realization of full-color FPDs, would require the development of phosphors that are not as susceptible to Coulombic aging or could operate at lower current densities.
To date, the operational voltage of FPDs has been limited by the physical and chemical characteristics of the phosphors used. Commercially available phosphors have a high threshold voltage typically ranging from about 100 to 120 electron volts (eV). Since currently available CRTs and FPDs use phosphors having a high threshold voltage, the operation of those display devices is highly power consumptive.
Thus, there is a pressing need for phosphor films that exhibit decreased Coulombic aging and/or lower threshold voltages.

Composition and method for preparing phosphor films exhibiting decreased coulombic aging


A steel for use in high strength pinion shaft which is not refined and used by applying high frequency hardening, with less occurrence of peeling during hobbing, having high surface hardness, impact value and torsional strength after high frequency hardening, and with less heat treatment strains during high frequency hardening, containing, on the mass % basis; C: 0.45-0.55%, Si: 0.10-0.50%, Mn: 0.50-1.20%, P: 0.025% or less, S: 0.025% or less, Mo: 0.15-0.25%, B: 0.0005-0.005%, Ti: 0.005-0.10%, and N: 0.015% or less, satisfying: 0.80≦Ceq 0.95 and f value≦1.0, and the balance of Fe and inevitable impurities, as well as a manufacturing method thereof.

The present invention concerns a steel for use in high strength pinion shaft for manufacturing a pinion shaft used in automobile steering systems, as well as a manufacturing method thereof.
In existent steering systems, rack & pinion systems utilizing an oil pressure have been predominant in which pinion shafts are used for the systems. The pinion shaft serves as a part for transmitting a rotational torque when a driver operates a steering wheel and converting rotational motion to linear motion by meshing with a geared portion of a rack bar, and it is one of important parts in the steering system.
The pinion shaft is manufactured by the combination of steel species and surface hardening heat treatment, for example, using case hardened steel (for example, JIS SMnC420, SCM420) and applying carburization hardening and tempering, or using carbon steel (for example, JIS S45C) or tough and hard steel (for example, JIS SCM440, SCM445) and applying high frequency hardening and tempering.
However, carburization hardening and tempering to the case hardened steel involves a problem of increasing the heat treatment cost and occurrence of heat treatment strains or abnormal heat treated layers.
On the other hand, in a case of applying high frequency hardening and tempering to carbon steels or tough and hard steels, while the cost is reduced and strains are decreased compared with carburization hardening and tempering to the case hardened steel, it results in a problem of increasing the cost by refining in a case of using a material applied with a refining treatment in order to ensure the inner hardness of the pinion shaft and easiness for high frequency hardening. On the other hand, in a case of using a not-refined steel instead of the material applied with the refining treatment, it results in a problem of lowering the performance of the pinion shaft because of low impact strength.
As the not-refined steel for use in shaft such as pinion shaft, JP-A No. 09-195000 discloses a not-refined steel containing: C: 0.20-0.50%, Si: 0.05-0.70%, Mn: exceeding 0.60 and up to 1.00%, S: 0.01-0.07%, V: 0.02-0.50%, N: 0.002-0.03%, P: 0-0.050%, Cu: 0-0.30%, Ni: 0-0.30%, Cr: 0-1.00%, Mo: 0-0.30, Al: 0-0.050%, Pb: 0-0.30%, Ca: 0-0.0100%, Te: 0-0.10%, Bi: 0-0.100% and the balance of Fe and inevitable impurities in which fn1≧0 and fn2≦0; fn1=C+(Si/10)+(Mn/6)+5N+1.65V+(Cr/3)−0.6, fn2=[C/(fn1+0.6)]−0.6.
Further, gear cutting is conducted in the manufacturing steps of the pinion shaft. Depending on the material used upon gear cutting, the geared surface is sometimes roughened to deteriorate the tooth form accuracy due to the effects of hardness and tissue (particularly, in those not applied with pre-heating treatment such as refining and annealing). When the form accuracy is lowered, since the state of the meshing surface in the tooth portion of rack and pinion is worsened, the wear resistance or pitting resistance is sometimes deteriorated. Further, depending on the lowering for the tooth form accuracy, state of friction at the gearing surfaces changes greatly to result in a problem of lowering the feeling in steering.
Further, for coping with the energy saving demand in view of recent global ecological problems, electromotive type power steering utilizing motors (EPS) have been developed and tended to be used more and more instead of hydraulic power steerings.
EPS sometimes have assist mechanisms different from those in the existent steering systems and, particularly, in a type of assisting the rotational torque of the pinion shaft, since larger force exerts on the meshing portion for the teeth portion of the rack and pinion, compared with the existent systems, the working conditions tend to become severer compared with the existent systems.
In a case where steels free of the refining treatment, that is, not-refined steels are put to gear cutting as they are by a hob or the like, this results in a problem that the gear cut surface becomes roughened to deteriorate the tooth fore accuracy and lower the wear resistance or pitting resistance. Further, in a case where high frequency hardening is applied to usual not-refined steels, since they have high ferrite content, ferrite remains in the high frequency hardened layer under usual high frequency heating conditions, failing to obtain a predetermined surface hardness thereby resulting in a problem of lowering the wear resistance and the pitting resistance. In a case where heating is conducted at higher temperature or for longer time as high frequency heating conditions in order not to remain ferrite, this results in a problem that the depth of the hardened layer increases to cause large heat treatment strains or crystal grains growth to lower the strength. Further, in a case of applying high frequency hardening to existent not-refined steels, it results in a problem of failing to obtain desired strength to torsion, bending, impact torsion or impact bending.

Steel for use in high strength pinion shaft and manufacturing method thereof


The first process for producing an optical fiber coupler includes a first step wherein at least one of the optical fibers to be used is stripped of the coating, a second step in which the bare portion of that optical fiber is heated for a predetermined time to diffuse the dopants, a third step wherein the other optical fibers which have not been heat-treated are stripped of their coating, a fourth step in which the bare portions of all the optical fibers are heated as they are brought into intimate contact, thereby forming a unitary portion, and a fifth step wherein the unitary portion is drawn via heating to form the coupling portion of an optical fiber coupler. The second process for producing an optical fiber coupler includes stripping the coating from at least one optical fiber, fixing the fiber so as to impart an axial stress thereto and then heating the bare portion of the stripped optical fiber thereby thinning the diameter of the heated portion, and then proceeding in the same manner as described with respect to the third through fifth steps of the first embodiment of the present invention. The processes according to the present invention enable a wide-band optical fiber coupler to be easily produced without using optical fibers of different structures but using optical fibers of identical structures.

1. Field of the Invention
The present invention relates to a process for producing an optical fiber coupler that provides a constant branching ratio over a broad wavelength range.
2. Brief Description of the Prior Art
An optical fiber coupler is an optical component that permits light to be branched or coupled between a plurality of optical fibers. Optical fiber couplers are known to be produced by either a melt drawing process or a polishing process. The melt drawing process is said to be best suited for the production of couplers single-mode fibers (see "Recent Techniques on Optical Fiber Couplers" in Optronics, No. 5, p. 125, 1988). This process starts with stripping part of the coating from a plurality of optical fibers, heating them to fuse the stripped fibers together, forming a bundle by twisting the fibers or arranging them parallel to one another, drawing the bundle under heating until its characteristics such as branching ratio attain predetermined values, and forming a coupling portion.
One of the important applications of optical fiber couplers is in branching of optical communication lines. In optical communications, light emitted at a plurality of wavelengths (e.g., 1.31 .mu.m and 1.55 .mu.m) is transmitted along each line. Thus, it is also desirable for optical fiber couplers to have constant branching characteristics over a broad wavelength range including emission wavelengths such as 1.31 .mu.m and 1.55 .mu.m. However, optical fiber couplers produced by the melt drawing process have the disadvantage that their branching ratio is largely wavelength dependent.
It has been proposed that this problem be resolved by melt drawing optical fibers having different outside diameters on cladding (see Takeuchi et al., "Broad Wavelength Range Optical Fiber Couplers 1" in C-207 of the Preprint for 1989 Autumn National Conference of the Institute of Electronics, Information and Communication Engineers) or by melt drawing optical fibers having different mode field diameters (see "Broad Wavelength Range Optical Fiber Couplers 2" in C-208 of the same preprint).
However, in order to produce optical fiber couplers of a predetermined branching ratio by these prior art methods, it has been necessary to use a plurality of optical fibers having different structures. Hence, it has been difficult to produce a desired optical fiber coupler using common commercially available single-mode optical fibers and this had made it necessary to use optical fibers of special structures.
An alternative process is determined in U.S. Pat. No. 4,798,438.
This process uses two optical fibers of identical structure, one of which is drawn preliminarily to a smaller diameter. The process is shown schematically in FIG. 6, in which numeral 21 refers to an optical fiber, 22a and 22b to a clamper, and 23 to a burner. First, the coating of the optical fiber 21 is partly stripped off. Thereafter, with both ends of the bare portion of the fiber being clamped by the clampers 22a and 22b, tension is applied to the fiber so that it is pulled in opposite directions indicated by arrows 61 and 62 in FIG. 6, whereby the bare portion is drawn as it is heated with the burner 23.
In this process, the diameter of the preliminarily drawn bare portion determines the branching ratio of the optical fiber coupler to be produced and, hence, it is important to draw the bare portion of the fiber with good control and high repeatability. However, the preliminary drawing step involves so many variables in connection with the draw speed, draw length, etc. that it is difficult to attain identically drawn diameters with separate fibers.

Process for producing an optical fiber coupler


Peptide antigens corresponding to amino acid residues 2-12, 1-12, 2-15 and 1-15 of parathyroid hormone (PTH), antibodies having an affinity to such peptide antigens and methods of producing the same. Such antigens, antibodies and methods producing the same according to the present invention are useful in determining bioactive intact PTH levels in serum, plasma, and/or cell culture media. Such antibodies further possess a high degree of species cross-reactivity, but substantially mitigated cross-reactivity to non-whole PTH peptide fragments and little to no recognition of the first amino acid residue of PTH.

Parathyroid hormone (PTH) and its importance in regulating the concentration of calcium ions in the blood are well-known. In this regard, such hormone is created by the parathyroid glands and, in combination with other factors, functions to regulate the blood calcium ion levels such that the same is maintained in a steady concentration in both cells and surrounding fluids. Essentially, PTH functions to release stored calcium in the body when serum calcium levels decrease. On the other hand, such secretion is suppressed to the extent the serum calcium concentration increases.
In its complete form PTH comprises a unique peptide comprised of 84 amino acids. The specific sequence of PTH, as provided for a plurality of species, namely, humans, rats, mice, bovids, dogs and pigs, are depicted in FIG. 1, and a variation thereof in FIG. 2, which illustrates the relatively consistent structure such hormone maintains between such identified species.
Given its significance in calcium metabolism for not only humans, but a variety of species, accurately measuring PTH has and continues to be of substantial clinical significance. As is well-documented, serum PTH levels serve as an important parameter for patients having diseases such as hypercalcemia, primary hyperparathyroidism and osteoporosis, among many others. PTH likewise becomes of substantial clinical importance in patients afflicted with chronic renal failure who, because of an excess in PTH production, can develop renal osteodystrophy.
Notwithstanding its important role in metabolism and clinical significance, substantial difficulties have and continue to exist with regard to determinating circulating biologically active PTH levels. First of all, it is well-known that PTH is normally present at extremely low levels, which are normally between 10 pg/ml to 65 pg/ml. Furthermore, it is known that the PTH peptide can be present in a variety of circulating PTH fragments, and in particular large non-(1-84) circulating PTH fragments which appear to co-migrate chromatographically with the (7-84) PTH molecule and are known to significantly interfere with conventional PTH assay measurements. Indeed, the large non-(1-84) PTH fragments may represent about one-half (2) of the PTH measured by a majority of current assays. Exemplary of the current shortcomings of the accurate measurement of PTH are set forth in published Patent Cooperation Treaty International Application No. PCT/US00/00855, International Publication No. W0/00/42437, entitled Methods for Differentiating and Monitoring Parathyroid and Bone Status Related Diseases, and Lepage, Raymond et al., A Non-(1-84) Circulating Parathyroid Hormone (PTH) Fragment Interferes With Intact PTH Commercial Assay Measurement In Uremic Samples, Clinical Chemistry 44:4, 1998 pages 805-809, the teachings of which are expressly incorporated herein by reference.
In an attempt to address such shortcomings, a new assay for detecting PTH levels was introduced by Scantibodies Laboratory, of Santee, Calif., which incorporates a tracer antibody having a binding specificity for the very end N-terminal fraction of human PTH, and more specifically, the first six amino acid residues thereof. As presently understood, such assay appears to minimize cross-reactivity with large non-(1-84) PTH fragments. However, to derive such antibodies requires substantial effort and expense in purifying the same. Moreover, such tracer antibodies have maximum recognition for only the first amino acid residue of PTH, and substantially reduced specificity for any subsequent residues thus obviating its use for some other species where the first amino acid is different. Such drawbacks are discussed in the article by John, M. R. et al., entitled A Novel Immunoradiometric Assay Detects Full-Length Human PTH but not Amino-Terminally Truncated Fragments: Implications for PTH Measurements in Renal Failure, The Journal of Clinical Endocrinology & Metabolism, Vol. 84, No. 11, 1999, p. 4287-4290, the teachings of which are expressly incorporated herein by reference.
Thus, there has been and continues to be a long felt need in the art for an assay binding partner and method of generating the same that is specific for bioactive intact PTH that can determine PTH levels With mitigated cross-reactivity to PTH peptide fragments. There is likewise a need in the art for improved PTH binding partners that can measure PTH levels in a more cost-effective manner and have a greater affinity for PTH that can be readily incorporated into immunoassay kits and the like. Still further there is a need for binding partners, namely, antibodies having a binding recognition that is specific to PTH and can be utilized to detect PTH levels over a wide-variety of species. Finally, there is a need in the art for an improved binding partner having a high binding affinity for PTH that may be readily derived using conventional mechanisms that requires minimal purification, results in greater binding recognition for intact PTH, possesses minimal cross reactivity to large non-(1-84) PTH fragments, and can be derived utilizing methods that generate higher antibody yields than prior art binding partners.

Antibodies and peptide antigens for producing antibodies having a selective binding specificity to bioactive intact parathyroid hormone (PTH) 1-84


Disclosed is a method for penetration of lipid bilayer membranes in order to insert at the tip of a hollow needle-shaped object, such as a micropipet-, into a container formed of a lipid bilayer membrane, wherein said container is placed between said needle-shaped object, with the tip of said needle-shaped object placed in contact with said conainer in such a way that it applies a mechanical force to the lipid membrane of said container, thus mechanically straining it, and a second electrode, whereupon a transient electric pulse of 1-to-103 V/cm is applied between the electrodes, resulting in a focused electrical field over said container C which induces a dielectric breakdown of the lipid bilayer causing the needle-shaped object to penetrate the container. Disclosed is also an electroinjection method based on the above method, wherein substances are introduced through the needle-shaped object and into the container after penetration of the needle-shaped object.

Today, there is a growing interest in inserting microelectrodes, microcapillaries and micropipet-tip-sensors into single cells. There is also a growing interest in incorporating sub-micron-sized sensing, sampling, and signal-amplifying particles, as well as large biopolymers into single cells and liposomes. Several ultrasensitive detection and sensing methods are based directly or indirectly on the use of colloidal particles. Examples include quantum dot bioconjugate sensors1,2, the family of Probes Encapsulated By Biologically Localized Embedding (PEBBLE) sensors,3 and silver (Ag) and gold (Au) colloids for use in Surface Enhanced Raman Spectroscopy (SERS) measurements4-6. One of the main limitations for practically using these techniques is the difficulty of noninvasive and quantitative introduction of colloidal particles into the cellular interior7. Furthermore, it would be attractive to direct the introduction of particles into specific subcellular compartments such as the cytosol, nucleus, or even organelles of individual cells.
GUVs are cell-sized liposomes composed of a single lipid bilayer with an entrapped aqueous compartment8. Such liposomes are attractive to use as ultra-small reaction containers in which the reaction under study is confined and separated from the external medium. As such they can be used for studies of biochemical reaction dynamics in compartments mimicking a natural intracellular-intraorganellar environment9-12.
For use as reaction containers, it is necessary to load vesicles with reactants, including biopolymers like DNA and colloid particles or organelles (synthetic or naturally derived). Loading of liposomes can, in principle, be performed by adding the particles during the preparation of the vesicles, since they upon formation trap a part of the medium in which they are formed. The trapping efficiency for small liposomes is, however, limited even for low-molecular-weight compounds and, entrapment of larger structures such as colloids, is of very low probability13,14.
Another approach for liposome-loading is to introduce the materials into preformed vesicles by using micromanipulation-based techniques developed for loading of single cells. One such technique that is feasible to use is the microinjection technique15.
By using microneedles made out of pulled glass capillaries with outer tip-diameters in the range of 200-500 nm, it is possible to penetrate the membrane wall of a liposome, or cell, and eject controlled volumes of a desired reagent inside the vesicle16. Injection volumes are typically in the picoliter to attoliter range and controlled by regulation of injection-time and injection-pressure. The pressure is usually generated by utilization of pressurized-air or oil-hydraulic systems.
All microinjection techniques are based on mechanical permeabilization of lipid membranes. When a mechanical point-load is applied, e.g. by a capillary, onto the membrane of a liposome or cell, the membrane is forced to stretch and the isotropic membrane tension, working in the plane of the membrane, is increased. At sufficiently high membrane tension, the structural integrity of the liposome, or cell, is momentarily lost as holes are formed in the membrane, releasing internal fluid in order to counteract the increase in membrane tension. This membrane rupture occurs at the site of the highest mechanical load, which is the loci where the point-load is applied, thus allowing the insertion of a microinjection capillary into the interior of the liposome or cell.
Whereas microinjection works well with certain cell-types and multilamellar liposomes, there are a few drawbacks to the microinjection techniques with unilamellar vesicles and many cell types. Lipid membrane bilayers are, typically, very elastic and the absence of internal supporting structures in unilamellar liposomes make them very difficult to penetrate by mechanical means. The outer diameter of a tip suitable for injection into thin-walled liposomes and smaller cells is about 200 nm, and the inner diameter is typically in the range of only 100 nm16,17. Such tips are very fragile and extremely difficult to view in a light microscope, making positioning difficult. The main drawback of using small inner-diameter injection tips is, however, the requirement of using ultrapure injection liquids in order to prevent clogging, limiting injection species to solutions of low- and medium-molecular-weight compounds. Micro-injection techniques are considered to be relatively invasive due to the large mechanical forces applied, inducing permanent membrane damage and even lysis of cells and liposomes.
An alternative approach to single-liposome or single-cell loading is to use microelectroporation18. This technique is based on the theory of electro-permeabilization. When exposing a liposome, or cell, to an electrical field, a potential drop is generated across the membrane. At sufficiently high field strength, the critical transmembrane potential Vc, of the membrane is exceeded, and small pores will form in the liposomal/cellular membrane due to dielectric membrane breakdown. The transmembrane potential Vm, at different loci on the membrane of a spherical vesicle during exposure to a homogeneous electric field of duration t, can be calculated fromVm=1.5 rs E cos α(1−exp(−t/τ))where E is the electric field strength, rs is the radius of the sphere, α is the angle in relation to the direction of the electric field, and τ is the capacitive-resistive time constant. Pore formation will occur at spherical coordinates exposed to the largest potential shift, which is at the poles facing the electrodes. Typical value for Vc for a cell-sized vesicle is ˜1V, and the corresponding electric field strength needed for exceeding the critical transmembrane potential Vc, is in the range of 1-10 kV/cm.
In microelectroporation, the analyte to be encapsulated is added to the exterior solution of the liposomes, or cells, and an electrical field is then applied locally, using microelectrodes. The amount of analyte that enters the vesicle is dependent on the analyte concentration gradient, membrane potential, duration of the applied field, and diffusion rate of the analyte19. Drawbacks to the electroporation technique are difficulties of quantitative loading, and loading of structures of sizes larger than the effective pore-diameter, which for electropermeabilized erythrocytes is in the range of 1-to-240 nm20,21. To improve quantitive loading, controlled amounts of analytes can be introduced via a small micropipette tip inserted into a hole pre-formed by electroporation (as described, for example, in JP 8322548). This approach, however, presents a number of disadvantages, including the need to apply a fairly strong electric field (˜1V) to form a hole for tip insertion.
By combining electroporation and the application of a mechanical force onto a membrane vesicle, the strength of the applied electrical field needed for membrane permeabilization may be substantially reduced25. This phenomenon is sometimes referred to as electromechanical destabilization. It has been shown that electrical fields established over lipid bilayer membranes imposes an electrocompressive mechanical stress σe, acting on the lipid membrane. This force works normal to the plane of the membrane and leads to a decrease in membrane thickness. If assuming that a lipid membrane behaves as a capacitor, then the electro-compressive force is proportional to the voltage drop V, over the membrane and thus to the strength of the applied electric field
      σ    e    =            1      2                          ɛɛ        o            ·              (                  V                      h            e                          )            where ε is the relative dielectric constant and ε0, is the permitivity and he, is the dielectric thickness of the membrane. The differential overall mechanical work dW, done on the lipid membrane is then simply the sum of the electro-compressive stress σe, and the isotropic membrane tension T, controlled by the amount of mechanical strain applied to the membrane
  dW  =            [                        T          _                +                              1            2                                                                        ɛɛ                o                                                          (                                  V                                      h                    e                                                  )                                      ·            h                              ]            dA  where h is the overall thickness of the lipid bilayer membrane, and dA is the change in membrane area. Consequently, when a mechanical strain is applied to a membrane vesicle, the trans-membrane potential needed to achieve permeabilization can be significantly reduced. Therefore this approach for membrane permeabilization may be even less invasive than electroporation since lower electric fields can be used, minimizing the risk of unwanted electrochemical reactions at the membrane surface of a cell or a liposome.

Combined electroporation and microinjection method for the penetration of lipid bilayer membranes


A tape cutting device that cuts off an empty tape, which is discharged from a tape feeder after supplying components to a component mounting apparatus by pitch-feeding a tape containing the components, by opening and closing two cutting blades actuated by a pneumatic actuator driven by a supply of a pressurized air from a pneumatic pressure source controlled by a control valve, comprising:                a blade closing mechanism which closes said two cutting blades when the supply of the pressurized air from the pneumatic pressure source to the pneumatic actuator is stopped.

1. Field of the Invention
This invention relates to a tape cutting device cutting off an empty tape discharged from a tape feeder by opening and closing operation of two cutting blades and a tape feeder changing carriage which includes such tape cutting device and with which an install and a removal of a plurality of tape feeders mounted thereon to the component mounting apparatus are performed.
2. Related Art
The tape feeder is attached to a predetermined position in the component mounting apparatus and supplies components to a pick-up position to a mount head by feeding a tape for supplying components. A so-called empty tape that is left after supplying components is cut off by opening/closing operation of two cutter blades in a tape cutting device disposed below the tape feeder, and collected in a box-shaped tape collecting device disposed below the tape cutting device.
When a plurality of such tape feeder changing carriages are installed to a component mounting apparatus, install operations and removal operations are usually troublesome and require heavy workload. Therefore, conventionally, there has been proposed a tape feeder changing carriage with which a plurality of tape feeders can be installed together to the component mounting apparatus. In such a tape feeder changing carriage, a feeder base to which the tape feeders are mounted is provided in a carriage body portion that is movable by operating a lever. The tape feeder changing carriage is able to install and remove the tape feeders collectively to the component mounting apparatus by attaching and detaching the carriage body portion to the component mounting apparatus. When the tape feeder changing carriage is attached to the component mounting apparatus, the tape cutting device provided in the component mounting apparatus enters into a space below the feeder base of the tape feeder changing carriage. The tape discharged from the tape feeder is guided to the tape cutting device by a tape guiding member provided on the tape feeder side or the component mounting apparatus side. See Japanese Patent No. 3861694.
However, as described above, in a conventional case that the tape discharged from the tape feeder is configured to pass through a member on the component mounting apparatus side (namely the tape cutting device), the operation to introduce the tape led from each tape feeder to the tape cutting device is allowed to be performed only after the tape feeder has been installed to the component mounting apparatus (namely, after the tape feeder changing carriage has been attached to the component mounting apparatus). Further, the operation to remove the tape feeder from the component mounting apparatus (namely, the operation to detach the tape feeder changing carriage from the component mounting apparatus) is allowed to be performed only after removing the empty tape extended from each tape feeder out of the tape cutting device. Accordingly, it takes time to perform the install operation and removal operation of the tape feeders, so that throughput of mounting the components by the component mounting apparatus is deteriorated.
Moreover, the conventional tape cutting device as described above is often configured such that two cutting blades are kept open when the device is not operated. Accordingly, there is a fear that foreign matters intervenes between two cutting blades to cause troubles.

Tape cutting device and tape feeder changing carriage


A suture anchor apparatus for anchoring a suture in a bone. The apparatus includes an anchor with an elongate tip, a threaded portion and a suture securing structure coupled to the threaded portion. The tip includes a leading end, a trailing end and a longitudinal axis extending therebetween. The tip further has a length measured from the leading end to the trailing end, a width measured at the trailing end and an aspect ratio equal to the length divided by the width. The threaded portion is coupled to the trailing end of the tip and extends back therefrom and includes a generally cylindrical root with a screw thread formed thereon. The root has an elongate axis collinear with the longitudinal axis of the tip and the threads having an outside diameter substantially greater than the width of the tip. The aspect ratio and length of the tip are configured to make the anchor stable with only the tip inserted into the bone.

Suture anchors are used in orthopedic surgery to, for example, reattach a ligament to a bone after the ligament has been separated from the bone by a sports injury. Suture anchors are inserted into the bone and include barbs, threads or other means to resist pullout force applied to the anchor. Anchors typically include an eyelet or other structure to secure a length of suture. The suture is used to draw a ligament against the bone. With the ligament held to the bone, preferably at or near the original attachment point, the ligament is able to reattach to the bone. Suture anchors are normally made of either a bio-absorbable compound or a bio-compatible material because the anchor is often covered by the reattached ligament once the healing process is completed and cannot be easily removed.
Suture anchors can be either removable or non-removable after initial placement. Non-removable suture anchors are typically hammered or pushed into the bone, either with or without a pre-drilled hole, and retained by barbs that resist pullout. Removable suture anchors are typically threaded and may be screwed into the bone for anchoring and unscrewed from the bone for removal. Some removable suture anchors include a hole-starting drill bit that bores a hole in the bone ahead of the threaded portion. This eliminates the need to pre-drill a pilot hole for the anchor. One drawback of such an anchor is that, as the drill bit bores through the bone, it may migrate and the path of the hole may be widened or misdirected from the originally intended location. It is therefore difficult to accurately place self-drilling anchors.
A suture anchor is best placed as close as possible to the original attachment point of the ligament to facilitate reattachment. However, with existing anchors, this is often difficult due to interference from surrounding soft tissue or bones. The first site chosen for an anchor may be determined to be unsuitable for various reasons that may not be known until after insertion. For instance, the underlying bone structure may be incapable of supporting the anchor properly. The anchor must then be re-sited in a different location. Re-siting is impossible with non-removable anchors, multiple anchors must be implanted instead.
Removable anchors make re-siting possible but existing removable anchors have several drawbacks. Existing removable anchors create a hole, either pre-drilled or drilled by the anchor, with a diameter and a depth corresponding to the size of the anchor. The hole is generally cylindrical in shape, but may be irregular and even larger than the root portion of the anchor if the drill was not maintained at a constant angle throughout the drilling process. As a result, the bone structure is weakened around the drilled hole. If the anchor must be re-sited, the surgeon must avoid the area around the previous hole, sometimes resulting in a placement that is less than surgically optimal.
With known removable anchors, the area within a diameter of the original hole is generally precluded from re-siting for several reasons. First, there is the likelihood that a hole drilled close to the original hole would migrate into the original hole resulting in further bone structure damage and another unusable hole. Second, the re-sited hole must not overlap the original hole or the threads in the overlapping area would have no bone purchase. Third, the re-sited hole must be moved a certain distance from the first hole, around which the bone structure has been weakened, to an area where the bone structure has not been weakened so that the full pullout strength is available to secure the ligament tightly to the bone.
Preferably, an anchor should be quickly, easily and removably insertable to an assessment position while producing the minimum impact on bone structure. When re-siting is necessary, the damage to the bone at the original site should not significantly impact the surgeon's choice for a second site. Furthermore, the anchor should be predictably insertable along a path to a precise final position.
Existing drivers for removable suture anchors also suffer from a number of deficits. In particular, some drivers utilize a small hex drive to couple to the anchor, and such drives are subject to stripping wherein the comers of the hex are rounded off. The surgeon must then grab the anchor with pliers or a similar device and attempt to remove it. Existing drivers are also sometimes difficult to load with the suture. With drivers that are cannulated to pass the suture, a special tool is often required to insert the suture through the driver. This arrangement can make use of a suture with a pre-attached needle difficult or impossible. In the case of drivers where the suture extends laterally rather than up through the driver, the suture can become tangled with the driver as the anchor is driven in. In either case, the needle remains exposed during installation of the suture, with the accompanying risk of an accidental needle stick. It is therefore an object of the present invention to provide a driver that can be used with sutures with pre-attached needles. It is also an object of the present invention to provide a driver which can be used without risk of an accidental needle stick.


Image content classification methods, systems and computer programs repeatedly scan an image having an array of image pixels, with at least one random neural network. Each scan corresponds to one of multiple texture patterns. A corresponding texture pattern is compared to each of multiple image portions for each of the multiple scans. A value is assigned to each image portion, corresponding to the texture pattern having the highest coincidence. An array of pixels corresponding to the assigned values for the image portions may then be displayed. Highly accurate results may be obtained, at high speed, without the need for lengthy expert analysis.

Image processing methods, systems and computer programs are widely used in consumer, commercial and military applications to analyze images. One important aspect of image analysis is image content classification.
In particular, real world images generally contain large amounts of information. A significant portion of this information may only be perceptible to a highly trained expert. In image content classification, information is extracted from an image into components or regions which represent homogeneous elements of information.
For example, Magnetic Resonance Imaging (MRI) of the human brain presents an image content classification challenge. Magnetic resonance images generally contain massive amounts of information which generally requires lengthy interpretation by even the most highly trained human experts. Thus, the development of better image content classification methods, systems and computer programs for MRI can have a major impact on the science of brain development and function, as well as in helping to clarify the neuroanatomical substrates of psychiatric and neurological disorders.
Unfortunately, state-of-the-art computerized tools and software for MRI content classification may lead to error rates exceeding 5-10%, which may not be sufficiently accurate to analyze neuroanatomical and developmental changes of the human brain. Other techniques may be more accurate, but may require lengthy analysis by an expert. For example, advanced image segmentation techniques may use T1-weighted scans, T2-weighted scans, fast spin echo and T1-weighted volume scans. Data may be analyzed using grid-square counting. Unfortunately, although these techniques may have calibrated error of 1-5%, they generally are based on lengthy analysis by an expert. These techniques therefore may be impractical as the volume of available MRI scans become large, and when a statistically significant set of scans are used to draw conclusions of scientific interest and clinical value.
In view of the above, there remains a need for image content classification systems, methods and computer programs which are highly accurate and which may also be performed at high speed, without requiring lengthy expert analysis.

Image content classification methods, systems and computer programs using texture patterns


According to one embodiment, a video server apparatus includes a table generator, an acquisition module, and a controller. The table generator generates a management table associating a contents ID with the contents data, and stores the management table in the memory. The acquisition module acquires contents management information from a change request source upon generation of a change request for the contents data. The controller refers to the management table based on the contents ID included in the contents management information, executes change processing for the contents data recorded in the memory based on a reference result of the management table.

A broadcast program play-out system stores contents data of broadcast programs in a video server in advance, and plays back and transmits the contents data toward transmitter or equipment in accordance with an instruction from an automation program control system (APC). In such on-air processing, conformation processes of the contents data are executed according to an on-air order before they are transmitted toward transmitter or equipment.
After the system transmits the contents data to the video server, contents files are often required to be partially replaced urgently. In general, broadcast contents data has a large size, and it takes much time to record the full data again. Hence, a need for transmitting only a difference to shorten a time until broadcasting has arisen. To this need, a solution to transmit difference contents data and to play them back as a playlist is available. However, the user is required to make troublesome processes since he or she has to save the difference contents data as independent files, and create a playlist. In addition, the contents data are to be saved in the form of a plurality of contents data and playlist. Also, since a change such as only a part of video or audio data cannot be coped with, even when only audio data is to be changed, video data of that part has to be replaced together.
When only ancillary data (ANC data) is to be replaced, a method of installing a dedicated replacement apparatus to cope with a change of only video, audio, or auxiliary data (for example, by installing a subtitle replacement server) is available. However, this results in high cost as the whole system.

Video server apparatus, video editing system, and control method of video server apparatus


An inductor (100) optimized for surface-mount vacuum-pickup automated circuit assembly eliminates the expense of an inductor housing. The inductor has a hollow rectangular ferrite core (101) and a winding defined by a stripline (102) deposited on the core surface. Winding ends are formed by conductive vias (103) in the core that open onto the core surface, where they connect and mount the inductor to a circuit board (150). A flat sheet (104) adhered to one face of the core provides a surface for vacuum pickup and for labeling of the inductor. The core of a passively tuneable inductor (200) defines multiple unconnected winding segments (102-103). Segment ends mount the inductor to the circuit board and connect the segments to circuit board striplines (254) that are laid out in a pattern to interconnect a number of the segments into a winding. The inductor is tuned by changing the stripline layout and thereby varying the number of interconnected segments. The core of an electromagnetic interference choke (300) defines two windings wound axially in parallel and radially in opposite directions. The core of a choke (500) that permits stacked mounting defines additional conductive vias (503) for connecting the windings of a second choke (300) mounted on the core to the circuit board. For electromagnetic isolation, the windings of the two chokes are oriented orthogonally to each other.

A widely-used device on PC boards is a ferrite toroid--a cylinder of ferrite material. With a wire looped several times through the toroid, the toroid is used as a fixed-impedance inductor. A technological challenge is to produce a ferrite inductor suitable for surface-mounting on a PC board without significantly adding to the cost of the toroid itself. Present designs of surface-mountable ferrite inductors result in a total cost that is about 20 times the cost of the toroid itself. Most of this cost is due to the housing for the toroid that makes the inductor suitable for automated surface-mount circuit assembly.

Stackable, passively-tunable, cost-reduced inductor


The invention provides a method of inhibiting ectopic calcification in an individual. The method consists of administering to the individual a therapeutically effective amount of osteopontin or a functional fragment thereof.

1. Field of the Invention
This invention relates generally to the field of medicine and, more specifically, to methods of inhibiting ectopic calcification.
2. Background Information
Deposition of calcium crystals in tissues other than teeth or bone, referred to as ectopic calcification, commonly occurs in association with renal failure, cardiovascular disease, diabetes and the aging process. A frequent finding in patients with renal failure, particularly those undergoing long-term hemodialysis and unable to appropriately regulate serum mineral balance, is calcification of internal organs, including the lung, heart, stomach and kidneys. Less commonly, hemodialysis patients develop painful calcified skin lesions that progress to non-healing ulcers or gangrene and may require amputation of the affected limb.
Ectopic calcification is also a common complication of the implantation of bioprosthetic heart valves and is the leading cause of replacement valve failure. Ectopic calcification also occurs in native heart valves and blood vessels in association with atherosclerosis, diabetes and cardiovascular disease. The deposition of minerals in the vasculature narrows the orifices and hardens the walls of the affected valves and blood vessels, resulting in reduced blood flow to the heart and peripheral organs. Therefore, ectopic calcification increases the risk of valve failure, stroke, ischemia and myocardial infarction.
One protein that is abundant at the sites of ectopic calcification, such as in atherosclerotic plaques and in calcified aortic valves, is osteopontin. Osteopontin has several known functions, including promoting cell adhesion, spreading and migration. Osteopontin colocalizes with sites of early calcification in coronary atherosclerotic plaques and its expression increases as atherosclerosis develops. These findings, combined with studies showing that osteopontin has calcium-binding properties in vitro, have led to the suggestion that osteopontin may be involved in ectopic calcification. Previous studies have not addressed the role of osteopontin in ectopic calcification in vivo.
Ectopic calcification, if left untreated, results in increased morbidity and death. Current therapies to normalize serum mineral levels or to inhibit calcification of vascular tissues or implants are of limited efficacy and cause unacceptable side effects.
Thus, there exists a need for an effective method of inhibiting ectopic calcification. The present invention satisfies this need and provides related advantages as well.

Methods of inhibiting ectopic calcification