The present invention relates to a kit intended for the deposition of nickel or cobalt in the cavities of a semiconductor substrate intended to form through-silicon vias (TSV) for making interconnections in integrated circuits in three dimensions.

The present invention relates generally to the fabrication of electronic devices, such as integrated circuits in three dimensions. It relates in particular to a kit of compositions and a method of metallization of an insulating substrate having cavities such as through-silicon vias, by electroless deposition of a metallic layer of nickel or cobalt.
To produce integrated circuits in three dimensions (3D), the chips are superposed and connected together by vertical interconnections commonly called through-silicon vias (TSVs) filled with electrically-conducting copper.
The vias are generally etched in the silicon, then metallized to the desired depth before thinning the silicon wafer. During metallization, the vias are therefore closed or "blind" (and are called "blind vias"). The shape and size of the vias vary depending on their function and their position in the silicon wafer. They are generally characterized by their depth, their aperture diameter, and their aspect ratio, defining the ratio of depth to diameter of the via. For example, a cylindrical via of aspect ratio 10:1 has a diameter that is one tenth of its depth. The vias are generally of cylindrical shape, but there are also tapered vias whose opening is wider than the bottom. Structures having through-silicon vias are generally metallized by a process similar to the "damascene process" used in the field of microelectronics for making interconnecting elements, whose dimensions are smaller than those of the through-silicon vias. This process comprises a succession of steps including:                etching the vias in the silicon wafer;        depositing an insulating layer generally consisting of silicon oxide or of an insulating polymer;        depositing a barrier layer or "liner" for preventing migration of the copper;        filling the vias by electrodeposition of copper; and        removing the excess copper from the surface of the silicon wafer by mechanical-chemical polishing of the substrate surface.
Before filling the vias with copper, it may be necessary to deposit a thin layer of metallic copper, called a seed layer, on the barrier layer; this lowers the electrical resistance of the surface of the barrier layer, and promotes uniform filling of the vias with copper.
The steps of depositing the barrier layer, of an optional seed layer, of filling with copper, and of polishing of the copper are commonly designated together with the expression "metallization of through-silicon vias".
The insulating layer generally consists of a derivative of silicon such as silicon oxide or silicon nitride, or of an insulating polymer.
It is necessary to deposit a layer on the insulator, for preventing the migration of copper atoms under the effect of the electric current densities applied during operation of the integrated circuit. This layer, called "barrier to the diffusion of copper" or simply "barrier", generally consists of tantalum (Ta), titanium (Ti), nickel (Ni), cobalt (Co), nickel-tungsten alloy (NiW), cobalt-tungsten alloy (CoW), nickel-boron alloy (NiB), cobalt-boron alloy (CoB), nickel-phosphorus alloy (NiP), cobalt-phosphorus alloy (CoP), tantalum nitride (TaN), titanium nitride (TiN), titanium-tungsten alloy (TiW), tungsten carbon nitride (WCN) or of a combination of these materials.
The barrier layer is generally deposited in the vapor phase (PVD, CVD, ALD) but can also be formed from a metal salt solution, which deposits the metal on the surface of the insulating substrate.
When the substrate is an electrical conductor, electrodeposition of the metal on the surface of the substrate can be effected by polarizing the latter electrically. Electrodeposition is carried out for example by passing a current between the substrate to be coated, constituting a first electrode, and a second electrode placed in a bath containing the metal ions, and optionally various agents for improving the properties of the coating formed, such as the evenness, resistivity and fineness of the deposit.
The deposition of metal on the barrier layer can also be carried out by a non-electrochemical process, also called autocatalytic or "electroless", which does not require electrical polarization of the substrate.
The invention finds application in particular in the deposition of a barrier layer based on nickel or cobalt in the course of a process for metallization of through-silicon vias. The substrate whose surface is to be coated is preferably a conducting or semiconducting substrate coated with an insulating layer having a collection of cavities notably intended to form through-silicon vias, such as those used for the fabrication of integrated circuits in three dimensions. The invention relates more particularly to a method of depositing a barrier layer based on nickel or cobalt, preferably in electroless conditions.
Electroless processes for depositing nickel-based barrier layers have already been described in the prior art.
Thus, patent application US 2005/0110149 describes a method of fabrication of a semiconductor device comprising an insulating intermediate layer based on silica covered with a monomolecular film of organic silane surface-modified with a compound containing palladium, the film thus modified being covered by an electroless process with a cobalt-based or nickel-based layer forming a barrier, on which a layer of copper can be deposited by electrodeposition.
A substantially similar method is described in patent application US 2008/0079154, which recommends, for improving the properties of adhesion between the different layers of the semiconductor device, carrying out two consecutive electroless treatments with a nickel-based compound (NiB), and then with a cobalt-based compound (CoWP).
Furthermore, repair of barrier layers based on titanium by electroless deposition of a thin layer of nickel and of boron has been suggested (FR 2 935713-A1).
Polyethylene-imines have already been used in electrodeposition solutions as copper complexing agents, notably for repairing copper seed layers, previously deposited on a barrier layer to copper diffusion (EP 1 479 793).
In document JP 2007-254 793, poly(allyl-amines) are proposed as nickel stabilizer in electroless processes, to prevent precipitation of reaction by-products on the nickel deposit.
The methods for deposition of barrier layers in the prior art, whether they are performed in the vapor phase, electrochemically or by an autocatalytic electroless reaction, make it possible to obtain a conformable barrier layer, i.e. matching, without discontinuity, the surface topography of the vias to be coated, and moreover for a wide range of aspect ratios. However, the bottom of the cavities is always less accessible to the deposition of material than the walls of the vias and the substrate surface, so that the thickness of the metallic barrier layer deposited at the bottom of the vias is always less than the thickness of the layer at the other levels of the deposit, whether on the walls of the via, at the opening of the via or on the substrate surface.
The nonuniform distribution of the deposit of the barrier layer on the surface of the cavities has essentially two drawbacks. Firstly, it makes subsequent filling of the vias with copper by electrodeposition more difficult. In fact, with smaller thickness of the metallic barrier layer, electrodeposition of copper on its surface in a subsequent step is more difficult, because of the lower current densities in the barrier layer resulting from the polarization of the substrate during the step of filling the vias with copper. Then, once the through-silicon vias are open through thinning of the silicon layer, the risks of electromigration of the copper atoms will be greater if the thickness of the barrier layer on the wall of vias is small, since the barrier function is less effective.

Method of depositing metallic layers based on nickel or cobalt on a semiconducting solid substrate; kit for application of said method

Abstract: The invention also relates to a method of metallization of the insulating surface of such a substrate which comprises contacting the surface with a liquid aqueous solution containing:                at least one metal salt of nickel or cobalt;        at least one reducing agent;        at least one polymer bearing amine functions, and        at least one agent stabilizing the metal ions.

Abstract: The step coverage of the layer of nickel or cobalt obtained can be greater than 80%, which facilitates subsequent filling of the vias with copper by electrodeposition.


A system and method for calculating current consumption characteristics of cells of semiconductor circuits is disclosed. According to the invention, the current consumption characteristics of the cells is calculated based on the status changes of the internal memories of the cells. The calculation of current consumption characteristics of cells according to the invention is not only more accurate, but also more efficient in terms of the time needed for logic simulation.

1. Field of the Invention
The present invention relates generally to a system for calculating current consumption characteristics of cells, such systems being used to design the layout of semiconductor integrated circuits. More particularly, this invention relates to a system for calculating current consumption characteristics of cells that takes into consideration the status change of an internal memory cell.
2. Description of the Related Art
There are apparatuses that compute power consumption based on logic simulations of semiconductor circuits in order to ensure low power consumption. As is well known, low power consumption has become necessary as integration and operation speeds of semiconductor circuits have become higher and faster. These conventional apparatuses are used to compute operational power consumption of a plurality of cells constituting a semiconductor circuit based on previously prepared current consumption characteristics of each cell in the development stage of the semiconductor circuit. Generally, the current consumption characteristics of each cell are provided by a cell characteristic calculating unit. The cell characteristic calculating unit computes the current consumption characteristics of each cell in accordance with a plurality of input terminal conditions. These input terminal conditions indicate changes in an input signal in a path which has an input terminal for receiving an input signal and an output terminal for outputting an output signal based on the input signal. Further, the operational power consumption of each cell is computed using power which is consumed at the time of charging or discharging the load capacitance of each cell. That is, cell power consumption is computed using the general equation Q=CV, where Q is a charge, C is the load capacitance, and V is a voltage. Generally, this equation is used because the charge may be taken as the sum of the current over a predetermined time.
For a cell having an internal memory, such as a sequential circuit, an input terminal condition with respect to a status change of the internal memory, as well as an input terminal condition with respect to the input-output relation, should be taken into consideration in calculating the current consumption characteristic of each cell. For a cell having an internal memory, the output signal may not vary even when the input signal has changed. Therefore, an input terminal condition for such a case should also be considered in computing the current consumption characteristics of each cell.
The reduction both in the load capacitance of cells and the power consumption due to the recent miniaturization of semiconductor circuits now demands consideration not only of the current consumption caused by charging and discharging the load capacitance of each cell, but also on the current consumption inside each cell. It is also often necessary to consider the case where the input voltage supplied from an external unit differs from the internal voltage of a cell or the case of conflicts caused by the mutual connection of the output terminals of a plurality of cells.
Accordingly, when current consumption characteristics of the individual cells are conventionally computed, a logic simulation of the semiconductor circuit is executed. Logic simulation of a semiconductor circuit having a huge number of cells may, therefore, take a considerable amount of time to determine current consumption.

System for calculating current consumption characteristics of cells


A graphical data-compressor for compressing received arbitrary graphical data for subsequent transmission; where the graphical data-compressor comprises an input for receiving the received arbitrary graphical data, the input being linked to an analyzer for analysis of the received arbitrary graphical data into constituent geometrical parts, the analyzer being linked to an analytic scene describer, for description of said constituent geometrical parts as an analytic description of the received arbitrary graphical data, the analytic scene describer being linked to a transmitter, the transmitter being for transmission of the analytic description.

Computer graphics applications tend to be data heavy, in that they generally require very large amounts of data to enable the graphical scenes associated therewith to be correctly rendered for viewing. This is especially true for applications involving virtual reality with moving scenes. 3D environments, where changes of viewing position may require redrawing of both the background and foreground objects displayed thereon are particularly data intensive. In general, the more accurately that the appearance of a 3D scene reflects reality, the more data is required to define it and the more effort is required to manipulate the data and render it into a displayable form.
As illustrated in FIGS. 1 and 2, networked computing comprises computers interacting via a data link. This can be generalized to a plurality of remote computer terminals, interacting with the same computer application via a network. The computers are often at a considerable distance from each other.
Where an application permits a plurality of users to view the same graphic interface, and where each terminal interface is updated with respect to interactions in real time, at least the changes to the currently viewed scene may require to be transferred to each terminal via the network. A change to an element within a dynamically changing scene such as a rotation, translation or transformation thereof generally requires the element to be redrawn. Sometimes changes may require regeneration of a whole scene, that is, the whole scene display may require redrawing.
Now the speed at which a computer application runs is a function of its complexity and the capability of the hardware. In networked computing however, particularly with data-intensive, heavy applications, the speed at which applications run, is often limited by the time required for necessary data to be transferred between computers. This data transfer time is a function of the bandwidth of the data transfer lines, and of the volume of data that requires transporting.
For networked computing in general, there is a desire to limit the quantity of data that is transported between computers, and efficient programming and data compression techniques are used to facilitate this data limiting. Some of these methods are specific to certain types of data. For example, some methods of data compression work best with text. Many graphical data compression techniques are most effective when dealing with 2D data, and only a few specific methods are suitable for 3D graphical data.
The Internet is a multiple-user, computing environment that potentially allows many users to interact with each other using the same application, enabling many players to play the same adventure game for example. To facilitate multiplayer interaction in a 3D virtual graphic environment in real-time, it is required that changes or moves made by one user, are transmitted to other users fast enough that correct sequencing is maintained, and preferentially the moves of one player appear instantaneously on the monitors of all other players. Achieving real-time updating of high-resolution 3D graphical displays at a plurality of user terminals is a challenging aim.
Apart from games and the like, virtual reality has also been applied to a variety of areas of human endeavor to simulate reality where, due to economic, safety and other considerations, it has been deemed preferable to use simulations rather than the real thing. Examples of this include prototyping objects of manufacture using computer aided design programs, anatomical simulations of the human body for pedagogic purposes in the training of doctors and surgeons, flight simulators for training aircraft pilots, and battlefield simulation for training military personnel such as tank drivers and gunners.
Now virtual reality often features changes in the appearance of virtual scene elements, perhaps as a result of rotation of objects represented, a change in viewing angle, or a change in position or movement of the object due perhaps to a user interaction. There may be a demand for fast scene regeneration, preferably in real time, and this puts a limitation on the amount of processing to affect the change. Particularly in networked computing, where the data defining an scene may require transferring between nodes on the network, there may be a requirement to limit the amount of data required to define the appearance of scene elements.
The common approach to giving an acceptable 3D appearance to a virtual scene on a 2D visual display unit (VDU), is to construct the 3D surface from elements and objects from which the scene is comprised of, namely polygonal facets. A polygonal facet is a flat element bounded by a closed loop. The boundary of the polygonal facet may be defined by the XYZ coordinates of the vertices thereof. In addition to representing a surface by polygonal facets, geometry can also be represented by polynomial and rational functions including piecewise polynomial and piecewise rational functions, and many solid-modeling environments extensively use freeform polynomial and rational curves and surfaces for defining shapes. Freeform functions can additionally be used for modeling objects whose shapes are comprised from simple geometrical elements. For example, geometric computer aided design (CAD), computer aided manufacturing (CAM) and Computer Aided Engineering (CAE) packages represent cylinders, spheres, cones and other simple geometrical shapes as rational equations, using Bezier and B-spline forms. Defining objects by rational equations is generally more compact than the multiple polygon faceted form that is typically used in virtual reality environments.
Further details concerning Bezier curves and associated methods may be obtained from Gerald Farin, Curves and Surfaces for CAGD, A Practical Guide, 4th Edition. Academic Press, N.Y., 1997, the contents of which are hereby incorporated by reference.
Higher data compression can be achieved, if, where appropriate, shapes and forms, or pieces thereof are represented as standard geometrical solid types, giving a size, position and orientation thereof in space. Thus a screen object representing, say, a tin can, may be compactly represented as being a cylinder having a certain position in space, a certain orientation and height, and a certain radius, that is in the analytical form: cylinder XPoint YPoint ZPoint Xdir Ydir Zdir R where (XPoint , YPoint , ZPoint) are the coordinates of a selected point associated with the cylinder such as the center of the base thereof, or the centroid thereof, (Xdir Ydir Zdir), define both the height of the cylinder and the orientation of its axis, and R is the radius of the cylinder. The above analytical representation is not limited to shapes that can be adequately modeled as basic primitives however. More complex shapes may often be represented as comprising a plurality of basic primitives. Thus, a bucket with a handle may be represented as an inverted truncated cone, the handle thereof being represented by an arc, perhaps a section of a circumference, for example. Such high-level representation has been considered for the compact transmission of geometry, see Shmueli and Elber [Shmueli O., and Elber G., An Architecture for Data Interaction Using Three Dimensional Environments, CS Technion Technical Report, CIS9623, Technion, December 1996], the contents of which are incorporated herein by reference. However, for virtual reality applications, such representation is generally unsuitable as the interfacing between the processor and the VDU at the client site is generally handled by dedicated graphics hardware circuitry for speed, and this hardware is specially adapted to handling polygons. Thus for non-polygonal data representations, more work is required at the client site to convert the geometry into a polygonal, displayable form.
A set of data points or function in two dimensions can be fitted with a polynomial of a suitable order. Where the required polynomial is of a particularly high order, a more practical approach than using a single approximating polynomial is to use splines. Splines are smooth piecewise polynomials that can be used to represent functions over large intervals. Because splines are smooth and easy to manipulate, they have become a standard tool for modeling arbitrary functions. The spline model is often used when the function to be modeled is only given as the solution of a functional equation.
A well-known type of spline is the NURBS, the name being an acronym of Non-Uniform Rational B-splines. Using NURBS is a popular method for representing curve and surface geometry in such diverse industries as Computer aided design (CAD), Computer aided manufacturing CAM, Computer aided engineering CAE, computer graphics, entertainment and 3-D animation, medical and geosciences.
High-level graphical representations are not highly portable between platforms. Nevertheless, Elber and Kim [Elber G., Kim M. S., Geometrical Shape recognition of Freeform Curves and Surfaces. Graphical Models and Image Processing, Vol. 59, No. 6, p.p. 417-433, November 1997] have demonstrated that higher level graphical representations may be recovered, using matching techniques, from B-splines, surfaces, curves etc. and may be transferred, between different solid modeling systems. Elber and Kim's approach uses tools from differential geometry, and carries out a process of reverse engineering to identify B-Splines or any other piecewise polynomial, and/or rational function. Having identified such a function, it then attempts to detect underlying shapes. Underlying shapes are detected by formulating necessary and sufficient conditions for a freeform curve to be a line or a circle. The approach also formulates the necessary and sufficient conditions for a freeform surface to be planar, spherical, a circular cone, a circular cylinder, a surface of revolution, a ruled surface, an extrusion surface or a sweep surface and may be extended to other shapes as well.
By way of example, suitable conditions for a rational planar curve to be circular are now given:
Let E(t) be the evolute of planar parametric curve C(t). (An evolute is the envelope of normals to a given curve, or, in other words, the locus of the centers of curvature).
E(t)=C(t)+N(t)/κ(t) where N(t) is the normal field of C(t) and κ(t) is the curvature of C(t). Then C(t) is circular, if E(t) degenerates into a single point.
It is further shown in Elber and Kim, that if C(t) is rational, then so is E(t), But then given C(t), one can evaluate E(t) as a rational form, say using B-spline representation, and examine all the control points of E(t) for similarity. If E(t) does degenerate into a single point, then C(t) is circular.
Similar approaches, also described by Elber and Kim, formulate the necessary and sufficient conditions for a freeform surface to be planar, spherical, a circular cone, a circular cylinder, a surface of revolution, a ruled surface, an extrusion surface or a sweep surface. These conditions are then used in similar robust algorithms that determine whether one of a predetermined list of shapes is present, and which may be used for the geometrical shape recognition of these basic lines and shapes. The shapes may then be used as basic primitives for analyzing the form of solid objects. Elber and Kim have thus shown the feasibility of improved transfer of geometric data between CAD platforms.
Another challenge is the conversion of low-level geometry into a high level description, particularly the conversion of low-level polygonal geometry into polynomial and rational forms. Although generally difficult, sometimes, such as when using the output from a 3D scanner, the problem is greatly simplified. The output of 3D scanners is generally an ordered set of point clouds. Instead of converting this point cloud into a mesh of polygonal data, the point cloud may be represented as a B-spline surface representing coarse information, and a pixel map holding the finer details. This approach was suggested by Krishnamurthy and Levoy [Krishnamurthy V. and Levoy M., Fitting Smooth Surfaces to Dense Polygonal Meshes, Computer Graphics Proceedings, Annual Conference Serious, Siggraph, August 1996, pp. 313-324, New Orleans, La.], the contents of which are hereby incorporated by reference. Alternatively, interpolation methods may be used on the set of unordered points or triangulations, and Farin has discussed interpolation methods of this type [Gerald Farin, Curves and Surfaces for CAGD, A practical guide, 4th Edition, Academic Press, New York, 1997], the contents of which are hereby incorporated by reference.
Finally, there have been some efforts made at the representation of 3D objects as high level polynomials and functional forms in order to achieve compact transmission of geometrical data, as discussed by Shmueli and Elber [Shmueli O. and Elber G., An Architecture for Data Interaction using three Dimensional Environments, CS Technion Technical Report, CIS9623, Technion, Haifa, Israel, December 1996], the contents of which are hereby incorporated by reference. By "functional" is meant the representation of a geometric entity by a procedural description of a basic geometrical form describing the entity followed by the parameters of the entity, thus providing the information needed for reconstruction of the entity. Shimueli and Elber describe a system for downloading and transmitting high-level polynomial descriptions to remote user sites, for display by a graphics system on a screen. The transformation is both fast and efficient, and highly detailed virtual scenes such as offices and show rooms may be transmitted in this manner using only dozens of kilobytes of data.

Low bandwidth transmission of 3D graphical data

Technion Research & Development Foundation Ltd.


The invention relates to new methods of RNA isolation that exploit the surprising discovery that RNA may be differentially precipitated from DNA. The subject methods result in the formation of an RNA-containing precipitate that has an RNA content at least two fold enriched with respect to DNA, as compared with the RNA to DNA ratio of the solution from which the RNA-containing precipitate is derived. The invention also includes various methods of DNA isolation that employ the selective precipitation of RNA. The degree of RNA enrichment achieved is often much greater than two fold; enrichment by a factor of ten or greater is frequently obtained. By precipitating RNA from a solution, the RNA may be collected by simple procedures such as centrifugation or filtration, thereby avoiding the need to bind the RNA to solid phase. The collected RNA precipitate may then be solubilized. One embodiment of the subject methods involves forming an RNA-containing nucleic acid composition, adding an RNA precipitate forming chaotropic salt to the nucleic acid composition in a sufficient concentration to form an RNA-containing precipitate, collecting the RNA-containing precipitate, and (optionally) solubilizing the precipitate. Preferred precipitate forming chaotropic salts are guanidine hydrochloride and guanidine thiocyanate. Other embodiments of the invention include kits for performing the methods of the invention. The invention also includes systems for performing the methods of the invention.

The preparation of relatively pure samples of nucleic acids such as DNA or RNA is an important step in many molecular biology procedures. Purification is necessary to ensure removal of impurities, e.g., cellular debris, that may interfere with subsequent molecular biological procedures. RNA purification has many uses such as in the preparation of cDNA and the monitoring of gene expression. While the purification of DNA from many types of cells is relatively straight forward, RNA purification is often problematic. Such difficulties include the need to inactivate ubiquitous RNA degrading enzymes and the lability of RNA in alkaline pH environments. Another difficulty with RNA purification is the frequent co-purification of RNA and DNA. Contaminating DNA may interfere with subsequent molecular biochemical or genetic analysis procedures because of the similar base pairing properties of DNA and RNA. Similarly, RNA may contaminate DNA preparations.
Numerous procedures have been developed for purifying RNA. These previously available RNA procedures suffer from one or more shortcomings such as the need for highly toxic chemicals, the use of an inconveniently large number of manipulations, genomic DNA contamination, a requirement for ultracentrifugation, the use of DNAses, RNAses, proteinase digestions, and contamination with inhibitors of genetic analysis procedures (e.g., PCR and base sequencing). Such RNA isolation methods usually include the cumbersome steps of adsorbing nucleic acids to a solid phase support and subsequently preferentially eluting the nucleic acid from the supports. Similar problems arise with previously available techniques for DNA isolation. Accordingly, it is of interest to provide new and improved methods of RNA and DNA purification. Ideally, such new methods are simple to perform and may easily be automated.


A device for detecting at least one flow characteristic of a fluid medium, in particular for detecting an air mass flow in the intake air of a motor vehicle, includes at least one flow channel, through which the fluid medium may flow, and at least one sensor element, which is situated in the flow channel, for detecting the flow characteristic. The sensor element has at least one heating element. The device includes at least one bidirectional electrical interface. The device is configured to receive information and transmit information via the bidirectional electrical interface.

Numerous devices for detecting at least one flow characteristic of a fluid medium are known from the related art. The flow characteristic may in principle be an arbitrary physically and/or chemically measurable flow characteristic. In particular, the flow characteristic may be a mass flow, in particular an air mass flow, a flow velocity, and/or a volume flow. The detection may be a quantitative and/or qualitative detection. The fluid medium may be an arbitrary gas and/or an arbitrary liquid. The fluid medium may particularly preferably be an exhaust gas of an internal combustion machine. For example, the gas may also be air in an intake system of an internal combustion machine, for example, of a motor vehicle. The present invention is described in particular hereafter with reference to hot-film air flow meters, as described, for example, in Robert Bosch GmbH: Sensoren im Kraftfahrzeug [Sensors in Motor Vehicles], 2010 edition, pages 146-148. The detection of the at least one flow characteristic of the fluid medium may relate in particular to a flow rate measurement, for example, of intake air in a motor vehicle. In this case, a thermal measuring method is preferably used. The thermal measuring method is distinguished, for example, by a direct detection of the flow characteristic, in particular a sought-after measured variable, particularly preferably the air mass, in particular by high dynamic response and/or by a broad detection range, for example, of the air mass flow.
The devices known from the related art may have some disadvantages. For example, a natural sensitivity with respect to a contamination of the device, in particular of a sensor element, may be disadvantageous. In the event of a shutdown of the internal combustion machine, for example, an internal combustion engine, gases in a crankcase of the internal combustion engine may relax. The gases, in particular oil-containing gases, may reach the device, in particular the air flow meter, via a crankcase ventilation and/or an intake manifold, and may accumulate there on the sensor element, for example. This may result in a degradation of measuring accuracy, for example. To prevent this, the sensor element may be heated, for example, during the shutdown, in particular during a shutdown case, for example, by at least one chip heater, in particular to prevent oil deposits.
A method for cleaning a measuring element around which a gas flow flows, and which contains at least one heatable element, is described in German Application No. DE 102 32 072 B4. The measuring element is accommodated on a thin diaphragm material, the diaphragm material being situated so it may oscillate. Periodic energizing, which is performed at intervals, of the at least one heatable element accelerates, via a control unit or a circuit intrinsic to the measuring element, the diaphragm material, which has locally differing coefficients of thermal expansion, in the direction of the surface normal of the diaphragm material.
Devices known from the related art, as described above, mostly have multiple disadvantages, for example, inefficient operation. Therefore, a device for detecting at least one flow characteristic of a fluid medium, which has optimum control of a heating element, for example, combined with minimization of power consumption and/or with adaptation to an available electrical voltage of a voltage supply, would be desirable.

Device for detecting at least one flow characteristic of a fluid medium


An organic light emitting display apparatus that can prevent corrosion during manufacturing is disclosed. The apparatus can have a remarkably enhanced yield. The apparatus includes: a substrate having a display area, a thin film transistor disposed inside the display area, an electrode power supply line disposed outside the display area, a pixel electrode disposed inside the display area of the substrate and electrically connected to the thin film transistor, an auxiliary conductive layer contacting the electrode power supply line at a side of the electrode power supply line, a pixel defining layer exposing the pixel electrode covering the auxiliary conductive layer and exposing the electrode power supply line. The apparatus also includes an intermediate layer disposed on the pixel electrode and comprising an emitting layer, and a counter electrode disposed on the intermediate layer and extending outside the display area of the substrate to contact the electrode power supply line.

1. Field
The present invention relates to an organic light emitting display apparatus, and more particularly, to an organic light emitting display apparatus that resists corrosion during a manufacturing process thereof, and the organic light emitting display apparatus can have a remarkably increased yield.
2. Description of the Related Technology
Generally, organic light emitting display apparatuses refer to display apparatuses including organic light emitting devices. The organic light emitting devices include a pixel electrode, a counter electrode disposed opposite the pixel electrode, and an intermediate layer interposed between the pixel electrode and the counter electrode and including a light emitting layer.
An organic light emitting display apparatus can be classified as an active matrix display or a passive matrix display according to a driving method of the organic light emitting devices. In an active matrix display apparatus, a thin film transistor (TFT) of each of a plurality of sub-pixels controls the emission of light from the sub-pixel. In a passive matrix display apparatus, a plurality of electrodes arranged in a matrix shape controls the emission of light from a plurality of sub-pixels. In the case of the active matrix display apparatus, counter electrodes of a plurality of sub-pixels are generally formed as one body and contact an electrode power supply line positioned outside a display area.
The electrode power supply line is covered by an insulating layer that exposes at least a part of the electrode power supply line. The counter electrode contacts the exposed part of the electrode power supply line. However, before forming the counter electrode to contact the electrode power supply line during the manufacturing thereof, a process of exposing a part of the electrode power supply line outside the insulating layer is performed. Thus, the surface of the electrode power supply line is oxidized during the exposing process. As a result, contact resistance is increased in the subsequently-formed structure in which the electrode power supply line contacts with counter electrode.

Organic light emitting display apparatus


A system is provided in which the spatial values (S1 to Sn) of the physical quantity are represented by measurement pulses (I1 to In), the temporal ordering of which represents the values, which are processed by processing units (U1 to Un) arranged in at least one row and each include an output (SOR1 to SORn). During successive processing cycles, a measurement pulse processed therein can be delivered to form the output signal (SU) of the system. Each processing unit includes an inhibiting unit (BI) for, in other units and during a given processing cycle, inhibiting the passage to the outputs of the other units respective measurement pulses processed therein and hence preventing them from forming the output signal, if the measurement impulses are temporally ordered later in the given processing cycle than the one processed in the unit concerned.

1. Field of the Invention
The present invention relates to a system for spatial analysis of a physical quantity whose spatial values are represented by respective measurement pulses whose order in time is representative of those values.
To be more precise, the invention concerns the analysis of information represented by analog signals produced by the cells of a sensor responsive to the local evolution of the physical quantity in a given space.
2. Description of the Related Art
In the context of the technology evoked briefly hereinabove, it is already known in the art, in order to reduce the quantity of information from a sensor of this kind and thus to simplify its analysis, to submit the signals generated by the cells of the sensor to a process of ordering in time by means of turning filters. This method classifies the information obtained by creating pulses whose position in time reflects the pertinence of the information; the pulses arriving earliest code the most pertinent information.
A particularly interesting application of this time order concept can be found in the domain of character recognition in which the stream of analog signals is produced by a series of photosensitive "pixels", for example, each pixel forming one of the cells of the sensor. It has been shown that in this case recognition can be effected using only a small proportion of the information contained in the image captured by the sensor. The processing of the information can be simplified in this way, and the power consumption of the circuits of the sensor reduced accordingly.
However, it will be noted that this concept may be applied whenever an observed phenomenon is reflected in the spatial evolution of a physical quantity, which evolution is represented by analog signals whose information content must be exploited.

System for spatial analysis of a physical quantity

CSEM Centre Suisse d'Electronique et de Microtechnique SA - Recherche et Developpement


A shift register, a method for driving the same, a gate driving circuit, and a display device are described. The shift register includes a pull-up control circuit which outputs the voltage of a signal input terminal, a pull-up circuit which outputs the voltage of a first clock signal input terminal, a pull-down control circuit which outputs the voltage of a second clock signal input terminal, or pulls down the voltage of the pull-down node, a pull-down circuit which pulls down voltages of the pull-up node and the signal output terminal to the first voltage terminal, respectively, a reset circuit which pulls down voltages of the pull-up node and the signal output terminal to the first voltage terminal, respectively, and a noise reduction control circuit which outputs the voltage of a noise reduction control signal terminal to the pull-down node in the blanking time of an image frame.

Liquid crystal displays (LCDs for short) have the advantages of low radiation, small volumes and low energy consumption, etc., and have been widely applied in electronic products such as notebooks, flat-screen televisions or mobile phones, etc.
In the reference, a GOA (Gate Driver on Array) circuit is usually arranged in the peripheral of the array substrate in a liquid crystal display for progressive scanning of gate lines. Exemplarily, in an image frame, the GOA circuit will scan the gate lines row by row from top to bottom or from bottom to top. Taking scanning the gate lines from top to bottom as an example, after the last row of gate lines is scanned, the GOA circuit needs to return back to the first row from the last row and proceeds at a step of scanning a next image frame. To avoid affection of the display, in the period of time of returning back to the first row from the last row, it is required that any shift register in the GOA circuit does not have a signal output, and the period of time is a blanking time.
However, in the blanking time, charges stored in part of the nodes or transistors of the GOA circuit do not get fully released due to the structure of the GOA circuit and the coupling capacitors of its internal transistors themselves. As such, in the blanking time, noise interference will be caused to the output terminal of a shift register in the GOA circuit, and the stability of the GOA circuit will be reduced.

Shift register, method for driving the same, gate driving circuit, and display device

HEFEI XINSHENG OPTOELECTRONICS TECHNOLOGY CO., LTD.


The present invention concerns a method for inactivating a virus for use in e.g. a vaccine, by treating the virus with an ethyleneimine at a pH of less than 7.0, and methods of treatment with the inactivated virus.

The invention relates to a method of preparing viruses for use in vaccines.
Inactivation of a virus can alter viral antigens, reducing the safety or efficacy of the vaccine. Ideally, the conditions and agent(s) for viral inactivation would selectively and irreversibly affect the viral genome.
Ethyleneimine monomer (EI) or binary ethyleneimine (BEI) are reagents used to modify nucleic acids preferentially at N-7, N-3, and N-1 of purines and to a lesser extent N-3 of pyrimidines. Alkylating agents enhance the opening of an imidazole ring of N-7 alkylated purines (e.g., guanine), thereby arresting replication. EI alkylates guanosine to form N-7 (aminoethyl)guanosine which has a higher imidazole ring opening rate than does N-7 (alkylguanosine). EI also modifies non-genomic components of the viron or nonviral biomolecules.
One undesirable side-effect of this nonspecific reactivity is the disruption of viral particles which reduces immunogenicity. Chemical modification of even a single amino acid can significantly change the resistance of protein toward proteinases and may reduce stability of vaccine during storage due to proteolysis of modified viral proteins. Preferential inactivation of protective epitopes can contribute to an imbalanced immune response and to potentiation of disease during subsequent infection. Modification of capsid components can inhibit the intracellular processing of viral proteins which are necessary for presentation of epitopes to T-cells. Third, modification of amino acid residues of viral proteins reduces viral antigenicity. Finally, chemical modification of proteins present in the initial virus-containing matter may alter their antigenic specificity. This is the primary cause of allergic reactions in humans after booster doses of inactivated rabies vaccine. Despite their inherently low selectivity, ethyleneimine monomer (EI or BEI) have been used as agents for production of the killed antiviral vaccines.


Computer-implemented systems and methods for managing virtual computing services. A service interface may receive from an administrative user an instruction indicating a configuration change for a first virtual computing service. A plurality of agents comprises a leader agent and at least one other agent. The leader agent may assign to the at least one other agent a plurality of jobs for implementing the configuration change. The at least one other agent may execute at least one of the plurality of jobs, where executing the at least one of the plurality of jobs comprises modifying a configuration of a virtual desktop site associated with the first virtual computing service.

Many enterprises utilize virtual computing services to manage the computing needs of their employees and other users. Virtual computing services allow enterprises to provide desktop functionality to users without the need to install all necessary software, such as operating systems, etc., on the local user devices. Typically, all or part of the software necessary to implement a virtual computing service (e.g., a virtual desktop, virtual application, or group of virtual applications) is hosted at a central processing location. Users utilize local machines to access a virtual computing service hosted by the central server.
Virtual computing services are often implemented using one or more virtual desktop sites or farms at the central processing location. Each virtual desktop site hosts one or more virtual computing services that are provided to local user devices. Virtual computing services can be deployed in different forms. In some implementations, the virtual desktop site hosts all of the functionality of a virtual desktop. The user, through the local machine, is provided with an operating system and applications executed remotely at the virtual desktop site. Some users may be provided with user-specific virtual desktops, with the central processing location maintaining user profile information and implementing local storage. In some implementations, the virtual desktop site streams a virtual desktop to a local user device such that some software components of the virtual desktop are executed at the local user device. Also, in some implementations, virtual desktop technology is utilized to provide users with applications that are executed at the central processing location, but accessed via the local user devices.
Virtual computing services provide advantages to users and to enterprise information technology (IT) groups. Users can have access to a common desktop and/or application regardless of the location or capabilities of the local user device that they utilize. IT groups benefit by having all virtually provided desktops and/or apps hosted at the central processing location. This simplifies software maintenance as updates and/or patches can be applied to the various virtual desktop sites and need not be separately pushed or otherwise installed to each local user device. Security is similarly simplified. The process of updating the central processing location, including the virtual desktop sites, however, creates additional complications.


A retrofit switch apparatus is designed to pair with a traditional switch device that has a traditional switch for accepting a first user manual operation to control a target device connected to the traditional switch device with an electrical wire. The retrofit switch apparatus has a cover body, a control cover, a control decoder, and a wireless transmitter. The cover body covers the traditional switch device. The control decoder and the wireless transmitter are disposed in the cover body.

IoT (Internet of Things) technologies are developed rapidly and various devices are invented for making human life more convenient. For example, wireless speakers, door locks, lights are easily controlled by a mobile phone via Bluetooth today.
Meanwhile, there are many traditional devices like lamp or downlight installed in a conventional house. It would be very helpful if certain innovative modifications are provided to turn these traditional devices into a controllable IoT network device.


Systems and methods for remotely testing the operational status of a remediation system installed within a building or structure are disclosed. An illustrative remote monitoring system can include a sensor adapted to sense at least one characteristic of the remediation system, an interface in communication with the sensor, a gateway in communication with the interface, and a remote computer located away from the building or structure. The interface can be configured to convert sensor signals received from the sensor into an output signal having a format or platform supported by the gateway. The remote computer can include an interface that can be used by a servicing agent to transmit and receive signals to and from the gateway for monitoring and testing the operation of the remediation system.

Vapor intrusion remediation systems are sometimes used in buildings or structures for removing volatile chemicals from subsurface soil or groundwater contamination. In certain radon-mitigation applications, for example, such remediation systems can be used to reduce or eliminate the presence of radon gasses within the interior of a home or office building. Typically, the remediation system will include a ventilation fan and a number of exhaust pipes for providing direct ventilation to the basement or ground floor of the building, or alternatively, for channeling the contaminated volatiles from under the foundation of the building directly to the ambient air.
The type of remediation system employed will typically vary depending on the type of building or structure that is to be ventilated. A subslab depressurization technique, for example, is often employed in radon reduction applications where a basement or slab-on-grade foundation is present. A submembrane suction technique, in turn, is often used in those radon reduction applications where a crawlspace is present. Other reduction techniques such as sealing, house/room depressurization, and heat recovery ventilation (HRV) may also be utilized to reduce the presence of volatile gasses in some cases. Other factors such as the types and levels of the volatile components present, the type of building construction, the cost of installation and operation, etc. will also have an impact on the particular type of remediation system employed.
Maintenance of the various components of the remediation system such as the ventilation fan and exhaust pipes must be periodically performed to ensure proper operation. Typically, such maintenance is performed by an in-person visit by a servicing agent contracted with the homeowner or building manager to service the remediation system. Such process is both costly and inefficient, often requiring the homeowner or building manager to be present during the servicing visit. Since a failure of the remediation system may occur without the knowledge of the building's occupants, there also may be periods of down-time in which remediation system is not fully operational, increasing the likelihood of vapor intrusion during the period of time between inspections.

Remote monitoring of remediation systems


A method for selecting a public land mobile network (PLMN) from a plurality of available PLMNs more particularly, one embodiment of the invention includes the steps of transmitting, via a mobile network, information related to the plurality of available PLMNs. The method further includes the step of receiving, at a mobile station, the information related to the plurality of available PLMNs, and responsive to the step of receiving, sending, to the mobile network, of a Non-Access-Stratum (NAS) signaling message including an identification data for selecting one PLMN from the plurality of available PLMNs. This Abstract is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims, 37 CFR 1.72(b).

1. Technical Field
The present invention relates generally to digital wireless telecommunications and, more particularly, but not by way of limitation, to a method, apparatus and system for selecting, by a mobile station, of a Public Land Mobile Network (PLMN) from a plurality of PLMNs.
2. History of Related Art
One of the most widely-used digital wireless telecommunications standards is the Global System for Mobile communications (GSM) standard, developed by the European Telecommunications Standards Institute. The GSM standard utilizes time division multiple access (TDMA) techniques. A GSM-compliant wireless communication system includes a base station subsystem (BSS). The BSS typically includes a plurality of base transceiver stations (BTSs) for transmitting and receiving radio frequency (RF) signals from a subscriber's mobile station (MS) and at least one base station controller (BSC) for managing radio resource and routing signals to and from the BTSs.
A Universal Mobile Telephone Service (UMTS) standard employs recently developed wide-band code division multiple access (W-CDMA) techniques. A UMTS-compliant system typically comprises a core network (CN) and a UMTS Radio Access Network (URAN) that includes a ground-based portion. The ground-based portion of the radio access network (RAN) is often referred to as the UMTS Terrestrial Radio Access Network (UTRAN) and comprises a radio network controller (RNC) and a base station (BS), which have analogous functionality to the BSC and the BTS of a GSM network, respectively.
A Public Land Mobile Network (PLMN) area is a geographical area in which a particular operator provides mobile communication services to users. From any location within the PLMN area, the user may set up calls to another user of the same mobile network, or to a user of another mobile network. Existing standards require a mobile station (MS) to locate a best possible PLMN for serving the mobile station by measuring signal strengths of Broadcast Control Channels (BCCH) sent by the mobile network. In most current systems, a radio network controller (RNC) or base station controller (BSC) of a mobile network is connected to a single PLMN. Therefore, in such systems, the BCCH channels include information related to the single PLMN. However, in other systems, the RNC/BSC may instead be connected to a plurality of PLMNs. The BCCH channels may, therefore, include information related to the plurality of PLMNs.

Method of and system for selecting a PLMN for network sharing


In a lens-fitted photo film unit having a main body portion containing a roll of unexposed photo filmstrip and having photographic mechanisms mounted thereto, and outer walls covering the main body portion, any clearance provided for relative movement between two adjacent members is made to be not less than any gap in outer walls of the film unit. Particle diameters of the sands, which may enter at any gap in the outer wall, are less than the gap and thus less than any clearance, so that the clearance is not clogged up with the sands.

1. Field of the Invention
The present invention relates to a lens-fitted photo film unit containing a roll of unexposed photo filmstrip and having simple photographic mechanisms. More particularly, the present invention relates to a preventive measure against malfunction of the photographic mechanisms of the lens-fitted photo film unit that is caused by particles or sand coming in the unit body.
2. Background Arts
Lens-fitted photo film units have been known as a devices available at a reasonable price which allow anyone to enjoy photography with ease anytime and anywhere without the need for loading film. The lens-fitted photo film unit, hereinafter referred to as the film unit, is constituted of a main body portion and outer walls covering the main body portion. The main body portion contains a roll of unexposed photo filmstrip and a cartridge shell for winding up the filmstrip one frame after each exposure. A taking lens and photographic mechanisms, such as a shutter mechanism and a film winding mechanism, are mounted to the main body portion.
The outer walls are provided with openings for exposing the taking lens, a film winding wheel and other necessary members. The outer walls also have slits for forming resilient operation members for actuating the photographic mechanisms, such as a shutter button, and for other purposes.
When the film unit is used in sandy or dusty locations, e.g. a beach or a construction site, sand or other particles may come in through the openings and slits of the outer walls, and sometimes hinder the operation of the mechanisms. Specifically, when the shutter blade is clogged with the sands, the film unit cannot work anymore.


Dinitroaniline compounds useful for the treatment of diseases caused by parasitic protozoa in subjects in need of such treatment. The compounds are particularly useful in the treatment of leishmaniasis. The compounds are preferably less cytotoxic to normal cells than oryzalin. Also provided are methods of treating subjects having diseases caused by parasitic protozoa, preferably humans. The method comprising administering a therapeutically effective amount of a dinitroaniline compound of the present invention to a subject in need of such treatment

There is a general lack of effective, inexpensive chemotherapeutic agents for the treatment of parasitic protozoal diseases that occur in the developing world. These parasitic protozoal diseases include leishmaniasis, including visceral leishmaniasis, mucocutaneous leishmaniasis, and cutaneous leishmaniasis; Chagas disease; human African trypanosomiasis, also known as African sleeping sickness; animal trypanosomiasis; and malaria.
Leishmaniasis currently threatens 350 million men, women and children in 88 countries around the world. The leishmaniases are parasitic diseases with a wide range of clinical symptoms: cutaneous, mucocutaneous and visceral. Visceral leishmaniasis—also known as kala azar is characterized by irregular bouts of fever, substantial weight loss, swelling of the spleen and liver, and anemia (occasionally serious). If left untreated, the fatality rate can be as high as 100%. In mucocutaneous forms of leishmaniasis, lesions can lead to partial or total destruction of the mucose membranes of the nose, mouth and throat cavities and surrounding tissues. These disabling and degrading forms of leishmaniasis can result in victims being humiliated and cast out from society. Cutaneous forms of the disease normally produce skin ulcers on the exposed parts of the body such as the face, arms and legs. The disease can produce a large number of lesions—sometimes up to 200—causing serious disability and invariably leaving the patient permanently scarred, a stigma which can cause serious social prejudice.
The leishmaniases are caused by different species belonging to the genus Leishmania a protozoa transmitted by the bite of a tiny 2 to 3 millimeter-long insect vector, the phlebotomine sandfly. Of 500 known phlebotomine species, only some 30 of them have been positively identified as vectors of the disease. Only the female sandfly transmits the protozoan, infecting itself with the Leishmania parasites contained in the blood it sucks from its human or mammalian host in order to obtain the protein necessary to develop its eggs. During a period of 4 to 25 days, the parasite continues its development inside the sandfly where it undergoes major transformation. When the now infectious female sandfly feeds on a fresh source of blood, its painful sting inoculates its new victim with the parasite, and the transmission cycle is completed.
The insect vector of leishmaniasis, the phlebotomine sandfly, is found throughout the world's inter-tropical and temperate regions. The female sandfly lays its eggs in the burrows of certain rodents, in the bark of old trees, in ruined buildings, in cracks in house walls, and in household rubbish, as it is in such environments that the larvae will find the organic matter, heat and humidity which are necessary to their development. In its search for blood (usually in the evening and at night), the female sandfly covers a radius of a few meters to several hundreds around its habitat. For a long time, little was known about the transmission cycles of the disease, but over the last few years, field research and the application of molecular biology have enabled substantial progress to be made in understanding the different links in the transmission chain. Moreover, simple new diagnostic techniques have recently been developed which are practical, reliable and inexpensive. These techniques are available to concerned countries for the early detection and rapid treatment of the disease.
The Leishmaniases are related to environmental changes such as deforestation, building of dams, new irrigation schemes, urbanization and migration of non-immune people to endemic areas. It seriously hampers productivity and vitally needed socioeconomic progress and epidemics have significantly delayed the implementation of numerous development programs. This is particularly true in Saudi Arabia, Morocco, the Amazon basin and the tropical regions of the Andean countries.
For many years, the public health impact of the leishmaniases has been grossly underestimated, mainly due to lack of awareness of its serious impact on health. Over the last 10 years endemic regions have been spreading further afield and there has been a sharp increase in the number of recorded cases of the disease. As declaration is obligatory in only 32 of the 88 countries affected by leishmaniasis, a substantial number of cases are never recorder. In fact, of the 1.5–2 million new cases estimated to occur annually, only 600,000 are officially declared
In addition, deadly epidemics of visceral leishmaniasis periodically flare up. For example, in the 1990s Sudan suffered a crisis with an excess mortality of 100,000 deaths among people at risk. An epidemic of cutaneous leishmaniasis is ongoing in Kabul, Afghanistan with an estimated 200,000 cases.
Chagas disease has a wide distribution in Central and South America, being found only in the American Hemisphere. It is endemic in 21 countries, with 16–18 million persons infected and 100 million people at risk. The disease is caused by Trypanosoma cruzi, a flagellated protozoan parasite which is transmitted to humans in two ways, either by a blood-sucking reduviid bug which deposits its infective feces on the skin at the time of biting, or directly by transfusion of infected blood. Humans and a large number of species of domestic and wild animals constitute the reservoir, and the vector bugs infest poor housing and thatched roofs.
The acute stage of the disease is generally seen in children, and is characterized by fever, swelling of lymph glands, enlargement of the liver and spleen, or local inflammation at the site of infection. But, commonly, there are no acute clinical manifestations, and those infected may remain without symptoms. In about one-third of acute cases, a chronic form develops some 10–20 years later, causing irreversible damage to the heart, esophagus and colon, with dilatation and disorders of nerve conduction of these organs. Patients with severe chronic disease become progressively more ill and ultimately die, usually from heart failure. There is, at present, no effective treatment for such cases.
Rural migrations to urban areas during the 1970s and 1980s changed the traditional epidemiological pattern of Chagas disease: it became an urban disease, as unscreened blood transfusion created a second way of transmission. Between 1960 and 1989, the prevalence of infected blood in blood banks in selected cities of South America ranged from 1.7% in Sao Paulo, Brazil to 53.0% in Santa Cruz, Bolivia, a percentage far higher than that of hepatitis or HIV infection.
Human African trypanosomiasis, known as sleeping sickness, is a vector-borne parasitic disease. Trypanosoma, the parasites concerned, are protozoa transmitted to humans by tsetse flies (glossina). Tsetse flies live in Africa, and they are found in vegetation by rivers and lakes, gallery-forests and vast stretches of wooded savannah. Sleeping sickness occurs only in sub-Saharan Africa, in regions where tsetse flies are endemic. For reasons as yet unknown, there are many regions where tsetse flies are found, but sleeping sickness is not. The rural populations that live in such environments and depend on them for agriculture, fishing, animal husbandry or hunting are the most exposed—along with their livestock—to the bite of the tsetse fly.
Sleeping sickness affects remote and rural areas where health systems are least effective, or non-existent. It spreads with socio-economic problems such as political instability, displacement of populations, war and poverty. It develops in foci whose size can range from a village to an entire region. Within a given focus, the intensity of the disease can vary considerably from one village to the next.
Human African trypanosomiasis takes two forms, depending on the parasite involved: Trypanosoma brucei gambiense (T.b. gambiense) is found in central and West Africa. It causes chronic infection, which does not mean benign. A person can be infected for months or even years without obvious symptoms of the disease emerging. When symptoms do emerge, the disease is already at an advanced stage. Trypanosoma brucei rhodesiense (T.b. rhodesiense) is found in southern and east Africa. It causes acute infection that emerges after a few weeks. It is more virulent than the other strain and develops more rapidly, which means that it is more quickly detected clinically.
Other sub-species of the parasite cause animal trypanosomiasis, which are pathogenic to animals and are often different from those that cause the disease in humans. Animals can carry parasites, especially T.b. rhodesiense; domestic and wild animals are a major reservoir. They can also be infected with T.b. gambiense, though the precise role of this reservoir is not well known. The two human and animal forms of the disease remain a major obstacle to the development of rural regions of sub-Saharan Africa: human loss, decimation of cattle and abandonment of fertile land where the disease is rife.
There have been three severe epidemics in Africa over the last century: one between 1896 and 1906, mostly in Uganda and the Congo Basin, one in 1920 in several African countries, and one that began in 1970 and is still in progress. The 1920 epidemic was arrested due to mobile teams systematically screening millions of people at risk. The disease had practically disappeared between 1960 and 1965. After that success, screening and effective surveillance were relaxed, and the disease has reappeared in endemic form in several foci over the last thirty years.
Sleeping sickness threatens over 60 million people in 36 countries of sub-Saharan Africa. Only 3 to 4 million people at risk are under surveillance, with regular examination or access to a health centre that can provide screening. Detection of the disease calls for major human and material resources, such as well-equipped health centers and qualified staff. Because such resources are lacking, most people with sleeping sickness die before they can ever be diagnosed. Almost 45,000 cases were reported in 1999, but the World Health Organization (WHO) estimates that the number of people affected is ten times greater. The 45,000 case figure shows not the true situation but rather the lack of screening in many foci. The real number of cases seems to be between 300,000 and 500,000. Reported cases in recent years are from countries where surveillance coverage is no more than 5%.
In certain villages of many provinces of Angola, the Democratic Republic of Congo and southern Sudan, the prevalence is between 20% and 50%. Sleeping sickness has become the first or second greatest cause of mortality, ahead of HIV/AIDS, in those provinces.
Countries are placed in four categories in terms of prevalence. In each country the spatial distribution of the disease is very diverse; it is found in foci and micro-foci. Countries where there is an epidemic of the disease, in terms of very high cumulated prevalence and high transmission: Angola, Democratic Republic of Congo and Sudan. Highly endemic countries, where prevalence is moderate but increase is certain: Cameroon, Central African Republic, Chad, Congo, Côte d'Ivoire, Guinea, Mozambique, Uganda and United Republic of Tanzania. Countries where the endemic level is low: Benin, Burkina Faso, Equatorial Guinea, Gabon, Kenya, Mali, Togo and Zambia. Countries whose present status is not clear: Botswana, Burundi, Ethiopia, Liberia, Namibia, Nigeria, Rwanda, Senegal and Sierra-Leone.
The disease is transmitted with the bite of the tsetse fly. At first the trypanosomes multiply in the blood, and that process can last for years with T.b. gambiense. Mother-to-child infection: the trypanosome can cross the placenta and infect the fetus, causing abortion and perinatal death. Accidental infections can occur in laboratories, for example, through the handling of blood of an infected person, although this is fairly rare. The early phase entails bouts of fever, headaches, pains in the joints and itching. The second, known as the neurological phase, begins when the parasite crosses the blood-brain barrier and infests the central nervous system. This is when the characteristic signs and symptoms of the disease appear: confusion, sensory disturbances and poor coordination. Disturbance of the sleep cycle, which gives the disease its name, is the most important feature. Without treatment, the disease is fatal. If the patient does not receive treatment before the onset of the second phase, neurological damage is irreversible even after treatment.
There are three stages to case management: Screening is the initial sorting of people who might be infected. This involves checking for clinical signs or the use of serological tests. Diagnosis shows whether the parasite is present. The only sign, one that has been known for centuries, is swollen cervical glands. Phase diagnosis shows the state of progression of the disease. It entails examination of cerebro-spinal fluid obtained by lumbar puncture and is used to determine the course of treatment. The long, asymptomatic first phase of T.b. gambiense sleeping sickness is one of the factors that makes treatment difficult. Diagnosis must be made as early as possible in order to preclude the onset of irreversible neurological disorders and prevent transmission. Case detection is difficult and requires major human, technical and material resources. Since the disease is rife in rural areas among poor people with little access to health facilities, this problem is all the more difficult.
If the disease is diagnosed early, the chances of cure are high, but early diagnosis of the disease, which would guarantee low-risk treatment on an outpatient basis, can rarely be achieved. The type of treatment depends on the phase of the disease: initial or neurological. Success in the latter phase depends on having a drug that can cross the blood-brain barrier to reach the parasite. Four drugs have been used until now. However drugs are old, difficult to administer in poor conditions and by no means always successful.
Malaria is a life-threatening parasitic disease transmitted by mosquitoes. Today approximately 40% of the world's population—mostly those living in the world's poorest countries—is at risk of malaria. The disease was once more widespread but it was successfully eliminated from many countries with temperate climates during the mid 20th century. Today malaria is found throughout the tropical and sub-tropical regions of the world and causes more than 300 million acute illnesses and at least one million deaths annually. Ninety per cent of deaths due to malaria occur in Africa, south of the Sahara—mostly among young children. Malaria kills an African child every 30 seconds. Many children who survive an episode of severe malaria may suffer from learning impairments or brain damage. Pregnant women and their unborn children are also particularly vulnerable to malaria, which is a major cause of perinatal mortality, low birth weight and maternal anemia.
Malaria parasites have become resistant to one drug after another and many insecticides are no longer useful against the mosquitoes which transmit the disease. Years of vaccine research have produced few hopeful candidates.
Because of the general lack of effective, inexpensive chemotherapeutic agents for treating parasitic protozoal diseases that occur in the developing world, new chemotherapeutic agents are needed. For example, it is estimated that approximately 1.5–2 million new cases of leishmaniasis occur each year due to infection by various Leishmania species.1 Pentavalent antimonial drugs are the first line treatment for leishmaniasis in most affected areas, with amphotericin B and pentamidine being used as alternatives.2 These agents must be administered by injection over several days to weeks, increasing the cost and inconvenience of the drugs. Resistance to antimonials has become a severe problem,3 and treatment with amphotericin B and pentamidine is frequently complicated by the occurrence of toxic side effects.2 Clearly, improved chemotherapeutics are needed against this disease, as well as the other parasitic diseases.

Antileishmanial dinitroaniline sulfanomides with activity against parasite tubulin


The invention relates to a synthetic oligosaccharide representing part of the repeating unit of the Clostridium difficile glycopolymer PS-I and having the sequence of the pentasaccharide a-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[a-L-Rhap-(1→3]-a-D-Glcp-(1→2)-a-D-Glcp or a synthetic fragment or derivative thereof. Preferably, the claimed synthetic oligosaccharide bears at least one linker L for conjugation to a carrier protein or for immobilization on a surface. Further aspects of the invention relate to advantageous methods for synthesizing said synthetic oligosaccharide and oligosaccharide-protein conjugate as well as to uses thereof, in particular as vaccines and diagnostic tools.

Clostridium difficile is a Gram-positive, spore forming anaerobic bacterium that colonizes the intestinal tract of humans thus leading to C. difficile infections (CDI). CDI has become the most commonly diagnosed cause of hospital-acquired diarrhea, particularly in the risk groups including elderly and immunodeficient patients as well as those receiving antibiotic treatment. A steep rise in CDI incidents over the past decade is attributed to the emergence of the hypervirulent, and now predominant strain ribotype 27, causing epidemic outbreaks with increased morbidity, mortality and high relapse rates. The costs to treat patients have greatly increased, particularly in the case of recurring CDI. Preventive methods, such as vaccination of risk groups, may be useful and cost-efficient means to avoid future infections. Although vaccination against C. difficile should be economically feasible (B. Y. Lee et al., Vaccine, 2010, 28, 5245) a vaccine has not yet been developed.
Carbohydrates exposed on the cell-surface of pathogens are often immunogenic and constitute potential candidates for vaccine development. When covalently connected to carrier proteins, carbohydrate antigen vaccines can elicit a long lasting T-cell dependent protection (C. Snapper and J. Mond, J. Immunol., 1996, 157, 2229). Several vaccines containing carbohydrates, isolated from biological sources, are in routine use (G. Ada and D. Isaacs, Clin. Microbiol. Infect., 2003, 9, 79). Vaccines based on synthetic carbohydrate antigens against bacteria, viruses, parasites and cancer are currently in preclinical and clinical development (a) R. D. Astronomo and D. R. Burton, Nature Rev., 2010, 9, 308; b) M.-L. Hecht, P. Stallforth, D. V. Silva, A. Adibekian and P. H. Seeberger, Curr. Opin. Chem. Biol., 2009, 13, 354).
The chemical structure of two C. difficile cell-surface polysaccharides, PS-I and PS-II has been elucidated recently (J. Ganeshapillai et al., Carbohydr. Res., 2008, 343, 703; WO 2009/033268 A1). Initial focus has been turned towards the PS-II hexasaccharide antigen that is believed to be common to several C. difficile strains (a) E. Danieli et al., Org. Lett., 2010, 13, 378; b) M. Oberli, M.-L. Hecht, P. Bindschädler, A. Adibekian, T. Adam and P. H. Seeberger, Chem. Biol., 2011, 18, 580). The synthetic PS-II hapten is immunogenic when conjugated to a carrier protein and antibodies found in the stool of C. difficile patients bind to the synthetic PS-II hexasaccharide (Oberli et al., ibid.). The pentasaccharide phosphate repeating unit PS-I was reported as [→4)-α-Rhap-(1→3)-β-Glcp-(1→4)-[α-Rhap-(1→3)]-α-Glcp-(1→2)-α-Glcp-(1→P] and it is suggested to be specific for the strain ribotype 27.
In conclusion, the pathogen C. difficile represents a major risk for patients and causes significant costs to health care systems. Unfortunately, however, currently no licensed vaccine against C. difficile is available.
Thus, a main object of the present invention is to provide novel and effective means to prevent and/or to treat C. difficile associated diseases, in particular related to the hypervirulent strain ribotype 027. A further object is to provide novel and effective means to detect C. difficile in a sample and/or a C. difficile infection in a subject. A further object is to provide novel and effective means to identify a certain strain of C. difficile in a sample and/or a C. difficile infected subject. A further object is to provide novel and effective standards for immunoassays for the detection of C. difficile.
The present inventors succeeded in the first total synthesis of a pentasaccharide derived from the repeating unit of the C. difficile polysaccharide PS-I, and its conjugation to the diphtheria toxoid Crm197.
Consequently, the above main object of the invention is achieved by providing the synthetic oligosaccharide, in particular pentasaccharide, the oligosaccharide-protein conjugate and the composition according to the invention. Further objects are achieved by providing the antibody, the methods of detection and identification, and the methods of synthesis according to the invention.

Oligosaccharides and oligosaccharide-protein conjugates derived from

Max-Planck-Gesellschaft zur Foerderung der Wissenschaften e. V.


A laser light wavelength shifter is provided with a semiconductor laser. The semiconductor laser emits through mode-locked resonating action a mode-lock resonated light which serves as a fundamental wave and is in turn wavelength shifted. Accordingly, the wavelength shifting can be executed at high efficiency with the use of a simple arrangement.

1. Field of the Invention
The present invention relates to a laser light wavelength shifter and more particularly, a laser light wavelength shifter for shifting a laser light emitted from a semiconductor laser to a shorter wavelength laser light.
2. Description of the Related Art
Semiconductor lasers are commonly employed as the laser light source for use in various types of laser apparatuses which have to be compact in size for matching their applications. Also, it is desired that the laser light on each application apparatus has a shorter wavelength for attaining optimum performance.
For example, a recording capability allowing more data to be written into and read out from a given area of a recording medium has acquired a considerable value added in the case of an optical disk system, a laser printer, a laser scanner, and other optoelectronic apparatuses. For this purpose, it is necessary to converge a laser light into a spot of a smaller diameter. When the wavelength of a laser light is .lambda. and the angle of convergence is .theta., the diameter of a laser spot .phi. is obtained from: EQU .phi.=2.lambda./.pi.tan.phi.
As understood, the smaller the laser wavelength .lambda., the smaller the spot diameter .phi. is focused. Thus, a shorter wavelength of laser light is needed for enhancement in the convergence of a laser light.
A laser source for producing a shorter wavelength of laser light is known as, e.g., an He-Cd laser, an excimer laser, or an Ar laser, each of which is too large in size to be successfully installed in any of the aforementioned laser apparatuses.
A semiconductor laser, which is a small-sized laser source, is eligible for installation in the laser application apparatuses described above. However, a technique of crystalline process required for producing such a semiconductor laser as satisfying the foregoing requirement has not yet been established. It will take some time before an improved laser producing a shorter wavelength of laser light is developed. So far, some laser light wavelength shifters have been proposed for shortening the wavelength of a laser light emitted from a known semiconductor laser to one half with the use of a second harmonics generator (abbreviated as SHG). An example of prior art laser light wavelength shifters will now be described.
A prior art shifter shown in FIG. 1 employs a single-mode semiconductor laser medium 31 as the light source for producing a single-mode fundamental wave which is essential for wavelength shift at high efficiency. In operation, a laser light emitted from the semiconductor laser 31 is converged by a condenser lens 32 onto the incident end of an SHG 33 formed of non-linear optical crystal using Cerenkov phase matching. Then, the SHG 33 decreases the wavelength of the laser light to a half.
Although the arrangement of the above-described shifter is simple, the single-mode semiconductor laser employed fails to produce a high power output of a single wavelength laser light which is as high as more than several hundreds of milliwatts. Accordingly, the efficiency of wavelength conversion stays low and no high power output of a wavelength shortened laser light (referred to as a frequency-doubled wave) will be obtained. Also, the frequency-doubled wave of Cerenkov phase matching propagates in a cone shape. Hence, a specific optical system is needed for convergence of the frequency-doubled wave.
Another prior art shifter shown in FIG. 2 has a multi-mode semiconductor laser 41 which serves as an exciting source and produces a high power of laser light. In operation, a laser light emitted from the multi-mode laser 41 is directed by a collimating lens 42 and dichroic mirror 43 to a solid laser medium 44 for excitation. Then, a solid laser resonator comprising the dichroic mirror 43, the solid laser medium 44, lenses 45 and 47, and a dichroic mirror 48 is activated for having a beam profile of appropriate convergence on an SHG crystal 46. As the result, a shifted light of which wavelength is a half of that of the input laser light is propagated from the SHG crystal 46 through the lens 47 and the dichroic mirror 48 for output.
As the wavelength shifting is carried out at two steps, the entire arrangement of this shifter becomes intricate. Also, a resultant frequency-doubled wave is more than 500 nm in the wavelength although its power is increased to a few milliwatts. The efficiency of shifting the output of a semiconductor laser is as low as about 1%. Hence, the laser has to be employed of high power supply, high power output type.


A method includes communicating a first signal at a transmitter. The first signal has a first frequency. The method also includes receiving a second signal at a receiver. The second signal has a second frequency, and the second signal comprises the first signal converted from the first frequency to the second frequency. In addition, the method includes determining whether the transmitter and receiver are functional using at least one of the first and second signals.

Communication devices typically include multiple transmitters and receivers. For example, military surveillance aircraft often include many different transceivers, some of which are used for observation and some of which are used for communication. It is often useful to determine whether the transceivers are functioning properly. As an example, technicians may wish to test the transmitters and receivers onboard the military surveillance aircraft before the aircraft is launched on a mission. Testing the transceivers typically requires that additional hardware be provided. The additional hardware communicates with a transceiver to test whether the transceiver can transmit and receive information properly.

System and method for testing transceivers


A method of controlling an inverter for converting a DC input to an AC output, the method including measuring a voltage of an AC output produced by the inverter; determining a drive voltage for controlling the inverter; and if a difference in amplitude and/or phase between the drive voltage and the measured voltage exceeds a predetermined threshold, modifying the drive voltage to reduce the difference in amplitude and/or phase between the drive voltage and the measured voltage. The method may be particularly useful for controlling an inverter during “islanded” operation with a variable load, and may therefore be useful e.g. in marine, battlefield, disaster relief and/or aviation electrical power systems.

Most inverter-connected generation is designed to work in "grid-connected" mode. This means that it treats the PCC (point of common coupling) as a reasonably stiff voltage source (e.g. such that an impedance between the PCC and the transmission network is small compared to a per-unit inverter impedance, and such that the transmission network can be treated as an infinite bus). In this mode, the inverter switching bridge can generally be controlled so that it produces controlled currents which result in controllable active and re-active power exports [1]. To control the currents with adequate fidelity to avoid damage to switches during faults generally requires high-bandwidth inner current loops with bandwidths of at least 1000 rad/s (at least 160 Hz) [2] for 50 Hz systems.
An inner current loop can be viewed as controlling an inverter based on a nominal output current, e.g. which take the form of "ideal" ("target" or "reference") currents, and usually involves the use of current limits so as to avoid the currents produced by the inverter from becoming too high. Current limits are generally easy to employ, since the reference currents can be clipped to levels safely below those which would cause damage to the solid-state inverter components.
To use such inner current loops, the target currents (the current references) generally need to be determined by mathematical methods or by outer control loops. This process is relatively easy during normal grid-connected operation, and there are multiple references to this (for example, [1], [3], [4]).
For inverters using inner current loops, it is not always obvious what the reference currents should be. This is particularly true in islanded or small power system operation when loads may be unbalanced or contain harmonic components, or during fault scenarios.
For example, in islanded scenarios, the required currents are determined by the connected loads (or other generators). If a new load is switched on, the currents must generally change to meet that new load. The loads may be unbalanced, and may even be single-phase loads. The loads may draw harmonic currents. Such issues have traditionally been addressed for UPS (Uninterruptible Power Supplies) by the use of "deadbeat" or similar controllers which determine the currents required to produce clean, balanced sinusoidal voltages at the UPS output terminals, at the target voltage magnitude and frequency. For example [5] [6]. Such schemes are established for the control of single inverter feeding a small power network. The schemes do not generally extend well to the use of multiple parallel inverters feeding the same network, due to the multiple controllers attempting to force frequency and voltage at closely coupled points of common coupling (PCC) (described in [7]). Parallel operation of such inverters generally requires high switching frequencies and also dedicated high-bandwidth communications between inverters. High switching frequencies are generally required since the switching frequency can limit the bandwidth of the inner current loop, which in turn can place limits on the bandwidths of any outer control loops which determine the current references.
For inverters of significant size (100 kW or more), switching speed is limited due to the acceptable switching losses. Switching frequencies of 1.5-4 kHz are typical. These switching frequencies generally preclude the use of dual nested current and voltage control loops, since the bandwidth of the voltage control loop will not be high enough to control the actual voltages to meet the balanced sinusoidal targets, leading to poor voltage power quality. In particular, if a load is added or removed, the finite control response time will result in voltage transients on the network, as the inverter transiently outputs currents which are incorrect to match the demand.
An alternative, in islanded scenarios, is the use of lower switching frequencies and lower bandwidth inner current loops, coupled to a voltage control loop, including droop controls which allows multiple inverters to be used in parallel, without high bandwidth communications. This is described in [7]. It requires the use of accurate state-space models of the filter inverter network, and Kalman filters to predict the response [8]. Although promising, this method has not yet been demonstrated in the public domain beyond simple use cases (i.e. balanced, sinusoidal, non-fault conditions).
During fault scenarios, the determination of the "ideal" currents to source can also be problematic. The emerging grid codes for renewable power sources and large inverters (or amalgamations of many small inverters) generally state that "maximum reactive power" should be exported by the inverter during a voltage dip (fault) [9] [10] [11] [12]. For three-phase faults, the reference currents can usually be determined relatively easily. For unbalanced faults, or faults containing transients or harmonics, it is often not clear what the ideal reference current should be, without intimate knowledge of the fault impedances. Thus, for example, a grid-code compliant response is shown in [4] for an unbalanced fault, by sourcing balanced currents, while [13] compares three control schemes which produce different balanced and unbalanced currents in response to the same fault conditions. While generally acceptable when connected to large "stiff" grids, such fault response would be highly undesirable within a power system which is not so stiff, or which contains a high proportion of inverter-connected sources with such a response. This is because the balanced "reactive" currents sourced into an unbalanced fault may result in significant voltage unbalance, possibly including overvoltage on un-faulted phases.
The conventional response of generating plant within power systems is provided by large synchronous generators. During faults, these generally behave as a balanced, sinusoidal voltage source, with a high rotational inertia, connected to the PCC via a transient inductance [14], which is typically in the region of 5-15% of the per-unit impedance of the machine. This generally gives rise to currents in the region of 6-20 times the rated values of the machine, for the duration of the fault. This may be acceptable for a wound machine for short periods of time, e.g. causing temperature rise in the windings but not permanent damage. The response of such machines is normally to continue sourcing balanced sinusoidal voltages. The currents which flow are generally determined by the fault impedances (balanced or unbalanced) and the network topology. Note that the action of the machine is generally always to tend to restore the voltages at the PCC to the balanced 1 pu sinusoidal case, and the rotational inertia tends to stabilise the frequency. The voltages at the PCC will generally not be held exactly to the balanced 1 pu sinusoidal condition, due to the finite value of the machine transient reactance. This reactance can also limit the currents which flow, to allowable levels (the "fault level").
Such response is highly desirable from inverters, during faults. However, in general this is not economically possible since the solid-state switching devices within the inverter may be damaged if any peak current greater than, for example, 2 pu (per-unit) flows for even a single part of a cycle. This is because allowing higher values of overcurrent require more expensive switch devices, or multiple switch devices in parallel.
In general terms, the inventor has found inner current loops to work well during "grid-connected" operation, but less well during "islanded" operation, especially if a fault develops.
None of the known methods for providing islanded or fault ride-through operation of inverters allows the use of an inner voltage (rather than inner current) control loop to provide a synchronous generator type response, while also providing overcurrent protection for the inverter devices, and also allowing the inverter to continue operation to ride-through the fault. An inner voltage loop can be viewed as controlling an inverter based on a nominal output voltage, e.g. a balanced three-phase voltage of nominal amplitude at 50 Hz.
The present invention has been devised in light of the above considerations.

Method of controlling an inverter and a controller for controlling an inverter