Methods and systems for operating an apertureless microscope for observing one or more features to a molecular sensitivity on objects are described. More particularly, the method includes moving a tip of a probe coupled to a cantilever in a vicinity of a feature of a sample, which emits one or more photons at a detected rate relative to a background rate of the sample based upon the presence of the tip of the probe in the vicinity of the feature. The method modifies the detected rate of the feature of the sample, whereupon the modifying of the detected rate causes the feature of the sample to enhance relative to background rate of the feature.

The present invention relates generally to high resolution microscopy techniques. More particularly, the invention provides methods and systems for improved high resolution scanning using apertureless near field scanning optical microscopes ("ANSOM") that image one or more fluorescent samples with single photon excitation, which we call fluorescence ANSOM ("FANSOM"). But it would be recognized that the invention has a much broader range of applicability. For example, the invention can be applied with other types of images such as Raman scattering, and other multiphoton processes. Additionally, the samples can range from a variety of different fields such as electronics, semiconductor, organic chemistry, life sciences, biotechnology, micro and nanomachining and micro and nanodevices, molecular and biological circuits, and others.
Over the years, significant development of different types of microscopy has occurred. As merely an example, visible light optical microscopy using far field optics including lenses and light evolved from a simple compound microscope that is capable of resolving sizes of about 200 nanometers and greater. Examples of samples that are capable of being viewed using far field optics include biological cells and tissues, and are capable of being viewed using far field optics include biological cells and tissues, and others, which are often, bulk in nature. The resolving ability of such far field optical microscopy is generally limited by the diffraction of light. The diffraction limit for optical resolution has been stretched somewhat for far field imaging of very specific samples to perhaps 150 nanometers using confocal microscopes and other, related, approaches. Accordingly, atomic force microscopes ("AFM") and scanning optical microscopes including near field scanning optical microscopes were developed. The AFM and near field scanning optical microscopy ("ANSOM") have been developed to overcome certain limitations of far field optics. The AFM and near field scanning microscopes have also found many applications in biology, chemistry, physics, and materials science.
Near field scanning optical microscopy allows one to take optical images with resolutions below the diffraction limit of light. More particularly, light propagating through a waveguide is forced through a subwavelength aperture, which is then scanned in close proximity to a sample. Such subwavelength aperture techniques create other limitations. Here, physical limitations relate to a skin depth of the metal used to coat the waveguide and various scanning artifacts, which yield resolutions of 30 to 50 nanometers, most typically 50 to 100 nanometers. Apertureless near field scanning microscopes have been proposed and demonstrated to overcome these limitations, among others. Conventional ANSOM often involves using an oscillating sharp probe, which is scanned over the sample. The probe perturbs an incident laser beam, by introducing phase shifts in an electric field or by a periodic occlusion of the sample. Detection techniques are generally used to discriminate light scattered by near field interactions from a far field contribution. Limitations also exist with such ANSOM techniques. Such limitations include contaminated images based upon certain artifacts of the sample topography, and may include others.
A pioneering approach for achieving high resolution spectroscopic information using a scanning microscope is described in U.S. Pat. No. 6,002,471, assigned to California Institute of Technology, Pasadena, Calif., and in the name of Stephen R. Quake ("Quake"). Quake generally provides a system and method for obtaining high resolution spectroscopic information. The system generally includes a support and first optical elements for directing an optical beam at a sample, which is on the support. An optical element for collecting light emitted from the sample to reduce a background noise is also included. Other elements include a spectral dissociating apparatus, a probe, and a probe detection apparatus coupled to the probe. As merely an example, the probe enhances the light level emitted from the sample in the vicinity of the probe. Because this occurs only when the probe is in the immediate vicinity of the sample, detection of this modulation results in very high spatial resolution and chemical detection sensitivity. Fluorescence ANSOM, called FANSOM, has also been demonstrated. Conventional FANSOM often uses a principle of a two photon excitation and electric field enhancement near a tip of the probe. See, T. J. Yang, Guillaume A. Lessard, and Stephen R. Quake, An apertureless near field microscope for fluorescence imaging, Applied Physics Letters, Volume 76, Number 3, Jan. 17, 2000 ("Yang, et al."). Yang, et al. reports certain results achieved using the FANSOM designed to image fluorescent samples with single photon excitation. FANSOM has demonstrated resolutions in the 10-20 nm range. Although FANSOM appears to be promising, certain practical limitations may still exist.
From the above, it is seen that improved high resolution scanning techniques are desired.

Method and system for scanning apertureless fluorescence mircroscope


A backlight device is provided. A backlight device according to an exemplary embodiment of the present invention includes: a lower cover enclosing a light guide plate and having a bottom cover and a side cover; and a printed circuit board attached to the lower cover and mounted with the light source, wherein the first opening is formed in the lower cover. The light source is inserted into the first opening and is positioned on an inner surface of the lower cover, and the printed circuit board is positioned at the outer surface of the lower cover.

(a) Field of the Invention
Embodiments of the present invention relate to a backlight device, a display device including the same, and a method of manufacturing a backlight device.
(b) Description of the Related Art
A display device is classified into a self-emissive display device displaying an image by emitting light by itself and a passive display device displaying an image by controlling the light emitted from a separate light source. A representative passive display device is a liquid crystal display.
Liquid crystal displays are now widely used as one type of flat panel display. A liquid crystal display has two display panels on which field generating electrodes such as pixel electrodes and a common electrode are formed, and a liquid crystal layer that is interposed between the panels, and a backlight module providing the light to the display panel having the liquid crystal layer is included. In the liquid crystal display, electro-potential is applied across the field generating electrodes so as to generate an electric field over the liquid crystal layer, and arrangement of liquid crystal molecules of the liquid crystal layer is determined by the electric field. Accordingly, the amount of the light emitted from the backlight module is controlled, thereby performing image display. The backlight module includes a light source emitting light, a light guide plate distributes the light coming from the light source to convert into planar light, and various optical films such as compensation films and diffusion films.
As a light source emitting light, a cold cathode fluorescent lamp (CCFL) and an external electrode fluorescent lamp (EEFL) are conventionally used, and recently a light emitting diode (LED) has been widely used.
When the number of light sources in the backlight module is increased, a manufacturing cost will be increased. Accordingly, a structure having minimum number of light sources has been designed. In this case, a current must be increased to compensate a weak light intensity according to the decreased number of light sources, however it causes a problem of heat generation.
The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.

Backlight device, display device including the same, and manufacturing method for backlight device


An information signal processing apparatus includes a data playback unit for playing back data from a recording medium on which featured data is recorded according to the setting of a first parameter series. An information file playback unit plays back the video/audio information files by selecting from the recording medium. A parameter setting unit selects one of the played back information files and sets parameter data corresponding to both the information file and the first or second parameter series. A playback period processing unit determines the playback period of the video/audio data recorded on the recording medium according to the featured data and either an initialization parameter data set in advance in accordance with the first and second parameter series, or the parameter data adjusted by the parameter setting unit. A playback control unit then performs playback control according to the signal from the playback period processing unit.

1. Field of the Invention
The present invention relates to a technology for special effect playback processing and special effect recording processing, such as digest playback and recording, on a recording/playback apparatus that records and plays back information signals, such as video signals and audio signals used in a broadcast program and the like, to and from a predetermined recording medium such as a magneto optical disc, hard disk drive (HDD), and a semiconductor memory. The present invention relates also to a signal processing technology for extracting predetermined featured data from image data and classifying predetermined images using the feature extraction data and predetermined parameter data that are set when the information is transmitted on a predetermined network such as the Internet.
2. Description of the Related Art
When recorded contents recorded for a long time are played back with a conventional VTR or a disc recording/playback apparatus within a shorter time for quickly understanding their content, the playback processing is performed about 1.5 to 2 times faster than the normal playback processing speed considering the speed at which audio information can be comprehended.
If an attempt is made to play back the content in a farther shorter time to play back its summary (digest playback), the audio output is too fast to comprehend its content. Therefore, the playback processing is usually performed by outputting only the image without audio sound.
One of the methods for solving this problem is to perform the digest playback in which the predetermined featured data is extracted from the recorded video/audio data, and only the predetermined featured periods are selected and played back according to a predetermined rule, or in which only the predetermined featured periods are selected and played back according to a predetermined rule using predetermined parameter data.
A technology for playing back a video using the featured data is to analyze the video structure by detecting featured data from vide/audio data and then play back the summary by carrying out similar chain detection as disclosed, for example, in Japanese Laid-Open Patent JP2000-285243A.
Furthermore, a technology for detecting a music period from audio signals, which is a technology for browsing a video by detecting audio feature, is described, for example, in Kenichi Minami, et al., "Video Indexing Using Music Information and Its Application" (Collective Papers from The Institute of Electronics, Information and Communication Engineers) (D-2 Vol. J81-D-2 No. 3 pp. 529-537, March, 1998) and Kenichi Minami et al., "Video Browsing Interface Using Audio Information" (Technical Reports from The Institute of Image Information and Television Engineers (Vol. 19, No. 7, pp. 1-6, 1995)).
A technology for skimming through a video from a predetermined image segment or a predetermined audio segment is also known. For example, the technology is found in Japanese Patent Application No. Hei 8-513478 "Method And Apparatus for Creating Searchable Digital Video Library And System And Method for Using The Library" and Japanese Patent Application No. Hei 8-513479 "Method And System for Skimming through Digital Audio And Video Data".
In addition, it is also possible to classify TV programs or image scenes recorded by a video camera according to similar images for use in editing or in playing back the digest of only the classified image scenes.
For the classifying processing, Japanese Laid-Open Patent JP2002-344872A and Japanese Laid-Open Patent JP2002-344852A disclose a technology for carrying out a predetermined similar image classification according to predetermined featured data and a predetermined threshold and a technology for displaying image data classified according to similarities in a predetermined format.
Depending upon the result of image classification, the desired classifying method may differ according to the user. For example, one user wants to change the classifying method, another user wants to extend the allowable range of similarities for similarity-based classification, and still another user wants to narrow the allowable range. See, for example, Patent Document 1: Japanese Laid-Open Patent JP2002-281449A.

Information signal processing apparatus and method, information signal processing system and method, and information signal playback apparatus and method


Provided is a parallel inverter device with which, among inverter devices each including a DC/AC inverter and the like, control of a parallel operation accompanied with an increase in power capacity or the like can be easily performed without using a control line for connecting between the inverter devices. A parallel inverter device (1) includes a switcher (15) in which, on an output line to which a load (40) is connected, two MOSFETs connected in series to the load are arranged so as to face each other so that their energization directions are opposite directions. ON/OFF of each MOSFET of the switcher (15) is controlled based on a polarity of an AC voltage output from a filter circuit (10) of the parallel inverter device (1) and a direction of a current flowing to the load (40) on the output line so that a cross current is interrupted. Further, a voltage difference or a phase difference between a load voltage and the AC voltage output from the filter circuit (10) is controlled so as to be reduced so that occurrence of the cross current is prevented.

In an inverter device for outputting AC power, redundancy design is adopted in order to support various usage modes. Accordingly, for an increase or expansion of an output capacity, in some cases, a plurality of inverter devices are connected in parallel to each other and used. When the inverter devices are connected in parallel to each other, a current may flow from an output of one inverter device to an output of another inverter device due to, for example, variations in magnitude of an AC voltage or frequency of an AC voltage of each inverter device or a shift in phase between a load voltage and the AC voltage of the inverter device, which may result in causing a cross current.
For example, in Patent Literature 1, the following inverter device is disclosed. That is, when the inverter devices are operated in parallel to each other, in order to suppress the occurrence of the cross current, reactive powers from mutual inverter devices are mutually transmitted and received by a control line, and target sine wave information holding information on an AC voltage to be output is corrected. The inverter device outputs an AC voltage corresponding to the target sine wave information so that changes in the mutual reactive powers are eliminated.
As an example, a configuration of the related-art inverter devices for performing a parallel operation by connecting the inverter devices to each other by a control line as in Patent Literature 1 is illustrated in FIG. 12. As illustrated in FIG. 12, a plurality of inverter devices 50 are connected in parallel to each other between a DC power supply 2 and a load 40. In order to prevent a cross current indicated by the broken line, a control line 52 for allowing communication and control between the inverter devices 50 is provided.


A shutter blade apparatus includes a shutter blade; a first pushing member including two first pushing portions configured to push a first surface of the shutter blade; and a second pushing member including a second pushing portion configured to push a second surface of the shutter blade, the second surface being opposite to the first surface. The second pushing portion is located between the two first pushing portions.

1. Field of the Invention
The present invention relates to a shutter blade apparatus including a shutter blade that blocks and unblocks an opening, a shutter unit, an image pickup apparatus, an exposure apparatus, and a method of manufacturing a device using the exposure apparatus.
2. Description of the Related Art
In general, reduction projection exposure apparatuses and the like have been used for manufacturing semiconductor devices and the like. The reduction projection exposure apparatuses reduce the size of patterns formed on originals, such as reticles, using reduction projection lenses and project the reduced patterns onto substrates such as wafers. The pattern of a reticle is transferred to several tens of positions on a wafer by alternately repeating step driving of an XY stage and exposure. Recently, in order to improve the productivity of the exposure apparatuses, efforts have been made to reduce the cycle time during exposure by increasing the opening and closing speed or the like of shutters disposed on paths of exposure light. Moreover, in order to reduce the time required for exposure, the sensitivity of a resist applied to wafers or the like has been rapidly improved.
According to the above-described known technology, a shutter blade constituting a shutter in a light-source optical system that generates an exposure light beam is inserted into a path of the exposure light beam so as to block the light beam. Thus, the size of the shutter blade needs to be larger than the cross-section of the exposure light beam. Moreover, when the shutter is closed, the shutter blade absorbs the heat of the exposure light beam, and can be deformed or melted. Accordingly, the surface of the shutter blade in general has a mirror-like finish so as to reflect the exposure light beam. In addition, when the exposure light beam reflected by the shutter blade travels back to the light source, thermal fluctuations can be generated in the light source. Therefore, the shutter blade in general is obliquely inserted into the path of the exposure light beam such that the light beam reflected by the shutter blade does not travel back to the light source. With this arrangement, the cross-section of the light beam blocked by the shutter blade becomes elliptical.
Therefore, the size of the shutter blade needs to be still larger than the cross-section of the light beam perpendicular to the light path when only one shutter blade is used for blocking the light beam. On the other hand, the opening and closing speed of the shutter needs to be increased in order to improve the throughput of the exposure apparatus. Accordingly, the weight of the shutter blade needs to be reduced while the required cross-section of the shutter blade is maintained. To this end, the thickness of the shutter blade may be reduced by using a light and heat-resistant metallic material for the shutter blade. Some known technologies intend to reduce the weight of the shutter blade while the cross-section required for blocking the exposure light beam is maintained. Japanese Patent Laid-Open No. 11-233423, for example, describes a shutter for exposure facilitating an increase in the opening and closing speed.
The known technology will now be described with reference to FIGS. 7A and 7B. A shutter 40 formed of a pair of rotary shutter units 40a and 40b is disposed on a path of an exposure light beam 100 to which a wafer or the like is exposed. The rotary shutter units 40a and 40b are synchronously rotated by motors 45a and 45b, respectively. As shown in FIG. 7B, for example, the exposure light beam 100 is blocked or unblocked by the rotation of shutter blades 41a to 43a and shutter blades 41b to 43b of the rotary shutter units 40a and 40b, respectively. That is, the rotary shutter unit 40a partially blocks the upper half or more of the exposure light beam 100 in a successive manner using the three shutter blades 41a to 43a that are obliquely inserted into the path of the exposure light beam 100. Similarly, the rotary shutter unit 40b partially blocks the lower half or more of the exposure light beam 100 in a successive manner using the three shutter blades 41b to 43b that are obliquely inserted into the path of the exposure light beam 100.
The three shutter blades 41a to 43a and the three shutter blades 41b to 43b of the rotary shutter units 40a and 40b, respectively, form light-shielding portions each having a central angle of 60° disposed at intervals of 60° in a circumferential direction of rotating shafts 44a and 44b, respectively. The shutter blades 41a to 43a and the shutter blades 41b to 43b of the rotary shutter units 40a and 40b, respectively, are rotated in connection with the rotation of the rotating shafts 44a and 44b driven by the motors 45a and 45b, respectively. The rotating positions of the shutter blades are detected by rotary encoders 46a and 46b. In the above-described known technology, the size of the shutter blades can be reduced as compared with the case where only one shutter blade is used for blocking the entire exposure light beam 100. Accordingly, the moment of inertia of the shutter blades can be reduced, thereby facilitating an increase in the opening and closing speed of the shutter.
However, in the known technology described in Japanese Patent Laid-Open No. 11-233423, the rotary shutter units 40a and 40b need to be synchronously rotated using the motors 45a and 45b, and a difference in velocity of approximately sub-milliseconds is generated by factors such as mechanical structures. Furthermore, in order to equalize the distribution of the amount of exposure light applied in the exposure area of the wafer, both edges of the shutter blades 41a to 43a and the shutter blades 41b to 43b shown in FIG. 7B crossing the exposure light beam 100 need to have the same shape. Thus, the difference in velocity between the shutter blades 41a to 43a and the shutter blades 41b to 43b can exert detrimental effects on the distribution of the amount of exposure light in the above-described known technology.
On the other hand, only one shutter blade is used for blocking an exposure light beam while the thickness of the shutter blade is reduced such that the weight of the shutter blade is reduced in some technologies. However, the amount of light when the shutter is closed needs to be smaller than or equal to one-millionth of that when the shutter is fully opened. Therefore, in order to improve the blocking performance of the shutter, a shielding plate needs to be disposed in the vicinity of an opening that is to be blocked or unblocked by the shutter blade so as to be adjacent to the shutter blade. At this moment, when the stiffness of the shutter blade is reduced due to the low-profiled shutter blade, the shutter blade can be deformed by the weight thereof or a centrifugal force or the like during the rotation thereof, and can come into contact with the shielding plate. This can prevent normal operation of the shutter.

Shutter blade apparatus, shutter unit, image pickup apparatus, exposure apparatus, and method of manufacturing device


A high temperature brazing fixture and method of manufacture for a gas turbine component made of a superalloy is disclosed herein. The high temperature brazing fixture includes a first and second frame member, a support member, and positioning member, all of which are made from the superalloy and fastened together using tab and tab lock couplings. The support member is configured to interface with and support the gas turbine engine component, and the positioning member is configured to interface with and position at least a first location of or hold a first dimension of the gas turbine component.

Brazing is a metal-joining process whereby a filler metal is heated above its melting point and distributed between two or more close-fitting parts by capillary action. In particular, the filler metal is brought slightly above its melting (liquidus) temperature while protected by a suitable atmosphere, usually a flux. It then flows over the base metal (known as wetting) and is then cooled to join the workpieces together by creating a metallurgical bond between them at the atomic level. It is similar to soldering, except the temperatures used to melt the filler metal are above 450° C. (842° F.), or, as traditionally defined in the United States, above 800° F. (427° C.).
Existing brazing fixtures support the components to be brazed, and are made using conventional methods. In particular, frames and workpiece supports/positioning members are machined, formed, and/or welded together such that a component may be placed into the fixture, brazed, and removed from the fixture. In addition, although parts may be oriented correctly when first placed in the fixture that is to support them during brazing, differences in thermal expansion rates between the parts and the fixture surface tend to distort and shift the parts with respect to each other, which can be unacceptable with precision parts. Accordingly, in order to perform at, and even withstand, the elevated temperatures required, Xu et al., in U.S. Pat. No. 6,129,257 describe a high temperature brazing fixture made of the same high temperature alloy as the workpiece to be brazed, such that the fixture exhibits the same coefficient of thermal expansion as the workpiece. Over time and repeated brazing operations, the fixture may come out of alignment and/or need to be reworked or replaced.
The present disclosure is directed toward overcoming one or more of the problems discussed above as well as additional problems discovered by the inventor.

High temperature brazing fixture and method of manufacture


Data locality optimization through object relocation may be implemented in a virtual machine including a just-in-time compiler. The just-in-time compiler generates load instruction maps for each compiled method. A profile collector is coupled to the just-in-time compiler to receive hardware profiling support. The profile collector takes samples of data cache misses. A garbage collector is coupled to the profile collector. The garbage collector deduces types of objects from the cache miss samples and adjusts garbage collection object copying heuristics to relocate objects for better cache locality based on those types.

This relates generally to processor-based systems and, particularly, to systems that use data caching.
Data caching involves storing frequently accessed data in a memory which can be rapidly accessed when the data is accessed. It may improve access time by holding the data in a location from which it may be more readily accessed.

Object relocation guided by data cache miss profile


A method and system for verifying authenticity of an application in a computing-platform operating in a Trusted Computing Group (TCG) domain is provided. The method includes computing one or more integrity measurements corresponding to one or more of the application, a plurality of precedent-applications, and an output file. The output file includes an output of the application, the application is executing on the computing-platform. Each precedent-application is executed before the application. The method further includes comparing one or more integrity measurements with re-computed integrity measurements. The re-computed integrity measurements are determined corresponding to one or more of the application, the plurality of precedent-applications, and the computing-platform.

The present invention generally relates to Trusted Computing Group (TCG) domain. More specifically, the present invention relates to verifying authenticity of an application executing on a computing-platform operating in TCG domain.
In a TCG domain, the security state of a computing-platform is attested by using Trusted Platform Module (TPM). TPM supports secure booting and secure reporting of an operational state of the computing-platform. At boot time a Core Root of Trust Measurement (CRTM) computes a hash of itself and of the BIOS and a configuration of the computing-platform, which corresponds to the BIOS and one or more hardware applications executing on the computing-platform. Thereafter, the BIOS computes a hash of a loader of the computing-platform. Then, the loader computes the hash of an operating system loaded on the computing-platform. Additionally, the operating system computes hash of the applications executing on the operating system. After computing each of the aforementioned hashes, a concatenated hash corresponding to each of the aforementioned hashes is stored in one or more Platform Configuration Registers (PCRs) of the TPM. The concatenated hash can be, verified by a verifier to determine authenticity of an operational state of the computing-platform. However, security state of the computing-platform also depends on content of configuration files and output of the applications executing on the computing-platform, which can be tampered by an intruder application.
In conventional applications, software programs are used to verify authenticity of an application and its output. However, the software programs can be tampered by an intruder application executing on the computing-platform.

Method and system to authenticate an application in a computing platform operating in trusted computing group (TCG) domain

International Business Machines Corporation


A method and a device for transferring data in a telecommunication system comprising a data transfer path (8) and devices (21, 22, 1) using the data transfer path for data transfer, data being transferred cyclically in messages (4) between the devices according to at least one cycle having a cycle time, whereby the device (1) is configured to monitor the cyclic communication on the data transfer path; determine, on the basis of the monitoring and the cycle time of said at least one cycle of the cyclic communication, at least one expected occurrence time slot of the cyclic communication; and transmit a message not belonging to the cyclic communication to the data transfer path on the basis of at least one determined occurrence time slot such that it does not collide with one or more messages of the cyclic communication occurring in the determined at least one occurrence time slot.

The invention relates to a method and a device for data transfer in a telecommunication system, and particularly to data transfer in a telecommunication system wherein data is transferred cyclically.
An example of a telecommunication system wherein data transfer takes place cyclically in accordance with certain cycle times is a conventional factory automation system comprising a programmable logic controller (PLC or a so-called SoftPLC, which means replacing a programmable logic execution unit by an application program to be run in a computer for the execution of the commands issued by a logic program), related actuators and sensors or other devices, as well as a bus, e.g. a bus called Profibus or the like, connecting these. Typically, the internal telecommunication of such a system is cyclic such that the transmitter of data, e.g. a PLC, transmits a certain (the same) message at certain intervals in accordance with a corresponding cycle time, i.e. in other words a cycle time refers to the time between the starting moments of transmission of two such successive messages. A message is delivered to a device connected to the bus, and the device typically replies by transmitting a reply message. When the cycle time is short enough, data can thus be transferred practically in real time e.g. between a PLC and another actuator, in which case e.g. the real time status information or the like on the actuator is available to the PLC. There are usually several such cycles in progress simultaneously, each having a certain cycle time. The cycle times of different cycles may differ from each other or they may be equal in length. In addition, in such a system a message cycle is usually always started by a device operating as a master, such as a PLC, while the rest of the devices only reply to the messages supplied from the master device. In such a case, each message cycle has a predetermined transfer time on a data transfer path, thus enabling collisions between messages, i.e. simultaneous transmissions to a data transfer path, to be prevented.
Development of data transfer systems and the Internet, for example, have enabled e.g. different remote control systems to be implemented in a simpler manner such that an automation system connected to a general-purpose telecommunication network, such as an Ethernet network, can be monitored and controlled from a control system also connected to the particular network. Furthermore, if the Ethernet network or the like is connected to the Internet, the control system can be connected to the system to be controlled via the Internet.
A problem with the above-described system is how to connect a telecommunication system based on cyclic data transfer to a general-purpose telecommunication system wherein message communication is not based on any regular cycles but takes place as necessary and e.g. in dependence on the load situation in the network. If a message coming outside the system, e.g. via the Internet, is to be delivered to the telecommunication system based on the described cyclic data transfer, and such a message is transferred directly to the system, it is possible that the message may collide with a message of the cyclic communication since no time slot is reserved in the system based on cyclic data transfer for such a message coming from outside. Furthermore, the larger the number of such messages of random character coming from outside a deterministic telecommunication system based on cyclic data transfer and being delivered to the system, the larger the average number of collisions between messages coming from outside and internal cyclic messages of the telecommunication system, in which case the internal data transfer of the telecommunication system becomes increasingly disturbed.
A prior art solution to this problem is disclosed in published application WO 99/13388 which discloses a device for controlling the communication between two telecommunication networks. In the solution disclosed in the publication, a particular intermediation device (proxy device) controls messages supplied to a deterministic network within a certain quota such that it only lets in a certain number of messages during a certain time period. The transfer quota of a device is predetermined according to the load situation of the network.
The problem potentially relating to this prior art solution is, however, that the solution is based on the assumption that by distributing the communication coming from outside a deterministic network evenly within a certain quota, the disturbances caused by the communication coming from outside to the internal communication of the network can be minimized within a certain probability. Particularly when the load of the network is high, collisions may nevertheless occur disturbingly often since the transmission path of the network is highly loaded, meaning that not much free transfer time exists, and the messages differing from the cyclic communication and coming from outside to the transmission path do not necessarily meet the free time slots of the cyclic communication often enough.

Method and device for data transfer in telecommunication system


Embodiments of the present invention generally relate to carrying out organic chemistry on solid supports comprising derivatised functionalities, methods for synthesizing said supports, methods for synthesizing compounds comprising amine groups or N-containing heterocycles using said solid supports, intermediate compounds linked to said supports and uses thereof.

The present invention relates to carrying out organic chemistry on solid supports comprising derivatised functionalities, methods for synthesising said supports, methods for synthesising compounds comprising amine groups or N-containing heterocycles using said solid supports, intermediate compounds linked to said supports and uses therefor. In particular, the invention relates to solid supports comprising derivatised amide or sulphone groups, methods for synthesising said supports, methods for synthesising compounds comprising tertiary amine groups or N-containing heterocyclic compounds using said supports and intermediate compounds comprising quaternary ammonium groups linked to said supports and uses therefor.
Solid phase chemistry is well known in the art, particularly in the fields of peptide and oligonucleotide synthesis. Advantages associated with solid phase synthesis include the ability to drive reactions to completion by use of excess reagents, ease of work up and potential automation of synthetic procedures. Organic compounds have traditionally been attached to the solid support by certain cleavable linker groups which yield, on cleavage, compounds in which polar functionality remains at the point of attachment, for example a CO2H, OH, NH2, CONH2 or a CONHR group. The synthesis of non-oligomeric organic compounds using resin-bound synthetic routes is a key component of the emerging technology of combinatorial chemistry (Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385-1401; Lowe, G. Acc. Chem. Res. 1995, 24, 309-317; Fruchtel, J. S.; Jung, G. Angew. Chem. Int. Ed. Engl. 1996, 35, 17-42).
One of the current limitations of this approach is the requirement for a xe2x80x9chandlexe2x80x9d to link small organic molecules onto a polymeric resin. In Merrifield peptide synthesis, for example, a carboxylic acid is linked via an ester group. Recently the range of linkers has increased (Fruchtel, J. S., and Jung G. supra).
Morphy J. R. et al. Tetrahedron Letters, 1996, 37, 3209-3212 report a novel linker strategy and describe a new type of linker and release system for resin-bound synthesis which is based upon Michael addition and Hofmann elimination (xcex2-elimination) reactions. The synthetic route is outlined in the following Scheme below:
where R1, R2 R3each represent an alkyl group and X is Br or I. Where 3a is a secondary amine (R2=H), conversion to a tertiary amine is achieved by reductive alkylation on the resin using a suitable aldehyde and NaBH(OAc)3 in 1% acetic acid/dimethylformamide for 18 hours at 20xc2x0 C.
The outlined synthetic route above utilises hydroxymethyl polystyrene resin derivatised with acryloylchloride to the acrylate ester 1. Michael addition of a secondary amine 2 gives the resin-bound tertiary amine 3. Alternatively, a primary amine 2 (R2=H) gives a resin-bound secondary amine which is converted into the tertiary amine 3 (R2=alkyl) by reductive alkylation. Quaternisation of the tertiary amine 3 with an alkyl halide 4 to give 5 introduces another site of diversity and activates the linker for cleavage by a facile Hofmann elimination reaction. Thus iPr2NEt (diisopropylethylamine; DIEA) at room temperature liberates the tertiary amine 6 into solution and regenerates the resin 1.
Since the resin linker 1 is regenerated after cleavage of the product and is functionalised via a Michael reaction, the resin is referred to as a REM resin (Morphy, supra).
A disadvantage of the above outlined reaction is that the ester derivatised resin, in this case originating from an acrylate ester, can be unstable under certain reaction conditions such as strong acid, strong base, or others reaction conditions including reagents such as Grignard reagents, and reducing agents such as LiAlH4 and the like. In such reaction conditions, cleavage at the ester bond may occur. Thus, the general applicability of the ester derivatised resin can be limited. and as a consequence, the solid phase synthesis of desired amine-containing compounds or N-containing heterocyclic compounds may not be realised.
The present invention seeks to mitigate against the disadvantages associated with the prior art and to provide derivatised solid supports which are stable to a wide range of chemistries and whereon a broad scope of amines or N-heterocyclic containing compounds can be prepared utilising the Hoffmann elimination reaction, as described above, to release the amines from the solid supports.
According to a first variant of the invention there is provided a solid support comprising a functionalised amide according to Formula (I).
wherein
represents the solid support;
B is a conventional spacer arm or a bond;
R is selected from H, (C1-C6)alkyl, optionally substituted with halogen. aryl(C1-C6)alkyl and aryl, optionally substituted with (C1-C6)alkoxy, OH or halogen;
W is selected from O and S;
Y is CHR4 where R4 is selected from H, (C1-C4)alkyl, optionally substituted with halogen, and phenyl, optionally substituted with CF3, (C1-C6)alkoxy;
Z is CR5R6xe2x80x94L where R5 and R6 are independently selected from H, (C1-C4)-alkyl, and phenyl; L is a leaving group; or
Y and Z together form CR4xe2x95x90CR5R6 wherein R4 and R5 are as defined above, or wherein R4 and R5 together with the carbon atoms to which they are bonded form a (C4-C8)cycloalkene ring.
The term (C1-C6)-alkyl as used in the definition of formula I means a straight or branched-chain alkyl group having from 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, pentyl and hexyl.
The term (C1-C4)alkyl means, likewise, a straight or branched-chain alkyl group having 1-4 carbon atoms.
The term (C1-C6)alkoxy means a (C1-C6)alkyloxy group, wherein (C1-C6)alkyl has the previously given meaning. A preferred (C1-C6)alkoxy group is methoxy. Preferred (C1-C6)alkoxy substituted aryl groups are 2-methoxyphenyl and 4-methoxyphenyl.
The term halogen means F, Cl, Br or I.
The term aryl means an aromatic ring system having from 6-12 carbon atoms, such as for example phenyl and naphthyl; a preferred aryl group is phenyl.
The term aryl(C1-C6)alkyl as used in the definition of formula I means an aryl group, having the meaning as previously defined, linked to a (C1-C6)alkyl group as previously defined, such as benzyl (phenylmethyl).
The term (C4-C8)cycloalkene ring, as used in the definition of formula I means a cycloalkene ring having 4-8 carbon atoms, like cyclobutene, cycloheptene, cyclohexene, cycloheptene and cyclooctene.
The term leaving group is known in the art of substitution reactions (Advanced Org. Chem (1992) (4th Ed.) March J, p 352, Wiley and Sons). Examples of well known leaving groups are Cl, Br, I, tosyloxy, mesyloxy, trifluoromethanesulphonyloxy, trifluoroethanesulphonyloxy (tresyloxy) and the like.
The conventional spacer arm B, as used in the definition of Formula I, means a chemical structure linking (or interspaced between) a functional group to the backbone structure of the solid support. B may be any conventional spacer arm commonly employed in solid phase organic chemistry. For instance, the spacer arm B of a chloromethylated or an aminomethylated polystyrene divinylbenzene (Merrifield) resin, is the methylene, xe2x80x94CH2xe2x80x94 group. Further examples of spacer arms B are (CH2)n, CH2(OCH2CH2)n wherein n=0, 1, 2, 3 or 4, CH2C(CH3)(PEG)2, PEG (polyethyleneglycol)-CH2 and the like. Examples of these and other suitable spacer arms can be found in The Combinatorial Chemistry Catalog, February 1997 (NovaBiochem) pp1-37.
In a preferred embodiment of the first main aspect of the invention, B is selected from (CH2)n and CH2(OCH2CH2)n and n is 0, 1 or 2; R is selected from H, (C1-C4)alkyl and phenyl; W is O; and Y and Z together form CR4xe2x95x90CR5R6 wherein R4, R5 and R6 are independently selected from H, CH3 and phenyl; or Y is CHR4 where R4 is selected from H, CH3 and phenyl and Z is CR5R6xe2x80x94L where L is a leaving group selected from Br, Cl, I, tosyloxy, mesyloxy and trifluoromethanesulphonyloxy.
In a further preferred embodiment, B is CH2; R is selected from H, CH3, C2H5, C3H7 (ie straight or branched-chain), and phenyl; W is O; and Y and Z together form CHxe2x95x90CH2 or Y is CH2 and Z is CH2xe2x80x94L where L is a leaving group selected from Br, Cl, I, tosyloxy, mesyloxy, and trifluoromethanesulphonyloxy.
In a particular preferred embodiment B is CH2; R is H; W is O; Yxe2x80x94Z is CHxe2x95x90CH2, and the solid support is the polystyrenedivinylbenzene support of a Merrifield resin.
The selection of a solid support may be made from conventional commercially available solid support materials such as resins, for example, aminomethyl polystyrene and the like. Other suitable solid support resins for use in the present invention can be found in, for example, The Combinatorial Chemistry Catalog, supra. Suitable solid supports include polystyrene optionally cross-linked with a cross-linking agent such as divinyl-benzene, acrylamides such as polyacrylamide, dimethylacrylamide, and polystyrene acrylamide, glass, silica gels, polyethylene glycol (PEG), polyethylene glycol-polystyrene (PEG-PS) resin, ARGOGEL(trademark) (Argonaut Tech. Inc.), cellulose, pore-glass, for example, is the form of pore-glass, beads, latex, and macroporous supports and the like.
The solid support as used in the invention may be in various physical forms, such as in the form of beads, the most commonly used polystyrene based resins (The Combinatorial Chemistry Catalog, vide supra), pins, such as polypropylene/polyethylene pins and the like; pellets; disks; capillaries; hollow or solid fibres. The solid support may be flat, or alternatively; or other shaped may be in the form of substantially spherical; beads, such as a polygonal shape, for example a hexagon.
The person skilled in the art will appreciate that the selection of a solid support will depend on the reaction conditions employed and/or envisaged in the synthesis of desired amines or N-heterocyclic containing compounds. Supports may be selected as appropriate with a view to such factors as the mildness or harshness of the reaction conditions employed. Macroporous solid supports can be viewed as those types wherein the structure remains substantially permanently swollen, irrespective of the choice of solvent. For example, those containing as the base material. polystyrene, styrene-divinylbenzene copolymer, glass, silica gel, polypropylene, polyvinyl alcohol, poly(2-hydroxyethyl methacrylate), oligo(ethyleneglycol) dimethacrylate polymer, polyacrylamide and Kiesel-guhr. Preferred supports include polystyrene cross-linked to varying degrees with divinylbenzene to give either a microporous or macroporous support, polyethyleneglycol (PEG) or PEG-derivatised polystyrene. Such supports may either be in the form of supports functionalised with appropriate groups such as NHR or functionalised with groups which may be converted to such NHR groups. The selection of solid support is not critical provided that it comprises appropriate NHR groups or is a solid support comprising groups capable of being functionalised to NHR groups. Such supports are known to the person skilled in the art, such as those made by converting a chloromethylated polystyrene resin to an amino functionalised resin via an appropriate alkylation reaction.
Generally, an amide-functionalised support of Formula (I) can be prepared from a suitable solid support such as a resin comprising an amine group, of Formula (II):
where B and R are as defined hereinabove, by acylation with a suitably activated acid derivative according to formula Yxe2x80x94Zxe2x80x94COOH, wherein Y and Z are as defined above, such as an activated ester derivative or an acid chloride derivative, after which the resulting amide may be optionally converted to a thioamide, for instance, by treatment with phosphorous pentasulfide. For instance, an amide functionalised support of Formula I can be prepared from a suitable so. support of Formula II by the addition of a suitable carbonyl chloride, such as an acid chloride, for example, acryloyl chloride or 3-bromopropionoyl chloride, under suitable reaction conditions, for example, in the presence of a tertiary amine base, such as diisopropyl ethyl amine (DIEA) in a suitable organic solvent, such as dichloromethane. Such reaction conditions are familiar to the man skilled in the art.
In a second aspect of the invention, there is provided a process for the preparation of a tertiary amine which comprises:
(i) adding a primary or secondary amine to an amide-functionalised support according to Formula (I) by way of a Michael addition to an unsaturated amide or by alkylating a propionamide having a leaving group L in the 3 position:
(ii) adding an alkylating agent to the product of step (i); and
(iii) performing a Hofmann elimination on the quaternary ammonium compound generated in step (ii).
In a variant of the second aspect of the invention there is provided a process for the preparation of a tertiary amine which comprises:
(i) adding a primary amine to an amide-functionalised support according to Formula (I) by way of a Michael addition to an unsaturated amide or by alkylating a propionamide having a leaving group L in the 3 position;
(ii) performing a reductive alkylation on the secondary amine produced in step (i) giving a tertiary amine;
(iii) adding an alkylating agent to the product of step (ii); and
(iv) performing a Hofmann elimination on the quaternary ammonium compound generated in step (iii).
Reference is made to the outline reaction Scheme 1, below:
The primary or secondary amine HNR7R8 may be any primary or secondary amine capable of undergoing a Michael addition to the amide-functionalised resin giving 3 (Route A).
R7 and R8 may be selected from H, branched or straight chain (C1-C6)alkyl such as methyl, ethyl, propyl, isopropyl, butyl, and sec.butyl, (C1-C6)alkyl ethers such as methyloxyethyl, arylalkyl such as phenylethyl, (C1-C6)alkyl-Oxe2x80x94(C1-C6)alkylene, vinyl (C1-C6) alkylene, such as allyl and the like.
Alternatively, R7 and R8 may form part of a ring structure, for example, in secondary amines such as ethyl isonipecotate (ethyl 4-piperidinecarboxylate), 4-benzyl piperidine, piperazine such as 1-phenyl piperazine, 1,2,3,4-tetrahydroisoquinoline, and proline. In general, the secondary amine can be any secondary amine which can be employed in a Michael addition reaction leading to compound 3.
The alkylating agent may be any alkylating agent such as an alkylating agent of the formula R9X, where X is selected from I, Br, Cl, trifluoromethanesulphonyloxy, and R9 is an alkyl group which can be added to compound 3 in the synthesis of the quaternary compound 5. Suitable R9 alkyl groups include branched or straight chain (C1-C6)alkyl such as methyl, ethyl, propyl, n-butyl, (C1-C6)alkyl ethers such as methyloxyethyl, arylalkyl such as phenylmethyl, (C1-C6)alkyl-Oxe2x80x94(C1-C6)alkylene, vinyl(C1-C6)alkylene, such as allyl and the like. The person skilled in the art will appreciate that generally the selection of R7, R8 and R9 is such that the groups are ones which are capable of being utilised in the generation of tertiary amines in the solid phase syntheses described herein. When selecting R7 and R8 groups when these relate to branched chain substituents, the skilled addressee will appreciate that a branch point comprising a quaternary carbon will not be located on an atom adjacent to the N.
It will be appreciated that, in addition to the three characteristic steps of the methodology (Michael addition, quaternisation, Hofmann), it is possible to add extra steps to elaborate the structure of the bound compound (for example, structure 3 of Scheme 1; structure 3 of Scheme 4) and thereby expand the diversity of a combinatorial library or array. As such, the man skilled in the art will also appreciate that the solid supports of the invention may be adapted for use in peptide synthesis, oligonucleotide synthesis and the like.
For example, an amine R7R8NH may be added to the resin, then R8 may be elaborated to R10, for example, via an addition or displacement reaction such as described by Hermkens P. H. H. et al. Tetrahedron 53 5643-5678, 1997. Quaternisation with an R9X and base catalysed cleavage may then provide an elaborated amine NR7R9R10 as outlined in scheme 2 below. A specific example would be the addition of ethyl isonipecotate to the resin, then addition of MeMgBr, quaternisation with methyl iodide, and cleavage with DIEA, giving compound (2) (see Scheme 2 below).
The person skilled in the art will appreciate that if one of the R groups (ie R7, R8 or R9) is removed subsequent to cleavage of the tertiary amine from the resin, a secondary amine will result. An example of a removable group could be p-methoxybenzyl, cleavable under acidic conditions such as TFA. In a variant of the second aspect of the invention a primary amine (instead of a secondary amine) may be used in step (i), giving rise to a secondary amine which may be converted to a tertiary amine by the introduction of a reductive alkylation step under appropriate reaction conditions, prior to the addition of the alkylating agent, such as R9X, of step (ii).
In the case where the amide functionalised support takes the form:
B, R, W, R4, R5, R6, and L are as defined hereinbefore. Examples of suitable resin derivatives of Formula (III) are as hereinbefore described.
The man skilled in the art will appreciate that the amide functionalised resin of Formula (III) may participate in an alkylation reaction with an appropriate primary or secondary amine to form a compound 3 as per the general description given hereinabove (Route B, Scheme 1).
In a third aspect of the invention there is provided as an intermediate in the obtaining of a tertiary amine a quaternary ammonium compound linked to a support according to the following Formula (IV):
wherein B, R, W, R4, R5, R6, R7, R8, and R9 are as defined hereinabove, and Xxe2x88x92 is a counteranion, such as Brxe2x88x92, Ixe2x88x92, or an acid derived anion.
In a preferred embodiment B is selected from (CH2)n and CH2(OCH2CH2)n; n is 0, 1 or 2; R is selected from H, (C1-C4) alkyl, and phenyl; W is O; and R4, R5 and R6 are H. In a further preferred embodiment B is CH2; R is selected from H, CH3, C2H5, C3H7 (ie straight or branched chain), and phenyl; W is O; and R4, R5 and R6 are H. In a still further preferred embodiment B is CH2; R is H; and R4 R5 and R6 are H.
In a fourth aspect of the invention, there is provided use of an amide functionalised support according to any one of Formulae (I), (III) or (IV) in the synthesis of a tertiary amine, or in the synthesis of N-containing heterocyclic compounds capable of quaternisation.
In a fifth aspect of the invention, there is provided, the use of an amide functionalised support according to any one of Formulae (I), (III), or (IV) in the manufacture of a combinatorial chemistry library or array of compounds.
In a second variant of the invention there is provided a sulphone functionalised solid support of Formula (V).
wherein
represents the solid support;
B is a conventional spacer arm or a bond;
C is O, NR, S, CH2 or SO2;
R is selected from H, (C1-C6)alkyl, optionally substituted with halogen, aryl(C1-C6)alkyl and aryl, optionally substituted with (C1-C6)alkoxy, OH or halogen;
b is an integer selected from 0 and 1;
D is selected from (C1-C6)alkylene, arylene, optionally substituted with halogen, and arylene(C1-C6)alkylene: or D is absent;
Y is CHR4 where R4 is selected from H, (C1-C4)alkyl, optionally substituted with halogen, and phenyl, optionally substituted with CF3, (C1-C6)alkoxy;
Z is CR5R6xe2x80x94L where R5 and R6 are independently selected from H, (C1-C4)-alkyl, and phenyl; L is a leaving group; or
Y and Z together form CR4xe2x95x90CR5R6 wherein R4 and R5 are as defined above, or wherein R4 and R5 together with the carbon atoms to which they are bonded form a (C4-C8)cycloalkene ring;
with the proviso that when D is absent C is not SO2, S or O, and when D is xe2x80x94CH2xe2x80x94, C is not SO2.
The term (C1-C6)alkylene as used in the definition of formula V means a bivalent radical having 1-6 carbon atoms, such as methylene, ethylene, trimethylene, 1 -methylethylene, tetramethylene, pentamethylene, hexamethylene. A preferred (C1-C6)alkylene group is methylene.
The term arylene means a bivalent aromatic radical of an aromatic ring system having from 6-12 carbon atoms, such as for example 1,2-phenylene, 1,3-phenylene, 1,4-phenylene or 1,4-naphthalenediyl; a preferred arylene group is 1,3-phenylene. The remaining terms in the definition of formula V have the meaning as previously given.
Preferred solid supports as used in the sulphone functionalised solid support of Formula (V) include polystyrene based resins. cross-linked to varying degrees with divinylbenzene to give either a microporous or macroporous support, polyethyleneglycol (PEG) or PEG-derivatised polystyrene.
In a preferred embodiment, B is selected from (CH2)n, CH2(OCH2CH2)n, xe2x80x94CH2C(CH3)(PEG)2 and PEGxe2x80x94CH2; n is 1 or 2; C is O or is absent; D is phenylene or is absent; and Y and Z together form CR4xe2x95x90CR5R6 wherein R4, R5 and R6 are independently selected from H, CH3 and phenyl; or Y is CHR4 and Z is CR5R6xe2x80x94L where R4, R5 and R6 are independently selected from H, (C1-C4)alkyl, and phenyl; and L is a leaving group; with the proviso that when D is absent C is not O.
In a further preferred embodiment B is CH2; C is O and D is 1,3-phenylene; or C and D are absent: Yxe2x80x94Z are xe2x80x94CHxe2x95x90CH2; or Y is CH2 and Z is CH2xe2x80x94L where L is a leaving group; and the solid support is the polystyrenedivinylbenzene support of a Merrifield resin.
In a particular preferred embodiment B is CH2; C is O and D is 1,3-phenylene; Y is CH2 and Z is CH2xe2x80x94L where L is Cl; and the solid support is the polystyrenedivinylbenzene support of a Merrifield resin.
Upon attachment of a primary or secondary amine (HNR7R8; derivatives 3 in Scheme 4) to this preferred sulphone functionalised solid support, the derivatised support was found (i) to be stable to alkoxides (e.g. sodium methoxide at room temperature), allowing, for example, transesterification reactions (such as the conversion of ethyl ester into methyl esters), and (ii) to be stable to Grignard reagents (e.g. phenylmagnesium bromide at room temperature), allowing, for example, resin bound esters to be converted to alcohols.
Amine derivatives (derivatives 3 in Scheme 4) prepared from another preferred sulphone functionalised Merrifield derived support according to formula V wherein B is CH2, C and D are absent and Xxe2x80x94Y represents CH2xe2x80x94CH2, were found, in addition to being stable to alkoxides and Grignard reagents, to be stable (iii) to strong acids (e.g. 6M HCl in dioxane at reflux) allowing, for example, cyclic ketals to be converted into ketones, to be stable to (iv) nucleophilic hydride reducing agents (e.g. sodium borohydride at room temperature) allowing, for example, imines to be converted to amines, and to be stable (v) to electrophilic hydride reducing agents (e.g. diborane-DMS complex at room temperature) allowing, for example, amides to be converted into amines.
The stability advantages mentioned for the sulphone functionalised supports of the invention in comparison with the prior art REM resins (Morphy et al. supra) allow a much wider range of chemical reactions to be carried out on the supports, and consequently increases the diversity of compound libraries which can be made using the supports of the invention.
Generally, a sulphone-functionalised support of Formula (V) can be prepared from a suitable solid support such as a resin comprising a leaving group, for example a resin of Formula (VI)
where (B) and L are as defined hereinabove. The solid support (VI) may be thiolated with a thiol compound of formula:
xe2x80x83HSxe2x80x94Yxe2x80x94Zxe2x80x94OH
wherein Y and Z are as defined herein. The resulting thioether alcohol may then be oxidised to a sulphone alcohol, followed by substitution of the OH group with an activating group (a leaving group L) such as Br, Cl, tosyloxy, mesyloxy, or trifluoromethanesulphonyloxy. Alternatively, compounds of Formula (V), wherein C is NR and D is absent, can be prepared by acylation of an amine-functionalised solid support with a sulphonyl chloride according to general formula Lxe2x80x94Zxe2x80x94Yxe2x80x94SO2xe2x80x94Cl wherein L, Y and Z are as defined herein. Synthesis of a support according to formula V can be illustrated with reference to Scheme 3 where HSxe2x80x94Yxe2x80x94Zxe2x80x94OH is mercaptoethanol, and a representative resin of Formula (VI) is Merrifield resin (a chloromethylated polystyrene resin) available from Novobiochem:
[(i) 10 eq. mercaptoethanol/Cs2CO3, DMF, 20xc2x0 C., 3 d.;(ii) excess m-CPBA, DCM, 20xc2x0 C., 12 h (or excess Oxone, aq. DMF, 20xc2x0 C., 12 h); (iii) PBr3, DCM, 20xc2x0 C., 16-24 h (or 10 eq. Mesyl Cl. DCM, 20xc2x0 C., 2 hr.)];
Reference is made to Scheme 4. 2xe2x80x2-Bromoethyl- and 2xe2x80x2-mesyloxyethyl sulfones 2 (L=Br or OMs) can be used as masked forms of a vinyl sulfone 6 in several reactions with secondary amines, such as tetrahydroiso-quinoline (THIQ), piperidines, morpholine, pyrolidine and dioctylamine and the like to give resin-bound tertiary amine products 3 (Route B). After washing, the resin bound tertiary amine products can be treated with an alkylating agent such as allyl bromide, to give quaternised ammonium salts 4, and these may then be treated with DIEA to effect Hofmann elimination and release tertiary amines 5 (as HBr salts) from the resin. As in the amide-functionalised synthesis of tertiary amines, it can be seen that compounds 6 can be recycled by re-reacting with more secondary amine (Route A).
Reference is again made to Scheme 4
In an alternative, an amine 8 may then be added to an appropriate resin of choice, such as hydroxymethyl polystyrene 7 to give 3. Alkylation of 3 provides 4 followed by a cleavage reaction giving 6. 6 may then undergo addition of secondary amine giving 3 followed by alkylation andxe2x80x94elimination generating a tertiary amine or N-containing heterocyclic compound with concomitant re-generation of the vinyl sulphone functionalised support.
In a further aspect of the invention there is provided a process for the preparation of a tertiary amine or an N-containing heterocyclic compound which comprises:
(i) adding a primary or secondary amine to a sulphone-functionalised support according to Formula (V) by way of a Michael addition to a vinyl sulphone or by alkylation using an ethyl sulphone having a leaving group in the 3 position forming a tertiary amine;
(ii) adding an alkylating agent forming a quaternary ammonium compound;
(iii) performing a Hofmann elimination on the quaternary ammonium compound generated in step (ii).
In a variant of the above aspect of the invention there is provided a process for the preparation of a tertiary amine which comprises:
(i) adding a primary amine to a sulphone-functionalised support according to Formula (V) by way of a Michael addition to a vinyl sulphone or by alkylation using an ethyl sulphone having a leaving group in the 3 position;
(ii) performing a reduction alkylation on the secondary amine produced in step (i) giving a tertiary amine;
(iii) adding an alkylating agent to the product of step (ii); and
(iv) performing a Hofmann elimination on the quaternary ammonium compound generated in step (iii).
In a third aspect of the invention there is provided as an intermediate in the obtaining of a tertiary amine a quaternary ammonium compound linked to a support according to the Formula (VII):
wherein B, C, D, R4, R5, R6 R7, R8, R9, and b are as defined hereinabove, and Xxe2x88x92 is a counteranion, such as Brxe2x88x92, Ixe2x88x92, or an acid derived anion.
B may be any conventional spacer such as (CH2)n, CH2(OCH2CH2)n, PEG-CH2, and xe2x80x94CH2C(CH3)(PEG)2; and n is 0, 1, 2, 3 or 4.
In a preferred embodiment B is selected from (CH2)n, CH2xe2x80x94(OCH2CH2)n, CH2C(CH3)(PEG)2, and PEG-CH2; n is 1 or 2; C is O or is absent; D is phenylene or is absent; and R4, R5 and R6 are independently selected from H, (C1-C4)alkyl, and phenyl: with the proviso that when D is absent C is not O. In a further preferment, B is CH2; C is O and D is phenylene or C and D are absent; and CHR4xe2x80x94CR5R6 is CH2xe2x80x94CH2.
In another aspect of the invention there is provided use of a sulphone-functionalised support according to Formulae (V) or (VII) in the synthesis of a tertiary amine or in the synthesis of an N-containing heterocycle capable of quaternisation.
In a still further aspect of the invention, there is provided use of a sulphone-functionalised support according to Formulae (V) or (VII) in the manufacture of a combinatorial chemistry library or an array of compounds.
It will be appreciated by the skilled adressee that the solid supports which serve as the starting material will be loaded with an amount of linking agent comprising amide or sulphone functionalities which enables chemical synthesis of compounds of interest to proceed. Generally, the amount of linking agent to be loaded onto the resin can be any amount provided that the chemical synthesis of compounds of interest can proceed. Typically, the amount of a linking agent which may be loaded onto the resin can be any amount from 0.05 mmol/gram resin depending on the chemical synthesis contemplated. Generally, the amount of linking agent for loading onto the resin can be between 0.1 and 2.0 mmol/gram resin, more preferably between 0.25 and 1.25 mmol/gram resin and most preferably between 0.4 and 1.0 mmol/gram resin.


The present invention relates to the use of certain polyalkylphenyl silanes in photoresists to generate positive tone resist images. The polyalkylphenyl silanes have the formula: ##STR1## where R is C2-C12 alkyl and n is about 150 to 7000.

There is a desire in the industry for higher circuit density in microelectronic devices made using lithographic techniques. One method of achieving higher area density is to improve resolution of circuit patterns in resist films. The use of shorter wavelength radiation (e.g. deep UV-220 to 280 nm) than the currently employed near and mid-UV spectral range (300 nm to 450 nm) offers the potential for improved resolution. However, with deep UV radiation, fewer photons are transfered for the same energy dose to achieve the same desired photochemical response. Further, current lithographic tools have greatly attenuated output in the deep UV spectral region. Therefore, there is a need in the art to develop resist materials which are more sensitive to radiation in deep UV.
Poly(bisalkyl)silanes and poly(methylphenyl)silane are known in the art for use as a resist e.g. in making bilayer photoresist, Miller et al., Materials for Microlithography, ACS Symposium Series 266, page 293, 1984. The bilayer resist comprises an imaging, oxygen plasma resistant polysilane layer over a planarizing polymer layer coated on a substrate. When the resist is imaged, the radiation causes photochemical degradation of the exposed polysilane into lower molecular weight material. Photochemical degradation is accompanied by a proportional amount of spectral bleaching which is used in the art to measure the degree of degradation. The degradation of the exposed polysilane enables wet development of a positive image with common organic solvents. The image is then transferred through the underlying polymer layer to the substrate by oxygen plasma development. However, current polysilanes lack sensitivity and require large radiation doses of 100 to 400 millijoules/cm.sup.2 for suitable imaging and therefore are generally less desirable for commercial use especially in deep UV. It is therefore an object of the present invention to provide improved photosensitive polysilanes for use as photoresist.
Other objects and advantages will become apparent from the following disclosure.

Process for use of photosensitive polysilanes as photoresist

International Business Machines Corporation


A controlling method of a clothes dryer for detecting an amount of laundry and a clothes dryer with the same are disclosed. A controlling method includes drying laundry by supplying hot air to a drum, determining an amount of laundry based on a drying time, and supplying fine droplets of water and/or steam to the drum according to the determined amount of laundry.

Field of the Disclosure
The disclosure relates to a home appliance. More particularly, to a controlling method of a home appliance, such as clothes dryer to detect an amount of laundry put therein and supply fine droplets of water and/or steam according to the detected laundry amount.
Discussion of the Related Art
Clothes dryers are home appliances for drying washed laundry by using hot air. Typically, a clothes dryer includes a drum for holding laundry, a driving source for driving the drum, a heating means for heating air drawn into the drum and a blower unit for sucking or discharging the air inside or from the drum.
Clothes dryers may be categorized based on a method of heating air. For example, a dryer may be categorized by its heating means into electric type dryers and gas type dryers. In the electric dryer, air is heated by using ohmic heating. In the gas type dryer, air is heated by heat generated by gas exhaustion. Dryers may be categorized into condensation type (circulation type) dryers and exhaustion type dryers. In the condensation type dryer, air is heat exchanged with laundry in the drum and the heat exchanged humid air is circulated, not discharged outside. The air is heat exchanged in a condenser and the condensed water is discharged outside. In the exhaustion type dryer, air is heat exchanged with laundry in the drum and the heat exchanged humid air is exhausted outside directly. Furthermore, dryers may be categorized based on a method of loading laundry into top loading type dryers and front loading type dryers. In the top loading type dryer, laundry is loaded through a top of the dryer. In the front loading type dryer, laundry is loaded through a front of the dryer.
Recently, steam dryers for drying laundry and using steam are being released. Steam is used to release or remove wrinkles from the laundry.

Controlling method of a dryer and a dryer with the same


The present disclosure relates to systems and methods for creating and using personas. The method includes receiving a first set of input signals associated with data from one or more source; receiving a second set of input signals associated with data from one or more source; converting the first set of input signals and the second set of input signals to a wavelet; constructing a persona based on the wavelet; storing the persona in a ledger; receiving a request for a decision related to a transaction; converting the request to a new wavelet; determining a difference between the new wavelet and the stored persona; generating a score based on the difference; and authorizing the transaction based on the score.

Extant methods of smart contract execution and fraud detection rely on models of transactions which attempt to determine which transactions are fraudulent. These models attempt to identify patterns in fraudulent activity. However, in cases where millions of transactions occur each day, such as for credit card transaction processing, large, complex models based on historical transactions introduce latency, slowing approval of a transaction and harming user experience.
In some scenarios, transaction authorizations exchange accuracy for speed. To increase approval speed, models are provided less data to reduce processing time. However, with less data, these models suffer from high rates of false-positive alerts, impacting user experience and impeding legitimate business.
Further, in order for trust to exist between parties who often do not know each other, parties must confirm their identities and qualifications for a transaction. For example, when applying for a loan, a person may have to verify address, income, and employment, all of which may be faked to fraudulently obtain a loan. Verification of these details is often costly and time consuming, resulting in decreased transaction volume, decreased profit, and decreased user experience.
Therefore, methods and systems that aid in verification of user identifies while also accelerating and improving fraud detection are desired.

Systems and methods for analyses and action approvals using a ledger


In one or more embodiments, an over-sampling method and corresponding over-sampling circuit efficiently generate an over-sampled signal by determining sampling phases in the over-sampled signal that are unused by downstream processing of the over-sampled signal, and skipping the generation of output values for the over-sampled signal that correspond to the unused sampling phases. In a communication receiver embodiment, determining the unused sampling phases comprises, with respect to currently estimated multipath delays of a received communication signal from which the over-sampled signal is derived, determining which sampling phases in the over-sampled signal will not be used by a downstream processing circuit having known processing delay assignment constraints. The known delay assignment constraints comprise Rake finger placement constraints or channel equalizer tap placement constraints, for example.

The present invention generally relates to signal processing, and particularly relates to signal interpolation processing.
A typical digital communication receiver converts baseband received analog signals as output by its "front-end" circuits into a corresponding discrete-time sequence of quantized values. According to the fundamental Nyquist criterion, sampling the baseband analog signal at or above twice its highest frequency allows the resulting discrete-time sequence to model the analog baseband signal with no loss of information.
However, practical digital signal processing algorithms, such as filtering, etc., may be implemented more easily if the analog baseband signal is over-sampled, meaning that the sampling rate used to generate the discrete-time sequence is above the Nyquist rate. For example, in a Wideband CDMA (WCMDA) signal processing context, the actual minimum sample rate equals 1.22 samples per "chip," which translates into one discrete-time sample per 0.82 chips in the received signal. One sample per ¾ chips, however, offers a more practical, "digital friendly" minimum sampling reference given digital processing implementation considerations. With that minimum, receiver over-sampling rates include 2× over-sampling ("OS2") at one sample per ½ chip, or 4× over-sampling ("OS4") at one sample per ¼ chip.
Receiver architecture and operation at least partially determines the preferred over-sampling parameters. Consider, for example, Rake receiver structures, which represent a common receiver design in WCDMA systems. A Rake receiver despreads and combines multipath copies of a received signal to maximally utilize the signal energy available to the receiver. In a simplified model, each despreading "finger" in a Rake receiver processes a copy of the transmit signal corresponding to one radio propagation path, based on correlating the received signal—represented by a sampled discrete-time sequence—with an appropriately delayed reference spreading sequence. The Rake receiver then sums the correlation results (despread values) from each finger using a set of combining weights.
As a simplification, one may assume that the delay spacing of individual Rake fingers follows the Nyquist minimum and in a "practical" WCDMA Rake receiver application, a minimum distance of ¾ chips represents a convenient choice for minimum finger placement. With that minimum separation and assuming non-grid based finger placement, fingers may end up at any delay that is a ¼ chip multiple. With grid-based finger placement, where fingers are placed to cover regions of signal energy instead by being placed to match individual physical path delays, the finger delays fall at ¾ chip multiples.
Nonetheless, samples corresponding to the ¼ chip spacing must be produced to allow for the ¾ chip minimum spacing. One approach to obtaining the desired OS4 samples comprises up-sampling an OS2 sequence (inserting zeros for every second sample of the OS2 sequence) and applying a Finite Impulse Response (FIR) filter, consisting of a predetermined number of filter taps, at the OS4 rate. While the resulting OS4 sequence contains no additional information compared to the OS2 sequence, it does permit use of simple Rake structures to effect optimal demodulation of the received symbol sequence.
However, those skilled in the art will appreciate that, when grid-based finger placement is used, not all samples corresponding to all multiples of ¼ chips are necessarily used during despreading. Interpolating the OS2 sequence to obtain these ultimately unused samples represents needless processing overhead and is a waste of receiver power. Of course, the same issue arises with other grid spacing/phase parameters, and in non-grid placement as well.
Similar issues arise in chip equalizer and other fractionally spaced equalizer structures. Channel equalizers use knowledge of multipath channel characteristics (path delays and coefficients) to compensate for the loss of code orthogonality in a received CDMA caused by Inter-Symbol-lnterference (ISI). However, not all delays are used for a given (tap) delay resolution. Knowing how the propagation channel taps are spaced, which is learned from channel estimation processing, allows the receiver to pick a reduced number of equalizer channel taps for equalization processing. That is, one can formulate a reduced-tap channel equalizer for certain multipath channel realizations, and these reduced-count taps correspond only to a limited subset of samples from the over-sampled baseband signal. For example, assume possible channel equalization taps at (1, 1.25, 1.5, 1.75, 2.0, 2.25, . . . ) and a 4× over-sampled signal having phases (0, 1, 2, and 3). Further, assume that for current channel conditions, the equalizer taps at x.25 are not used ("x" equals 1, 2, . . . ). In this case, the "phase 1" samples in the over-sampled signal are unneeded and their computation in an interpolation filter represents wasted receiver processing.
More generally, many over-sampled signal generation applications include delay-based processing, wherein over-sampled signal samples corresponding to certain processing delays are used and other samples corresponding to other processing delays are not. Generating output values represents wasted receiver processing to the extent that the output values correspond to delays not of interest for subsequent processing of the over-sampled signal.

Method and apparatus for efficient signal interpolation


A traveling condition determination device for use in a vehicle includes an imaging unit for periodically capturing an image of a road on which the vehicle is traveling, a recognition unit for recognizing a marker on a side of the road relative to the vehicle, a detection unit for detecting an angle of the vehicle relative to the marker recognized by the recognition unit, a storage unit for storing the angle of the vehicle detected by the detection unit in an analyzable manner and a determination unit for determining a traveling condition of the vehicle based on the angle stored in the storage unit.

A navigation system for use in a vehicle conventionally determines a current position of the vehicle based on an autonomous navigation method and a radio navigation method. The autonomous navigation method determines the current position of the vehicle by employing measurement of geomagnetism, direction and/or vehicle speed as well as map data. That is, an estimated position of the vehicle based on the measurement is adjusted and "matched" with, for example, a position of a road to be suitably displayed on a map in a display unit of the navigation system. This process is called as "Map matching." The radio navigation method determines the current position of the vehicle by employing radio signals received from plural satellites for map matching. Some of the currently available navigation systems use both of the autonomous navigation method and the radio navigation method for accurately determining the current position of the vehicle.
The navigation system in a disclosure of the Japanese Patent Document JP-A-2003-227725 uses a camera disposed on a vehicle for capturing image of a road and precisely determining a type of the road, that is, a local road, an expressway or the like.
However, the navigation system of the above-described type is not capable of determining a traveling condition of the vehicle at a specific moment such as going into an intersection, going into a parking lot by leaving a local road or the like.

Traveling condition determination device


A prosthetic component with a pneumatic device for knee articulation formed of an upper part adapted to support a socket element for a stump of a thigh, and a lower part intended to receive a tube extended by an ankle and foot. The two parts are connected to each other by an assembly of pivoted links forming a deformable prism. Movement of the two parts between two stable positions of complete extension and flexure, about the variable axis of rotation defined by these connections, is controlled by a pneumatic cylinder having an upper chamber and a lower chamber separated by a piston and communicating with each other by an air duct with adjustable flow. In each of the stable positions, the pressure of air in the chambers is greater than 1 bar and is preferably between 4 and 7 bar.

The invention relates to a prosthetic component with a pneumatic device for articulation of the knee.
Such a prosthetic component is an essential element of an artificial leg prosthesis called an "above the knee", that is to say which has a foot, an ankle, a lower part of the leg hereinafter called a "leg", a knee and a socket for receiving the stump of the thigh.
The patient can perform a balancing movement with this type of prosthesis. If this movement is controlled in an appropriate manner, the ability to walk in a relatively natural way can thus be restored.
A large number of means for controlling the relative movement of the upper part of the prosthetic device (supporting the socket) with respect to its lower part (connected to the leg) are known from the prior art.
The basic function which this prosthetic device must perform is that of damping and propelling, which is generally provided by the use of springs, hydraulic or pneumatic cylinders, or by any combination of these means.
The British patent application GB-A-2,252,503, published on Aug. 12, 1992, gives an example of use of a pneumatic cylinder for controlling the movement of a prosthesis. The opening of the valve of the cylinder of the prosthetic component is controlled by a micro-processor as a function of the speed of walking. The use of a computer for producing the control signals for the valve of the cylinder as a function of the signal coming from an angle transducer between the thigh and the leg permits a sophisticated control of movements. However, this knee prosthesis component is pivoted about a fixed axis of rotation and therefore possesses movement characteristics rather far from those of a human knee.
The international patent application WO 93/22,991 published on Nov. 25, 1993 describes a mechanical articulation reproducing the kinematics of the normal human knee. The movement of the lower part of the articulation is guided by studs moving in curved grooves in the upper part, in such a manner that the axis of rotation is variable and no longer fixed.
The same kinematics can be produced by interconnection links as is shown in the European patent application EP-A1-0,590,386 filed by the German company Otto Bock Orthopadische Industrie and published on Apr. 6, 1994.
The international patent application WO 92/22,267 published on Dec. 23, 1992 has already shown a simultaneous embodiment of the above principles: a variable axis of rotation obtained by a set of links and a pneumatic cylinder having a function of damping and propulsion. The control of the flexure and extension of the articulation being however produced differently by the flow of a fluid in a hydraulic cylinder controlled by an electro-magnetic valve.
The pneumatic prosthetic component for articulation of he knee sold by the Proteval company under the name "Acphapend" has the advantages of the first three prior devices but is an entirely mechanical and pneumatic product, which is consequently simpler and more reliable.
In certain conditions of use, particularly for running, a prosthesis having a hydraulic system is more suitable. The device described in the WO 92/22,267 specification can thus represent a good compromise. However, the mass of fluid renders the device significantly heavier than an entirely pneumatic apparatus, and thus tiring for its user.
The European patent application EP-A1-0,628,296 filed by the Chas. A. Blatchford & Sons company and published on Dec. 14, 1994 describes a control system for a prosthesis which uses the same principles as those described in the GB-A-2,252,503 specification. The patient is also provided with a electronic circuit for automatic control. It is clear that the possibility of no longer having to make adjustments on the prosthetic component as such is a significant comforting factor for the patient; further, these adjustments can then be made during walking.
It is in taking account of all these constraints that the new prosthetic component for articulation of the knee according to the present invention has been conceived; an entirely mechanical and pneumatic product, similar to the product known under the "Acphapend" name, it also provides a little more closely the same characteristics, adjustable at will, as those of a hydraulic knee. Combining, on the one hand, the comfort of remote adjustment of the orthopaedic characteristics which are a feature of electronic systems and, on the other hand, the stiffness necessary in certain sporting activities exhibited only by hydraulic knees, whilst being lighter, more simple and more reliable than these latter, the invention offers advantages unknown at present in the state of the art.

Prosthetic component with pneumatic device for knee articulation


The present invention involves a type of nanoporous macrocycle-containing cross-linked polymeric membrane, a method of making the membrane, and the use of such a novel membrane system for natural gas liquids (NGL) recovery, fuel gas conditioning, natural gas pre-treatment, sulfur removal from fluidized catalytic cracking (FCC) and other naphtha streams, as well as aromatic separations such as aromatic/paraffin separation and xylene separation. The nanoporous macrocycle-containing cross-linked polymeric membrane is prepared from a diisocyanate-terminated polyether or a diisocyanate-terminated polyester, that is crosslinked with a nanoporous macrocycle comprising hydroxyl functional groups such as α-, β-, and γ-cyclodextrins.

In the past 30-35 years, the state of the art of polymer membrane-based gas separation processes has evolved rapidly. Membrane-based technologies have advantages of both low capital cost and high-energy efficiency compared to conventional separation methods. Membrane gas separation is of special interest to petroleum producers and refiners, chemical companies, and industrial gas suppliers. Several applications have achieved commercial success, including carbon dioxide removal from natural gas and from biogas and enhanced oil recovery, and also in hydrogen removal from nitrogen, methane, and argon in ammonia purge gas streams.
However, it was demonstrated in practice that the membrane performance can deteriorate very quickly without the use of a pretreatment system. The major reason for the loss of membrane performance is heavy hydrocarbon liquid condensation on the membrane surface. Condensation can be prevented by providing a sufficient dew point margin for operation, based on the calculated dew point of the membrane product gas. UOP's MemGuard™ system, a pretreatment regenerable adsorbent system that uses molecular sieves, was developed to remove water as well as heavy hydrocarbons ranging from C6 to C35 from the natural gas stream, hence, to lower the dew point of the stream. The selective removal of heavy hydrocarbons by a pretreatment system can significantly improve the performance of the membranes.
Although these pretreatment systems can effectively remove heavy hydrocarbons from natural gas streams to control the dew point of natural gas, the cost is very high. Some commercial membrane projects showed that the cost of the pretreatment system was as high as 10 to 40% of the total cost (pretreatment system and membrane system) depending on the feed composition. Reduction of the pretreatment system cost or total elimination of the pretreatment system would significantly reduce the membrane system cost for natural gas upgrading. On the other hand, in recent years, more and more membrane systems have been applied to large offshore natural gas upgrading projects. For offshore projects, the footprint is a big constraint. Hence, reduction of footprint is very important for offshore projects. The footprint of the pretreatment system is also very high at more than 10-50% of the footprint of the whole membrane system. Therefore, the removal of the pretreatment system from the membrane system will remarkably reduce the cost and footprint of the membrane system especially for offshore natural gas applications such as floating production storage and offloading vessel (FPSO) applications.
Conditioned natural gas has been used as fuel gas in gas engines and turbines in the hydrocarbon processing industry particularly for offshore platforms and remote locations and will be used in future floating liquefied natural gas (FLNG) and FPSO applications. To improve the reliability and reduce unscheduled downtime of the equipment that is used for fuel gas conditioning, a simple fuel gas conditioning technology is required. Rubbery polymeric membranes that can selectively and efficiently permeate heavy hydrocarbons and other contaminants such as CO2, H2S, and water vapor will allow conditioning of fuel gas.
A rubbery polymeric membrane that can selectively permeate condensable heavy hydrocarbon vapors such as C3+ hydrocarbons and can reject non-condensable gases such as methane can also be used for natural gas liquid (NGL) recovery.
The present invention describes a new type of nanoporous macrocycle-containing cross-linked polymeric membranes. The introduction of nanoporous macrocycles such as α-, β-, and γ-cyclodextrins (CDs) to rubbery polymeric membranes in the present invention significantly improves both permeance and selectivity of the rubbery polymeric membranes for separations.

This patent is subject to a terminal disclaimer.

Nanoporous macrocycle-containing cross-linked polymeric membranes for separations