The present invention provides a composition comprising vesicles and encapsulated within the vesicles, nucleic acid comprising less than 1000 nucleotides, wherein the vesicles comprise an amphiphilic block copolymer having a hydrophilic and a hydrophobic block.

Recently, researchers have tried to exploit the natural ability of RNAs to mobilize and transcript genetic information for therapeutic purposes. Such methods normally involve the interference with dysfunctional nucleic acids or proteins and/or the stimulation of the production of therapeutic genes. Particularly important is a process that uses synthetic double-stranded RNA, known as RNA interference (RNAi). This operates via post-transcriptional gene silencing, mediating the resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and therefore regulating the expression of protein-coding genes. It appears evident that the efficient cytosolic delivery of RNAs is a vital step in almost all RNAi-based gene-silencing experiments. Efficient cytosolic delivery of nucleic acids is, however, a very difficult task. Synthetic siRNAs can be delivered to cells in culture via electroporation or by using either cationic lipids or polymers. However, these approaches are limited by the transient nature of the response and in some cases by vector-mediated toxicity, (Mittal, V. Improving the Efficiency of RNA Interference in Mammals. Nature Rev. Genet. 5, 355-365 (2004)).
WO2002/044321 describes the sequence and structural requirements for small RNAs mediating RNA interference and therapeutic uses of interfering RNA. Using a drosophila in vitro system, it is demonstrated that 19-23 nucleotide short RNA fragments are the sequence-specific mediators of RNA.
Alnylam Pharmaceuticals Inc. have developed a variety of therapeutic compositions comprising siRNAs. Some of these are disclosed in, for instance, WO2004/030634. Sirna Therapeutics, Inc. are also active in this area. Their U.S. Pat. No. 7,022,828, for example, describes siRNA treatment of diseases or conditions related to levels of IKK-gamma.
EP1527176 describes novel forms of interfering RNA molecules. The molecules are double-stranded structures in which the strands are at least partially complementary to one another, and wherein the double-stranded structure is blunt ended. WO02006/069782, by the same Applicant, describes delivery agents for introducing small nucleic acids, such as those in EP1527176, into cells. The delivery agents are lipid compositions comprising a first lipid component, a first helper lipid and a shielding compound (for instance PEG) which is removable from the lipid composition under in vivo conditions.
We have recently reported on a very efficient, non-toxic and non-inflammatory vector for the delivery of (plasmid) DNA within human cells, (Lomas, H. et al. Biomimetic pH Sensitive Polymersomes for Efficient DNA Encapsulation and Delivery. Adv. Mater. Vol 19 (2007), 4238-4243). The combination of this type of polymer with DNA is described in our patent application WO03/074090. In this application, 2-(dimethyl) ethyl methacrylate (DMA)—MPC polymers are used to form DNA-polymer complexes. Depending upon the block lengths and pendant groups of the respective components of the copolymer, it is now known that the interaction with DNA can be tailored to produce DNA condensates (polyplexes) or have the DNA encapsulated within a vesicle of the material. The latter is based on the self-assembly of pH sensitive poly (2-methacryloxyethyl phosphorylcholine)-poly (2-(diisopropylamino)-ethyl methacrylate), (PMPC-PDPA) block copolymers into nanometer-sized vesicles, also known as polymersomes, (Du, J., Tang, Y., Lewis, A. L. & Armes, S. P. pH-Sensitive Vesicles Based on a Biocompatible Zwitterionic Diblock Copolymer. J. Am. Chem. Soc. 127, 17982-17983 (2005)).
Tan et al in Biomacromolecules 2007, 8, 448-454 describe polyethylene oxide-poly(dimethylamino)ethyl methacrylate (PEO-b-PDMA) and PEO-b-poly(diethylamino)ethyl methacrylate (PEO-b-PDEA) copolymers as a self-assembling non-viral vector for plasmid DNA delivery. Similarly, Tan et al in Langmuir vol, 22 No. 8, 2006, 3744-3750 describe complexes of PEO-b-PDEA copolymers with plasma DNA. Neither of these references discuss the formation of complexes with smaller strands of nucleic acid.

Amphiphilic block copolymers for nucleic acid delivery

Abstract: Methods of forming vesicles and methods of delivering nucleic acid, in particular, iRNA into cells, are also provided.


Formulations and processes for shelf-stable, gelled, gelatin confections which have a texture akin to gelatin dessert gels.

Recently it has been known to produce gelatin gels of somewhat firmer texture for use as snack items. These snacks, known as JELL-O.RTM. gelatin JIGGLERS.TM. are made by increasing the weight of the gelatin dessert mix which is combined with a given quantity of boiling water by about 60%. These JIGGLERS.TM. gelatin snacks have a short, somewhat more firm texture than gelatin dessert gels, but are neither room temperature stable in terms of resistance to microbiological growth nor free from melting at room temperature.
It is also known to produce gelatin-containing candies, the candies known as GUMMY BEARS.TM. being both microbially-stable and non-melting at room temperature, have a tough and chewy texture which is unlike the texture of gelatin desserts and there is little meltaway sensation.


A method and apparatus for reducing noise correlation in a partial response channel through optimization of a look-ahead maximum likelihood (ML) detector. In the method of the present invention, the ML detector is optimized in light of the noise correlation generated by the partial response channel. The improved ML detector provides comparable performance to, or better performance than, a Viterbi detector in the presence of colored noise. In the present invention, a set of finite impulse response (FIR) transversal filters are used as the ML estimator for the look-ahead detector. The weighted sum outputs of the FIR filters are compared to a set of thresholds based on previously detected data to make the decision for current detection. The present invention improves the ML detector's performance and reduces its complexity by optimizing the coefficients of the FIR filters in the presence of the correlated or colored noise. The SNR (signal-to-noise ratio) of each FIR filter is determined for a range of coefficients based on the noise autocorrelation of the channel for a given user density, and the coefficients providing the highest SNR are selected for each decision function. The result is a noise whitening ML detector providing improved performance and lower complexity than prior art ML detectors.

1. Field of the Invention
The present invention relates to the field of signal processing in a channel, and, in particular, to signal processing in a partial response channel.
2. Background
In magnetic recording devices, such as magnetic disks and tapes, a recording head is used to read and write information to and from a magnetic surface. In a typical rotating medium-based storage system, data is stored on magnetic disks in a series of concentric "tracks." These tracks are accessed by a read/write head that detects variations in the magnetic orientation of the disk surface. The read/write head moves back and forth radially on the disk under control of a head-positioning servo mechanism so that it can be selectively positioned over a selected one of the tracks. Once in position over a track, the servo mechanism causes the head to trace a path that follows the center line of the selected track.
Generally, the inductive recording head consists of a slit toroid made up of high permeability magnetic material and wound by several conductor turns. The toroid contains a gap which is positioned over the data tracks on the magnetic recording surface. To record, a current is generated through the conductor windings, altering the magnetic field in the toroid. At the location of the gap, the amplitude of the magnetic field is large enough to record on the magnetic material of the storage device to a sufficient depth. The amplitude of the magnetic field falls off sharply away from the gap.
By manipulating the current through the conductor windings, the magnitude and direction of the magnetic flux at the location of the gap can be modulated in such a fashion as to encode information into the magnetic surface of the storage device. A pattern of external and internal fields are created as the head and recording surface are moved relative to each other. These patterns are similar to a series of bar magnets of changing polarities. The polarity transitions are then readable as transitions in the magnetic flux at the recording surface. In read mode, as the magnetic storage surface moves across the gap in the head, the magnetic field of the storage surface is detected at the gap, and a voltage is induced in the coil proportional to the rate of change of the flux. The read channel then processes this analog voltage signal, typically converting the flux transitions into a series of pulses, and converts the analog signal into digital data.
Magnetic storage devices sometimes use analog peak detection to process incoming read signals. However, as recording density, or "user density" (Du), increases the analog peak detection scheme becomes unreliable because of the large amount of inter-symbol interference (ISI) between adjacent pulses. Alternatively, a partial response maximum likelihood (PRML) channel can be used to increase the user density. However, this method requires very good equalization of the read signal to shape the read signal into the desired partial response (PR) target waveform.
User density (D.sub.u) is a measure of how the pulse width relates to the data rate in the form of a ratio of the analog signal pulse-width at 50% magnitude over the length of the data period. A higher user density means that signal pulses resulting from read transitions are spread over a larger number of clock cycles, increasing the interaction or overlap of adjacent pulses, and resulting in greater ISI.
A partial response channel does not remove ISI from the channel signal. Instead, the signal is equalized to provide a target pulse waveform having predefined values at specific sampling instants. The effects of ISI on the target pulse waveform are predicted and incorporated into a pulse detection scheme which determines the occurrence of a signal pulse based on the sample history of the waveform and model waveform prediction. The history of the sample waveform is matched to a set of model waveforms, and the most likely model waveform is used to decode the signal into binary data. Hence, it is often referred to as "maximum likelihood" detection.
Partial response channels are therefore more robust than analog peak detectors in the presence of ISI. However, as described below, a problem exists in PR channels due to the equalization required to generate the target pulse waveform, as well as the process used to generate a signal metric for determining the most likely waveform. The PR equalizer and ML estimator used to generate the signal metric each serve to correlate noise in the channel. As a result, ML detector performance is impaired by a reduction in signal-to-noise gain.
The most commonly used maximum likelihood (ML) detector is the Viterbi detector, which is optimized for detection of signals in the presence of white noise. It is, however, somewhat complicated to implement especially for higher orders of PR channels (e.g. EPR4, EEPR4) and very inefficient for parallel/pipeline implementation architectures. Furthermore, its performance degrades as the noise become correlated. Look-ahead ML detector hardware requirements are usually less than that for a Viterbi detector, and look-ahead detectors are more suitable for parallel/pipeline implementation. However, the performance of look-ahead ML detectors is usually inferior to a Viterbi detector.
Look-ahead detectors are described in A. M. Patel's article "A New Digital Signal Processing Channel of Data Storage Products," Digest of the Magnetic Recording Conference, June 1991, pp. E6-E7; in A. M. Patel, et al., "Performance Data for a Six-Sample Look-Ahead (1.7) ML Detection Channel," IEEE Transactions on Magnetics, vol. 29, no. 6, pp. 4012-4014, November 1993; and in Patel's U.S. Pat. No. 4,945,538. A look-ahead detector is also described in U.S. Pat. No. 5,311,178 to T. Pan and R. G. Yamasaki.
The Patel and Pan/Yamasaki channels use partial response signaling to limit the number of isolated pulse non-zero samples. The Patel channel is equalized to EPR4 with three non-zero samples, and the Pan/Yamasaki channel is equalized to EEPR4 (or E.sup.2 PR4) where the four non-zero samples, .alpha., .beta., .beta. and .alpha., are 1, 3, 3 and 1, respectively. Both channels use the (1,7) RLL code to simplify signal detection.
Run-length limited (RLL) codes are useful because they place upper and lower bounds on the number of clock cycles occurring between transitions. The upper bound is very important because clock recovery is based on the occurrence of these transitions. For example, a long train of zeros in a data sequence produces no transitions and the clock recovery circuit has no input pulse with which to synchronize its tracking. In this situation, the data recovery timing might drift out of phase. RLL codes ensure that sufficient transitions occur for the clock recovery circuit to maintain the correct timing phase and frequency. Also, by maintaining the lower bound on the number of zeros between consecutive ones, signal pulses in the read channel are separated to reduce the intersymbol interference (ISI) caused by interaction between adjacent signal pulses.
The (1,7) RLL code is characterized by a minimum of one "0" and a maximum of seven "0's" between consecutive "1's". In the modified non-return-to-zero (NRZI) format, where each "1" is represented by a transition, and each "0" is represented by the lack of a transition, the (1,7) RLL code is sufficient for clock recovery purposes. Further, by maintaining the minimum of one "0" between consecutive "1's", transitions are separated so as to be differentiable from one another.
FIG. 1 illustrates, with solid curve 100, an isolated Lorentzian pulse equalized and sampled for EEPR4, and a minimum distance error event shown as a dashed curve 101. The pulse is the result of applying a positive unit step transition, e.g. a transition from a magnetic read head, to a (1-D)(1+D).sup.3 channel (EEPR4). The circles on solid waveform 100 show the isolated pulse samples for EEPR4. Samples of minimum distance error event 101 are indicated by diamonds. Minimum distance error event 101 is equivalent to the isolated pulse (100) shifted by one code period in time.
In most ML detectors, including the Viterbi detector, the square of the Euclidean distance between two sequences is often used as the signal metric. The Euclidean distance is defined as the square root of the sum of the squared error terms between two waveforms at each sampling instant. The squared Euclidean distance error of a sample combination is defined as: ##EQU1## where ya, yb, yc, yd and ye are the expected values for the model waveform; y.sub.0, y.sub.1, y.sub.2, y.sub.3 and y.sub.4 are consecutive sample values; and d.sub.i is the sample error at y.sub.i.
In FIG. 1, the isolated pulse waveform 100 and the minimum distance error event 101 have sample errors of values 0, 1, 2, 0, 2 and 1 for samples y.sub.M1, y.sub.0, y.sub.1, y.sub.2, y.sub.3 and y.sub.4, respectively, where y.sub.M1 is referred to as a look-back sample. The squared Euclidean distance between sampled waveform 100 and the minimum distance error event 101 is labeled d.sub.MIN.sup.2. d.sub.MIN.sup.2 is equal to the sum of the squares of these values, which adds up to a value of 10.
In the ML detector of U.S. Pat. No. 5,311,178, thresholds for each decision function are determined by minimizing the error between an expected sample model waveform and the nearest valid sample model waveform. For this reason, the thresholds for each function are dependent on the present state, as the next valid states are determined by the present state.
In the calculation of the Euclidean distance for use as a signal metric, for a first model waveform to be selected over a second model waveform, EQU E.sub.1.sup.2 -E.sub.2.sup.2 <0 [2]
where E.sub.1.sup.2 is the squared Euclidean distance between the first model waveform and the sampled signal, and E.sub.2.sup.2 is the squared Euclidean distance between the second model waveform and the sampled signal. The squared terms of the sampled signal are canceled out to yield a linear decision function. This will generate the following threshold decision: EQU (ya.sub.2 -ya.sub.1)y.sub.0 +(yb.sub.2 -yb.sub.1)y.sub.1 +(yc.sub.2 -yc.sub.1)y.sub.2 +(yd.sub.2 -yd.sub.1)y.sub.3 +(ye.sub.2 -ye.sub.1)y.sub.4 <(ya.sub.2 -ya.sub.1)(ya.sub.2 +ya.sub.1)+. . . +(ye.sub.2 -ye.sub.1)(ye.sub.2 +ye.sub.1) [3]
where y.sub.0, y.sub.1, y.sub.2, y.sub.3 and y.sub.4 are the actual sample values; ya.sub.1, yb.sub.1, yc.sub.1, yd.sub.1 and ye.sub.1 are the expected values for the first model waveform; and ya.sub.2, yb.sub.2, yc.sub.2, yd.sub.2 and ye.sub.2 are the expected values for the second model waveform.
For the sample points at which the model waveforms are equal, the products including the factor (yk.sub.2 -yk.sub.1), where k is the associated sample point, are canceled. In the negative phase, i.e. for negative transitions, the thresholds are the same, but the inequalities are reversed and the decision functions are multiplied by "-1".
The peak check decision functions from FIG. 5A of U.S. Pat. No. 5,311,178 are shown below for .alpha.=1 and .beta.=3. Fw (Fz in the patent) is normalized with a sign change. EQU a. Fx=Fy=0.5y.sub.0 +y.sub.1 -y.sub.3 [ 4] EQU b. Fw=0.5y.sub.0 +y.sub.1 -0.5y.sub.3 +0.5y.sub.4 [ 5]
y.sub.0, y.sub.1, y.sub.2, y.sub.3 and y.sub.4 are sequential code rate sample values. The linear equations Fx, Fy and Fw have sample values that are multiplied by coefficients which maximize the detection threshold between all possible signal waveform patterns and their minimum distance error waveforms. For example, each decision function (Fx, Fy, etc.) can be represented by the following equation: ##EQU2## where c.sub.i are the coefficients chosen to maximize detection, and k is the number of samples used in the ML detection scheme.
From equation [6], it can be shown that each decision equation has the same form as an FIR filter. Therefore, the detected noise and the detector noise bandwidth are affected by the decision function. Further, in the prior art, decision functions are designed under the assumption that the noise at the sampled input of the detector is additive white Gaussian noise (AWGN). However, partial response channels comprise filter and equalizer components for shaping the input waveform to the target PR pulse. The PR equalizer, in particular, typically supplies high frequency boost to provide pulse-slimming of the input pulse.
The filter and equalizer components in the PR channel shape the noise of the system in the same manner as the input pulse, thereby coloring, or correlating, the input noise according to the filter and equalizer frequency response functions. The target pulse signal at the input of the detector thus contains a noise component that is no longer white in nature, but has an effective noise bandwidth. For this reason, performance of the decision functions within the detector is reduced due to the correlation of noise. A partial response channel is desired that achieves optimum decision performance in the presence of colored noise.

Method and apparatus for reducing noise correlation in a partial response channel


An exposure apparatus and method exposes a substrate via a projection optical system and a liquid supplied to an immersion area below the projection optical system. First and second movable members move below the projection optical system. The first movable member has a mount area that mounts a substrate located in a hole of an upper surface of the first movable member. The upper surface outside the hole can maintain at least a part of the immersion area outside the substrate mounted in the hole. A drive system drives the first and second movable members to move the first and second movable members below the projection optical system relative to the liquid immersion region to replace one member positioned below the projection optical system with the other member such that the liquid immersion area is maintained below the projection optical system.

1. Field of the Invention
The present invention relates to exposure apparatus, and device manufacturing methods, and more particularly to an exposure apparatus used in a lithography process where electronic devices such as semiconductor devices, liquid crystal display devices, or the like is manufactured, and a device manufacturing method that uses the exposure apparatus.
2. Description of the Related Art
In a lithography process for producing electronic devices such as semiconductor devices (integrated circuits), liquid crystal display devices, or the like, projection exposure apparatus are used that transfer the image of a pattern formed on a mask or a reticle (hereinafter generally referred to as a 'reticle') via a projection optical system onto each of the shot areas of a photosensitive substrate (hereinafter referred to as a 'substrate' or a 'wafer') such as a wafer, a glass plate, or the like whose surface is coated with a resist (photosensitive agent). As this type of projection exposure apparatus, conventionally, a reduction projection exposure apparatus by a step-and-repeat method (the so-called stepper) has been frequently used. However, recently, a projection exposure apparatus by a step-and-scan method (the so-called scanning stepper) that performs exposure by synchronously scanning the reticle and the wafer is also gathering attention.
The resolution of the projection optical system equipped in the exposure apparatus becomes higher when the wavelength (hereinafter also referred to as 'exposure wavelength') of the exposure light used becomes shorter, or when the numerical aperture (NA) of the projection optical system becomes larger. Therefore, the exposure wavelength used in the projection exposure apparatus is becoming shorter each year due to finer integrated circuits, along with the increase in the numerical aperture of the projection optical system. The exposure wavelength currently mainly used is 248 nm of the KrF excimer laser, however, a shorter wavelength of 193 nm of the ArF excimer laser has also been put to practical use.
In addition, along with resolution, depth of focus (DOF) is also important when exposure is performed. Resolution R and depth of focus 8 can be expressed as in the equations below.R=k1·λ/NA  (1)δ=k2·λ/NA2  (2)
In this case, λ is the exposure wavelength, NA is the numerical aperture of the projection optical system, and k1 and k2 are process coefficients. From equations (1) and (2), it can be seen that when exposure wavelength λ is shortened and numerical aperture NA is enlarged (increased NA) to increase resolution, depth of focus δ becomes narrow. In a projection exposure apparatus, when exposure is performed, an auto-focus method is used to make the surface of the wafer match the image plane of the projection optical system. Accordingly, it is desirable for depth of focus δ to have a certain amount of width. Therefore, methods have been proposed in the past to substantially widen the depth of focus, such as the phase shift reticle method, the modified illumination method, the multi-layer resist method, and the like.
As is described above, in the conventional projection exposure apparatus, the depth of focus is becoming narrow due to the shorter exposure wavelength and the increased numerical aperture. And, in order to cope with higher integration, the exposure wavelength is presumed to be shorter in the future. If such a situation continues, the depth of focus may become so small that margin shortage may occur during the exposure operation.
Therefore, as a method of substantially shortening the exposure wavelength while increasing (widening) the depth of focus when compared with the depth of focus in the air, an immersion exposure method (hereinafter also appropriately referred to as 'immersion method') has been proposed. In the immersion method, resolution is improved by filling the space between the end surface of the projection optical system and the wafer surface with liquid such as water or an organic solvent to make use of the fact that the wavelength of the exposure light in the liquid becomes 1/n of the wavelength in the air (n is the refractive index of the liquid which is normally around 1.2 to 1.6). In addition, in the immersion method, the depth of focus is substantially increased n times when compared with the case where the same resolution is obtained by a projection optical system (supposing that such a projection optical system can be made) that does not employ the immersion method. That is, the depth of focus is substantially increased n times than that in the air.
However, in the case the immersion method above is merely applied to a projection exposure apparatus by the step-and-repeat method, the liquid spills from the space between the projection optical system and the wafer when the wafer is moved in between shots by a step movement to the exposure position for the next shot area after exposure of a shot area has been completed. Therefore, the liquid has to be supplied again, and the recovery of the liquid could also be difficult. In addition, in the case when the immersion method is applied to a projection exposure apparatus by the step-and-scan method, because exposure is performed while moving the wafer, the liquid has to be filled in the space between the projection optical system and the wafer while the wafer is being moved.
Considering such points, a proposal has been recently made on 'an invention related to a projection exposure method and a unit where a predetermined liquid flows along the moving direction of a substrate, so that the liquid fills in the space between the end portion of an optical element on the substrate side of a projection optical system and the surface of the substrate when the substrate is moved in a predetermined direction,' (for example, refer to patent document 1 below).
Besides such a proposal, as a proposal for improving resolution as in the immersion exposure method, a lithography system is known that places a solid immersion lens in the section between a projection lithography lens system (projection optical system) and a sample (for example, refer to patent document 2 below).
According to the invention disclosed in patent document 1 below, exposure with high resolution and a larger depth of focus than the depth of focus in the air can be performed by the immersion method, and the liquid can also be filled in the space between projection optical system and the substrate in a stable manner, or in other words, can be held, even when the projection optical system and the wafer relatively moves.
However, in the invention disclosed in patent document 1 below, because the supply piping, the recovery piping, and the like are arranged outside the projection optical system, the degree of freedom is limited for peripherals such as sensors of various kinds like a focus sensor or an alignment sensor that have to be arranged around the projection optical system.
In addition, in the invention according to patent document 1 below, in the case there is a flow in the liquid filled in the space between the projection optical system and the substrate, when the liquid is irradiated by the exposure light on exposure, temperature inclination or pressure inclination relative to the direction of the flow may occur within the projection area of the pattern in the space between the projection optical system and the substrate. Especially when the space in between the projection optical system and the substrate is large, or in other words, the layer of liquid is thick, such temperature inclination or pressure inclination could be the cause of aberration such as inclination of image plane, which could lead to partial deterioration in the transfer accuracy of the pattern, which in turn could be the cause of deterioration in the line width uniformity of the transferred image of the pattern. Accordingly, the layer of liquid is preferably thin. However, in this case, the space in between the projection optical system and the substrate becomes narrow, which makes it difficult to arrange a focus sensor.
In addition, in the invention according to patent document 1 below, it is difficult to recover the liquid completely, and the probability was high for the liquid used for immersion to remain on the wafer after exposure. In such a case, temperature distribution in the atmosphere or a refractive index change in the atmosphere occurs by the heat of vaporization generated when the remaining liquid evaporates, and these phenomena could be the cause of measurement errors in a laser interferometer system that measures the position of the stage on which the wafer is mounted. Furthermore, the remaining liquid on the wafer could move to the back of the wafer, which could make the wafer stick to the carrier arm and difficult to separate.
Meanwhile, in the lithography system according to patent document 2 below, the distance between the solid immersion lens (hereinafter shortened appropriately as 'SIL') and the sample is maintained at around 50 nm or under. However, in the lithography system in the near future whose target is to transfer and form a fine pattern onto a sample (such as a wafer) at a line width of around 70 nm or under, when an air layer whose thickness is 50 nm exists between the SIL and the sample, it becomes difficult to obtain sufficient resolution in the image of the fine pattern referred to above. That is, in order to obtain sufficient resolution in the fine pattern above, the distance between the SIL and the sample has to be maintained at a maximum of 30 nm or under.
However, in the lithography system according to patent document 2 below, because a configuration using air bearings is employed to maintain the distance between the SIL and the sample, it is difficult to obtain sufficient vibration damping due to the nature of air bearings. As a result, the distance between the SIL and the sample could not be maintained at 30 nm or under.
As is described, in the conventional examples disclosed in patent documents 1 and 2 below and the like, various points are found that should be improved.
Patent Document 1: the pamphlet of International Publication Number WO99/49504
Patent Document 2: the description of U.S. Pat. No. 5,121,256

Exposure apparatus and device manufacturing method


A film cartridge has ah interior spring that first engages the leader of a filmstrip as the leader is initially wound into the cartridge housing and then is distorted from its original shape by further movement of the leader into the housing. When a door connected to the cartridge housing is closed, the spring is maintained distorted in engagement with the leader,opening the door frees the spring, allowing the spring to propel the leader from the cartridge housing by recovering its original shape.

1. Field of the invention
The invention relates generally to the field of photography, and in particular to film cartridges. More specifically, the invention relates to a film cartridge that is capable of propelling or thrusting a film leader from inside to outside the cartridge housing.
2. Description of the Prior Art
Commonly assigned, prior art U.S. Pat. No. 5,046,682, issued Sep. 10, 1991, discloses a film cartridge in which a film roll whose outermost convolution is a film leader is coiled about a spool rotationally supported inside the cartridge housing. A pair of flexible, independently rotatable flanges are coaxially arranged on the spool to radially confine the film leader within respective skirted peripheries of the flanges to prevent the leader from substantially contacting an interior wall of the cartridge housing. A stripper projecting from the interior wall is received between a leading end of the film leader and the next-inward convolution of the film roll to free the leader from the flanges and guide it into a lighttight passageway out of the cartidge housing responsive to rotation of the spool in a film unwinding direction. The stripper frees the film leader from the flanges by inducing the leader to flex the flanges away from each other at their skirted peripheries during unwinding rotation of the spool.


Telephone exchange with associated voice mail device is connected to a calling subscriber after a predetermined time if the called subscriber does not answer the call, as well as method to store such voice messages in such a device, whereby the voice mail device is able to store voice messages arriving from the calling subscriber and intended for the called subscriber and to send them to the called subscriber on his request. The telephone exchange comprises means which will also connect all further calls for the called subscriber to the voice mail device as soon as one switch-over after timeout of the called subscriber to the voice mail device has been executed. Hence, the exchange recognizes that the called subscriber is not ready to speak and switches all further arriving calls to the voice mail device.

Telephone exchanges with speech storage equipment are already known and are mostly called voice-mail equipment in the profession. Such voice mail devices are very explicitly described by EP 0,087,849 and EP 0,336,524, for example. A method and a device for storing telephone messages in a private telephone branch exchange are also known from EP 0,304,653.
The task of these devices is for called subscribers, who cannot be reached at the moment, to initiate a fixed call transfer to the voice mail device, or for the device to initiate a call transfer after a predetermined waiting time, if the called subscriber does not answer the call.
If a call is transferred to the voice mail device and it answers the call, the telephone set signals the number of the called subscriber by means of Dual Tone Multiple Frequency (DTMF) signals, which automatically connect the calling subscriber with the personal mailbox of the called subscriber and allows him to record his voice message.
Exchange installations with call transfer have been known for a long time. All the devices in these installations are reset to their starting condition after the voice connection is terminated. As mentioned, if the called subscriber has not activated a call transfer to the voice mail device, the call transfer of a new call is only activated after a predetermined time has passed.
The known devices have the disadvantage that if the subscriber is not ready to answer, each new call first reaches the subscriber station and is only connected with the voice mail device if the receiver of the called subscriber's telephone set has not been lifted or answered within the predetermined waiting time. This is considered to be disturbing to other persons who are present in the room at that time. In addition, the time span before the call is connected passes without being used by the calling subscriber, i.e., in a wasteful manner.


A computer program product for accessing a database is a program product for accessing a database by allowing a computer to execute a plurality of screen components, including a step of designating order of the plurality of screen components to be executed by the computer. Each of the plurality of screen components includes: a step of generating a part except for a “where” clause in an SQL statement in accordance with definition given from the outside for each screen component; a step of generating a screen for inputting and/or outputting data; and a step of generating the “where” clause in the SQL statement in accordance with definition given from the outside for each screen component. Since the screen component as a part of the database access program processes the steps in accordance with definition given from the outside, the screen component can be used by another database access program. Thus, general versatility is obtained and development efficiency is improved.

1. Field of the Invention
The present invention relates to a computer program product for accessing a database, a computer-readable recording medium in which the program is recorded, and a database operating method. More particularly, the present invention relates to a database access program product which can be easily applied to a process adapted to business operations, a computer-readable recording medium in which the program is recorded, and a database operating method.
2. Description of the Background Art
Conventionally, in system development using a computer, reduction in development cost, shortening of delivery, and improvement in quality are important subjects. In order to achieve the subjects, attempts such as shift from a design method centering on procedures to a design method centering on data, introduction of an RAD (Rapid Application Development) method, and component programming have been made and certain effects are obtained.
For example, productivity is largely improved by introduction of a design development method centering on data. According to the RAD method, a development cycle can be shortened by building a prototype in accordance with a request of the user, recognizing the request of the user more specifically on the basis of a result of the prototyping, and correcting the prototype. As a result, in a system in which the RAD method is introduced, mainly, shortening of the periods of external designing and detailed designing and reduction in cost can be achieved. As a result, the proportion of the phase of program generation is becoming relatively large in the whole system development.
Recently, the number of cases of employing an intranet for a development platform of a backbone system of a company is increasing. In a networked company, it is efficient to construct a backbone system by using an application server. Typically, in system development of an application server, a tag language which is an extension of the HTML (HyperText Markup Language) is used. The tag language is easy to learn and is evaluated as an intranet development tool with high productivity.
However, as the environments of companies are becoming tougher, requirements for system development are becoming higher. Concretely, as the business cycle of a company is being shortened, further shortening of delivery is requested. A company capable of providing a product at lower cost is advantageous.
Since the proportion of the phase of program generation in system development is becoming relatively large, it is important to improve the productivity in the phase. It seems to be most efficient to promote component programming.
The component programming decreases the number of processes necessary for system development and contributes to enhancement of competitiveness of system development from the viewpoints of reduction in a period necessary for the system development and reduction in the cost of the system development. By using only a sufficiently reliable program as a component, the component programming can contribute to improvement in quality of a system. Therefore, it is important to perform component programming efficiently and built an application program by efficiently combining components prepared by the component programming.
However, the function of component programming of the tag language conventionally used for development of an intranet system is weak. Consequently, as long as the conventional tag language is used as it is, it is obvious that improvement of productivity cannot be expected so much.
FIG. 18 is a block diagram showing the configuration of a general system of an intranet using a database (DB). Referring to FIG. 18, a general intranet 600 includes an application server 612, a DB server 614 and a plurality of client PCs 616 which can perform communication with each other via a network 610 by using a protocol called HTTP (Hyper Text Transfer Protocol).
On client PC 616, a general browser 630 operates.
On DB server 614, an RDBMS (Relational DataBase Management System) 622 operates.
On application server 612, a WWW server 618 operates. The "WWW" is an abbreviation of "World Wide Web". The substance of WWW server 618 is a Java (R) servlet engine 620. Java (R) servlet engine 620 supplies information (HTML source) for forming a screen used to access RDBMS 622 to browser 630 in accordance with a request given from browser 630 of client PC 616 via network 610. Browser 630 displays the screen and returns information entered by the user to Java (R) servlet engine 620. Java (R) servlet engine 620 accesses RDBMS 622 in accordance with information given and returns the HTML source for displaying a result to browser 630. Browser 630 displays the result, thereby responding to the request of the user.
In such a manner, intranet 600 processes requests from the plurality of client PCs 616 by WWW server 618 which operates on application server 612 and returns the result to the browser on each client, thereby performing a business process using RDBMS 622.
In the case of developing a program adapted to a number of business operations, screens to be displayed on the browser have to be generated one by one. In this case, by copying a necessary part in a business program generated and modifying only different parts, another business program can be generated. However, in the case where a bug is found in the original business program, all of the generated business programs have to be checked in order to remove the bug.
In order to avoid the problem, a component common to business programs is used as a module and called as a so-called subroutine. In the case of using the common component as a module, it is sufficient to correct only the module including the bug and it is unnecessary to correct a higher-order business program using the module.
However, a program is conventionally designed in modules on the unit basis of a series of processes for accessing RDBM 622, such as a process for displaying a screen used to input conditions for access, a process of accessing RDBMS 622 on the basis of the inputted conditions, and a process of displaying data obtained as a result of the access. When a series of processes is designed as a module, the use of the module is limited to the series of the processes and a problem such that general versatility cannot be obtained occurs.
Although it is also possible that a series of processes is divided into a plurality of parts and the parts are respectively modularized in order to give general versatility, the number of the modules generated increases and it causes a problem such that efficiency of generating a business program deteriorates.

Computer program product for accessing database, recording medium recording database access program therein, and database access method


The present invention provides an external apparatus connected to an imaging apparatus over a network, the imaging apparatus including an imaging unit which captures an image of a vessel being a subject, the external apparatus including an obtaining unit which obtains image data including the vessel captured by the imaging unit, a display unit which displays the image data, an analyzing unit which extracts vessel estimation information regarding an arbitrary vessel included in the image data based on the image data, a receiving unit which receives vessel information based on a wireless communication from the vessel, and a comparing unit which compares the vessel estimation information and the vessel information, wherein, in a case where the vessel estimation information and the vessel information are not matched, the display unit displays a warning in addition to the image data.

For purpose of prevention of nuisance, smuggling, and illegal entries of suspicious vessels, visual vessel monitoring has been performed in the past. However, visual vessel monitoring has a problem of poor visibility under a bad weather or during night time. Many vessels passing through a narrow strait may cause a state of intensive congestion, because of which it is difficult to sufficiently monitor all vessels entering into a predetermined field of view.
In order to solve the problem, for example, PTL 1 discloses a technology for aiding visual monitoring by using a translucent display apparatus to present vessel information regarding a radar or an automatic ship identification system (hereinafter, AIS) to the field of view of a human who is performing vessel monitoring. This technology can facilitate visual vessel detection under conditions with poor visibility.
An AIS (automatic ship identification system) is a mechanism for mutual communication of the type of vessel, the position of a vessel, a course, a speed, a destination, a cargo, etc. by using radio waves in a VHF band between neighboring vessels and a land station for safe sailing of vessels on the ocean.


A personal safety and security light used to deter aggressors, visually and audibly alert people within proximity, and illuminate surrounding areas. The personal safety and security light includes a casing, a plurality of lights, a microcontroller, a sound emitting device, a power supply and a trigger. The plurality of lights is externally mounted on the casing to illuminate the surround area from the casing. The sound emitting device audibly alerts nearby people for help or intervention. The microcontroller conducts power from the power supply to the plurality of lights and the sound emitting device when the trigger completes the circuit. The microcontroller controls the duration, intensity and sequence pattern for the plurality of lights and the sound emitting device. The trigger toggles the circuit open or closed to actuate the microcontroller that begins the sequence for the plurality of lights and the sound emitting device.

Many attacks occur using the cover of darkness during non-daylight hours. Aggressors believe it's easier to prey on their victims in low light areas, making it hard to identify them or having a more subtle approach to the victim. A need for a personal safety device that allows for users to protect themselves from aggressors that may be more physically capable than they are is necessary. Personal security devices give you peace of mind and protect you when needed. Personal security devices need to be small enough to fit into your personal life so that they can be carried anytime and anywhere. There are several means of protection that are intended to be used when the aggressor strikes, such as pepper spray, electric shock devices, or other implements to fend off the aggressor as they are assaulting there victim. Most methods are used when the aggressor is striking and may not be accessible or may be obvious to the aggressor when drawn. Extremely bright light has been proven to be an effective non-lethal and legal "weapon" to temporarily blind an aggressor and in order to get away or draw attention from rescuers. A very bright light disorients and readjusts the aggressor's vision in the cover of darkness and illuminating the area to increase the odds of identifying the aggressor.
Therefore, it is an object of this invention to present a device that allows the user to conceal a portable alarm device that deters aggressors before or during an attack through the use of light and sound. The personal safety and security light is golf-ball sized and has a rip-cord, which doubles as a key chain. If the rip-cord is pulled an internal timer is triggered and within seconds about a dozen super bright light emitting diode (LED) lights spread throughout the outside of the ball, blasting blinding light with incredible brightness. That light can be used against oncoming aggressors to blind them and also to cause attention alerting bystanders to come for rescue, decreasing the risk of an attack and increasing the odds of evading the aggressor.


An improved method for compiler support of garbage collection. Live reference data to support a garbage collection process are stored in null operation instructions (NOPs) of an instruction set within the native code. This allows the live reference information to be encoded near the call instruction and thus the information can be retrieved in constant time. This may decease the amount of processing resources required for garbage collection.

The random access memory (RAM) of a computing system is typically a fixed-size resource. The RAM must be managed properly to maintain system performance. In run-time environments (e.g., JAVA) the memory management is handled by the system. Memory management includes a process known as garbage collection, which is a process of recycling memory. When a computing program is running it allocates and uses portions of memory on an on-going basis. At some point the program may no longer need to use a particular portion of memory, for example, the memory was allocated for a particular purpose that is no longer relevant. The portions that are no longer being used (garbage) are identified (collected) so that they can be recycled for future use. When garbage collection begins, the garbage collection algorithm must determine all live objects. That is, the garbage collection process marks all objects that are currently being used by the program (live references) and all other objects are considered garbage. The garbage collector (GC) relies on the system compiler to provide a live reference enumeration root set, i.e., live reference information. To provide this information to the GC, the compiler must keep track of which objects should be added to, or deleted from, the live reference information. The live reference information is constantly changing because at different points of program execution some objects are being created and some are no longer used. Typically garbage collection occurs at the time of a function call (call) that requests new memory. A function call passes control to a subroutine and after the subroutine is executed, control returns to the next instruction in the main program. Therefore, to provide the live reference information to the GC, the compiler should be able to determine the live references at each call site. Typically, the compiler stores the live reference information by keeping a list of call sites with corresponding live reference information for each call site stored somewhere in memory. At compilation time, the compiler generates native code to be executed by the computing system and also stores a garbage collection map.
FIG. 1 illustrates a typical storage scheme for live reference information in accordance with the prior art. System 100, shown in FIG. 1, includes native code storage 105 and garbage collection information storage 110. Garbage collection information storage 110 includes method garbage collection information storage 111 that contains a list of all variables for the program and live reference information storage 112. The program contained in native code section 105 consists of a set of instructions, some of which are calls. When the program is being executed and a request for new memory is made (e.g., at a call), the GC inquires of the compiler for a list of live references at that point in the program. So, for example, native code storage 105 contains calls A, B, and C. When garbage collection takes place at one of these calls, the address of the call site at which garbage collection happened is provided to the compiler. The compiler must then go to live reference information storage 112 of garbage collection information storage 110 and traverse the list until the specific address is found. That is, the compiler has to search through the list of all call sites until it finds the one where garbage collection has occurred. At this point the GC has access to the live reference information to perform the garbage collection function.
Storing this information separately taxes the system's processing resources because the live reference information is obtained through a search of what may be a large list. The size of the list depends upon the number of calls in the method. Typically, the list may be indexed to reduce the information access time.

Method for providing garbage collection support

Abstract: The compiler determines which references are live at each call. The compiler may also determine the number of bits that may be used to store those references. In one embodiment the number of NOPs is sufficient to store the information. In an alternative embodiment, NOPs are artificially inserted to store the information. Because a sufficient number of NOPs are typically present anyway, the method of one embodiment of the present invention does not significantly increase the size of the code.


Inhibitors of parasitic dihydroorotate dehydrogenase enzyme (DHOD) are candidate therapeutics for treating malaria. Illustrative of such therapeutic agents include the compound:

The present invention relates to novel anti-malarial agents and inhibitors of dihydroorotate dehydrogenase.
Malaria is a disease that is prevalent in many developing countries. Nearly 40% of the world's population is at risk for contracting this disease, which has been a major cause of mortality throughout history. In the United States travelers to these endemic regions are at risk for contracting the disease. The widespread emergence of drug resistance in many tropical countries has compromised many of the current chemotherapies and there is a continued need for new chemotherapeutic approaches.
Malaria is a disease caused by a parasite transmitted by the bite of an infected female Anopheles mosquito. When an infecting sporozoite parasite enters the bloodstream it rapidly infects both liver and red blood cells and differentiates into merozoites. Asexual reproduction of the merozoite within erythrocytes results in the rupture and subsequent reinfection of other red blood cells. This cyclic process results in clinical symptoms, which include headaches, sweating, vomiting, malaise, delirium and acute fever and may be fatal if not treated. Malaria in humans is caused by 4 species of parasitic protozoa belonging to the genus Plasmodium. Of these, P. falciparum is the most deadly and the greatest threat to travelers abroad while P. malariae, P. vivax and P. ovale, though infrequently fatal in healthy adults, can cause morbidity in the endemic areas.
Various medications are presently used for the treatment of malaria. However, many of these medications are costly and some exhibit significant toxicity and undesirable side effects in humans. The most common drug for treating malaria is chloroquine. Other drugs include quinine, melfloquine, atovaquone/proguanil, doxycycline, artesunate, hydroxychloroquine, halofantrine, pyrimethamine-sulfadoxine, and primaquine. Drug choice often depends on one of the four types of malaria parasites.
Malaria parasites rely on de novo pyrimidine biosynthesis to provide precursors for DNA and RNA synthesis, hence for proliferation. The parasite does not have pyrimidine nucleoside or base salvage pathways, thus the enzymes in the de novo pathway are essential to parasite survival. In contrast, mammalian cells have salvage pathways that provide an alternative route to these essential metabolites.
Dihydroorotate dehydrogenase (DHODH) is an essential enzyme of the pyrimidine salvage pathway, and a number of lines of evidence suggest that it is an important target for the development of new chemotherapy against malaria. DHODH is a flavin-dependent mitochondrial enzyme that catalyzes the fourth reaction in the salvage pathway; coenzyme Q is utilized as the oxidant. The enzyme has a number of properties that make it a particularly strong candidate as a new drug target in the parasite Inhibitors of human DHODH have proven efficacy for the treatment of rheumatoid arthritis demonstrating that the target pathway can be effectively blocked in vivo. The X-ray structures of DHODH reveal that the inhibitor binding pocket of the enzyme is highly variable between species, providing a structural basis for the design of species-specific inhibitors.
A need exists for a method of treating malaria. There is also a need for an anti-malarial agent to overcome current drug resistance problems with existing therapy. Further, anti-malarial agents are needed that selectively inhibit malarial DHODH but exhibit no substantial toxicity against mammalian, especially human DHODH.
Accordingly, this invention provides novel potent anti-malarial agents and methodology of treating malaria using novel potent anti-malarial agents. The invention also provides potent anti-malarial agents that are selective inhibitors of P. falciparum dihydroorotate dehydrogenase and active against chloroquine-sensitive and resistant malarial strains.

This patent is subject to a terminal disclaimer.

Antimalarial agents that are inhibitors of dihydroorotate dehydrogenase

Abstract: and a triazolopyrimidine class of compounds that conform to Formula IX:

Abstract: and their solvates, stereoisomers, tautomers and pharmaceutically acceptable salts.

BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM


A dimmer and a lighting apparatus are provided. The dimmer apparatus includes a rectifier unit, a controller, a voltage divider and a voltage converter. The rectifier unit rectifies an AC power and generates a first operating voltage. The voltage divider outputs a voltage division of the first operating voltage. The controller integrates the voltage division to obtain an average voltage, and provides a pulse width modulation (PWM) signal based on the average voltage. The voltage converter drives a light emitting diode (LED), and adjusts a driving voltage and a driving current of the LED according to the PWM signal. Wherein, the controller also adjusts the PWM signal according to a feedback signal generated by the voltage converter.

1. Field of the Invention
The present invention relates to a dimmer apparatus. More particularly, the present invention relates to a dimmer apparatus adapted to a light-emitting diode lamp.
2. Description of Related Art
A dimmer apparatus is generally applied to a lighting apparatus for controlling a power supply, so that not only a light-emitting device (for example, a bulb) of the lighting apparatus can be turned on/off, but also a light-emitting effect of the lighting apparatus can be fine-tuned. FIG. 1 is a diagram illustrating a conventional lighting apparatus. Referring to FIG. 1, the lighting apparatus 100 includes a power supply 102, a dimmer 104 and a bulb 106. The power supply 102 provides an input voltage, wherein the input voltage can be an alternating current (AC) power. When a user adjusts a light-emitting effect of the bulb 106 through the dimmer 104, the dimmer 104 can provide a voltage according to a conducting condition, so as to fine-tune the light-emitting effect of the bulb 106. Further, regarding a circuit structure, the light-emitting device (for example, a conventional tungsten bulb) of the conventional lighting apparatus generally has a characteristic as that of a resistor.
With a general technology trend of energy-saving and carbon reduction, a light-emitting diode (LED) lamp gradually becomes a main option for the light-emitting apparatus. Therefore, based on a cost consideration, in the related art, the bulb 106 is replaced by the LED lamp, while the power supply 102 and the dimmer 104 are not changed. Though, regarding the circuit structure, the LED lamp generally has a characteristic as that of a capacitor, so that when the user adjusts the brightness of the LED lamp through the dimmer 104, after the AC power output from the power supply 102 is conducted through the dimmer 104, the voltage provided by the dimmer 104 may result in a flickering phenomenon of the LED lamp.

Cal-Comp Electronics & Communications Company Limited


A method and apparatus for producing a batch of mail items. A number of sheets are assembled to at least two documents, wherein at least two of the documents each contain at least two sheets. Each of the sheets in the batch is provided with a unique identification code unique to each sheet in the batch. The documents are assembled to one or more mail items. At least one unique identification code is read and the read unique identification codes are tested against a criterion. An error message is provided if the characteristic does not meet the criterion.

The invention relates to a method and an apparatus for producing a batch of mail items. The invention further relates to a method and an apparatus for providing identification codes. Further, the invention relates to a method and apparatus for generating identification codes. The invention also relates to a system for processing sheets into mail items and to a computer program.
From U.S. Pat. No. 4,800,505, a system and method for preparing a batch of mail items to be sent are known. The system comprises an apparatus for marking each mail item with a selected identification code. To this end, an identification code is provided on the main document of the item. The identification codes are cyclically sequential and thus define the order in which the items are processed. The system further has a detector for detecting the identification code provided and means for retrieving parameter values coupled to the identification code from a database. The retrieved parameter values are then used by the system to process the items. If an identification code is detected which does not correspond to the order, the system is stopped and an operator is alerted, so that he can correct the error.
A disadvantage of the known system is that, while it is true that errors in the order of the mail items can be detected, other errors, such as errors in the mail items themselves, are not detected.

System, apparatuses, methods and computer program for producing a batch of mail items and providing and generating identification codes


The present invention provides a liquid crystal display device which enables costs to be reduced, excels in productivity, and enables a high contrast ratio over a wide viewing angle range to be realized. The present invention is a liquid crystal display device including a first polarizer, a second-type (nx<ny≦nz) birefringent layer, a first λ/4 plate (nx>ny≧nz), a liquid crystal cell, a second λ/4 plate having an Nz coefficient different from the first λ/4, and a second polarizer in this order, wherein an in-plane slow axis of the first λ/4 plate forms generally 45 degrees as to an absorption axis of the first polarizer, an in-plane slow axis of the second λ/4 plate is generally orthogonal to the in-plane slow axis of the first λ/4 plate, an absorption axis of the second polarizer is orthogonal to the absorption axis of the first polarizer, an in-plane fast axis of the second-type birefringent layer is generally orthogonal to the absorption axis of the first polarizer, and black display is performed by aligning liquid crystal molecules within a liquid crystal layer in a manner generally perpendicular to substrate faces.

Liquid crystal display devices have widely been employed as display devices of various information processing apparatuses including computers and televisions. In particular, TFT type liquid crystal display devices (hereinafter, also referred to as "TFT-LCD") have come into widespread use, and further market growth is anticipated, leading to demand for further improvement in image quality. Hereinafter, description will be made with a TFT-LCD as an example, but the present invention is not restricted to this, and is applicable to liquid crystal display devices in general, and is applicable to, for example, passive-matrix liquid crystal display devices and plasma address liquid crystal display devices.
A system most widely heretofore employed in TFT-LCD has been a so-called TN (Twisted Nematic) mode wherein liquid crystals having positive dielectric anisotropy are horizontally aligned between substrates which face each other. Liquid crystal display devices according to the TN mode are characterized in that the alignment directions of adjacent liquid crystal molecules in one of the substrates are twisted 90 degrees as to the alignment directions of adjacent liquid crystal molecules in the other substrate. With such a TN mode liquid crystal display device, inexpensive manufacturing technology has been established, and industrially matured, but it has been difficult to realize a high contrast ratio.
On the other hand, there have been known liquid crystal display devices of a so-called VA mode wherein liquid crystals having negative dielectric anisotropy are vertically aligned between substrates which face each other. With the VA mode liquid crystal display devices, liquid crystal molecules are aligned in a direction generally perpendicular to the substrate faces when voltage is not applied, and accordingly, liquid crystal cells hardly exhibit any birefringence and optical rotation, so light passes through the liquid crystal cell with little change in the polarization state thereof. Accordingly, a pair of polarizers (linear polarizers) are disposed upward and downward of the liquid crystal cell so that absorption axes thereof are mutually orthogonal (hereinafter, also referred to as "Cross Nicol polarizer"), whereby substantially complete black display can be realized when no voltage is applied. When voltage equal to or larger than a threshold voltage is applied (hereinafter, simply abbreviated as "when voltage is applied"), liquid crystal molecules are inclined so as to be generally in parallel to the substrates, and exhibit large birefringence, so white display can be realized. Accordingly, such VA mode liquid crystal display devices can readily realize a very high contrast ratio.
With such a VA mode liquid crystal display device, when the inclination directions of liquid crystal molecules when voltage is applied are one direction, asymmetry occurs in the viewing angle property of the liquid crystal display device. Accordingly, an alignment division type VA mode, which is a so-called MVA mode (multi-domain type VA mode), is widely employed wherein the inclination directions of liquid crystal molecules are divided into multiple directions within a pixel, using architectural devising for pixel electrodes, or methods for providing alignment control means such as protrusions or the like within a pixel.
In the MVA mode, from the perspective of maximizing transmittance in a white display state, design is ordinarily made so that the axial direction of the polarizer and the inclination directions of liquid crystal molecules form an angle of 45 degrees. This is because transmittance when sandwiching a birefringent medium between Cross Nicol polarizers is proportional to sin2 (2α) when assuming that an angle that the axis of a polarizer and the slow axis of the birefringent medium form is α (units: rad). In a typical MVA mode, the inclination azimuthal directions of liquid crystal molecules may be divided into four domains of 45 degrees, 135 degrees, 225 degrees, and 315 degrees. Even in such an MVA mode wherein the inclination directions of liquid crystal molecules have been divided into four domains, Schlieren texture or alignment to an unintentional direction has frequently been observed at boundaries between domains or in the vicinity of alignment control means, causing transmittance loss.
In order to solve such a problem, a VA mode liquid crystal display device employing a circularly-polarizing plate has been studied (e.g., see PTL 1). According to such a liquid crystal display device, transmittance when sandwiching a birefringent medium between mutually orthogonal right and left circularly-polarizing plates does not depend on the angle that the axis of the polarizer and the slow axis of the birefringent medium form, and accordingly, even when the inclination azimuthal directions of liquid crystal molecules are other than 45 degrees, 135 degrees, 225 degrees, and 315 degrees, if the inclinations of the liquid crystal molecules can be controlled, desired transmittance can be secured. Accordingly, for example, a circular protrusion may be disposed in the center of a pixel to incline liquid crystal molecules to all azimuthal directions, or liquid crystal molecules may be inclined to a random azimuthal direction without completely controlling the inclination azimuthal directions thereof. Note that, within the present Specification, the VA mode employing a circularly-polarizing plate will also be referred to as circularly-polarized VA mode or circularly-polarized mode. On the other hand, a VA mode employing a linearly-polarizing plate will also be referred to as linearly-polarized VA mode or linearly-polarized mode. Also, a circularly-polarizing plate is typically, as well known, configured of a combination of a linearly-polarizing plate and a λ/4 plate.
Further, circularly-polarized light has a property that left handedness and right handedness are switched at the time of being reflected at a mirror or the like, and accordingly, for example, when disposing a left circularly-polarizing plate on a mirror to input light thereinto, the light which has transmitted through the circularly-polarizing plate and been transformed into left handed circularly-polarized light is reflected at the mirror, the light is transformed into right handed circularly-polarized light, the right handed circularly-polarized light thereof cannot transmit through the left circularly-polarizing plate, and consequently, it has been known that the circularly-polarizing plate has an antireflection optical function. The antireflection optical function of such a circularly-polarizing plate can prevent unnecessary reflection in the event of observing a display device in a bright environment such as outdoor or the like, and accordingly, it has been known that there is an effect to improve contrast ratio in a bright environment of a display device such as a VA mode liquid crystal display device. Here, the unnecessary reflection is considered to be primarily reflection due to a transparent electrode or metal wiring of a TFT device, existing within a display device. Unless this unnecessary reflection is prevented, even with a display device which realizes generally complete black display in a dark room environment, light amount at the time of black display of the display device increases when observing in a bright environment, and consequently, the contrast ratio deteriorates.
As described above, in the circularly-polarized VA mode employing a circularly-polarizing plate, a transmittance improvement effect and an unnecessary reflection prevention effect can be obtained, but with a conventional circularly-polarized AV mode liquid crystal display device, there is room for improvement in that the contrast ratio in an oblique view angle is low, and sufficient viewing angle property is not obtained. To this end, various viewing angle property improvement techniques employing a birefringent layer (retardation film) have been proposed. For example, PTL 1 has disclosed the following (A) method, PTL 2 has disclosed the following (B) method, PTL 3 has disclosed the following (C) method, PTL 4 has disclosed the following (D) method, and NPL 1 has disclosed the following (E) method.
(A) Method employing two λ/4 plates satisfying a relation of nx>ny>nz
(B) Method employing a combination of two λ/4 plates satisfying a relation of nx>ny>nz and one or two second-type birefringent layers satisfying a relation of nx<ny≦nz
(C) Method employing a combination of two λ/4 plates satisfying a relation of nx>nz>ny and a birefringent layer satisfying a relation of nx=ny>nz
(D) Method further employing a combination of one or two lambda/2 plates satisfying a relation of nx>nz>ny in the method in (C)
(E) Method employing a combination of two uniaxial λ/4 plates (so-called A plate satisfying a relation of nx>ny=nz), and a birefringent layer satisfying a relation of nx=ny>nz, and a birefringent layer satisfying a relation of nx>nz>ny
However, there has still been room for improvement in the viewing angle property even with the above (A), (B), and (C) methods. Also, with the above (C), (D), and (E) methods, there has been room for improvement in that there is needed a biaxial retardation film satisfying a relation of nx>nz>ny (satisfying a relation of 0<Nz<1) which is difficult to be manufactured and high in costs.
Therefore, the present inventor has studied various ways to solve the above problem, and has proposed the following (F) method (see PTL 5).
(F) Method employing a combination of two λ/4 plates, a third-type birefringent layer satisfying a relation of nx=ny>nz, a first-type birefringent layer satisfying a relation of nx>ny≧nz, and a second-type birefringent layer satisfying a relation of nx<ny≦nz
However, with the above (F) method, improvement in the viewing angle property is realized by optimally designing Nz coefficients (parameters representing biaxiality) of the two λ/4 plates, but under a design condition employing two general-purpose biaxial λ/4 plates satisfying a relation of nx>ny≧nz (Nz≧1.0), there is room for improvement regarding the viewing angle property.
Therefore, as a result of further study, the present inventor has found that a circularly-polarized VA mode liquid crystal display device whereby a high contrast ratio can be obtained over a wide view angle range can readily be manufactured by taking two λ/4 plates (first and second λ/4 plates) as biaxial λ/4 plates satisfying a relation of nx>ny≧nz, Nz coefficients thereof are adjusted to generally the same, and disposing a birefringent layer satisfying a relation of nx<ny≦nz at least between the first λ/4 plate and the first polarizer or between the second λ/4 and the second polarizer, and has previously filed a patent application of this (see PTL 6 and PTL 7).
Also, with regard to a circularly-polarizing plate manufacturing method, there has been disclosed a method for manufacturing a polarizing plate according to roll-to-roll lamination technology using a λ/4 plate having an in-plane slow axis in an oblique direction as to a flow direction (machine direction) (e.g., see NPL 2). According to this method, the Nz coefficient of the λ/4 plate can be controlled from 1.1 to 2.0.


An imaging system for performing forward scanning imaging for application to therapeutic and diagnostic devises used in medical procedures. The imaging system includes forward directed optical coherence tomography (OCT), and non-retroreflected forward scanning OCT. Also interferometric imaging and ranging techniques and fluorescent, Raman, two-photon, and diffuse wave imaging can be used. The forward scanning mechanisms include a cam attached to a motor, pneumatic devices, a pivoting device, piezoelectric transducers, electrostatic driven slides for substantially transverse scanning; counter-rotating prisms, and offset lenses are used for arbitrary scanning. The imaging system of the invention is applied to hand held probes including probes integrated with surgical probes, scalpels, scissors, forceps and biopsy instruments. Hand held probes include forward scanning lasers. The imaging system is also applicable to laparoscopes and endoscopes for diagnostc and therapeutic intervention in body orifices, canals, tubes, ducts, vessels and cavities of the body. The imaging system includes application to surgical and high numerical aperture microscopes. An important application of the invention is implantation of the optical probe for periodic or continuous extraction of information from the tissue site where implanted.

This invention relates generally to the field of optical imaging and more specifically to the field of optical image guided procedures.
There is a pressing need for new high-resolution (xcx9c10 xcexcm) imaging and visualization technology across a wide range of fields including medicine, medical and biological research, and materials and packaging research, development, and manufacturing. Improved visualization can enable new diagnostic capabilities such as in diagnostic screening of the esophagus for adenocarcinoma or in locating voids in multi-layer polymer packages. In addition, improved visualization enables new image guided procedures such as guiding an atherectomy catheter to remove small unstable plaques from a coronary artery without puncturing the arterial wall.
MRI, x-rays, ultrasound, and optics have all found important roles in imaging applications. In many applications optical imaging offers certain advantages over other approaches because it is non-ionizing, non-contact, and can achieve high resolution. There are a variety of types of optical imaging techniques concurrently available including optical coherence tomography (OCT) and other interferometric imaging techniques, fluorescence and other spectroscopic imaging techniques, Raman imaging, diffuse-wave optical imaging, and two-photon imaging techniques.
OCT is an interferometric imaging technology and thus has the properties of very high sensitivity and large dynamic range. OCT achieves depth resolution via a combination of the focal properties of the imaging optics used and the coherence properties of the optical source used. The use of OCT and other interferometric imaging modalities has three fundamental advantages over standard direct detection optical imaging techniques: 1) the ability to achieve nearly shot-noise-limited detection and thus high sensitivity ( greater than 140 dB), 2) the ability to achieve high dynamic range ( greater than 100 dB) as the received signal is proportional to the electric field, not the intensity as in direct detection, and 3) the ability to perform high-resolution phase-sensitive temporal gating yielding significantly improved depth discrimination (xcx9c1 xcexcm).
Most previous work on scanning methods used in probe modules that attach to OCT or other optical imaging systems have focused on utilizing galvanometric or stepper based transverse scanning to produce multi-dimensional images. For instance, U.S. Pat. Nos. 5,459,570 and 5,321,501 describe several OCT imaging embodiments and their application in ophthalmology. These patents include methods which scan a beam in transverse patterns on the retina or on the anterior eye using galvanometer controlled mirrors or rotating mirrors. For endoscopes and catheters, methods have been described which scan a beam in a circumferential transverse direction perpendicular to the longitudinal axis of the catheter or endoscope. For example U.S. Pat. Nos. 5,393,467, 5,459,570 and 5,321,501 describe forms of these techniques.
It is an object of this invention to provide a forward directing imaging system that is useful for diagnostic and therapeutic intervention during medical procedures. The imaging system described has application to hand-held probes, laparoscopes, endoscopes, catheters, guidewires, trocars, microscopes, tissue probes, needles, scissors, scalpels, and other instruments either as xe2x80x9cstand-alonexe2x80x9d implementation or as a new implementation used in conjunction within, or external to, an existing instrument.
In one embodiment, the present forward directing imaging system includes forward directed optical coherence tomography (OCT) in a probe including a scanning mechanism. In another embodiment the system uses non-retroreflected OCT and includes a light source, a sample illuminator, a reference arm, a beam splitter, a sample light collector, a detector to generate a signal in response to incident light, and a beam combiner positioned to direct light from a sample light collector and a reference arm to a detector where output from the detector is analyzed by a computer.
In another embodiment the optical probe imaging system includes a scanning mechanism capable of causing a lens and optical fiber to move substantially orthogonally to the longitudinal axis of the housing. In one embodiment, the scanning mechanism includes a motor and a cam attached to the motor. The motor causes rotation of the cam moving the lens and optical fiber to orthogonally to the longitudinal axis of the probe housing to scan a sample. Other embodiments of the scanning mechanism which cause the lens and fiber to move orthogonally to scan a sample include a piezoelectric transducer, or by a wire around a pivot, pneumatic devices, or by an electrostatically driven slide.
In another embodiment of the optical imaging system, the scanning mechanism includes counter rotating prisms or rotating offset lenses that generate arbitrary scanning patterns on a sample.
In another embodiment of the invention the forward scanning OCT imaging system may be applied in a hand-held probe, or surgical tools such as probes, scalpels, scissors, forceps and biopsy instruments. Embodiments of these devices include the application of surgical laser fibers.
In yet another embodiment, the optical probe is an endoscope used to examine natural orifices, canals, tubes, ducts and vessels of the body. The invention contemplates a surgical grinding endoscope which uses a cutting element in the forward or side direction combined with the forward imaging capabilities of the optical probe.
In another embodiment of this invention, the OCT imaging system is used with a laparoscope to perform diagnostics and surgical procedures within body cavities. The laparoscope embodiment also contemplates the use of forward scanning lasers.
In still another embodiment of the invention, the imaging system is applied to a surgical microscope for procedures requiring an en face as well as a cross sectional view into the tissue. The imaging system is also applied to a high numerical aperture microscope in yet another embodiment of the invention
Another important embodiment of the invention is for therapeutics such as atherectomy, transurethral prostatectomy, and cervical imaging. It is contemplated that the optical probes of this invention are implantable to allow for continuous or periodic extraction of information from the tissue site where implanted.

Methods and apparatus for forward-directed optical scanning instruments


A system for accessing page table entries is disclosed. The system provides access to a page table entry mapping a predetermined physical page of memory. The system includes a physical page data base having an entry for each physical page of memory. Each physical page data base entry contains backlink information regarding an associated physical page of memory. The present system obtains a physical page data base entry associated with the predetermined physical page of memory from the physical page data base. The system uses a reserved page table entry, for example mapped by shared space, to build a virtual window. The virtual window provides a virtual address that may be used to access the page table entry mapping the predetermined physical page of memory. The virtual address provided by the virtual window is mapped to physical memory by the reserved page table entry. In a further aspect of the invention, the present system determines whether the page table entry mapping the predetermined physical page of memory is accessible in the current process context. If the page table entry mapping the predetermined physical page of memory is not currently accessible, a virtual window is built using the reserved page table entry. If the page table entry mapping the predetermined physical page of memory is currently accessible, no virtual window is built. An organization of the page table into a tree structure is further disclosed.

One of the elements within a computer operating system is memory management. Memory management consists of hardware and software that controls the allocation and use of physical memory. The effect of memory management is exemplified in multiprogramming systems in which several processes reside in memory at the same time. Memory management typically includes a virtual memory system. The virtual memory system provides the CPU (central processing unit) with mapping information. The CPU generates virtual addresses when an image is executed. Before these virtual addresses can be used to access instructions and data, they must be translated into physical addresses. Memory management software maintains tables of mapping information (page tables) that keep track of where each page of virtual addresses is located in physical memory. The CPU uses this mapping information when it translates virtual addresses to physical addresses. The mapping of virtual addresses through page tables in a virtual memory system provides a large virtual address space, and allows programs to run on hardware with smaller physical memory configurations.
The range of virtual addresses is referred to as the virtual address space. The virtual address space is that set of virtual addresses accessible by the current process. A process is current when its process context is loaded into the CPU and the process is actively executing. Only one process may be current on a given CPU at a given time. In existing systems, the virtual address space is divided into a shared address space, sometimes referred to as the system address space, and a per-process address space. The per-process address space is referred to as process private space. The shared address space maps code and data shared by all processes, and that is available to any process that is current. The shared address space may for example contain operating system code and data used by all processes. The process private space maps code and data associated with and available to one specific process only when that specific process is current. When the process context is changed, a new process is made current, and the mapping of process private space is changed to map process private space to process private code and data of that process.
A page table is typically used to map the virtual address space to physical memory, in units of "pages". A page is a multibyte unit of memory having a predetermined size. The specific size of a page varies from system to system. A page table contains page table entries (PTEs), each one of which defines a relationship (referred to as a "mapping") between a single virtual page and a physical page of memory. The physical address of a physical page of memory is referred to as a page frame number (PFN). Thus a given virtual page of memory is "mapped" to a page of physical memory by a specific PTE, and similarly that physical page of memory is "mapped" to the virtual page by that specific PTE. The PTE in that case is referred to as "mapping" the virtual page and the physical page of memory.
In existing computer systems, page table entries within a page table may be located in either process private or shared space. Where page table entries mapping process private space for a given process are located within process private space, the contents of those page table entries can ordinarily only be accessed when that specific process is current. Thus for a process to access the process private page table entries of another process, a context switch is required. However context switching is expensive and efficient design requires that context switching be minimized.
The operating system must occasionally access the contents of a page table entry as a consequence of managing virtual and physical memory. For example, the operating system may need to access the page table entry mapping a page of virtual addresses to a specific given physical page of memory. This may occur as a result of completion of an asynchronous I/O request, in which a process issues the I/O request, and then relinquishes control of the CPU until the I/O request completes. At the completion of the I/O request, the operating system may need to access a number of PTEs indicated by the requesting process in the I/O request. However, when the I/O request completes, the original requesting process may not be current. Accordingly, the access must be performed independent of the process context in which the access was initiated. As a result, the operating system may need to access a page table entry mapping process private space of a requesting process that is not current. Changing process context whenever such a page table entry must be accessed would be prohibitively costly.
Generally, there are three categories of page table entries that must be accessed by the operating system:
(1) page table entries which map the process private space of a given process, and which are accessible through that process's process private space, where that process is current, PA1 (2) page table entries which map the process private space of a given process, and which are accessible through that process's process private space, where that process is not current, and PA1 (3) page table entries which map shared space, and which are accessible through shared space, and therefore accessible regardless of which process is current.
Therefore there is required a new system which permits access to page table entries by the operating system regardless of whether the page table entry to be accessed is mapped into shared space, the process private space of the current process, or the process private space of a process that is not current. The new system should provide access to page table entries with a minimum of context switching, regardless of which process is currently executing.

Universal PTE backlinks for page table accesses


A plurality of ultrasound imaging system receptacles are arranged either vertically one above the other or horizontally side-by-side, each receptacle having an insertion slot for receiving the contact pads of an inserted ultrasound transducer connector. All of a number of connectors may be inserted into corresponding receptacles, and the system functions to mutually exclusively engage a single receptacle with its inserted connector. An electrical circuit arrangement is provided for automatically sensing the transducer in use without an operator having to make the selection manually. An interconnect and actuation scheme permits the multiport connector/receptacle arrangement to be manufactured at low cost. The modest size of the connectors and the receptacle assembly allows their placement at convenient locations on the system, and the simple basic design of the connector allows for submersion in liquid disinfectants.

1. Field of the Invention
This invention relates to the field of ultrasound transducers, and in particular to an improved ultrasound transducer connector and multiport imaging system receptacle assembly of an ultrasound imaging system.
2. Brief Description of the Prior Art
Prior art imaging systems have included receptacles for two or three different transducer types. That is, two or three transducers are plugged into the system at any one time, and the selection of the transducer which is to be active is under control of the imaging system in response to operator input. The receptacles are normally located in the lower front face of the system because of its close proximity to the printed wiring board card cage assembly within the system console.
Existing transducer connectors which have a 256 channel (and higher) capacity are large, clumsy, expensive, and not submersible in fluids for cleaning and sterilization. The corresponding system receptacles are expensive and, in general located on the lower front surface of the imaging system because that location is in proximity to the electronics. This location is not the most convenient one for the operator, however. The industrial designer has little latitude in locating these receptacles.
Switching between transducers is accomplished in the prior art with electrically operated reed relays or FET switches (one for each channel and auxiliary function) which are expensive and inherently require a significant quantity of printed wiring board real estate.
There is thus a need in the art for a multiport connector and receptacle arrangement in which the transducer in use may be automatically selected without need for reed relays or FET switches, and in which the receptacles may be located in a more convenient location for the operator, which has other important operating features yet is lower in cost, and which employs submersible transducer connectors. The present invention fulfills these needs.

Ultrasound transducer connector and multiport imaging system receptacle arrangement