Macrocyclization of amino acids or linear peptides upon reaction with amphoteric amino aldehydes and isocyanides is provided.

Peptides play vital roles by mediating a wide range of biological processes, acting as hormones, antibiotics, and signaling molecules. Due to the highly specific interaction with their biological targets, peptides have been widely used in medicine. However, the enormous therapeutic potential of peptides is not always easy to realize due to their low bioavailability. This shortcoming is a consequence of the degradation of peptides by endo- and exopeptididases, which results in poor in vivo stability of peptides. Compared to their linear counterparts, cyclic peptides are more resistant to degradation. There are two main reasons for this stability. Firstly, exopeptidases cannot cleave the cyclic peptide at its (non-existent) ends. Secondly, cyclic peptides, especially those with a small-to-medium ring size, are protected against endopeptidases because the constrained cyclic peptide backbone prevents the adaptation of the required extended conformation during proteolysis. In addition, the reduced charge and intramolecular hydrogen bonding within cyclic peptides facilitate passive membrane permeability, which contributes to their enhanced bioavailability. Most significantly, conformational constraints imposed on the amino acid sequence by the cyclic topology maximize enthalpic interactions between cyclic peptides and their biochemical targets while ensuring favourable entropy of binding.
There has been enormous interest in both naturally occurring and synthetic cyclic peptides as scaffolds that pre-organize an amino acid sequence into a rigid conformation.1 Amongst the vast number of known cyclic peptides, rigid small-to-medium sized rings have been of particular interest. Various cyclolactamization and non-peptidic cyclization methods2 have been developed.
The macrocyclization of linear precursors is afflicted by several thermodynamic and kinetic challenges that arise from the conformational preferences of linear peptides. The chain/ring conformational equilibrium is the central obstacle facing synthesis of cyclic molecules from acyclic precursors. Short linear peptides can easily adopt a circular conformation, which is driven by ion pairing between the N- and C-termini (Scheme 1, A).3 Despite the unfavorable entropy, these circular conformations are thermodynamically favoured due to the enthalpy garnered through electrostatic and other polar interactions. As shown in Scheme 1. conventional activation reagents tend to remove the zwitterionic character of the peptide, rendering it incapable of forming ion pairs. Consequently, without enthalpic contribution from electrostatics and other polar interactions, the activated peptide adopts a random linear conformation (Scheme 1. B). In order for macrocyclization to occur, the activated peptide must adopt a pre-cyclization conformation (C) prior to forming the desired cyclic molecule (D). High dilution, on the order of 10−4 or greater, is essential to limiting the formation of by-products arising from cyclodimerization,4 cyclotrimerization, and polymerization.5 Unfortunately, dilution brings about long reaction times, which in turn provoke background processes such as epimerization. Amongst the most challenging cyclizations are those attempted on linear peptides containing less than seven residues.6,7

Another common challenge in exploring macrocyclic chemistry space has to do with late-stage modification. This is a historic challenge for macrocyclic compound libraries built in the biotechnology and pharmaceutical companies. Their typical cyclization techniques (ring-closing metathesis, Huisgen cycloaddition) do not naturally lend themselves to further elaboration. Functional group handles must be built in prior to cyclization to achieve this goal.

Cyclic amino acid molecules and methods of preparing the same

The Governing Council of the University of Toronto


The invention is drawn to the enzymatic decarboxylation of 2-keto-L-gulonic acid (2-KLG) to produce xylose. The invention is also drawn to a method to detect xylose in vitro or in vivo (intracellularly), which employs an L-xylose dehydrogenase.

1. Field of the Invention
The present invention relates to a novel enzymatic method to produce xylose and a method of detecting xylose in vitro.
2. Background Art
Xylose is a pentose sugar. D-xylose is the form found primarily in plants and animals. Xylose is recognized as being useful as an additive; as a food; as a pre-cursor for xylitol; as a sweetener; as a glucose substitute for diabetic patients (xylose does not provoke insulin response like glucose); as a therapeutic for decreasing transaminase and ketone levels in hepatitis patients, for connective tissue disorders and for osteoarthritis; and for industrial uses, such as dyeing, tanning, furfural production, paint, acetic acid production, lactic acid production, biodegradeable plastic polymer production, glue, resins, vitamin C production, and ethanol fuel production.
Xylose is a major component of hemicellulose. Hemicellulose is a component of lignocellulose, which is found in plants, for example, forage plants, woody plants, bark, beechwood, corn husks, oat hulls, canes, coffee grounds, straw, and bulk plant products. Xylose can be recovered from agricultural waste and hardwood in good yield by acid hydrolysis, using acetic acid or sulfuric acid. However, acid hydrolysis of hemicellulose results in the presence of varying amounts of many hexoses and pentoses, including arabinose, galactose, mannose, rhamnose, and glucose, in the same preparation as the xylose.
Acid hydrolysis of lignocellulose, however, liberates different sugars, such as a mixture of D- and L-sugars, as well as furfurals, acetic acid, hydroxybenzoic acid and vanillin, among others. Therefore, processing xylose from bulk plant products or from sources of hemicellulose or lignocellulose suffers from the disadvantage of the presence of many products from the acid hydrolysis, making the extraction of xylose from the by-products costly. Some of these side products, in particular the furfurals, inhibit the growth of microorganisms. Therefore, one disadvantage of using sources of hemicellulose and lignocellulose for the production of xylose is that many of the products produced by acid hydrolysis of hemicellulose and lignocellulose inhibit microbial metabolism and subsequent utilization of the sugars (Ooi et al., Electron. J Envrion. Agric. Food Chem. 1(3), (2002)). Because of the numerous side products, additional purification of the xylose product is required.
Therefore, there exists a need for improved methods of producing xylose, which produces fewer by-products.

Enzymatic decarboxylation of 2-keto-L-gulonic acid to produce xylose


Disclosed are various embodiments for generating implicit user ratings for a media item. A ratings analyzer tracks user interaction with a network content server configured to present a media item to a plurality of users and then generates an interaction history for each user based at least upon corresponding user interaction with the media item presented by the network content server. A user interaction metric may be generated based at least upon each interaction history associated with the plurality of users and a user interface may be encoded for display where the user interface comprises the user interaction metric.

Users may listen to music, audio books, or watch movies, TV shows, or other media items over a network. Before a user decides whether to select a particular media item for playback, the user may access one or more media item reviews/ratings. In this respect, a particular media item may be associated with one or more reviews/ratings that have been generated by other users. These reviews/ratings may be authored by other users for the purpose of providing explicit feedback about a particular media item. However, it may be the case that a relatively small amount of users provide feedback for a particular media item.


In an aspect of managing resource exhaustion, a method includes receiving a program code that is configured for generating a random number. The generating is identified as vulnerable to a resource exhaustion. The method also includes identifying a statement in the program code at which a value of a variable associated with the generating of the random number is affected, inserting a hooking code in the statement for monitoring the variable at the statement, and running the program code in a plurality of iterations. A consumption level of the resource is varied in the plurality of iterations. The method further includes monitoring a plurality of values of the variable in the plurality of iterations. The method also includes executing a regression analysis on the plurality of values and returning a root cause of the vulnerability.

The present invention relates generally to information systems, and more specifically, to security and maintainability of information systems.
The operation of a computerized device, system or network is typically dependent on resources. Such resources may be memory, hard disk, sensors communication ports and the like.
In some cases the resources are exhausted. Such a case may be a denial of service attack which is an attempt to make a machine or network resource unavailable to its intended users. This denial of service can decrease service availability, causing issues for customers and providers.

Detecting vulnerability to resource exhaustion


Protecting material from contamination by an illicit substance or object during unauthorized or illegal action, performed by children, teenagers, animals Providing material inside a closed container having an access opening, aligning a trap with access opening, mounting aligned trap within the container, and adding decoy material to trap Closed container having access opening, for containing the material, and trap mountable within container, alignable with access opening, and suitable for holding decoy material Trap with decoy material intercepts and traps illicit substance or object introduced via access opening into container, preventing the illicit substance or object from contacting protected material inside container Unique alignment and mounting via appropriate shape, configuration, dimensions, of trap relative to access opening, and amount of decoy material, produce a protective visual illusion against a perpetrator performing unauthorized or illegal action Optional automatic in-situ testing/monitoring quality or/and quantity of decoy material in mounted trap.

The present invention relates to security of materials, and more particularly, to a method, corresponding system, and corresponding device, for protecting a material from contamination by an illicit substance or object, particularly as a result of an unauthorized or illegal act, such as that performed by children, teenagers, as well as that often performed by animals, such as by birds or insects or/and by small land animals, for example, rodents, squirrels, and snakes. The present invention is particularly applicable to a large volume, for example, of at least several hundreds of liters, and up to several millions of liters, of essentially any type of liquid or/and solid phase material, presently contained and stored, or intended to be stored, in a closed container, tank, reservoir, receptacle, or similar type of closed storage entity whose inside is potentially accessible to humans or/and animals, wherein the material may be considered at risk from contamination caused by an unauthorized or illegal act, such as that performed by children, teenagers, or animals, and therefore needs to be protected against such acts.
In a wide variety of different governmental, commercial, and private, sectors and areas of activities, a large volume, for example, of at least several hundreds of liters, and up to several millions of liters, of a given liquid or/and solid phase material is commonly contained and stored in a closed container, tank, reservoir, receptacle, or similar type of closed storage entity whose inside is accessible to humans or/and animals, herein generally and equivalently referred to as a closed internally accessible container, or as a closed container, or for brevity, as a container, of appropriate size and materials of construction. Just a few specific examples of such a stored material are water, a petroleum based liquid fuel, such as gasoline, diesel fuel, or airplane fuel, a raw or intermediate material used for processing or manufacturing a finished product, such as a human edible food product, a pharmaceutical product, or a chemical product, and a finished product obtained from completion of a manufacturing process. One or more access openings are often configured as part of the construction of the cover of the closed container. Access openings are typically used by authorized personnel for performing a variety of legitimate actions or activities. For example, for entering and providing maintenance (cleaning, repairing) to the inside of the container; for adding material from an outside source to the container; for removing material from the container to an outside receiver; for ventilating the container; for determining the level of the material inside the container; for removing a sample of the material from the container, for the purpose of testing or/and monitoring the quality of the material, for example, in terms of pre-determined parameters of physical, chemical, or/and biological, properties, characteristics, and behavior (activity), of the material; or for any combination of such authorized actions or activities.
A given large volume of a contained material is typically stored in a designated storage location, either inside or outside of a building or other type of designated storage entity, within the grounds or boundaries of a governmental, commercial, or private, property, facility, or complex. Moreover, such grounds or boundaries are typically part of an overall, multi-faceted, security environment, characterized by security conditions and arrangements involving different types and amounts of security equipment or hardware and security procedures. Commonly known and employed types of security equipment or hardware are walls, fences (non-electronic, electronic), locks (non-electronic, electronic), or similar physical barriers, security guards, guard dogs, electronic alarms, electronic visual surveillance devices such as video cameras and motion detectors, and electronic audio surveillance devices such as sound detectors. A commonly employed security procedure is based on the concept of 'response time', relating to how quickly on-site or/and off-site security personnel respond to a 'break' in a given type of security equipment or hardware in the overall secure environment.
Actual security conditions and arrangements of a given stored material depend upon several factors, such as the type, active or potential hazard level, value, size, location, accessibility, and eventual use, of the stored material. For example, a large volume of water used by a nuclear power plant, in particular, for cooling the nuclear reactor, is typically stored in an extremely high level security environment, such as one featuring all of the above types of security equipment or hardware, along with a relatively short response time to a security break. As other examples, a large volume of a petroleum based liquid fuel, such as gasoline or diesel, a large volume of a raw or intermediate material for manufacturing or processing a finished product, such as a human edible food product, a pharmaceutical product, or a chemical product, and a finished product obtained from completion of a manufacturing process, is typically stored in a moderate level security environment, such as one featuring some or most, but not all, of the above types of security equipment or hardware, along with a relatively moderate response time to a security break. Another example, particularly common in many regions of the world, is a large volume of public drinking water stored in a closed container or reservoir housed in an elevated 'water tower' type of 'stand-alone' structure, typically located within a community, a town, or a larger population center, featuring a relatively low level security environment, such as one including only fences or/and locks, without any electronic means of security, along with a relatively long response time to a security break due to the uncertainty in accurately determining the time of an actual entry through, or break of, a fence or lock by an unauthorized person or animal.
In principle, essentially any large volume of material stored in a closed container, regardless of the level of the overall security environment, at one time or another, may be considered at risk from contamination by unauthorized or illegal introduction of an illicit substance or object, for example, via an access opening in the cover of the container, as a result of an unauthorized or illegal act, such as that performed by children, teenagers, as well as that often performed by animals, such as by birds or insects or/and by small land animals, for example, rodents, squirrels, and snakes.
Herein, an illicit substance or object is any substance or object in the possession of a perpetrator or perpetrators (such as children, teenagers, or/and animals) about to perform, or in the process of performing, an unauthorized or illegal act involving introduction of that substance or object to a material stored in a closed container. Additionally, herein, an illicit substance or object may also be the perpetrator or perpetrators (such as children, teenagers, or/and animals) themselves, for example, introducing themselves, via an access opening in the cover of the container, to the material stored in the container.
For the applicable regions of the world, the large volume of public drinking water stored in a closed container or reservoir housed in a water tower type of structure is considered a highly attractive or desirable for serving as a likely target of contamination by a potential perpetrator (such as children, teenagers, or animals), but, is typically provided a relatively low level security environment including a relatively long response time to a security break. Additionally, a large volume of a petroleum based liquid fuel, or of a raw or intermediate material used for processing or manufacturing a finished product, or a finished product obtained from completion of a manufacturing process, may also be considered highly attractive or desirable for serving as likely targets of contamination by a potential perpetrator (such as children, teenagers, or animals), but, may also be stored in relatively low level security environments including a relatively long response time to a security break. Thus, for these and similar cases, there exists an anomaly, and therefore, a potential flaw or limitation, regarding the overall security environment, in general, and regarding the security conditions and arrangements, in particular, provided for protecting a given stored material.
Clearly, the type (reversible or/and irreversible) and extent of contamination by an illicit substance or object introduced into a given stored material depend upon the physical, chemical, or/and biological, properties, characteristics, and behavior (activity), and size, of the stored material, of the illicit substance or object, and of the interaction of the illicit substance or object with the stored material. Furthermore, duration of the interaction of the illicit substance or object with the stored material is another important factor determining the type and extent of contamination of the stored material. Thus, following a break in the overall security environment of the stored material and subsequent introduction of an illicit substance or object into the material, and depending upon the actual security conditions and arrangements in operation, duration of interaction of the illicit substance or object with the material is a function of (i) the time required for the security equipment or hardware to discover and identify the break in security, (ii) the additional time taken for notifying (on-site or/and off-site) security personnel, (iii) the additional time taken by the security personnel to respond to the break in security, (iv) the additional time required for notifying the appropriate materials handling personnel (typically, not the same as security personnel) for handling the contaminated material, and (v) the additional time required for properly responding to potential release of the contaminated material from the container or reservoir, and if applicable, from the designated storage location, of the contaminated material.
Moreover, and relatedly, there is the important issue regarding the type and extent of potential damage to infrastructure or/and injury (including possible death) of humans caused by exposure of these entities to the contaminated material, following possible release of the contaminated material from the storage environment. In a bad scenario, release of a contaminated material could lead to a situation of destruction of infrastructure or/and injury (including death) of humans, for example, on a large scale.
All of the above types of conventional or/and high-tech security environments, conditions, and arrangements (equipment or hardware and procedures), used for protecting a material from contamination by an illicit substance or object as a result of an unauthorized or illegal act, such as that performed by children, teenagers, as well as that often performed by animals, such as by birds or insects or/and by small land animals, for example, rodents, squirrels, and snakes, are primarily focused on discovering, identifying, and targeting, the break in security, and to a certain extent, also to slow down, impede, or obstruct, further progress or duration of, the break in security. However, once contamination by the unauthorized or illegal introduction of the illicit substance or object into the material is made, for example, via an access opening in the cover of the container, 'the clock starts ticking' regarding potential or actual damage to infrastructure or/and injury (including possible death) of humans caused by exposure of these entities to the contaminated material, following release of the contaminated material from the broken security storage environment.
Accordingly, a significant limitation which is common to all of the above types of conventional or/and high-tech security environments, conditions, and arrangements, is the lack of additional security conditions and arrangements (equipment or hardware or/and procedures), following a break in the overall security environment of the stored material, for 'preventing' contamination of the material by unauthorized or illegal introduction of an illicit substance or object into the storage container.
There is thus a need for, and it would be highly advantageous to have a method, corresponding system, and corresponding device, for protecting a material from contamination by an illicit substance or object, particularly as a result of an unauthorized or illegal act, such as that performed by children, teenagers, as well as that often performed by animals, such as by birds or insects or/and by small land animals, for example, rodents, squirrels, and snakes. There is a need for such an invention which provides security conditions (equipment or hardware and a procedure), whereupon following a break in the overall security environment of a material stored in a closed container or reservoir, operation of the invention 'prevents' contamination of the protected material by unauthorized introduction of an illicit substance or object into the storage container or reservoir. Moreover, there is a need for such an invention which is generally applicable to essentially any type and quantity (particularly large volumes) of liquid or/and solid phase material, which is generally applicable to essentially any type, and essentially any geometrical shape or configuration and dimensions, of closed storage containers, which is relatively inexpensive to fully implement, which is readily implemented in new or existing storage environments, and which is commercially applicable.
Furthermore, there is a need for such an invention which, as either part of, or separate from, ensuring the protection and security of the material, optionally, may additionally be implemented for automatically in-situ testing or/and monitoring the quality or/and quantity (amount) of the decoy material in the mounted (and aligned or non-aligned) trap, in particular, by testing or/and monitoring pre-determined parameters of physical, chemical, or/and biological, properties, characteristics, and behavior (activity), or/and, level (height), of the decoy material therein.

Protecting a material from contamination


An integrated circuit device has reduced stress concentration on the IC chip for prevention of package cracks in the device. Recessed portions are formed in the package at positions corresponding to at least the corner portions of the IC chip to reduce the stress concentration generated at the corner portions of the IC chip.

A conventional integrated circuit device in which an IC chip is molded in a resin is constructed as shown in FIG. 10.
In the above-mentioned conventional integrated circuit device, since the coefficient of linear expansion of the molding resin is approximately ten times as high as that of the IC chip and the lead frame, strain is produced in the resin having a high coefficient of contraction, as shown by the arrow in FIG. 11, due to a difference in temperature between the molding process at about 170.degree.C. in general and the cooling process at room temperature. As a result, stress is concentrated at the corner portions of the IC chip, thus raising a problem in that package cracks and passivation cracks are easily produced.

Integrated circuit package having stress reducing recesses


The present invention relates to a method for face-to-face weaving of a pile fabric on a weaving machine, pile forming pile warp yarns (6, 7, 8, 9, 16, 17, 18, 19) being interlaced alternately around a weft yarn (1) in the upper fabric and around a weft yarn (1) in the lower fabric and non pile forming pile warp yarns (6, 7, 8, 9, 16, 17, 18, 19) being interlaced in one of the backing fabrics in accordance with a predetermined pattern, the said weaving machine comprising at least three weft insertion means and that at each weft insertion cycle only one weft yarn is inserted, the non pile forming pile warp yarns (6, 7, 8, 9, 16, 17, 18, 19) to be interlaced are positioned on a different level (N1, N2) and, in successive series of four weft insertion cycles (a, b, c, d) each time during two successive weft insertion cycles one weft yarn (1) being inserted (a, b) under the two levels (N1, N2) and one weft yarn (1) being inserted above the two levels (N1, N2) and each time, during two other successive weft insertion cycles (c, d) one weft yarn (1) being inserted in each of these weft insertion cycles between the said levels (N1, N2).

The present invention relates to a method for manufacturing face-to-face woven pile fabrics, two backing fabrics being woven above one another on a weaving machine by inserting weft yarns in successive weft insertion cycles between binding and tension warp yarns, the pile warp yarns forming a pile in at least one part of the pile fabric by being alternately interlaced around a weft yarn in the upper backing fabric and around a weft yarn in the lower backing fabric and pile warp yarns forming no pile in at least another part of the pile fabric and being interlaced in one of the backing fabrics in accordance with a predetermined pattern. More particularly, the present invention is relating to a high density pile fabric manufactured in accordance with the present method.
Furthermore, the present invention relates to a weaving machine provided for the method according to the invention to be carried out.
Hand-knotted fabrics are characterized by:                a high density;        a delicate design in many colours (six colours and more);        a nice back.
When weaving there is an evolution to systematically increase the density of pile fabrics. Where in weaving, the weaving reed used to be a restriction for densities above 550 pile warp yarns per metre, because the number of reed dents per metre was restricted to 550, the European patent publication EP 1 347 086 proposes a method for the densities of a pile fabric to be increased by providing two pile warp systems per reed dent in combination with a suitable arrangement of the backing warp yarns in this reed dent in order to realize a certain separation between the pile warp yarns of the two pile warp systems within the same reed dent.
In this manner, it will be possible to produce fabrics having 700 and even 800 pile warp systems per metre in the weft direction. It is possible to apply this method with 1/1 V-weave as represented in EP 1 347 086 on a double rapier weaving machine, the pattern forming pile warp yarn being interlaced alternately in each fabric around a weft at the back of the fabric and then around a weft on the pile face of the fabric.
With this method therefore, only half the pile will be interlaced around a weft at the back of the fabric, so that the other half of the pile will be interlaced less securely on the pile face of the said fabric, which may be deduced immediately from the pattern which will be observed at the back of the fabric. This pattern will contain only half of the pile points and therefore is less delicate than the pattern at the front of the fabric.
In a 1/2 V-weave all pile warp yarns are indeed interlaced around a weft at the back of the fabric. Here, the pile warp yarns being interlaced securely, which is clearly shown by the pattern at the back of the carpet. The pattern at the back clearly corresponds to the pattern at the front, because of which, a quality may be approached which will be better in accordance with a hand-knotted carpet than the one of a 1/1 V-weave which is not fully interlaced through to the back of the fabric.
Only, when weaving the 1/2 V texture by means of the multiple rapier technique, the problem may occur that mixed contours are produced, preventing delicate designs from being formed, which is rather inconvenient in fabrics of this density.
Mixed contour mean that two pile tufts of a different pile warp yarn (colour) will occur between two successive wefts in a face-to-face fabric, which will be crossing and standing upright next to one another in a face-to-face fabric. Because the two pile tufts are crossing with this colour change, they will take up a wrong position with respect to one another in accordance with what is desired and this will cause the pattern of the fabric to become indistinct.
It is known that certain mixed contours may occur in one of the fabrics or in both fabrics at certain colour (pile warp yarn) changes, dependent on the positions taken up by the yarns of these changing pile warp yarns when they are not forming the pattern and are interlaced as dead pile. Thus:                when the pile change occurs from a pile warp yarn being interlaced as a dead pile in the upper fabric, to a pile warp yarn being interlaced in the lower fabric, a mixed contour will never be produced;        when the pile change occurs from a pile warp yarn being interlaced as a dead pile in the upper fabric, to a pile warp yarn being interlaced in the upper fabric, a mixed contour will be produced in the upper fabric;        when the pile change occurs from a pile warp yarn being interlaced as a dead pile in the lower fabric, to a pile warp yarn being interlaced in the lower fabric, a mixed contour will be produced in the lower fabric;        when the pile change occurs from a pile warp yarn being interlaced as a dead pile in the lower fabric, to a pile warp yarn being interlaced in the upper fabric, a mixed contour will be produced in both fabrics;
Such mixed contour effects may be avoided by providing two lines of the same colour (the same pile warp yarn) in the card design after one another and to apply to them the method described in the European patent publication EP 9 27782 and, of at least one of the pile warp yarns involved in the pile change, one lift plan before the pile change or one lift plan after the pile change being replaced by a correction lift plan.
In practice, such correction lift plans may be applied automatically to the processing software transforming the design into a file in order to activate the Jacquard machine. However, in order to be able to apply this method, a number of rules have to be respected as indicated when setting up the design, namely that the correction lift plan may only be applied to produce the effect expected, when during two successive pile plans the pile is formed by one and the same pile warp yarn.
In the very delicate patterns to be woven by means of the devices as described above, applying these applications to the design is very labour intensive. Moreover, the liberty of designing in delicate drawings will be restricted.
Moreover, the fact of mixed contours occurring or not, depends on the position of the pile warp yarns in the weaving creel, for the position of the pile warp yarns will determine in which fabric the pile will be interlaced.
Although, from a technical point of view, it is possible to avoid mixed contours, we find that in practice, quite some fabrics are still showing mixed contours. Moreover the delicate designing requires (typical of fabrics imitating hand-knotted carpets) a freedom of designing, which is not always to be realized by avoiding mixed contours as described above. Double colour rows in order to avoid mixed contours are sometimes inconvenient to the delicacy of a design.
The 1/1V method and the 1/2V method as described before, moreover, have the disadvantage that they are restricted to about 40 pile warp yarns per centimetre with double rapier weaving machines which are normally used.
At higher densities of pile warp yarns, there will be problems as to the perfectness of the quality of the back and the dead pile protruding from the back of the fabric. This certainly is the case with acrylic and woolen yarns having a surface which is more coarse. With polypropylene yarns also, which are smoother, these problems will occur, but in that case rather from 42 to 45 pile warp yarns per centimetre.
This means, that a fabric having a high density and many colours will cause problems to be woven, both with a 1/1V and 1/2V weave, on a double rapier weaving machine in the following structures:                600 pile warp systems per metre in 7 chore and more:        700 pile warp systems per metre in 6 chore and more:        800 pile warp systems per metre in 5 chore and more.

Method for manufacturing high density pile fabrics


An assembly for use in a projection system includes a plurality of optical elements, such as one or more mirrors, a light engine, and a screen, and a monolith. The optical elements are coupled to the monolith to provide a central element of reference, thereby enabling alignment based on the central element of reference.

One of the most efficient methods for making a large display is to use projected images. Conventionally, the most advanced projection systems use imaging devices such as digital micro-mirror (DMD), Liquid Crystal on Silicon (LCoS), or transmissive LCD micro-displays. Typically, one or two fold mirrors are used in projection displays in order to fold the optical path and reorient it to reduce the cabinet depth of projection displays. In a single fold mirror rear projection display, the light engine converts digital images to optical images with one or more microdisplays, and then projects the optical image to a large mirror which relays the optical images through a rear projection screen to a viewer in front of the screen. The light engine also manages light colors to yield full color images and magnifies the image. In a two fold mirror rear projection display, the projected optical images from the light engine are reflected off of a first fold mirror to a second fold mirror, and then through the rear projection screen to a viewer. The two fold mirror structure provides additional reduction in TV cabinet depth over one fold mirror structures, but typically requires additional cabinet height below the screen. The height of the cabinet below the screen is called chin height and it grows as the light engine projects to a first fold mirror typically positioned below the screen.
Because the imaging devices in projection displays are small, typically less than 1″ in diagonal, they are inexpensive to manufacture. However, the small images generated by the imaging devices require magnification factors up to 100 in order to yield the 50″-80″ diagonal image typical in consumer projection televisions. However, the large amount of magnification can cause large alignment issues from just a small miscalibration or error in the position of the light engine or mirrors.
Rear projection televisions (RPTVs) made today typically have separate mechanical assemblies for the projector (known as a light engine), the structures that hold the mirrors, and the surrounding enclosure. This is introduces the following problems:                The light engine lens must be designed to match the throw distance of the cabinet's optical assembly. However, since light engines are designed and built separately from the rest of the system, this "lens matching" problem often delays the completion of the light engine design.        The light engine, mirror and screen positions in the cabinet determine the overall angle that the projected light hits the back of the screen. These angles are required to begin the design of the screen Fresnel lens. Since the relative positions of the engine, mirrors and screen are determined after the engine is designed and selected, the tooling of the Fresnel lens and the integration of the product cannot be completed until late in the project. This results in an increased overall project length, and delays product time to market.        Once the light engine is installed in the cabinet the alignment of the picture on the screen is not guaranteed. Various adjustments need to be made in the optical path to correctly size and position the image, often resulting in excessive manufacturing cycle time.        Light engines are complex optical systems and are typically built by specially trained technicians in a clean room environment. The remaining optical path is typically built by minimally trained workers in a traditional TV production line environment.        However, the complex optical adjustments are made at this second stage of manufacturing. The results are not good: dirt and dust are introduced into the optical system and the system is difficult to align correctly.        During shipping of the calibrated system from the factory to the dealer or customer, various parts of this patchwork optical assembly can shift position causing the image to become misaligned.
As such, a new optical assembly and method are needed to overcome the above-mentioned disadvantages.

Integrated optical assembly and method for projection displays


A computer system includes program instructions to generate a first virtual keypad for entry of a first portion of a password, wherein the first portion includes a first value and a second value. The program instructions receive the first portion, wherein the first portion includes a first number of keys selected equal to the first value and the second value present in the first number of keys selected. The program instructions generate a second virtual keypad for entry of a second portion, wherein the second portion includes a third and a fourth value. The program instructions receive the second portion, wherein the second portion includes a second number of keys selected equal to the third value and the fourth value present in the second number of keys selected. The program instructions determine to grant a user access to an account associated with the account password.

The present invention relates generally to password inputs and more particularly to the utilization of virtual keypads for portion based password inputs.
Mobile devices currently allow for users to utilize numerous applications and perform functions such as online banking and online commerce. Online banking and online commerce along with other mobile device functions typically involve the use of security features to protect the private information associated with a user. Security features can include unlocking a mobile device prior to accessing content on the mobile device or entry of a numerical password or personal identification number (PIN) to protect the user's account information, such as credit card and bank account information. Mobile devices with touch screens or automated teller machine (ATM) allow for the user to access personal information in public areas, where the user takes precautions to ensure password inputs are not viewable to the public. A person looking in the direction of the user inputting the password has the ability to see each digit of a numerical password or PIN being entered.

This patent is subject to a terminal disclaimer.

Utilization of multiple keypads for password inputs

International Business Machines Corporation


A ball grid array (BGA) package for an integrated circuit device includes an integrated circuit device having a plurality of terminals, and two largest dimensions that define a major plane. A package substrate material encloses the integrated circuit device, and is formed, in a plane parallel to the major plane, into a polygon having at least five sides. An array of contacts on an exterior surface of the package substrate material is electrically coupled to the plurality of terminals. Contacts in the array of contacts are distributed in a pattern of contact positions, and the center of each contact position may be separated from the center of each nearest other position by a separation distance that is identical throughout the pattern. Each position may be occupied by a contact, or positions in a sub-pattern may lack a contact and may be available for insertion of at least one via.

The background description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the inventors hereof, to the extent the work is described in this background section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted to be prior art against the subject matter of the present disclosure.
A ball grid array (BGA) is a type of surface-mount packaging used for integrated circuits. A BGA package includes an array of solder balls on a surface of the BGA package. Any individual solder ball may be coupled to a pin of an integrated circuit device within the BGA package. When the BGA package is assembled to a printed circuit board (PCB), electrical connections are formed using the array of solder balls to couple an integrated circuit device within the BGA package to other circuits and interfaces on the PCB.


The present invention relates to a pharmaceutical composition comprising an insulin compound in a concentration that is sufficient to maintain a therapeutically effective level of the insulin compound in blood plasma for at least 3 days characterized by having a pharmacokinetic profile in vivo with substantially no burst of the insulin compound. The present invention further relates to the use of an insulin compound for preparing said pharmaceutical composition as well as a kit of parts comprising said pharmaceutical composition.

Insulin therapy is characterized by a high need for keeping the insulin drug release within very strict levels as the therapeutic window is narrow, and the adverse effects of hyperinsulinemia can potentially be life threatening. Numerous insulin preparations have been commercialized, with different action profiles to suit specific needs of the diabetic population. Fast acting insulin analogs are administered just before meals, in order to control the peak in plasma glucose following food ingestion, whereas long acting insulin analogs are typically given once or twice a day to provide a steady basal insulin level.
Recent developments have also included oral insulin and inhaled insulin. However, because insulin is a protein, when taken orally it is easily digested by the stomach and gastrointestinal system. Alternatively, inhalable insulin delivered through an inhaler into the lungs was commercially available for a limited period (Exubera®, Pfizer discontinued in 2007). This formulation provided insulin for a period of hours, still requiring patients to continue injecting a long-acting basal insulin. Further disadvantages of the inhalable insulin included manufacturing difficulties resulting in a cost-prohibitive delivery system. As a result, all commercially available insulin formulations must be administered either by subcutaneous or intravenous injection.
The plasma profile of the various available insulins are characterized by having different plasma profiles. Said plasma profiles can be described by having a maximum and a minimum plasma concentration which is dependent on the formulation and type of insulin used. It is of high importance to obtain a plasma profile which is as reproducible from patient to patient and within patients in order to be able to predict the plasma glucose lowering effect of the administered insulin. Additionally, in the case of multiple administrations of basal insulin, it is desirable to have as little difference between the maximum plasma concentration and the minimum plasma concentration as possible. This will lead to a more constant plasma concentration of insulin, and therefore a more uniform glucose lowering effect over the entire dosing interval.
Current standard basal insulin therapy consists of daily or twice daily administrations of long acting basal insulins such as NPH insulin, insulin glargine or insulin detemir. Though development of newer insulin analogs has aimed to reduced the variability of insulinotropic effects, the glucose lowering effect of these long acting formulations are still characterized by large inter- and intra-subject variations as described by Heise et al. (Diabetes, 2004 (53), 1614-1620). In this study insulin detemir displayed the least pharmacokinetic variation, with a coefficient of variation of 15 as compared to CV of NPH insulin and insulin glargine of 26 and 34, respectively. This rather large variability is a major obstacle to obtaining optimal glucose control, as it is difficult to predict the exposure to the insulin molecules.
The same study investigated the pharmacodynamic variation as assessed by glucose infusion rates (GIR). This evaluation also demonstrated that insulin detemir had lower within-subject variability than both NPH insulin and insulin glargine with respect to the pharmacodynamic marker GIR. Furthermore, this study demonstrated that the insulin effect on glucose infusion rates did not last throughout the full dosing period of 24 hours, clearly demonstrating the need for a long acting insulin, that offer full glucose lowering action for the full duration between doses. To circumvent the problem of current daily basal insulins not lasting a full 24 hours, some patients split their basal insulin dosage into two daily injections, in order to obtain better glucose control throughout the day.
Therefore, there is a clear need for novel long acting preparations of insulin, that continuously release insulin throughout the entire period between administrations.
In addition, even if patients can manage their blood glucose with daily injections of basal insulin, initiation of insulin therapy meets reluctance due to the daily injection regime. This is undesirable, as the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recognize insulin as first line treatment after oral metformin as offering the best treatment outcome. (D M Nathan et al., Diabetologica (2008) 51:8-11).
If the injection frequency of insulin treatment could be reduced, it is likely that the psychological barrier to initiation of insulin therapy would be reduced, hence allowing patients to start insulin therapy at an earlier stage, greatly improving their health status.
A challenge in developing long-acting basal insulin formulations lies in the narrow therapeutic range for insulin, and large peak-to-trough variations in insulin pharmacokinetics as well as burst effects should be avoided under all circumstances.
Several approaches to reducing the frequency of administration, while still retaining the insulin release within narrow limits have been proposed, but have failed to extend the duration of glucose lowering effects beyond a couple of days, while still being characterized by having a small ratio between the maximum plasma concentration and the minimum plasma concentration.
WO 06003014 describes a hydrogel capable of releasing insulin with the possibility of reduced dosing frequency as compared to standard daily basal insulin injections. However, the insulin is released at a rate too fast for ensuring strict insulinotropic control for periods extending 2 days. In fact the insulin is released with a half life of approximately 30 hours, meaning that the prodrug must be administered at least every 30 hours in order for the peak to trough ratio to be below 2 at steady state.
The concept of preparing a reversible polymer conjugate of insulin has been explored by Shechter et al. and described in scientific articles and patent applications (e.g. (European Journal of Pharmaceutics and Biopharmaceutics 2008(70), 19-28) and WO 2004/089280). The insulin is conjugated to a 40 kDa PEG polymer through a 9-hydroxymethyl-7-(amino-3-maleimidopropionate)-fluorene-N-hydroxysucinimide spacer molecule. Hydrolysis of said spacer molecule releases insulin with a half life of approximately 30 hours, meaning that the prodrug must be administered at least every 30 hours in order for the peak to trough ratio to be below 2 at steady state.
Other attempts of reducing the insulin dosing frequency have been made. Hinds et al (Journal of Controlled Release, 2005 (104), 447-460) describe a method of producing a once weekly insulin, by first permanently PEGylating the insulin molecule and then subsequently microencapsulating the PEGylated insulin in PLGA microparticles. PLGA encapsulation of proteins has been shown to cause side reactions of the polymer esters with peptide or protein amino groups. Lactic acid acylation products have been observed after exposure of the formulations to buffered solutions at neutral pH. (Nat. Biotechnol. 18 (2000) 52-57; Pharm. Res. 11 (1994) 865-868; Pharm. Res. 19 (2002) 175-181).
Specifically for insulin, detrimental effects of polymer formulations have been demonstrated (Pharm. Dev. Technol. 4 (1999) 633-642; Pharm. Dev. Technol. 5 (2000) 1-9).
In the abovementioned case, the insulin has undergone substantial structural modification through permanent modification by a high molecular weight polymer entity as PEGylation of insulin apparently serves to protect the peptide from deterioration in the PLGA polymer formulation.
Unfortunately, such high molecular weight modified insulins may exhibit reduced efficacy by diminished receptor binding and may also exhibit injection site reactions such as lipodystrophy due to the extended presence of high concentrations of the high molecular weight insulin in the subcutaneous tissue. Furthermore, such PEGylated insulins will exhibit a lower distribution volume, which is of particular disadvantage in the treatment of diabetes.
In addition, the pharmacokinetic profile of the released insulin conjugate is characterized by an initial burst-like release immediately following administration, which is followed by a drop in insulin conjugate plasma concentration, followed by an increase in insulin conjugate plasma concentration over the following days. This pharmacokinetic profile is typical of microencapsulated drug formulations and can lead to an unpredictable glucose response in subjects treated with such formulation.
Therefore the challenge remains to develop long-acting insulin without compromising the insulin pharmacodynamics effects by permanent attachment of a high molecular weight entity.
The situation is further complicated by the fact that insulin is known to readily undergo side reactions that are related to the presence of three disulfide bridges in the molecule. For instance, insulin may be split into A and B chains by disulfide bond cleavage or dimers or oligomers may be formed due to disulfide interchange reactions. Such disulfide reshuffling is particularly likely, if insulin molecules are forced into close contact in a random way ("Stability of insulin: studies on the physical and chemical stability of insulin in pharmaceutical formulation", Jens Brange, Springer, 1994). This intrinsic lability of the insulin molecule has significantly hampered progress in long-acting depot development and prevented the use of other polymer formulations where insulin is encapsulated in a way similar to an amorphous precipitate which is well known to give rise to various degradation products arising from extensive disulfide exchange.
The rate of side reactions is further influenced by the concentration of insulin, with the rate being higher when insulin is present in high concentration. It is therefore challenging to formulate high concentration long acting insulin formulations, in which insulin does not undergo undesirable side reactions.
Therefore, there is a clear need for novel long acting preparations of insulin that continuously release structurally intact insulin throughout the entire period between administrations, which at the same time retains a small ratio between the highest and lowest insulin plasma concentration in order to avoid too high or too low insulin concentrations, that can be potentially harmful for a patient.
The insulin requirement for diabetics is highly individual, with the dose depending on several physiological factors, including pancreatic beta cell function, insulin sensitivity, body weight and dietary intake. It is not uncommon for patients to require 40 IU of insulin or more per day. This is equivalent 280 IU/week which corresponds to 12.6 mg human insulin per week. In order to minimize the discomfort for the patient, this should be formulated in a small volume, for example one milliliter. It is therefore an object of the current invention, to provide an insulin formulation, in which the concentration of insulin is at least 10 mg/mL, while still releasing structurally intact insulin and displaying a substantially burstless pharmacokinetic profile. Furthermore, as a consequence, it is an object of the current invention that a single dose of the long acting insulin can be administered as a single injection of the formulation, containing at least 10 mg insulin compound.
US2007/0207210 A1 describes a method of preparing amorphous microparticles of high molecular weight proteins, and in particular antibodies. Insulin is mentioned in an example as being formulated in up to 400 mg/ml according to the disclosure. However, the object of the invention is to provide a formulation with similar pharmacokinetic profile to native protein, hence not to provide a sustained release. US2007/0207210 A1 therefore does not offer a solution to reducing the dosing frequency of insulin.


An observation lock detector block receives I&Q correlations and generates error measurement vectors, each including phase, frequency, code, pseudorange, and covariance residual estimates, and generates validity indicator and confidence indicator vectors, one of which error measurement vectors is an output as a selected error measurement vector with a respective validity indicator and confidence indicator vector, both of which selected vectors are communicated to a navigation solution processor in a ultratightly coupled navigation system for providing improved estimations of a navigation solution, the indicators indicating the usefulness of measurement errors, the prefilter detector block comprising discriminators, sequential filters, observation lock detectors and a measurement selector for selecting measurement vector based on phase, frequency, and code discriminations, the measurement errors being residual estimates that are indicated as valid or invalid for dynamic propagation of the residuals in a navigation receiver for improved performance, especially in low signal-to-noise environments, such as, for use in an ultratight GPS navigation system.

Navigation systems are increasing dependency upon the global positioning system (GPS). The navigation receiver should be able to withstand intentional or unintentional signal interference with robust signal acquisition and tracking. For this reason, inertial navigation systems have been coupled to GPS signal tracking and acquisition systems for improved signal tracking and acquisition of the received signal. Inertial navigation systems (INS) have an inertial measurement unit (IMU) for processing inertial measurements. Coupling navigation data with the GPS signal tracking and acquisition system improves signal tracking and acquisition. When the inertial measurements of a navigation processor are used with a GPS signal tracking and acquisition system, the combined system is said to be coupled. The tightly coupled GPS and INS system uses validated pseudorange and pseudorange rate measurements from the GPS receiver instead of the processed position and velocity measurements. In addition, inertial measurement unit data is usually used to assist the receiver tracking loops and enable more noise filtering than would be possible without tracking loop aiding.
The tightly coupled systems have been used with validated pseudorange and pseudorange rate measurements. More recently, ultratight GPS and INS coupling has been proposed which drives all signals from the INS navigation solution for a period of time, and then, examines all signals with respect to the error of the navigation solution. Ultratight receivers do not attempt to control code replicas for exact code phase alignment with the incoming signal but merely seek to observe the deviation of the incoming signal from locally generated replicas and feed that deviation information back to the code replica generators. Ultratight coupling has shown to be more robust in the presence of noise. Ultratight coupling does not require that the replica code track or lock onto the incoming signal. Ultratight coupling systems have been disclosed in U.S. Pat. No. 6,516,021. Observation lock detectors have been developed to extend the concept of lock detection to ultratightly coupled systems. The observation lock detectors enables error measurements to be validated before applying the error measurement to the navigation state estimate, and provides a metric of system performance.
All GPS receivers whether uncoupled, loosely coupled, tightly coupled, or ultratightly coupled correlate inphase and quadrature early E, prompt P, and late L, GPS signal replicas with the incoming GPS signal resulting in early, prompt, and late quadrature correlations that are denoted as IE, QE, IP, QP, IL, QL. These quadrature correlations have a nonlinear relationship to the difference between each replica code or carrier phase and that of the incoming received signal. The quadrature correlations are therefore used to determine the difference in the replicas code and carrier phase and that of the incoming signal. The difference between the replica code or carrier phase and that of the incoming signal is used to refine the estimate of the navigation state solution because the code and carrier phase of the incoming signal are related to the true range from the receiver to the transmitting satellite as the code and carrier phase of the replicas are related to the estimated range from the receiver to the satellite.
In ultratightly coupled receivers, a prefilter is typically a sequential filter that filters the quadrature correlation outputs to estimate one or more quantities such as a pseudorange error Δρ, pseudorange error rate Δ{dot over (ρ)}, a pseudorange error acceleration Δ{umlaut over (ρ)}, carrier phase error φ, a carrier frequency error φ′, carrier phase acceleration error φ″, a total electron content error ΔTEC, a total electron content error rate ΔTEC′, as well as a measurement covariance matrix M. The output of the prefilter is received by a lock detector. When the estimates are valid, then the estimates are forwarded to the navigation state estimator as measurements for determining the navigation solution.
A plurality of nonlinear transforms of the quadrature correlation outputs, called discriminators, are often used in tracking loop systems. Three types of discriminators are commonly used: carrier phase discriminators, carrier frequency discriminators, and code discriminators. The carrier phase discriminators may simply be the quadrature correlation outputs or a product of the quadrature correlation outputs, which results in the data bits being stripped off. The carrier phase discriminators provide the most information, but the carrier phase discriminators are also the most nonlinear so that carrier phase information may not be easily extracted by a sequential filter. When all of the epoch information can be extracted from the carrier phase discriminators by the sequential filter, there is no need to use the other carrier frequency discriminators or the code discriminators. The phase discriminators contain the most epoch information of received signal epoch timing. The carrier frequency discriminator's functions of the correlator outputs possess no carrier phase information but do contain carrier frequency information. The carrier frequency discriminators do not provide as much epoch information as the carrier phase discriminator. However, the carrier frequency discriminator provides information that is more readily extracted by a sequential filter. Sequential filter processing of epoch timing information from carrier frequency discriminators is less accurate than a sequential filter processing of epoch timing information from carrier phase discriminators, but the sequential filter processing of epoch timing information from carrier frequency discriminators is more robust. The code discriminators provide the least epoch information, but that epoch information provided is the most easily extracted by a sequential filter. A sequential filter processing of epoch timing information from the code discriminators is the most robust but less accurate than sequential filters processing of epoch timing information from the carrier phase discriminators or the carrier frequency discriminators. Existing conventional tracking loop systems use multiple discriminators in conjunction with lock detectors to ensure that the most accurate epoch timing information is being processed only when valid. The less accurate discriminators are used only when the epoch information from the carrier phase discriminators cannot be reliably extracted. Multiple sequential prefilters have been proposed to solve the multipath problem. However, each of the sequential filters employed corresponds to a different multipath assumption. Parallel sequential prefilters have been used. Each of the parallel sequential prefilters have a different assumed noise level and apply the prefilters to the same I&Q correlations. As such, existing systems use a signal discriminator as input to the sequential filters. Consequently, existing navigation systems do not ensure that the most accurate and reliable epoch timing information is being extracted, validated, and used to compute the navigation solution. These and other disadvantages are solved or reduced by the present invention.

Ultratight coupling prefilter detection block


In a double-wrap band brake assembly, an intermediate band is provided with a first friction material forming a first friction surface from a portion of the intermediate band near an apply bracket to a predetermined intermediate portion thereof, the first friction surface working for forming a lubricant film. The intermediate band is further provided with a second friction material having a thickness that is larger than a thickness of the first friction material and forming a second friction surface from the predetermined intermediate portion to a vicinity of a coupling portion of the intermediate band with a pair of outer bands, the second friction surface working for removing the lubricant film.

1. Field of the Invention
The present invention relates to a double-wrap brake band assembly which is used in an automatic transmission, or the like, for a car, and to a technology for facilitating and securing a braking control.
2. Related Background Art
A band brake apparatus is widely used for braking a transmission element or rotation element in an automatic transmission for a car or in a general industrial machine. A band brake apparatus generally comprises a brake band which is formed by attaching a frictional material to the inner peripheral surface of one steel plate in an annular form. This brake band is constricted by an actuator to fasten a transmission element or a rotation element disposed on the inner side thereof to apply the brake. Therefore, recently, in order to reduce the working power of the actuator and to enhance the controllability of the brake, there is proposed a double-wrap band brake assembly which employs a double-wrap brake band.
As illustrated in FIG. 20 and FIG. 21 (a view seen in the direction indicated by the arrow F in FIG. 20), a double-wrap brake band 3 of a double-wrap band brake assembly is mainly composed of an annular middle band 11 and a pair of annular outer bands 15 which are welded to the middle band 11 through a coupling plate 13 in a state that the respective free ends thereof of the outer bands 15 are opposed to the free end of the middle band 11. Frictional materials 17 and 19 are attached to the inner peripheral surfaces of the middle band 11 and the outer bands 15, respectively. While an anchor bracket 21 which is latched by an anchor pin 5 on the side of a main body casing 1 is welded to the working ends of the outer bands 15, an apply bracket 25 for receiving a force in the direction in which the middle band 11 and the outer bands 15 are constricted by means of a push rod (apply pin) 23 of an actuator 7 is welded to the working end of the middle band 11. In this double-wrap brake band 3, when the apply pin 23 of the actuator 7 is operated in the direction indicated by the arrow in FIG. 20, the middle band 11 and the outer bands 15 are constricted so as to brake a transmission element (hereinafter called the drum) 27 which is fitted in the double-wrap brake band 3.
Incidentally, when the conventional double-wrap band brake assembly is used to brake a rotation element or the like of an automatic transmission, it sometimes becomes a hindrance to a smooth gear change operation. For example, in the above-described double-wrap brake band 3, when it is driven by the apply pin 23 and constricted to thereby come into sliding contact with the drum 27, the bands 11 and 15 wrap around the drum 27 therein by the self engagement effect. As a result, as indicated by the broken line in FIG. 4, a value of the dynamic friction coefficient at the beginning of braking momentarily rises so as to apply the brake on the drum 27 rapidly, whereby, as indicated by the broken line in FIG. 5, a ratio of torque transmission reaches 100% in an extremely short period, and a comparatively large gear change shock is brought about. Particularly, in an area with a small throttle angle in which the transmission torque is comparatively small, a correct braking control is required. However, in the double-wrap band brake assembly, a working stroke of the apply pin 23 is large, which results in a deteriorated response performance and a large torque capacity. As a result, it is very difficult to control a servo pressure and a servo working amount. That is, it is desirable that the bands 11 and 15 come into sliding contact with the drum 27 with a predetermined sliding at the beginning of the brake. However, if the servo pressure and the servo working amount fluctuate, the brake is applied with a little or no sliding amount so as to produce a great transmission shock.
On the other hand, the present inventors, et al., attempted to cause practically no self engagement effect described above by positively introducing an automatic transmission oil into between the double-wrap brake band 3 and the drum 27. However, in this case, with advance of constriction of the double-wrap brake band 3 and the removal of the automatic transmission oil, the dynamic friction coefficient between the double-wrap brake band 3 and the drum 27 gradually increases correspondingly, as shown by the two dot chain line in FIG. 4. Thereby, the drum 27 is slowly braked and, as indicated by the broken line in FIG. 5, a comparatively long time is required for obtaining 100% of the torque transmission ratio. As a result, it becomes difficult to detect a brake starting point of the double-wrap band brake assembly, so that driving control of another transmission element of the automatic transmission can not be smoothly effected.


In a multi-processor system, a page descriptor can be updated in a memory coupled to a processor without stopping operations of other processors. Each processor has a page descriptor comparator including a calculated address register which stores a physical page address for an address calculation, and an updated address register which stores a physical page address to be updated. The page descriptor comparator also has a reset page descriptor (RSTPD) mode register which indicates a mode of the processor, and a coincidence detector. If the RSTPD mode register is active, the coincidence detector detects coincidence between the calculated address register and the updated address register.

The present invention relates to a multi-processor system and method for controlling an access to a page descriptor for paging, and more particularly to a multi-processor system and method for controlling an access to a page descriptor which is being reset (e.g., updated).
Paging systems use fixed-length blocks called "pages" and assign the pages to fixed regions of physical memory called "page frames". Referring to FIG. 1, each logical address comprises two parts: a page address and a displacement. The displacement is a relative address in a page. For each logical page address, there is the corresponding physical address of a page frame in main or secondary memory. A page table stores page descriptors specifying pages. Each page descriptor has a physical page address. Each physical address (e.g., effective address) comprises the physical page address and the displacement.
In a conventional multi-processor system with paging, while a page descriptor is updated by a certain processor, an access to the page descriptor by other processors is prohibited. Moreover, during the updating process and prior to performing other processes, the other processors must wait for completion of the updating, for example, by performing a loop of "firmware" instructions.
However, normal operations cannot be performed until the updating operation of the page descriptor is completed, since the other processors are in "waiting" (pause) states. This waiting by the other processors lowers the system performance since the other processors are idle.

Multi-processor system and method for controlling access to a page descriptor during the process of updating the page descriptors


A method of monitoring runtime memory usage by a program. The method can include retrieving data from a first region of virtual memory that has been allocated to the program and compressing the data. A data compression rate can be measured. The method further can include generating a notification comprising notification data indicating that the first region of memory was not efficiently used by the program during execution when the data compression exceeds a threshold value or the data compression rate exceeds a statistical value determined from an application's memory usage.

Modern computing systems utilize virtual (or logical) memory. Virtual memory is a concept that, when implemented by a computer and its operating system, maps virtual storage addresses to physical storage addresses, which generally frees software programmers from being concerned about the availability of data storage. Virtual memory also allows programmers to use a contiguous range of memory, or storage addresses for stored data, that may be larger than the amount of physical memory (RAM) available to the computer.
In addition to managing the mapping of virtual storage addresses to real storage addresses, a computer implementing virtual memory also manages storage swapping between active storage (RAM) and hard disks or other high volume storage devices. Virtual storage is typically committed in units called "pages" that form virtual memory regions ranging from a few kilobytes up to several megabytes in size. Managing storage in this manner allows multiple programs to safely run simultaneously on the computer.
In certain programming languages, including C and Pascal, heaps are used to manage allocation of virtual memory. A heap is an area of pre-reserved storage that a program process can use to store data in some calculatable amount that won't be known until the program is running. For example, a program may accept different amounts of input from one or more users for processing and then perform processing on all the input data at once. Having a certain amount of heap storage already obtained from the operating system facilitates storage management and is generally more efficient than asking the operating system for storage every time it is needed. A process manages its allocated heap by requesting heap memory blocks as needed and returning the blocks when they are no longer needed. Heaps often become fragmented, wasting memory in the virtual address space and, correspondingly, wasting space in physical memory. Heap fragmentation can also contribute to memory overhead that can result in "thrashing" and poor system wide performance in a heavily-loaded system.
To aid application developers in optimizing memory usage, it would be beneficial to provide a notification to the developers when memory is not being efficiently used.

Use of memory compression algorithm to assess efficiency of memory usage


A cart includes a frame, a holding portion supported by the frame and in which a product is stored, a lifting unit configured to raise and lower the holding portion, an imaging device directed towards an inside of the holding portion, and a controller. The controller is configured to acquire an image of a product captured by the imaging device, determine whether the product has been continuously imaged by the imaging device over a predetermined time period, and upon determining that the product has been imaged over the predetermined time period, control the lifting unit to lower the holding portion.

In recent years, a shopping cart provided with a scanner that reads information from a product has been used in larger retail stores such as a supermarket. Such a cart can be designed so that the scanner automatically reads product information when the product is placed in the cart. For example, with appropriate settings of an imaging direction and range for the scanner an image of the product in the cart can be acquired.
However, in a case where many products are placed in the cart, some of the products may be located close to the scanner. In such a case, a product near the scanner may hinder reading of another new product, or a product that has been read may be read twice.


A wet-mateable connector unit for use in vertical or substantially vertical orientation in a subsea gas well has an outer shell and a movable wall inside the shell surrounding a pressure compensated chamber containing dielectric fluid. The chamber wall is exposed to ambient pressure outside the connector unit. At least one relief valve is mounted in the connector unit and has an inlet in communication with the upper end of the chamber and an outlet in communication with the external environment surrounding the connector unit. The relief valve opens to release gas from the upper end of the chamber when the differential pressure between the chamber and external environment exceeds a predetermined valve cracking pressure. A plurality of relief valves may be provided.

1. Field of the Invention
The present invention relates generally to connector assemblies having releasably mateable plug and receptacle units designed for use underwater or in other hostile environments, and is particularly concerned with a connector unit and method for downhole connectors exposed to gas for extended periods of time.
2. Related Art
There are many types of connectors for making electrical and fiber-optic cable connections in harsh environments, such as underwater or subsea electrical, optical and hybrid electrical and optical connectors which can be repeatedly mated and de-mated underwater at great ocean depths. These connectors typically consist of releasably mateable connector units or plug and receptacle units, each attached to cables or other devices intended to be joined by the connectors to form completed circuits. Each connector unit contains one or more electrical and/or optical contacts or junctions for engagement with the junctions in the other unit when the two units are mated together. To completely isolate the contacts to be joined from the ambient environment, one or both connector units house the contacts in fluid-filled, pressure-compensated chambers. The fluid may be a dielectric fluid or oil in the case of an electrical connector. The dielectric fluid is typically pressure compensated by means of a movable or flexible member, such as a piston or a flexible bladder, forming a wall of the dielectric chamber.
In oil and gas well connector applications, the plug and receptacle units of wet-mateable downhole electrical connectors are mated and de-mated at a point downhole or subsea in order to releasably connect power or signal to downhole equipment such as pumps, sensors, or the like, with the connector units oriented vertically or at an angle. One of the connector units is connected to the downhole equipment while the other connector unit is at the end of a power supply or signal communication cable. In gas well applications where the connector is exposed to gas for extended durations, the gas can permeate through the flexible bladder or the piston seals of the dielectric chamber and dissolve in the dielectric fluid. If the ambient pressure is reduced at a sufficiently high rate, the dissolved gas can come out of solution and expand. This expansion causes an increase in internal pressure in the connector, which can exceed the design limits of the pressure compensation devices such as pistons or bladders, potentially causing failure of those devices and thus electrical or optical failure of the whole connector.

Wet-mateable connector unit with gas pressure relief


A method for diagnosing a tumor in the central nervous system of a mammal is carried out by contacting a bodily fluid from the mammal with a ligand which binds to inter-alpha trypsin inhibitor.

The invention relates to cancer diagnosis.
Effective treatment for patients with cancers of the central nervous system (CNS) is, for the most part, an unmet challenge, and the incidence of both primary and metastatic brain tumors appears to be increasing. The prognosis of patients with malignant gliomas and brain metastases remains poor.
Cytological examination to detect malignant cells in the cerebrospinal fluid (CSF) is a standard method by which diseases such as leptomeningeal carcinomatosis are diagnosed. The absence of malignant cells is a primary endpoint for most therapeutic interventions. However, false negatives are often encountered. The inability to estimate or detect the residual burden of disseminated cells by conventional imaging technologies (computerized axial tomography (CT) scan or magnetic resonance imaging (MRI)) compromises decision making on prognosis and treatment.
The invention provides an accurate and reliable method of diagnosing primary brain tumors or brain metastases. A method for diagnosing a tumor in the CNS of a mammal is carried out by contacting a bodily fluid from the mammal with a detectable ITI ligand and measuring the amount of bound ITI ligand in the sample of bodily fluid. For example, the ligand is a monoclonal antibody or polyclonal antisera which binds to an ITI polypeptide, e.g., an ITI light chain polypeptide; a sample of bodily fluid is contacted with the antibody under conditions sufficient to form an antigen-antibody complex and the complex(es) detected. Alternatively, the ligand is a synthetic or proteolytically-generated peptide that binds to the ITI light chain. For detection purposes, the ligand, e.g., ITI-specific antibody, is directly or indirectly labelled using, e.g., a calorimetric or radioisotopic marker. The amount of the immune complex (which contains ITI antigen bound to ITI-specific antibody) is quantitated to determine the level of ITI in the fluid, and the level of ITI in the fluid is compared to a normal control level of ITI (e.g., a previously determined baseline value or the level of ITI from a subject known to be cancer-free). ITI is elevated in the bodily fluids of patients with CNS tumors as a result of secretion of ITI by disseminated cancer cells or as a result of breakdown of the ECM, which causes leakage of serum ITI into the CSF. Alternatively, tumor cells stimulate production of ITI by surrounding tissues in the brain such as choroid plexus and astrocytes. An elevated level of ITI compared to a normal control level indicates the presence of a tumor in the CNS of the tested mammal. For example, the presence of a tumor is indicated by an amount of ITI in a test sample which is at least two-fold greater than that in a normal control or normal baseline amount of ITI in a CNS bodily fluid such as (CSF). For example, the amount of ITI in the test sample is 2-7 fold greater than normal. The level of ITI in a CNS bodily fluid is indicative of a neurological tumor.
The bodily fluid is a preferably a CNS-derived fluid. By CNS is meant a bodily tissue of the brain or spinal cord. For example, a CNS-derived fluid is cerebrospinal fluid or the supernatant of a cell lysate of cells of the brain, spinal cord, or cells found in the CSF. Other bodily fluids such as blood, serum, urine, saliva, sputum, perspiration, lung effusion, or ascites fluid are tested for the level of ITI as an indication of CNS pathology.
Also with the invention is a method for prognosis of a tumor in the CNS of a mammal, which is carried out by (a) contacting a bodily fluid, e.g., a CNS-derived fluid, from the mammal with an antibody reactive with an ITI polypeptide, e.g., an ITI light chain, under conditions sufficient to form an antigen-antibody complex and detecting the antigen-antibody complex; (b) quantitating the amount of complex to determine the level of ITI in the fluid; and (c) comparing the level of ITI in the fluid with a normal control level of ITI. Changes in the severity of the disease are monitored by comparing changes in the level of ITI in bodily fluids of the patient over time. An increasing level of ITI, e.g., in the CSF, over time indicates an adverse prognosis, e.g,. increased CNS pathology. Such temporal data is used to determine a course of treatment for the patient.
The invention features a monoclonal antibody that binds to an epitope of ITI light chain. The antibody binds to residues within or proximal to an active site of the ITI light chain. When incubated in the presence of ITI and a serine protease, the antibody inhibits ITI-mediated inhibition of serine protease activity. Preferably, the antibody, e.g., mAb 69.31, does not bind to an octapeptide sequence of Urinary Trypsin Inhibitor fragment (UTI), Arg-Gly-Pro-Cys-Arg-Ala-Phe-Ile (SEQ ID NO:1).
Reagents, e.g., an ITI-specific antibody such as mAb 69.31, for carrying out the diagnostic or prognostic assay may be packaged together as a kit. For example, the antibody is immobilized on a solid phase and packaged together with other reagents suitable for detecting ITI-ligand complexes. For example, enzyme-conjugated reagents may be included; ITI may also be included as a standard or control reagent. The solid phase component of the kit onto which an antibody or antigen is immobilized is preferably an assay plate, an assay well, a nitrocellulose membrane, a bead, a dipstick, or a component of an elution column. For example, the capture antibody, e.g., mAb 69.31, is immobilized and a secondary antibody is used to detect the immune complex (e.g., an ITI antigen bound to the mAb 69.31 antibody. The kit may optionally contain a purified ITI polypeptide or purified ITI complex as a control. The polypeptide or complex is purified from natural sources or recombinantly produced. The kit may also contain a second antibody or other detectable marker. The second antibody or marker is labelled, e.g., using a radioisotope, fluorochrome, or other means of detection.
Also within the invention is a method of inhibiting metastases of a systemic cancer into the CNS of a mammal by administering to the mammal an ITI composition, e.g., an ITI polypeptide or a nucleic acid encoding an ITI polypeptide. For example, a sythetic oligonucleotide encoding an ITI polypeptide is administered. The ITI composition is administered by infusion directly into the CSF of the mammal. For therapeutic administration, the ITI polypeptide is administered in its native form as a molecular complex in which an ITI light chain is bound to an ITI heavy chain. The method may include a step of identifying a mammal at risk of developing a brain metastases. For example, the following cancers have a tendency to metastasize to the CNS, e.g, the brain: breast cancer, lung cancer, ovarian cancer, kidney cancer, malignant melanoma, esophageal cancer, head and neck cancers, testis cancer, choriocarcinoma, prostate cancer, bone cancers, and soft tissue sarcomas. Individuals diagnosed as having such cancers are among those at risk of developing a metastases of the cancer to the CNS. Individuals suspected of having CNS cancer are also identified by detecting clinical symptoms such as headache, nausea or vomiting, seizures, altered mental status, altered speech, visual abnormalities, and/or paralysis. A CT scan or MRI is often used to diagnose brain metastases. However, the assays of the invention provide significant advantages, e.g., increased sensitivity, over such conventional diagnostic tools. The claimed assays accurately and reliably detect the presence of tumor very early (prior to the time at which a tumor is detected by the appearance of physical symptoms or by CT or MRI).
A method of inhibiting metastases of a primary CNS cancer in a mammal is also within the invention. The therapy is carried out by administering to into a mammal an ITI polypeptide, e.g., by direct infusion into the CSF of the mammal. Individuals having been diagnosed with the following CNS cancer types are treated according to the invention: astrocytoma, glioma, or metastases into the brain from other cancer types such as leukemias or carcinomas.
Other features and advantages of the invention will be apparent from the following detailed description, the drawings, and the claims.

Methods for detecting cancer of the central nervous system

Rhode Island Hospital, A Lifespan Partner


A spoon basket of a dishwasher is provided. The spoon basket includes a basket for storing silverware, a cap that is disposed on top of the basket to move up and down, and a basket handle that extends a predetermined distance from the basket and supports the cap.

A dishwasher is a machine for washing dishes and has an upper spray arm and a lower spray arm installed in a tub. The spray arms spray pressurized wash liquid onto dishes to clean them of food deposits.
A dishwasher has a dish rack installed inside to hold dishes. A separate spoon basket for storing silverware, cooking utensils, etc. is additionally installed on one end of the dish rack. Accordingly, silverware does not fall through holes at the bottom of the dish rack onto the floor of the tub when it is stored along with dishes in the dish rack. Also, arranging silverware after a dishwashing cycle is easier because the silverware is collectively stored in the rack.
A spoon basket for installation in a dish rack as described above is disclosed in Korean Utility Model No. 20-1997-0001 115, filed by the applicant of this invention, which is hereby incorporated by reference.
In related art dishwasher spoon baskets, however, the downside of storing silverware and utensils collectively is that longer items, such as ladles have a tendency to fall out of the basket or to lean sideways and interfere with adjacently stored large dishes or the dishwasher door.


A docking station with a filter that sits inline in a process gas channel and that alternatively receives a loopback plate, a sensor plate and a removable purifier cartridge for particle removal as well as the removal of trace amounts of moisture, oxygen, and other chemical impurities from a gas stream. The removable purifier cartridge comprises a purifying medium with a pair of sealing poppet valves that automatically close when the cartridge is removed from the docking station. A block body is included in the docking station with gas line fittings for close gland-to-gland separations, while the purifier cartridge is off to one side, and not positioned directly in line between the glands.

1. Field of the Invention
The invention relates generally to gas filters and purifiers and more specifically to devices that remove both particles and chemical impurities from gases used to fabricate integrated circuits in the semiconductor industry.
2. Description of the Prior Art
Semiconductor processing requires the use of a wide variety of gases in the fabrication process. The conductivity of semiconductor materials is controlled by the careful introduction of certain impurities, such as phosphorus and boron. Unwanted impurities, or even the right ones in the wrong amounts, can spoil all the semiconductor wafers subject to the contamination. Semiconductor manufacturers go to great lengths to buy pure silicon ingots, design and operate class 100, class 10, and class 1 cleanrooms, and even require personnel to wear lint-free "bunny suits" to reduce the risk of contamination.
Gas producers take great care to supply contamination-free gases, but contaminants inevitably creep in. The semiconductor industry therefore customarily uses filters and purifiers at the point-of-use near where the gas is actually used in the process. As such, space is at a premium. Available space is also shrinking with successive generations of equipment as the tools that use them are getting smaller and smaller. Periodic replacement of both filters and purifiers is needed, and this requires that connectors and valves be included and the filters and purifiers located so as to accommodate service. Both the valves and the location needs consume more valuable space.
Several manufacturers worldwide produce a range of purifiers that use various purifying agents internal to the devices. SAES Pure Gas (San Luis Obispo, Calif.) produces a purifier that uses a gettering alloy that must be heated during regeneration. Japan Pionics, Nippon Sanso, Advanced Technology Materials, Inc. (New Milford, Conn.), and Ergenics (Wyckoff, N.J.) also make commercially available purifiers. Matheson Electronics Product Group, Semi-Gas Division (San Jose, Calif.), produces a line of purifiers that are filled with a highly reactive resin that is commercially marketed as NANOCHEM.RTM.. The NANOCHEM resin does not require heating during use and is much less expensive to operate than the types that do require heating. The NANOCHEM, however, must be protected from exposure to air. Also, none of the resin material should be allowed to come close to welds as they are being made, because welding a purifier closed can cause the NANOCHEM resin material to melt. Such melting can release enough contaminants to saturate the remaining resin in the purifier.
As integrated circuit semiconductor device geometries decrease, the purification of gases used in fabrication needs to be closer to the point of use. The number of conventional filter-purifiers is limited in such applications. Some otherwise acceptable filter-purifiers are only available in a gland-to-gland dimension of 3.31 inches and have unacceptably low flow rates. Many prior art devices are, at times, difficult to install, because they have an outer radius of 0.75 inches, which is more than the port-center-to-back dimension of the majority of mass flow controllers (MFCs) that they are used with. Standoff brackets are often required to raise the MFCs and other manifold components to accommodate such filter-purifiers.
Equipment gas manifolds are increasingly using smaller footprints. A modular block approach to purification is needed for such applications and to allow for the industry trend toward smaller gland-to-gland and vertical height dimensions.
Modern-day users require purification systems that are located close to the point of use, e.g., inside the housing of a mass flow controller. However, such locations are crowded and provide inadequate room in-line with the process gas flows to accommodate the necessary filter and purification units. The life times and range of process gas applications of conventional units in such tight spaces are very limited. Frequent filter-purifier changes can compromise the very gas distribution system being protected, because each change allows some contaminating outside gases, e.g., water vapor and air, to enter.
At the time a process gas panel is ordered, manufactured and/or installed, it may not be clear what, if any gas purification system needs to be included. In prior art equipment, the adding-on of a gas purification system in a gas panel is difficult because of the tight spaces and can compromise the gas distribution channel by introducing contaminants during the installation of the purifier.

Process gas docking station with point-of-use filter for receiving removable purifier cartridges


The invention provides proteins attached to solid supports, and methods of preparing such solid support-bound proteins are provided. The proteins are attached to solid supports by means of an unnatural amino acid incorporated into the protein, which unnatural amino acid includes a reactive group that can react with a second reactive group that is attached to a solid support.

Recent advances in genomics have culminated in sequencing of entire genomes of several organisms, including human. Genomics alone, however, cannot provide a complete understanding of cellular processes that are involved in disease, development and other biological phenomena, because such processes are mediated by polypeptides. Given that huge numbers of polypeptides are encoded by the genome of an organism, the development of high throughput technologies for analyzing polypeptides is of paramount importance.
One key technology that can enable high throughput, highly parallel analysis of polypeptides is the protein array (also called a microarray). A protein microarray typically consists of many polypeptides, each of which is attached to a solid support. The polypeptides in the microarray can be contacted with other molecules to determine, for example, whether the molecule binds to or otherwise interacts with one or more of the polypeptides in the array. For example, one can identify a previously unknown receptor for a ligand of interest by contacting a polypeptide array with the ligand and determining which polypeptide in the array binds the ligand. As another example, one can quickly identify all polypeptides that are phosphorylated by a particular kinase by contacting a protein array with the kinase and detecting those polypeptides that become phosphorylated. Yet another use for protein arrays is to detect small molecules and other moieties that alter the enzymatic or binding activity of polypeptides.
For many applications, it is desirable that each polypeptide in an array be attached to the solid support in a consistent orientation. Attachment of every polypeptide in the array at or near its amino terminus or its carboxyl terminus, for example, can help ensure that the active site or sites of each polypeptide are accessible to potentially interacting molecules. Moreover, the attachment of the polypeptide should not disrupt the conformation of the polypeptide, particularly if one desires to detect an activity of the immobilized polypeptides. Thus, a need exists for improved protein arrays, and methods for their preparation. The present invention fulfills these and other needs.


A circuit board having a power supply, an electrical device having a circuit board, and a method for producing a circuit board are disclosed. In an embodiment a circuit board includes a power supply, a carrier substrate and an energy store with a first layer stack having a first electrode layer with a first electrode, a second electrode layer with a second electrode, and an electrolyte layer arranged therebetween, which has an electrolyte, wherein the first electrode, the second electrode and the electrolyte are solid states.

In general, electrical circuits require electrical energy to operate. It is possible to supply electrical circuits with electrical energy from an external energy source by means of a power connection. Alternatively, it is possible to arrange a battery or an accumulator on the upper side of a circuit board and to use it as an energy source.
As a result of the continuing trend towards miniaturisation of electrical components, the volume of a battery is occupying, in relative terms, a larger and larger proportion of the total volume of an electrical device.
In the case of those devices which do not have a battery, there is always a risk of a sudden loss of contact and, consequently, of the circuit no longer being supplied with electrical power.

Circuit board having power supply, electrical device having circuit board, and method for producing a circuit board