A novel Zantedeschia cultivar, designated 7033-01, is disclosed. The invention relates to the seeds of Zantedeschia cultivar 7033-01, to the plants of Zantedeschia cultivar 7033-01 and to methods for producing a Zantedeschia plant produced by crossing the cultivar 7033-01 with itself or another Zantedeschia variety. The invention further relates to hybrid Zantedeschia seeds and plants produced by crossing the cultivar 7033-01 with another Zantedeschia cultivar.

The present invention relates to a new and distinctive Zantedeschia cultivar, designated 7033-01. The genus is restricted to the African continent with several species being recognized, including Z. aethiopica (Richardia Africana) referred to as the Common Calla; Z. aethiopica minor; Z. elliottiana and Z. angustiloba (R. Pentlandii) referred to as the Yellow Callas; Z. rehmannii referred to as the Pink Calla; Z. albo-maculata, the Spotted Calla and Z. melanoleuca, the Black-throated Calla.
These deciduous perennials are native to South Africa. They can be planted in a greenhouse that has a minimum temperature of 50° F. or outside where climates are mild. They are mainly grown for their attractive, large flower spathes, which are usually produced in the spring and summer. Calla Lilies or Arum Lilies, as they are commonly known, are grown in large quantities by commercial growers because they are commonly used for decoration at Easter, weddings, funerals and throughout the spring and early summer months.
The flower spathes of the common Zantedeschia are often white with a yellow spadix and it produces glossy, plain, arrow-shaped leaves. Some varieties grow 2 to 3 feet high. The spathes of the Yellow or Golden Callas, Z. elliottiana, are yellow with spotted leaves that are arrow or ovate-shaped. Z. rehmannli, the Pink Calla or Pink Arum, produces lavender-red, rose-red, violet-red or pink spathes and is a smaller plant (growing up to 16 inches) than the white or yellow flowered varieties. Its leaves are lanceolate and plain.
Zantedeschia are an excellent cut flower and last a long time in water. The striking Zantedeschia "flower" is actually many tiny flowers arranged in a complex spiral pattern on the central column (spadix). The tiny flowers are arranged in male and female zones on the spadix. The top portion of the spadix is male flowers and the lower part is female. If you look through a microscope, you may see the stringy pollen emerging from the male flowers which consist largely of anthers. The female flowers have an ovary with a short stalk above it, which is the style where the pollen is received. The spadix is surrounded by the white or colored spathe. It is believed that the whiteness of the spathe is not caused by pigmentation, but is an optical effect produced by numerous airspaces beneath the epidermis.
The Z. aethiopica flowers are faintly scented, which attracts various crawling insects and bees that are responsible for pollinating the flowers. Cross pollination occurs as the anthers of each flower ripen before the ovaries. A white crab spider of the family Thomisidae visits the flower to eat the insects. This spider does not spin webs and uses its whiteness as camouflage against the spathe. The spathe turns green after flowering and covers the ripening berries. It rots away when these are ripe and the succulent yellow berries attract birds, which are responsible for seed dispersal.
There are numerous steps in the development of any novel, desirable plant. Plant breeding begins with the analysis and definition of problems and weaknesses of the current germplasm, the establishment of program goals, and the definition of specific breeding objectives. The next step is selection of germplasm that possess the traits to meet the program goals. The goal is to combine in a single variety an improved combination of desirable traits from the parental germplasm. These important traits may include vigorous growth, height, color, disease, insect and virus tolerance.
Choice of breeding or selection methods depends on the mode of plant reproduction, the heritability of the trait(s) being improved, and the type of cultivar used commercially (e.g., F1 hybrid cultivar, pureline cultivar, etc.). For highly heritable traits, a choice of superior individual plants evaluated at a single location will be effective, whereas for traits with low heritability, selection should be based on mean values obtained from replicated evaluations of families of related plants.
The complexity of inheritance influences choice of the breeding method. Backcross breeding is used to transfer one or a few favorable genes for a highly heritable trait into a desirable cultivar. This approach has been used extensively for breeding disease-resistant cultivars. Various recurrent selection techniques are used to improve quantitatively inherited traits controlled by numerous genes. The use of recurrent selection in self-pollinating crops depends on the ease of pollination, the frequency of successful hybrids from each pollination, and the number of hybrid offspring from each successful cross.
Each breeding program should include a periodic, objective evaluation of the efficiency of the breeding procedure. Evaluation criteria vary depending on the goal and objectives, but should include gain from selection per year based on comparisons to an appropriate standard, overall value of the advanced breeding lines, and number of successful cultivars produced per unit of input (e.g., per year, per dollar expended, etc.).
Promising advanced breeding lines are thoroughly tested and compared to appropriate standards in environments representative of the commercial target area(s). The best lines are candidates for new commercial cultivars; those still deficient in a few traits may be used as parents to produce new populations for further selection.
These processes, which lead to the final step of marketing and distribution, usually take from six to 12 years from the time the first cross is made and may rely on the development of improved breeding lines as precursors. Therefore, development of new cultivars is a time-consuming process that requires precise forward planning, efficient use of resources, and a minimum of changes in direction.
A most difficult task is the identification of individuals that are genetically superior, because for most traits the true genotypic value is masked by other confounding plant traits or environmental factors. One method of identifying a superior plant is to observe its performance relative to other experimental plants and to a widely grown standard cultivar. If a single observation is inconclusive, replicated observations provide a better estimate of its genetic worth.
The goal of plant breeding is to develop new, unique and superior Zantedeschia cultivars and hybrids. The breeder may initially select and cross two or more parental lines, followed by self pollination and selection, producing many new genetic combinations. The breeder can theoretically generate billions of different genetic combinations via crossing, selfing and mutations. The breeder has no direct control at the cellular level. Therefore, two breeders will never develop the same line, or even very similar lines, having the same Zantedeschia traits.
Each year, the plant breeder selects the germplasm to advance to the next generation. This germplasm is grown under unique and different geographical, climatic and soil conditions, and further selections are then made, during and at the end of the growing season. The cultivars which are developed are unpredictable. This unpredictability is because the breeder's selection occurs in unique environments, with no control at the DNA level (using conventional breeding procedures), and with millions of different possible genetic combinations being generated. A breeder of ordinary skill in the art cannot predict the final resulting lines he develops, except possibly in a very gross and general fashion. The same breeder cannot produce the same cultivar twice by using the exact same original parents and the same selection techniques. This unpredictability results in the expenditure of large amounts of research monies to develop superior new Zantedeschia cultivars.
The development of new Zantedeschia cultivars requires the development and selection of Zantedeschia varieties, the crossing of these varieties and selection of superior hybrid crosses. The hybrid seed is produced by manual crosses between selected male-fertile parents or by using male sterility systems. These hybrids are selected for certain single gene traits such as vigorous growth, greater height, color, floriferousness, disease tolerance and pollen production which indicate that the seed is truly a hybrid. Additional data on parental lines, as well as the phenotype of the hybrid, influence the breeder's decision whether to continue with the specific hybrid cross.
Pedigree breeding and recurrent selection breeding methods are used to develop cultivars from breeding populations. Breeding programs combine desirable traits from two or more cultivars or various broad-based sources into breeding pools from which cultivars are developed by selfing and selection of desired phenotypes. The new cultivars are evaluated to determine which have commercial potential.
Mass and recurrent selections can be used to improve populations of either self- or cross-pollinating crops. A genetically variable population of heterozygous individuals is either identified or created by intercrossing several different parents. The best plants are selected based on individual superiority, outstanding progeny, or excellent combining ability. The selected plants are intercrossed to produce a new population in which further cycles of selection are continued.
Backcross breeding has been used to transfer genes for a simply inherited, highly heritable trait into a desirable homozygous cultivar or inbred line which is the recurrent parent. The source of the trait to be transferred is called the donor parent. The resulting plant is expected to have the attributes of the recurrent parent (e.g., cultivar) and the desirable trait transferred from the donor parent. After the initial cross, individuals possessing the phenotype of the donor parent are selected and repeatedly crossed (backcrossed) to the recurrent parent. The resulting plant is expected to have the attributes of the recurrent parent (e.g., cultivar) and the desirable trait transferred from the donor parent.
Descriptions of other breeding methods that are commonly used for different traits and crops can be found in one of several reference books (e.g., Allard, 1960; Simmonds, 1979; Sneep et al., 1979; Fehr, 1987).
Proper testing should detect any major faults and establish the level of superiority or improvement over current cultivars. In addition to showing superior performance, there must be a demand for a new cultivar that is compatible with industry standards or which creates a new market. The introduction of a new cultivar will incur additional costs to the seed producer, the grower, processor and consumer for special advertising and marketing, altered seed and commercial production practices, and new product utilization.


A method and system for processing information in a social network system are disclosed. The method includes: in a network system, especially in a social network system, adding a piece of information having a new information structure to serve as a basic unit for expression intension of a user while enabling a user to be capable of continuously releasing a piece of information having a simple structure as a basic unit for expressing intensions. This information having the new structure describes relative locations of multiple basic units expressing meanings when being exhibited, and the meanings thereof are expressed by using a combination of the recited basic units in a manner of the multiple basic units. As such, information expression efficiency in the system is improved, and the information screening capability is enhanced, thereby naturally implementing structured reorganization of the information and significantly improving the information processing capability of the system.

Conventional social networks, for example, Facebook, Twitter and various forums, BBS and the like, most uses one piece of information as a basic information unit for expressing users' intensions and meanings, which has an information structure significantly simpler relative to an HTML file featuring free composing and expression. In this case, when editing the information, the users almost do not need to explain how their released information is exhibited, and the social networks would process and exhibit the information released by the user according to a predetermined format. In addition, in logic, a user interface provided by the system enables the user perform an operation, such as, release, forward and comment, by using one piece of information as an integrity. As such, great convenience is brought to exchanges between users.
With development to an on-line trend of people's life and popularity of short-text information, people's daily communication and information exchanges are simultaneously recorded in a network space.
However, in the related art, information is restricted to a short text and thus the meanings or intentions of people are hard to be expressed, or people need to compose pieces of long information to express their intentions or meanings, thereby losing the advantages of short texts. In addition, a social network using the short-text information as basic information exchange units is subjected to flood of fragmented short-text information, and failure to effectively search for the short texts due to lack of a screening mechanism.
It is a constant difficulty as how to determine a basic information structure of a piece of information in the social network such that the user enjoys convenience like releasing information in an IM system, conveniently and quickly expresses complicated intentions and meanings, fully utilizes masses of fragmented information generated in on-line activities, and greatly improves the search quality and efficiency.
In addition, in the conventional search technology, each time upon search, the user almost evaluate, screen and comprehensively understand search results. However, there is still no convenient channel for releasing the achievements of the above activities to a network system, and thus the quality of the searched information source gains a slow improvement.

Method and system for processing information in social network system


In accordance with one or more embodiments herein, a system for monitoring the condition of a road surface traveled by a plurality of vehicles, each comprising at least one sensor, is provided. The system comprises a central processing arrangement arranged to: map at least a part of the road surface with a number of cells; receive road surface data for the cells, which road surface data is based on measurements made by the sensors as the plurality of vehicles travel on the road surface; and calculate a probability for at least one road surface parameter for each cell traveled by the plurality of vehicles based at least on road surface data received from the plurality of vehicles.

Systems that provide vehicles with information about the road conditions may be used to increase road safety for conventional vehicles, but will become increasingly important with the introduction of autonomously driving vehicles. If a vehicle has information about e.g. the friction on the road, and/or whether there is damage such as potholes in the road, warnings can be given to the driver/vehicle, and the driver/vehicle can adapt to the road condition. For example, automatic braking systems can adapt to the friction on the road.
US20150224925 describes a method for determining a state of a pavement. Data received from at least one sensor that measures a local friction coefficient is assigned to individual image sectors of a camera image collected by a forward facing camera. Image analysis then provides a classification of individual pavement segments in camera images to different classes, such as e.g. dry, wet, snow-covered or icy, and friction coefficients are assigned to these segments based on previously collected local friction coefficients for image segments belonging to the same class. The method may use a camera image divided into a two-dimensional grid in the plane of the pavement, in which case friction coefficients are assigned to the cells of the grid.
U.S. Pat. No. 9,108,640 describes a method for monitoring and reporting road quality. Various sensors are used for determining road quality in a vehicle, and this data is transmitted, together with the vehicle's location, though a mobile network to a central server for distribution in road quality reports. A method for determining an average road quality indication based on aggregated data from multiple vehicles is also described. This method may involve calculating a weighted mean, giving more weight to road quality indications coming from trusted and known sources than those coming from non trusted and unknown sources.
US20120053755 describes a method of calculating the occupancy probability for a road surface using occupancy grid maps.


The present disclosure provides a method of detecting a target analyte, by binding the target analyte and a probe with at least one fluorophore to form a fluid composition. The fluid composition is excited within a laser cavity. The method comprises measuring a laser emission from the fluid composition based on an interaction between the target analyte and the probe. In certain aspects, the method provides hybridizing the target analyte and the probe, prior to the exciting. In certain variations, the methods comprise detecting a target analyte by measuring a laser emission from the fluid composition based on an interaction between the target analyte, where the interaction is probe energy transfer, intercalation, hybridization of the target analyte and the probe, or combinations thereof. The energy transfer can include fluorescence resonance energy transfer (FRET), FRET with a molecular-beacon, or cavity-assisted radiative energy transfer, by way of non-limiting example.

This section provides background information related to the present technology which is not necessarily prior art.
Rapid, cost-effective, specific, and high-throughput detection of DNA sequences is a topic of major scientific interest. For example, its application areas include clinical diagnosis of genetic and pathogenic diseases, single nucleotide polymorphism genotyping, drug discovery, environmental studies, homeland security, and forensic analysis. Numerous analytical techniques, such as electrochemical sensors, capillary electrophoresis, optical sensors, mechanical sensors, have been developed to detect DNA, including fluorescence based detection.
Considerable efforts have been made to develop DNA detectors and analyzers, particularly for example, single-nucleotide polymorphisms (SNPs) that differentiate the target single-stranded DNA (ssDNA) from those with a single-base mismatch owing to the key role of DNA in the transfer of genetic information. Many technological advances have been made to provide tools to analyze SNPs. Most of those technologies utilize fluorescence from the dye labeled on a DNA probe, which adds costs and detection processes. In comparison, high resolution melt (HRM) analysis is a unique technology that relies on intercalating saturation dyes to monitor double-stranded DNA (dsDNA). Saturation dye has a very high fluorescence quantum yield in the presence of dsDNA, but its quantum yield diminishes when the dsDNA becomes ssDNA at relatively high temperature. HRM uses the saturation dye directly and does not require any costly labeling processes. HRM has to scan the temperature to differentiate SNPs, which slows detection. Additionally, the fluorescence difference between the target DNA and single-based mismatched DNA is small. It would be desirable to have a method, system and apparatus for rapid detection of target DNA or other target analytes.

Sensitive intracavity biosensing platform and methods for detection therewith

The Regents Of The University Of Michigan


Distributed storage systems support SQL while also providing scalability and fault tolerance by utilizing an SQL library (the SQL execution component) layered on top of a transactional key-value system (the storage component). The SQL library comprises a parser and an execution engine running at the client, while the storage component comprises a key-value system for storing the data. The SQL library parses SQL queries received from client applications and maps them to transactions on the key-value system. The key-value system stores data items identified by key and provides concurrency control mechanisms to handle concurrent transactions. The key-value system may be a distributed system with several storage servers, each attached to one or more storage devices.

Large-scale web-based applications may use a distributed storage system to store application data such as data about its users, customers, internal state, etc. Existing storage systems for web-based applications include both traditional database systems that generally feature use of the Standard Query Language (SQL) and "NoSQL" storage systems that do not use SQL. SQL is a well-known and widely-used query interface featuring powerful functionality via use of a declarative language that is more concise than imperative programming languages, such that a few lines of SQL may equate to hundreds of lines of code used to implement the same functionality using a NoSQL system.
In general, traditional database systems using SQL are difficult and expensive to scale because they utilize costly special hardware and/or have high overhead (e.g., expensive system administrators to partition data and tune performance). Over the past ten years, however, many companies that develop and utilize large-scale web applications have replaced traditional SQL database systems with specialized custom-built storage systems without SQL that feature better performance, better scalability, and reduced costs (both hardware and overhead). However, these "NoSQL" storage systems provide only a subset of the functionality available in traditional SQL database systems. For example, NoSQL storage systems may lack joins, subqueries, secondary keys, aggregation, and other features offered by SQL.
Consequently, web applications utilizing NoSQL storage systems that need this missing functionality must provide it themselves, which in turn increases the effort and cost of developing such applications for operation with NoSQL storage system. Furthermore, NoSQL storage systems generally feature custom interfaces and query languages that are specific to that storage system (i.e., are non-standard and ad-hoc); as a result, web applications developed to use one specific NoSQL system may not work with other NoSQL storage systems without significant changes being made to such web applications to make them compatible with the custom interface and query language featured by the other NoSQL storage system.

Distributed SQL query processing using key-value storage system


The present invention relates to a throttle-valve housing having a continuous throttle opening for a throttle-valve which is arranged on a throttle-valve shaft, and a housing having a housing cover and a housing body. An electric drive and a first electronic mechanism for the drive are arranged in the housing, for displacing the throttle-valve shaft. The throttle-valve housing is especially non-complex in terms of production and assembly, and can be especially easily connected to other electronic mechanisms of the motor vehicle. To this end, the first electronic mechanism for the electric drive and the second electronic mechanism for appliances outside the housing are arranged in the cover of the housing. Both the first electronic mechanism of the electric drive for the throttle-valve shaft and the second electronic mechanism for the electrical appliances, can be brought into contact with the electrical appliances outside the housing by means of electrical connections which are at least partially arranged in the cover of the housing.

The invention relates to a throttle body, in particular for an internal combustion engine of a motor vehicle, with a continuous throttle opening for a throttle valve which is pivotably arranged on a throttle-valve shaft and with a housing, the housing comprising a housing cover and a housing body, an electric servodrive and a first electronic mechanism being arranged in the housing for pivoting the throttle-valve shaft. The invention also relates to an electronic module, which comprises electronic mechanisms for a motor vehicle and a base element which can be closed by a cover element, the motor vehicle having a multiplicity of electrical appliances and a throttle body, the throttle body comprising a housing with a continuous throttle opening for a throttle valve which is pivotably arranged on a throttle-valve shaft and an electric servodrive, arranged in the housing, for pivoting the throttle-valve shaft.
To control the amount of fresh gas to be fed to the internal combustion engine of a motor vehicle, throttle bodies are usually used. Throttle bodies comprise a housing with a continuous throttle opening and a throttle member arranged in the throttle opening. The throttle member assumes a specific position in the throttle opening for a specific amount of fresh gas to be allowed to pass through. To this end, the throttle member can be mechanically or electronically activated.
It may be the case that, in a part-range, for example the idling range, the throttle valve of a throttle body can be moved by a servodrive and, in the remaining range, it can be moved with the aid of a wire cable coupled to the gas pedal of the motor vehicle. Alternatively, however, it may also be the case that the throttle valve can be moved by a servodrive in its entire adjusting range. In the case of these last-mentioned systems, there is no mechanical connection between the set point input, in particular the gas pedal, and the throttle valve. In the case of these electronic gas-pedal or drive-by-wire systems as they are known, the power requirement is converted into an electrical signal when initiated by the pressing down of the gas pedal. The electrical signal is fed to a control unit, which in turn generates from the electrical signal an activation signal for the servodrive.
In order in the case of electronic gas-pedal systems to avoid errors in the transmission of the activation signal from the control unit for driving the throttle-valve shaft, there are throttle bodies in which the control unit for the servodrive is integrated into the housing of the throttle body. The control unit may in this case be integrated into an electronic mechanism arranged in the housing. The electronic mechanism is in this case intended for further functions of the throttle body, for example for the activation of a position control of the throttle-valve shaft and the acquisition and storage of data of the throttle body. Integration of an electronic mechanism into the housing of the throttle body is often particularly complex in terms of production and assembly, since the housing must additionally have a receptacle for the electronic mechanism. What is more, the assembly of the throttle body requires an additional assembly step, in which the electronic mechanism is integrated into the housing of the throttle body.
Even if transmission errors of the activation signal of the servodrive for the throttle valve can be avoided particularly reliably by integrating the electronic mechanism for the throttle body into the housing of the throttle body, it may however prove to be problematical to connect the electronic mechanism of the throttle body to the remaining electronic mechanisms of the motor vehicle. A connection of the electronic mechanism of the throttle body to the remaining electronic mechanisms of the motor vehicle is required in order, for example, to coordinate the position of the throttle valve with the operation of an ignition device and/or an injection device. This connection of the electronic mechanism of the throttle body to other electronic mechanisms, in particular electronic control mechanisms, of the motor vehicle involves particularly great complexity in terms of assembly for the installation of the throttle body or electronic gas-pedal system in a motor vehicle. The further electrical appliances activated by the other electronic mechanisms of the motor vehicle may in this case be arranged both inside and outside the internal combustion engine in the motor vehicle. Furthermore, the signals to be exchanged between the electronic mechanism of the throttle body and the other electronic mechanisms may be falsified on account of interference pulses, possibly resulting in faulty signal transmission or, in the extreme case, no transmission at all. Furthermore, each cable to be laid in the motor vehicle represents additional complexity in terms of assembly.


A label for an antibody or protein is described that is both site-selective and unusually stable in vivo. The label has a general formula given by Formula (I) wherein R1 is a metal chelator, a fluorophore or a click-chemistry synthon.

The subject matter disclosed herein relates to site-selective biological radiolabels that are stable in vivo.
The ability of many biomolecules to selectively and specifically target cellular biomarkers has long been harnessed for both nuclear imaging and radiotherapy. This exploitation uses the ligation of a radioactive payload to the biomolecule. In the case of peptides and proteins, this is typically performed through the ligation of reactive, bifunctional probes to amino acids within the biomolecule, most often lysines. While controlling the site of this conjugation is fairly easy with small peptides—which rarely possess more than one or two copies of each amino acid—this becomes a much bigger problem with larger biomolecules. For example, most antibodies contain dozens of lysines distributed throughout their macromolecule structure. The indiscriminate attachment of a bifunctional chelator to these lysines can lead to the formation of thousands of different regioisomers. Not surprisingly, this so-called "random" approach to bioconjugation has low reproducibility and produces highly heterogeneous conjugates. In addition, this strategy can result in payloads being inadvertently grafted to bioactive sites in the biomolecule, rendering a portion of the conjugates inoperative.
To circumvent these issues, researchers have turned their attention to strategies allowing for better control over the site of the ligation reaction, known as "site-specific" bioconjugations. Conjugations to cysteine—a thiol-bearing amino acid present in small numbers in proteins—with maleimide-bearing probes have become a staple of this field and have been used extensively over the last three decades. The prevalence of this strategy is rooted mainly in its simplicity and efficiency. Many proteins contain disulfide bridges that can be easily reduced to form the reactive thiols, and the Michael addition between the maleimide and the sulhydryl group can be performed at physiological pH and room temperature, reliably leading to the formation of a succinimidyl thioether linkage within an hour (see FIG. 1).
While the ligation between thiols and maleimides represents an undeniable improvement over random conjugation methods, the reaction suffers from drawbacks as well. Indeed, maleimide-based conjugates display limited stability in physiological media because the succinimidyl thioether linkage can undergo a retro-Michael reaction that leads to the release of the payload or its exchange with other molecules containing free thiols (most often serum albumin, cysteine, and glutathione). Several studies focused on antibody-drug conjugates have reported on this phenomenon as well as the off-target uptake of payload that it creates. These studies have also been devoted to boosting the hydrolysis of the succinimyl moiety by modifying its vicinity, which ultimately prevents the thiol exchange and the off-target uptake of the drug. In the context of nuclear imaging and radiotherapy, this retro-Michael reaction can lead to the release of the radioactive payload and in vivo radiolabeling of endogeneous biomolecules through thiol exchange reactions (see FIG. 1). This "leakage" causes higher uptake in non-target tissues and lower uptake in target tissues, ultimately resulting in higher radiation doses to healthy tissues, reduced imaging contrast, and lower therapeutic ratios. Several alternatives which create more-stable linkages with thiols than maleimides have been used for the bioconjugation and radiolabeling of antibodies, most notably tosylates, bromo- and iodo-acetyls, and vinyl sulfones. However, each of these options has drawbacks as well, including lower reactivity with thiols as well as reactivity with other amino acids.
An article published in 2013 (Toda, N., Asano, S. & Barbas, C. F. (2013) Rapid, stable, chemoselective labeling of thiols with Julia-Kocieński-like reagents: A serum-stable alternative to maleimide-based protein conjugation. Angew. Chem. Int. Ed. 52, 12592-125%, hereafter "Toda et al.") holds particular promise in this area. In this work, the Barbas Laboratory described the creation of an oxadiazolyl methyl sulfone-based reagent that could selectively react with thiols at a rate comparable to maleimides and form more stable conjugates than those obtained with the latter (Scheme 1).

This reagent was used to label different THIOMABs—antibodies engineered to bear a free cysteine residues—with fluorescein, and these phenyloxadiazole-based conjugates displayed higher stability over time in serum than their maleimide-based cousins. Yet despite the benefits of this ligation over maleimide-thiol conjugations, this construct has scarcely been used since its publication. This is especially obvious in radiochemistry, in which only two reports describe the use of the reagent or its derivatives. In the first, Zhang et al. (Zhang, Q., Dall'Angelo, S., Fleming, I. N., Schweiger, L. F., Zanda, M. & O'Hagan, D. (2016) Last-step enzymatic [18F]-fluorination of cysteine-tethered RGD peptides using modified Barbas linkers. Chem.-Eur. J. 22, 10998-11004) used this reagent along with other methylsulfone-oxadiazole derivatives to incorporate an azide moiety into an RGD peptide. In the second, a team in Switzerland designed an 18F-labeled prosthetic group based on this reagent which seemed to offer substantial advantages over traditional maleimide-based prosthetic groups for IF-labeling (Chiotellis, A., Sladojevich, F., Mu, L., Herde, A. M., Valverde, I. E., Tolmachev, V., Schibli, R., Ametamey, S. M. & Mindt, T. L. (2016) Novel chemoselective 18F-radiolabeling of thiol-containing biomolecules under mild aqueous conditions. Chen Commun. 52, 6083-6086).
The infrequent use of this reagent was somewhat surprising at first, especially since it is commercially available from Sigma-Aldrich. In three attempts at ordering, the product was discovered to contain complex mixtures of degradation products containing less than 15% of the desired compound. In light of these setbacks, synthesis of the reagent according to the published procedure was considered, but it appeared that this synthesis was far from trivial for radiochemical and molecular imaging laboratories that lack sophisticated organic chemistry equipment.
It would therefore be desirable to create an easily accessible phenyloxadiazole-based reagent for thiol conjugations that can be obtained through a robust route that could be carried out with basic organic chemistry equipment.
The discussion above is merely provided for general background information and is not intended to be used as an aid in determining the scope of the claimed subject matter.

Reagent for site-selective bioconjugation of proteins or antibodies

Research Foundation of the City University of New York


An electronic apparatus includes a housing provided with first and second connectors, a first fixing member receiving element positioned on the side of the first connector opposite to the second connector side, a second fixing member receiving element positioned on the side of the second connector opposite to the first connector side, and a third fixing member receiving element positioned between the first connector and the second connector. First and second plugs are removably connected to the first and second connectors. The first fixing member receiving element fixes one fixing member of the first plug. The second fixing member receiving element fixes one fixing member of the second plug. The third fixing member receiving element fixes either the other fixing member of the first plug or the other fixing member of the second plug.

1. Field
The present invention is related to an electronic apparatus, in particular to the structure for connecting external apparatuses to the electronic apparatus.
2. Description of the Related Art
A portable computer referred to as a notebook comprises a main unit including a keyboard, and a liquid crystal display unit supported by the main unit. The main unit includes a flat, box-like housing. A plurality of connectors are placed in a line at a side surface of the housing to permit connection of external apparatuses having the same function but different types of connecting portions.
Japanese Patent Application KOKAI Publication No. 7-28559 discloses such a portable computer wherein the connectors are covered to prohibit external apparatuses having the same function from being concurrently connected to the housing, and the connector covers provided to the housing permit one of the connectors to be selectively exposed.
There is a kind of plug that is used by connecting the plug body to a connector and securing the plug body to the housing by screws. Such a plug comprises a casing, a plug body, and a pair of screws provided on both sides of the plug body, and the plug body and the pair of screws are contained in the casing.
When such a plug is to be used, it is necessary to provide the housing with screw bosses on both sides of a connector. Therefore, between two adjacent connectors, a screw boss belonging to one connector and a screw boss belonging to the other connector are placed side by side. In addition, it is necessary to place adjacent connectors with a sufficient space in between to prevent the casings of plugs, respectively corresponding to the connectors, from interfering with each other when they are concurrently connected.
However, in regard to a portable computer, there is an instance where adjacent connectors are not used concurrently, such as adjacent connectors for connection of a plurality of external apparatuses having the same function but different types of connecting portions. In such an instance, these connectors do not need to be placed with a sufficient space to allow concurrent connection of their respective corresponding plugs as stated above.
Also, there is a demand for further downsizing and functional advancement of portable computers, and it is desirable that various components contained in a housing be placed at a high density. Therefore, there is a demand for reduction of the space occupied by such connectors as those that are placed adjacent to each other but are not used concurrently.

Electronic apparatus with two connectors with a common fixing member


A method includes detecting a feature of an input pattern using a plurality of feature detectors, selecting at least one of the feature detectors based on their output values, and calculating a feature quantity of the input pattern based on an output value from at least one selected feature detector.

1. Field of the Invention
The present invention relates to a method of realizing highly accurate feature detection even when variation occurs, for example, in a size or direction of a detection target pattern.
2. Description of the Related Art
In the field of pattern recognition, there has been a strong demand for a method capable of realizing accurate feature detection regardless of variation in a size or a direction of a recognition target. There has also been a strong demand to know what type of variation a pattern has received.
For example, a method has been discussed for efficiently detecting a face image even in a non-frontal view (Japanese Patent Application Laid-Open No. 2004-133637). According to this method, a correlation is obtained between an input image and a template image of a predetermined size. The template image represents an average face image. When it is determined that the input image is not a frontal view, the template image is rotated by a predetermined angle or angles which are sequentially updated, and collation is repeated.
A method has also been described for preparing affine transformation parameters each corresponding to variation of a human face image which is a recognition target, detecting the face image after inverse transformation, and combining a plurality of detection results (Japanese Patent Application Laid-Open No. 2000-90191). In this case, the variation corresponds to positional shifting of the face image, inclination, a change in vertical direction, or a change in horizontal direction. As a combining method, a highest point or decision by majority is employed.
However, according to the aforementioned conventional transformation based method, many templates or parameters need to be prepared for pattern variation and, to obtain a highly accurate estimation about variation, a large amount of processing is needed. As the method for combining many detection results, the highest point or the decision by majority is not sufficient to estimate features regarding variation with a high degree of accuracy.

Method and apparatus for detecting a feature of an input pattern using a plurality of feature detectors, each of which corresponds to a respective specific variation type and outputs a higher value when variation received by the input pattern roughly matches the respective specific variation type


A receiver for recovering data from a received symbol of signal samples generated in accordance with Orthogonal Frequency Division Multiplexing (OFDM) includes a pilot assisted channel estimator operable to generate an estimate of a transmission channel through which the received OFDM symbol has passed. The OFDM symbol includes pilot signals provided at different sub-carrier locations for each of a set of OFDM symbols, the sub-carrier locations of the pilot signals being repeated for subsequent sets of symbols. The pilot assisted channel estimator includes a pilot extractor, a time interpolation filter controller and an adaptive bandwidth interpolation filter.

In multi-carrier modulation systems, such as OFDM systems, pilot symbols are often embedded at known sub-carrier locations within OFDM symbols in order to facilitate estimation of the channel through which the OFDM symbol has passed. An example of an OFDM system, which employs both scattered pilot signals and continuous pilot signals is that used for the DVB-T standard as disclosed in EN 300 744 Digital Video Broadcasting (DVB) Framing structure, channel coding and modulation for digital terrestrial television ([8]). Continuous pilot signals are pilot signals transmitted at the same relative sub-carrier location within the symbol, whereas scattered pilots are pilot signals transmitted at different sub-carrier locations for each of a set of OFDM symbols, the location of the pilots being repeated for a subsequent set of symbols.
As disclosed in "Mobile reception of 2K and 8K DVB-T Signals," by Erik Stare, Proceedings of IBC '98 pp 473-478 ([4]) pilot signals can be used in pilot-assisted channel estimation during demodulation of the OFDM symbol. As the pilots only occur at predetermined separated locations in both the frequency and time dimensions, interpolation is used to estimate the amplitude and phase response of the channel at sample points where no pilot carrier has been transmitted within a currently received OFDM symbol. Following both time and frequency interpolation, a sample of the channel frequency response can be generated (fully sampled version) for each sample in the received OFDM symbol. The estimated channel can therefore be cancelled from the received symbol, so that data conveyed by the symbol can be recovered. However, the interpolation can introduce noise into the channel estimate thereby degrading the performance of the receiver.

This patent is subject to a terminal disclaimer.


A fluidic latch device may include an input port, an additional input port, an output port, an additional output port, a pressure chamber, an additional pressure chamber, and a flexible membrane. The pressure chamber may include an inlet coupled to the input port by a first fluid channel and an outlet coupled to the output port by a second fluid channel, and the additional pressure chamber may include an additional inlet coupled to the additional input port by a third fluid channel and an additional outlet coupled to the additional output port by a fourth fluid channel. The flexible membrane may separate the pressure chamber and the additional pressure chamber and be configured to (1) block, when the membrane is in an expanded state, the outlet of the pressure chamber and (2) block, when the membrane is in an additional expanded state, the additional outlet of the additional pressure chamber.

Fluidic systems are small mechanical systems that involve the flow of fluids. Fluidic systems can be used in many different fields, such as biomedical, chemical, genetic, biochemical, pharmaceutical, haptics, and other fields. Fluidic systems may be made up of various composable fluidic devices that may be coupled together to form a composite fluidic system. A fluidic valve is a basic component of fluidic systems and may be used for stopping, starting, or otherwise controlling flow of a fluid in a fluidic system. Conventional fluidic valves may be actuated via fluid pressure, with a piezoelectric material, or a spring-loaded mechanism, for example.
Fluidic devices are fluid handling devices that function analogous to electronic devices. Fluidic circuits and systems are often used to perform tasks and operations typically performed by conventional electronic circuits and systems. In some fields, fluidic systems may be replacing these electronic circuits and systems. Conventional fluidic valves may be used to perform tasks and operations similar to conventional electrical transistors such as performing control functions, performing logic operations (e.g., binary logical operations), and storing or transmitting information. Accordingly, the present disclosure recognizes a need and provides solutions for improved fluidic valves and systems and methods used for controlling fluid flows and pressures in fluidic systems.


An optical film, a color filter substrate, manufacturing methods thereof and display devices are provided, in the field of liquid crystal display technology. The color filter substrate includes a base, a color resistant layer and a diffusion layer. The color resistant layer and the diffusion layer are arranged on the base, and the color resistant layer and the base are arranged at the same side of the diffusion layer. The color resistant layer comprises a plurality of color resistant blocks which are arranged in an array. The diffusion layer comprises a plurality of diffusion structures which are arranged to be in one-to-one correspondence to the plurality of color resistant blocks. Each of the plurality of diffusion structures is configured to diffuse light vertically emitted from the color filter substrate.

A liquid crystal display has become a widely used display device owning to its numerous advantages. A liquid crystal display mainly comprises a liquid crystal display panel and a backlight module, wherein the liquid crystal display panel generally comprises an array substrate, a color filter substrate, and a liquid crystal layer arranged between the array substrate and the color filter substrate.
In the existing liquid crystal display, the light emitted from the backlight module is generally divergent. When a viewer looks directly at the liquid crystal panel, the line of sight is vertical to the panel. In this case, the light received by the viewer's eyes is the light vertically incident on the liquid crystal layer in the backlight module, and the viewer can clearly see a picture on the panel. When the viewer looks obliquely at the liquid crystal panel, the line of sight is tilted relative to the panel. In this case, the light received by the viewer's eyes is the light obliquely incident on the liquid crystal layer in the backlight module. Since the refractive indexes of liquid crystal molecules in different directions are different, there is an optical path difference when light passes through the liquid crystal layer vertically and passes through the liquid crystal layer obliquely. Therefore, the refraction angles of the liquid crystal layer to the light are also different, so that the contrast of the picture seen by the viewer deteriorates and even the color shift occurs. In addition, the larger the visible angle is, the worse the contrast is, and the more serious the color shift is.

Optical film, color filter substrate, manufacturing methods thereof, and display devices

HEFEI BOE OPTOELECTRONICS TECHNOLOGY CO., LTD.


A method of determining an amount of wear in a spherical working surface of a bearing ring of a spherical plain bearing, the method including providing a reference groove of predetermined depth in an unworn working surface, using the reference groove and axial end faces of the bearing ring as reference surfaces for centering and aligning a measuring tool. The tool having a first surface, and a protrusion that extends from the first surface in radial direction and is adapted to fit into the reference groove and two or more radial openings that extend from a second surface of the tool. Determining the amount of wear by measuring the radial distance to the spherical working surface through each of the radial openings and comparing the measured value with a reference value measured using the tool for an unworn working surface comprising a reference groove of the same predetermined depth.

An apparatus for measuring wear of rod end bearings is disclosed in U.S. Pat. No. 3,845,735. An indicator pin is mounted in a radially extending through-hole in the outer ring, such that one end of the pin is in contact with a spherical outer surface (working surface) at an axially central location of the inner ring, while the other end of the pin protrudes from the through-hole by a known amount when the bearing is in an unworn condition. After a period in service, wear is measured by compressing the bearing and manually depressing the pin until it contacts the working surface of the inner ring. A reduction in the amount by which the pin protrudes is indicative of wear.
This solution has the disadvantage that it is necessary to machine a cavity through the outer ring, which compromises its structural integrity. Also, it is possible to detect wear at only one location on the working surface. Depending on the application loads, the working surface may not experience a uniform amount of wear along an axial profile of the surface.
An example of a plain bearing with visual wear indication features is disclosed in GB 2421769. The plain bearing is a bushing whose outer surface is provided with shallow recesses of closely controlled radial depth, axial width and circumferential length. During a maintenance inspection, after a period of service in which wear will have occurred, the visual appearance of the worn pattern of recesses is compared with a chart which interprets the wear pattern and extent.
In applications where an amount of unacceptable wear is measured in the scale of microns, a visual comparison against a chart may not provide a reliable indication of the extent of the wear.
There is still room for improvement.

Method of determining wear in a bearing surface


This invention concerns liquid perfluoro-n-alkanes for use in applications demanding high transparency at UV wavelengths ranging from about 150 to 165 nm, especially 157 nm. Uses include optical couplants, optical cements, optical elements, optical inspection media for semiconductor wafers and devices, and most especially immersion photolithography at 157 nm exposure wavelength.

Much progress in the electronics industry comes from circuit size reduction. This is most directly accomplished by running photolithographic processes at ever-shorter wavelengths of light. The electronics industry is currently implementing photolithographic processes employing wavelengths in the so-called "vacuum ultra-violet" (VUV). Processes using 193 nanometer (nm) light are undergoing commercialization while 157 nm wavelength light is under development as a next generation candidate.
One new development in the field is so-called immersion photolithography at 157 nm exposure wavelength as described in Switkes et al, J. Vac. Sci. Technol. B, 19 (6), 2353 6, November/December 2001; and, M. Switkes et al, "Resolution enhancement of 157-nm photolithography at 157 nm exposure wavelength by liquid immersion", Proc. SPIE Vol. 4691, pp. 459-465 (2002). In immersion photolithography at 157 nm exposure wavelength, the optical source, the target surface, or the entire lithographic apparatus is immersed in a highly transparent high refractive index liquid. Realization of the potential benefits of this technology is dependent upon identifying liquids with exceptionally high transparency in the VUV with excellent photochemical stability, as described, for example, in M. Switkes, R. R. Kunz, M. Rothschild, R. F. Sinta, P. M. Gallagher-Wetmore, and V. J. Krukonis, "Liquids for immersion photolithography at 157 nm exposure wavelength at short wavelengths", Proc. SPIE Vol. 5040, 690-699 (2003).
Switkes et al, Microlithography World, May 2003, pp. 4ff, further demonstrate that 157 nm light in a high refractive index medium can simulate the effects of much shorter wavelength light for photolithographic purposes.
Considerable emphasis in the art has been placed on identifying organic polymeric compositions suitable for use in the VUV. See for example WO 0185811 and WO 137044, which disclose fluorinated polymeric compositions having high transparency at 157 nm. Considerably less emphasis has been placed upon lower molecular weight organic liquids, which may be employed as an immersion medium in immersion photolithography in which a liquid medium is used between the projection lens of the optical stepper and the photoresist-coated substrate (typically a silicon wafer), which will receive and detect the photolithographic image. Whether polymeric or not, any material residing in the light path between the source and the target needs to be highly transparent and photochemically stable at VUV wavelengths. As disclosed in the references hereinabove cited, suitable liquids can also be used as inspection media for immersion inspection of patterned objects such as semiconductor wafers, wherein the effectively reduced wavelength will produce higher resolution imaging of small size defects.
According to Switkes et al, "Liquids for immersion photolithography at 157 nm exposure wavelength at short wavelengths," op.cit., an immersion liquid layer should desirably be at least 1 mm thick for mechanical reasons and at least 95% transparent for good optical performance. A reasonable estimate of the needed absorbance for an immersion liquid is A/cm=0.22, as determined from the equationA/cm≦[log10(To/T)]/h=[log10(100%/95%)]/0.1=0.22                Where To=light intensity in the absence of immersion fluid                    T=light intensity with immersion fluid present            h=distance from lens to resist in centimetersIn general, of course, the more transparent the better.
All known organic materials absorb to some extent at 157 nm. The issue is whether liquids can be found that are sufficiently transparent to be practical. It is known in the art that short chain hydrocarbons H(CH2)nH and short chain fluorocarbons F(CF2)nF are relatively transparent compared to their longer-chain homologues. See for example, B. A. Lombos et al, Chemical Physics Letters, 1, 42 (1967); G. Belanger et al, Chemical Physics Letters, 3(8), 649(1969); and K. Seki et al, Phys. Scripta, 41,167(1990).
E. Albrecht et al, CERN Document Server: Preprints (2002) 1-14, ep/ep-2002-099, 16 Dec. 2002, (URL:http://documents.cern.ch/archive/electronic/cern/preprints/ep/ep-2002-099.pdf.) discloses that gas phase perfluoro-n-alkanes up to perfluorobutane are sufficiently transparent below 160 nm for use as Cherenkov detectors particularly when impurites such as oxygen, water, and hydrocarbons have been removed. However, gases exhibit very low refractive index and therefore are not suitable for use in immersion photolithography at 157 nm exposure wavelength.
Liquids having the high transparency of perfluoro-n-alkane vapors but with higher refractive index, and the requisite photochemical stability for practical use in immersion photolithography at 157 nm exposure wavelength, and other applications, in the VUV are not identified in the art.

Use of perfluoro-n-alkanes in vacuum ultraviolet applications


An image forming apparatus including a hinge assembly to mutually hinge-connect a main body and a cover unit of the image forming apparatus and the hinge assembly is provided. The image forming apparatus includes a main body, a cover unit configured to be disposed on an upper side of the main body to press a manuscript, and at least one hinge assembly configured to connect the cover unit to the main body, wherein the hinge assembly includes a first body detachably mounted on the main body, a second body of which a part is fastened to the cover unit and another part is hinge-connected with the first body, a pressing unit accommodated in the first body to press the second body upward, and a pressing force adjuster configured to adjust a hinge force between the first body and the second body.

1. Field
Embodiments relate to a hinge assembly and an image forming apparatus having the same, and more particularly to a hinge assembly that hinge-connects a main body of an image forming apparatus and a cover unit to each other and an image forming apparatus having the same.
2. Description of the Related Art
An image forming apparatus is an apparatus which performs a document scanning function, such as a copy machine, a scanner, or a multifunction peripheral (MFP), and includes a main body having a scan transparent plate on which a document to be scanned is put and a cover unit that can hide the scan transparent plate.
Typically, the cover unit is pivotally connected to the main body through at least one hinge assembly. As a type of hinge assembly for connecting the cover unit and the main body to each other, a hinge assembly, which applies a variable elastic pressing force to the cover unit in accordance with an opening angle of the cover unit so that the cover unit can have a pre-stop function, may be used.
In such a hinge assembly, a coil spring is generally mounted as an elastic member that provides the elastic pressing force. It is ideal that the spring constant of such a coil spring is kept uniform. However, if the coil spring is used for a long time, the spring constant of the coil spring becomes relatively smaller than the spring constant when the coil spring is first manufactured due to plastic deformation of the coil spring.
There is a problem that, if the spring constant of the coil spring becomes smaller due to the long-term use of the coil spring, it is difficult to achieve smooth pre-stop of the cover unit. Further, due to impact that is applied to the main body as the cover unit is abruptly closed at high speed and collided with an upper side of the main body, the scan transparent plate and the cover unit may be damaged.
In order to prevent the above-described problem, there is a method to replace the hinge assembly with new one on a regular basis, but, it costs a lot to repair and replace the hinge assembly.

Hinge assembly and image forming apparatus having the same


Implementations of the present invention relate to a method and a corresponding device for shaping a workpiece, in which the lifting of the workpiece from the tool after a shaping process is automated. One implementation of the method relates to (a) placing the workpiece in a shaping position on a first tool of the shaping machine, (b) moving the tools of the shaping machine toward one another, (c) shaping the workpiece between the tools, (d) subsequently moving the tools away from one another, (e) identifying a triggering time when the relative motion of the tools has reached a reference position.,(f) determining a lifting time, which may be a function of the triggering time, and (g) initiating a lifting motion of the workpiece from the first tool by at least one handling device at lifting time.

1. Field of the Invention
The invention relates to a method and a device for shaping a workpiece.
2. Background and Related Art
Percussive shaping machines such as hammers and screw presses, in particular flywheel screw presses, are known for industrial forging of workpieces. Percussive shaping machines comprise a working region in which two tools are movable, generally in a straight line, relative to one another. The workpiece is positioned between the two tools, and is then shaped by the impact force or impact energy from the striking of the tools on the workpiece and the resulting shaping energy.
According to VDI-Lexikon "Produktionstechnik Verfahrenstechnik" [Manufacturing Process Engineering], Prof. Dr. Hiersig, Publisher, VDI-Verlag, 1995, pages 1107-1113, forging hammers may be subdivided into anvil hammers—which in turn are subdivided into drop hammers and double-acting hammers—and counterblow hammers. An anvil hammer comprises an anvil (or support) as a tool that is stationary with respect to the workpiece, and a striking hammer, or hammer for short, as a tool that is movable, generally vertically, with respect to the workpiece and to the anvil. A counterblow hammer comprises two striking hammers that are movable, vertically or also horizontally, with respect to one another and relative to the base or the hammer frame. The drives for the hammers of forging hammers are generally hydraulic or pneumatic. In the actual shaping or work procedure, both the hammer frame and the hammer drives of a forging hammer are relieved of the shaping force so as not to overload the forging hammer. For screw presses, the workpiece that is moved is generally referred to as a tappet. The tappet is moved by a spindle in a straight line toward the stationary tool. The drive of the spindle, and thus of the tappet, is provided by a drive motor and/or a flywheel as an energy store. Before striking the workpiece located on the stationary tool, the spindle or tappet is decoupled from the drive, and the kinetic energy imparted to the tappet is (partially) transformed into shaping energy (VDI-Lexikon, see above).
For automatic handling of workpieces during pressing or forging, the use of handling devices such as manipulators and industrial robots is known from VDI-Lexikon "Produktionstechnik Verfahrenstechnik," Prof. Dr. Hiersig, Publisher, VDI-Verlag, 1995, pages 848, 849, and 1214. Such handling devices have grippers for grasping and temporarily holding workpieces, and insert the workpieces into or remove them from the forging machine. Manipulators are manually controlled motion devices which as a rule have distinct, process-specific controls or programs. Industrial robots are universally applicable automatic motion devices with a sufficient number of degrees of freedom, implemented by a corresponding number (5 to 6) axes of motion, and a freely programmable control for achieving practically any given motion trajectories of the workpiece within an area which the industrial robot can traverse or reach.
One problem with the use of such handling devices is the high impact forces from a percussive shaping machine, which during the shaping impact can impose significant stress and cause damage to the handling device when the handling device holding the workpiece is struck by the hammer or tappet. To solve this problem, DE 42 20 796 A1 and DE 100 60 709 A1 have proposed handling devices which can be flexibly positioned during the impact to damp the impact forces and vibrations transmitted from the workpiece to the drive, and which can be rigidly positioned during transport of the workpiece.
Automated handling of workpieces in forging processes with percussive shaping machines has not yet achieved widespread acceptance in actual practice. Instead, in practice the workpiece is still manually held in the forging hammer using a gripping tool, since appropriately trained operators control the correct handling of the workpiece when it is struck by the hammer along with the striking tool. After the hammer is reversed, the operator lifts the workpiece and places it back in the tool before the hammer strikes again with the next lift, or immediately places the workpiece in a depositing device.

Method and device for shaping and then lifting a workpiece


Humans Serum Albumin (HSA) or an HSA fusion protein is expressed in plant plastids. A plastid transformation vector is made which contains an expression cassette that contains regulatory sequences, the coding region for HSA or an HSA fusion protein and a selectable marker coding sequence. The vector is used to transform a plant where the plant expresses the HSA or HSA fusion protein. HSA is isolated and purified from the plant. A preferred plant is tobacco.

Research efforts have been made to synthesize high value pharmacologically active recombinant proteins in plants. Recombinant proteins such as vaccines, monoclonal antibodies, hormones, growth factors, neuropeptides, cytotoxins, serum proteins an enzymes have been expressed in nuclear transgenic plants (May et al., 1996). It has been estimated that one tobacco plant should be able to produce more recombinant protein than a 300-liter fermenter of E. coli. In addition, a tobacco plant produces a million seeds, thereby facilitating large-scale production. Tobacco is also an ideal choice because of its relative ease of genetic manipulation and an impending need to explore alternate uses for this hazardous crop.
A primary reason for the high cost of production via fermentation is the cost of carbon source co-substances as well as maintenance of a large fermentation facility. In contrast, most estimates of plant production are a thousand-fold less expensive than fermentation. Tissue specific expression of high value proteins in leaves can enable the use of crop plants as renewable resources. Harvesting the cobs, tubers, seeds or fruits for food and feed and leaves for value added products should results in further economy with no additional investment.
However, one of the major limitations in producing pharmaceutical proteins in plants is their low level of foreign protein expression, despite reports of higher levee expression of enzymes and certain proteins. May et al. (1998) discuss this problem using the following examples. Although plant derived recombinant hepatitis B surface antigen was as effective as a commercial recombinant vaccine, the levels of expression in transgenic tobacco were low (0.01% of total soluble protein). Even though Norwalk virus capsid protein expressed in potatoes caused oral immunization when consumed as food (edible vaccine), expression levels were low (0.3% of total soluble protein). A synthetic gene coding for the human epidermal growth factor was expressed only up to 0.001% of total soluble protein in transgenic tobacco. Human serum albumin has been expressed only up to 0.02% of the total soluble protein in transgenic plants.
Therefore, it is important to increase levels of expression of recombinant proteins in plants to exploit plant production of pharmacologically important proteins. An alternate approach is to express foreign proteins in chloroplasts of higher plant. Foreign genes (up to 10,000 copies per cell) have been incorporated into the tobacco chloroplast genome resulting in accumulation of recombinant proteins up to 30% of the total cellular protein (McBride et al., 1994).
The aforementioned approaches (except chloroplast transformation) are limited to eukaryotic gene expression because prokaryotic genes are expressed poorly in nuclear compartment. However, several pharmacologically important proteins (such as insulin, human serum albumin, antibodies, enzymes etc.) are currently produced in prokaryotic systems (such as E. coli.) via fermentation.
Chloroplasts are prokaryotic compartments inside eukaryotic cells. Since the transcriptional and translational machinery of the chloroplast is similar to E. coli. (Brixey et al., 1997), it is possible to express prokaryotic genes at very high levels in plant chloroplasts than in the nucleus. In addition, plant cell contain up to 50,000 compies of the circular plastid genome (Bendich 1987) which may amplify the foreign gene like a "plasmid in the plant cell," thereby enabling higher levels of expression. Therefore, chloroplasts are an ideal choice for expression of recombinant proteins that are currently expressed in E. Coli (such as insulin, human serum albumin, vaccines, antibodies, etc.). We exploited the chloroplast transformation approach to express a pharmacological protein that is of no value to the plant to demonstrate this concept, GVGVP (SEQ ID NO 20) gene has been synthesized with a codon preferred for prokaryotic (EG121) or eukaryotic (TG131) expression. Based on transcript levels, chloroplast expression of this polymer was a hundred-fold higher than nuclear expression in transgenic plants (Guda et al., 1999) Recently, we observed 16.966-fold more tps 1 transcripts in chloroplast transfomants than the highly expressing nuclear transgenic plants (Lee et al. 200, in review).
Research on human proteins in the past years has revolutionized the use of these therapeutically valuable proteins in a variety of clinical situations. Since the demand for these proteins is expected to increase considerably in the coming years, it would be wise to ensure that in the future they will be available in significantly larger amounts, preferably on a cost-effective basis. Because most genes can be expressed in many different systems, it is essential to determine which system offers the most advantages for the manufacture of the recombinant protein. An ideal expression system would be one that produces a maximum amount of safe, biologically active material at a minimum cost. The use of modified mammalian cells with recombinant DNA techniques has the advantage of resulting in products, which are closely related to those of natural origin. However, culturing these cells is intricate and can only be carried out on limited scale.
The use of microorganisms such as bacteria permits manufacture on a larger scale, but introduces the disadvantage of producing products, which differ appreciably from the products of natural origin. for example, proteins that are usually glycosylated in humans are not glycosylated by bacteria. Furthermore, human proteins that are expressed at high levels in E. coli frequently acquire an unnatural conformation, accompanied by intracellular precipitation due to lack of proper folding and disulfide bridges. Production of recombinant proteins in plants has many potential advantages for generating biopharmaceuticals relevant to clinical medicine. These include the following: (i) plant systems are more economical than industrial facilities using fermentation systems; (ii) technology is available for harvesting and processing plant/plant products on a large scale; (iii) elimination of the purification requirement when the plant tissue containing the recombinant protein is used as a food (edible vaccines); (iv) plants can be directed to target proteins into stable, intracellular compartments as chloroplasts, or expressed directly in chloroplasts; (v) the amount of recombinant product that can be produced approaches industrial-scale levels; and (vi) health risks due to contamination with potential human pathogens/toxins are minimized.
It has been estimated that one tobacco plant should be able to produce more recombinant protein than a 300-liter fermenter of E. coli (Crop Tech, VA). In addition, a tobacco plant can produce a million seeds, facilitating large-scale production. Tobacco is also an ideal choice because of its relative ease of genetic manipulation and an impending need to explore alternate uses for this hazardous crop. However, with the exception of enzymes (e.g. phytase), levels of foreign proteins produced in nuclear transgenic plants are generally low, mostly less than 1% of the total soluble protein (Kusnadi et al. 1997). (Cholera Toxin Subunit B filing) Protein accumulation levels of recombinant enzymes, like phytase and xylase were high in nuclear transgenic plants (14% and 4.1% of total soluble tobacco leaf protein respectively). This may be because their enzymatic nature made them more resistant to proteolytic degradation. May et al. (1996) discuss this problem using the following examples. Although plant derived recombinant hepatitis B surface antigen was as effective as a commercial recombinant vaccine, the levels of expression in transgenic tobacco were low (0.0066% of total soluble protein). Even though Norwald virus capsid protein expressed in potatoes caused oral immunization when consumed as food (edible vaccine), expression levels were low (0.3% of total soluble protein).
In particular, expression of human proteins in nuclear transgenic plants has been disappointingly low: e.g. human Interferon-β0.000017% of fresh weight, human serum albumin 0.02% and erythropoietin 0.0026% of total soluble protein (see table 1 in Kusnadi et al. 1997). A synthetic gene coding for the human epidermal growth factor as expressed only up to 0.001% of total soluble protein in transgenic tobacco (May et al. 1996). The cost of producing recombinant proteins in alfalfa leaves was estimated to be 12-fold lower than in potato tubers and comparable with seeds (Kusnadi et al 1997). However, tobacco leaves are much larger and have much higher biomass than alfalfa. Planet Biotechnology has recently estimated that at 50 mg/liter of mammalian cell culture or transgenic goat's milk or 50 mg/kg of tobacco leaf expression, the cost of purified IgA will be $10,000, 1000 and 50/g, respectively (Daniell et al. 2000). the cost of production of recombinant proteins will be 50-fold lower than that of E. coli fermentation (with 20% of 5% of biomass doubled the cost of production of E. coli (Petridis et al. 1995). Expression level less than 1% of total soluble protein in plants has been found to be not commercially feasible (Kusnadi et al. 1997). Therefore, it is important to increase levels of expression of recombinant proteins in plants to exploit plant production of pharmacologically important proteins.
An alternate approach is to express foreign proteins in chloroplasts of higher plants. We have recently integrated foreign genes (up to 10,000 copies per cell) into the tobacco chloroplast genome resulting in accumulation of recombinant proteins up to 46% of the total soluble protein (De Cosa et al, 2001). Chloroplast transformation utilizes two flanking sequences that, through homologous recombinant, insert foreign DNA into the spacer region between the functional genes of the chloroplast genome, thereby targeting the foreign genes to a precise location. This eliminates the position effect and gene silencing frequently observed in nuclear transgenic plants. Chloroplast genetic engineering is an environmentally friendly approach, minimizing concerns of out-cross of introduced traits via pollen to weeds or other crops (Bock and Hagemann 200, Heifetz 2000). Also, the concerns of insects developing resistance to biopesticides are minimized by hyper-expression of single insecticidal proteins (high dosage) or expression of different types of insecticides in a single transformation event (gene pyramiding). Concerns of insecticidal proteins on non-target insects are minimized by lack of expression in transgenic pollen (De Cosa et al. 2001).
Importantly, a significant advantage in the production of pharmaceutical proteins in chloroplasts is their ability to process eukaryotic proteins, including folding and formation of disulfide bridges (Drescher et al. 1998). Chaperonin proteins are present in chloroplasts (Roy, 1989; Veirling, 1991) that function in folding and assembly of prokaryotic/eukaryotic proteins. Also, proteins are activated by disulfide bond oxido/reduction cycles using the chloroplast thioredoxin system (Reulland and Miginiac-Maslow, 1999) or chloroplast protein disulfide isomersase (Kim and Mayfield, 1997). Accumulation of fully assembled, disulfide bonded form of human somatotropin via chloroplast transformation (Staub et al. 2000), oligomeric form of CTB (Henriques and Daneill, 2000) and the assembly of heavy/light chains of humanized Guy's 13 antibody in transgenic chloroplasts (Panchal et al. 2000) provide strong evidence for successful processing of pharmaceutical proteins inside chloroplasts. Such folding and assembly should eliminate the need for highly expensive in vitro processing of pharmaceutical proteins. For example, 60% of the total operating cost in the production of human insulin is associated with in vitro processing (formation of disulfide bridges and cleavage of methionine, Petridis et al. 1995).
Another major cost of insulin production is purification. Chromatography accounts for 30% of operating expenses and 70% of equipment in production of insulin (Petridis et al. 1995). Therefore, new approaches are needed to minimize or eliminate chromatography in insulin production. One such approach is the use of GVGVP (SEQ ID NO. 20) as a fusion protein to facilitate single step purification without the use of chromatography. GVGVP (SEQ ID NO. 20) is a Protein Based Polymer (PBP) made form synthetic genes. At lower temperatures this polymer exists as more extended folds into dynamic structures called .beta.-spirals that further aggregate by hydrophobic association to form twisted filaments Urry, 1991; Urry et al., 1994). Inverse temperature transition offers several advantages. It facilitates scale up of purification from grams to kilograms. Milder purification condition requires only a modest change in temperature and ionic strength. This should also facilitate higher recovery, faster purification and high volume processing. Protein purification is generally the slow step (bottleneck) in pharmaceutical product development. Though exploitation of this reversible inverse temperature transition properly, simple and inexpensive extraction and purification may be performed. The temperature at which the aggregation takes place can be manipulated by engineering biopolymers containing varying numbers of repeats and changing salt concentration in solution (McPherson et al., 1996). Chloroplast mediated expression of insulin-polymer fusion protein should eliminate the need for the expensive fermentation process as well as reagents needed for recombinant protein purification and downstream processing.
Oral delivery of insulin is yet another powerful approach that can eliminate up to 97% of the production cost of insulin (Petridis et al., 1995). For example, Sun et al. (1994) have shown that feeding a small dose of antigens conjugated to the receptor binding non-toxic B subunit moiety of the cholera toxin (CTB) suppressed systemic T cell-mediated inflammatory reactions in animals. Oral administration of a myelin antigen conjugated to CTB has been shown to protect animals against encephalomyelitis, even when given after disease induction (Sun et al., 1996). Bergerot et al. (1997) reported that feeding small amounts of human insulin conjugated to CTB suppressed beta cell destruction and clinical diabetes in adult non-obese diabetic (NOD) mice. The protective effect could be transferred by T cells from CTB-insulin treated animals and was associated with reduced insulitis. These results demonstrate that protection against autoimmune diabetes can indeed be achieved by feeding small amounts of a pancreas islet cell auto antigen linked to CTB (Bergerot et al. 1997). Conjugation with CTB facilitates antigen delivery and presentation to the Gut Associated Lymphoid Tissues (GALT) due to its affinity for the cell surface receptor GM1-ganglioside located on GALT cells, for increased uptake and immunologic recognition (Arakawa et al. 1998). Transgenic potato tubers expressed up to 0.1% CTB-insulin fusion protein of total soluble protein, which retained GM1-ganglioside binding affinity and native autogenicity for both CTB and insulin. NOD mice fed with transgenic potato tubers containing micro gram quantities of CTB-insulin fusion protein showed a substantial reduction in insulitis and a delay in the progression of diabetes (Arkawa et al., 1998). However, for commercial exploitation, the levels of expression should be increased in transgenic plants. Therefore, we propose here expression of CTB-insulin fusion in transgenic chloroplasts of nicotine free edible tobacco to increase levels of expression adequate for animal testing.
Taken together, low levels of expression of human proteins in E. coli should make chloroplasts an alternate compartment for expression of these proteins. Production of human proteins in transgenic chloroplasts should also dramatically lower the production cost. Large-scale production of insulin in tobacco in conjunction with an oral delivery system can be a powerful approach to provide treatment to diabetes patients at an affordable cost and provide tobacco farmers alternate uses for this hazardous crop. Therefore, it is first advantageous to use poly(GVGVP) (SEQ ID NO. 20) as a fusion protein to enable hyper-expression of insulin and accomplish rapid one step purification of the fusion peptide utilizing the inverse temperature transition properties of this polymer. It is further advantageous to develop insulin-CTB fusion protein for oral delivery in nicotine free edible tobacco (LAMD 605).

Expression of human serum albumin in plastids

University of Central Florida Research Foundation, Inc.


Arithmetic circuits calculate d−1 energy values (hi2 to hid) indicating energies generated by 2-body to d-body coupling on the basis of a plurality of weight values indicating strength of 2-body to d-body coupling of 2 to d neurons including a first neuron whose output value is allowed to be updated and n-bit output values of n neurons. An adder circuit calculates a sum of these values, and a comparator circuit compares a value based on a sum of the sum and a noise value with a threshold, to determine the output value of the first neuron. An update circuit outputs n-bit updated output values in which one bit has been updated on the basis of a selection signal and the output value of the first neuron. The holding circuit holds the updated output values and outputs the updated output values as the n-bit output values used by the arithmetic circuits.

Neumann computers are not very suitable for solving multivariable optimization problems. However, to solve these problems, there is a method which uses an ising device (also referred to as a Boltzmann machine) that uses an ising energy function. Such an ising device performs calculation by replacing a problem to be calculated with an ising model, which is a model representing the behavior of a ferromagnetic spin.
An ising device can be modeled by using a neural network. In such cases, each of the units (bits) included in the ising device functions as a neuron that outputs 0 or 1 on the basis of states of the other bits and weight values (also referred to as coupling coefficients) each of which indicates coupling strength between the corresponding bit and one of the other bits. For example, the ising device performs simulated annealing to obtain, as a solution, a combination of bit states from which a minimum value of the above energy function (also referred to as a cost function, an objective function, etc.) is obtained.
To shorten the calculation time, realizing such an ising device with hardware modules has conventionally been proposed.
A conventional ising device uses an energy function (which will hereinafter be referred to as a second-order energy function) including a weight value of coupling strength between two bits. One possible way to apply an ising device to more variety of optimization problems is to use an energy function (which will hereinafter be referred to as a high-order energy function) including weight values indicating mutual coupling strength among three or more bits.
There has been proposed a method for solving an optimization problem using a high-order energy function. In this method, an optimization problem using a high-order energy function is solved by converting the optimization problem into an optimization problem using a plurality of second-order energy functions.
Japanese Laid-open Patent Publication No. 07-200512, Aug. 4, 2015
C. R. Schneider and H. C. Card, "Analog CMOS Deterministic Boltzmann Circuits", IEEE Journal of Solid-State Circuits, VOL. 28, No. 8, pp. 907-914, August 1993
R. Babbush, B. O'Gorman, and A. Aspuru-Guzik, "Resource Efficient Gadgets for Compiling Adiabatic Quantum Optimization Problems", arXiv: 1307.8041v1, [quant-ph], Jul. 31, 2013
V. S. Denchev, S. Boixo, S. V. Isakov, N. Ding, R. Babbush, V. Smelyanskiy, J. Martinis, and H. Neven, "What is the Computational Value of Finite Range Tunneling?", arXiv: 1512.02206v4, [quant-ph], Jan. 26, 2016
However, when converting an optimization problem using a high-order energy function into an optimization problem using second-order energy functions, "ancillary bit" has conventionally been introduced. Addition of this ancillary bit could slow down the convergence into an optimal solution or decrease the number of usable bits in simulated annealing.

Information processing apparatus, ising device, and information processing apparatus control method


The invention provides a deployment mechanism 60 for deploying an auxiliary wing surface device 30 from an aircraft wing body 20, the deployment mechanism providing a first connector portion 75, 576 for connecting the deployment mechanism to the aircraft wing body, a second connector portion 65 for connecting the deployment mechanism to the auxiliary wing surface device, and a telescopic rod 61 linking the first and second connector portions, the telescopic rod comprising an inner rod 64 extendable from inside of an outer rod 63 to increase the length of the telescopic rod, such that the distance between the first and second connector portions can be increased. The invention also provides an aircraft wing 10, 510, an aircraft and a method of operating an aircraft.

The present invention concerns deployment mechanisms for use on aircraft wings. More particularly, but not exclusively, this invention concerns deployment mechanisms for deploying an auxiliary wing surface device from an aircraft wing body. The invention also concerns aircraft wings, an aircraft and methods of operating aircraft.
Modern aircraft wings are designed to maximise the angle of attack during take-off and landing operations. This often involves the wing having high-lift devices, with air-profiled surfaces, that can be extended and retracted along a predefined path in relation to the main wing body. These devices can be extended from the leading edge or from the trailing edge of the main wing body.
Prior art methods of deploying the high-lift devices generally comprise a power drive unit, gears, rotary (or possibly linear) actuators, a drive shaft, rotation control sensors and a set of linkages. This makes them bulky, heavy and complicated. An alternative method that has been used to deploy a trailing edge flap comprises a flap track beam with a mechanical gear and ball screw spindle attached to it. A ball nut is attached to the flap using a gimble arrangement. Movement of the nut along the stationary spindle deploys the flap and the gimble arrangement allows the flap to rotate into the desired orientation.
There are three main types of high-lift device; slats, drooped noses and Krueger flaps. Krueger flaps are generally used on a leading edge of a main wing body which is designed to maximise laminar flow along the upper wing surface. A typical Krueger flap, in its retracted position, forms at least part of the leading edge of the main wing body. This means that the profile of the Krueger flap is blended with the lower profile of the leading edge. This means that laminar flow when the flap is stowed (i.e. during cruise) is not disturbed.
However, as Krueger flaps are often used with narrow profiled wings designed for laminar flow, and because the Krueger flap stows within the profile of the wing, the deployment mechanisms needed to extend and retract the Krueger flaps need to be small. A small size of deployment mechanism is also needed so that a minimum required clearance to other systems in the wing (for example in the leading edge of the wing) and to other structures (e.g. a fuel tank) in the wing can be achieved.
The present invention seeks to mitigate the above-mentioned problems. Alternatively or additionally, the present invention seeks to provide an improved deployment mechanism, especially for a Krueger flap.


A skin treatment product and method includes steps of detoxifying cleansing, tightening, and moisturizing skin, by applying bentonite paste, followed by a skin moisturizer, to provide improved skin health and appearance. A single packaging contains bentonite paste and the skin moisturizer. The bentonite paste may be applied in a first step to extract oils, toxins, bacteria and other materials from the skin. After the bentonite paste dries and is removed, the moisturizer is applied to the skin, preferably a vitamin and/or mineral infused moisturizer. In one embodiment, the skin moisturizer is in the form of a skin mask. Following moisturizing the skin, a third step may be to nourish the skin. The skin treatment may be applied to facial skin, feet, hands, or any skin surface.

The present invention relates to skin treatments and in particular to packaging a bentonite paste and mask based skin treatment.
Skin health and appearance is an important issue to many people. Damaged skin is a source of embarrassment to many people. Various products and methods are available to improve skin health and appearance, but they do not provide a complete solution. Often products are not used in a manner to obtain the greatest benefit, for example, face masks applied to facial skin with blocked pores.

Bentonite and skin treatment combination method and packaging


A system that allows for channel and platform agnostic automated scheduling. A user that is registered with the system may add an automated assistant into a pre-existing communication thread or channel, such as a short messaging service (“SMS”) conversation between multiple friends. Any user in the thread may interact with the assistant even if not registered with the system. Once present, the assistant analyzes messages sent to the thread for wake words that trigger actions or responses by the system, including automated scheduling actions. When scheduling is invoked, the system will find acceptable times based on top-down and bottom-up availability provided by registered users, and will propose meeting times until one is accepted by some or all of the participants. Once accepted, the system will confirm the meeting, update linked calendars, and provide reminders to attendees.

For many, it is difficult to find the time to meet with friends, family, and others, whether for leisure or to complete some specific task. Even when free time is available opportunities are missed due to forgetfulness, lack of communication or awareness of opportunities, or a desire to avoid the stress and aggravation that often comes with reaching out, confirming availability, selecting a meeting location, and arranging other details.
While various software platforms and other technologies provide tools or aids to promote or facilitate the process of scheduling a meeting, they often do not remedy the deficiencies that make scheduling an activity that is easier to avoid or put off to another day. Further still, many such platforms themselves have various barriers to use, such as requiring the installation of software applications to one or more devices, configuration of user accounts for each participant to the meeting, web browser requirements that must be met by each participant (e.g., unsupported browsers, inconsistent experience across browsers), and device requirements that must be met by each participant (e.g., unsupported mobile devices, inconsistent experience across mobile devices). Due to these deficiencies, avoidance of use of these conventional technologies becomes an additional barrier or reason to delay scheduling a meeting.
What is needed, therefore, is an improved system for communicating and confirming scheduling in a platform and channel agnostic manner.


A gas turbine engine rotor stack includes one or more longitudinally outwardly concave spacers. Outboard surfaces of the spacers may be in close facing proximity to inboard tips of vane airfoils. The airfoils have dihedral and sweep.

The invention relates to gas turbine engines. More particularly, the invention relates to gas turbine engine compressor vanes.
A gas turbine engine typically includes one or more rotor stacks associated with one or more sections of the engine. A rotor stack may include several longitudinally spaced apart blade-carrying disks of successive stages of the section. A stator structure may include circumferential stages of vanes longitudinally interspersed with the rotor disks. The rotor disks are secured to each other against relative rotation and the rotor stack is secured against rotation relative to other components on its common spool (e.g., the low and high speed/pressure spools of the engine).
Numerous systems have been used to tie rotor disks together. In an exemplary center-tie system, the disks are held longitudinally spaced from each other by sleeve-like spacers. The spacers may be unitarily formed with one or both adjacent disks. However, some spacers are often separate from at least one of the adjacent pair of disks and may engage that disk via an interference fit and/or a keying arrangement. The interference fit or keying arrangement may require the maintenance of a longitudinal compressive force across the disk stack so as to maintain the engagement. The compressive force may be obtained by securing opposite ends of the stack to a central shaft passing within the stack. The stack may be mounted to the shaft with a longitudinal precompression force so that a tensile force of equal magnitude is transmitted through the portion of the shaft within the stack.
Alternate configurations involve the use of an array of circumferentially-spaced tie rods extending through web portions of the rotor disks to tie the disks together. In such systems, the associated spool may lack a shaft portion passing within the rotor. Rather, separate shaft segments may extend longitudinally outward from one or both ends of the rotor stack.
Desired improvements in efficiency and output have greatly driven developments in turbine engine configurations. Efficiency may include both performance efficiency and manufacturing efficiency.
Interstage sealing has been one area of traditional concern. Traditional sealing systems utilize abradable seal material carried on inboard vane platforms and interacting with knife edge runners on one or both of the adjacent blade platforms or on connecting structure.
U.S. patent application Ser. Nos. 10/825,255, 10/825,256, and 10/985,863 of Suciu and Norris (hereafter the Suciu et al. applications, disclosures of which are incorporated by reference herein as if set forth at length) disclose engines having one or more outwardly concave interdisk spacers. With the rotor rotating, a centrifugal action may maintain longitudinal rotor compression and engagement between a spacer and at least one of the adjacent disks. The '255 and '256 applications show knife edge sealing runners on the spacers whereas the '863 application shows inboard free tips on vane airfoils in close running proximity to the spacers.