Abstract: Methods and compositions are provided for modifying one or more target loci in a cell. Such methods comprise providing a cell comprising a first polynucleotide encoding a first selection marker operably linked to a first promoter active in the cell, wherein the first polynucleotide further comprises a first recognition site for a first nuclease agent. A first nuclease agent is introduced into a cell, wherein the first nuclease agent induces a nick or double-strand break at the first recognition site. Further introduced into the cell is a first targeting vector comprising a first insert polynucleotide flanked by a first and a second homology arm that correspond to a first and a second target site located in sufficient proximity to the first recognition site. At least one cell is then identified comprising in its genome the first insert polynucleotide integrated at the target locus.

Abstract: Compositions and methods are provided for making rat pluripotent and totipotent cells, including rat embryonic stem (ES) cells. Compositions and methods for improving efficiency or frequency of germline transmission of genetic modifications in rats are provided. Such methods and compositions comprise an in vitro culture comprising a feeder cell layer and a population of rat ES cells or a rat ES cell line, wherein the in vitro culture conditions maintain pluripotency of the ES cell and comprises a media having mouse leukemia inhibitory factor (LIF) or an active variant or fragment thereof. Various methods of establishing such rat ES cell lines are further provided. Methods of selecting genetically modified rat ES cells are also provided, along with various methods to generate a transgenic rat from the genetically modified rat ES cells provided herein. Various kits and articles of manufacture are further provided.

Abstract: Methods and compositions are provided for modifying one or more target loci in a cell. Such methods comprise providing a cell comprising a first polynucleotide encoding a first selection marker operably linked to a first promoter active in the cell, wherein the first polynucleotide further comprises a first recognition site for a first nuclease agent. A first nuclease agent is introduced into a cell, wherein the first nuclease agent induces a nick or double-strand break at the first recognition site. Further introduced into the cell is a first targeting vector comprising a first insert polynucleotide flanked by a first and a second homology arm that correspond to a first and a second target site located in sufficient proximity to the first recognition site. At least one cell is then identified comprising in its genome the first insert polynucleotide integrated at the target locus.

Abstract: Methods and compositions are provided for generating F0 fertile XY female animals. The methods and compositions involve making XY pluripotent or totipotent animal cells, in vitro cell cultures, or embryos that are capable of producing a fertile female XY animal in an F0 generation. Such cells, embryos, and animals can be made by silencing a region of the Y chromosome. Optionally, the cells can also be cultured in feminizing medium such as a low-osmolality medium and/or can be modified to decrease the level and/or activity of an Sry protein. Methods and compositions are also provided for silencing a region of the Y chromosome in an XY pluripotent or totipotent animal cell, or in vitro cell cultures, embryos, or animals derived therefrom, by maintaining an XY pluripotent or totipotent animal cell in a feminizing medium.

Abstract: Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

Abstract: Disclosed herein are novel methodologies of treating fragile X syndrome and related disorders by inhibiting mGlu5-relevant signaling pathways via the reduction of ?-arrestin2 protein levels or the diminution of mGlu5 and ?-arrestin2 protein interactions.

Abstract: Disclosed herein are novel methodologies of treating fragile X syndrome and related disorders by inhibiting mG1u5-relevant signaling pathways via the reduction of ?-arrestin2 protein levels or the diminution of mG1u5 and ?-arrestin2 protein interactions.

Abstract: Subjects having elevated signaling of a mammalian target of rapamycin (mTOR) are treated with compositions that include at least one compound that activates a Group 1 mGluR. In an embodiment, the subject has tuberous sclerosis complex (TSC). In an embodiment, the compound is a Group 1 mGluR agonist. In another embodiment, the compound is a Group 1 mGluR positive allosteric modulator.

Abstract: A unitary flexible body having an anchor portion wrapping about the wrist to secure the body there, the anchor portion freely offset from the thumb, palm and dorsum of the hand, the body having a support extension extending distally from the anchor portion in supporting relation with the Thenar Emminence of the palm, and extending part way about the thumb via the web space between the thumb and forefinger, and having terminal attachment to said anchor portion.

Abstract: In a thumb wrap, the combination comprising a user's hand and wrist flexible wrap, a generally tubular portion to receive the user's thumb, said tubular portion being integral with the hand and wrap, a securing strap endwise seamlessly integral with the hand and wrist wrap, and extending with elongation to be wrapped over the hand and wrist wrap palmwise and endwise of the tubular portion and then to be wrapped between the user's thumb and forefinger, and then back over the hand and wrist wrap for tensioned tightening and for the effecting thumb positively supported securement.

Abstract: A unitary flexible body having an anchor portion wrapping about the wrist to secure the body there, the anchor portion freely offset from the thumb, palm and dorsum of the hand, the body having a support extension extending distally from the anchor portion in supporting relation with the Thenar Emminence of the palm, and extending part way about the thumb via the web space between the thumb and forefinger, and having terminal attachment to said anchor portion.

Abstract: A generic backhaul protocol is provided for passing telecommunication signaling messages according to multiple signaling protocols between a gateway and a media gateway controller. A message in accordance with the generic backhaul protocol includes a message header that indicates the signaling protocol and/or the channel being used on the gateway. The message also includes a message body that contains a protocol data unit encapsulating signaling data in accordance with a signaling protocol.

Abstract: Systems and methods for generating a user interface are described. In one described system, an aspect associated with an article is identified. Next, an insert comprising a search result is generated based, at least in part, on the aspect. The insert is then caused to be output in association with the aspect.

Abstract: An apparatus including a compartment to store a medicament, a communication facility to exchange data with a health information provider, a display system to present information to a user, and a timekeeping subsystem to activate the display at a predetermined time is described and claimed. Methods of using similar devices, and computer software to control such devices, are also described and claimed.

Abstract: Communicating voice over a packet-switching network is implemented on a telecommunications network that includes the packet-switching network, two coding units coupled to the packet-switching network and to an originating node and a terminating node, respectively, and at least one signaling apparatus. The first of the two coding units is configured to extract signaling data associated with the voice call and transmit the signaling data and its network address to the signaling apparatus. Signaling data for establishing the voice call is received by the signaling apparatus, and a network address of the coding unit in the packet-switching network is obtained. The second coding unit is controlled to establish a bearer channel with the first coding unit for carrying the voice data through the packet-switching network, based on the network address.

Abstract: A mobile router is configured for optimized utilization of reverse routing headers, to specify a path between an originating mobile router and a home agent. Reverse routing headers enable each mobile router within the path to the home agent to specify its care of address, enabling the home agent to establish a bidirectional tunnel to the originating mobile router via the corresponding mobile router. The mobile router selectively updates the reverse routing header in a received packet by inserting the source address value of the received packet into the reverse routing header and inserting its corresponding care of address into the source address field, based on whether the mobile router lacks a routing table entry that specifies reachability of a most recent entry in the reverse routing header via the source address value. The mobile router also may request the originating mobile router to increase the reverse routing header size.

Abstract: A schema-based service for Internet access to per-user services data, wherein access to data is based on each user's identity. The service includes a schema that defines rules and a structure for each user's data, and also includes methods that provide access to the data in a defined way. The services schema thus corresponds to a logical document containing the data for each user. The user manipulates (e.g., reads or writes) data in the logical document by data access requests through defined methods. In one implementation, the services schemas are arranged as XML documents, and the services provide methods that control access to the data based on the requesting user's identification, defined role and scope for that role. In this way, data can be accessed by its owner, and shared to an extent determined by the owner.

Abstract: An arm brace comprising an elongated relatively stiff support configured for application adjacent the inner side of the arm and for nesting adjacent the obtusely angled inner side zone of the partly bent arm opposite the elbow; retainer straps carried by the support near opposite ends thereof, to be independently tightened about the arm at retention locations spaced from a shallow angle shaped mid-section of the support, whereby the user's arm is maintained in shallowly bent condition by the brace.