The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a BCMA monoclonal antibody, conferring specific immunity against BCMA positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas, multiple myeloma and leukemia.

The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), such as where the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an Ig light chain (or functional fragment thereof).

A modular engineered tissue construct includes a plurality of fused self-assembled, scaffold-free, high-density cell aggregates. At least one cell aggregate includes a plurality of cells and a plurality of biocompatible and biodegradable nanoparticles and/or microparticles that are incorporated within the cell aggregates. The nanoparticles and/or microparticles acting as a bulking agent within the cell aggregate to increase the cell aggregate size and/or thickness and improve the mechanical properties of the cell aggregate as well as to deliver bioactive agents.

Provided herein are methods of treatment to regenerate, restore or rejuvenate a tissue. Methods include making adult somatic and germ cells pluripotent for administration to a patient. Alternatively, created pluripotent cells may be differentiated to the desired tissue type and administered to a patient to repair or enhance the target tissue.

A recombinant vector comprises simian adenovirus 36, simian adenovirus 42.1, simian adenovirus 42.2 and/or simian adenovirus 44 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses one or more simian adenovirus-36, -42.1, -42.2 or -44 gene(s) is also described. Methods of using the vectors and cell lines are provided.

Non-naturally occurring peptides are provided that act as a Src SH2 domain antagonist of cardiotonic steroids. Pharmaceutical compositions comprising the peptides are also provided along with vectors encoding the peptides. Methods of treating a Src-associated disease and reducing Src activity in a cell are further provided and include administering or contacting a cell with an effective amount of the peptide.

Materials and methods for treating and preventing American Foulbrood disease in honeybees, such as materials and methods for using phage lysin enzymes to lyse Paenibacillus larvae, are provided herein.

The present invention relates to the use of the miRNA expression profile, particularly of miR-199a-5p, and the target genes regulated thereby for the diagnosis, prognosis and use of miR-199a-5p inhibitors for treating fibroproliferative disorders.

The invention relates to polynucleotide agents targeting the complement component C5 gene, and methods of using such polynucleotide agents to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

In one aspect, the invention relates to a method of loading exosomes with oligonucleotide cargo, by incubating an oligonucleotide comprising one or more hydrophobic modifications with a population of exosomes for a period of time sufficient to allow loading of the exosomes with the oligonucleotide. Exosomes loaded with hydrophobic ally modified oligonucleotide cargo, and uses thereof, are also provided.

Provided herein are compositions and methods for modifying a predetermined nucleic acid sequence. A programmable nucleoprotein molecular complex containing a polypeptide moiety and a specificity conferring nucleic acid (SCNA) which assembles in-vivo, in a target cell, and is capable of interacting with the predetermined target nucleic acid sequence is provided. The programmable nucleoprotein molecular complex is capable of specifically modifying and/or editing a target site within the target nucleic acid sequence and/or modifying the function of the target nucleic acid sequence.

The invention provides diagnostic and therapeutic targets for pulmonary disease, in particular, fibrotic lung disease. The inventors have found that a genetic variant MUC5B gene is associated with increased expression of the gene, increased risk of developing a pulmonary disease, and an improved prognosis and survival among those developing the pulmonary disease.

By a genome-wide gene analysis of expression profiles of known or putative gene sequences in peripheral blood and biopsy samples, the present inventors have identified a consensus set of gene expression-based molecular biomarkers for distinguishing liver transplantation patients who have Acute Rejection (AR), Hepatitis C Virus Recurrence (HCV-R), both AR/HCV-R, or Acute Dysfunction No Rejection (ADNR). These molecular biomarkers are useful for diagnosis, prognosis and monitoring of liver transplantation patients.

Provided herein are methods for the prognosis of prostate cancer progression in a patient by analyzing the gene expression in a tumor sample obtained from the patient the prognosis of prostate cancer progression in a patient by analyzing the gene expression in a tumor sample obtained from the patient. In particular, gene expression levels of GCOM1, MEX3D, TRPM4, ATPAF1, PTRF, GLYATL1, FLNA, OBSCN, STRA13, WHSCl, ARFGAP3, KDM2A, FAM83H, CLDN7, CNOT6, and B3GNT9 are measured. Kits containing means for the measurement of gene expression as described herein and methods for treatment of prostate cancer are also provided.

The present invention concerns cancer biomarkers. In particular, the invention concerns HGF as a biomarker for patient selection and patient prognosis in cancer, as well as methods of therapeutic treatment, articles of manufacture and methods for making them, diagnostic kits, methods of detection and methods of advertising related thereto.

This disclosure relates to methods, computer products, computer-implemented methods, and systems for predicting the probability or risk of prostate cancer recurrence and tumor aggressiveness in a patient. The method is based, in part, on the patient's risk profile that includes the presence/degree of specific copy number variations and predictive clinical factors. The methods and systems can be used to aid in treatment selection.

Fibrous structures that exhibit a novel combination of properties and to methods for making such fibrous structures are provided.

The invention provides for a proteomic approach for identification of specific bacterial protein profiles that may be used in the development of methods for the diagnosis of bacterial chronic sinusitis. The invention provides for methods for determining the presence of pathogenic bacteria in the upper respiratory tract of a subject using protein profiles of the pathogenic bacteria. The invention also provides for methods of diagnosing a bacterial infection of the upper respiratory tract of a subject using protein profiles of a pathogenic bacteria. In addition, the invention provides for devices, immunoassays and kits for identifying pathogenic bacteria in the upper respiratory tract.

This invention relates to novel monoclonal antibodies that specifically bind to the alpha-folate receptor. In some embodiments, the antibodies inhibit a biological activity of folate receptor-α (FR-α). The antibodies are useful in the treatment of certain cancers, particularly cancers that have increased cell surface expression of the alpha-folate receptor (“FR-α”), such as ovarian, breast, renal, colorectal, lung, endometrial, or brain cancer. The invention also relates to cells expressing the monoclonal antibodies, antibody derivatives, such as chimeric and humanized monoclonal antibodies, antibody fragments, and methods of detecting and treating cancer using the antibodies, derivatives, and fragments.

Described herein are methods and compositions for treatment of immune-related diseases or disorders by modulating DD1α activity, alone or in combination with modulation of PD-1 activity. In some embodiments, the methods and compositions described herein are directed to treatment of cancer and/or infections (e.g., bacterial infection, and/or fungal infection). In some embodiments, the methods and compositions described herein are directed to treatment of autoimmune diseases and/or inflammation. In some embodiments, the methods and compositions described herein are directed to treatment of asthma, and allergy. Methods for identifying patients who are more likely to be responsive to and benefit from an immunotherapy that targets DD1α and/or PD-1 activity or expression are also described herein.

The present invention provides methods for assessing whether a subject is at risk of developing a neurological disorder, diagnosing or confirming whether a subject is afflicted with a neurological disorder, assessing whether PD has progressed in a subject afflicted with PD, assessing whether a neurological disorder is developing in a subject who has been identified as being at risk of developing the neurological disorder, assessing whether a subject afflicted with a neurological disorder is likely to benefit from a therapy, assessing whether a subject afflicted with a neurological disorder has benefited from a therapy, treating a subject afflicted with a neurological disorder, and prophylactically treating a subject who has been identified as being at risk of developing a neurological disorder. The present invention also provides epitopes, compounds and compositions relating to these methods.

A cold rolling mill is described wherein the unstressed shape of metal sheet is continuously sensed during rolling by a plurality of negligible displacement force sensors perpendicularly disposed relative to the pass line at a mill location producing a tensile stress above 4,000 p.s.i. in the metal sheet being rolled. The output signals from those sensors underlying opposite edges of the metal sheet are compared to equalize reduction at the sheet edges while the difference between the force measured by a centrally situated sensor and the average force measured by the sensors underlying opposite edges of the sheet provide a signal indicative of the roll bending force required to produce flat sheet.

A button and pin assembly machine for producing badges and the like comprising buttons having rearwardly extending rims adapted to receive and retain respective pin structures therein, in which the buttons are sequentially supplied to a pin-forming head and supported thereat with the button rim encircling the end of such head, straight pin blanks being sequentially supplied to said head, with a portion of a pin blank being inserted into the head and rotated thereby with respect to a stationary abutment to curl an end of such blank sufficiently to enable its insertion in the rim of a button disposed thereat, said head having means for forming a bend in the portion of the pin blank inserted in such head to resiliently bias the pointed end of the pin blank toward the button.

Portions of a pin-on button are cut and assembled as a result of a plurality of operations in a machine having a vertical press. Cutter and work deforming tools are displaced by a single press ram to cut blanks and deform the blanks onto a button top placed in one of two die assemblies positioned in alignment below the work deforming tool on the lower end of the ram.

Device for forming buttons from a pin-on back plate, a front plate, and a cover over the front plate, with the device having a pair of button-forming dies alternately shiftable into operation alignment with a forming punch which on descent with the successively aligned dies cooperates with the latter to assemble the separate button parts into a button, and a cover-blanking punch and die set above the forming punch, of which the blanking die is topmost and has a die aperture open at the top and bottom and a cutting edge at the bottom of the aperture, with the blanking die being by the forming punch raised into blanking cooperation with the blanking die, and the forming punch being moved upwardly and downwardly by manually operable means.

Device for forming buttons from a pin-on back plate, a front plate, and a cover over the front plate, with the device having a pair of button-forming dies alternately shiftable into operative alignment with a forming punch which on descent into the successively aligned dies cooperates with the latter to assemble the separate button parts into a button, and a blanking punch and die set above the forming punch, of which the blanking punch is raised into cooperation with the blanking die for blanking a cover from a supply sheet, and a handlever operatively connected with the punches for simultaneously lowering the forming punch and raising the blanking punch.

Apparatus for the manufacture of a laminated button comprising a metallic backing plate having a transverse peripheral edge and an outwardly extending flange, an illustrated paper sheet and a protective acetate covering. The apparatus comprises a pneumatically operated press which receives the plate, illustrated sheet and covering, and, with a single downward movement, causes the sheet to conform to the plate and be crimped between the transverse edge and flange.

A machine for the manufacture of buckles, buttons or the like which comprises an upper tool and a lower tool. The lower tool has an outer, spring-mounted frame and an inner core piece displaceable vertically with respect to the surrounding frame. The lower tool is adapted to support the assembled button after the opening stroke of the upper tool. A device is provided for lifting the core piece of the lower tool relative to the surrounding frame up to about the height of a transversely directed stream of blast air serving for discharging the product from the lower tool.

A button covering device having a platform with a central opening which forms a well to receive a button to be covered and the fabric for covering the button. A pair of sliding plates having contoured recesses are mounted on the platform whereby the contoured recesses may be positioned to overlap the opening to gather the fabric over the rear of the button.

A method for fabrication of a relatively low cost display or communicative novelty button in which a consumable restrictor sheet is placed over a vacuum draw type female mold cavity. The restrictor sheet may be of cardboard and be apertured with a diameter smaller than the mold cavity diameter. A thermoplastic sheet material is then placed over the restrictor sheet, heated to reach a formable state and vacuum drawn through the restricted aperture and down so that the sheet comes into contact with and generally conforms to the desired shape defined by the mold cavity. The plastic sheet material may then be trimmed near the edge of the restrictor sheet to leave a button shell mounted on a restrictor sheet which may then be used for purposes of display. The restrictor sheet also enables fabrication with an inwardly facing peripheral groove that may be used to secure a pin fastener. An alternate form of fastener in which a portion of the remaining plastic sheet is used is also disclosed.

A fabric covered button comprising a button head having a peripheral groove for receiving a locking ring. The fabric is secured to the button head and the marginal edge thereof is retained within the groove by the locking ring.

Apparatus for assembling covered buttons in which a first die assembly including a first punch carrying a first sleeve which sequentially receives a piece of covering material and the button shell with its flange extending toward the open end of the sleeve. A second assembly including a second sleeve having a bore one end of which is formed with a first cam surface extending axially inwardly of the above. The second sleeve is spring loaded to an extended position on a supporting post having a centrally located button back fastener receiving cavity in the end thereof with a second cam surface extending inwardly from the outer edge of the end to the bottom of a recess surrounding the cavity. An annular boss at the inner edge of the recess around the cavity is elevated to allow the material and the shell flange to curl inwardly under the button back. In the retracted position of the second sleeve on the post, the second cam surface forms a continuation of the first. In operation, when the first assembly carrying the covering piece and the shell moves toward the second assembly, the first sleeve stops against the spring loaded bottom sleeve and the punch continues forcing the material down so that the material is tucked inward by the beveled or curved surface of the second sleeve. Upon continued relative movement of the assemblies, the shell flange acts on the cam surface of the second sleeve to force the sleeve to its retracted position and the shell flange is moved inwardly of the back wall under the continued action of the first post, the extent of the inward movement of the shell flange being determined by the thickness of the material of the covering piece, as well as the height of the shell and the type of back used.

Applicant's invention relates to a process and apparatus for the high speed welding in large quantities of various geometric shaped jump rings to buttons, pendants and other jewelry by utilizing composite jump ring apparatus having first and second projections extending from the jump rings at different locations so that they may function in automatic welding machines.

An improved method of forming and assembling two-part merchandise display hooks, including new design features of the hook itself, enable two-part hooks to be manufactured and assembled at extremely low cost. Wire from a continuous length is gripped and bent to form the outer portion of the hook. The wire is then severed and bent in a single operation to form a hook-mounting portion. While the severed wire remains gripped by its shaped outer end, a preoriented and guided base member is applied over the just-formed mounting portion of the wire. A retractable bend-forming member is withdrawn when the base member is applied to the wire, to enable the bent portion to be fully received within the plastic base. Major manufacturing economies are realized.

A device is disclosed for pressing objects by lifting the objects into a waiting pressing shaft. The shaft includes a forming element at its lower end for forming the object, and the shaft is engaged by its upper end through a pivot member to an air cylinder in a manner which provides a force advantage to the air cylinder. Also, a system for pressing objects is disclosed, in which the press device is employed in conjunction with a turntable for sequential and continuous pressing operations.

A machine for automatically joining front and back parts of buttons employs a turntable with nests that are rotated through a series of stations at which the parts are placed in the nests in a desired orientation, joined, and checked for defects. Orientation of the parts is achieved by video imaging of a first part as it is randomly placed in a nest, and computer-controlled placement of the second part based on the ascertained position of the first part.

A method and apparatus for substantially automatically joining front and back parts of buttons employs a turntable with retaining means that are rotated through a series of stations at which the parts are placed in the retaining means in a desired orientation, joined, and checked for defects. A human operator places button front parts at a first station, and the remaining stations carry out the assembly and quality control steps automatically. Placement at the first station determines the alignment and orientation of the two buttons.

A punch button (32) has a central disc (36) integral with and separable from an outer peripheral annular ring (38). The disc and ring are joined by a breakaway portion (40) of reduced thickness. A pair of peel points or pilot cuts (50 and 52) may be provided on distally opposite sides of the disc, and if so, the disc is initially separable from the ring at the peel points and then rotatable about a rotation axis perpendicular to an axis through the distally opposite pilot cuts. The punch button is formed by providing a strip of material of a first thickness, placing the strip in a die, performing an inner cut with the die and partially cutting through the strip to yield first and second subpieces joined to each other by material of a second reduced thickness, and performing an outer cut with the die and cutting all the way through the strip to yield a piece composed of the first and second subpieces providing the disc and ring. The pilot cuts are performed by the die during performance of the inner cut and to a deeper depth than the inner cut. All of the cuts are performed in a singular die step operation wherein an outer punch (58) is moved toward an inner punch (66) in one axial direction to perform the inner cut, the pilot cuts, and a portion of the outer cut, and continuing movement of the outer punch in the one direction and simultaneously moving the inner punch in the same direction in unison with the outer punch to complete the outer cut.

A universal assembly machine manufactures button medallions. The machine comprises a rotatably indexable die table to which are mounted pickup and crimp dies. The die table indexes about a center column of the machine frame. A ram die is advancable and retractable in a pickup stroke and a crimp stroke by means of a handle. The ram die includes a ram outer ring that is rotatable by means of a shifter post joined to the die table. Indexing the die table causes the shifter post to rotate the ram outer ring into a pickup mode or a crimp mode to suit the ram pickup and crimp strokes, respectively. The universal assembly machine also manufactures buttons with flat backs. To make a button medallion a flat back button is loaded into the pickup die. The ram die is advanced in a third press stroke to bend the shell frusto-conical wall of the flat back button inwardly to be flat and parallel to the flat back. The thin edge of the button medallion enables it to be used as an attractive embellishment on flat surfaces.

A universal assembly machine manufactures conventional buttons with formed backs. The machine comprises a rotatably indexable die table to which are mounted pickup and crimp dies. The die table indexes about a center column of the machine frame. A ram die is advancable and retractable in a pickup stroke and a crimp stroke by means of a handle. The ram die includes a ram outer ring that is rotatable by means of a shifter post joined to the die table. Indexing the die table causes the shifter post to rotate the ram outer ring into a pickup mode or a crimp mode to suit the ram pickup and crimp strokes, respectively. The universal assembly machine also manufactures buttons with flat backs by using a different crimp die pedestal than is used with the formed backs. An adapter on the crimp die pedestal used with formed backs allows that crimp die pedestal to also be used for manufacturing buttons with flat backs. The invention also embraces button medallions. A flat back button is loaded into the pickup die, and the die table is indexed. The ram die is advanced in a third press stroke to bend the shell frusto-conical wall of the flat back button inwardly to be flat and parallel to the flat back.

Disclosed is a wireless surround sound speaker system wherein a transmitter broadcasts a variety of FM signals that correspond to the individual speaker channels commonly found in a surround sound system. Receivers, individually equipped with signal receiving, conditioning and amplification components, are configured to receive any one of the broadcast signals in a remote location and are used to drive a conventional loudspeaker in that location. Powered by wall socket or via DC battery packs, the receivers, used in conjunction with the transmitter, provide surround sound capabilities without the need for complex and difficult wiring.