Abstract: The instant application is directed to single- or double-stranded interfering RNA molecules (e.g., siRNA) that target an alpha-synuclein (SNCA) gene. The interfering RNA molecules may contain specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri-branched, or tetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5? phosphorus stabilizing moiety and/or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject identified as having a synucleinopathy.

Abstract: The present disclosure provides single- or double-stranded interfering RNA molecules (e.g., siRNA) that target a SiglecS (CD33) gene. The interfering RNA molecules may contain specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri-branched, or tetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5? phosphorus stabilizing moiety and/or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject identified as having a neuroinflammatory disease (e.g., Alzheimer's disease).

Abstract: The present disclosure provides single- or double-stranded interfering RNA molecules (e.g., siRNA) that target a chromosome 9 open reading frame 72 (C9orf72) gene. The interfering RNA molecules may contain specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri-branched, ortetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5? phosphorus stabilizing moiety and/or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject identified as having amyotrophic lateral sclerosis or frontotemporal dementia.

Abstract: The present disclosure provides single- or double-stranded interfering RNA molecules (e.g., siRNA) that target an ataxin-3 (ATXN3) gene. The interfering RNA molecules may contain specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri-branched, or tetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5? phosphorus stabilizing moiety and/or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject identified as having a spinocerebellar ataxia (e.g., spinocerebellar ataxia type 3).

Abstract: The present disclosure provides single- or double-stranded interfering RNA molecules (e.g., siRNA) that target a MutS Homolog 3 (MSH3) gene. The interfering RNA molecules may contain specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri-branched, or tetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5? phosphorus stabilizing moiety and/or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject identified as having Huntington's Disease.

Abstract: The present disclosure provides single- or double-stranded interfering RNA molecules (e.g., siRNA) that target a PRNP gene. The interfering RNA molecules may contain specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri-branched, or tetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5? phosphorus stabilizing moiety and/or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject identified as having a prion disease or a high-penetrance PRNP mutation.

Abstract: The present disclosure provides single- or double-stranded interfering RNA molecules (e.g., siRNA) that target a SCN9A gene. The interfering RNA molecules may contain specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri¬branched, ortetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5? phosphorus stabilizing moiety and/or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject experiencing pain or identified as having a pain disorder.

Abstract: Methods, systems, and apparatuses, including computer programs encoded on computer-readable media, for enrollment analysis including receiving historical data related to an entity and a first set of applicants. A model is generated based on the historical data. The model includes a set of factors. First data between the entity and a second plurality of potential applicants is received. A first factor score for each factor for each of the second plurality of potential applicants is generated based on the model. Second data between the entity and the applicants is received. The second data reflects interactions that occur after the first data. A second factor score for each factor is generated for each potential applicant based on the model. A priority range for each factor is received. A subset of the second plurality of potential applicants is identified based a second factor score that is within the priority range.

Abstract: Microglia are an essential part of the immune system in the central nervous system, as well as potential sources of disease. Gene silencing employs short interfering RNA (siRNA) to selectively target genes that are the source of such diseases. By employing branched siRNA, distribution of the siRNA throughout the CNS, including to the resident microglial cells, may be enhanced as compared to unbranched siRNA. Methods and compositions for the use of branched siRNA in a therapy are contained herein.

Abstract: The present disclosure provides single- or double-stranded short interfering RNA (siRNA) molecules having specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri-branched, ortetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5? phosphorus stabilizing moiety and/or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject identified as having a disease.

Abstract: The present invention is a method and system to precisely locate objects of interest in any given image scene space, which finds the presence of objects based upon pattern matching geometric relationships to a master, known set. The method and system prepares images for feature and attribute detection and identifies the presence of potential objects of interest, then narrows down the objects based upon how well they match a pre designated master template. The method by which matching takes place is done through finding all objects, plotting its area, juxtaposing a sweet spot overlap of its area on master objects, which in turn forms a glyph shape. The glyph shape is recorded, along with all other formed glyphs in an image's scene space and then mapped to form sets using a classifier and finally a pattern matching algorithm.

Abstract: The present invention is a method and system to precisely locate objects of interest in any given image scene space, which finds the presence of objects based upon pattern matching geometric relationships to a master, known set. The method and system prepares images for feature and attribute detection and identifies the presence of potential objects of interest, then narrows down the objects based upon how well they match a pre designated master template. The method by which matching takes place is done through finding all objects, plotting its area, juxtaposing a sweet spot overlap of its area on master objects, which in turn forms a glyph shape. The glyph shape is recorded, along with all other formed glyphs in an image's scene space and then mapped to form sets using a classifier and finally a pattern matching algorithm.

Abstract: A company project management system. The novel system includes a database server for providing multiple users with access to a project file, which includes a schedule for a project with a plurality of tasks and task dependencies, and a statusing system for concurrently obtaining performance updates from multiple users and updating the schedule in the project file with the performance updates in real time as the performance updates are obtained. In a preferred embodiment, the statusing system is adapted to control when tasks can be updated based on task dependencies such that updating for a task with dependencies is disabled unless the dependencies have been fulfilled. The statusing system may also include a tool for allowing a user to add a plurality of sub-tasks to a parent task and enter performance updates for the sub-tasks. The statusing system automatically updates the parent task based on the updates obtained for the sub-tasks.

Abstract: A method of determining the presence and level of microorganisms and/or chemicals in samples taken from generally any non-laboratory substance or environment. The method preferably comprises one or a combination of the steps of (a) prescreening for threshold levels of targeted microorganisms and/or (b) confirming the presence of targeted microorganisms or chemicals by mass spectrometry fingerprint analysis.

Abstract: The invention provides methods, kits, and apparatus for increasing the sensitivity of immunoassays performed on environmental samples by reducing sample matrix effects.

Abstract: Assemblies and methods for positioning and securing a window or door unit within a rough opening of a building or other structure. In one example, the assembly includes a jamb member and a jamb liner coupled with the jamb member. The jamb liner includes a retaining member sized and shaped to receive and engage a fastener at a plurality of locations therein. In another example, the retaining member includes at least one flange to engage the fastener and a groove to seat a fastener head.

Abstract: A window or door assembly including a jamb member and a jamb liner having a fastener opening coupled along the jamb member. A sash is moveably coupled along the jamb liner. The window or door assembly includes a structural filler coupled over a portion of the jamb liner, and the structural filler substantially conceals the fastener opening. The structural filler includes a flange sized and shaped to engage with the sash, and the flange substantially prevents movement of the sash over the structural filler. In one option, the flange extends along the structural filler and the sash. The structural filler further includes a contact surface engaged with the jamb liner and a projection rotatably coupled with the jamb liner, and the structural filler rotates in a first direction around the projection.

Abstract: A window drive mechanism includes a bracket and a cam slide moveably coupled to the bracket. In one option, the bracket is coupled to a window frame. An elongate arm is rotatably coupled to a sash substantially adjacent to a first end of the arm. In one option, the elongate arm is rotatably coupled to the bracket substantially adjacent to a second end of the arm. In another option, the elongate arm is moveably coupled to the cam slide between the first end and the second end. An actuator arm is coupled to the cam slide and operable to move the cam slide. A method for making a window assembly optionally includes providing a window frame and coupling a window drive mechanism to the window frame.

Abstract: A Postal Authority regulated e-Mail messaging application is provided over a public network to a plurality of mailers and addressees using authenticated transaction records. The application transmits at least one e-Mail message through at least one e-Mail account configured for a specific class of service. The application creates transaction records relevant to the specific class of service based upon details of completed transactions. Electronic postmarks are obtained to authenticate transaction records. Authenticated transaction records are sent to the mailer. A unique identifier of an electronic postmark is embedded in the e-Mail message. The e-Mail message incorporating the unique identifier is sent to at least one addressee. Authenticated e-Mail messages and transaction records are created and protected from undetectable modification.

Abstract: An impact resistant window assembly includes a bracket assembly that has a bracket portion with a first position and a second position. The bracket assembly is disposed within the window jamb assembly when the bracket portion is disposed in the first position, and the bracket portion disposed over a portion of the interior portion of the sash when the bracket portion is disposed in the second position.