Abstract: Alzheimer's disease (AD) is the most common type of dementia in aging adults with the number of people living with AD projected to increase, making the search for treatments and tools to diagnose and measure disease progression increasingly urgent. In particular, ideal biomarkers for diagnosis of AD should not only have high specificity for disease versus non-disease and high sensitivity for distinguishing between disease types but also should be able to detect changes at a very early stage of the disease. Using microglia activation as an early event of AD's onset, the present inventors have identified a panel of biomarkers in CSF which has the potential to diagnose, stage and determine the likelihood of developing AD.

Abstract: A bi-laminate polymer coated metal substrate, vehicle trim member formed therefrom, and method of manufacture thereof are provided. The bi-laminate polymer coated metal substrate includes a monolithic metal substrate having a first area with a first polymeric material bonded thereto and a second area, different from the first area, with a second polymeric material bonded thereto. A substantially tear resistant, protective substrate is releasably bonded to the first polymeric material, with the first polymeric material being sandwiched between the protective substrate and the metal substrate. The protective substrate is selectively removable from the first polymeric material to expose the first polymeric material as a finish surface.

Abstract: Alzheimer's disease (AD) is the most common type of dementia in aging adults with the number of people living with AD projected to increase, making the search for treatments and tools to diagnose and measure disease progression increasingly urgent. In particular, ideal biomarkers for diagnosis of AD should not only have high specificity for disease versus non-disease and high sensitivity for distinguishing between disease types but also should be able to detect changes at a very early stage of the disease. Using microglia activation as an early event of AD's onset, the present inventors have identified a panel of biomarkers in CSF which has the potential to diagnose, stage and determine the likelihood of developing AD.

Abstract: A bi-laminate polymer coated metal substrate, vehicle trim member formed therefrom, and method of manufacture thereof are provided. The bi-laminate polymer coated metal substrate includes a monolithic metal substrate having a first area with a first polymeric material bonded thereto and a second area, different from the first area, with a second polymeric material bonded thereto. A substantially tear resistant, protective substrate is releasably bonded to the first polymeric material, with the first polymeric material being sandwiched between the protective substrate and the metal substrate. The protective substrate is selectively removable from the first polymeric material to expose the first polymeric material as a finish surface.

Abstract: The disclosure provides a method for assaying for a target analyte, comprising providing a plurality of samples which may comprise the target analyte, wherein each sample is differentially labelled with a mass label or a combination of mass labels, wherein the mass labels are from a set of mass labels, wherein each mass label is an isobaric mass label comprising a mass spectrometrically distinct mass marker group, such that the samples can be distinguished by mass spectrometry and determining from the mass spectrum the quantity of the target analyte in each sample.

Abstract: The present invention concerns materials and methods relating to pancreatic cancer and personalized medicine as applied to pancreatic cancer. Particularly, the invention relates to materials and methods for the determination of significantly modulated protein phosphorylation and/or expression as well as the activity of signalling pathways collectively providing a tumour profile that can guide selection of the most appropriate treatment regime based on the likelihood of tumour recurrence or the identity of activated drug targets in pancreatic cancer.

Abstract: The present invention provides materials and methods relating to screening for compounds useful in the treatment of Alzheimer's disease and related conditions. In particular, screening methods using tyrosine kinases are provided, as are methods relating to the role of tyrosine kinases as therapeutic targets.

Abstract: Methods of screening for candidate compounds capable of inhibiting activity of fyn in phosphorylating tau protein at Y394 or binding to fyn to inhibit interaction with tau protein at Y394, including determining whether, and optionally the extent, the candidate compounds have these capabilities under conditions where fyn has these capabilities in the absence of the candidate compound. Methods of screening for substances capable of promoting dephosphorylation of tau protein by a phosphatase at a site of tau protein including contacting a candidate substance, the tau protein and a phosphatase capable of dephosphorylating the tau protein under conditions where the phosphatase is capable of dephosphorylating the site in absence of the candidate substance, where the kinase is fyn; determining whether, and optionally the extent, the candidate substance promotes dephosphorylation of the tau protein at the site; and selecting the candidate substance which promotes dephosphorylation of the tau protein the sites.

Abstract: Methods and apparatus for producing an object, the method comprising: performing an Additive Manufacturing process to produce an intermediate object from provided metal or alloy, whereby the intermediate object comprises regions having a contaminant concentration level above a threshold level; based upon one or more parameters, determining a temperature and a duration; and performing, on the intermediate object, a contaminant dispersion process by, for a duration that is greater than or equal to the determined duration, heating the intermediate object to a temperature that is greater than or equal to the determined temperature and less than the melting point of the metal or alloy, the contaminant dispersion process being performed so as to disperse, within the intermediate object, a contaminant from regions of high contaminant concentration to regions of low contaminant concentration until the intermediate object comprises no regions having a contaminant concentration level above the threshold level.

Abstract: Disclosed are methods of processing an object, the object being made of a metal or an alloy, the object having a plurality of open cavities, the method comprising: performing a sealing process on the object to seal the openings of the open cavities, thereby forming a plurality of closed cavities; and reducing the sizes of the closed cavities by performing a consolidation process on the object having the closed cavities. Sealing process may comprise shot peening or coating the object. A consolidation process may comprise a hot isostatic pressing process. The sizes of the closed cavities may be reduced until the closed cavities are no longer present in the object.

Abstract: Methods for screening for substances capable of modulating the phosphorylation of tau protein are disclosed, and in particular paired helical filament (PHF) tau, and the use of such modulators in the treatment of tauopathies. The assays and screening methods are based on the identification of new phosphorylation sites in PHF tau and new kinases and combinations of kinases as therapeutic targets, in particular the identification of casein kinase 1 as a kinase which phosphorylates tau protein.

Abstract: Disclosed is a method of producing an object, the object being made of metal or an alloy, having a desired shape and being non-porous, the method comprising: providing some metal or alloy having a first average solute level; using the provided metal or alloy, performing a net-shape or near-net shape manufacturing process to produce an intermediate object, the intermediate object having the desired shape, being non-porous, and having a second average solute level, the second average solute level being greater than or equal to the first average solute level; and performing a solute level changing process on the intermediate object to change the solute level of at least the bulk of the intermediate object such as to provide the intermediate object with a third average solute level, thereby providing the object, the third average solute level being different to the second.

Abstract: Methods and compositions relating to Alzheimer's disease are provided, including proteins that are differentially expressed in Alzheimer's disease as compared to the normal state. Further provided are methods, particularly experimental paradigms, for the identification of differential expressed proteins that are potential molecular targets for compounds to treat or prevent Alzheimer's disease. Also provided are methods for the identification and therapeutic use of compounds for the prevention and treatment of Alzheimer's disease.

Abstract: The present invention provides methods of screening for candidate compounds useful in the treatment of Alzheimer's disease and related conditions by inhibiting specific phosphorylation of tau protein by tyrosine kinase c-Abl.

Abstract: A molding for attachment to a flange portion includes a retention portion having first and second legs defining a channel for receiving the flange portion, and a support member coupled to the retention portion and movable relative thereto. The support member includes an outboard surface and an inboard surface. A film is disposed along the outboard surface of the support member. A clip is formed along and extends out from the first leg of the retention portion. The clip is engageable with the support member to lock the support member in place relative to the retention portion for positioning the film along the flange portion.

Abstract: An integrated reveal molding is provided for a motor vehicle door frame having a header section defining a window opening. The integrated reveal molding includes an upper reveal adapted to be mounted to the header section. The upper reveal includes a reveal surface disposed outboard of the header section. A reveal is secured along the reveal surface. The integrated reveal molding also includes a glass run co-extruded with the upper reveal. The glass run includes a window receiving channel for engagement with a window pane. The integrated reveal molding is formed as an extruded member from thermoplastic vulcanisate (TPV) of different durometer values to meet varying flexibility and durability requirements.

Abstract: A method of manufacturing a shaped part, the method including: (I) providing a partially consolidated porous part that has been made from a powder; (II) permeating the porous part with a volatile liquid (e.g. water, ethanol), so that the liquid is present in the pores of the porous part; and (V) forming the shaped part by applying a laser beam to a spot on the surface of the liquid-permeated part to cause the volatile liquid to heat in the spot region, causing the powder particles to separate in the spot region, so that a portion of the part is ablated in the spot region. The porous part may be made from metallic or ceramic powder and has been partially consolidated for integrity, but is ablated by this lower energy, liquid-assisted laser process, prior to further strengthening. The method allows bespoke, complex shaped parts such as aerospace parts or medical implants to be made inexpensively, especially shaped titanium parts.

Abstract: Methods and compositions relating to Alzheimer's disease are provided. Specifically, proteins that are differentially expressed in the Alzheimer's disease state relative to their expression in the normal state are provided. Proteins associated with Alzheimer's disease are identified and described. Methods of diagnosis of Alzheimer's disease using the differentially expressed proteins are also provided, as are methods for the identification and therapeutic use of compounds for the prevention and treatment of Alzheimer's disease.

Abstract: The disclosure provides a method for assaying for a target analyte, comprising providing a plurality of samples which may comprise the target analyte, wherein each sample is differentially labelled with a mass label or a combination of mass labels, wherein the mass labels are from a set of mass labels, wherein each mass label is an isobaric mass label comprising a mass spectrometrically distinct mass marker group, such that the samples can be distinguished by mass spectrometry and determining from the mass spectrum the quantity of the target analyte in each sample.