Abstract: The invention relates to the preparation of gamma amino acids of formula (I) and pharmaceutically acceptable salts, solvates and prodrugs thereof, and to intermediates used for their preparation. (formula I) wherein R1 is selected from an alkyl group, an alkenyl group, an alkynyl group and a cycloalkyl group, each of which may be optionally substituted and * denotes a chiral center. In particular, the present invention provides an efficient synthesis of (S)-pregabalin which is suitable for carrying out on an industrial scale.

Abstract: An object/test material interaction microti iridic device comprising a sample inlet adapted to receive a fluid sample comprising a plurality of objects, an outlet adapted to output the fluid sample from the device, at least one internal surface defining a flow cavity within the device, wherein the flow cavity extends between and is connected to the sample inlet and the outlet for flow of the fluid sample through the flow cavity, the flow cavity comprises a test area to which at least one test material is attached and which is situated in the flow cavity for flow of the fluid sample over the test area, and the flow cavity has an aspect ratio which, when the flow cavity is substantially filled by the fluid sample, provides a substantially constant shear force between the test area and the fluid sample flowing over the test area. The invention further comprises a system incorporating the device, methods of use of the device and system, and methods of analyzing interactions.

Abstract: A method or assay for determining whether an individual is a HNF1A-MODY carrier is described and comprising a step of assaying a biological sample from the individual to detect increased abundance of a micro RNA molecule selected from miR103, miR551b, or miR224, or detect decreased abundance of a micro RNA molecule selected from miR503, and miR539. Increased abundance of one or more of miR103, miR551b, or miR224 or decreased abundance of one or more of miR503 and miR539, indicates that the individual is a HNF1A-MODY carrier. A method for treating metabolic disorders, especially diabetes mellitus, is also described.

Abstract: A method of diagnosing metastatic potential of a breast cancer in an individual with breast cancer is described. The method comprises a step of assaying a breast cancer tumour sample from the patient for expression of A Disintegrin And Metalloproteinase 22, (ADAM22), wherein expression of ADAM22 correlates with increased potential for metastasis compared with a patient who is ADAM22 negative. The invention also describes an agent for use in the treatment of metastatic breast cancer in a patient, in which the agent is selected from leucine-rich, glioma-inactivated protein 1 (LGI1) protein (SEQ ID NO:1) and an LGI1 peptide mimic capable of mimicking the ADAM22 binding activity of LGI1 by binding to the LGI1 binding domain of ADAM22 (SEQ ID NO: 4) and which is capable of inhibiting migration of endocrine resistant breast cancer cells.

Abstract: A method of diagnosing metastatic potential of a breast cancer in an individual with breast cancer is described. The method comprises a step of assaying a breast cancer tumor sample from the patient for expression of A Disintegrin and Metalloproteinase 22, (ADAM22), wherein expression of ADAM22 correlates with increased potential for metastasis compared with a patient who is ADAM22 negative. The invention also describes an agent for use in the treatment of metastatic breast cancer in a patient, in which the agent is selected from leucine-rich, glioma-inactivated protein 1 (LGI1) protein (SEQ ID NO:1) and an LGI1 peptide mimic capable of mimicking the ADAM22 binding activity of LGI1 by binding to the LGI1 binding domain of ADAM22 (SEQ ID NO: 4) and which is capable of inhibiting migration of endocrine resistant breast cancer cells.

Abstract: A method of producing microcapsules of the type having a core and a coating encapsulating the core comprises the steps of providing a core-forming fluid stream and a coating-forming fluid stream, providing a two spray nozzle arrangement having a core nozzle disposed concentrically about a second nozzle, spraying the core-forming fluid stream from the core nozzle and the coat-forming fluid stream from the concentric nozzle to produce microcapsules, and solidifying the microcapsules upon formation in a suitable gas. Spray drying or spray chilling may be employed as the means of solidifying the microcapsules. Microcapsules having a core and a solid coat are also described.

Abstract: The invention relates to the use of angiogenin, or a fragment or variant thereof, to treat diseases or conditions characterised by neuronal injury or death, or axonal degeneration, especially neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). The invention also describes a plurality of mutations of the human angiogenin gene which are associated with a neurodegenerative disease phenotype, and particularly a ALS phenotype. Also described is a method of assessing whether an individual is afflicted with, or generically predisposed to develop, a disease or condition characterised by neuronal injury or death, or axonal degeneration.

Abstract: A process for producing a collagen/hydroxyapatite (HA) composite scaffold comprises the steps of forming a homogenous suspension of collagen and HA in an acidic solution, lyophilizing the suspension until a desired final freezing temperature is reached to produce the composite scaffold, and optionally cross-linking the composite scaffold, wherein the ratio of HA to collagen is at least 1:10 (w/w). Also provided is a collagen/hydroxyapatite (HA) composite scaffold comprising a homogenous distribution of hydroxyapatite within a porous, crosslinked, collagen matrix, wherein the ratio of HA to collagen is at least 1:10 (w/w). Suitably, the composite scaffold has a porosity of at least 99% (v/v), and a compressive stiffness of at least 0.3 KPa. Composite scaffolds of the invention may be used to provide osteoconductive bone implants and tissue engineering implants.

Abstract: The invention relates to a method for producing a multi-layer collagen scaffold. The method generally comprises the steps of: preparing a first suspension of collagen and freezing or lyophilising the suspension to provide a first layer; optionally preparing a further suspension of collagen and adding the further suspension onto the layer formed in the previous step to form a further layer, and freezing or lyophilising the layers, wherein when the layer formed in the previous step is formed by lyophilisation the lyophilised layer is re-hydrated prior to addition of the next layer; optionally, repeating the aforementioned step to form one or more further layers; and preparing a final suspension of collagen and pouring the final suspension onto the uppermost layer to form a final layer, and freeze-drying the layers to form the multi-layer collagen composite scaffold.

Abstract: The invention relates to a method for producing a multi-layer collagen scaffold. The method generally comprises the steps of: preparing a first suspension of collagen and freezing or lyophilising the suspension to provide a first layer; optionally preparing a further suspension of collagen and adding the further suspension onto the layer formed in the previous step to form a further layer, and freezing or lyophilising the layers, wherein when the layer formed in the previous step is formed by lyophilisation the lyophilised layer is re-hydrated prior to addition of the next layer; optionally, repeating the aforementioned step to form one or more further layers; and preparing a final suspension of collagen and pouring the final suspension onto the uppermost layer to form a final layer, and freeze-drying the layers to form the multi-layer collagen composite scaffold.

Abstract: The invention provides a computer-implemented method and system for predicting quantitatively whether an adjuvant or neoadjuvant chemotherapeutic treatment will be or is being successful in treating an individual suffering from cancer.

Abstract: A method of diagnosing metastatic potential of a breast cancer in an individual with breast cancer is described. The method comprises a step of assaying a breast cancer tumour sample from the patient for expression of ADAM22, wherein expression of ADAM22 correlates with increased potential for metastasis compared with a patient who is ADAM22 negative. The invention also describes an agent for use in the treatment of metastatic breast cancer in a patient, in which the agent is selected from LGI1 protein (SEQ ID NO:1) and an LGI1 peptide mimic capable of mimicking the ADAM22 binding activity of LGI1 by binding to the LGI1 binding domain of ADAM22 (SEQ ID NO: 4) and which is capable of inhibiting migration of endocrine resistant breast cancer cells.

Abstract: Compounds comprising a metal complex having the structure [X—Y—Z-Mn+]p+.B are disclosed in which X is a histone deacetylase inhibitor, Mn+ is a DNA-binding heavy metal ion, Y is an aliphatic or aromatic spacer or is absent, and Z is a mono- or bi-dentate or chelating donor linker, or a bridging linker, P+ designates the charge on the complex ion, which may be positive, negative or absent and B is a counterion or is absent. The linker Z is labile and its metal complex X—Y—Z-Mn+ is capable of being hydrolysed in-vivo. The compounds find application in the treatment of cancer.

Abstract: The invention relates to a method for identification of an individual at increased risk of thrombosis or an atherothrombotic event, or a major bleeding event, comprising a step of assaying a biological sample from the individual for the presence of a SNP in the PPARGC1?, CNTN4, LZTS1 and KCNE4 genes, wherein the presence of a SNP in the PPARGC1?, CNTN4, LZTS1 and KCNE4 genes correlates with the individual being at increased risk of thrombosis or an atherothrombotic event, or a major bleeding event. Typically, the SNP is selected from the SNPs provided in Tables 1 and 2.

Abstract: The invention relates to a method for producing a multi-layer collagen scaffold. The method generally comprises the steps of: preparing a first suspension of collagen and freezing or lyophilising the suspension to provide a first layer; optionally preparing a further suspension of collagen and adding the further suspension onto the layer formed in the previous step to form a further layer, and freezing or lyophilising the layers, wherein when the layer formed in the previous step is formed by lyophilisation the lyophilised layer is re-hydrated prior to addition of the next layer; optionally, repeating the aforementioned step to form one or more further layers; and preparing a final suspension of collagen and pouring the final suspension onto the uppermost layer to form a final layer, and freeze-drying the layers to form the multi-layer collagen composite scaffold.

Abstract: The invention relates to the use of angiogenin, or a fragment or variant thereof, to treat diseases or conditions characterised by neuronal injury or death, or axonal degeneration, especially neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). The invention also describes a plurality of mutations of the human angiogenin gene which are associated with a neurodegenerative disease phenotype, and particularly a ALS phenotype. Also described is a method of assessing whether an individual is afflicted with, or generically predisposed to develop, a disease or condition characterised by neuronal injury or death, or axonal degeneration.

Abstract: The invention relates to a method for producing a multi-layer collagen scaffold. The method generally comprises the steps of: preparing a first suspension of collagen and freezing or lyophilizing the suspension to provide a first layer; optionally preparing a further suspension of collagen and adding the further suspension onto the layer formed in the previous step to form a further layer, and freezing or lyophilizing the layers, wherein when the layer formed in the previous step is formed by lyophilization the lyophilized layer is re-hydrated prior to addition of the next layer; optionally, repeating the aforementioned step to form one or more further layers; and preparing a final suspension of collagen and pouring the final suspension onto the uppermost layer to form a final layer, and freeze-drying the layers to form the multilayer collagen composite scaffold.

Abstract: The invention is based on the finding that the human RPT4 protein/gene can function as a therapeutic target for solid tumour type cancers, especially solid tumours of the colon, and that reducing the abundance of RPT4 in tumour cells causes a significant increase in cancer cell death, and potently decreases the survival and proliferation of cancer cells in tumour growth assays (FIGS. 3 and 4). A further, but linked, aspect of the invention is based on the finding that inhibitors of RPT4 significantly decrease the viability of chemotherapeutic-resistant tumours, especially solid tumours, especially colorectal solid tumours (FIG. 5). A further, but linked, aspect is based on the finding that the efficacy of conventional chemotherapeutic therapy, for example 5-FU/oxaliplatin therapy, is significantly improved when combined with treatment with a RPT4 inhibitor (FIG. 6).

Abstract: Described are methods for assessing recurrence status in a breast cancer patient that include assaying a biological sample from the patient for a level of a biomarker selected from such as S100? or HOX-C1I, where positive detection of one or both of the biomarkers indicates a positive recurrence status. The method can be used for prognosis of poor disease free survival in a breast cancer patient, where positive detection of one or both of the biomarkers indicates poor disease survival. The method may also be used for diagnosis of recurrence, where positive detection of circulating S100? is a diagnostic variable of recurrence. The method of diagnosis is carried out on a patient who is undergoing first line therapy and/or a patient who has had surgery to remove a primary breast tumour.

Abstract: The invention relates to the use of angiogenin, or a fragment or variant thereof, to treat diseases or conditions characterized by neuronal injury or death, or axonal degeneration, especially neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). The invention also describes a plurality of mutations of the human angiogenin gene which are associated with a neurodegenerative disease phenotype, and particularly a ALS phenotype. Also described is a method of assessing whether an individual is afflicted with, or generically predisposed to develop, a disease or condition characterized by neuronal injury or death, or axonal degeneration.