Abstract: A branched monodispersed polyethylene glycol represented by the formula (1): wherein X1 is a functional group that forms a covalent bond upon a reaction with a functional group present in a biofunctional molecule; n is an integer of 4 to 50, which represents number of repeating units of ethylene oxide units; and L1 represents a single bond, —NH—, -L2-(CH2)m1- or -L2-(CH2)m1-L3-(CH2)m2-, L2 represents an ether bond, an amide bond, an urethane bond or a single bond, L3 represents an ether bond, an amide bond or an urethane bond, and m1 and m2 represent each independently an integer of 1 to 5.

Abstract: The disclosure concerns a class of hemoglobin based oxygen carriers (HBOCs) comprising a first hemoglobin protein cross-linked by a chemical reaction that is followed by a strain-promoted alkyne-azide cycloaddition (SPAAC) reaction or by a strain-promoted alkyne-nitrone cycloaddition (SPANC) in the absence of added copper salts to a second modified cross-linked hemoglobin protein. The resulting construct is an HBOC that is capable of binding oxygen and releasing same in a useful manner upon addition in an appropriate solution to the circulatory system of a patient. The disclosure also concerns a method of production of the HBOC where a first and second hemoglobin protein are produced by covalently linking hemoglobin to an angle strained cycloalkyne moiety.

Abstract: We here describe an exercise system and control method thereof to obtain exercise protocols relating to the individual user's optimal exercise intensity. The system and method comprise the monitoring of the transition between the aerobic and anaerobic training zones and an estimate of the maximal lactate steady state, which is an important physiological indicator of the user's cardio respiratory fitness. Together with individual models of how the user's heart rate responds to exercise intensity, it is possible to predict the needed exercise intensity that should be performed to obtain the wanted exercise goal. The analysis can (preferably) be performed in real-time during exercise.

Abstract: The present invention relates generally to methods for preparing polyethylene glycol (“PEG”) conjugated hemoglobin (“Hb”) using reduced reactant ratios. More specifically, the present invention relates to methods for preparing PEG conjugated Hb (“PEG-Hb”) with enhanced yield and purity.

Abstract: Provided herein are compounds, compositions and methods for the treatment of liver disorders, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, provided herein are compounds according to Formula I: or a pharmaceutically acceptable salt, solvate, tautomeric or polymorphic form thereof.

Abstract: The present invention relates to methods for the formation of inter-molecular disulphide bonds, including (poly)peptides/proteins, nucleic acids, vectors, host cells and bacteriophages used in these methods. Furthermore the invention relates to the use of this method for the improved display of (poly)peptides/proteins on the surface of bacteriophage particles.

Abstract: The present invention provides a pharmaceutical composition containing a hemoglobin-based oxygen carrier for treating cancer, preventing recurrence and metastasis of cancerous tumor. The composition can be used alone or in combination with at least one chemotherapeutic agent such as 5FU, Bortezomib, doxorubicin, cisplatin, or any combination thereof. The hemoglobin-based oxygen carrier in the composition is capable of targeting a surface receptor expressed on cancerous cells and facilitating the uptake of both hemoglobin-based oxygen carrier and the chemotherapeutic agent by the cancerous cells via a receptor-mediated mechanism. The hemoglobin-based oxygen carrier inhibits the expression of hypoxic response elements such as HIF1 ?, VEGF, ET1, VHL, etc. The pharmaceutical composition of the present invention is also useful for inducing the apoptosis or cell death of a type of self-renewing and tumor-initiating cells called cancer stem cells which are located in the hypoxic niche of a cancerous tumor.

Abstract: The invention relates to a method of diagnosis of vCJD in a diagnostic sample of a valid body tissue taken from a human subject, which comprises detecting an increased concentration of a protein in the diagnostic sample, compared with a sample of a control human subject, the protein being: beta-actin (SwissProt Acc. No. P60709), apolipoprotein A-IV precursor (SwissProt Acc. No. P06727); haptoglobin beta-chain consisting of residues 162-406 (SwissProt Acc. No. P00738); haemoglobin beta chain (SwissProt Acc. No. P02023); or alpha-1-antitrypsin (SwissProt Acc. No. P01009); or a decreased concentration of a protein in the diagnostic sample, compared with a sample of a control, normal human subject, the protein being plasma protease (C1) inhibitor precursor (SwissProt Acc. No. P05155); complement component 1, s sub-component (SwissProt Acc. No. P09871); butyrylcholinesterase precursor (SwissProt Acc. No. P06276); complement component C4B (SwissProt Acc. No. P01028); lumican (SwissProt Acc. No.

Abstract: The present invention relates to succinimide-activated nitroxyl compounds and methods for the synthesis of such compounds. The present invention also relates to the use of succinimide-activated nitroxyl compounds to prepare nitroxylated proteins, for example nitroxylated heme proteins (e.g., nitroxylated hemoglobin and nitroxylated myoglobin). The nitroxylated proteins are optionally also conjugated to a polyalkylene oxide (PAO), for example to a polyethylene glycol (PEG). Polynitroxylated heme proteins are useful as oxygen therapeutic agents (OTAs). The invention further relates to pharmaceutical compositions of the nitroxylated proteins and methods for the use of nitroxylated proteins in the treatment of various conditions.

Abstract: PEGylated diaspirin-crosslinked hemoglobin conjugates having high oxygen affinity are described which have enhanced nitrite reductase activity to deliver oxygen, carbon monoxide, nitric oxide or mixtures thereof to tissues to treat various diseases and conditions.

Abstract: The present disclosure provides POZ derivatives having a range of active functional groups allowing conjugation of POZ derivatives to a variety of target molecules under a wide range of reaction conditions to produce a hydrolytically stable target molecule-POZ conjugate. Furthermore, the present disclosure provides novel methods of synthesis for the disclosed POZ derivatives and hydrolytically stable target molecule-POZ conjugates created using the disclosed terminally activated monofunctional POZ derivatives. In one embodiment, the POZ derivative is a terminally activated monofunctional POZ derivative.

Abstract: Microspheres are produced by contacting a solution of a macromolecule or small molecule in a solvent with an antisolvent and a counterion, and chilling the solution. The microspheres are useful for preparing pharmaceuticals, nutraceuticals, cosmetic products and the like of defined dimensions.

Abstract: A novel hemoglobin-albumin complex which has high stability of the oxygenated form, has high biocompatibility, and is easily prepared (synthesized), and an artificial plasma expander and an artificial oxygen carrier containing the complex are provided. The hemoglobin-albumin complex of the invention is characterized by having hemoglobin as the core, and albumin as the shell bound via a crosslinker to the above hemoglobin. Also, the artificial oxygen carrier of the invention is characterized by containing the hemoglobin-albumin complex of the invention.

Abstract: The present invention provides a pharmaceutical composition containing hemoglobin-based therapeutic agent for treating cancer. The hemoglobin moiety can target cancer cells and the therapeutic moiety (i.e. active agent/therapeutic drug) can kill the cancer cells efficiently. The hemoglobin-based therapeutic agent used in the present invention can be used in the treatment of various cancers such as pancreatic cancer, leukemia, head and neck cancer, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal cancer, esophageal cancer, prostate cancer, stomach cancer and brain cancer. The composition can be used alone or in combination with other therapeutic agent(s) such as chemotherapeutic agent to give a synergistic effect on cancer treatment, inhibiting metastasis and/or reducing recurrence. The presently claimed hemoglobin-based 5FU-two-dye conjugate and/or hemoglobin-based 5FU-one-dye conjugate can also be used in live-cell imaging and diagnostic imaging.

Abstract: A modified hemoglobin oxygen transport agent useful in the treatment of hypoxia and related conditions is disclosed. The composition consists primarily of carbohydrate shielded hemoglobin or a hybrid hemoglobin molecule to deliver oxygen in hypoxia stage. The carbohydrate shielded hemoglobin therapy is based on oxidation physiology, which is believed to play key roles in ischemia, anemia and other conditions related to hypoxia.

Abstract: The invention provides methods, compositions, and medical kits comprising a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders and preservation of blood products. In one aspect, the invention provides methods, compositions, and medical kits comprising an inorganic nitrite salt and a nitrite-reductase promoter, such as an allosteric modulator of hemoglobin, for use in treating medical disorders, such as cancer, cardiovascular disorders, ischemic conditions, hemolytic conditions, and bacterial infections. Exemplary inorganic nitrite salts include sodium nitrite and arginine nitrite. Exemplary allosteric modulators of hemoglobin described herein include alkyl-substituted and acyl-substituted di-nitroheterocycles.

Abstract: The invention relates to a sterile preparation which can be implanted on or in organic tissues, comprising: a natural or modified globin material which is insoluble at physiological pH and/or a material obtainable from globin which has been modified to be soluble at physiological pH, the said materials being biocompatible and biodegradable in the organism; an agent selected from natural or synthetic polymeric adhesive agents, polymeric tissue enhancement or filling agents, more particularly an agent based on crosslinked hyaluronic acid or on polylactic acid, and a polymeric wound cicatrization agent, specifically oxidized cellulose; with the provisos that, if the preparation comprises the said material obtainable from globin modified so as to be at least partly soluble, the said polymeric adhesive agent, if present, is not hyaluronic acid or carboxymethylcellulose and the said polymeric enhancement or filling agent, if present, is an agent based on crosslinked hyaluronic acid, and that, if the preparation com

Abstract: The present invention provides PEGylated hemoglobins and PEGylated albumins comprising polyethylene glycol (PEG) conjugated to hemoglobin or to albumin, wherein the PEG is a maleimide PEG, an alkylamide PEG, an iodoacetamide PEG, a p-nitro thio-phenyl PEG, a vinyl sulfone PEG, or a mixed disulfide PEG; and PEGylated albumins and PEGylated hemoglobins comprising polyethylene glycol (PEG) attached to a thiolated amino group of albumin or hemoglobin, wherein the amino group is thiolated using dithio sulfo succinimidyl propionate (DTSSP) or dithiosuccinimidyl propionate (DTSP) or dithiobispropionimidate. The invention also provides methods of preparing PEGylated hemoglobins and PEGylated albumins comprising a) reacting hemoglobin or albumin with a thiolating agent and with a PEGylating agent, and b) capping unPEGylated reactive thiols of hemoglobin or albumin with N-ethyl maleimide.

Abstract: While tumor hypoxia is recognized as a key barrier to effective chemo and radiation therapy of solid tumor malignancies, and an important biological mediator of more aggressive tumor phenotype and behavior for over 50 years, prior attempts to improve tumor oxygenation have relied on increasing the total amount of oxygen bound to each molecule of natural hemoglobin (e.g. through hyperbaric oxygen treatments), increasing the ease of release of oxygen from hemoglobin (through the introduction of exogenous allosteric small molecules), or increasing the total amount of oxygen in the body by injecting perfluorocarbon emulsions, or polymerized or pegylated compositions of natural human or bovine hemoglobin. The embodiments provide a novel approach of introducing into the vascular system agents that possess inherently higher-affinities for molecular oxygen that that of natural human hemoglobin, and coupling these agents with inert carriers that shield them from unwanted biological interactions within the body.

Abstract: A nutritional supplement, a method for increasing the bacterial mass in the rumen of a ruminant and a nutritional preparation and corresponding uses. A nutritional supplement including proteins with a degree of hydrolysis above 28% and/or which have more than 23 mg ?-amino nitrogen per gram of protein and/or have more than 10% of free amino acids. The hydrolyzed proteins are animal proteins, preferably hemoglobin. The supplement is supplied orally, included in a nutritional preparation, in liquid, concentrated or dehydrated form.

Abstract: A high temperature-stable and highly purified ?-? cross-linked tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. The dimeric form of hemoglobin is degenerated and purification processes are performed on red blood cells obtained from whole blood. Controlled hypotonic lysis in an instant cytolysis apparatus prevents the lysis of white blood cells. Nucleic acids from white blood cells and the phospholipids impurities are not detected. The blocking of reactive sulfhydryl groups in hemoglobin by a sulfhydryl reagent is performed in an oxygenated environment. Flowthrough column chromatography is used to remove different plasma protein impurities. N-acetyl cysteine is added to the ?-? cross-linked tetrameric hemoglobin solution to maintain a low level of met-hemoglobin. The stabilized hemoglobin is preserved in an infusion bag with aluminum overwrap to prevent formation of inactive met-hemoglobin from oxygen intrusion.

Abstract: According to the present invention there is provided a specific binding member which is specific for and binds directly to the ED-B oncofoetal domain of fibronectin (FN). The invention also provides materials and methods for the production of such binding members.

Abstract: The present invention provides a pharmaceutical composition containing a hemoglobin-based oxygen carrier for treating cancer, preventing recurrence and metastasis of cancerous tumor. The composition can be used alone or in combination with at least one chemotherapeutic agent such as 5FU, Bortezomib, doxorubicin, cisplatin, or any combination thereof. The hemoglobin-based oxygen carrier in the composition is capable of targeting a surface receptor expressed on cancerous cells and facilitating the uptake of both hemoglobin-based oxygen carrier and the chemotherapeutic agent by the cancerous cells via a receptor-mediated mechanism. The hemoglobin-based oxygen carrier inhibits the expression of hypoxic response elements such as HIF1?, VEGF, ET1, VHL, etc. The pharmaceutical composition of the present invention is also useful for inducing the apoptosis or cell death of a type of self-renewing and tumor-initiating cells called cancer stem cells which are located in the hypoxic niche of a cancerous tumor.

Abstract: Provided are hemoglobins having at least two chemical modifications that lower oxygen affinity, hemoglobins chemically modified by the addition of glyceraldehyde-3-phosphate, and hemoglobins having at least two specific chemical modifications. PEGylated versions of these hemoglobins are also provided, as are certain tetraPEGylated and diPEGylated hemoglobins. Methods of modifying a hemoglobin are additionally provided, as are methods of making a hemoglobin. Pharmaceutical compositions and blood substitutes using these hemoglobins are further provided, as are methods of treating a subject using these pharmaceutical compositions and blood substitutes.

Abstract: Microspheres are produced by contacting a solution of a macromolecule or small molecule in a solvent with an antisolvent and a counterion, and chilling the solution. The microspheres are useful for preparing pharmaceuticals, nutraceuticals, cosmetic products and the like of defined dimensions.

Abstract: The present invention relates generally to a method of purifying proteins. More specifically, the present inventions relates to a method of purifying haptoglobin and hemopexin from the same starting material, and uses thereof.

Abstract: The invention is directed to blood proteins produced in monocot seeds and isolated therefrom for use in therapeutic compositions, as well as to methods of making these isolated blood proteins and to therapeutic compositions comprising them.

Abstract: The present invention relates to a marker which can be used to diagnose a diabetic retinopathy patient and determine the progression of diabetic retinopathy, a composition for diagnosing diabetic retinopathy, which comprises an agent for measuring the level of a gene or protein associated with the marker, and the use thereof.

Abstract: The present invention relates to biomarkers for preeclampsia as well as treatment of this disease. In particular, the invention relates to methods for diagnosis or aiding in the diagnosis of preeclampsia of a pregnant female mammal to detect elevated levels of free haemoglobin, particularly free fetal haemoglobin. This facilitates and makes possible early diagnosis and clinical intervention when a preeclamptic condition is found. In addition, the invention relates to a method to treat female mammals with preeclampsia with the purpose to reverse the pathological conditions associated with this disease.

Abstract: The present invention concerns a method of modifying the surface of a cellulosic material, wherein a modifying compound is attached to the cellulosic material through a linker, which linker is a conjugate that has been activated by functionalization prior to adsorption to form an activated conjugate, and wherein the entire method is carried out in aqueous media, as well as an intermediate product suitable for attaching to a modifying compound, the intermediate product comprising said functionalized conjugate linker that has been adsorbed to a cellulosic material.

Abstract: The present invention is a method for preparing stable HBOC solutions. Specifically, the method comprises the steps of deoxygenating a PEG-Hb conjugate and adding one or more antioxidants during or following the deoxygenating step to form a stabilized PEG-Hb conjugate. The Hb in the PEG-Hb conjugate is not crosslinked and the stabilized PEG-Hb conjugate has a p50 less than that of native SFH from the same animal source when measured under the same conditions. Specifically, the p50 is 6±2 mmHg or less than 10 mmHg.

Abstract: The present invention relates to a modified porphyrin-based oxygen-carrying protein, such as haemoglobin, which has been found, in its unmodified state to have a low affinity site of electron transfer and a high affinity electron transfer between a reductant and ferryl haem iron via one or more protein amino acids. The invention provides such proteins that comprise a modification to enhance this pathway.

Abstract: Hemoglobin, its variants, and glycated forms of each are determined individually in a multiplex assay that permits correction of the measured level of HbA1c to account for glycated variants and other factors related to the inclusion of the variants in the sample. New antibodies that are particularly well adapted to the multiplex assay are also provided.

Abstract: The present invention concerns a novel retinoic acid regulated gene whose expression product displays useful morphogenic/mitogenic properties. The present invention further concerns an isolated nucleic acid of SEQ ID NO:1 encoding a retinoic acid regulated expression product having an amino acid sequence of SEQ ID NO:2.

Abstract: The present invention relates to blood products, and more particularly to compositions comprising a modified oxygenated hemoglobin having a high affinity for oxygen and methods for making such compositions. Such compositions according to the present invention have better stability to auto oxidation and superior oxygen carrying characteristics.

Abstract: This disclosure relates to methods of using nitrite to detoxify stroma-free hemoglobin based blood substitutes. In particular, methods are described for using a blood substitute comprised of about equimolar amounts of nitrite and hemoglobin (e.g., nitrite-metHb) to treat, prevent, or ameliorate diseases of the blood in a subject, or as a blood replacement in a subject.

Abstract: An antibody that binds to Mucin17 (Muc17) is disclosed. The antibody of the present invention preferably binds to the peptide of SEQ ID NO:3 and does not bind to the peptide of SEQ ID NO:4 or the peptide of SEQ ID NO:5. Also disclosed are an anti-cancer agent, preferably an anti-cancer agent for pancreatic cancer, which comprises the antibody of the present invention, as well as a method of diagnosing cancer using the antibody of the present invention, preferably the antibody of the present invention that does not bind to the secreted-form of Muc17.

Abstract: Site-specific modifications of proteins at their N-termini are provided. In particular, a chemical modification of proteins at their N-termini via a transamination reaction to form homogeneous adducts such as, the corresponding oxime derivatives is provided. Methods of making and using the adducts in radio-labelling, molecular imaging applications, and treatment of disorders such as cancer, Crohn's disease, arthritis, atherothrombosis and plaque rupture are also provided.

Abstract: The present invention relates generally to methods for preparing polyethylene glycol (“PEG”) conjugated hemoglobin (“Hb”) using reduced reactant ratios. More specifically, the present invention relates to methods for preparing PEG conjugated Hb (“PEG-Hb”) with enhanced yield and purity.

Abstract: While tumor hypoxia is recognized as a key barrier to effective chemo and radiation therapy of solid tumor malignancies, and an important biological mediator of more aggressive tumor phenotype and behavior for over 50 years, prior attempts to improve tumor oxygenation have relied on increasing the total amount of oxygen bound to each molecule of natural hemoglobin (e.g. through hyperbaric oxygen treatments), increasing the ease of release of oxygen from hemoglobin (through the introduction of exogenous allosteric small molecules), or increasing the total amount of oxygen in the body by injecting perfluorocarbon emulsions, or polymerized or pegylated compositions of natural human or bovine hemoglobin. The embodiments provide a novel approach of introducing into the vascular system agents that possess inherently higher-affinities for molecular oxygen that that of natural human hemoglobin, and coupling these agents with inert carriers that shield them from unwanted biological interactions within the body.

Abstract: The disclosure relates to metal organic frameworks or isoreticular metal organic frameworks, methods of production thereof, and methods of use thereof.

Abstract: A method for changing conformation of globular proteins is provided. The method controls the concentration of the globular proteins and the adsorption time of the globular proteins from the aqueous solution to the air/liquid interface, so that the main conformation of the globular proteins in a protein monolayer can be changed into ?-sheet or ?-helix. Meanwhile, the protein monolayer having the conformation of ?-sheet or ?-helix can be vertically deposited and transferred onto a substrate for various applications according to needs. The present invention can change three-dimensional structures of biological molecules and remain original functions thereof without additionally using any physical/chemical treatment to change the conformation of the globular proteins.

Abstract: A promoter for transformation of a plant, in particular an aboveground organ specific promoter, a recombinant plant expression vector including the promoter, a method of producing target protein using the recombinant plant expression vector, target protein produced by the method, a method of producing a transformed plant using the recombinant plant expression vector, a transformed plant produced by the same, and a seed of the plant.

Abstract: The present invention relates to a kit and a probe for detecting porous dental hydroxyapatite, comprising a protein capable of binding porous dental hydroxyapatite or a detector thereof. The invention also relates to a method for detecting a condition involving porous dental hydroxyapatite comprising detecting in or on a tooth or a sample of the tooth of a subject a protein bound to porous dental hydroxyapatite. The invention also relates to methods for detecting a hypomineralisation developmental dental defect or detecting intact and/or broken MIH enamel, and to a kit and method for removing a protein bound to porous dental hydroxyapatite.

Abstract: The invention relates to methods and uses of modulating fetal hemoglobin expression (HbF) in a hematopoietic progenitor cells via inhibitors of BCL11A expression or activity, such as RNAi and antibodies.

Abstract: The present invention relates generally to methods for preparing polyethylene glycol maleimide (“PEG-Mal”). More specifically, the present invention relates to methods for synthesizing desired molecular weight PEG-Mal by direct ethoxylation of N-(2-hydroxyethyl)maleimide under specific reaction conditions.

Abstract: The present disclosure relates to a multifunctional biomemory device in which a protein having a redox potential substituted with a metal ion is directly immobilized on a substrate. The present disclosure provides an operating method in which the redox state of the protein is controlled by applying three different potentials. The present disclosure provides a biomemory device in which the metal ion of a metalloprotein is substituted to allow for artificial control of the redox potential. The present disclosure provides a new-concept biomemory device as an information storage device based on the principle of electron transfer of a naturally occurring biomolecule.

Abstract: Provided is a monoclonal antibody, or an antigen binding fragment thereof, which binds specifically to an epitope within the sequence KPGAKKDTKDSRPKL (Sequence ID No. 2) of AGR2. Such monoclonal antibodies are of prognostic and diagnostic utility in the investigation of cancer, particularly metastatic cancer. The antibodies described may also be used in prognosis or diagnosis of inflammatory diseases. Also provided are kits and solid supports comprising such antibodies, as well as the therapeutic use of antibodies of the invention.

Abstract: A polyion Complex (PIC) polymeric micelle is formed by interaction between a bioactive protein and a dendritic block copolymer of opposite charge. The conventional low stability of PIC micelles with bioactive proteins vis-à-vis ionic strength is offset by the stability provided by the dendritic block. The overall process for preparing the micelles is facilitated by the simplicity of the drendritic block copolymer synthesis.

Abstract: The present invention describes neuroprotective and multifunctional intra- and inter-molecular redox coupled polynitroxylated pegylated carboxy hemoglobins as high therapeutic index agents for un-met medical needs or diseases, which require acute or chronic alleviation of oxidative stress and correction of inadequate blood flow resulting from physical injury, ischemia, reperfusion injury, and inflammation injury in either or both pre-hospital and in-hospital transfusion and critical care medicine. These hemoglobins are triple-modified with a focus on therapeutic activities rather than oxygen carrying ability.