Baltimore, MD, United States
Baltimore, MD, United States

The Johns Hopkins University is a private research university in Baltimore, Maryland. Founded in 1876, the university was named after its first benefactor, the American entrepreneur, abolitionist, and philanthropist Johns Hopkins. His $7 million bequest—of which half financed the establishment of The Johns Hopkins Hospital—was the largest philanthropic gift in the history of the United States at the time. Daniel Coit Gilman, who was inaugurated as the institution's first president on February 22, 1876, led the university to revolutionize higher education in the U.S. by integrating teaching and research.The first research university in the Western Hemisphere and one of the founding members of the American Association of Universities, Johns Hopkins has ranked among the world’s top universities throughout its history. The National Science Foundation has ranked the university #1 among U.S. academic institutions in total science, medical, and engineering research and development spending for 31 consecutive years. Johns Hopkins is also ranked #12 in the U.S. News and World Report undergraduate program rankings for 2014 and was also ranked 11th in the U.S. News and World Report Best Global University Rankings of 2014, outranking Princeton University, Yale University, University of Pennsylvania, and Cornell University.Over the course of almost 140 years, 36 Nobel Prize winners have been affiliated with Johns Hopkins . Founded in 1883, the Blue Jays men’s lacrosse team has captured 44 national titles and joined the Big Ten Conference as an affiliate member in 2014.Johns Hopkins is organized into ten divisions on campuses in Maryland and Washington, D.C. with international centers in Italy, China, and Singapore. The two undergraduate divisions, the Krieger School of Arts and science and the Whiting School of Engineering, are located on the Homewood campus in Baltimore's Charles Village neighborhood. The medical school, the nursing school, and the Bloomberg School of Public Health are located on the Medical Institutions campus in East Baltimore. The university also consists of the Peabody Institute, the Applied Physics Laboratory, the Paul H. Nitze School of Advanced International Studies, the education school, the Carey Business School, and various other facilities. Wikipedia.

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Johns Hopkins University | Date: 2016-08-15

A surgical system provides hands-free control of at least one surgical tool includes a robot having a tool connector, a smart tool attached to the tool connector of the robot, and a feedback control system configured to communicate with the smart tool to provide feedback control of the robot. The smart tool includes a tool that has a tool shaft having a distal end and a proximal end, a strain sensor arranged at a first position along the tool shaft, at least one of a second strain sensor or a torque-force sensor arranged at a second position along the tool shaft, the second position being more towards the proximal end of the tool shaft than the first position, and a signal processor configured to communicate with the strain sensor and the at least one of the second strain sensor or the torque-force sensor to receive detection signals therefrom. The signal processor is configured to process the detection signals to determine a magnitude and position of a lateral component of a force applied to the tool shaft when the position of the applied force is between the first and second positions. The feedback system controls the robot to move in response to at least the magnitude and position of the lateral component of the force applied to the tool shaft when the position of the applied force is between the first and second positions so as to cancel the force applied to the tool shaft to thereby provide hands-free control of the at least one surgical tool.

Johns Hopkins University | Date: 2016-08-19

The present invention provides a low-risk, unobtrusive and noninvasive method and device for treatment of obesity and eating disorders. In embodiments, the device is a gastric device suitable for placement in a stomach of a subject. The device may be composed of a sponge material which absorbs fluid upon implantation and expands in volume, thereby functioning as a space occupying device in the stomach to cause early satiety.

The present invention is directed to an innovative pedicle probe that uses a force-sensing electromechanical system coupled with haptic and visual feedback. The probe of the present invention reduces the rate of pedicle screw breaches during spinal fusion surgery. The probe provides an effective guidance system to aid surgeons in detecting and preventing cortical bone breaches, thereby minimizing risk of intraoperative injury to the patient. Moreover, the probe invention decreases surgeon reliance on intraoperative radiation, reducing harmful exposure to both patients and surgeons.

The present invention provides a method of administering a therapeutic agent directly to the brain parenchym through a compromised region of the blood-brain barrier in a subject having a brain disorder, that involves first disrupting the blood-brain barrier (BBB) at an isolated region by locally administering an effective amount of a hyperosmolar agent at said region using a catheter, followed by administering a therapeutically effective amount of a therapeutic agent. The step of disrupting the BBB is carried out with non-invasive MR (magnetic resonance) imaging with a contrast agent to visualize local parenchymal transcatheter perfusion at said isolated BBB region thereby indicating that the BBB region is compromised. The method of the invention allows for highly precise drug delivery to the brain through blood brain barrier disruption at specifically controlled regions.

Johns Hopkins University | Date: 2015-02-12

The present invention is directed to a computer application for monitoring and tracking leg and foot movements and positions and a device for facilitating the computer tracking of the leg and foot movements. The application uses an accelerometer, gyroscope or other movement detectors in available devices such as a phone, movement tracker, personal music device, tablet computing device, other similar device or a device specifically designed to detect movements and positions and to track the movement and changes in position of the patients leg and foot. The device can be held onto the patients leg using a band type device that is easy to use and comfortable during sleep or by incorporation into a comfortable wearable band. The application includes a user interface and a backend for use by physicians or other healthcare staff to review and diagnose the patients leg and foot movement patterns.

A method, computer-readable medium and system of planning, guiding and/or monitoring a therapeutic procedure, can include: receiving a non-labeled therapeutic agent by a subject, said non-labeled therapeutic agent comprises at least one type of water-exchangeable proton that is exchangeable with protons in surrounding water molecules so as to enhance detection by a chemical exchange saturation transfer (CEST) process; acquiring a plurality of CEST magnetic resonance images of said non-labeled therapeutic agent within a region of interest of said subject for a corresponding plurality of times; and assessing at least one of a therapeutic plan or therapeutic effect of said non-labeled therapeutic agent in tissue of said subject based on said plurality of magnetic resonance images

Johns Hopkins University | Date: 2016-07-27

The presently disclosed subject matter provides methods for continuously generating uniform polyelectrolyte complex (PEC) nanoparticles comprising: flowing a first stream comprising one or more water-soluble polycationic polymers at a first variable flow rate into a confined chamber; flowing a second stream comprising one or more water-soluble polyanionic polymers at a second variable flow rate into the confined chamber; and impinging the first stream and the second stream in the confined chamber until the Reynolds number is from about 1,000 to about 20,000, thereby causing the one or more water-soluble polycationic polymers and the one or more water-soluble polyanionic polymers to undergo a polyelectrolyte complexation process that continuously generates PEC nanoparticles. Compositions produced from the presently disclosed methods and a device for producing the compositions are also disclosed.

University of Illinois at Urbana - Champaign, Vanquish Oncology and Johns Hopkins University | Date: 2016-08-22

The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds.

Johns Hopkins University and Showa Pharmaceutical University | Date: 2016-12-12

In DN-DISC1 mice, a mouse model for major mental illnesses, the model that expresses pathological phenotypes relevant to schizophrenia, mood disorders, and addiction simultaneously, the inventors of the present invention found pronounced levels of oxidative stress in the prefrontal cortex, but not in the striatum. These mice also displayed greater amounts of GAPDH-Siah1 binding, a protein-protein interaction that is activated under exposure to oxidative stress. The present inventors investigated the role of oxidative stress in other organ systems. As detailed herein, the inventors found that GAPDH-Siah1 binding was increased in mouse models of cardiac failure. It was also found, that certain novel analogs of deprenyl, significantly inhibited GAPDH-Siah1 binding in cardiac tissue. Thus, with experimental data provided herein, it is clear that this GAPDH-Siah1 binding cascade is a crucial mechanism involved in major mental illness, such as schizophrenia, mood disorders, and addiction, as well as in stress-associated diseases involving other organs where GAPDH is expressed. The present invention provides compounds and composition comprising analogs of deprenyl and their use in the inhibition of nuclear GAPDH-Siah1 binding and the activation of p300 and MEF2. Also provided herein are methods of prevention and treatment of stress induced disorders of the body, including, for example, major mental illness, such as schizophrenia, mood disorders, and addiction, as well as in stress-associated diseases involving other organs, such as cardiac hypertrophy, in vivo, comprising administering to a mammal a therapeutically effective amount of analogs of deprenyl.

Johns Hopkins University | Date: 2016-09-16

The Vertebral Osteotomy Saw Guide allows precise osteotomies to be performed through the vertebral column in conjunction with a thread-wire saw. The guide is designed so that it can mount to rods commonly used during spinal surgery for spinal stabilization. The mount of the guide is a polyaxial mount, allowing the angle of the guide mount to be adjusted and locked to create a desired cutting plane to produce a precise osteotomy. The guide itself consists of two interdigitated pulley wheels that allow the thread-wire saw to pass smoothly through the guide. The simple, but unique design of the guide allows a surgeon to perform an osteotomy through the vertebral column cutting from one side of the vertebral column to the other. This unique orientation allows the osteotomy to be performed away from critical structures in the region (the spinal cord, aorta, and inferior vena cava).

The present invention is directed to a method for combining assessment of different factors of dyssynchrony into a comprehensive, non-invasive toolbox for treating patients with a CRT therapy device. The toolbox provides high spatial resolution, enabling assessment of regional function, as well as enabling derivation of global metrics to improve patient response and selection for CRT therapy. The method allows for quantitative assessment and estimation of mechanical contraction patterns, tissue viability, and venous anatomy from CT scans combined with electrical activation patterns from Body Surface Potential Mapping (BSPM). This multi-modal method is therefore capable of integrating electrical, mechanical, and structural information about cardiac structure and function in order to guide lead placement of CRT therapy devices. The method generates regional electro-mechanical properties overlaid with cardiac venous distribution and scar tissue. The fusion algorithm for combining all of the data suggests cardiac segments and routes for implantation of epicardial pacing leads.

The present invention is directed to a method for real-time characterization of spatially-resolved tissue optical properties using OCT/LCI. Imaging data are acquired, processed, displayed and stored in real-time. The resultant tissue optical properties are then used to determine the diagnostic threshold and to determine the OCT/LCI detection sensitivity and specificity. Color-coded optical property maps are constructed to provide direct visual cues for surgeons to differentiate tumor versus non-tumor tissue. These optical property maps can be overlaid with the structural imaging data and/or Doppler results for efficient data display. Finally, the imaging system can also be integrated with existing systems such as tracking and surgical microscopes. An aiming beam is generally provided for interventional guidance. For intraoperative use, a cap/spacer may also be provided to maintain the working distance of the probe, and also to provide biopsy capabilities. The method is usable for research and clinical diagnosis and/or interventional guidance.

Johns Hopkins University | Date: 2016-10-27

Synthetic representative HCV subtypes, including a 1a and 1b genome, dubbed Bole1a and Bole1b, are provided using an inventive method of Bayesian phylogenetic tree analysis, ancestral sequence reconstruction and covariance analysis. Bole1a branches centrally among 390 full-genome sequences used in its design, a carefully curated 143 sequence full-genome dataset, and separate genomic regions including an independent set of 214 E1E2 sequences from a Baltimore cohort. Bole1a is phylogenetically representative of widely circulating strains. Full genome non-synonymous diversity comparison and 9-mer peptide coverage analysis showed that Bole1a is able to provide more coverage (94% and 78% respectively) than any other sequence in the dataset including H77, a traditional reference sequence. Bole1a also provides unsurpassed epitope coverage when compared to all known T cell epitopes.

The present inventors employed cyclodextrins for use as a proteoglycan substitute to engineer a biomimetic collagen-based matrix composition. The resulting incorporation of cyclodextrin in the inventive collagen compositions increased collagen thermal stability and reduced collagen fibrogenesis. As a result, a thick, transparent and mechanically strong collagen-based composition was formed. This cyclodextrin-collagen composition holds a great potential to be used as a therapeutic eye patch for corneal repair. Methods for making these inventive compositions and their use are also provided.

Johns Hopkins University | Date: 2016-09-23

We found that FIZZ1/RELM is inducible by hypoxia in lung. The hypoxia-upregulated expression of FIZZ1/RELM was located in the pulmonary vasculature, bronchial epithelial cells, and type II pneumocytes. Recombinant FIZZ1/RELM protein stimulates rat pulmonary microvascular smooth muscle cell (RPSM) proliferation dose-dependently. Therefore, we renamed this gene as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 inhibits HIMF-activated Akt phosphorylation. It also inhibits HIMF-stimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. HIMF also has angiogenic and vasoconstrictive activity. Notably, HIMF increases pulmonary arterial pressure and vascular resistance more potently than either endothelin-1 or angiotensin II.

Johns Hopkins University | Date: 2016-11-17

The invention provides chimeric proteins and nucleic acids encoding these which can be used to generate vaccines against selected antigens. In one aspect, a chimeric protein comprises an antigen sequence and a domain for trafficking the protein to an endosomal compartment, irrespective of whether the antigen is derived from a membrane or non-membrane protein. In one preferred aspect, the trafficking domain comprises a lumenal domain of a LAMP polypeptide. Alternatively, or additionally, the chimeric protein comprises a trafficking domain of an endocytic receptor (e.g., such as DEC-205 or gp200-MR6). The vaccines (DNA, RNA or protein) can be used to modulate or enhance an immune response against any kind of antigen. In one preferred aspect, the invention provides a method for treating a patient with cancer by providing a chimeric protein comprising a cancer-specific antigen or a nucleic acid encoding the protein to the patient.

The present invention provides novel methods for treating Th2-mediated immune disorders and enhancing Th1-mediated immune responses in a subject comprising administering to the subject, a pharmaceutical composition comprising a serum-glucocorticoid regulated kinase 1 (SGK1) inhibitor and a pharmaceutically acceptable carrier. Methods for treating a wide range of autoimmune diseases are also taught. The present invention also provides methods for augmenting the treatment of subjects having viral or parasitic infections, or which have cancerous tumors.

The present invention provides pharmaceutical compositions for treating neuromyelitis optica (NMO) comprising a therapeutically effective amount of loop C sequence-containing peptide of aquaporin-4 (AQP4) water channel, or a therapeutically effective fragment or variant thereof. The invention also provides methods for treating NMO by administering therapeutically effective amounts of loop C sequence-containing peptide(s) of AQP4, optionally in an immunosuppressive setting, and also provides diagnostics for detection of NMO in a subject, screening methods for identification of NMO-treating therapeutics and NMO model systems.

Johns Hopkins University | Date: 2016-10-25

Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.

A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Colloidally stable non-viral gene vector delivery systems capable of overcoming various biological barriers, are disclosed. The gene vectors are biodegradable, non-toxic and highly tailorable for use in specific applications. The vectors include a mixture of biodegradable copolymers, such as PBAE, and biodegradable polymers conjugated with hydrophilic, neutrally charged polymer, such as PEG. The gene vectors demonstrate broad vector distribution and high transgene delivery in vivo, providing an efficient non-viral gene delivery system for localized therapeutic gene transfer. Methods of using the vectors to overcome biological barriers including mucus gel and extracellular matrix are provided. Methods of formulating the vectors are also provided.

Johns Hopkins University and University of Illinois at Chicago | Date: 2015-04-22

The present invention provides novel indoleamide compounds for treating tuberculosis, including drug-resistant M-tuberculosis, compositions comprising the indoleamides and methods of using the indoleamides in conjunction with other biologically active agents for the treatment of tuberculosis in a subject in need thereof.

The present invention provides compounds or a pharmaceutically acceptable salts, solvates, stereoisomers, or prodrugs thereof which can block the Atg8-Atg3 protein-protein interaction, which is associated with autophagy in apicomplexan organisms. Pharmaceutical compositions comprising these compounds and their use for the suppression and treatment of various parasitical diseases are also provided.

Johns Hopkins University and Intonation Research Laboratories | Date: 2015-03-09

A series of phenelzine analogs comprising a phenelzine scaffold linked to an aromatic moiety and their use as inhibitors of lysine-specific demethylase 1 (LSD1) and/or one or more histone deacetylases (HDACs) is provided. The presently disclosed phenelzine analogs exhibit potency and selectivity for LSD1 versus MAO and LSD2 enzymes and exhibit bulk, as well as, gene specific histone methylation changes, anti-proliferative activity in several cancer cell lines, and neuroprotection in response to oxidative stress. Accordingly, the presently disclosed phenelzine analogs can be used to treat diseases, conditions, or disorders related to LSD1 and/or HDACs, including, but not limited to, cancers and neurodegenerative diseases.

The present invention provides compounds of formula I which are capable of inhibition of the activation of hNav1.1 or hNav1.6 sodium channels in neurons. Pharmaceutical compositions comprising these compounds are also provided. Methods for prevention and treatment of neurological disorders, including, for example, seizures and seizure disorders, including Lennox-Gastaut Syndrome, Dravet syndrome, epileptic encephalopathies, autism, Familial hemiplegic migraine (FHM), anxiety disorders, including Post-traumatic stress disorder (PTSD), panic disorder and obsessive-compulsive disorder, neuropathic pain, and Rett syndrome by administration of these compounds are also provided.

Johns Hopkins University | Date: 2015-02-17

In one aspect, the present invention is directed to a multi-lumen catheter with self-sealing hub and an attachable extension assembly. In a preferred aspect, the present invention can allows removal of the external fluid connections of an elongated percutaneous medical article, such as a catheter or cannula. The percutaneous medical article suitably contains a distal septum that prevents fluid movement within the intraluminal space of the percutaneous medical article, when the fluid connections are removed. A single-use, disposable extension set of one or more single lumen lines with associated clamp and cap is attached for intraluminal access and removed following clinical use. Retaining the catheter transition allows the catheter to be secured using methods common to the art.

Johns Hopkins University | Date: 2015-02-17

The present invention describes a securement device that maintains proper placement of a percutaneous catheter and incorporates a universal fitting for the attachment of various, interchangeable, active and passive technologies. The securement device includes a unique catheter hub that enables attachment of active technology to provide diagnostic, therapeutic, and monitoring applications of physiologic, anatomic, and other clinically relevant properties or conditions. The securement device also includes a primary semi-flexible polymeric retention member (the base) positioned atop, or integrated with, a thin flexible adhesive pad. The adhesive pad has a first surface with an adhesive substrate and a second surface configured to receive the base. The hub is received within the base and a cap is used to secure the hub to the base.

Johns Hopkins University | Date: 2016-08-18

The identification of mutations that are present in a small fraction of DNA templates is essential for progress in several areas of biomedical research. Though massively parallel sequencing instruments are in principle well-suited to this task, the error rates in such instruments are generally too high to allow confident identification of rare variants. We here describe an approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose. One example of this approach, called Safe-SeqS for (Safe-Sequencing System) includes (i) assignment of a unique identifier (UID) to each template molecule; (ii) amplification of each uniquely tagged template molecule to create UID-families; and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are truly mutant (super-mutants) if 95% of them contain the identical mutation. We illustrate the utility of this approach for determining the fidelity of a polymerase, the accuracy of oligonucleotides synthesized in vitro, and the prevalence of mutations in the nuclear and mitochondrial genomes of normal cells.

Johns Hopkins University and Duke University | Date: 2016-11-16

We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.

Johns Hopkins University | Date: 2015-02-19

A system for controlling gene expression in yeast comprises a repressible gene expression plasmid that has a regulator binding sequence for camR and a target gene sequence. The system also includes a transcription enhancer expression plasmid; wherein said transcriptional activator protein binds to the regulator binding sequence in the absence of a transcriptional inhibitor. The system is used in a method for controlling expression of the target gene through the use of camphor. The target gene is expressed in the absence of camphor but unexpressed if camphor is added to a solution of cells containing the plasmids.

Johns Hopkins University | Date: 2015-05-06

A device and methods of use thereof for isolating one or more microorganisms from a biological sample, the device comprising a polymeric surface having one or more cationic polymers covalently grafted thereto, wherein the one or more cationic polymers have a selective affinity for the one or more microorganisms.

Johns Hopkins University and Lieber Institute For Brain Development | Date: 2015-03-20

RNA polymerase I (Pol I) is a dedicated polymerase for the transcription of the 47S ribosomal RNA precursor subsequently processed into the mature 5.8S, 18S and 28S ribosomal RNAs and assembled into ribosomes in the nucleolus. Pol I activity is commonly deregulated in human cancers. Based on the discovery of lead molecule BMH-21, a series of pyridoquinazolinecarboxamides were synthesized as inhibitors of Pol I and activators of the destruction of RPA194, the Pol I large catalytic subunit protein. The present invention identifies a set of bioactive compounds, including purified stereoisomers, that potently cause RPA194 degradation that function in a tightly constrained chemical space. Pharmaceutical compositions comprising these compounds and their uses in cancer and other Pol I related diseases is also provided.

Rational design of immunotherapeutics relies on clear knowledge of the immunodominant epitopes of antigens. Current methods for identifying kinetically stable peptide-MHC complexes are in many cases inadequate for a number of reasons. Disclosed herein is a reductionistic system incorporating known participants of MHC class II antigen processing in solution to generate peptide pools from antigens, including those for which no immunodominant epitope has yet been identified, that are highly enriched for proteolytic fragments containing their immunodominant epitopes. HLA-DM-mediated editing contributes significantly to immunodominance and is exploited in discovering immunodominant epitopes from novel or previously uncharacterized antigens, particularly antigens associated with pathogens, tumors or autoimmune diseases.

Johns Hopkins University | Date: 2015-04-30

The present invention provides compositions comprising PAMAM dendrimers conjugated with one or more biologically active agents, and their use systemically to target activated microglia/macrophages in retina/choroid and generally, inflammatory and/or angiogenic diseases of the eye.

Johns Hopkins University | Date: 2016-10-11

Implantable pressure-actuated systems to deliver a drug and/or other substance in response to a pressure difference between a system cavity and an exterior environment, and methods of fabrication and use. A pressure-rupturable membrane diaphragm may be tuned to rupture at a desired rupture threshold, rupture site, with a desired rupture pattern, and/or within a desired rupture time. Tuning may include material selection, thickness control, surface patterning, substrate support patterning. The cavity may be pressurized above or evacuated below the rupture threshold, and a diaphragm-protective layer may be provided to prevent premature rupture in an ambient environment and to dissipate within an implant environment. A drug delivery system may be implemented within a stent to release a substance upon a decrease in blood pressure. The cavity may include a thrombolytic drug to or other substance to treat a blood clot.

Johns Hopkins University | Date: 2015-05-12

A synthetic gene delivery platform with a dense surface coating of hydrophilic and neutrally charged PEG, capable of rapid diffusion and widespread distribution in brain tissue, and highly effective gene delivery to target cells therein has been developed. Nanoparticles including nucleic acids, are formed of a blend of biocompatible hydrophilic cationic polymers and they hydrophilic cationic polymer conjugated to hydrophilic neutrally charged polymers such as polyethylene glycol. The nanoparticles are coated with polyethylene glycol at a density that imparts a near neutral charge and optimizes rapid diffusion through the brain parenchyma. Methods of treating a disease or disorder of the brain including administering a therapeutically effective amount of nano particles densely coated with polyethylene glycol are also provided.

Johns Hopkins University | Date: 2016-12-12

Ophthalmic suture materials made from biocompatible and biodegradable polymers with high tensile strength for use in drug delivery, methods of making them, and method of using them for ocular surgery and repair have been developed. The suture materials are made from a combination of a biodegradable, biocompatible polymer and a hydrophilic biocompatible polymer. In a preferred embodiment the suture materials are made from a poly(hydroxyl acid) such as poly(1-lactic acid) and a polyalkylene oxide such as poly(ethylene glycol) or a polyalkylene oxide block copolymer. The sutures entrap (e.g., encapsulate) one or more therapeutic, prophylactic or diagnostic agents and provide prolonged release over a period of at least a week, preferably a month.

The present invention provides bivalent and multivalent ligands with a view to improving the affinity and pharmacokinetic properties of a urea class of PSMA inhibitors. The compounds and their synthesis can be generalized to multivalent compounds of other target antigens. Because they present multiple copies of the pharmacophore, multivalent ligands can bind to receptors with high avidity and affinity, thereby serving as powerful inhibitors. The modular multivalent scaffolds of the present invention, in one or more embodiments, contains a lysine-based (, -) dialkyne residue for incorporating two or more antigen binding moieties, such as PSMA binding Lys-Glu urea moieties, exploiting click chemistry and one or more additional lysine residues for subsequent modification with an imaging and/or therapeutic nuclides or a cytotoxic ligands for tumor cell killing.

Johns Hopkins University | Date: 2015-02-19

The present invention relates to the field of wound healing. Specifically, the present invention provides compositions and methods for promoting skin regeneration, more specifically, the generation of de novo hair follicles. In one embodiment, a method for stimulating hair follicle neogenesis in a subject comprises the step of administering to the subject an effective amount of a TLR3 agonist. In certain embodiments, the TLR3 agonist is a double stranded RNA (dsRNA). The present invention is also directed to treating common male pattern hair loss.

The disclosed subject matter provides certain N-substituted hydroxylamine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the disclosed subject matter provides methods of using such compounds or pharmaceutical compositions for treating, preventing, or delaying the onset and/or development of a disease or condition. In some embodiments, the disease or condition is selected from cardiovascular diseases, ischemia, reperfusion injury, cancerous disease, pulmonary hypertension and conditions responsive to nitroxyl therapy.

Johns Hopkins University and Northwestern University | Date: 2015-05-06

Low-molecular weight gadolinium (Gd)-based MR contrast agents for PSMA-specific Ti-weighted MR imaging are disclosed. The (Gd)-based MR contrast agents exhibit high binding affinity for PSMA and exhibit specific Ti contrast enhancement at PSMA+ cells. The PSMA-targeted Gd-based MR contrast agents can be used for PSMA-targeted imaging in vivo. 86Y-labeled PSMA-binding ureas also are provided, wherein the PSMA-binding ureas also are suitable for use with other radiotherapeutics.

Johns Hopkins University | Date: 2016-04-07

The present invention provides a system and method for increasing construction site safety. The present invention reduces the risk of a construction or similar large vehicle or piece of mobile machinery hitting a construction worker. The system uses low-power wireless beacons embedded in a construction workers hardhat or otherwise on the construction workers person. The low-power wireless beacon interacts with sensor modules around the construction site, on construction vehicles, on construction equipment, or any other suitable placement known to or conceivable by one of skill in the art. The sensor modules send alert signals to a display accessible to a driver of the vehicle, and/or a foreman on the construction site. While the present invention is discussed herein in the context of construction safety, it should be noted that such a system can be applied to any situation where tracking and alert generation would be beneficial.

Johns Hopkins University | Date: 2016-08-30

An attachment device includes a robot-engaging portion having a recess formed in an outer surface thereof for receiving a finger of a robot. The attachment device also includes a tool-engaging portion coupled to the robot-engaging portion. The tool-engaging portion is configured to be coupled to a tool that is to be used by the robot to perform a task. A damping member is positioned at least partially between the robot-engaging portion and the tool-engaging portion. The damping member is configured to be adjusted to vary a magnitude of oscillations that are transferred from the tool-engaging portion to the robot-engaging portion.

Stichting Katholieke University and Johns Hopkins University | Date: 2016-11-30

The present invention relates, in general, to a prostate-specific antigen, PCA3. In particular, the present invention relates to nucleic acid molecules coding for the PCA3 protein; purified PCA3 proteins and polypeptides; recombinant nucleic acid molecules; cells containing the recombinant nucleic acid molecules; antibodies having binding affinity specifically to PCA3 proteins and polypeptides; hybridomas containing the antibodies; nucleic acid probes for the detection of nucleic acids encoding PCA3 proteins; a method of detecting nucleic acids encoding PCA3 proteins or polypeptides in a sample; kits containing nucleic acid probes or antibodies; bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess, or prognose a mammal afflicted with prostate cancer; therapeutic uses; and methods of preventing prostate cancer in an animal.

Johns Hopkins University | Date: 2016-09-29

The present invention relates to the field of biomarkers. More specifically, the present invention relates to assay reagents useful in detecting neurogranin. In a specific embodiment, the present invention provides an isolated antibody or fragment thereof that specifically binds to neurogranin. In another embodiment, the present invention provides a polynucleotide aptamer that specifically binds neurogranin.

Johns Hopkins University | Date: 2015-03-11

The present invention provides an in vitro directed evolution selection system to create modified methyltransferases which improve methyltransferase specificity and use it to optimize and provide fusion proteins comprising a zinc finger methyltransferase derived from M.SssI. The resulting fusion proteins show increased target methylation specificity and greatly decreased non-target methylation compared to wild-type enzyme activity. Methods of use of such fusion proteins in both prokaryotic and eukaryotic cells are also provided.

A method for determining past exposure to chemical agents or heavy metals may include coating a capture material with a capture reagent. The capture reagent may be selected based on an ability of the capture reagent to bind with a target antibody, and the target antibody may be an indicator associated with a particular chemical agent or heavy metal. The method may further include interrogating a clinical sample associated with an individual by forming a mixture of the capture material and the clinical sample, and determining an exposure status of the individual to the particular chemical agent or heavy metal based on whether the capture material demonstrates capture of the indicator.

A method of assessing tissue vascular permeability for nanotherapeutics using non-labeled dextran can include: receiving a non-labeled, physiologically-tolerable dextran solution by a subject; acquiring a plurality of magnetic resonance images of a distribution of the dextran solution within at least one region of interest of the subject for a corresponding plurality of times; and assessing a tissue vascular permeability of the at least one region of interest to dextran particles in the dextran solution based on differences between the plurality of magnetic resonance images, wherein the dextran solution is a substantially mono-disperse solution of dextran particles of one size.

The present invention is in the area of pluripotent stem cells and more particularly deals with a method to differentiate a vascular network from stem cells.

Johns Hopkins University | Date: 2016-09-07

A detection system may include processing circuitry configured to receive synthetic aperture radar image data that has been or will be divided into a plurality of image tiles and perform initial screening to reject image tiles not having a threshold level of energy. The processing circuitry may be further configured to perform advanced screening to eliminate image tiles based on background noise to generate screened image tiles and generate a feature vector for an energy return of the screened image tiles. The processing circuitry may also be configured to determine a classification of a target associated with the feature vector.

Johns Hopkins University and Oklahoma Medical Research Foundation | Date: 2016-09-07

The present invention relates to the field of inflammatory bowel disease. More specifically, the present invention relates to the use of cytokines to detect, diagnose, and assess inflammatory bowel disease. In one embodiment, a method for diagnosing Crohns Disease (CD) in a patient comprises the steps of (a) collecting a sample from the patient; (b) measuring the levels of at least one cytokine in the sample collected from the patient; and (c) comparing the levels of the at least one cytokine with predefined cytokine levels, wherein a correlation between the cytokine levels in the patient sample and predefined cytokine levels indicates that the patient has CD. In a specific embodiment, the at least one cytokine comprises Interferon (IFN)-gamma, Interleukin (IL)-1beta, IL-6, IL-8, IL-12, IL-17 and CXCL10.

Johns Hopkins University | Date: 2015-11-19

An antenna is provided including an electromagnetic metasurface. The electromagnetic characteristics of the antenna are dynamically tunable.

A system for detecting and tracking a curvilinear object in a three-dimensional space includes an image acquisition system including a video camera arranged to acquire a video image of the curvilinear object and output a corresponding video signal, the video image comprising a plurality n of image frames each at a respective time t_(i), where i=1, 2, . . . , n; and a data processing system adapted to communicate with the image acquisition system to receive the video signal. The data processing system is configured to determine a position, orientation and shape of the curvilinear object in the three-dimensional space at each time t_(i )by forming a computational model of the curvilinear object at each time t_(i )such that a projection of the computation model of the curvilinear object at each time ti onto a corresponding frame of the plurality of image frames of the video image matches a curvilinear image in the frame to a predetermined accuracy to thereby detect and track the curvilinear object from time t_(1 )to time t_(n).

A serial digital data acquisition receiver (SDDAR) or system of receivers may include an opto-isolator assembly, sampling logic and a USB interface. Both a CLK signal and a DATA signal may each pass through the opto-isolator assembly upon receipt of the CLK and DATA signals at the SDDAR or system. The sampling logic may be operably coupled to the opto-isolator assembly and be configured to determine a point at which to sample the DATA signal based on state changes in the CLK signal. The USB interface may be operably coupled to the sampling logic and an output terminal. The USB interface may be configured to provide telemetry data for processing, display or recording at the output terminal, and may be configured to enable the SDDAR or system to be powered from the output terminal.

Johns Hopkins University | Date: 2015-05-15

A method, system and computer readable medium of: providing feature data of at least one organ at risk or target volume of said patient from a database of non-transitory data stored on a data storage device of prior patients data; generating, using a data processor, a distribution of dose points of the at least one organ at risk or target volume of said patient based on said feature data; calculating, using the data processor, at least one of (i) a probability of toxicity for the at least one organ at risk or (ii) a probability of treatment failure for the at least one target volume, based on said distribution of dose points; assessing, using the data processor, a dosimetric-outcome relationship based on the calculated probability; and automatically formulating, using the data processor, a treatment plan using the dosimetric-outcome relationship to minimize the at least one treatment-related risk.

Johns Hopkins University | Date: 2016-09-02

A method for providing malware protection in connection with processing circuitry including hardware resources and software resources managed by a primary operating system may include providing a trusted operating system to control access to a portion of a local storage area of the hardware resources. In this context, only the trusted operating system is configured to enable writing to the portion of the local storage area. The method may further include storing backup files for the primary operating system in the portion of the local storage area responsive to the trusted operating system granting access to write to the portion of the local storage area.

An embodiment in accordance with the present invention includes a method for estimating the permeability of fractured rock formations from the analysis of a slow fluid pressure wave, which is generated by pressurization of a borehole. Wave propagation in the rock is recorded with TFI. Poroelastic theory is used to estimate the permeability from the measured wave speed. The present invention offers the opportunity of measuring the reservoir-scale permeability of fractured rock, because the method relies on imaging a wave, which propagates through a large rock volume, on the order of kilometers in size. Traditional methods yield permeability for much smaller rock volumes: well logging tools only measure permeability in the vicinity of a borehole. Pressure transient testing accesses larger rock volumes; however, these volumes are much smaller than for the proposed method, particularly in low-permeability rock formations.

Iglesias P.A.,Johns Hopkins University
Current Opinion in Cell Biology | Year: 2012

The actin cytoskeleton in motile cells has many of the hallmarks of an excitable medium, including the presence of propagating waves. This excitable behavior can account for the spontaneous migration of cells. A number of reports have suggested that the chemoattractant-mediated signaling can bias excitability, thus providing a means by which cell motility can be directed. In this review, we discuss some of these observations and theories proposed to explain them. We also suggest a mechanism for cell polarity that can be incorporated into the existing framework. © 2011 Elsevier Ltd.

Treangen T.J.,Johns Hopkins University | Salzberg S.L.,Johns Hopkins University
Nature Reviews Genetics | Year: 2012

Repetitive DNA sequences are abundant in a broad range of species, from bacteria to mammals, and they cover nearly half of the human genome. Repeats have always presented technical challenges for sequence alignment and assembly programs. Next-generation sequencing projects, with their short read lengths and high data volumes, have made these challenges more difficult. From a computational perspective, repeats create ambiguities in alignment and assembly, which, in turn, can produce biases and errors when interpreting results. Simply ignoring repeats is not an option, as this creates problems of its own and may mean that important biological phenomena are missed. We discuss the computational problems surrounding repeats and describe strategies used by current bioinformatics systems to solve them. © 2011 Macmillan Publishers Limited. All rights reserved.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-33-2015 | Award Amount: 30.12M | Year: 2016

The vision of EU-ToxRisk is to drive a paradigm shift in toxicology towards an animal-free, mechanism-based integrated approach to chemical safety assessment. The project will unite all relevant disciplines and stakeholders to establish: i) pragmatic, solid read-across procedures incorporating mechanistic and toxicokinetic knowledge; and ii) ab initio hazard and risk assessment strategies of chemicals with little background information. The project will focus on repeated dose systemic toxicity (liver, kidney, lung and nervous system) as well as developmental/reproduction toxicity. Different human tiered test systems are integrated to balance speed, cost and biological complexity. EU-ToxRisk extensively integrates the adverse outcome pathway (AOP)-based toxicity testing concept. Therefore, advanced technologies, including high throughput transcriptomics, RNA interference, and high throughput microscopy, will provide quantitative and mechanistic underpinning of AOPs and key events (KE). The project combines in silico tools and in vitro assays by computational modelling approaches to provide quantitative data on the activation of KE of AOP. This information, together with detailed toxicokinetics data, and in vitro-in vivo extrapolation algorithms forms the basis for improved hazard and risk assessment. The EU-ToxRisk work plan is structured along a broad spectrum of case studies, driven by the cosmetics, (agro)-chemical, pharma industry together with regulators. The approach involves iterative training, testing, optimization and validation phases to establish fit-for-purpose integrated approaches to testing and assessment with key EU-ToxRisk methodologies. The test systems will be combined to a flexible service package for exploitation and continued impact across industry sectors and regulatory application. The proof-of-concept for the new mechanism-based testing strategy will make EU-ToxRisk the flagship in Europe for animal-free chemical safety assessment.

Louisiana College, The Regents Of The University Of California and Johns Hopkins University | Date: 2016-04-20

Administration of an HNO/NO^() donating compound, such as Angelis salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure. Moreover, administration of the HNO/NO^( )donating compound isopropylamine (IPA)/NO (Na(CH_(3))_(2)CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NO^() donating compound Angelis salt. Additionally, in contrast to the effects observed with NO donors, administration of an HNO/NO^( )donor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent. Further, HNO/NO^( )exerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy.

Louisiana State University, The Regents Of The University Of California and Johns Hopkins University | Date: 2014-09-17

Administration of an HNO/NO^(+) donating compound, such as Angelis salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure. Moreover, administration of the HNO/NO^() donating compound isopropylamine (IPA)/NO (Na(CH_(3))_(2)CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NO^() donating compound Angelis salt. Additionally, in contrast to the effects observed with NO^() donors, administration of an HNO/NO^() donor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent. Further, HNO/NO^() exerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy.

Xing M.,Johns Hopkins University | Haugen B.R.,Aurora University | Schlumberger M.,University Paris - Sud
The Lancet | Year: 2013

Substantial developments have occurred in the past 5-10 years in clinical translational research of thyroid cancer. Diagnostic molecular markers, such as RET-PTC, RAS, and BRAFV600E mutations; galectin 3; and a new gene expression classifier, are outstanding examples that have improved diagnosis of thyroid nodules. BRAF mutation is a prognostic genetic marker that has improved risk stratification and hence tailored management of patients with thyroid cancer, including those with conventionally low risks. Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid cancers as shown in clinical trials; such treatments are likely to become a component of the standard treatment regimen for patients with thyroid cancer in the near future. These novel molecular-based management strategies for thyroid nodules and thyroid cancer are the most exciting developments in this unprecedented era of molecular thyroid-cancer medicine.

Cheung K.J.,Johns Hopkins University | Gabrielson E.,Johns Hopkins University | Werb Z.,University of California at San Francisco | Ewald A.J.,Johns Hopkins University
Cell | Year: 2013

Carcinomas typically invade as a cohesive multicellular unit, a process termed collective invasion. It remains unclear how different subpopulations of cancer cells contribute to this process. We developed three-dimensional (3D) organoid assays to identify the most invasive cancer cells in primary breast tumors. Collective invasion was led by specialized cancer cells that were defined by their expression of basal epithelial genes, such as cytokeratin-14 (K14) and p63. Furthermore, K14+ cells led collective invasion in the major human breast cancer subtypes. Importantly, luminal cancer cells were observed to convert phenotypically to invasive leaders following induction of basal epithelial genes. Although only a minority of cells within luminal tumors expressed basal epithelial genes, knockdown of either K14 or p63 was sufficient to block collective invasion. Our data reveal that heterotypic interactions between epithelial subpopulations are critical to collective invasion. We suggest that targeting the basal invasive program could limit metastatic progression. © 2013 Elsevier Inc.

Applied Genetic Technologies Corporation, Johns Hopkins University and Foundation University | Date: 2015-10-02

The present invention includes methods and compositions for the production of high titer recombinant Adeno-Associated Virus (rAAV) in a variety of mammalian cells. The disclosed rAAV are useful in gene therapy applications. Disclosed methods based on co-infection of cells with two or more replication-defective recombinant herpes virus (rHSV) vectors are suitable for high-titer, large-scale production of infectious rAAV.

Oklahoma Medical Research Foundation and Johns Hopkins University | Date: 2014-06-26

The present invention relates to a system and a medium for analyzing one or more analytes in rheumatoid arthritis subjects to determine whether the subject is at increased risk of diseases such as a cardiovascular disease, the subjects current cardiovascular disease burden, and the likelihood of cardiovascular disease progression in the subject. In addition, the present invention further provides methods for analyzing data to determine risk of cardiovascular disease, current cardiovascular disease burden, and the likelihood of cardiovascular disease progression in a rheumatoid arthritis subject.

Agency: Cordis | Branch: FP7 | Program: CP-FP-SICA | Phase: SSH.2012.4.1-1 | Award Amount: 3.09M | Year: 2013

Mesmerized by the contrast between spectacular growth in Asia and the Pacific Rim and the Wests hard times, many observers have overlooked a major reconfiguration of the Atlantic space. The North America Europe link continues to be the strongest and largest of the relationships between any two continents. But their decline in relative terms is slowly being matched by the rise of Africa, Latin America and a newly energised Arab region, all of which are increasing their interregional links and gaining weight in global affairs. Both positive factors, such as the opportunities for better management of shared resources, and negative ones, like the illegal flow of narcotics that harms the whole region, emerge as potential drivers for cooperation, competition or conflict. The main objective of this project is to analyse fundamental trends in the Atlantic basin and to show how changing economic, energy, security, human, institutional and environmental links are transforming the wider Atlantic space. Research will map the interconnections between those issue areas across the Atlantic. It will also track the transformation of region to region relationships between Africa, the Americas and Europe from a variety of perspectives from all the Atlantic regions and powers. The project will include a prospective exercise where future scenarios for the Atlantic space will be outlined, in order to identify the opportunities for, and obstacles to, stronger cooperation both on issues limited to the Atlantic and on global challenges. The partners also aim to reach policy relevant conclusions for the EUs Atlantic agenda, including a review of the EUs interregional links with the other three littoral continents, its strategic partnerships with the USA, Mexico, Brazil and South Africa and a holistic approach to the whole area all of them crucial aspects of the role that the EU can play in todays changing world.

Johns Hopkins University and MED EL Elektromedizinische Geraete GmbH | Date: 2014-02-14

A vestibular stimulation electrode lead is described for conducting electrical stimulation signals generated by an implanted vestibular stimulation module. An extra-vestibular lead branch carries the stimulation signals from the stimulation module to a vestibular entry location. A stopper collar is bent away at a first discrete angle from a distal end of the extra-vestibular lead branch to penetrate into a vestibular structure at the entry location. An intra-vestibular electrode array is bent away at a second discrete angle from the stopper collar and has an outer surface with one or more electrode contacts for delivering the stimulation signals to vestibular neural tissue at a target location within the vestibular structure. The first and second discrete angles form a geometry of the stopper collar and intra-vestibular electrode array that limits insertion of the intra-vestibular electrode array beyond the target location within the vestibular structure.

Dana-Farber Cancer Institute, Johns Hopkins University and University of Pennsylvania | Date: 2015-02-10

Described herein are methods of generating a protein binding domain that specifically binds to gp120 in a specific conformational state, comprising contacting gp120 with a CD4-mimetic compound, thereby forming gp120 in the specific conformational state; and generating antibodies to gp120 in the specific conformation state. Relatedly, the disclosure also describes methods of neutralizing HIV-1, comprising contacting HIV-1 with an effective amount of a CD4-mimetic compound, thereby forming HIV-1 having gp120 in a specific conformational state; and contacting the HIV-1 in the specific conformational state with an antibody.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-14-2015 | Award Amount: 5.87M | Year: 2016

The main objective of the project is to provide a treatment of the neurological symptoms of patients with Ataxia Telangiectasia (AT), a rare progressively disabling and life-shortening genetic disease for which no therapy is currently available. To achieve this, a pivotal Phase III study will be conducted, to allow regulatory filing to obtain market authorization in EU and USA by 2019. EryDex is an innovative product, developed by EryDel, used to administer dexamethasone sodium phosphate by ex-vivo encapsulation in autologous erythrocytes, which are infused into the patient. EryDex provides long-term delivery of low doses of dexamethasone without the typical steroid side effects and has reached a successful Phase II trial conducted in AT patients. The phase III trial will be an international, multi-center, 1 year, randomized, prospective, double-blind, placebo-controlled, designed to assess the effect of 2 dose ranges of EryDex, administered monthly by IV infusion, on neurological symptoms of AT patients. The protocol of the trial and the regulatory path to registration has already been agreed upon with EMA and FDA. An international patient registry will also be set with the aim of establishing and maintaining a comprehensive clinical database of patients with AT and closely related conditions, enabling the monitoring of AT epidemiology, the development of an evidence-based natural history of the condition, identification of biomarkers as well as development of clinical guidelines. The AT NEST, the first scale to assess symptoms specific to AT patients, coordinated by the AT centre at the Johns Hopkins University, will be tested in the study and if validated will represent the 1st scale assessing chief areas of impairment specific to AT. In parallel to the clinical trial, investigations into the molecular mechanisms of action of EryDex will be performed with the objective to provide the validation of a new biomarker predictive of treatment efficacy.

Johns Hopkins University and The United States Gov | Date: 2015-08-06

A device for at least one of receiving and transmitting electromagnetic radiation includes a feedhorn having a substantially smooth, electrically conducting inner surface extending from an open end to a feed end, the inner surface being substantially rotationally symmetrical about a longitudinal axis, wherein an orthogonal distance from a point on the longitudinal axis to the substantially smooth, electrically conducting inner surface increases monotonically as the point on the longitudinal axis is selected at successively greater distances from the feed end of the feedhorn towards the open end of the feedhorn such that a profile of the substantially smooth, electrically conducting inner surface of the feedhorn is monotonically increasing. The feedhorn has an operating bandwidth and the feedhorn provides a maximum of 30 dB cross polarization response over at least 15% of the operating bandwidth. A method of producing a feedhorn for receiving or transmitting electromagnetic radiation includes determining a profile of an inner surface of the feedhorn based on constraints required to achieve a plurality of operating parameters, providing a pre-machined feedhorn having an initial inner surface, and machining the initial inner surface of the pre-machined feedhorn to substantially match the profile determined to achieve the plurality of operating parameters for the feedhorn. The determining the profile includes a constraint for the profile to be a monotonically increasing profile relative to a rotational symmetry axis of the inner surface of the feedhorn going from a narrow end to a wide end of the feedhorn.

Johns Hopkins University and Genzyme | Date: 2015-07-15

To gain a better understanding of breast tumor angiogenesis, breast endothelial cells (ECs) were isolated and evaluated for gene expression patterns. When transcripts from breast ECs derived from normal and malignant breast tissues were compared, genes that were specifically elevated in tumor-associated breast endothelium were revealed. These results confirm that neoplastic and normal endothelium in human breast are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.

Chakravarti A.,Johns Hopkins University | Clark A.G.,Cornell University | Mootha V.K.,Massachusetts General Hospital
Cell | Year: 2013

Technologies for genome-wide sequence interrogation have dramatically improved our ability to identify loci associated with complex human disease. However, a chasm remains between correlations and causality that stems, in part, from a limiting theoretical framework derived from Mendelian genetics and an incomplete understanding of disease physiology. Here we propose a set of criteria, akin to Koch's postulates for infectious disease, for assigning causality between genetic variants and human disease phenotypes. © 2013 Elsevier Inc.

Manuel H.,CSIC - National Center for Metallurgical Research | Manuel H.,Johns Hopkins University
New England Journal of Medicine | Year: 2010

Deaths from pancreatic ductal adenocarcinoma, also known as pancreatic cancer, rank fourth among cancer-related deaths in the United States, yet the causes of pancreatic cancer remain unknown. This review article summarizes recent progress in the understanding and management of pancreatic cancer. Copyright © 2010 Massachusetts Medical Society.

Mattson M.P.,U.S. National Institute on Aging | Mattson M.P.,Johns Hopkins University
Cell Metabolism | Year: 2012

Evolution favored individuals with superior cognitive and physical abilities under conditions of limited food sources, and brain function can therefore be optimized by intermittent dietary energy restriction (ER) and exercise. Such energetic challenges engage adaptive cellular stress-response signaling pathways in neurons involving neurotrophic factors, protein chaperones, DNA-repair proteins, autophagy, and mitochondrial biogenesis. By suppressing adaptive cellular stress responses, overeating and a sedentary lifestyle may increase the risk of Alzheimer's and Parkinson's diseases, stroke, and depression. Intense concerted efforts of governments, families, schools, and physicians will be required to successfully implement brain-healthy lifestyles that incorporate ER and exercise. © 2012 Elsevier Inc.

Longo V.D.,University of Southern California | Mattson M.P.,U.S. National Institute on Aging | Mattson M.P.,Johns Hopkins University
Cell Metabolism | Year: 2014

Fasting has been practiced for millennia, but, only recently, studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism, and bolster cellular protection. In lower eukaryotes, chronic fasting extends longevity, in part, by reprogramming metabolic and stress resistance pathways. In rodents intermittent or periodic fasting protects against diabetes, cancers, heart disease, and neurodegeneration, while in humans it helps reduce obesity, hypertension, asthma, and rheumatoid arthritis. Thus, fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions. © 2014 Elsevier Inc.

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