Nashville, TN, United States
Nashville, TN, United States

Vanderbilt University is a private research university located in Nashville, Tennessee, United States. Founded in 1873, the university is named in honor of shipping and rail magnate "Commodore" Cornelius Vanderbilt, who provided the school its initial $1 million endowment despite having never been to the South. The Commodore hoped that his gift and the greater work of the university would help to heal the sectional wounds inflicted by the Civil War.Today Vanderbilt enrolls approximately 12,000 students from all 50 U.S. states and over 90 foreign countries in four undergraduate and six graduate and professional schools. Several research centers and institutes are affiliated with the university, including the Vanderbilt Institute for Public Policy Studies, Freedom Forum First Amendment Center, Dyer Observatory, and Vanderbilt University Medical Center, the only Level I trauma center in Middle Tennessee. With the exception of the off-campus observatory and satellite medical clinics, all of university's facilities are situated on its 330-acre campus in the heart of Nashville, 1.5 miles from downtown. Despite its urban surroundings, the campus itself is a national arboretum and features over 300 different species of trees and shrubs. Wikipedia.


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Patent
Vanderbilt University | Date: 2016-10-26

Method of limiting development of acute kidney injury (AKI) and treating AKI using pyridoxamine are described, together with methods for monitoring efficacy of pyridoxamine therapy.


The present invention relates to compositions and methods for treating diseases associated with dyslipidemia, including hypercholesterolemia, hypertriglyceridemia, steatohepatitis, atherosclerosis, obesity, hyperglycemia, metabolic syndrome, and related aspects of and conditions associated with metabolic syndrome. The compositions and methods disclosed herein are useful for regulating the lipid balance (lipid homeostasis) in a subject. Compositions and methods including a Nuclear Transport Modifier may be administered to a subject to modulate the transport of transcription factors, mediated by nuclear import adaptors, into the nucleus of a cell resulting in a decrease in cholesterol and triglyceride levels in the blood and liver, a decrease in atherosclerotic lesion size, a decrease in body weight and in hyperglycemia, a reduction of fatty liver inflammation, and an improvement in liver function.


Patent
Vanderbilt University | Date: 2016-08-04

An apparatus for moving an elongate rod longitudinally and rotationally, and a method of moving the elongate rod longitudinally and rotationally, are provided. A translation member has a first translation member end held relatively stationary and a longitudinally spaced second translation member end which is selectively movable longitudinally with respect to the first translation member end via actuation of the translation member. The second translation member end is operatively connected to selectively impart longitudinal motion to the elongate rod. A rotation member has a first rotation member end held relatively stationary and a longitudinally spaced second rotation member end which is selectively rotatable with respect to the first rotation member end via actuation of the rotation member. The second rotation member end is operatively connected to selectively impart rotational motion to the elongate rod.


Patent
Vanderbilt University | Date: 2016-08-11

A device for manipulating a wire includes a first structure and a second structure pivotably mounted with respect to each other so as to define respective facing surfaces configured for alternating between a closed position and at least one open position, where each of the respective facing surfaces includes one or more detent elements and one or more tooth elements extending therefrom. In the device, the tooth elements of the first structure and the second structure are in an interlocking and overlapping arrangement in at least the closed position. Further, each of the tooth elements has a concave surface for defining a passage between the facing surface in the at least one open position. Additionally, each of the detent elements is arranged to face the concave surface of one of the tooth elements of an opposite one of the respective facing surfaces in the closed position.


The invention relates to a system of fluidic valves and pumps and associated fluidic channels integratable into a bio-object microfluidics module. The module can include input and output buses; upstream and downstream interconnection bus control valves (CVs) coupled to the input and output buses, respectively. It may include arterial, venous, wash and waste bus lines, each connecting between the upstream and downstream interconnection bus CVs. It may also include an input CV connecting to the arterial bus line, upstream interconnection bus CV, bio-object and inlets, and an output CV connecting to the bio-object, input CV, downstream interconnection bus CV and outlets; and a pump connecting between the input CV and bio-object. The system of fluidic valves and pumps can be arranged to provide MicroFormulator functionality enabling precise mixtures of drugs, chemicals, or biochemicals to be delivered in a time-dependent fashion to biological entities housed in individual wells or chambers.


Patent
Vanderbilt University | Date: 2015-04-08

Systems and methods are described for isolation, separation and detection of a molecular species using a low resource device for processing of samples. Methods include isolation, separation and detection of whole cells.


Patent
Vanderbilt University and Yale University | Date: 2016-09-14

Methods, compositions, devices, and kits for treating and/or reducing the risk of developing a condition associated with fibrosis and/or collagen deposition are provided. The method of treating and/or reducing the risk of developing a condition associated with fibrosis and/or collagen deposition in a subject includes administering an effective amount a miRNA-762 inhibitor to the subject, wherein the subject is identified as having a risk of developing and/or a need for treatment of the condition associated with fibrosis and/or collagen deposition. The kit includes a vial containing an miRNA-762 inhibitor and a device for use in a surgery creating a risk of fibrosis and/or collagen deposition. The composition includes a pharmaceutical composition comprising a miRNA-762 inhibitor and a second agent selected from the group consisting of: an angiotensin-converting enzyme (ACE) inhibitors, an angiotensin receptor blocker (ARB), another antihypertensive agent, a steroid, and combinations thereof.


The present disclosure provides for rapid identification of mechanism of action (MOA) for drugs and toxins, and does so in a rapid (30 days or less) fashion. The methods use a combination of high throughput bioinformatics and pathway analysis that examine a wide variety of biological parametics.


Patent
Vanderbilt University and Pfizer | Date: 2015-02-20

Disclosed herein are improved optical detection methods comprising interferometric detection systems and methods of detecting a binding interaction between a sample comprising uncultured tissue homogenate and an analyte, together with various applications of the disclosed techniques. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.


Patent
Vanderbilt University | Date: 2016-06-09

Pre-coated analysis substrates, and methods of making the substrates and using them to analyze animal tissue, are described. The pre-coated analysis substrates can be made by forming a matrix surface on an analysis substrate; adding a protease to the matrix surface to form a pre-coated analysis substrate; and placing an animal tissue specimen on the matrix surface. The animal tissue can then be analyzed by allowing the protease to partially digest the animal tissue specimen; and analyzing the partially digested animal tissue specimen by mass spectrometry.


Patent
Vanderbilt University | Date: 2016-12-06

Systems and methods for imaging a target are provided. A system includes a detector and a substantially bitelecentric lens assembly positioned between the detector and the target. A first optical assembly is configured to focus light received from the substantially bitelecentric lens assembly onto the detector. The substantially bitelecentric lens assembly and the first optical assembly are configured to produce a collimated light space between the substantially bitelecentric lens assembly and the first optical assembly. A second optical assembly is positioned within the collimated light space.


Patent
Vanderbilt University | Date: 2016-09-26

Systems and methods for establishing a serial treatment plan to correct a muscular-skeletal deformity of a subject are described herein. A method can include receiving an image of a portion of the subjects body having the muscular-skeletal deformity, processing the image of the portion of the subjects body to establish a quantitative measure of the muscular-skeletal deformity, and determining a therapeutic state to correct the muscular-skeletal deformity. The therapeutic state can include an adjustment of the portion of the subjects body. In addition, at least one characteristic of the adjustment of the portion of the subjects body can be related to the quantitative measure of the muscular-skeletal deformity.


Patent
Vanderbilt University | Date: 2016-08-04

A dynamic alarm system that can assess the background noise in a clinical environment with sub-minute time sampling and change the alarm output to a desired signal-to-noise ratio (SNR) below ambient noise (negative SNR) to minimize clinician fatigue and ameliorate deleterious patient outcomes, while preserving clinician performance.


Patent
Vanderbilt University | Date: 2017-03-15

The invention regards the modulation of TGF- activity by administering to a subject an antibody that binds to TGF-, thereby increasing bone growth, bone formation, bone mass and bone strength. The antibody acts to increase osteoblast number and function while at the same time decreasing osteoclast number and function. Such drugs are useful in the treatment of diseases or disorders such as osteoporosis, Pagets disease, metastatic bone cancer, myeloma bone disease, bone fractures, etc.


Patent
Al Biomedical Corporation and Vanderbilt University | Date: 2017-02-15

Device and method for visibly highlighting areas of a region including an imager configured to image the region with a sensitivity to at least one of wavelength, light level, or contrast greater than the human eye, an overlay element configured to visibly highlight areas of the region and registered to the imager to produce alignment of imaged features with highlighted features at the same location on the region, and at least one of a controller executing a program or logic configured to process acquired images from the imager to identify areas of the region determined not visible to the human eye, and control the overlay element to visibly highlight those areas on the region.


In one aspect, the invention relates to substituted 2-(4-heterocyclylbenzyl)isoindolin-1-one analogs compounds, derivatives thereof, and related compounds which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M_(1) (mAChR M_(1)); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.


Schaffner W.,Vanderbilt University
New England Journal of Medicine | Year: 2014

A 23-year-old man sustained abdominal trauma in a motorcycle accident that required a surgical splenectomy. He received the 23-valent pneumococcal polysaccharide vaccine (PPSV23) after surgery. Six months after his surgery, he calls his primary care provider because he has fever. What is the appropriate management? Are other prophylactic measures available and indicated? Copyright © 2014 Massachusetts Medical Society.


Egli M.,Vanderbilt University
Annual Review of Biochemistry | Year: 2014

For a biological oscillator to function as a circadian pacemaker that confers a fitness advantage, its timing functions must be stable in response to environmental and metabolic fluctuations. One such stability enhancer, temperature compensation, has long been a defining characteristic of these timekeepers. However, an accurate biological timekeeper must also resist changes in metabolism, and this review suggests that temperature compensation is actually a subset of a larger phenomenon, namely metabolic compensation, which maintains the frequency of circadian oscillators in response to a host of factors that impinge on metabolism and would otherwise destabilize these clocks. The circadian system of prokaryotic cyanobacteria is an illustrative model because it is composed of transcriptional and nontranscriptional oscillators that are coupled to promote resilience. Moreover, the cyanobacterial circadian program regulates gene activity and metabolic pathways, and it can be manipulated to improve the expression of bioproducts that have practical value. Copyright © 2014 by Annual Reviews.


Hamilton J.H.,Vanderbilt University | Hofmann S.,Helmholtz Center for Heavy Ion Research | Oganessian Y.T.,Joint Institute for Nuclear Research
Annual Review of Nuclear and Particle Science | Year: 2013

We describe the discoveries of new superheavy nuclei (a) with Z=107112 produced in cold fusion reactions between 208Pb and 209Bi and beams of A > 50 and (b) with Z=113118 in hot fusion reactions between actinide nuclei and 48Ca. We also discuss the facilities used in these measurements. We compare the behavior of the α-decay energies and half-lives, spontaneous fission half-lives, cross sections, and excitation functions with expectations from theoretical calculations. Finally, we outline future research directions, including studies of the detailed properties of nuclei synthesized at higher yields, searches for new elements with Z=119 and 120, and developments of new facilities. © Copyright ©2013 by Annual Reviews. All rights reserved.


Patent
Vanderbilt University and University of Oregon | Date: 2015-07-27

Compositions and methods for inhibiting thrombosis without compromising hemostasis are described. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The disclosure further includes pharmaceutical compositions comprising the disclosed anti-factor XI monoclonal antibodies, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier. Methods of the disclosure include administering the compositions described above to a subject in need thereof for the purpose of inhibiting thrombosis, reducing a required dose of an antithrombotic agent in the treatment of thrombosis, treating metastatic cancer, or treating an acute inflammatory reaction.


Patent
Vanderbilt University and NEC Corp | Date: 2014-08-28

A fast change planning system includes: a state machine set division unit 11 which divides a state machine set made up of one or more state machines, into a state machine group set; and a state machine set integration unit 12 which integrates transition orders derived from each of the state machine groups obtained by dividing the state machine group set.


Patent
Vanderbilt University and NEC Corp | Date: 2014-08-28

A change planning system includes a state machine set conversion unit 11 which converts a state machine set made up of one or more state machines, into a single state machine including one or more states, wherein a state in a state machine included in the state machine set transitions to another state according to a transition condition designating a state in a state machine included in the state machine set other than the state machine, wherein a state in the single state machine corresponds to a state of all state machines in the state machine set, and wherein, while the transition condition according to which the state in the state machine makes a predetermined transition is satisfied, the state in the single state machine transitions to another state corresponding to another state of all state machines that results from the predetermined transition.


Patent
Vanderbilt University and NEC Corp | Date: 2014-08-28

A change management system includes a system definition expansion unit 11 which generates information of a state machine set made up of one or more state machines, from a system definition. The system definition includes one or more primitives and any number of wirings. Each of the primitives includes any number of wire ports. Each of the wire ports includes one state machine. Each of the wirings connects to two wire ports included in different primitives. The system definition expansion unit 11 generates the information of the state machine set, by connecting existing definitions of the primitives by the wirings.


Patent
Vanderbilt University and University of Oregon | Date: 2014-12-12

Disclosed herein are monoclonal antibodies specific for factor XI (fXI) that prevent activation of fXI by factor XIIa (fXIIa). The monoclonal antibodies are universal fXI antibodies, capable of binding all mammalian species tested. The anti-fXI monoclonal antibodies prolong clotting time in mammalian plasmas. Moreover, administration of the fXI monoclonal antibodies disclosed herein results in inhibition of thrombosis without altering hemostasis in animal models of thrombosis. Thus, provided herein are monoclonal antibodies specific for fXI that block activation of fXI by fXIIa, compositions and immunoconjugates comprising such antibodies and their methods of use.


Grant
Agency: GTR | Branch: EPSRC | Program: | Phase: Training Grant | Award Amount: 3.94M | Year: 2014

The achievements of modern research and their rapid progress from theory to application are increasingly underpinned by computation. Computational approaches are often hailed as a new third pillar of science - in addition to empirical and theoretical work. While its breadth makes computation almost as ubiquitous as mathematics as a key tool in science and engineering, it is a much younger discipline and stands to benefit enormously from building increased capacity and increased efforts towards integration, standardization, and professionalism. The development of new ideas and techniques in computing is extremely rapid, the progress enabled by these breakthroughs is enormous, and their impact on society is substantial: modern technologies ranging from the Airbus 380, MRI scans and smartphone CPUs could not have been developed without computer simulation; progress on major scientific questions from climate change to astronomy are driven by the results from computational models; major investment decisions are underwritten by computational modelling. Furthermore, simulation modelling is emerging as a key tool within domains experiencing a data revolution such as biomedicine and finance. This progress has been enabled through the rapid increase of computational power, and was based in the past on an increased rate at which computing instructions in the processor can be carried out. However, this clock rate cannot be increased much further and in recent computational architectures (such as GPU, Intel Phi) additional computational power is now provided through having (of the order of) hundreds of computational cores in the same unit. This opens up potential for new order of magnitude performance improvements but requires additional specialist training in parallel programming and computational methods to be able to tap into and exploit this opportunity. Computational advances are enabled by new hardware, and innovations in algorithms, numerical methods and simulation techniques, and application of best practice in scientific computational modelling. The most effective progress and highest impact can be obtained by combining, linking and simultaneously exploiting step changes in hardware, software, methods and skills. However, good computational science training is scarce, especially at post-graduate level. The Centre for Doctoral Training in Next Generation Computational Modelling will develop 55+ graduate students to address this skills gap. Trained as future leaders in Computational Modelling, they will form the core of a community of computational modellers crossing disciplinary boundaries, constantly working to transfer the latest computational advances to related fields. By tackling cutting-edge research from fields such as Computational Engineering, Advanced Materials, Autonomous Systems and Health, whilst communicating their advances and working together with a world-leading group of academic and industrial computational modellers, the students will be perfectly equipped to drive advanced computing over the coming decades.


Grant
Agency: GTR | Branch: AHRC | Program: | Phase: Research Grant | Award Amount: 4.16M | Year: 2012

Over the last decade, the creative industries have been revolutionised by the Internet and the digital economy. The UK, already punching above its weight in the global cultural market, stands at a pivotal moment where it is well placed to build a cultural, business and regulatory infrastructure in which first movers as significant as Google, Facebook, Amazon or iTunes may emerge and flourish, driving new jobs and industry. However, for some creators and rightsholders the transition from analogue to digital has been as problematic as it has been promising. Cultural heritage institutions are also struggling to capitalise upon new revenue streams that digitisation appears to offer, while maintaining their traditional roles. Policymakers are hampered by a lack of consensus across stakeholders and confused by partisan evidence lacking robust foundations. Research in conjunction with industry is needed to address these problems and provide support for legislators. CREATe will tackle this regulatory and business crisis, helping the UK creative industry and arts sectors survive, grow and become global innovation pioneers, with an ambitious programme of research delivered by an interdisciplinary team (law, business, economics, technology, psychology and cultural analysis) across 7 universities. CREATe aims to act as an honest broker, using open and transparent methods throughout to provide robust evidence for policymakers and legislators which can benefit all stakeholders. CREATe will do this by: - focussing on studying and collaborating with SMEs and individual creators as the incubators of innovation; - identifying good, bad and emergent business models: which business models can survive the transition to the digital?, which cannot?, and which new models can succeed and scale to drive growth and jobs in the creative economy, as well as supporting the public sector in times of recession?; - examining empirically how far copyright in its current form really does incentivise or reward creative work, especially at the SME/micro level, as well as how far innovation may come from open business models and the informal economy; - monitoring copyright reform initiatives in Europe, at WIPO and other international fora to assess how they impact on the UK and on our work; - using technology as a solution not a problem: by creating pioneering platforms and tools to aid creators and users, using open standards and released under open licences; - examining how to increase and derive revenues from the user contribution to the creative economy in an era of social media, mash-up, data mining and prosumers; - assessing the role of online intermediaries such as ISPs, social networks and mobile operators to see if they encourage or discourage the production and distribution of cultural goods, and what role they should play in enforcing copyright. Given the important governing role of these bodies should they be subject to regulation like public bodies, and if so, how?; - consider throughout this work how the public interest and human rights, such as freedom of expression, privacy, and access to knowledge for the socially or physically excluded, may be affected either positively or negatively by new business models and new ways to enforce copyright. To investigate these issues our work will be arranged into seven themes: SMEs and good, bad and emergent business models; Open business models; Regulation and enforcement; Creators and creative practice; Online intermediaries and physical and virtual platforms; User creation, behaviour and norms; and, Human rights and the public interest. Our deliverables across these themes will be drawn together to inform a Research Blueprint for the UK Creative Economy to be launched in October 2016.


Patent
Vanderbilt University and University of Oregon | Date: 2014-04-01

The present invention relates to compositions and methods for inhibiting thrombosis without compromising hemostasis. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The invention further includes pharmaceutical compositions comprising the anti-factor XI monoclonal antibodies of the invention, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier. Methods of the invention comprise administering the compositions described above to a subject in need thereof for the purpose of inhibiting thrombosis, reducing a required dose of an antithrombotic agent in the treatment of thrombosis, treating metastatic cancer, or treating an acute inflammatory reaction.


Patent
Vanderbilt University and University of Oregon | Date: 2015-11-03

Methods and systems for detecting a gold nanorod (GNR) contrast agent in an optical coherence tomography (OCT) image of a sample are disclosed. In one example approach, a method comprises separating the OCT image at the location into short and long wavelength halves around a center wavelength of the OCT system, calculating a ratio between the short and long wavelength halves, and indicating a gold nanorod contrast agent at the location based on the ratio. In some examples, spectral fractionation may be employed to further divide the short and long wavelength halves into sub-bands to increase spectral contrast, reduce noise, and increase accuracy in detecting GNR in a sample.


Patent
Vanderbilt University and University of Oregon | Date: 2013-03-04

The present invention relates to compositions and methods for inhibiting thrombosis without compromising hemostasis. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The invention further includes pharmaceutical compositions comprising the anti-factor XI monoclonal antibodies of the invention, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier. Methods of the invention comprise administering the compositions described above to a subject in need thereof for the purpose of inhibiting thrombosis, reducing a required dose of an antithrombotic agent in the treatment of thrombosis, treating metastatic cancer, or treating an acute inflammatory reaction.


Patent
Vanderbilt University | Date: 2015-03-18

The leading cause of graft failure is the subsequent development of intimal hyperplasia, which represents a response to injury that is thought to involve smooth muscle proliferation, migration, phenotypic modulation, and extracellular matrix (ECM) deposition. Surgical techniques typically employed for vein harvest - stretching the vein, placing the vein in low pH, solutions, and the use of toxic surgical skin markers - are shown here to cause injury. The invention therefore provides for non-toxic surgical markers than also protect against stretch-induced loss of functional viability, along with other additives. Devices and compositions for reducing physical stress or protecting from the effects flowing therefrom, also are provided.


Patent
Vanderbilt University and University of Oregon | Date: 2013-01-31

Disclosed herein are monoclonal antibodies specific for factor XI (fXI) that prevent activation of fXI by factor XIIa (fXIIa). The monoclonal antibodies are universal fXI antibodies, capable of binding all mammalian species tested. The anti-fXI monoclonal antibodies prolong clotting time in mammalian plasmas. Moreover, administration of the fXI monoclonal antibodies disclosed herein results in inhibition of thrombosis without altering hemostasis in animal models of thrombosis. Thus, provided herein are monoclonal antibodies specific for fXI that block activation of fXI by fXIIa, compositions and immunoconjugates comprising such antibodies and their methods of use.


Patent
University of Oregon and Vanderbilt University | Date: 2016-04-06

The present invention relates to compositions and methods for inhibiting thrombosis without compromising hemostasis. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The invention further includes pharmaceutical compositions comprising the anti-factor XI monoclonal antibodies of the invention, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier. Methods of the invention comprise administering the compositions described above to a subject in need thereof for the purpose of inhibiting thrombosis, reducing a required dose of an antithrombotic agent in the treatment of thrombosis, treating metastatic cancer, or treating an acute inflammatory reaction. Methods for making an anti-factor XI monoclonal antibody, or epitope-binding fragments, variants, or derivatives thereof, are also provided.


Patent
Technion Research & Development Foundation Ltd. and Vanderbilt University | Date: 2015-04-02

Methods and systems that remove impurities from phosphogypsum (PG), including from radium and heavy metal salts, and produce gypsum binders and products. In one embodiment, PG is reacted with a chloride solution in an acidic environment under mechanical manipulation and/or heat followed by galvanic and/or zeolite absorption removal of impurities.


Patent
Vanderbilt University, Aronora Inc. and University of Oregon | Date: 2013-12-06

Provided are antibodies that selectively bind to and inhibit activation of coagulation factor XII. Methods of treatment employing these antibodies are described herein.


Patent
Vanderbilt University | Date: 2014-02-25

The leading cause of graft failure is the subsequent development of intimal hyperplasia, which represents a response to injury that is thought to involve smooth muscle proliferation, migration, phenotypic modulation, and extracellular matrix (ECM) deposition. Surgical techniques typically employed for vein harveststretching the vein, placing the vein in low pH, solutions, and the use of toxic surgical skin markersare shown here to cause injury. The invention therefore provides for non-toxic surgical markers than also protect against stretch-induced loss of functional viability, along with other additives. Devices and compositions for reducing physical stress or protecting from the effects flowing therefrom, also are provided.


Blakely R.D.,Vanderbilt University | Edwards R.H.,University of California at San Francisco
Cold Spring Harbor Perspectives in Biology | Year: 2012

The regulated exocytosis that mediates chemical signaling at synapses requires mechanisms to coordinate the immediate response to stimulation with the recycling needed to sustain release. Two general classes of transporter contribute to release, one located on synaptic vesicles that loads them with transmitter, and a second at the plasma membrane that both terminates signaling and serves to recycle transmitter for subsequent rounds of release. Originally identified as the target of psychoactive drugs, these transport systems have important roles in transmitter release, but we are only beginning to understand their contribution to synaptic transmission, plasticity, behavior, and disease. Recentwork has started to provide a structural basis for their activity, to characterize their trafficking and potential for regulation. The results indicate that far from the passive target of psychoactive drugs, neurotransmitter transporters undergo regulation that contributes to synaptic plasticity. © 2012 Cold Spring Harbor Laboratory Press; all rights reserved.


Young J.D.,University of Connecticut | Young J.D.,Vanderbilt University
Bioinformatics | Year: 2014

Summary: 13C flux analysis studies have become an essential component of metabolic engineering research. The scope of these studies has gradually expanded to include both isotopically steady-state and transient labeling experiments, the latter of which are uniquely applicable to photosynthetic organisms and slow-to-label mammalian cell cultures. Isotopomer network compartmental analysis (INCA) is the first publicly available software package that can perform both steady-state metabolic flux analysis and isotopically non-stationary metabolic flux analysis. The software provides a framework for comprehensive analysis of metabolic networks using mass balances and elementary metabolite unit balances. The generation of balance equations and their computational solution is completely automated and can be performed on networks of arbitrary complexity. © The Author 2013. Published by Oxford University Press.


Kaverina I.,Vanderbilt University | Straube A.,University of Warwick
Seminars in Cell and Developmental Biology | Year: 2011

Microtubules define the architecture and internal organization of cells by positioning organelles and activities, as well as by supporting cell shape and mechanics. One of the major functions of microtubules is the control of polarized cell motility. In order to support the asymmetry of polarized cells, microtubules have to be organized asymmetrically themselves. Asymmetry in microtubule distribution and stability is regulated by multiple molecular factors, most of which are microtubule-associated proteins that locally control microtubule nucleation and dynamics. At the same time, the dynamic state of microtubules is key to the regulatory mechanisms by which microtubules regulate cell polarity, modulate cell adhesion and control force-production by the actin cytoskeleton. Here, we propose that even small alterations in microtubule dynamics can influence cell migration via several different microtubule-dependent pathways. We discuss regulatory factors, potential feedback mechanisms due to functional microtubule-actin crosstalk and implications for cancer cell motility. © 2011 Elsevier Ltd.


Alvarez-Buylla A.,University of California at San Francisco | Ihrie R.A.,Vanderbilt University
Seminars in Cell and Developmental Biology | Year: 2014

Sonic hedgehog (Shh) is a pleiotropic factor in the developing central nervous system (CNS), driving proliferation, specification, and axonal targeting in multiple sites within the forebrain, hindbrain, and spinal cord. Studies in embryonic CNS have shown how gradients of this morphogen are translated by neuroepithelial precursors to determine the types of neurons and glial cells they produce [1,2]. Shh also has a well-characterized role as a mitogen for specific progenitor cell types in neural development [3,4]. As we begin to appreciate that Shh continues to act in the adult brain, a central question is what functional role this ligand plays when major morphogenetic and proliferative processes are no longer in operation. A second fundamental question is whether similar signaling mechanisms operate in embryonic and adult CNS. In the two major germinal zones of the adult brain, Shh signaling modulates the self-renewal and specification of astrocyte-like primary progenitors, frequently referred to as neural stem cells (NSCs). It also may regulate the response of the mature brain to injury, as Shh signaling has been variously proposed to enhance or inhibit the development of a reactive astrocyte phenotype. The identity of cells producing the Shh ligand, and the conditions that trigger its release, are also areas of growing interest; both germinal zones in the adult brain contain Shh-responsive cells but do not autonomously produce this ligand. Here, we review recent findings revealing the function of this fascinating pathway in the postnatal and adult brain, and highlight ongoing areas of investigation into its actions long past the time when it shapes the developing brain. © 2014 Elsevier Ltd.


Patent
Calidris Therapeutics Ltd., University of Illinois at Urbana - Champaign, The United States Of America and Vanderbilt University | Date: 2012-05-25

The invention provides a peptide or peptidomimetic that is derived from or based upon the amino acid sequence of the C-terminal -helix or hypervariable region (HVR) or a Ras protein, a nucleic acid encoding the peptide or peptidomimetic, and methods employing the same.


Grant
Agency: Department of Defense | Branch: Air Force | Program: STTR | Phase: Phase I | Award Amount: 99.96K | Year: 2012

ABSTRACT: DoD and government information systems need to dynamically and securely share information between different US, allied, and coalition agencies at multiple levels of classification and need-to-know. As the amount of data available to intelligence analysts continues to increase greatly, DoD and government agencies are showing increasing interest in cloud computing platforms. Cloud computing not only allows users fast and efficient access to vast amounts of data, but also supplies a framework for powerful distributed applications that can help analyze the data in a timely, actionable manner. However, the most advanced cloud computing systems use public deployments, which do not factor in advanced confidentiality, privacy, and trust issues inherent in confidentiality and need-to-know. Moreover, cloud computing systems are also prone to cascading and propagating errors, and do not presently meet the DoD"s stringent reliability requirements. In order to make cloud computing a viable and popular platform for confidential DoD/IC systems, Infoscitex (IST) proposes Security Optimization and Fault Tolerance in Cloud Architecture (SOFTCloud), which offers a robust suite of security, privacy, and fault-tolerance improvements to cloud infrastructure. SOFTCloud is designed to ensure need-to-know, prevent cascading failures, and protect against attacks on data pedigree. BENEFIT: SOFTCloud"s infrastructure improvements, such as proactive fast failover and backup resource overbooking, prevent cascading failures by isolating anomalies where they occur and rapidly fixing these anomalies. SOFTCloud"s primary-backup replication consumes fewer resources than traditional (active-active) replication while delivering comparable performance. Thus, SOFTCloud supports more end users, balances loads better across applications and users, and makes cloud computing tenable for resource-constrained environments. SOFTCloud"s hierarchical data management system ensures need-to-know in the cloud and prevents targeted attacks. Additionally, SOFTCloud"s robust digital watermarking prevents the cloud from being used for malicious purposes and ensures data pedigree against cropping, scrambling, ambiguity and unauthorized removal attacks. There is a widespread need for SOFTCloud in military, government, and commercial markets. SOFTCloud"s key military and government application is in sharing data and applications across service branches (Air Force, Navy, Army, Marines) and government agencies (e.g., FBI, CIA, DHS). Data and applications may also be shared with coalition forces (UK, Australia, etc.) as well. Commercial applications include improvements on cloud infrastructure in e-commerce, as well as making the cloud tenable for high-security and high-privacy data used in the healthcare and banking industries.


Patent
The United States Of America, University of Illinois at Urbana - Champaign, 1058638 B.C. Ltd. and Vanderbilt University | Date: 2016-02-04

A method of inhibiting Ras activity in a cell comprising introducing a peptide or peptidomimetic into the cell, wherein the peptide or peptidomimetic is derived from or based upon the amino acid sequence of the C-terminal -helix or hypervariable region (HVR) or a Ras protein.


Patent
President And Fellows Of Harvard College and Vanderbilt University | Date: 2012-12-10

The invention provides integrated Organ-on-Chip microphysiological systems representations of living Organs and support structures for such microphysiological systems.


Shridhar R.,Moffitt Cancer Center | Shibata D.,H. Lee Moffitt Cancer Center and Research Institute | Chan E.,Vanderbilt University | Thomas C.R.,Oregon Health And Science University
CA Cancer Journal for Clinicians | Year: 2015

Answer questions and earn CME/CNE The management of squamous cell carcinomas of the anal canal has evolved from surgery as first-line treatment to curative chemoradiation, with surgery reserved for salvage. Significant progress has been made in understanding how to most effectively deliver chemotherapy and reduce toxicity through advancements in radiation delivery. The purpose of this article is to review the multimodality approach to the diagnosis and management of anal cancer based on a review of the published data and in light of available guidelines. CA Cancer J Clin 2015;65: 139-162. © 2015 American Cancer Society.


Taylor W.D.,Vanderbilt University | Aizenstein H.J.,University of Pittsburgh | Alexopoulos G.S.,New York Medical College
Molecular Psychiatry | Year: 2013

The 'Vascular Depression' hypothesis posits that cerebrovascular disease may predispose, precipitate or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between LLD, vascular risk factors and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in LLD, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor, influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression, but also provide guidance on the potential repurposing of pharmacological agents that may improve LLD outcomes. © 2013 Macmillan Publishers Limited.


Graham T.R.,Vanderbilt University | Burd C.G.,University of Pennsylvania
Trends in Cell Biology | Year: 2011

Phosphatidylinositol 4-kinases (PI4Ks) regulate vesicle-mediated export from the Golgi apparatus via phosphatidylinositol 4-phosphate (PtdIns4. P) binding effector proteins that control vesicle budding reactions and regulate membrane dynamics. Evidence has emerged from the characterization of Golgi PI4K effectors that vesicle budding and lipid dynamics are tightly coupled via a regulatory network that ensures that the appropriate membrane composition is established before a transport vesicle buds from the Golgi. An important hub of this network is protein kinase D, which regulates the activity of PI4K and several PtdIns4. P effectors that control sphingolipid and sterol content of Golgi membranes. Other newly identified PtdIns4. P effectors include Vps74/GOLPH3, a phospholipid flippase called Drs2 and Sec2, a Rab guanine nucleotide exchange factor (GEF). These effectors orchestrate membrane transformation events facilitating vesicle formation and targeting. In this review, we discuss how PtdIns4. P signaling is integrated with membrane biosynthetic and vesicle budding machineries to potentially coordinate these crucial functions of the Golgi apparatus. © 2010 Elsevier Ltd.


Warfel J.M.,Center for Biologics Evaluation and Research | Edwards K.M.,Vanderbilt University
Current Opinion in Immunology | Year: 2015

Pertussis has re-emerged as an important public health concern. In the 1990s whole-cell pertussis vaccines were replaced with less reactogenic acellular vaccines consisting of purified pertussis components. However, recent data show that protection from acellular pertussis vaccines is not long-lasting. Antibody levels wane rapidly following vaccination, likely a result of the inability of acellular pertussis antigens to stimulate long-lasting B cell memory. In addition, T cell responses to acellular pertussis vaccines are mixed Th2/Th1, while whole-cell pertussis vaccination and infection stimulate Th17 responses, important for host defense against extracellular mucosal pathogens. Consistent with this T cell skewing, acellular vaccines did not prevent colonization or transmission following challenge in nonhuman primates while whole-cell vaccinated and previously infected animals cleared the infection more rapidly. © 2015 Elsevier Ltd.


Yang L.,U.S. National Cancer Institute | Pang Y.,U.S. National Cancer Institute | Moses H.L.,Vanderbilt University
Trends in Immunology | Year: 2010

Transforming growth factor β (TGF-β) plays an important role in tumor initiation and progression, functioning as both a suppressor and a promoter. The mechanisms underlying this dual role of TGF-β remain unclear. TGF-β exerts systemic immune suppression and inhibits host immunosurveillance. Neutralizing TGF-β enhances CD8+ T-cell- and NK-cell-mediated anti-tumor immune responses. It also increases neutrophil-attracting chemokines resulting in recruitment and activation of neutrophils with an antitumor phenotype. In addition to its systemic effects, TGF-β regulates infiltration of inflammatory/immune cells and cancer-associated fibroblasts in the tumor microenvironment causing direct changes in tumor cells. Understanding TGF-β regulation at the interface of tumor and host immunity should provide insights into developing effective TGF-β antagonists and biomarkers for patient selection and efficacy of TGF-β antagonist treatment.


Patent
University of Pennsylvania and Vanderbilt University | Date: 2012-10-17

Provided are compositions for inhibiting a biological activity of an aldoketo reductase family 1, member C3 (AKR1 C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1 C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.


Patent
Vanderbilt University and University of Pennsylvania | Date: 2016-10-12

Provided are compositions for inhibiting a biological activity of an aldo-keto reductase family 1, member C3 (AKR1C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.


Patent
Vanderbilt University and University of Pennsylvania | Date: 2016-04-19

Provided are compositions for inhibiting a biological activity of an aldo-keto reductase family 1, member C3 (AKR1C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.


McCaffrey L.M.,McGill University | Montalbano J.,University of Virginia | Mihai C.,McGill University | Macara I.G.,Vanderbilt University
Cancer Cell | Year: 2012

Loss of epithelial organization is a hallmark of carcinomas, but whether polarity regulates tumor growth and metastasis is poorly understood. To address this issue, we depleted the Par3 polarity gene by RNAi in combination with oncogenic Notch or Ras61L expression in the murine mammary gland. Par3 silencing dramatically reduced tumor latency in both models and produced invasive and metastatic tumors that retained epithelial marker expression. Par3 depletion was associated with induction of MMP9, destruction of the extracellular matrix, and invasion, all mediated by atypical PKC-dependant JAK/Stat3 activation. Importantly, Par3 expression is significantly reduced in human breast cancers, which correlates with active aPKC and Stat3. These data identify Par3 as a regulator of signaling pathways relevant to invasive breast cancer. © 2012 Elsevier Inc.


Ye J.,Louisiana State University | McGuinness O.P.,Vanderbilt University
American Journal of Physiology - Endocrinology and Metabolism | Year: 2013

Chronic inflammation is a characteristic of obesity and is associated with accompanying insulin resistance, a hallmark of type 2 diabetes mellitus (T2DM). Although proinflammatory cytokines are known for their detrimental effects on adipose tissue function and insulin sensitivity, their beneficial effects in the regulation of metabolism have not drawn sufficient attention. In obesity, inflammation is initiated by a local hypoxia to augment angiogenesis and improve adipose tissue blood supply. A growing body of evidence suggests that macrophages and proinflammatory cytokines are essential for adipose remodeling and adipocyte differentiation. Phenotypes of multiple lines of transgenic mice consistently suggest that proinflammatory cytokines increase energy expenditure and act to prevent obesity. Removal of proinflammatory cytokines by gene knockout decreases energy expenditure and induces adult-onset obesity. In contrast, elevation of proinflammatory cytokines augments energy expenditure and decreases the risk for obesity. Anti-inflammatory therapies have been tested in more than a dozen clinical trials to improve insulin sensitivity and glucose homeostasis in patients with T2DM, and the results are not encouraging. One possible explanation is that anti-inflammatory therapies also attenuate the beneficial effects of inflammation in stimulating energy expenditure, which may have limited the efficacy of the treatment by promoting energy accumulation. Thus, the positive effects of proinflammatory events should be considered in evaluating the impact of inflammation in obesity and type 2 diabetes. © 2013 the American Physiological Society.


Yu H.-Y.,Kaiser Permanente | Friedlander D.F.,Vanderbilt University | Patel S.,Boston University | Hu J.C.,University of California at Los Angeles
CA Cancer Journal for Clinicians | Year: 2013

Answer questions and earn CME/CNE The use of robotic assistance facilitates minimally invasive surgery and has been widely adopted across multiple specialties. This article reviews the published literature on use of this technology for treatment of oncologic conditions. PubMed searches were performed for articles published between 2000 and 2012 using the keywords "robotic" or "robotic surgery" in conjunction with "oncology" or "cancer." Although the most common use for robotics was to treat urologic oncologic conditions, it has also been widely adopted for gynecologic, general, thoracic, and head and neck surgeries. For several procedures, there is evidence that robotics offers short-term benefits such as shorter lengths of stay and lower intraoperative blood loss, with safety profiles and oncologic outcomes comparable to open or conventional laparoscopic approaches. However, long-term oncologic outcomes are generally lacking, and robotic surgeries are more costly than open or laparoscopic surgeries. Robotic technology is widely used in oncologic surgery with demonstrated short-term advantages. However, whether the benefits of robotics justify the higher costs warrant large comparative effectiveness studies with long-term outcomes. © 2012 American Cancer Society. Copyright © 2012 American Cancer Society, Inc.


Grant
Agency: National Aeronautics and Space Administration | Branch: | Program: STTR | Phase: Phase I | Award Amount: 125.00K | Year: 2013

Longhurst Engineering, PLC, and Vanderbilt University propose an in-space friction stir welding (FSW) machine for joining complex structural aluminum components. The proposed FSW machine is innovative because it can be deployed by 2 people and be used to weld complex surfaces that extend beyond linear welding applications. The in-space FSW machine is a 3 axis system that can be mounted to work pieces of varying geometry, position, and orientation through the use of a high performance vacuum system or mechanical clamps. The key enabler of the proposed FSW machine is a self adjusting and self aligning FSW (SAA-FSW) tool that eliminates the need for automated actuators. In addition, a collection of force reduction techniques will be included as part of the system. When combined together, it is theorized that the effect will be significant and will lead to the advancement of FSW by reducing structural rigidity requirements of FSW machines.Our work plan begins by determining the net effect of the combined force reduction techniques. Substantial effort is given to the development of a preliminary SAA-FSW tool which includes experimental welding. Lastly, a preliminary set of engineering plans will be delivered based upon the results from the development of the SAA-FSW tool and force reduction techniques.


Walczak C.E.,Indiana University Bloomington | Gayek S.,Vanderbilt University | Ohi R.,Vanderbilt University
Annual Review of Cell and Developmental Biology | Year: 2013

The microtubule (MT) cytoskeleton supports a broad range of cellular functions, from providing tracks for intracellular transport, to supporting movement of cilia and flagella, to segregating chromosomes in mitosis. These functions are facilitated by the organizational and dynamic plasticity of MT networks. An important class of enzymes that alters MT dynamics is the depolymerizing kinesin-like proteins, which use their catalytic activities to regulate MT end dynamics. In this review, we discuss four topics surrounding these MT-depolymerizing kinesins. We provide a historical overview of studies focused on these motors and discuss their phylogeny. In the second half, we discuss their enzymology and biophysics and give an overview of their known cellular functions. This discussion highlights the fact that MT-depolymerizing kinesins exhibit a diverse range of design principles, which in turn increases their functional versatility in cells. © 2013 by Annual Reviews. All rights reserved.


McMahon D.G.,Vanderbilt University | Iuvone P.M.,Emory University | Tosini G.,Morehouse School of Medicine
Progress in Retinal and Eye Research | Year: 2014

The retinal circadian system represents a unique structure. It contains a complete circadian system and thus the retina represents an ideal model to study fundamental questions of how neural circadian systems are organized and what signaling pathways are used to maintain synchrony of the different structures in the system. In addition, several studies have shown that multiple sites within the retina are capable of generating circadian oscillations. The strength of circadian clock gene expressionand the emphasis of rhythmic expression are divergent across vertebrate retinas, with photoreceptors as the primary locus of rhythm generation in amphibians, while in mammals clock activity is most robust in the inner nuclear layer. Melatonin and dopamine serve as signaling molecules to entrain circadian rhythms in the retina and also in other ocular structures. Recent studies have also suggested GABA as an important component of the system that regulates retinal circadian rhythms. These transmitter-driven influences on clock molecules apparently reinforce the autonomous transcription-translation cycling of clock genes. The molecular organization of the retinal clock is similar to what has been reported for the SCN although inter-neural communication among retinal neurons that form the circadian network is apparently weaker than those present in the SCN, and it is more sensitive to genetic disruption than the central brain clock. The melatonin-dopamine system is the signaling pathway that allows the retinal circadian clock to reconfigure retinal circuits to enhance light-adapted cone-mediated visual function during the day and dark-adapted rod-mediated visual signaling at night. Additionally, the retinal circadian clock also controls circadian rhythms in disk shedding and phagocytosis, and possibly intraocular pressure. Emerging experimental data also indicate that circadian clock is also implicated in the pathogenesis of eye disease and compelling experimental data indicate that dysfunction of the retinal circadian system negatively impacts the retina and possibly the cornea and the lens. © 2013 Elsevier Ltd.


Rodriguez-Boulan E.,City College of New York | Macara I.G.,Vanderbilt University
Nature Reviews Molecular Cell Biology | Year: 2014

Epithelial cells require apical-basal plasma membrane polarity to carry out crucial vectorial transport functions and cytoplasmic polarity to generate different cell progenies for tissue morphogenesis. The establishment and maintenance of a polarized epithelial cell with apical, basolateral and ciliary surface domains is guided by an epithelial polarity programme (EPP) that is controlled by a network of protein and lipid regulators. The EPP is organized in response to extracellular cues and is executed through the establishment of an apical-basal axis, intercellular junctions, epithelial-specific cytoskeletal rearrangements and a polarized trafficking machinery. Recent studies have provided insight into the interactions of the EPP with the polarized trafficking machinery and how these regulate epithelial polarization and depolarization. © 2014 Macmillan Publishers Limited. All rights reserved.


Patent
Rutgers University and Vanderbilt University | Date: 2012-07-25

Methods for regulating cancer cell growth and survival, inhibiting cancer cell growth, promoting cancer cell death, and/or treating a cancer make use of antagonists of a type I BMP receptor. In some embodiments the cancer is a lung cancer and the cancer cell is a lung cancer cell.


Grant
Agency: Department of Defense | Branch: Navy | Program: STTR | Phase: Phase I | Award Amount: 79.93K | Year: 2015

This STTR will focus on demonstrating feasible methods to integrate additive manufacturing (AM) structure, processing, and property-geometry modeling methods that will facilitate the qualification and certification of AM-fabricated 4340 steel alloy parts and enable their rapid deployment. During the Phase I feasibility demonstrations the contractor and Research Institute (RI) will define and develop a concept for innovative real-time process models for AM of 4340 robotic pulsed-arc, wire feed materials. They will demonstrate the feasibility to monitor and model the fabrication process and predict the resulting material micro-structures and mechanical properties of the fabricated materials and conduct an initial structural test to confirm properties of the feature shape.

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