Single Action Potentials and Subthreshold Electrical Events Imaged in Neurons with a Fluorescent Protein Voltage Probe

Jin, L.,Han, Z.,Platisa, J.,Wooltorton, Julian R.A.,Cohen, Lawrence B.,Pieribone, Vincent A. Cell Press 2012 Neuron Vol.75 No.5

Monitoring neuronal electrical activity using fluorescent protein-based voltage sensors has been limited by small response magnitudes and slow kinetics of existing probes. Here we report the development of a fluorescent protein voltage sensor, named ArcLight, and derivative probes that exhibit large changes in fluorescence intensity in response to voltage changes. ArcLight consists of the voltage-sensing domain of Ciona intestinalis voltage-sensitive phosphatase and super ecliptic pHluorin that carries the point mutation A227D. The fluorescence intensity of ArcLight A242 decreases by 35% in response to a 100mV depolarization when measured in HEK293 cells, which is more than five times larger than the signals from previously reported fluorescent protein voltage sensors. We show that the combination of signal size and response speed of these new probes allows the reliable detection of single action potentials and excitatory potentials in individual neurons and dendrites.

Poster Presentation Abstracts ; Effects of Flavonoids on Cytosolic Phospholipase A2 in Guinea-pig Epidermis

(Hyun Pyo Kim),(Vincent A . Ziboh) 한국응용약물학회 1999 학술대회 Vol.1999 No.2

ACCURACY AND EFFICIENCY OF A COUPLED NEUTRONICS AND THERMAL HYDRAULICS MODEL

MICHAEL A. POPE,VINCENT A. MOUSSEAU 한국원자력학회 2009 Nuclear Engineering and Technology Vol.41 No.7

This manuscript will discuss a numerical method where the six equations of two-phase flow, the solid heat conduction equations, and the two equations that describe neutron diffusion and precursor concentration are solved together in a tightly coupled, nonlinear fashion for a simplified model of a nuclear reactor core. This approach has two important advantages. The first advantage is a higher level of accuracy. Because the equations are solved together in a single nonlinear system, the solution is more accurate than the traditional “operator split” approach where the two-phase flow equations are solved first, the heat conduction is solved second and the neutron diffusion is solved third, limiting the temporal accuracy to 1st order because the nonlinear coupling between the physics is handled explicitly. The second advantage of the method described in this manuscript is that the time step control in the fully implicit system can be based on the timescale of the solution rather than a stability-based time step restriction like the material Courant limit required of operator-split methods. In this work, a pilot code was used which employs this tightly coupled, fully implicit method to simulate a reactor core. Results are presented from a simulated control rod movement which show 2nd order accuracy in time. Also described in this paper is a simulated rod ejection demonstrating how the fastest timescale of the problem can change between the state variables of neutronics, conduction and two-phase flow during the course of a transient.

ACCURACY AND EFFICIENCY OF A COUPLED NEUTRONICS AND THERMAL HYDRAULICS MODEL

Pope, Michael A.,Mousseau, Vincent A. Korean Nuclear Society 2009 Nuclear Engineering and Technology Vol.41 No.7

This manuscript will discuss a numerical method where the six equations of two-phase flow, the solid heat conduction equations, and the two equations that describe neutron diffusion and precursor concentration are solved together in a tightly coupled, nonlinear fashion for a simplified model of a nuclear reactor core. This approach has two important advantages. The first advantage is a higher level of accuracy. Because the equations are solved together in a single nonlinear system, the solution is more accurate than the traditional "operator split" approach where the two-phase flow equations are solved first, the heat conduction is solved second and the neutron diffusion is solved third, limiting the temporal accuracy to $1^{st}$ order because the nonlinear coupling between the physics is handled explicitly. The second advantage of the method described in this manuscript is that the time step control in the fully implicit system can be based on the timescale of the solution rather than a stability-based time step restriction like the material Courant limit required of operator-split methods. In this work, a pilot code was used which employs this tightly coupled, fully implicit method to simulate a reactor core. Results are presented from a simulated control rod movement which show $2^{nd}$ order accuracy in time. Also described in this paper is a simulated rod ejection demonstrating how the fastest timescale of the problem can change between the state variables of neutronics, conduction and two-phase flow during the course of a transient.

A Mouse Model for Conditional Secretion of Specific Single-Chain Antibodies Provides Genetic Evidence for Regulation of Cortical Plasticity by a Non-cell Autonomous Homeoprotein Transcription Factor

Bernard, Clé,mence,Vincent, Clé,mentine,Testa, Damien,Bertini, Eva,Ribot, Jé,rô,me,Di Nardo, Ariel A.,Volovitch, Michel,Prochiantz, Alain Public Library of Science 2016 PLoS genetics Vol.12 No.5

<▼1><P>During postnatal life the cerebral cortex passes through critical periods of plasticity allowing its physiological adaptation to the environment. In the visual cortex, critical period onset and closure are influenced by the non-cell autonomous activity of the Otx2 homeoprotein transcription factor, which regulates the maturation of parvalbumin-expressing inhibitory interneurons (PV cells). In adult mice, the maintenance of a non-plastic adult state requires continuous Otx2 import by PV cells. An important source of extra-cortical Otx2 is the choroid plexus, which secretes Otx2 into the cerebrospinal fluid. Otx2 secretion and internalization requires two small peptidic domains that are part of the DNA-binding domain. Thus, mutating these “transfer” sequences also modifies cell autonomous transcription, precluding this approach to obtain a cell autonomous-only mouse. Here, we develop a mouse model with inducible secretion of an anti-Otx2 single-chain antibody to trap Otx2 in the extracellular milieu. Postnatal secretion of this single-chain antibody by PV cells delays PV maturation and reduces plasticity gene expression. Induced adult expression of this single-chain antibody in cerebrospinal fluid decreases Otx2 internalization by PV cells, strongly induces plasticity gene expression and reopens physiological plasticity. We provide the first mammalian genetic evidence for a signaling mechanism involving intercellular transfer of a homeoprotein transcription factor. Our single-chain antibody mouse model is a valid strategy for extracellular neutralization that could be applied to other homeoproteins and signaling molecules within and beyond the nervous system.</P></▼1><▼2><P><B>Author Summary</B></P><P>Classically, cell signaling is based on the secretion of molecules that bind cell surface receptors. Lipophilic agents can do without cell-surface receptors due to their ability to diffuse through the plasma membrane, but this is normally not the case for proteins, which cannot pass the membrane barrier. However, homeoprotein transcription factors represent an exception as they are secreted and internalized by live cells owing to two peptidic domains. An important illustration of this novel signaling mechanism is provided by Otx2, a homeoprotein that travels from the choroid plexus to specific inhibitory neurons in the cerebral cortex, where it regulates physiological plasticity throughout life. Because the two transfer peptides are in the DNA-binding domain of Otx2, it is impossible to mutate them without altering both cell signaling and cell-autonomous functions. We have therefore developed a mouse in which a secreted anti-Otx2 single-chain antibody can be induced to trap extracellular Otx2 while leaving its cell autonomous function untouched. We show that neutralizing extracellular Otx2 modifies the expression of plasticity genes in the visual cortex, thus providing the first genetic demonstration for homeoprotein signaling in a mammal.</P></▼2>

PHYTOREMEDIATION POTENTIAL OF IXORA COCCINEA IN PB CONTAMINATED SOILS

Sacramento. Jan Vincent A,Javier. Karlo John,Geronimo. Franz Kevin F,Cleofas. Dolores. S.D,Rubio Christabel Jane P. 한국방재학회 2017 Journal of Disaster Management Vol.2 No.3

Numerous methods have been operated to relieve the environment of contamination of heavy metals. One of which is the use of chemical and thermal technology. However, this method was proven to be costly and operates far less than the optimum. It was discovered that plants can detoxify soils, therefore resulting in cleaner groundwater free from heavy metal contamination, a method referred to as phytoremediation. In this study, the ability of Ixora Coccinea to aid in phytoremediation was evaluated. Sixty-day old Ixora Coccinea plants were replanted in pots containing 1.3kg of soil mixed thoroughly with a lead (Pb) and distilled water solution with a concentration of 16.9 mg/ml. Every 15 days, for a period of 90 days, three plants were harvested for laboratory analysis testing. The samples were acid digested and analyzed of its Pb content using Inductively Coupled Plasma (ICP). The reduction of Pb gradually increased with respect to time, attaining a maximum of 38.1% reduction on day 60 of culture, but declined afterwards. On average, the Pb uptake rate of Ixora Coccinea was 15.3%. In a patch of land, plants spaced 240mm away from each other would absorb a maximum of 127.1 mg/kg of Pb with a depth of 200mm.

Successful Trastuzumab-Deruxtecan Rechallenge After Interstitial Lung Disease: A Case Report

Vincent A. de Weger,Tim Schutte,Inge R.H.M. Konings,Catharina Willemien Menke-van der Houven van Oordt 한국유방암학회 2023 Journal of breast cancer Vol.26 No.5

Trastuzumab deruxtecan (T-DXd) is used to treat human epidermal growth factor receptor 2-positive advanced breast cancer. Interstitial lung disease (ILD) is a severe adverse event associated with T-DXd. Current guidelines recommend permanent discontinuation of T-DXd after Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 ILD. Here, we describe a case of successful rechallenge with T-DXd after CTCAE grade 2 treatment-induced ILD. After discontinuation of T-DXd, ILD was treated with steroids until complete resolution. Given the initial beneficial antitumor response, retreatment was discussed during disease progression. In a shared decision with the patient, T-DXd was restarted at the lowest registered dose, along with low-dose steroids. ILD did not reoccur. Importantly, both clinical and radiological responses to the treatment were observed, with an improvement in the patient’s quality of life. This case demonstrates that retreatment with T-DXd after a grade 2 ILD event is feasible and yields clinical benefit.

Porphyrins Fused with Strongly Electron-Donating 1,3-Dithiol-2-ylidene Moieties: Redox Control by Metal Cation Complexation and Anion Binding

Bill, Nathan L.,Ishida, Masatoshi,Bä,hring, Steffen,Lim, Jong Min,Lee, Sangsu,Davis, Christina M.,Lynch, Vincent M.,Nielsen, Kent A.,Jeppesen, Jan O.,Ohkubo, Kei,Fukuzumi, Shunichi,Kim, Dongho,S American Chemical Society 2013 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.135 No.29

<P>A new class of redox-active free base and metalloporphyrins fused with the 1,3-dithiol-2-ylidene subunits present in tetrathiafulvalene, termed MTTFP (M = H<SUB>2</SUB>, Cu, Ni, Zn), have been prepared and characterized. The strong electron-donating properties of MTTFP were probed by electrochemical measurement and demonstrated that oxidation potentials can be tuned by metalation of the free base form, H<SUB>2</SUB>TTFP. X-ray crystal structures of H<SUB>2</SUB>TTFP, ZnTTFP, and CuTTFP revealed that a severe saddle-shape distortion was observed with the dithiole rings bent out of the plane toward one another in the neutral form. In contrast, the structure of the two-electron oxidized species (CuTFFP<SUP>2+</SUP>) is planar, corresponding to a change from a nonaromatic to aromatic structure upon oxidation. A relatively large two-photon absorption (TPA) cross-section value of H<SUB>2</SUB>TTFP<SUP>2+</SUP> (1200 GM) was obtained for the free base compound, a value that is much higher than those typically seen for porphyrins (<100 GM). Augmented TPA values for the metal complexes were also seen. The strong electron-donating ability of ZnTTFP was further enhanced by binding of Cl<SUP>–</SUP> and Br<SUP>–</SUP> as revealed by thermal electron-transfer between ZnTTFP and Li<SUP>+</SUP>-encapsulated C<SUB>60</SUB> (Li<SUP>+</SUP>@C<SUB>60</SUB>) in benzonitrile, which was “switched on” by the addition of either Cl<SUP>–</SUP> or Br<SUP>–</SUP> (as the tetrabutylammonium salts). The X-ray crystal structure of Cl<SUP>–</SUP>-bound ZnTTFP was determined and provided support for the strong binding between the Cl<SUP>–</SUP> anion and the Zn<SUP>2+</SUP> cation present in ZnTTFP.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2013/jacsat.2013.135.issue-29/ja404830y/production/images/medium/ja-2013-04830y_0015.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja404830y'>ACS Electronic Supporting Info</A></P>

Gravitation search-based hybrid algorithm for solving inverse kinematics of an n -link redundant manipulator

S A R Sheik Masthan,Kanagaraj G,Yu Vincent F 한국CDE학회 2023 Journal of computational design and engineering Vol.10 No.5

Inverse kinematics is one of the most complicated problems in robotics. The inverse kinematics calculation is the basis for any industrial robot’s ability to plan and follow a trajectory. This paper proposes a hybrid algorithm, e3GSA, based on the gravitational search algorithm (GSA) for solving the inverse kinematics problem of an n-link redundant robot manipulator. The algorithm’s efficiency was evaluated using a fitness function comprising of position error, orientation error, and collision error, and it was found to perform better than the conventional GSA in simulations. A generalized framework was proposed and tested by simulating a 6-, 8-, and 12-link robot manipulators. Experimental validation is carried out using a 6-link robot manipulator, which shows that the simulation data are on par with the experimental data. The proposed algorithm was also found to perform adaptively with faster convergence rates and lesser computation time, making it a better choice for other engineering problems that can be transformed into optimization problems.

Portal cavernography during endoscopic retrograde cholangiopancreatography: from bilhemia to hemobilia

Rawad A. Yared,Paraskevas Gkolfakis,Arnaud Lemmers,Vincent Huberty,Thierry Degrez,Jacques Devière,Daniel Blero 대한소화기내시경학회 2023 Clinical Endoscopy Vol.56 No.4

Portobiliary fistulas are rare but may lead to life-threatening complications. Biliary plastic stent-induced portobiliary fistulas during endoscopic retrograde cholangiopancreatography have been described. Herein, we present a case of portal cavernography and recurrent hemobilia after endoscopic retrograde cholangiopancreatography in which a portobiliary fistula was detected in a patient with portal biliopathy. This likely indicates a change in clinical presentation (from bilhemia to hemobilia) after biliary drainage that was successfully treated by placement of a fully covered, self-expandable metallic stent.