HERE WE PROPOSE THAT PROPERLY DESIGNED NANOWIRES AT THE INTERFACE BETWEEN TWO MATERIALS OF DIFFERING REFRACTIVE INDEX CREATE NEGLIGIBLE SHADOWING. MOST OPTOELECTRONIC DEVICES, SUCH AS SOLAR CELLS AND LIGHT EMITTING DIODES (LEDS), NEED ELECTRICAL CONTACTS ON THE TOP SURFACE OF THE DEVICE, BUT THESE CAUSE LIGHT REFLECTION AND ABSORPTION LOSSES. SO FAR THIS HAS BEEN VIEWED AS AN UNAVOIDABLE COMPROMISE LIMITING THE OVERALL ENERGY CONVERSION EFFICIENCY OF OPTOELECTRONIC DEVICES. INSTEAD WE PROPOSE THAT METALS CAN BE MADE, FOR MANY PRACTICAL PURPOSES, FULLY TRANSPARENT. OUR PRELIMINARY RESULTS SUGGEST THAT IT IS POSSIBLE TO HAVE ZERO, AND EVEN NEGATIVE EFFECTIVE SHADOW FACTORS, AND WE PROPOSE TO EXPERIMENTALLY DEMONSTRATE NANOSTRUCTURED TOP CONTACTS WITH NEAR ZERO SHADOW FACTORS IN A BROADBAND WAVELENGTH RANGE. THIS PROPOSAL MIGHT ENABLE A NEW GENERATION OF HIGHLY EFFICIENT SOLAR CELLS AND LIGHT EMITTING DIODES.

THE ENERGY STORAGE USING BATTERIES HAS BECOME A PRIORITY ISSUE, AND ONE OF THE MOST IMPORTANT RESEARCH LINES IS THE SEARCH FOR NEW MATERIALS FOR ELECTRODES IN NA-ION BATTERIES. THE PROPOSAL IS BASED ON AN ANOMALOUS RESULT OBTAINED RECENTLY DURING THE EVALUATION OF THIN LAYERS OF NIO ON COPPER AS A POSSIBLE ELECTRODE FOR NA-ION BATTERIES. THE USUAL MAXIMUM DISCHARGE CAPACITY DURING THE FIRST CHARGE-DISCHARGE CYCLES IS 400 MAHG-1, A VALUE THAT GRADUALLY DECREASES WITH THE NUMBER OF CYCLES. HOWEVER, IN THIS ANOMALOUS CASE, THE CYCLING BEHAVIOR WAS RADICALLY DIFFERENT, SINCE THERE IS A CONTINUOUS INCREASE IN THE CHARGE AND DISCHARGE CAPACITIES, REACHING VALUES AS HIGH AS 9300 MAHG-1 AT THE END OF THE CYCLING. THIS BEHAVIOR IS RELATED TO THE INTERACTION BETWEEN MATERIALS, AND THE FORMATION OF A NEW MATERIAL. THE FINAL GOAL OF THE PROPOSAL IS TO SYNTHESIZE THIS NEW MATERIAL THROUGH SEVERAL SPECIFIC OBJECTIVES: MODELING AND THERMODYNAMIC CALCULATION OF THE REACTIONS INVLOVED, PROCESSING OF THE NEW MATERIAL FROM COMMERCIAL PRODUCTS (NIO, CU, NA, SODIUM SALTS, ETC.) BASED ON THE RESULTS OF THE THERMODYNAMIC STUDY, AND OPTIMIZATION OF THE SYNTHESIS CONDITIONS CONSIDERING THE REACTION ATMOSPHERE, VOLTAGE AND CURRENT, PHYSICAL-CHEMICAL CHARACTERIZATION OF THE NEW MATERIAL BOTH FROM THE CHEMICAL COMPOSITION AND STRUCTURAL POINT OF VIEW, AND ELECTROCHEMICAL CHARACTERIZATION AS AN ELECTRODE FOR NA-ION BATTERIES. THE MOST IMPORTANT POINT OF THIS PROPOSAL IS THE FEASIBLE POSSIBILITY OF SYNTHESIZING THIS NEW MATERIAL WITH EXCELLENT PROPERTIES AS AN ELECTRODE FOR NA-ION BATTERIES, REACHING CAPACITY VALUES OF AT LEAST 10 TIMES THE CURRENT VALUES. IN ADDITION TO THIS HIGH SCIENTIFIC IMPACT, THIS MULTIDISCIPLINARY WORK WOULD BRING SOCIAL AND ECONOMIC ADVANTAGES IN THE DEVELOPMENT OF NEW LI-FREE BATTERIES AND REDUCTION OF FOSSIL FUEL CONSUMPTION.

SCIENTIFIC SPACE MISSIONS FOR THE COSMIC MICROWAVE BACKGROUND (CMB) STUDY HAVE BEEN HAPPENING FROM COBE TO PLANCK, WITH INCREASING RESOLUTION AND SENSITIVITY OF THEIR DETECTORS. AT PRESENT THERE ARE SEVERAL PROJECTS STILL NOT FUNDED BY THE SPACE AGENCIES --CORE (ESA), INDOCORE (ESA/ISRO), PICO (NASA)-- AND ONE IN PHASE A --LITEBIRD (JAXA)--, ALL OF THEM WITH THE MAIN OBJECTIVE OF DETECTING THE PRIMORDIAL BACKGROUND OF GRAVITATIONAL WAVES THROUGH THE PRECISE MEASUREMENT OF THE CMB POLARIZATION. FOR INSTRUMENTS PRESENTING THE REQUIRED LEVEL OF SENSITIVITY, IT IS NECESSARY TO DEVELOP NEW CALIBRATION STRATEGIES THAT ALLOW THE REDUCTION OF SYSTEMATIC ERRORS DOWN TO THE REQUIRED LEVEL, TO BE ABLE TO OPTIMALLY EXPLOIT THE LOW NOISE OF THE PROPOSED INSTRUMENTATION. UNTIL NOW, IN THE CMB SPACE MISSIONS, PLANETS, GALACTIC OBJECTS AS THE CRAB NEBULA AND EVEN THE MOON OR THE SUN, HAVE BEEN USED AS CALIBRATION SOURCES. HOWEVER THE EMITTED POLARIZED LIGHT OF THESE SOURCES IS NOT KNOWN IN THE OVERALL FREQUENCY RANGE OR WITH THE REQUIRED ACCURACY. WE PROPOSE A VIABILITY STUDY OF A LOW-COST AND SMALL ANCILLARY CALIBRATION SATELLITE THAT WOULD ALLOCATE, AS PAYLOAD, A SET OF SIGNAL SOURCES COVERING THE OVERALL OPERATION FREQUENCY BAND OF THE PARTICULAR SPACE MISSION¿S INSTRUMENTATION. THIS SATELLITE WOULD ALLOW KNOWING THE CALIBRATION SOURCE WITH THE ACCURACY REQUIRED TO ACHIEVE THE SCIENTIFIC GOALS. COST REDUCTION POSSIBILITIES, OFFERED BY THE USE OF PREDEFINED PLATFORMS AS CUBESAT, WILL BE STUDIED, AIMING FOR A BUDGET OF ABOUT SEVERAL MILLION EUROS. IN THIS PROJECT WE WILL FOCUS IN THE PROPOSAL LITEBIRD TO STUDY THE VIABILITY OF THE CALIBRATION SATELLITE, BUT THIS STUDY CAN BE EASILY APPLIED TO THE REST OF PREVIOUSLY CITED MISSIONS AND EVEN TO OTHER SCIENTIFIC MISSIONS OPERATING IN DIFFERENT FREQUENCY BANDS.

FUTURE SPACE SCIENCE MISSIONS AND INSTRUMENTATION IN GROUND BASED ARE, SO FAR, LIMITED BY THE AVAILABILITY OF HIGH SENTITVITY IMAGING DETECTOR ARRAY TECHNOLOGY FOR THE MM-FIR WAVELENGTH RANGE (3 MM TO 30 and 956;M). SUPERCONDUCTING KINETIC INDUCTANCE DETECTORS (KIDS) WERE PROPOSED, A DECADE AGO, TO PROVIDE LARGE FORMAT CAMERA DUE TO ITS INTRINSIC POSSIBILITY OF MULTIPLEXING IN THE FREQUENCY DOMAIN, ALLOWING THOUSANDS OF PIXELS TO BE READ OUT THROUGH A SINGLE CABLE. HOWEVER, THESE DETECTORS HAVE ALREADY DEMONSTRATED VERY LOW OPTICAL EFFICIENCY IN LOW BACKGROUND IN THE THZ RANGE AND, IN ADDITION, THEY OPERATE AT EXTREMELY LOW TEMPERATURE (FEW MK). AS A RESULT, AN ALTERNATIVE IS NECESSARY TO PROVIDE THE REQUIRED LARGE ARRAY DETECTOR OPERANTING IN THE THZ RANGE WITH SENSITIVITIES MATCHING THAT REQUIRED FOR FUTURE SPACE MISSIONS WITH LARGE CRYOGENIC TELESCOPES (4-6 K). IN THIS PROJECT, WE PROPOSE TO FOLLOW THE RECENTLY CLAIMED DETECTION OF A CHANGE OF KINETIC INDUCTANCE ON GRAPHENE WITH THE APPLIED VOLTAGE GATE EXPLORE THE POSIBILITY TO USE 2D MATERIALS FOR THE DEVELOPMENT OF A NEW GENERATION OF STATE-OF-THE-ART KINETIC INDUCTANCE DETECTOR FOR ASTRONOMICAL OBSERVATIONS IN THE FAR-IR. THIS TYPE OF 2D DETECTORS HAVE THE POTENTIAL TO OPEN A UNIQUE POSSIBILITY FOR SPACE OBSERVATORIES TO OPERATE WITH THE ULTIMATE SENSITIVITY, ONLY LIMITED BY THE LOW BACKGOUND PROVIDED BY CRIOGENIC TELESCOPES, KEEPING THE INTRISIC MULTIPLEXING CAPABILITY (LARGE CAMERAS) WITH THE ADVANTAGE TO OPERATE AT HIGHER TEMPERATURES ( 30K) THAN THE MOST SENSITIVE DETECTOR USED NOWADAYS (TENS OF MK). IN ADDITION, THIS TYPE OF NEW DETECTORS WILL BE USED IN A WIDE RANGE OF APPLICATIONS.

THE ULTIMATE GOAL OF THE VERSUS PROJECT IS THE FIRST OBSERVATION OF REPULSIVE CASIMIR-LIFSHITZ FORCES IN MACROSCOPIC PLANE-PARALLEL SYSTEMS. TO THIS END, IT WILL FOCUS ON THE DESIGN, FABRICATION, AND CHARACTERIZATION OF OPTICAL MATERIALS THAT ALLOW CONTROLLING THE INTENSITY AND NATURE OF THE CASIMIR-LIFSHITZ FORCE, SO THAT LEVITATION PHENOMENA CAN BE OBSERVED AND CHARACTERIZED DUE TO THE BALANCE BETWEEN THE LATTER AND GRAVITY FORCE. THIS RADICALLY NEW APPROACH MAKES USE OF OPTICAL SPECTROSCOPIC TECHNIQUES (BASED ON OPTICAL INTERFEROMETRY BETWEEN THE PARTIALLY REFLECTED AND TRANSMITTED LIGHT AT THE INTERFACES OF THE PLANE-PARALLEL SYSTEM) FOR CHARACTERIZING THE EQUILIBRIUM DISTANCE AT WHICH THE SYSTEM LEVITATES OVER A SUBSTRATE. ACCORDING TO VERY RECENT RESULTS ATTAINED BY THE APPLICANT GROUP, IT IS POSSIBLE TO FIND MATERIALS WHOSE OPTICAL CONSTANTS AND DENSITIES ARE SUCH THAT WHEN THEY ARE IMMERSED IN A FLUID THEY CAN LEVITATE OVER A SUBSTRATE AS A RESULT OF THE AFOREMENTIONED FORCE BALANCE. OUR GROUP HAS RECENTLY DEMONSTRATED THEORETICALLY THAT THERE IS A NUMBER OF MATERIALS THAT PREPARED IN THIN FILMS (< 1 MICROMETER) CAN LEVITATE SEVERAL TENS OR HUNDREDS OF NANOMETERS OVER A CAREFULLY SELECTED SUBSTRATE. SPECIFICALLY, THIN LAYERS MADE OF TEFLON, POLYSTYRENE OR SILICON DIOXIDE IMMERSED IN GLYCEROL ARE EXPECTED TO LEVITATE OVER A SILICON WAFER, BEING POSSIBLE TO TUNE THE EQUILIBRIUM DISTANCES AT WHICH SUCH LAYERS WILL BE SUSPENDED THROUGH THEIR THICKNESSES AND TEMPERATURE OF THE SYSTEM. THE DEVISED SELF-STANDING THIN FILMS (IN SINGLE LAYERS OR MULTILAYER ARRANGEMENTS) MUST BE COMPACT, MECHANICALLY STABLE, OF SMOOTH SURFACES, OF CONTROLLED THICKNESS, AND CHEMICALLY COMPATIBLE WITH THE FLUID IN WHICH THEY ARE IMMERSED. THE MACROSCOPIC OBSERVATION OF REPULSIVE CASIMIR-LIFSHITZ FORCES, NEVER REPORTED BEFORE, THROUGH OPTICAL SPECTROSCOPIC MEASUREMENTS WOULD CONSTITUTE AN UNPRECEDENTED MILESTONE IN THE FIELD OF FUNDAMENTAL MATTER INTERACTIONS.

OUR PROJECT PRESENTS A DEVICE BASED ON A REDOX FLOW CELL USING SEMI-SOLID ELECTRODES THAT OBVIATES THE NEED OF AN ION-SELECTIVE MEMBRANE. WE PROPOSE A COMPLETELY DIFFERENT CELL DESIGN THAT AVOIDS ITS NEED BY REVERTING THE REQUIREMENTS FOR ELECTRON AND ION CONDUCTORSAT THE PLACE OF THE ION-CONDUCTING MEMBRANE WE USE AN ELECTRON-CONDUCTING PLATE THAT BLOCKS ION FLOW. AT BOTH SIDES WE PLACE TWO FLOWABLE ELECTRODES. THE TWO DIFFERENT REDOX COUPLES ARE ELECTRONICALLY IN CONTACT THROUGH THE MIDDLE OF THE CELL, BUT AT OPEN CIRCUIT REACTIONS CANNOT PROCEED BECAUSE OF CHARGE ACCUMULATION AT BOTH SIDES, THAT CHARGES THE ELECTRODE-ELECTROLYTE INTERFACE. TO ACCESS THESE INTERFACES WE INTRODUCE A ¿WIRELESS¿ CONTACT TO THE FLOWABLE ELECTRODES. THIS CONTACT IS PROVIDED BY IONS RELEASED BY A CAPACITIVE HALF-CELL, WHICH WILL BE ABLE TO NEUTRALIZE THE IONIC ACCUMULATION IN THE MIDDLE COMPARTMENTS BY AN IONIC CURRENT, WHICH IN TURN WILL CHARGE ITS INTERFACE AND SUSTAIN AN ELECTRONIC CURRENT. THE CAPACITIVE HALF-CELLS MAY BE SEEN AS IONIC TO ELECTRONIC CURRENT TRANSLATORS. THE OVERALL DEVICE WILL THEN CONSIST OF TWO EXTERNAL CAPACITIVE HALF-CELLS SEPARATED BY THE TWO BATTERY HALF CELLS. THE COUPLED CAPACITIVE PART WILL BE A SEMI SOLID FLOWABLE CAPACITOR. THE COUPLING OF THE LOW-RATE BATTERY HALF-CELLS WITH THE CAPACITIVE PARTS EFFECTIVELY PROVIDES A BATTERY-SUPERCAPACITOR HYBRID DEVICE, ABLE TO POTENTIALLY ACHIEVE INTRINSICALLY HIGH POWER AND ENERGY. IN ADDITION, THE USE OF A DENSE SEPARATOR AVOIDS ANY MIXING BETWEEN THE ELECTROLYTES, AND MAKES POSSIBLE A COMPLETELY INDEPENDENT CHOICE OF BOTH, ANOLYTE AND CATHOLYTE. FOR A PROOF OF CONCEPT OF THIS DEVICE WE CHOSE AQUEOUS ZN/O2 AS BATTERY CHEMISTRY. THE SLUGGISH KINETICS OF METAL AIR BATTERIES WILL BE COMPENSATED BY THE CAPACITIVE COMPONENT, WHICH ALSO INFERS LONGER DURABILITY.

THIS IS A PROOF-OF-CONCEPT PROPOSAL: TO ESTABLISH WHETHER THE EXPRESSION OF A BACTERIAL B-LACTAMASE CAN BE USED AS A TOOL FOR MONITORING CHANGES IN THE LEVELS OF GENE EXPRESSION IN VIVO. THE SUCCESS OF THIS PROJECT WILL LEAD TO THE GENERATION OF TRANSGENIC ANIMALS OF GREAT VALUE IN PRECLINICAL RESEARCH. IN VIVO NONINVASIVE IMAGING IS THE TOOL OF CHOICE IN PRECLINICAL RESEARCH TO EVALUATE THE EVOLUTION OF DISEASES AND THEIR RESPONSE TO THERAPY. THE OBTAINING OF IN VIVO IMAGES OF GENES BY POSITRON EMISSION TOMOGRAPHY (PET) IS THE TECHNIQUE CHOSEN FOR THIS PURPOSE. THE CURRENT PET IRGS HAVE SEVERAL DRAWBACKS, BEING DIFFICULT TO DETERMINE TO WHAT EXTENT THE SIGNAL DETECTED IS DUE TO A TRANSCRIPTIONAL OR PHOSPHORYLATION CHANGE, INDEPENDENTLY OF THE PROMOTER ACTIVITY AND THE NON-SPECIFICITY DUE TO THE INTERACTION OF THE LABELED LIGAND WITH THE ENDOGENOUS PROTEINS. IN ADDITION, SOME OF THESE CONTROLS ARE HIGHLY IMMUNOGENIC, WHICH LIMITS THEIR USE TO IMMUNO-RESISTANT ANIMALS. TO OVERCOME THESE LIMITATIONS, WE PLAN TO DEVELOP AN IRG SYSTEM BASED ON THE EXPRESSION OF A MODIFIED FORM OF A BACTERIAL B-LACTAMASE. IT IS A MUTANT VARIANT IN THE CATALYTIC CENTER THAT BINDS IRREVERSIBLY TO B-LACTAM ANTIBIOTICS. THE AMOUNTS OF THIS B-LACTAMASE EXPRESSED FROM THE PROMOTER WILL BE QUANTIFIED BY PET, AFTER THE ADMINISTRATION OF AN AMPICILLIN DERIVATIVE (DOTA-AMPICILLIN), WITH HIGH AFFINITY FOR B-LACTAMASE, RADIOACTIVELY LABELED WITH GALLIUM (68GA). ACTION PLAN: 1) GENERATE A STABLE CELL LINE EXPRESSING THE B-LACTAMASE GENE UNDER THE CONTROL OF THE CYTOMEGALOVIRUS (CMV) PROMOTER; 2) INJECTION OF THE POSITIVE B-LACTAMASE CELLS IN MICE TO GENERATE A XENOGRAFT; 3) SYSTEMIC ADMINISTRATION OF 68GALLIUM-AMPICILLIN; AND 4) IMAGE OF THE IN VIVO DISTRIBUTION BY PET.

THE ABILITY TO DETECT AND MEASURE NON-INVASIVELY THE PROPAGATION OF ELECTRICAL ACTIVITY ALONG A NEURAL PATHWAY IN REAL TIME AND WITH A SPATIAL RESOLUTION THAT ALLOWS THE IDENTIFICATION OF THE ANATOMICAL PATH IN THE WORKING HUMAN BRAIN IS AMONG THE MOST RELEVANT, AMBITIOUS AND SO FAR UNSOLVED PROBLEMS IN NEUROSCIENCE. TECHNOLOGIES SUCH AS ELECTRO-ENCEPHALOGRAPHY (EEG) AND MAGNETO-ENCEPHALOGRAPHY (MEG) OR FUNCTIONAL MAGNETIC RESONANCE IMAGING (FMRI) HAVE NOT ACCOMPLISHED THIS TASK YET. THE MAIN AIM OF THIS PROPOSAL IS TO DEMONSTRATE THAT A NEW TECHNIQUE GROUNDED ON BASIC ANATOMICAL, PHYSIOLOGICAL AND PHYSICAL-CHEMICAL PRINCIPLES AND DIFFUSION IMAGING THEORY WILL ALLOW US TO DERIVE DIRECT MEASUREMENTS OF ELECTRICAL ACTIVITY IN ANATOMICAL BRAIN CONNECTIONS IN VIVO. NON-INVASIVE FUNCTIONAL MAGNETIC RESONANCE IMAGING (FMRI) ALLOWS US TO MAP THE DISTRIBUTED NEURAL SYSTEMS ACTIVATED BY SPECIFIC PARADIGMS. HOWEVER, THE DYNAMIC ELECTRICAL ACTIVITY CARRIED BY THE THOUSANDS OF CONNECTIONS BETWEEN THESE BRAIN AREAS REMAINS TO BE ELUCIDATED. MEASUREMENTS OF WATER MOLECULE DIFFUSION ALONG FIBER TRACTS BY DIFFUSION MAGNETIC RESONANCE IMAGING PROVIDES A STATIC MAP THE NEURAL CONNECTIONS BETWEEN BRAIN CENTERS, BUT DOES NOT CAPTURE THE ELECTRICAL ACTIVITY ALONG THE AXONS OF THESE FIBER TRACTS. HEREIN WE PROPOSE TO TEST A MODEL FOR DIFFUSION MRI BASED ON A HYPOTHESIZED ¿ANISOTROPY REDUCTION DUE TO AXONAL EXCITATION¿ (¿AREX¿) AND EXAMINE THE POTENTIAL CHANGES IN WATER MOBILITY ACCOMPANYING THE MOVEMENT OF IONS DURING THE PROPAGATION OF ACTION POTENTIALS ALONG AXONAL TRACTS. AS THIS MODEL EXAMINES THE PERPENDICULAR MOVEMENT OF WATER MOLECULES (ACCOMPANYING THE MOVEMENT OF IONS) DUE TO THE PROPAGATION OF ACTION POTENTIALS ALONG AXONAL TRACTS, WE PROPOSE THAT THE MEASUREMENT OF WATER MOLECULE DIFFUSION THAT RELIES ON THESE DYNAMIC PROPERTIES OF AXON TRACTS BE TERMED DYNAMIC DIFFUSION IMAGING (DDI).

TUBERCULOSIS (TB) IS AMONG THE TOP TEN CAUSES OF DEATH WORLDWIDE. ACCURATE DIAGNOSTICS THAT LEAD TO PROPER DRUG TREATMENT REGIMES PLAY, ALONG WITH A THOROUGH SURVEILLANCE, A KEY ROLE IN THE CONTROL OF THE DISEASE. WHOLE GENOME SEQUENCING (WGS) HAS DEMONSTRATED TO BE A PROMISING TOOL FOR THE CONTROL OF TUBERCULOSIS, BEING CAPABLE OF SIMULTANEOUSLY PREDICTING DRUG RESISTANT PHENOTYPES AND ESTABLISHING DETAILED EPIDEMIOLOGICAL RELATIONSHIPS. IN THIS PROJECT, WE AIM TO CAPTURE AND SEQUENCE TUBERCULOSIS FROM AIR DROPLETS RELEASED BY TB INFECTED PATIENTS, INSTEAD OF THE TRADITIONAL SPUTUM SAMPLE. BACILLARY LOAD IS EXPECTED TO BE LOWER IN AIR DROPLETS THAN IN SPUTUM, YET IT PRESENTS SEVERAL ADVANTAGES, CONTAINING MUCH LESS AMOUNT OF HUMAN DNA, INHIBITORS, AND BEING MUCH MORE HOMOGENEOUS AND CLEAN SAMPLES. THIS, COUPLED TO TB ENRICHMENT PROTOCOLS DEVELOPED IN OUR LABORATORY DURING SAF2013, WILL ALLOW US TO ACHIEVE UNPRECEDENTED SENSITIVITY PERFORMING WGS IN RESPIRATORY SAMPLES. REMARKABLY, SEQUENCING TB FROM AIR DROPLETS, WILL ALLOW ACCESS TO THE GENOME OF THE INFECTING AGENT THAT IS BEING TRULY TRANSMITTED, OPENING NEW PATHS TO THE RESEARCH AND UNDERSTANDING OF TB EPIDEMIOLOGY. PARTICULARLY, THIS WILL MAKE A GREAT DIFFERENCE REGARDING PATIENTS WITH LIGHT SYMPTOMS, FOR WHOM OBTAINING A SPUTUM IS NOT POSSIBLE. WE WILL ACHIEVE THIS BY USING A SIMPLE AND AFFORDABLE DEVICE, WHICH CONSISTS IN A MODIFIED MASK WITH RETENTION FILTERS THAT WILL CAPTURE THE EXHALED BACILLI DURING PATIENT BREATHING AND COUGHING. AFTER APPLYING OUR TB ENRICHMENT METHODS, WE WILL DECIDE TO EITHER, PROCEED WITH DIRECT WGS, OR FIRST PERFORM A WHOLE GENOME AMPLIFICATION. IN ORDER TO MAKE THIS DECISION, WE WILL DEVELOP A MULTIPLEX QPCR ASSAY, CAPABLE OF QUANTIFYING BACTERIAL, HUMAN AND TB DNA IN A SINGLE REACTION. IF SUCCESSFUL, THIS DEVICE AND MOLECULAR PROTOCOLS WOULD BE EASILY IMPROVED AND DEVELOPED FOR A PATENT, ALLOWING THEREFORE AN EASY TRANSFERENCE TO DEVELOPING COUNTRIES DUE TO ITS MINIMAL COSTS

UNDERSTANDING THE DEVELOPMENTAL MECHANISMS THAT UNDERLIE THE INCREASE IN SIZE AND FUNCTIONAL COMPLEXITY OF THE HUMAN CEREBRAL CORTEX IS A FUNDAMENTAL CHALLENGE OF BASIC RESEARCH, THE IMPACT OF WHICH EXTENDS FROM BIOLOGY TO ANTHROPOLOGY. OUR CURRENT UNDERSTANDING OF THE EMERGENCE OF THE ANATOMICAL AND FUNCTIONAL NEURONAL ENSEMBLES DURING DEVELOPMENT IS ESSENTIALLY BASED ON DATA FROM RODENTS COMBINED WITH THE DOGMATIC RADIAL UNIT HYPOTHESIS. WHEREAS THIS HYPOTHESIS EXPLAINS MANY ASPECTS OF CORTICAL DEVELOPMENT IN RODENTS WITH A SMALL AND SMOOTH CORTEX, IT IS INSUFFICIENT TO EXPLAIN THE DEVELOPMENT AND FOLDING OF THE MUCH LARGER AND COMPLEX CEREBRAL CORTEX OF HIGHER MAMMALS, LIKE CARNIVORES AND PRIMATES INCLUDING HUMAN. WE HAVE PROPOSED THE RADIAL DIVERGENCE HYPOTHESIS, WHERE INDIVIDUAL PROGENITOR CELLS GIVE RISE TO SIBLING NEURONS THAT DISPERSE TANGENTIALLY TO FORM MULTIPLE ANATOMICAL AND FUNCTIONAL COLUMNS IN THE CORTEX, AND ITS FOLDING. THE CORTICLONES PROJECT WILL TEST THIS NOVEL AND GROUNDBREAKING HYPOTHESIS BY GENERATION A TRANSGENIC FERRET (WITH A FOLDED CORTEX) AND APPLYING A SPECTRUM OF INTERDISCIPLINARY AND COMPLEMENTARY APPROACHES. AFTER LABELING CLONES OF INDIVIDUAL CORTICAL NEURONS, WE WILL ANALYZE THEIR TOPOGRAPHY ACROSS FOLDS, FISSURES AND CORTICAL AREAS. THEN WE WILL FUNCTIONALLY ANALYZE THE DIFFERENT NEURONS IN EACH CLONE BY OPTICAL IMAGING OF INTRINSIC SIGNALS, MAPPING THEIR RESPONSE PROPERTIES OVER THE CORTICAL SURFACE. THIS ORIGINAL AND INTERDISCIPLINARY COMBINATION OF APPROACHES IS THE GREAT ASSET OF THIS PROJECT, AS IT WILL ALLOW US TO FINALLY PROOF OR REFUTE A DOGMA ABOUT THE BASIC MECHANISM OF CORTICAL DEVELOPMENT AND FUNCTIONAL SPECIFICATION. THE SUCCESSFUL EXECUTION OF THIS PROJECT WILL ENABLE US TO BETTER UNDERSTAND THE DEVELOPMENTAL MECHANISMS THAT PROMOTE THE MAXIMIZATION OF COGNITIVE FUNCTION IN HIGHER MAMMALS.