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BACKGROUND: Several validated clinical scales measure the severity of essential tremor (ET). Their assessments are subjective and can depend on familiarity and training with scoring systems. METHOD: We propose a multi-modal sensing using a wearable inertial measurement unit for estimating scores on the Fahn-Tolosa-Marin tremor rating scale (FTM) and determine the classification accuracy within the tremor type. 17 ET participants and 18 healthy controls were recruited for the study. Two movement disorder neurologists who were blinded to prior clinical information viewed video recordings and scored the FTM. Participants drew a guided Archimedes spiral while wearing an inertial measurement unit placed at the mid-point between the lateral epicondyle of the humerus and the anatomical snuff box. Acceleration and gyroscope recordings were analyzed. The ratio of the power spectral density between frequency bands 0.5-4 Hz and 4-12 Hz, and the sum of power spectrum density over the entire spectrum of 2-74 Hz, for both accelerometer and gyroscope data, were computed. FTM was estimated using regression model and classification using SVM was validated using the leave-one-out method. RESULTS: Regression analysis showed a moderate to good correlation when individual features were used, while correlation was high ([Formula: see text] = 0.818) when suitable features of the gyro and accelerometer were combined. The accuracy for two-class classification of the combined features using SVM was 91.42% while for four-class it was 68.57%. CONCLUSION: Potential applications of this novel wearable sensing method using a wearable Inertial Measurement Unit (IMU) include monitoring of ET and clinical trials of new treatments for the disorder.
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Temblor Esencial , Dispositivos Electrónicos Vestibles , Humanos , Temblor Esencial/diagnóstico , Temblor , Aceleración , AcelerometríaRESUMEN
Commonly used methods to assess the severity of essential tremor (ET) are based on clinical observation and lack objectivity. This study proposes the use of wearable accelerometer sensors for the quantitative assessment of ET. Acceleration data was recorded by inertial measurement unit (IMU) sensors during sketching of Archimedes spirals in 17 ET participants and 18 healthy controls. IMUs were placed at three points (dorsum of hand, posterior forearm, posterior upper arm) of each participant's dominant arm. Movement disorder neurologists who were blinded to clinical information scored ET patients on the Fahn-Tolosa-Marin rating scale (FTM) and conducted phenotyping according to the recent Consensus Statement on the Classification of Tremors. The ratio of power spectral density of acceleration data in 4-12 Hz to 0.5-4 Hz bands and the total duration of the action were inputs to a support vector machine that was trained to classify the ET subtype. Regression analysis was performed to determine the relationship of acceleration and temporal data with the FTM scores. The results show that the sensor located on the forearm had the best classification and regression results, with accuracy of 85.71% for binary classification of ET versus control. There was a moderate to good correlation (r2 = 0.561) between FTM and a combination of power spectral density ratio and task time. However, the system could not accurately differentiate ET phenotypes according to the Consensus classification scheme. Potential applications of machine-based assessment of ET using wearable sensors include clinical trials and remote monitoring of patients.
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Temblor Esencial , Dispositivos Electrónicos Vestibles , Aceleración , Temblor Esencial/diagnóstico , Mano , Humanos , TemblorRESUMEN
Wireless security research using Radio Frequency (RF) data is complex and costly, often requiring expensive equipment and extensive offline processing. To make wireless research more accessible, we have integrated RF signal features with the existing IEEE 802.11 frame layer 2/3 data using the Software Defined Networking (SDN) paradigm. Combining low-cost RF hardware, a novel SDN processing method, and unique RF processing architecture has resulted in a framework that enables advanced wireless security and control research at a significantly lower cost. The method for enabling such functionality consist of the following stages:â¢During the demodulation process, extract Carrier Frequency Offset (CFO) and Pilot Sub-Carrier Offset from the Frequency Offset Correction section, in addition to the Vector Magnitude from the equalization section.â¢Append the new RF information to the wireless frame buffer and pass it to the SDR kernel driver module to further process before transferring them to a P4 application via a single API instantiation.â¢Compile a custom P4 application that combines the new RF features alongside higher OSI layer features to perform advanced networking, security, or control plane operations.
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Various research activities require the programming of a large numbers of devices. This programming can be difficult to co-ordinate and organise, and requires considerable labour time. These issues often mean that testing on real hardware is abandoned or taken only to small scale implementation thus limiting the real-world findings. The method described in this paper adopts a three-tiered approach to programming large numbers of devices. Tier 1 is comprised of a single Master Controller which is networked to individual tower modules, these towers form the final 2 tiers with the Local Controller as tier 2 and up-to 15 target devices forming tier 3. The Master Controller co-ordinates and distributes the code for each device to the Local Controller which then programs the target devices. In the domain of networking this allows for: â¢Large networks of varied protocols to be programmed quickly, since towers are programmed in parallel, additional towers don't extend programming times.â¢Distributed networks are possible since towers are controlled over Ethernet.â¢Dramatically reduced labour time and defect rates due to human error in setting up devices.â¢This paper presents the implementation of this method for IoT Networking research with ESP-01 Target devices.
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Smartphones have changed the way the people behave, their expectations, and interact with other people. Being more young people centric, these are now ubiquitous in the education environment which has higher representation of the youth, and have dramatically changed how our students behave in the classroom, what they expect, and how they learn. These devices offer both an opportunity and a threat to the education process and educators must take them into account when designing any education activity. We may wish them away, but that is getting less possible by the day. This paper investigates two scenarios, and these case studies highlight what can go right and wrong, and suggests processes that make it more likely that an educational process will be enhanced by the use of smart phones.
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Educación , Aprendizaje , Teléfono Inteligente , Adolescente , Humanos , EnseñanzaRESUMEN
We prove the hitherto hypothesized sequential dissociation of Fe(CO)5 in the gas phase upon photoexcitation at 266 nm via a singlet pathway with time-resolved valence and core-level photoelectron spectroscopy with an x-ray free-electron laser. Valence photoelectron spectra are used to identify free CO molecules and to determine the time constants of stepwise dissociation to Fe(CO)4 within the temporal resolution of the experiment and further to Fe(CO)3 within 3 ps. Fe 3p core-level photoelectron spectra directly reflect the singlet spin state of the Fe center in Fe(CO)5, Fe(CO)4, and Fe(CO)3 showing that the dissociation exclusively occurs along a singlet pathway without triplet-state contribution. Our results are important for assessing intra- and intermolecular relaxation processes in the photodissociation dynamics of the prototypical Fe(CO)5 complex in the gas phase and in solution, and they establish time-resolved core-level photoelectron spectroscopy as a powerful tool for determining the multiplicity of transition metals in photochemical reactions of coordination complexes.
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Two-color (x-ray+infrared) electron spectroscopy is used for investigating laser-assisted KLL Auger decay following 1s photoionization of atomic Ne with few-femtosecond x-ray pulses from the Linac Coherent Light Source. In an angle-resolved experiment, the overall width of the laser-modified Auger-electron spectrum and its structure change significantly as a function of the emission angle. The spectra are characterized by a strong intensity variation of the sidebands revealing a gross structure. This variation is caused, as predicted by theory, by the interference of electrons emitted at different times within the duration of one optical cycle of the infrared dressing laser, which almost coincides with the lifetime of the Ne 1s vacancy.
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Argon gas at a high pressure (â¼80 bar) has been expanded using a miniaturized pulsed valve at room temperature, producing a supersonic beam of cold, large argon droplets. Atoms of silver are subsequently embedded into the droplet using the pick-up technique. The resulting Ag(n)Ar(droplet) distribution was analyzed using multiphoton laser ionization time-of-flight mass spectrometry. Besides bare metal clusters, snowballs of silver monomers and dimers encapsulated in up to 50 argon atoms have been observed. The influence of the solvent on the optical absorption of the solute was studied for embedded Ag(8) using resonant two-photon ionization in the ultraviolet. A redshift and broadening of the Ag(8)Ar(droplet) optical spectrum compared to that measured in pure [Federmann et al., Eur. Phys. J. D 1999, 9, 11] and Ar-doped helium droplets [Diederich et al., J. Chem. Phys.2002, 116, 3263] was observed, which is attributed to the interaction with the larger Ar matrix environment.
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Two-photon excitation of a single-photon forbidden Auger resonance has been observed and investigated using the intense extreme ultraviolet radiation from the free electron laser in Hamburg. At the wavelength 26.9 nm (46 eV) two photons promoted a 3d core electron to the outer 4d shell. The subsequent Auger decay, as well as several nonlinear above threshold ionization processes, were studied by electron spectroscopy. The experimental data are in excellent agreement with theoretical predictions and analysis of the underlying multiphoton processes.
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Metal clusters serve as model systems to study basic problems of electronic correlation. Vacuum ultraviolet light from the free-electron laser FLASH ionizes 5d electrons from mass-separated negatively charged clusters, thus transiently leading to core-ionized neutral systems. Shielding of the core hole affects the electron binding energy. From the strong deviation from expectations of the metallic droplet and jellium models we conclude on reduced electronic shielding once the cluster size falls below about 20 atoms. This suggests a metal-to-nonmetal transition, in agreement with previous local density approximation calculations.
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Large-scale production of gene therapeutics comprising equine infectious anaemia virus (EIAV) -based lentiviral vectors (LVs) would benefit from the development of producer cell lines enabling the generation of larger quantities of vector than achievable by transient systems. Such cell lines would contain three vector components (Gag/Pol, VSV-G envelope and genome expression constructs). As the vesicular stomatitis virus (VSV-G) envelope protein is cytotoxic, its expression must be regulated. It is also desirable to regulate Gag/Pol expression to minimise metabolic burden on the cell. The Tet repressor (TetR) system was selected to regulate expression of VSV-G and Gag/Pol, necessitating the introduction of a fourth construct, encoding TetR, into the cell line. We have generated an inducible packaging cell line that shows tight control of the packaging components, and high-titre vector production on transient transfection of the EIAV genome. The cell line is stable for at least 7 weeks in the absence of selective pressure. To verify that this packaging cell line can support the generation of producer cell lines it was transfected stably with an EIAV genome cassette encoding ProSavin; a gene therapeutic for Parkinson's disease. Producer cell lines were generated, which on induction, yielded ProSavin with titres comparable to the transient system.
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Regulación de la Expresión Génica/genética , Vectores Genéticos , Virus de la Anemia Infecciosa Equina/genética , Lentivirus/genética , Glicoproteínas de Membrana/genética , Proteínas Represoras/genética , Proteínas del Envoltorio Viral/genética , Animales , Antibacterianos/farmacología , Western Blotting , Técnicas de Cultivo de Célula/métodos , Línea Celular , Células Clonales , Doxiciclina/farmacología , Proteínas de Fusión gag-pol/genética , Regulación de la Expresión Génica/efectos de los fármacos , Terapia Genética/métodos , Inestabilidad Genómica/genética , Sistemas de Lectura Abierta , Plásmidos , ADN Polimerasa Dirigida por ARN , Proteínas Represoras/farmacología , Transfección/métodos , Ensamble de Virus/genética , Replicación ViralRESUMEN
Two-color multiphoton ionization of atomic helium was investigated by combining extreme ultraviolet (XUV) radiation from the Free Electron Laser in Hamburg with an intense synchronized optical laser. In the photoelectron spectrum, lines associated with direct ionization and above-threshold ionization show strong variations of their amplitudes as a function of both the intensity of the optical dressing field and the relative orientation of the linear polarization vectors of the two fields. The polarization dependence provides direct insight into the symmetry of the outgoing electrons in above-threshold ionization. In the high field regime, the monochromaticity of the XUV radiation enables the unperturbed observation of nonlinear processes in the optical field.
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Effective gene therapy for haemophilia A necessitates a vector system that is not subject to a pre-existing immune response, has adequate coding capacity, gives long-term expression and preferably can target non-dividing cells. Vector systems based on lentiviruses such as equine infectious anaemia virus (EIAV) fulfil these criteria for the delivery of factor VIII (FVIII). We have found that B domain-deleted (BDD) FVIII protein inhibits functional viral particle production when co-expressed with the EIAV vector system. Although particle numbers (as measured by reverse transcriptase activity) are near normal, RNA genome levels are reduced and measurement of integrated copies revealed the virus is severely defective in its ability to transduce target cells. This is due to the absence of sufficient vesicular stomatitis virus glycoprotein (VSV-G) envelope on viral particles derived from cells expressing FVIII. By using an internal tissue-specific promoter, that has low activity in the producer cells, to drive expression of FVIII we have overcome this inhibitory effect allowing us to generate titres approaching those obtained with vector genomes encoding reporter genes. Furthermore, we report that codon optimization of the full-length FVIII gene increased vector titres approximately 10-fold in addition to substantially improving expression per integrated vector copy.
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Factor VIII/genética , Vectores Genéticos , Virus de la Anemia Infecciosa Equina/genética , Línea Celular , Codón , Terapia Genética , Hemofilia A/terapia , Humanos , Reacción en Cadena de la Polimerasa , Regiones Promotoras GenéticasRESUMEN
We report the creation of solid-density aluminum plasma using free-electron laser (FEL) radiation at 13.5nm wavelength. Ultrashort pulses were focused on a bulk Al target, yielding an intensity of 2x10;{14}Wcm;{2} . The radiation emitted from the plasma was measured using an xuv spectrometer. Bremsstrahlung and line intensity ratios yield consistent electron temperatures of about 38eV , supported by radiation hydrodynamics simulations. This shows that xuv FELs heat up plasmas volumetrically and homogeneously at warm-dense-matter conditions, which are accurately characterized by xuv spectroscopy.
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Few-photon multiple ionization of Ne and Ar atoms by strong vacuum ultraviolet laser pulses from the free-electron laser at Hamburg was investigated differentially with the Heidelberg reaction microscope. The light-intensity dependence of Ne2+ production reveals the dominance of nonsequential two-photon double ionization at intensities of I<6x10(12) W/cm2 and significant contributions of three-photon ionization as I increases. Ne2+ recoil-ion-momentum distributions suggest that two electrons absorbing "instantaneously" two photons are ejected most likely into opposite hemispheres with similar energies.
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Recent advances in avian transgenesis have led to the possibility of utilizing the laying hen as a production platform for the large-scale synthesis of pharmaceutical proteins. Ovalbumin constitutes more than half of the protein in the white of a laid egg, and expression of the ovalbumin gene is restricted to the tubular gland cells of the oviduct. Here we describe the use of lentiviral vectors to deliver transgene constructs comprising regulatory sequences from the ovalbumin gene designed to direct synthesis of associated therapeutic proteins to the oviduct. We report the generation of transgenic hens that synthesize functional recombinant pharmaceutical protein in a tightly regulated tissue-specific manner, without any evidence of transgene silencing after germ-line transmission.
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Animales Modificados Genéticamente , Pollos/genética , Proteínas del Huevo/biosíntesis , Proteínas del Huevo/genética , Oviductos/metabolismo , Proteínas Recombinantes/biosíntesis , Animales , Pollos/metabolismo , Proteínas del Huevo/uso terapéutico , Clara de Huevo/química , Femenino , Vectores Genéticos , Humanos , Virus de la Anemia Infecciosa Equina/genética , Interferón beta-1a , Interferón beta/biosíntesis , Interferón beta/genética , Interferón beta/fisiología , Masculino , Ratones , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMEN
Because of the stochastic nature of self-amplified spontaneous emission (SASE), it is crucial to measure for single pulses the spectral characteristics of ultrashort pulses from the vacuum ultraviolet free electron laser (FLASH) at DESY, Germany. To meet this particular challenge, we have employed both photon and photoelectron spectroscopy. Each FEL pulse is composed of an intense and spectrally complex fundamental, centered at a photon energy of about 38.5 eV, with a bandwidth of 0.5% accompanied by higher harmonics, each carrying an intensity of typically 0.3 to 0.6% of that of the fundamental. The correlation between the harmonics and the fundamental is in remarkable agreement with a simple statistical model of SASE FEL radiation.
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Suspensions of binary mixtures of hard-sphere poly-methylmethacrylate colloidal particles were studied at six different size ratios alpha. The main aim was to determine the range of size ratios over which the binary colloidal crystals AB2 and AB13 are stable. Combining these results with those of earlier work, we found stability of AB2 for 0.60 approximately > alpha approximately > 0.425, in good agreement with theoretical predictions by computer simulation and cell model methods. AB13 was observed for 0.62 approximately > alpha approximately > 0.485, the lower limit being significantly smaller than the theoretical prediction of about 0.525. Rough measurements of crystallization rates showed that AB2 tended to crystallize fastest at small size ratios, whereas the opposite was true for AB13. These findings should provide a guide to the optimum conditions for materials applications of these binary colloidal crystals.
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The ability of human immunodeficiency virus (HIV)- and equine infectious anaemia virus (EIAV)-based vectors to transduce cell lines from a range of species was compared. Both vectors carried the vesicular stomatitis virus G (VSV-G) envelope protein and encoded an enhanced green fluorescent protein (eGFP) gene driven by a human cytomegalovirus (CMV) early promoter. Immunostaining for viral core proteins and VSV-G was used to demonstrate that the HIV and EIAV vector preparations contained similar numbers of virus particles. Various cell lines were transduced with these vectors and the transduction efficiency was estimated by measuring eGFP expression. Efficient transduction by both vectors was observed in human, hamster, pig, horse, cat and dog cell lines, although EIAV vector was about 10-fold less efficient in human, hamster and pig cells normalised to the total number of viral particles. This could be partly explained by the lower RNA genome levels per particle for EIAV as measured by real-time RT-PCR. Rodent cells appeared to be transduced inefficiently with both vectors, but when the CMV promoter was substituted with the EF1alpha promoter in the HIV vectors, the expression level increased leading to an increase in the measurable level of transduction.
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Terapia Genética/métodos , Vectores Genéticos/farmacología , VIH/genética , Virus de la Anemia Infecciosa Equina/genética , Transducción Genética/métodos , Animales , Gatos , Bovinos , Línea Celular , Cricetinae , Citomegalovirus/genética , Perros , Expresión Génica , Terapia Genética/veterinaria , Vectores Genéticos/genética , Proteínas Fluorescentes Verdes , Células HeLa , Caballos , Humanos , Proteínas Luminiscentes/genética , Ratones , Factor 1 de Elongación Peptídica/genética , Regiones Promotoras Genéticas , Conejos , Ratas , Especificidad de la Especie , Porcinos , Virus de la Estomatitis Vesicular Indiana/genética , Proteínas del Envoltorio Viral/genéticaRESUMEN
The biogenesis of microtubules in the cell comprises a series of complex steps, including protein-folding reactions catalyzed by chaperonins. In addition a group of evolutionarily conserved proteins, called cofactors (A to E), is required for the production of assembly-competent alpha-/beta-tubulin heterodimers. Using fission yeast, in which alp11(+), alp1(+), and alp21(+), encoding the homologs for cofactors B, D, and E, respectively, are essential for cell viability, we have undertaken the genetic analysis of alp31(+), the homolog of cofactor A. Gene disruption analysis shows that, unlike the three genes mentioned above, alp31(+) is dispensable for cell growth and division. Nonetheless, detailed analysis of alp31-deleted cells demonstrates that Alp31(A) is required for the maintenance of microtubule structures and, consequently, the proper control of growth polarity. alp31-deleted cells show genetic interactions with mutations in beta-tubulin, but not in alpha-tubulin. Budding yeast cofactor A homolog RBL2 is capable of suppressing the polarity defects of alp31-deleted cells. We conclude that the cofactor-dependent biogenesis of microtubules comprises an essential and a nonessential pathway, both of which are required for microtubule integrity.