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1.
Nat Commun ; 15(1): 5259, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898091

RESUMEN

Highly sensitive, low-power, and chip-scale H2 gas sensors are of great interest to both academia and industry. Field-effect transistors (FETs) functionalized with Pd nanoparticles (PdNPs) have recently emerged as promising candidates for such H2 sensors. However, their sensitivity is limited by weak capacitive coupling between PdNPs and the FET channel. Herein we report a nanoscale FET gas sensor, where electrons can tunnel between the channel and PdNPs and thus equilibrate them. Gas reaction with PdNPs perturbs the equilibrium, and therefore triggers electron transfer between the channel and PdNPs via trapping or de-trapping with the PdNPs to form a new balance. This direct communication between the gas reaction and the channel enables the most efficient signal transduction. Record-high responses to 1-1000 ppm H2 at room temperature with detection limit in the low ppb regime and ultra-low power consumption of ~ 300 nW are demonstrated. The same mechanism could potentially be used for ultrasensitive detection of other gases. Our results present a supersensitive FET gas sensor based on electron trapping effect in nanoparticles.

2.
J Biol Chem ; 299(12): 105482, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37992806

RESUMEN

Bromodomains (BDs) regulate gene expression by recognizing protein motifs containing acetyllysine. Although originally characterized as histone-binding proteins, it has since become clear that these domains interact with other acetylated proteins, perhaps most prominently transcription factors. The likely transient nature and low stoichiometry of such modifications, however, has made it challenging to fully define the interactome of any given BD. To begin to address this knowledge gap in an unbiased manner, we carried out mRNA display screens against a BD-the N-terminal BD of BRD3-using peptide libraries that contained either one or two acetyllysine residues. We discovered peptides with very strong consensus sequences and with affinities that are significantly higher than typical BD-peptide interactions. X-ray crystal structures also revealed modes of binding that have not been seen with natural ligands. Intriguingly, however, our sequences are not found in the human proteome, perhaps suggesting that strong binders to BDs might have been selected against during evolution.


Asunto(s)
Proteoma , Factores de Transcripción , Humanos , Proteoma/metabolismo , Factores de Transcripción/metabolismo , Dominios Proteicos , Secuencias de Aminoácidos , Péptidos/metabolismo , Unión Proteica , Acetilación
3.
JAMA ; 330(6): 512-527, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37459141

RESUMEN

Importance: There are limited efficacious treatments for Alzheimer disease. Objective: To assess efficacy and adverse events of donanemab, an antibody designed to clear brain amyloid plaque. Design, Setting, and Participants: Multicenter (277 medical research centers/hospitals in 8 countries), randomized, double-blind, placebo-controlled, 18-month phase 3 trial that enrolled 1736 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia) with amyloid and low/medium or high tau pathology based on positron emission tomography imaging from June 2020 to November 2021 (last patient visit for primary outcome in April 2023). Interventions: Participants were randomized in a 1:1 ratio to receive donanemab (n = 860) or placebo (n = 876) intravenously every 4 weeks for 72 weeks. Participants in the donanemab group were switched to receive placebo in a blinded manner if dose completion criteria were met. Main Outcomes and Measures: The primary outcome was change in integrated Alzheimer Disease Rating Scale (iADRS) score from baseline to 76 weeks (range, 0-144; lower scores indicate greater impairment). There were 24 gated outcomes (primary, secondary, and exploratory), including the secondary outcome of change in the sum of boxes of the Clinical Dementia Rating Scale (CDR-SB) score (range, 0-18; higher scores indicate greater impairment). Statistical testing allocated α of .04 to testing low/medium tau population outcomes, with the remainder (.01) for combined population outcomes. Results: Among 1736 randomized participants (mean age, 73.0 years; 996 [57.4%] women; 1182 [68.1%] with low/medium tau pathology and 552 [31.8%] with high tau pathology), 1320 (76%) completed the trial. Of the 24 gated outcomes, 23 were statistically significant. The least-squares mean (LSM) change in iADRS score at 76 weeks was -6.02 (95% CI, -7.01 to -5.03) in the donanemab group and -9.27 (95% CI, -10.23 to -8.31) in the placebo group (difference, 3.25 [95% CI, 1.88-4.62]; P < .001) in the low/medium tau population and -10.2 (95% CI, -11.22 to -9.16) with donanemab and -13.1 (95% CI, -14.10 to -12.13) with placebo (difference, 2.92 [95% CI, 1.51-4.33]; P < .001) in the combined population. LSM change in CDR-SB score at 76 weeks was 1.20 (95% CI, 1.00-1.41) with donanemab and 1.88 (95% CI, 1.68-2.08) with placebo (difference, -0.67 [95% CI, -0.95 to -0.40]; P < .001) in the low/medium tau population and 1.72 (95% CI, 1.53-1.91) with donanemab and 2.42 (95% CI, 2.24-2.60) with placebo (difference, -0.7 [95% CI, -0.95 to -0.45]; P < .001) in the combined population. Amyloid-related imaging abnormalities of edema or effusion occurred in 205 participants (24.0%; 52 symptomatic) in the donanemab group and 18 (2.1%; 0 symptomatic during study) in the placebo group and infusion-related reactions occurred in 74 participants (8.7%) with donanemab and 4 (0.5%) with placebo. Three deaths in the donanemab group and 1 in the placebo group were considered treatment related. Conclusions and Relevance: Among participants with early symptomatic Alzheimer disease and amyloid and tau pathology, donanemab significantly slowed clinical progression at 76 weeks in those with low/medium tau and in the combined low/medium and high tau pathology population. Trial Registration: ClinicalTrials.gov Identifier: NCT04437511.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Femenino , Anciano , Masculino , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/psicología , Método Doble Ciego , Resultado del Tratamiento , Disfunción Cognitiva/etiología , Disfunción Cognitiva/tratamiento farmacológico , Encéfalo , Anticuerpos Monoclonales/uso terapéutico
4.
Nucleic Acids Res ; 51(13): 6841-6856, 2023 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-37246713

RESUMEN

Horizontal gene transfer is tightly regulated in bacteria. Often only a fraction of cells become donors even when regulation of horizontal transfer is coordinated at the cell population level by quorum sensing. Here, we reveal the widespread 'domain of unknown function' DUF2285 represents an 'extended-turn' variant of the helix-turn-helix domain that participates in both transcriptional activation and antiactivation to initiate or inhibit horizontal gene transfer. Transfer of the integrative and conjugative element ICEMlSymR7A is controlled by the DUF2285-containing transcriptional activator FseA. One side of the DUF2285 domain of FseA has a positively charged surface which is required for DNA binding, while the opposite side makes critical interdomain contacts with the N-terminal FseA DUF6499 domain. The QseM protein is an antiactivator of FseA and is composed of a DUF2285 domain with a negative surface charge. While QseM lacks the DUF6499 domain, it can bind the FseA DUF6499 domain and prevent transcriptional activation by FseA. DUF2285-domain proteins are encoded on mobile elements throughout the proteobacteria, suggesting regulation of gene transfer by DUF2285 domains is a widespread phenomenon. These findings provide a striking example of how antagonistic domain paralogues have evolved to provide robust molecular control over the initiation of horizontal gene transfer.


Asunto(s)
Conjugación Genética , Proteobacteria , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Transferencia de Gen Horizontal , Proteobacteria/genética , Percepción de Quorum/genética , Factores de Transcripción/metabolismo , Activación Transcripcional
5.
Sci Adv ; 7(49): eabj6711, 2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34860555

RESUMEN

Electrical sensors have been widely explored for the analysis of chemical/biological species. Ion detection with single charge resolution is the ultimate sensitivity goal of such sensors, which is yet to be experimentally demonstrated. Here, the events of capturing and emitting a single hydrogen ion (H+) at the solid/liquid interface are directly detected using sub­10-nm electrical double layer­gated silicon nanowire field-effect transistors (SiNWFETs). The SiNWFETs are fabricated using a complementary metal-oxide-semiconductor compatible process, with a surface reassembling step to minimize the device noise. An individually activated surface Si dangling bond (DB) acts as the single H+ receptor. Discrete current signals, generated by the single H+-DB interactions via local Coulomb scattering, are directly detected by the SiNWFETs. The single H+-DB interaction kinetics is systematically investigated. Our SiNWFETs demonstrate unprecedented capability for electrical sensing applications, especially for investigating the physics of solid/liquid interfacial interactions at the single charge level.

6.
Alzheimers Dement (N Y) ; 7(1): e12136, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34095437

RESUMEN

INTRODUCTION: A previous phase 2b study supported the use of the 5-HT6 receptor antagonist intepirdine as adjunctive therapy to donepezil for Alzheimer's disease (AD) dementia. A phase 3 study, MINDSET, was performed to test this hypothesis. METHODS: MINDSET was a global, double-blind, randomized, placebo-controlled trial in 1315 mild-to-moderate AD dementia patients on stable donepezil. Patients received 35 mg/day intepirdine or placebo for 24 weeks. The co-primary endpoints were change from baseline to week 24 on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL). RESULTS: There were no statistically significant differences between intepirdine and placebo groups (adjusted mean [95% confidence interval]) on the co-primary endpoints ADAS-Cog (-0.36 [-0.95, 0.22], P = 0.2249) and ADCS-ADL (-0.09 [-0.90, 0.72], P = 0.8260). Intepirdine demonstrated a favorable safety profile similar to placebo. DISCUSSION: Intepirdine as adjunctive therapy to donepezil did not produce statistical improvement over placebo on cognition or activities of daily living in mild-to-moderate AD dementia patients.

7.
Biochemistry ; 60(9): 648-662, 2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33620209

RESUMEN

Almost all eukaryotic proteins receive diverse post-translational modifications (PTMs) that modulate protein activity. Many histone PTMs are well characterized, heavily influence gene regulation, and are often predictors of distinct transcriptional programs. Although our understanding of the histone PTM network has matured, much is yet to be understood about the roles of transcription factor (TF) PTMs, which might well represent a similarly complex and dynamic network of functional regulation. Members of the bromodomain and extra-terminal domain (BET) family of proteins recognize acetyllysine residues and relay the signals encoded by these modifications. Here, we have investigated the acetylation dependence of several functionally relevant BET-TF interactions in vitro using surface plasmon resonance, nuclear magnetic resonance, and X-ray crystallography. We show that motifs known to be acetylated in TFs E2F1 and MyoD1 can interact with all bromodomains of BRD2, BRD3, and BRD4. The interactions are dependent on diacetylation of the motifs and show a preference for the first BET bromodomain. Structural mapping of the interactions confirms a conserved mode of binding for the two TFs to the acetyllysine binding pocket of the BET bromodomains, mimicking that of other already established functionally important histone- and TF-BET interactions. We also examined a motif from the TF RelA that is known to be acetylated but were unable to observe any interaction, regardless of the acetylation state of the sequence. Our findings overall advance our understanding of BET-TF interactions and suggest a physical link between the important diacetylated motifs found in E2F1 and MyoD1 and the BET-family proteins.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Factor de Transcripción E2F1/metabolismo , Proteína MioD/metabolismo , Factores de Transcripción/metabolismo , Acetilación , Proteínas de Ciclo Celular/química , Cristalografía por Rayos X , Factor de Transcripción E2F1/química , Histonas/química , Humanos , Lisina/química , Modelos Moleculares , Proteína MioD/química , Conformación Proteica , Dominios Proteicos , Procesamiento Proteico-Postraduccional , Factores de Transcripción/química
8.
Protein Sci ; 30(2): 464-476, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33247496

RESUMEN

Chemical modifications of histone tails influence genome accessibility and the transcriptional state of eukaryotic cells. Lysine acetylation is one of the most common modifications and acetyllysine-binding bromodomains (BDs) provide a means for acetyllysine marks to be translated into meaningful cellular responses. Here, we have investigated the mechanism underlying the reported association between the Bromodomain and Extra Terminal (BET) family of BD proteins and the essential histone variant H2A.Z. We use NMR spectroscopy to demonstrate a physical interaction between the N-terminal tail of H2A.Z and the BDs of BRD2, BRD3, and BRD4, and show that the interaction is dependent on lysine acetylation in H2A.Z. The BDs preferentially engage a diacetylated H2A.Z-K4acK7ac motif that is reminiscent of sequences found in other biologically important BET BD target proteins, including histones and transcription factors. A H2A.Z-K7acK11ac motif can also bind BET BDs-with a preference for the second BD of each protein. Chemical shift perturbation mapping of the interactions, together with an X-ray crystal structure of BRD2-BD1 bound to H2A.Z-K4acK7ac, shows that H2A.Z binds the canonical AcK binding pocket of the BDs. This mechanism mirrors the conserved binding mode that is unique to the BET BDs, in which two acetylation marks are read simultaneously by a single BD. Our findings provide structural corroboration of biochemical and cell biological data that link H2A.Z and BET-family proteins, suggesting that the function of H2A.Z is enacted through interactions with these chromatin readers.


Asunto(s)
Proteínas de Ciclo Celular/química , Histonas/química , Factores de Transcripción/química , Acetilación , Cristalografía por Rayos X , Humanos , Unión Proteica , Dominios Proteicos , Relación Estructura-Actividad
9.
Proc Natl Acad Sci U S A ; 117(43): 26728-26738, 2020 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-33046654

RESUMEN

Cyclic peptide library screening technologies show immense promise for identifying drug leads and chemical probes for challenging targets. However, the structural and functional diversity encoded within such libraries is largely undefined. We have systematically profiled the affinity, selectivity, and structural features of library-derived cyclic peptides selected to recognize three closely related targets: the acetyllysine-binding bromodomain proteins BRD2, -3, and -4. We report affinities as low as 100 pM and specificities of up to 106-fold. Crystal structures of 13 peptide-bromodomain complexes reveal remarkable diversity in both structure and binding mode, including both α-helical and ß-sheet structures as well as bivalent binding modes. The peptides can also exhibit a high degree of structural preorganization. Our data demonstrate the enormous potential within these libraries to provide diverse binding modes against a single target, which underpins their capacity to yield highly potent and selective ligands.


Asunto(s)
Biblioteca de Péptidos , Péptidos Cíclicos , Sitios de Unión , Descubrimiento de Drogas , Humanos , Péptidos Cíclicos/química , Péptidos Cíclicos/metabolismo , Unión Proteica , Dominios Proteicos , Factores de Transcripción/química , Factores de Transcripción/metabolismo
10.
Atmos Meas Tech ; 13(6)2020.
Artículo en Inglés | MEDLINE | ID: mdl-34497673

RESUMEN

Mobile platform measurements provide new opportunities for characterizing spatial variations of air pollution within urban areas, identifying emission sources, and enhancing knowledge of atmospheric processes. The Aclima, Inc. mobile measurement and data acquisition platform was used to equip four Google Street View cars with research-grade instruments, two of which were available for the duration of this study. On-road measurements of air quality were made during a series of sampling campaigns between May 2016 and September 2017 at high (i.e., 1-second [s]) temporal and spatial resolution at several California locations: Los Angeles, San Francisco, and the northern San Joaquin Valley (including non-urban roads and the cities of Tracy, Stockton, Manteca, Merced, Modesto, and Turlock). The results demonstrate that the approach is effective for quantifying spatial variations of air pollutant concentrations over measurement periods as short as two weeks. Measurement accuracy and precision are evaluated using results of weekly performance checks and periodic audits conducted through the sampler inlets, which show that research instruments located within stationary vehicles are capable of reliably measuring nitric oxide (NO), nitrogen dioxide (NO2), ozone (O3), methane (CH4) black carbon (BC), and particle number (PN) concentration with bias and precision ranging from <10 % for gases to <25 % for BC and PN at 1-s time resolution. The quality of the mobile measurements in the ambient environment is examined by comparisons with data from an adjacent (< 9 m) stationary regulatory air quality monitoring site and by paired collocated vehicle comparisons, both stationary and driving. The mobile measurements indicate that U.S. EPA classifications of two Los Angeles stationary regulatory monitors' scales of representation are appropriate. Paired time-synchronous mobile measurements are used to characterize the spatial scales of concentration variations when vehicles were separated by <1 to 10 kilometers (km). A data analysis approach is developed to characterize spatial variations while limiting the confounding influence of diurnal variability. The approach is illustrated using data from San Francisco, revealing 1-km scale differences in mean NO2 and O3 concentrations up to 117 % and 46 %, respectively, of mean values during a two-week sampling period. In San Francisco and Los Angeles, spatial variations up to factors of 6 to 8 occur at sampling scales of 100 - 300m, corresponding to 1-minute averages.

11.
Atmos Environ X ; 72020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-33748742

RESUMEN

Mobile mapping of air pollution has the potential to provide pollutant concentration data at unprecedented spatial scales. Characterizing instrument performance in the mobile context is challenging, but necessary to analyze and interpret the resulting data. We used robust statistical methods to assess mobile platform performance using data collected with the Aclima Inc. mobile air pollution measurement and data acquisition platform installed on three Google Street View cars. They were driven throughout the greater Denver metropolitan area between July 25, 2014 and August 14, 2014, measuring ozone (O3), nitrogen dioxide (NO2), nitric oxide (NO), black carbon (BC), and size-resolve particle number counts (PN) between 0.3 µm and 5.0 µm diameter. August 6, 2014 was dedicated to parked and moving collocations among the three cars, allowing an assessment of measurement precision and bias. We used the median absolute deviation (MAD) to estimate instrument precision from outdoor, parked collocations. Bias was assessed by measurements obtained from parked cars using the standard deviation of median values over a collocated measurement period, as well as by Passing-Bablok regression statistics while the cars were moving and collocated. For the moving collocation periods, we compared the distribution of 1-σ standard deviations among the 3 cars to the estimated distribution assuming only measurement uncertainty (precision and bias). The distribution of mobile measurements agreed well with the theoretical uncertainty distribution at the lower end of the distribution for O3, NO2, and PN. We assert that the difference between the actual and theoretical distributions is due to real spatial variability between pollutants. The agreement between the parked car estimates of uncertainty and that measured during the mobile collocations (at the lower quantiles) provides evidence that on-road collocation while parked could be sufficient for estimating measurement uncertainties of a mobile platform, even when extended to the moving environment.

12.
Nat Nanotechnol ; 14(11): 1056-1062, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31591525

RESUMEN

Solid-state nanopore technology presents an emerging single-molecule-based analytical tool for the separation and analysis of nanoparticles. Different approaches have been pursued to attain the anticipated detection performance. Here, we report the rectification behaviour of protein translocation through silicon-based truncated pyramidal nanopores. When the size of translocating proteins is comparable to the smallest physical constriction of the nanopore, the frequency of translocation events observed is lower for proteins that travel from the larger to the small opening of the nanopore than for those that travel in the reverse direction. When the proteins are appreciably smaller than the nanopore, an opposite rectification in the frequency of translocation events is evident. The maximum rectification factor achieved is around ten. Numerical simulations reveal the formation of an electro-osmotic vortex in such asymmetric nanopores. The vortex-protein interaction is found to play a decisive role in rectifying the translocation in terms of polarity and amplitude. The reported phenomenon can be potentially exploitable for the discrimination of various nanoparticles.

13.
ACS Sens ; 4(2): 427-433, 2019 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-30632733

RESUMEN

The sensitivity of metal oxide semiconductor field-effect transistor (MOSFET) based nanoscale sensors is ultimately limited by noise induced by carrier trapping/detrapping processes at the gate oxide/semiconductor interfaces. We have designed a Schottky junction gated silicon nanowire field-effect transistor (SiNW-SJGFET) sensor, where the Schottky junction replaces the noisy oxide/semiconductor interface. Our sensor exhibits significantly reduced device noise, 2.1 × 10-9 V2 µm2/Hz at 1 Hz, compared to reference devices with the oxide/semiconductor interface operated at both inversion and depletion modes. Further improvement can be anticipated by wrapping the nanowire by such a Schottky junction, thereby eliminating all oxide/semiconductor interfaces. Hence, a combination of the low-noise SiNW-SJGFET device with a sensing surface of the Nernstian response limit holds promises for future high signal-to-noise ratio sensor applications.


Asunto(s)
Nanocables , Relación Señal-Ruido , Silicio/química , Transistores Electrónicos , Diseño de Equipo
14.
ACS Sens ; 2(8): 1160-1166, 2017 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-28745041

RESUMEN

Low-frequency noise (LFN) is of significant implications in ion sensing. As a primary component of LFN for ion sensing in electrolytes, the solid/liquid interfacial noise remains poorly explored especially regarding its relation to the surface binding/debinding dynamic properties. Here, we employ impedance spectroscopy to systematically characterize this specific noise component for its correlation to the dynamic properties of surface protonation (i.e., hydrogen binding) and deprotonation (i.e., hydrogen debinding) processes. This correlation is facilitated by applying our recently developed interfacial impedance model to ultrathin TiO2 layers grown by means of atomic layer deposition (ALD) on a TiN metallic electrode. With an excellent fitting of the measured noise power density spectra by the model for the studied TiO2 layers, we are able to extract several characteristic dynamic parameters for the TiO2 sensing surface. The observed increase of noise with TiO2 ALD cycles can be well accounted for with an increased average binding site density. This study provides insights into how detailed surface properties may affect the noise performance of an ion sensor operating in electrolytes.

15.
Atmos Pollut Res ; 8(5): 873-884, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30505154

RESUMEN

The Desert Southwest Coarse Particulate Matter Study was undertaken to further our understanding of the spatial and temporal variability and sources of fine and coarse particulate matter (PM) in rural, arid, desert environments. Sampling was conducted between February 2009 and February 2010 in Pinal County, AZ near the town of Casa Grande where PM concentrations routinely exceed the U.S. National Ambient Air Quality Standards (NAAQS) for both PM10 and PM2.5. In this desert region, exceedances of the PM10 NAAQS are dominated by high coarse particle concentrations, a common occurrence in this region of the United States. This work expands on previously published measurements of PM mass and chemistry by examining the sources of fine and coarse particles and the relative contribution of each to ambient PM mass concentrations using the positive matrix factorization receptor model (Clements et al., 2014). Coarse particles within the region were apportioned to nine sources including primary biological aerosol particles (PBAPs - 25%), crustal material (20%), re-entrained road dust (11%), feedlot (11% at the site closest to a cattle feedlot), secondary particles (10%), boron-rich crustal material (9%), and transported soil (6%), with minor contributions from ammonium nitrate, and salt (considered to be NaCl). Fine particles within the region were apportioned to six sources including motor vehicles (37%), road dust (29%), lead-rich (10%), with minor contributions from brake wear, crustal material, and salt. These results can help guide local air pollution improvement strategies designed to reduce levels of PM to below the NAAQS.

16.
Hum Psychopharmacol ; 31(2): 135-43, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26876224

RESUMEN

OBJECTIVE: Alpha BRAIN® is a nootropic supplement that purports to enhance cognitive functioning in healthy adults. The goal of this study was to investigate the efficacy of this self-described cognitive enhancing nootropic on cognitive functioning in a group of healthy adults by utilizing a randomized, double blind, placebo-controlled design. METHODS: A total of 63-treatment naïve individuals between 18 and 35 years of age completed the randomized, double-blind, placebo controlled trial. All participants completed a 2-week placebo run in before receiving active product, Alpha BRAIN® or new placebo, for 6 weeks. Participants undertook a battery of neuropsychological tests at randomization and at study completion. Primary outcome measures included a battery of neuropsychological tests and measures of sleep. RESULTS: Compared with placebo, Alpha BRAIN® significantly improved on tasks of delayed verbal recall and executive functioning. Results also indicated significant time-by-group interaction in delayed verbal recall for the Alpha BRAIN® group. CONCLUSIONS: The use of Alpha BRAIN® for 6 weeks significantly improved recent verbal memory when compared with controls, in a group of healthy adults. While the outcome of the study is encouraging, this is the first randomized controlled trial of Alpha BRAIN®, and the results merit further study.


Asunto(s)
Suplementos Dietéticos , Nootrópicos/administración & dosificación , Preparaciones Farmacéuticas/administración & dosificación , Administración Oral , Adolescente , Adulto , Método Doble Ciego , Función Ejecutiva , Humanos , Recuerdo Mental , Pruebas Neuropsicológicas , Sueño , Percepción del Habla , Resultado del Tratamiento , Adulto Joven
17.
Nanotechnology ; 26(37): 375201, 2015 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-26302818

RESUMEN

We present the first realization of a monolithically integrated piezoelectronic transistor (PET), a new transduction-based computer switch which could potentially operate conventional computer logic at 1/50 the power requirements of current Si-based transistors (Chen 2014 Proc. IEEE ICICDT pp 1-4; Mamaluy et al 2014 Proc. IWCE pp 1-2). In PET operation, an input gate voltage expands a piezoelectric element (PE), transducing the input into a pressure pulse which compresses a piezoresistive element (PR). The PR resistance goes down, transducing the signal back to voltage and turning the switch 'on'. This transduction physics, in principle, allows fast, low-voltage operation. In this work, we address the processing challenges of integrating chemically incompatible PR and PE materials together within a surrounding cage against which the PR can be compressed. This proof-of-concept demonstration of a fully integrated, stand-alone PET device is a key step in the development path toward a fast, low-power very large scale integration technology.

18.
Neuropsychology ; 29(4): 550-60, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25893972

RESUMEN

OBJECTIVE: The imagination inflation effect is a type of memory distortion defined as an increased tendency to falsely remember that an item has been seen, or an action has been performed, when it has only been imagined. For patients with very mild Alzheimer's disease (AD), susceptibility to the imagination inflation effect could have significant functional consequences in daily life. METHOD: We assessed whether patients with very mild AD were more or less susceptible to the imagination inflation effect when compared with healthy older adults. In the first session, participants were read an action statement such as "fill the pillbox" and engaged in 1 of 3 activities: listened to the statement being read, performed the action, or imagined performing the action. During the second session, participants imagined action statements from the first session, as well as new action statements. During the recognition test, participants were asked to determine whether action statements were or were not performed during the first session. RESULTS: We found that imagining performing actions increased the tendency of patients with very mild AD to falsely recall the action as having been performed to an extent similar to that of healthy older adults. CONCLUSION: We concluded that, similar to healthy older adults, patients with very mild AD were susceptible to the imagination inflation effect, which we attributed to difficulties with source monitoring and reliance on familiarity.


Asunto(s)
Envejecimiento/psicología , Enfermedad de Alzheimer/psicología , Disfunción Cognitiva/psicología , Imaginación , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Memoria , Recuerdo Mental , Reconocimiento en Psicología
19.
Alzheimers Dement (Amst) ; 1(4): 387-94, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27239520

RESUMEN

INTRODUCTION: We investigated whether event-related potentials (ERP) collected in outpatient settings and analyzed with standardized methods can provide a sensitive and reliable measure of the cognitive deficits associated with early Alzheimer's disease (AD). METHODS: A total of 103 subjects with probable mild AD and 101 healthy controls were recruited at seven clinical study sites. Subjects were tested using an auditory oddball ERP paradigm. RESULTS: Subjects with mild AD showed lower amplitude and increased latency for ERP features associated with attention, working memory, and executive function. These subjects also had decreased accuracy and longer reaction time in the target detection task associated with the ERP test. DISCUSSION: Analysis of ERP data showed significant changes in subjects with mild AD that are consistent with the cognitive deficits found in this population. The use of an integrated hardware/software system for data acquisition and automated data analysis methods make administration of ERP tests practical in outpatient settings.

20.
Am J Alzheimers Dis Other Demen ; 29(8): 718-22, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24829061

RESUMEN

There are numerous measures for detecting the presence of dementia and quantifying its severity and progression. We analyzed the relations between scores on 5 commonly used measures (Mini-Mental State Examination, Montreal Cognitive Assessment, Alzheimer's Disease Assessment Scale-Cognitive Subscale, Activities of Daily Living Scale, and Global Deterioration Scale) of 101 successive admissions to a memory clinic. Patients were included in the analysis only if they received a diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) pathophysiological process or probable AD and if they received all measures. Regression analysis yielded 20 linear equations that allow for conversion between test scores on any 2 measures. Further, participants were grouped by MMSE scores with regard to level of disease severity, allowing for the creation of a quick reference table for estimating an approximate score range between measures. Results from this study provide a useful tool for clinicians when comparing between multiple different instruments that measure the mental status and functional ability of individuals with AD and MCI due to AD pathology.


Asunto(s)
Actividades Cotidianas , Enfermedad de Alzheimer/diagnóstico , Disfunción Cognitiva/diagnóstico , Escala del Estado Mental , Estudios de Cohortes , Humanos , Modelos Lineales , Pruebas Neuropsicológicas , Psicometría , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
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