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1.
Mol Ecol ; 33(6): e17284, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38258354

RESUMEN

Zooplankton undergo a diel vertical migration (DVM) which exposes them to gradients of light, temperature, oxygen, and food availability on a predictable daily schedule. Disentangling the co-varying and potentially synergistic interactions on metabolic rates has proven difficult, despite the importance of this migration for the delivery of metabolic waste products to the distinctly different daytime (deep) and nighttime (surface) habitats. This study examines the transcriptomic and proteomic profiles of the circumglobal migratory copepod, Pleuromamma xiphias, over the diel cycle. The transcriptome showed that 96% of differentially expressed genes were upregulated during the middle of the day - the period often considered to be of lowest zooplankton activity. The changes in protein abundance were more spread out over time, peaking (42% of comparisons) in the early evening. Between 9:00 and 15:00, both the transcriptome and proteome datasets showed increased expression related to chitin synthesis and degradation. Additionally, at 09:00 and 22:00, there were increases in myosin and vitellogenin proteins, potentially linked to the stress of migration and/or reproductive investment. Based on protein abundances detected, there is an inferred switch in broad metabolic processes, shifting from electron transport system in the day to glycolysis and glycogen mobilization in the afternoon/evening. These observations provide evidence of the diel impact of DVM on transcriptomic and proteomic pathways that likely influence metabolic processes and subsequent excretion products, and clarify how this behaviour results in the direct rapid transport of waste metabolites from the surface to the deep ocean.


Asunto(s)
Copépodos , Transcriptoma , Animales , Transcriptoma/genética , Proteoma/genética , Copépodos/genética , Proteómica , Perfilación de la Expresión Génica , Zooplancton
2.
Microb Cell Fact ; 22(1): 171, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37661274

RESUMEN

Polyhydroxyalkanoate (PHA) is one of the most promising materials for replacing petroleum-based plastics, and it can be produced from various renewable biomass sources. In this study, PHA production was conducted using Halomonas sp. YLGW01 utilizing mixed volatile fatty acids (VFAs) as carbon sources. The ratio and concentration of carbon and nitrogen sources were optimized through mixture analysis and organic nitrogen source screening, respectively. It was found that the highest cell dry weight (CDW) of 3.15 g/L and PHA production of 1.63 g/L were achieved when the ratio of acetate to lactate in the mixed VFAs was 0.45:0.55. Furthermore, supplementation of organic nitrogen sources such as soytone resulted in a ninefold increase in CDW (reaching 2.32 g/L) and a 22-fold increase in PHA production (reaching 1.60 g/L) compared to using inorganic nitrogen sources. Subsequently, DO-stat, VFAs consumption rate stat, and pH-stat fed-batch methods were applied to investigate and evaluate PHA productivity. The results showed that when pH-stat-based VFAs feeding was employed, a CDW of 7 g/L and PHA production of 5.1 g/L were achieved within 68 h, with a PHA content of 73%. Overall, the pH-stat fed-batch strategy proved to be effective in enhancing PHA production by Halomonas sp. YLGW01 utilizing VFAs.


Asunto(s)
Halomonas , Polihidroxialcanoatos , Halomonas/genética , Ácidos Grasos Volátiles , Carbono , Ácido Láctico , Nitrógeno
3.
Sensors (Basel) ; 23(21)2023 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-37960666

RESUMEN

In this paper, we propose a data classification and analysis method to estimate fire risk using facility data of thermal power plants. To estimate fire risk based on facility data, we divided facilities into three states-Steady, Transient, and Anomaly-categorized by their purposes and operational conditions. This method is designed to satisfy three requirements of fire protection systems for thermal power plants. For example, areas with fire risk must be identified, and fire risks should be classified and integrated into existing systems. We classified thermal power plants into turbine, boiler, and indoor coal shed zones. Each zone was subdivided into small pieces of equipment. The turbine, generator, oil-related equipment, hydrogen (H2), and boiler feed pump (BFP) were selected for the turbine zone, while the pulverizer and ignition oil were chosen for the boiler zone. We selected fire-related tags from Supervisory Control and Data Acquisition (SCADA) data and acquired sample data during a specific period for two thermal power plants based on inspection of fire and explosion scenarios in thermal power plants over many years. We focused on crucial fire cases such as pool fires, 3D fires, and jet fires and organized three fire hazard levels for each zone. Experimental analysis was conducted with these data set by the proposed method for 500 MW and 100 MW thermal power plants. The data classification and analysis methods presented in this paper can provide indirect experience for data analysts who do not have domain knowledge about power plant fires and can also offer good inspiration for data analysts who need to understand power plant facilities.

4.
Nanotechnology ; 34(9)2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36541520

RESUMEN

Tunnel field-effect transistors (TFETs) have garnered great interest as an option for the replacement of metal-oxide-semiconductor field-effect transistors owing to their extremely low off-current and fast switching suitable for low-power-consumption applications. However, conventional doped TFETs have the disadvantage of introducing undesirable random dopant fluctuation (RDF) events, which cause a large variance in the threshold voltage and ambipolar leakage current at negative gate voltages. In this study, a simple approach for charge plasma-based doping-less TFETs (DL-TFETs), including the Ge/Si bilayer frame, which affects the RDF and low on-current issues, was developed by the commercially available Silvaco Atlas device simulator. The use of the Ge/Si bilayer enhances the on-current and point subthreshold swing to 1.4 × 10-6A and 16.6 mV dec-1, respectively. In addition, the dependencies of the Ge/Si junction boundary position and Ge content were examined systematically to attain a firm understanding of the electrical features in DL-TFETs.

5.
Graefes Arch Clin Exp Ophthalmol ; 260(11): 3505-3515, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35678840

RESUMEN

PURPOSE: To evaluate the retinal vasculature and vasoreactivity of patients with hypertension (HTN) using spectral domain optical coherence tomography angiography (SD-OCTA). METHODS: Patients with and without a diagnosis of HTN were included in this cross-sectional observational study. All eyes were imaged with SD-OCTA using 3 mm × 3 mm and 6 mm × 6 mm centered on both the fovea and optic disk. A second 6 mm × 6 mm scan was taken after a 30 s breath-hold. Vessel density (VD), vessel skeletonized density (VSD), and fractal dimension (FD) were calculated using customized MATLAB scripts. Vessel diameter index (VDI) was obtained by taking the ratio of VD to VSD. Vasoreactivity was measured by subtracting the VD or VSD before and after breath-hold (∆VD, ∆VSD). RESULTS: Twenty-three eyes with HTN (17 patients) and 17 control eyes (15 patients) were included. In the 6 mm × 6 mm angiogram centered on fovea, the superficial capillary plexus (SCP) VD (ß = - 0.029, p = 0.012), VSD (ß = - 0.004, p = 0.043) and the choriocapillaris VD (ß = - 0.021, p = 0.030) were significantly decreased in HTN compared to control eyes. Similarly, FD was decreased in both the SCP (ß = - 0.012, p = 0.013) and choriocapillaris (ß = - 0.009, p = 0.030). In the 3 mm × 3 mm angiogram centered on optic disk, SCP VDI (ß = - 0.364, p = 0.034) was decreased. ∆VD and ∆VSD were both reduced in the DCP (ß = - 0.034, p = 0.032; ß = - 0.013, p = 0.043) and ∆VSD was elevated in the choriocapillaris of HTN eyes (ß = 0.004, p = 0.032). CONCLUSIONS: The study used SD-OCTA to show significant differences in the retinal vasculature of hypertensive patients. It was also the first to demonstrate the potential of OCT-A to investigate retinal vascular reactivity in patients with HTN.


Asunto(s)
Hipertensión , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodos , Estudios Transversales , Vasos Retinianos , Fóvea Central/irrigación sanguínea , Microvasos , Hipertensión/complicaciones , Hipertensión/diagnóstico
6.
Nanotechnology ; 32(14): 14LT01, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33316794

RESUMEN

The n+-base width of a two-terminal vertical thyristor fabricated with n++(top-emitter)-p+(base)-n+(base)-p++(bottom-emitter) epitaxial Si layers was designed to produce a cross-point memory cell without a selector. Both the latch-up and latch-down voltages increased linearly with the n+-base width, but the voltage increase slope of the latch-up was 2.6 times higher than that of the latch-down, and the memory window increased linearly with the n+-base width. There was an optimal n+-base width that satisfied cross-point memory cell operation; i.e. ∼180 nm, determined by confirming that the memory window principally determined the condition of operation as a cross-point memory cell (i.e. one half of the latch-up voltage being less than the latch-down voltage and a sufficient voltage difference existing between the latch-up and latch-down voltages). The vertical thyristor designed with the optimal n+-base width produced write/erase endurance cycles of ∼109 by sustaining a memory margin (I on /I off ) of 102, and the cross-point memory cell array size of 1024 K sustained a sensing margin of 99 %, which is comparable with that of current dynamic random-access memory (DRAM). In addition, in the cross-point memory cell array, a ½ bias scheme (i.e. a memory array size of 1024 K for 0.02 W of power consumption) resulted in lower power consumption than a [Formula: see text] bias scheme (i.e. a memory array size of 256 K for 0.02 W of power consumption).

7.
Nanotechnology ; 32(5): 055301, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33179607

RESUMEN

Magnetic tunneling junction (MTJ) materials such as CoFeB, Co, Pt, MgO, and the hard mask material such as W and TiN were etched with a reactive ion beam etching (RIBE) system using H2/NH3. By using gas mixtures of H2 and NH3, especially with the H2/NH3( 2:1) ratio, higher etch rates of MTJ related materials and higher etch selectivities over mask materials (>30) could be observed compared to those etching using pure H2( no etching) and NH3. In addition, no significant chemical and physical damages were observed on etched magnetic materials surfaces and, for CoPt and MTJ nanoscale patterns etched by the H2/NH3( 2:1) ion beam, highly anisotropic etch profiles >83° with no sidewall redeposition could be observed. The higher etch rates of magnetic materials such as CoFeB by the H2/NH3( 2:1) ion beam compared to those by H2 ion beam or NH3 ion beam are believed to be related to the formation of volatile metal hydrides (MH, M = Co, Fe, etc) through the reduction of M-NHx( x = 1 ∼ 3) formed in the CoFeB surface by the exposure to NH3 ion beam. It is believed that the H2/NH3 RIBE is a suitable technique in the etching of MTJ materials for the next generation nanoscale spin transfer torque magnetic random access memory (STT-MRAM) devices.

8.
Nanotechnology ; 31(12): 12LT01, 2020 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-31739301

RESUMEN

We proposed a dislocation sink technology for achieving Si1-x Ge x multi-bridge-channel field-effect-transistor beyond 5 nm transistor design-rule that essentially needs an almost crystalline-defect-free Si1-x Ge x channel. A generation of a dislocation sink via H+ implantations in a strain-relaxed Si0.7Ge0.3 layer grown on a Si substrate and a following annealing almost annihilate completely misfit and threading dislocations located near the interface between a relaxed Si0.7Ge0.3 layer and a Si substrate. A real-time (continuous heating from room temperature to 600 °C) in situ high-resolution-transmission-electron-microscopy and inverse-fast-Fourier-transform image observation at 1.25 MV acceleration voltage obviously demonstrated the annihilation process between dislocation sinks and remaining misfit and threading dislocations during a thermal annealing, called the [SiI or GeI + V Si or V Ge â†’ Si1-x Ge x ] annihilation process, where SiI, GeI, V Si, and V Ge are interstitial Si, interstitial Ge, Si vacancy, and Ge vacancy, respectively. In particular, the annihilation process efficiency greatly depended on the dose of H+ implantation and annealing temperature; i.e. a maximum annihilation process efficiency achieved at 5 × 1015 atoms cm-2 and 800 °C.

9.
Clin Gastroenterol Hepatol ; 14(8): 1081-5, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27189913

RESUMEN

Intestinal transplantation remains a life-saving option for patients with severe intestinal failure. With the advent of advanced tissue engineering techniques, great strides have been made toward manufacturing replacement tissues and organs, including the intestine, which aim to avoid transplant-related complications. The current paradigm is to seed a biocompatible support material (scaffold) with a desired cell population to generate viable replacement tissue. Although this technique has now been extended by the three-dimensional (3D) printing of geometrically complex scaffolds, the overall approach is hindered by relatively slow turnover and negative effects of residual scaffold material, which affects final clinical outcome. Methods recently developed for scaffold-free 3D bioprinting may overcome such obstacles and should allow for rapid manufacture and deployment of "bioprinted organs." Much work remains before 3D bioprinted tissues can enter clinical use. In this brief review we examine the present state and future perspectives of this nascent technology before full clinical implementation.


Asunto(s)
Gastroenterología/métodos , Enfermedades Gastrointestinales/terapia , Impresión Tridimensional , Investigación Biomédica/tendencias , Gastroenterología/tendencias , Humanos
10.
Nanotechnology ; 27(29): 295705, 2016 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-27292593

RESUMEN

By fabricating CoFeB/MgO/CoFeB-based perpendicular-magnetic tunnel junction (p-MTJ) spin-valves stacked with a [Co/Pd] n -SyAF layer based on a TiN bottom electrode on a 12 inch Si wafer (001) substrate, we investigated how the bridging layers of Ta, Ti, and Pt and their thickness variation affected the tunneling magneto-resistance (TMR) ratio of Co2Fe6B2 pinned-layer behavior in magnetic-tunnel-junctions. TMR ratios for Ta, Ti, and Pt bridging layers were observed to be 64.1, 70.2, and 29.5%, respectively. It was confirmed by high resolution transmission electron microscopy (HR-TEM) that this difference resulted from CoFeB/MgO/CoFeB MTJ layers with Ta and Ti bridging layers being textured well with a bcc (100) structure, indicating that Ta and Ti bridging layers bridged SyAF fcc (111) and MTJ bcc (100). On the other hand, the MTJ layer with Pt bridging layer was incorrectly textured, indicating that a Pt bridging layer is unsuitable to bridge SyAF fcc (111) and MTJ bcc (100) due to Pt being diffused into the CoFeB pinned-layer. In addition, perpendicular magnetic anisotropy (PMA) behavior of the CoFeB pinned-layer was found to depend strongly on a bridging layer thickness; higher TMRs of Ta and Ti were observed at the optimal bridging layers' thickness, which enable the realization of PMAs of the pinned-layer and ferro-coupling of the pinned-layer with the lower-SyAF layer. Among the three bridging materials (Ta, Ti, and Pt), we observed that Ti showed the highest TMR ratio and widest thickness range for a high TMR ratio, indicating that a higher TMR ratio is needed to obtain the best deposition process margin.

11.
Nanotechnology ; 27(48): 485203, 2016 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-27796272

RESUMEN

For the double MgO based perpendicular magnetic tunneling junction (p-MTJ) spin-valves with a top Co2Fe6B2 free layer ex situ annealed at 400 °C, the tunneling-magnetoresistance ratio (TMR) strongly depended on the platinum (Pt) seed layer thickness (t Pt): it peaked (∼134%) at a specific t Pt (3.3 nm). The TMR ratio was initially and slightly increased from 113%-134% by the enhancement of the magnetic moment of the Co2Fe6B2 pinned layer when t Pt increased from 2.0-3.3 nm, and then rapidly decreased from 134%-38.6% by the degrading face-centered-cubic crystallinity of the MgO tunneling barrier when t Pt increased from 3.3-14.3 nm.

12.
Nanotechnology ; 26(47): 475705, 2015 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-26536817

RESUMEN

We design a Co2Fe6B2/MgO-based p-MTJ spin-valve without a [Co/Pt] n lower synthetic-antiferromagnetic (SyAF) layer to greatly reduce the 12-inch wafer fabrication cost of the p-MTJ spin-valve. This spin-valve achieve a tunneling magnetoresistance (TMR) of 158% and an exchange field (H ex) of 1.4 kOe at an ex situ annealing temperature of >350 °C, which ensures writing error immunity. In particular, the TMR ratio strongly depends on the body-center-cubic capping-layer nanoscale thickness (t bcc), i.e., the TMR ratio peaks at t bcc = 0.6 nm.

13.
Nanotechnology ; 26(19): 195702, 2015 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-25895901

RESUMEN

The TMR ratio of Co2Fe6B2/MgO-based p-MTJ spin valves stacked with a [Co/Pd]n-SyAF layer decreased rapidly when the ex situ magnetic annealing temperature (Tex) was increased from 275 to 325 °C, and this decrease was associated with degradation of the Co2Fe6B2 pinned layer rather than the Co2Fe6B2 free layer. At a Tex above 325 °C the amorphous Co2Fe6B2 pinned layer was transformed into a face-centered-cubic (fcc) crystalline layer textured from [Co/Pd]n-SyAF, abruptly reducing the Δ1 coherence tunneling of perpendicular-spin-torque electrons between the (100) MgO tunneling barrier and the fcc Co2Fe6B2 pinned layer.

14.
Nanotechnology ; 25(43): 435204, 2014 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-25297517

RESUMEN

Flexible conductive-bridging random-access-memory (RAM) cells were fabricated with a cross-bar memory cell stacked with a top Ag electrode, conductive polymer (poly(n-vinylcarbazole): PVK), electrolyte (polyethylene oxide: PEO), bottom Pt electrode, and flexible substrate (polyethersulfone: PES), exhibiting the bipolar switching behavior of resistive random access memory (ReRAM). The cell also exhibited bending-fatigue-free nonvolatile memory characteristics: i.e., a set voltage of 1.0 V, a reset voltage of -1.6 V, retention time of >1 × 10(5) s with a memory margin of 9.2 × 10(5), program/erase endurance cycles of >10(2) with a memory margin of 8.4 × 10(5), and bending-fatigue-free cycles of ∼1 × 10(3) with a memory margin (I(on)/I(off)) of 3.3 × 10(5).

15.
Phys Chem Chem Phys ; 16(34): 18205-10, 2014 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-25054543

RESUMEN

We found that Cd0.5Zn0.5S-ZnS core (4.2 nm in diameter)-shell (1.2 nm in thickness) quantum dots (QDs) demonstrated a typical energy-down-shift (2.76-4.96 → 2.81 eV), which absorb ultra-violet (UV) light (250-450 nm in wavelength) and emit blue visible light (∼442 nm in wavelength). They showed the quantum yield of ∼80% and their coating on the SiNX film textured p-type silicon solar-cells enhanced the external-quantum-efficiency (EQE) of ∼30% at 300-450 nm in wavelength, thereby enhancing the short-circuit-current-density (JSC) of ∼2.23 mA cm(-2) and the power-conversion-efficiency (PCE) of ∼1.08% (relatively ∼6.04% increase compared with the reference without QDs for p-type silicon solar-cells). In particular, the PCE peaked at a specific coating thickness of the Cd0.5Zn0.5S-ZnS core-shell QD layer; i.e., the 1.08% PCE enhancement at the 8.8 nm thick QD layer.

16.
Int J Biol Macromol ; 254(Pt 1): 127475, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37863147

RESUMEN

Polyhydroxybutyrate (PHB) is a well-known biodegradable bioplastic synthesized by microorganisms and can be produced from volatile fatty acids (VFAs). Among VFAs acetate can be utilized by Halomonas sp. YLGW01 for growth and PHB production. In this study, Halomonas sp. JJY01 was developed through introducing acetyl-CoA acetyltransferase (atoAD) with LacIq-Ptrc promoter into Halomonas sp. YLGW01. The effect of expression of atoAD on acetate was investigated by comparison with acetate consumption and PHB production. Shake-flask study showed that Halomonas sp. JJY01 increased acetate consumption rate, PHB yield and PHB production (0.27 g/L/h, 0.075 g/g, 0.72 g/L) compared to the wild type strain (0.17 g/L/h, 0.016 g/g, 0.11 g/L). In 10 L fermenter scale fed-batch fermentation, the growth of Halomonas sp. JJY01 resulted in higher acetate consumption rate, PHB yield and PHB titer (0.55 g/L/h, 0.091 g/g, 4.6 g/L) than wild type strain (0.35 g/L/h, 0.067 h/h, 2.9 g/L). These findings demonstrate enhanced acetate utilization and PHB production through the introduction of atoAD in Halomonas strains.


Asunto(s)
Halomonas , Hidroxibutiratos , Hidroxibutiratos/metabolismo , Halomonas/genética , Halomonas/metabolismo , Acetil-CoA C-Acetiltransferasa/metabolismo , Polihidroxibutiratos , Acetatos/metabolismo , Poliésteres/metabolismo
17.
Nanomaterials (Basel) ; 14(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38921931

RESUMEN

This work highlights the novel approach of incorporating potassium iodide (KI) doping during the synthesis of In0.53P0.47 core quantum dots (QDs) to significantly reduce the concentration of vacancies (i.e., In vacancies; VIn-) within the bulk of the core QD and inhibit the formation of InPOx at the core QD-Zn0.6Se0.4 shell interfaces. The photoluminescence quantum yield (PLQY) of ~97% and full width at half maximum (FWHM) of ~40 nm were achieved for In0.53P0.47/Zn0.6Se0.4/Zn0.6Se0.1S0.3/Zn0.5S0.5 core/multi-shell QDs emitting red light, which is essential for a quantum-dot organic light-emitting diode (QD-OLED) without red, green, and blue crosstalk. KI doping eliminated VIn- in the core QD bulk by forming K+-VIn- substitutes and effectively inhibited the formation of InPO4(H2O)2 at the core QD-Zn0.6Se0.4 shell interface through the passivation of phosphorus (P)-dangling bonds by P-I bonds. The elimination of vacancies in the core QD bulk was evidenced by the decreased relative intensity of non-radiative unpaired electrons, measured by electron spin resonance (ESR). Additionally, the inhibition of InPO4(H2O)2 formation at the core QD and shell interface was confirmed by the absence of the {210} X-ray diffraction (XRD) peak intensity for the core/multi-shell QDs. By finely tuning the doping concentration, the optimal level was achieved, ensuring maximum K-VIn- substitution, minimal K+ and I- interstitials, and maximum P-dangling bond passivation. This resulted in the smallest core QD diameter distribution and maximized optical properties. Consequently, the maximum PLQY (~97%) and minimum FWHM (~40 nm) were observed at 3% KI doping. Furthermore, the color gamut of a QD-OLED display using R-, G-, and B-QD functional color filters (i.e., ~131.1%@NTSC and ~98.2@Rec.2020) provided a nearly perfect color representation, where red-light-emitting KI-doped QDs were applied.

18.
bioRxiv ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38617345

RESUMEN

Membrane-bound particles in plasma are composed of exosomes, microvesicles, and apoptotic bodies and represent ~1-2% of the total protein composition. Proteomic interrogation of this subset of plasma proteins augments the representation of tissue-specific proteins, representing a "liquid biopsy," while enabling the detection of proteins that would otherwise be beyond the dynamic range of liquid chromatography-tandem mass spectrometry of unfractionated plasma. We have developed an enrichment strategy (Mag-Net) using hyper-porous strong-anion exchange magnetic microparticles to sieve membrane-bound particles from plasma. The Mag-Net method is robust, reproducible, inexpensive, and requires <100 µL plasma input. Coupled to a quantitative data-independent mass spectrometry analytical strategy, we demonstrate that we can collect results for >37,000 peptides from >4,000 plasma proteins with high precision. Using this analytical pipeline on a small cohort of patients with neurodegenerative disease and healthy age-matched controls, we discovered 204 proteins that differentiate (q-value < 0.05) patients with Alzheimer's disease dementia (ADD) from those without ADD. Our method also discovered 310 proteins that were different between Parkinson's disease and those with either ADD or healthy cognitively normal individuals. Using machine learning we were able to distinguish between ADD and not ADD with a mean ROC AUC = 0.98 ± 0.06.

19.
bioRxiv ; 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38645098

RESUMEN

A thorough evaluation of the quality, reproducibility, and variability of bottom-up proteomics data is necessary at every stage of a workflow from planning to analysis. We share real-world case studies applying adaptable quality control (QC) measures to assess sample preparation, system function, and quantitative analysis. System suitability samples are repeatedly measured longitudinally with targeted methods, and we share examples where they are used on three instrument platforms to identify severe system failures and track function over months to years. Internal QCs incorporated at protein and peptide-level allow our team to assess sample preparation issues and to differentiate system failures from sample-specific issues. External QC samples prepared alongside our experimental samples are used to verify the consistency and quantitative potential of our results during batch correction and normalization before assessing biological phenotypes. We combine these controls with rapid analysis using Skyline, longitudinal QC metrics using AutoQC, and server-based data deposition using PanoramaWeb. We propose that this integrated approach to QC be used as a starting point for groups to facilitate rapid quality control assessment to ensure that valuable instrument time is used to collect the best quality data possible.

20.
bioRxiv ; 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38260300

RESUMEN

Alzheimer's disease (AD) is a prevalent and costly age-related dementia. Heritable factors account for 58-79% of variation in late-onset AD, but substantial variation remains in age-of- onset, disease severity, and whether those with high-risk genotypes acquire AD. To emulate the diversity of human populations, we utilized the AD-BXD mouse panel. This genetically diverse resource combines AD genotypes with multiple BXD strains to discover new genetic drivers of AD resilience. Comparing AD-BXD carriers to noncarrier littermates, we computed a novel quantitative metric for resilience to cognitive decline in the AD-BXDs. Our quantitative AD resilience trait was heritable and genetic mapping identified a locus on chr8 associated with resilience to AD mutations that resulted in amyloid brain pathology. Using a hippocampus proteomics dataset, we nominated the mitochondrial glutathione S reductase protein (GR or GSHR) as a resilience factor, finding that the DBA/2J genotype was associated with substantially higher GR abundance. By mapping protein QTLs (pQTLs), we identified synaptic organization and mitochondrial proteins coregulated in trans with a cis-pQTL for GR. We found four coexpression modules correlated with the quantitative resilience score in aged 5XFAD mice using paracliques, which were related to cell structure, protein folding, and postsynaptic densities. Finally, we found significant positive associations between human GSR transcript abundance in the brain and better outcomes on AD-related cognitive and pathology traits in the Religious Orders Study/Memory and Aging project (ROSMAP). Taken together, these data support a framework for resilience in which neuronal antioxidant pathway activity provides for stability of synapses within the hippocampus.

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