Water-repelling behavior of the 1-D hematite nano-network.

Hematite is an attractive material used as electron transport layer in perovskite-based solar cells. Being hydrophilic in nature it attracts moisture, which can be damaging for perovskite layers. Therefore, it is important to make hematite moisture repelling, which can be beneficial for applications in solar cells or for protecting iron surfaces from further rust formation. In this work, we demonstrate that the systematic irradiation of nanostructured hematite with low-energy argon ions (Ar+) at various ion fluences can change the surface wettability as well as promote the formation of junctions between nanorods. The nano-welded network of the irradiated hematite turns out to be hydrophobic. Using TRI3DYN simulations, ion-induced surface roughening, the presence of surface oxygen vacancies, and joining between adjacent nanorods are predicted. Furthermore, the water-repelling behavior of the irradiated nano-network is evaluated using density functional theory (DFT) simulations by determining the interaction of water molecules with the surface. The interconnected hematite nano-network also shows a notable improvement in electrical conductivity.

Computational design of novel MAX phase alloys as potential hydrogen storage media combining first principles and cluster expansion methods.

Finding a suitable material for hydrogen storage under ambient atmospheric conditions is challenging for material scientists and chemists. In this work, using a first principles based cluster expansion approach, the hydrogen storage capacity of the Ti2AC (A = Al, Ti, Cr, Mn, Fe, Co, Ni, Cu, and Zn) MAX phase and its alloys was studied. We found that hydrogen is energetically stable in Ti-A layers in which the tetrahedral site consisting of one A atom and three Ti atoms is energetically more favorable for hydrogen adsorption than other sites in the Ti-A layer. Ti2CuC has the highest hydrogen adsorption energy than other Ti2AC phases. We find that the 83.33% Cu doped Ti2AlxCu1-xC alloy structure is both energetically and dynamically stable and can store 3.66 wt% hydrogen under ambient atmospheric conditions, which is higher than that stored by both Ti2AlC and Ti2CuC phases. These findings indicate that the hydrogen capacity of the MAX phase can be significantly improved by doping an appropriate atom species.

A critical review on solar chimney power plant technology: influence of environment and geometrical parameters, barriers for commercialization, opportunities, and carbon emission mitigation.

Solar chimney power plant (SCPP) is one of the promising technologies to convert solar energy into carbon-free power generation. It has cost competitiveness, environment friendly and longer service life. Although remarkable advancements were achieved, commercialization aspect of the SCPP has not been established so far. Feasibility assessment of the large-scale plants was carried out by researchers in different climatic conditions across the globe but none of the studies materialized to date. However, it is almost four decades from the development of the first prototype, and no studies have been discussed the barriers to commercialization of the SCPP yet. Therefore, in this present study, a-state-of-the-art review has been presented which discussed the overview of SCPP technologies, factors affecting the flow and performance characteristics of the plant and major barriers in the commercialization aspect of the plant. The overview of SCPP technology including its global status and recent advances are spotlighted. The power potential and carbon emission mitigation of the SCPP based on the climatic condition and geographical location was studied by taking India as an example. In addition to that, the major challenges and opportunities in the SCPP are also addressed. Based on the analysis, a few recommendations are given for commercialization the plant.

Vascular Endothelial Growth Factor Receptor-1 Modulates Hypoxia-Mediated Endothelial Senescence and Cellular Membrane Stiffness via YAP-1 Pathways.

Hypoxia-induced endothelial cell (EC) dysfunction has been implicated as potential initiators of different pathogenesis, including Alzheimer's disease and vascular dementia. However, in-depth structural, mechanical, and molecular mechanisms leading to EC dysfunction and pathology need to be revealed. Here, we show that ECs exposed to hypoxic conditions readily enter a senescence phenotype. As expected, hypoxia upregulated the expression of vascular endothelial growth factor (VEGFs) and its receptors (VEGFRs) in the ECs. Interestingly, Knockdown of VEGFR-1 expression prior to hypoxia exposure prevented EC senescence, suggesting an important role of VEGFR-1 expression in the induction of EC senescence. Using atomic force microscopy, we showed that senescent ECs had a flattened cell morphology, decreased membrane ruffling, and increased membrane stiffness, demonstrating unique morphological and nanomechanical signatures. Furthermore, we show that hypoxia inhibited the Hippo pathway Yes-associated protein (YAP-1) expression and knockdown of YAP-1 induced senescence in the ECs, supporting a key role of YAP-1 expression in the induction of EC senescence. And importantly, VEGFR-1 Knockdown in the ECs modulated YAP-1 expression, suggesting a novel VEGFR-1-YAP-1 axis in the induction of hypoxia-mediated EC senescence. In conclusion, VEGFR-1 is overexpressed in ECs undergoing hypoxia-mediated senescence, and the knockdown of VEGFR-1 restores cellular structural and nanomechanical integrity by recovering YAP-1 expression.

A Steady-State Approach for Studying Valley Relaxation Using an Optical Vortex Beam.

Spin-valley coupling in monolayer transition-metal dichalcogenides gives rise to valley polarization and coherence effect, limited by intervalley scattering caused by exciton-phonon, exciton-impurity, and electron-hole exchange interactions (EHEIs). We explore an approach to tune the EHEI by controlling the exciton center of mass momentum (COM) utilizing the photon distribution of higher-order optical vortex beams. By virtue of this, we have observed exciton-COM-dependent valley depolarization and decoherence, which gives us the ability to probe the valley relaxation time scale in a steady-state measurement. Our steady-state technique to probe the valley dynamics can open up a new paradigm to explore the physics of excitons in two-dimensional systems.

Alteration of Wettability of Copper-Copper Oxide Nanocomposites through Cu-O Bond Breaking Swayed by Ultraviolet and Electron Irradiation.

Converting a nonwetting surface to a highly wetting one, aided by ultraviolet radiation, is well explored. Here, in this work, we show just the reverse behavior of a copper-copper oxide nanocomposite surface where ultraviolet radiation turned the superhydrophilic surface to a superhydrophobic one. This observation is explained both experimentally and theoretically using first-principles density functional theory-based calculations considering the metal-oxygen (Cu-O) bond breaking and related change in surface chemistry. This observation has further been corroborated with electron irradiation on the same nanocomposite material. To the best of our knowledge, for the first time, we show that the radiation-induced breaking of the copper-oxygen bond makes the nanostructure surface energetically unfavorable for water adsorption.

A comprehensive review on the factors affecting thermochemical conversion efficiency of algal biomass to energy.

Algae are one of the most viable feedstock options that can be converted into different bioenergies viz., bioethanol, biobutanol, biodiesel, biomethane, biohydrogen, etc. owing to their renewable, sustainable and economic credibility features. Algal biomass to fuel biorefining process is generally classified into three categories as chemical, biochemical and thermochemical methods. The present article aims to provide a state-of-the-art review on the factors affecting the thermochemical conversion process of algal biomass to bioenergy. Further, reaction conditions of each techniques (torrefaction, pyrolysis, gasification and hydrothermal process) influence biochar, bio-oil and syngas yield were discussed. Reaction parameters or factors such as reactor temperature, residence time, pressure, biomass load/feedstock composition, catalyst addition and carrier gas flow affecting process efficiency in terms of product yield and quality were spotlighted and extensively discussed with copious literature. It also presents the novel insights on production of solid (char), liquid (bio-oil) and gaseous (syngas) biofuel through torrefaction, pyrolysis and gasification, respectively. It is found that the energy intensive drying was more efficient mode involved in thermochemical process for wet algal biomass. However other modes of thermochemical process were having unique feature on improving the product yield and quality. Among the various factors, reaction temperature and residence time were relatively more important factors which affected the process efficiency. The other factors signposted in this review will lay a roadmap to researchers to choose an optimal thermochemical conditions for high quality end product. Lastly, the perspectives and challenges in thermochemical conversion algae biomass to biofuels were also discussed.

Recent advances in thermochemical methods for the conversion of algal biomass to energy.

Thermochemical techniques are being operated for the complete conversion of diverse biomasses to biofuels. Among the feedstocks used for thermochemical processes, algae are the promising biomass sources owing to their advantages over other feedstocks such as biomass productivity, renewability and sustainability. Due to several advantages, algal biomass is considered as a source for third generation biofuel. This review work aims to provide a state-of-the-art on the most commonly used thermochemical methods namely torrefaction, pyrolysis, and gasification processes. Furthermore, the production of biofuels from algal biomass was comprehensively articulated. Different algal strains used in thermochemical techniques and their conditions of operation were compared and discussed. The yield and quality of solid (char), liquid (bio-oil) and gaseous (syngas) products obtained through thermochemical methods were reviewed and analysed to understand the efficacy of each technique. End product percentage, quality and advantages of the torrefaction, pyrolysis, and gasification were summarized. It is found that the biofuel produced from the torrefaction process was easy to store and deliver and had higher utilization efficiency. Among the existing thermochemical methods, the pyrolysis process was widely used for the complete conversion of algal biomass to bio-oil or char. This study also revealed that the gasification (supercritical) method was the most energy efficient process for conversion of wet algal biomass. The reactor used in the thermochemical process and its subprocess was also highlighted. This study revealed that the fixed bed reactor was suitable for small scale production whereas the fluidized bed reactor could be scaled up for industrial production. In addition to that environmental impacts of the products were also spotlighted. Finally, the perspectives and challenges of algal biomass to bioenergy conversion were addressed.

Development of double porous poly (ε - caprolactone)/chitosan polymer as tissue engineering scaffold.

Polymer blend made from poly(ε - caprolactone)/chitosan (PCL/CHT) offers interesting opportunities for biological applications. The paper presents a new way to fabricate PCL/CHT double-porosity (macrovoids with interconnected microporosity) membrane materials from a chemical optimization of the solvent and non-solvent phases and from a modified phase inversion technique. By varying the PCL/CHT proportion, it is shown that it is possible to improve the chemical and physical properties of the CHT carbohydrate polymer. The PCL/CHT membranes are fully characterized in term of physico-chemical properties (ATR-FTIR, XRD and DSC) to understand the miscibility of the two-polymer blend. Morphological characterization by SEM shows that by increasing CHT wt% in the blend, the size of the macrovoids was increasing. Rapid enzymatic degradation of PCL from all the blend was found by using lipase (from P. cepacia). The mechanisms at the origin of the morphological structuration of the material is also discussed. To test the ability to operate these materials as small diameter vascular scaffolds, cell culture with human umbilical vein endothelial cells (HUVECs) were carried out on the membrane and the results analyzed with laser scanning confocal microscopy (LSCM). Data suggest that the blend membrane with higher concentration of CHT polymer wt% have suitable properties that promote high number of cells on the surface by maintaining cellular cytoskeleton integrity within 3 days. The blend membrane with a double porous morphology could be potentially applicable in future for small diameter vascular graft application. The surface macrovoids (20-90 µm) could be useful for three-dimensional cellular adhesion and proliferation and interconnected microporous spongy network (7-20 µm) is expected to transfer essential nutrients, oxygen, growth factor between the macrovoids and the supernatant.

Double porous poly (Ɛ-caprolactone)/chitosan membrane scaffolds as niches for human mesenchymal stem cells.

In this paper, we developed membrane scaffolds to mimic the biochemical and biophysical properties of human mesenchymal stem cell (hMSC) niches to help direct self-renewal and proliferation providing to cells all necessary chemical, mechanical and topographical cues. The strategy was to create three-dimensional membrane scaffolds with double porosity, able to promote the mass transfer of nutrients and to entrap cells. We developed poly (Ɛ-caprolactone) (PCL)/chitosan (CHT) blend membranes consisting of double porous morphology: (i) surface macrovoids (big pores) which could be easily accessible for hMSCs invasion and proliferation; (ii) interconnected microporous network to transfer essential nutrients, oxygen, growth factors between the macrovoids and throughout the scaffolds. We varied the mean macrovoid size, effective surface area and surface morphology by varying the PCL/CHT blend composition (100/0, 90/10, 80/20, 70/30). Membranes exhibited macrovoids connected with each other through a microporous network; macrovoids size increased by increasing the CHT wt%. Cells adhered on the surfaces of PCL/CHT 100/0 and PCL/CHT 90/10 membranes, that are characterized by a high effective surface area and small macrovoids while PCL/CHT 80/20 and PCL/CHT 70/30 membranes with large macrovoids and low effective surface area entrapped cells inside macrovoids. The scaffolds were able to create a permissive environment for hMSC adhesion and invasion promoting viability and metabolism, which are important for the maintenance of cell integrity. We found a relationship between hMSCs proliferation and oxygen uptake rate with surface mean macrovoid size and effective surface area. The macrovoids enabled the cell invasion into the membrane and the microporosity ensured an adequate diffusive mass transfer of nutrients and metabolites, which are essential for the long-term maintenance of cell viability and functions.

Nanomechanical insights: Amyloid beta oligomer-induced senescent brain endothelial cells.

Senescent cells accumulate in various peripheral tissues during aging and have been shown to exacerbate age-related inflammatory responses. We recently showed that exposure to neurotoxic amyloid ß (Aß1-42) oligomers can readily induce a senescence phenotype in human brain microvascular endothelial cells (HBMECs). In the present work, we used atomic force microscopy (AFM) to further characterize the morphological properties such as cell membrane roughness and cell height and nanomechanical properties such as Young's modulus of the membrane (membrane stiffness) and adhesion resulting from the interaction between AFM tip and cell membrane in Aß1-42 oligomer-induced senescent human brain microvascular endothelial cells. Morphological imaging studies showed a flatter and spread-out nucleus in the senescent HBMECs, both characteristic features of a senescent phenotype. Furthermore, the mean cell body roughness and mean cell height were lower in senescent HBMECs compared to untreated normal HBMECs. We also observed increased stiffness and alterations in the adhesion properties in Aß1-42 oligomer-induced senescent endothelial cells compared to the untreated normal HBMECs suggesting dynamic reorganization of cell membrane. We then show that vascular endothelial growth factor receptor 1 (VEGFR-1) knockdown or overexpression of Rho GTPase Rac 1 in the endothelial cells inhibited senescence and reversed these nanomechanical alterations, confirming a direct role of these pathways in the senescent brain endothelial cells. These results illustrate that nanoindentation and topographic analysis of live senescent brain endothelial cells can provide insights into cerebrovascular dysfunction in neurodegenerative diseases such as Alzheimer's disease.

Nanoscale modification of one-dimensional single-crystalline cuprous oxide.

In this work we report for the first time a method to modify the surface of Cu2O nanowires in a controllable way and physically weld them into a network form, which contributes to higher electrical conductivity as well as a strong water-repelling nature. We have used state-of-the-art theoretical calculations to support our experimental observations. We demonstrate how varying the irradiation fluence can modulate the surface and decorate the nanowire with a uniform distribution of Cu8O nanocrystals due to preferential sputtering. While several well studied joining techniques are available for carbon and metal-based nanowires, the same information for ceramic nanowires is scarce at present. The current study sheds light into this and a state-of-the-art 3D simulation technique predicts most of the modifications including surface modulation, oxygen depletion and welding. The welded network shows higher electrical conductivity than the unwelded assembly. With Cu2O being of p-type the current ion beam joining technique shows a novel path for fabricating p-i-n junctions or solar cell devices through bottom-up approach. Furthermore, we have explored the response of this network to moisture. Our calculation based on density functional theory predicts the hydrophilic nature of individual copper oxide nanowires both before and after irradiation. However, the network shows a strong water-repelling nature, which has been explained quantitatively using the Cassie-Baxter model.

Assessment of disease activity in Takayasu arteritis: A quantitative study with computed tomography angiography.

BACKGROUND: Identifying disease activity in Takayasu arteritis (TAK) is challenging. This study aimed to investigate the value of quantitative characterization with computed tomography angiography in the assessment of disease activity in patients with TAK. METHODS: We retrospectively analysed the data on 162 aortic CT angiography from 140 TAK patients. Patients were categorized based on disease activity according to the National Institutes of Health criteria into two groups: active disease group (n = 65) and inactive disease group (n = 97). RESULTS: Patients with active TAK had a thicker wall compared with patients with inactive TAK (5.2 ±â€¯2.4 mm vs. 2.5 ±â€¯0.8 mm, p < 0.001). The relative post-contrast enhancement ratio of the thickened wall was higher in active TAK than in inactive TAK (1.5 ±â€¯0.3 vs. 1.1 ±â€¯0.2, p < 0.001). Given a thickness cutoff of 3.3 mm, sensitivity for active-phase TAK was 83.1%, specificity 89.7%, positive predictive value 84.4%, and negative predictive value 88.8%. With a relative post-contrast enhancement ratio cutoff of 1.2, sensitivity for active-phase TAK was 89.2%, specificity 76.3%, positive predictive value 71.6%, and negative predictive value 91.3%. In receiver-operating characteristic curves comparison, maximal wall thickness and relative post-contrast enhancement ratio were superior to C-reactive protein and erythrocyte sedimentation rate for determining active phase disease (p < 0.05). CONCLUSIONS: Quantitative characterization with CT angiography was a useful tool to assess disease activity in TAK patients. Maximal wall thickness and relative post-contrast enhancement ratio have a high sensitivity and specificity for detecting TAK activity.

Tunable Microstructured Membranes in Organs-on-Chips to Monitor Transendothelial Hydraulic Resistance.

Tissue engineering is an interdisciplinary field, wherein scientists from different backgrounds collaborate to address the challenge of replacing damaged tissues and organs through the in vitro fabrication of functional and transplantable biological structures. Because the development and optimization of tissue engineering strategies rely on the complex interaction of cells, materials, and the physical-chemical tissue microenvironment, there is a need for experimental models that allow controlled studies of these aspects. Organs-on-chips (OOCs) have recently emerged as in vitro models that capture the complexity of human tissues in a controlled manner, while including functional readouts related to human organ physiology. OOCs consist of multiple microfluidic cell culture compartments, which are interfaced by porous membranes or hydrogels in which human cells can be cultured, thereby providing a controlled culture environment that resembles the microenvironment of a certain organ, including mechanical, biochemical, and geometrical aspects. Because OOCs provide both a well-controlled microenvironment and functional readouts, they provide a unique opportunity to incorporate, evaluate, and optimize materials for tissue engineering. In this study, we introduce a polymeric blend membrane with a three-dimensional double-porous morphology prepared from a poly(ɛ-caprolactone)-chitosan blends (PCL-CHT) by a modified liquid-induced phase inversion technique. The membranes have different physicochemical, microstructural, and morphological properties depending on different PCL-CHT ratios. Big surface pores (macrovoids) provide a suitable microenvironment for the incorporation of cells or growth factors, whereas an interconnected small porous (macroporous) network allows transfer of essential nutrients, diffusion of oxygen, and removal of waste. Human umbilical vein endothelial cells were seeded on the blend membranes embedded inside an OOC device. The cellular hydraulic resistance was evaluated by perfusing culture medium at a realistic transendothelial pressure of 20 cmH2O or 2 kPa at 37°C after 1 and 3 days postseeding. By introducing and increasing CHT weight percentage, the resistance of the cellular barrier after 3 days was significantly improved. The high tuneability over the membrane physicochemical and architectural characteristics might potentially allow studies of cell-matrix interaction, cell transportation, and barrier function for optimization of vascular scaffolds using OOCs. Impact Statement Organs-on-chips (OOCs) offer interesting potential for progress in the treatment of diseases and injury in the growing field of tissue engineering and regenerative medicine. The article presents a new way to develop polymer membrane with a tunable microstructured morphology and to implement this biomaterial inside an OOC device. The reader should find measurements of the transendothelial hydraulic resistance in real time during endothelial cells culture: a simple and controlled way of mimicking human physiological condition for vascular tissue regeneration. This combination of novel biomaterial inside an OOC will explore innovative ideas in tissue engineering field.

Image quality and radiation dose of two prospective ECG-triggered protocols using 128-slice dual-source CT angiography in infants with congenital heart disease.

This study aims to investigate the image quality and radiation dose of prospective ECG-triggered 128-slice dual-source CT (DSCT) angiography in the delineation of coronary arteries in infants with congenital heart disease (CHD). Sixty-three infants with CHD were randomly assigned into two groups: prospective ECG-triggered sequential protocol (group 1) and high-pitch spiral protocol (group 2). Patients were selected to the protocols randomly. A five-point scoring system was applied to study the capability of detecting coronary arteries. A score of < 3 represents non-diagnostic. Effective radiation dose (ED) was calculated. The visualized rate for original, proximal, middle and distal segments of the coronary arteries was 98%, 95%, 94% and 83%, respectively in group 1, 93%, 82%, 53% and 34%, respectively in group 2. There were no significant demographic differences in the identification rate between the two groups as to the original and most of the proximal segments. Significant demographic differences were found in middle and distal segments (p < 0.05). The mean ED of the high pitch group and the sequential group was 0.33 ± 0.11 mSv and 0.63 ± 0.16 mSv, respectively. Both the prospective ECG-gated high-pitch mode and the sequential mode for 128-slice DSCT allow satisfactory delineation of original and most of the proximal segments of coronary arteries in infants with CHD. However, an ECG-gated sequential mode is recommended when detailed anatomic assessment of the whole coronary arteries are needed since the ECG-gated high-pitch mode is limited in the delineation of middle and distal segments of the coronary arteries.

VEGF receptor-1 modulates amyloid ß 1-42 oligomer-induced senescence in brain endothelial cells.

Aggregated amyloid ß (Aß) peptides in the Alzheimer's disease (AD) brain are hypothesized to trigger several downstream pathologies, including cerebrovascular dysfunction. Previous studies have shown that Aß peptides can have antiangiogenic properties, which may contribute to vascular dysfunction in the early stages of the disease process. We have generated data showing that brain endothelial cells (ECs) exposed to toxic Aß1-42 oligomers can readily enter a senescence phenotype. To determine the effect of Aß oligomers on brain ECs, we treated early passaged human brain microvascular ECs and HUVECs with high MW Aß1-42 oligomers (5 µM, for 72 h). For controls, we used no peptide treatment, 5 µM Aß1-42 monomers, and 5 µM Aß1-42 fibrils, respectively. Brain ECs treated with Aß1-42 oligomers showed increased senescence-associated ß-galactosidase staining and increased senescence-associated p21/p53 expression. Treatment with either Aß1-42 monomer or Aß1-42 fibrils did not induce senescence in this assay. We then measured vascular endothelial growth factor receptor (VEGFR) expression in the Aß1-42 oligomer-treated ECs, and these cells showed significantly increased VEGFR-1 expression and decreased VEGFR-2 levels. Overexpression of VEGFR-1 in brain ECs readily induced senescence, suggesting a direct role of VEGFR-1 signaling events in this paradigm. More importantly, small interfering RNA-mediated knockdown of VEGFR-1 expression in brain ECs was able to prevent up-regulation of p21 protein expression and significantly reduced induction of senescence following Aß1-42 oligomer treatment. Our studies show that exposure to Aß1-42 oligomers may impair vascular functions by altering VEGFR-1 expression and causing ECs to enter a senescent phenotype. Altered VEGFR expression has been documented in brains of AD patients and suggests that this pathway may play a role in AD disease pathogenesis. These studies suggest that modulating VEGFR-1 expression and signaling events could potentially prevent senescence and rejuvenate EC functions, and provides us with a novel target to pursue for prevention and treatment of cerebrovascular dysfunction in AD.-Angom, R. S., Wang, Y., Wang, E., Pal, K., Bhattacharya, S., Watzlawik, J. O., Rosenberry, T. L., Das, P., Mukhopadhyay, D. VEGF receptor-1 modulates amyloid ß 1-42 oligomer-induced senescence in brain endothelial cells.

Morvan's syndrome-is a pathogen behind the curtain?

Morvan's syndrome is a rare syndrome of likely autoimmune etiology characterized by peripheral nerve hyperexcitability, dysautonomia, insomnia, and fluctuating delirium with prominent hallucinations. Since its first mention in 1890, less than 100 cases have been described in literature. The largest existing review includes details of 29 cases. This case series describes 4 cases (M = 4) of Morvan's syndrome which presented between May and November 2017 to a single tertiary care referral teaching hospital in north India. All the four patients manifested behavioral abnormalities, sleep disturbances, hallucinations, autonomic dysfunction, and clinical signs of peripheral nerve hyperexcitability, mostly as myokymia. Two of the patients had Anti-CASPR2 (contactin-associated protein 2) antibodies. Three of them had electromyography features of peripheral nerve hyperexcitability and only one had elevated cerebrospinal fluid protein level. We hypothesize that Morvan's syndrome and other less characterized autoimmune encephalitis/peripheral nervous system syndromes may have infectious triggers. A possible viral trigger may result in generation of autoantibodies which result in the typical manifestations. We base these hypotheses on the finding of four cases of an orphan disease within a short period of time in a limited geographical distribution.

Combination anti-Aß treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice.

Drug development for Alzheimer's disease has endeavored to lower amyloid ß (Aß) by either blocking production or promoting clearance. The benefit of combining these approaches has been examined in mouse models and shown to improve pathological measures of disease over single treatment; however, the impact on cellular and cognitive functions affected by Aß has not been tested. We used a controllable APP transgenic mouse model to test whether combining genetic suppression of Aß production with passive anti-Aß immunization improved functional outcomes over either treatment alone. Compared with behavior before treatment, arresting further Aß production (but not passive immunization) was sufficient to stop further decline in spatial learning, working memory, and associative memory, whereas combination treatment reversed each of these impairments. Cognitive improvement coincided with resolution of neuritic dystrophy, restoration of synaptic density surrounding deposits, and reduction of hyperactive mammalian target of rapamycin signaling. Computational modeling corroborated by in vivo microdialysis pointed to the reduction of soluble/exchangeable Aß as the primary driver of cognitive recovery.