Probe Test Research Articles

An integrated 60 GHz differential-fed patch array antenna in low-cost QFN package

—This paper presents a low-cost and easy-assembly AiP solution for 60 GHz radar sensor applications based on the QFN package. Using traditional PCB process, a 60 GHz differential-fed patch array antenna is proposed. To improve the bandwidth and gain performance, four rectangular parasitic elements are introduced. For miniaturization, a compact differential-fed structure is implemented. To ensure encapsulation and protection, a low-cost plastic package lid is utilized, and its impact on the antenna performance is analyzed theoretically by a transmission-line model. For demonstration, an antenna prototype is designed, fabricated and measured with a balun and probe test structure. With and without the package lid, the 10 dB impedance bandwidth of the proposed antenna is from 55.2 to 66.5 GHz, and from 55.6 to 66.3 GHz, respectively. Moreover, the gain is higher than 7.7 and 7.5dBi, respectively. Measurement results validate negligible impact of proposed package lid on antenna performance, affirming transmission-line model's effectiveness in design methodology.

Pavement cells distinguish touch from letting go.

A micro-cantilever technique applied to individual leaf epidermis cells of intact Arabidopsis thaliana and Nicotiana tabacum synthesizing genetically encoded calcium indicators (R-GECO1 and GCaMP3) revealed that compressive forces induced local calcium peaks that preceded delayed, slowly moving calcium waves. Releasing the force evoked significantly faster calcium waves. Slow waves were also triggered by increased turgor and fast waves by turgor drops in pressure probe tests. The distinct characteristics of the wave types suggest different underlying mechanisms and an ability of plants to distinguish touch from letting go.

Anti-Inflammatory and Antioxidant Properties of Squalene in Copper Sulfate-Induced Inflammation in Zebrafish (Danio rerio).

Long-term or excessive oxidative stress can cause serious damage to fish. Squalene can be added to feed as an antioxidant to improve the body constitution of fish. In this study, the antioxidant activity was detected by 2,2-diphenyl-1-acrylhydrazyl (DPPH) test and fluorescent probe (dichloro-dihydro-fluorescein diacetate). Transgenic Tg (lyz: DsRed2) zebrafish were used to evaluate the effect of squalene on CuSO4-induced inflammatory response. Quantitative real-time reverse transcription polymerase chain reaction was used to examine the expression of immune-related genes. The DPPH assay demonstrated that the highest free radical scavenging exerted by squalene was 32%. The fluorescence intensity of reactive oxygen species (ROS) decreased significantly after 0.7% or 1% squalene treatment, and squalene could exert an antioxidative effect in vivo. The number of migratory neutrophils in vivo was significantly reduced after treatment with different doses of squalene. Moreover, compared with CuSO4 treatment alone, treatment with 1% squalene upregulated the expression of sod by 2.5-foldand gpx4b by 1.3-fold to protect zebrafish larvae against CuSO4-induced oxidative damage. Moreover, treatment with 1% squalene significantly downregulated the expression of tnfa and cox2. This study showed that squalene has potential as an aquafeed additive to provide both anti-inflammatory and antioxidative properties.

Effects of the skirt length and embedment depth on the capacity of a skirted spudcan foundation under combined loading

Skirted spudcan foundations can provide a considerable bearing capacity and moment fixity for resisting the complex combined vertical, horizontal, and moment loadings arising from the harsh environment in the offshore oil and gas industry. These potential benefits are conducive to the extension of mobile jack-up drilling rigs into deep water. In this study, a series of probe tests were carried out using finite element analysis to investigate the effects of the skirt length and embedment depth on the bearing capacity of skirted spudcan foundations in soft clay under combined loading. The results indicate that both the skirt length and the embedment depth can significantly affect the behavior of a skirted spudcan and apparently improve the various bearing capacities under combined loading. As the skirt length and embedment depth increase, the failure envelope's size gradually expands and the failure envelope's shape changes accordingly. A spudcan with a skirt length of 0.25D embedded in about 2D of sediments is suggested to obtain an optimal application in practice. A closed-form algebraic expression was derived to interpret and predict the behavior of skirted spudcan foundations, which properly considers the effects of the skirt length and embedment depth.

Examination of the utility of the COVID-19 detection kit, TRC Ready® SARS-CoV-2 i for nasopharyngeal swabs.

The reverse transcription polymerase chain reaction (RT-PCR) offers high sensitivity, but has some drawbacks, such as the time required for the RNA extraction. Transcription reverse-transcription concerted reaction (TRC) Ready® SARS-CoV-2 i is easy to use and can be performed in about 40 minutes. TRC Ready® SARS-CoV-2 i and real-time one-step RT-PCR using the TaqMan probe tests of cryopreserved nasopharyngeal swab samples from patients diagnosed with COVID-19 were compared. The primary objective was to examine the positive and negative concordance rates. A total of 69 samples cryopreserved at -80° C were examined. Of the 37 frozen samples that were expected to be RT-PCR positive, 35 were positive by the RT-PCR method. TRC Ready® SARS-CoV-2 i detected 33 positive cases and 2 negative cases. One frozen sample that was expected to be RT-PCR positive was negative on both TRC Ready® SARS-CoV-2 i and RT-PCR. In addition, one frozen sample that was expected to be RT-PCR positive was positive by the RT-PCR method and negative by TRC Ready® SARS-CoV-2 i. Of the 32 frozen samples that were expected to be RT-PCR negative, both the RT-PCR method and TRC Ready® SARS-CoV-2 i yielded negative results for all 32 samples. Compared with RT-PCR, TRC Ready® SARS-CoV-2 i had a positive concordance rate of 94.3% and a negative concordance rate of 97.1%. TRC Ready® SARS-CoV-2 i can be utilized in a wide range of medical sites such as clinics and community hospitals due to its ease of operability, and is expected to be useful in infection control.

Classifying and clustering noisy images using subset learning based on convolutional neural networks

AbstractA high yield rate is a key factor related to success in the competitive global semiconductor manufacturing business market. Wafer bin maps (WBMs) can be used as one measure of the output quality of a semiconductor manufacturing process. A WBM is the image results from a number of circuit probe (CP) tests on a wafer after the completion of a manufacturing process. The specific defect patterns on WBMs provide crucial information for engineers to trace the causes of defects in the complicated manufacturing process. This study is aimed toward investigating major practical challenges in current WBM analyses. Our approach involved utilizing a small, carefully labeled subset to reduce the labor requirements and human recognition bias related to identification of very noisy images. The first proposed procedure classified the noisy defect patterns by using convolutional neural networks (CNNs) trained with a small subset of labeled WBMs in the early batches. The second proposed procedure provided the proper clusters of noisy defect patterns using the features extracted from the trained CNNs. This procedure made it possible to generate various clusters of WMBs and integrate them in label space. The third procedure separated the new pattern from the existing defect patterns with the help of a supplemental dataset from a similar wafer product. The evaluation of the three proposed procedures was done with simulation data generated from real sets of WBMs, which were added with random noise to maintain confidentiality. The evaluation results demonstrated the practical validity of the proposed procedures.

The Undiscovered Ultradiffuse Galaxies of the Local Group

Ultradiffuse galaxies (UDGs) are attractive candidates to probe cosmological models and test theories of galaxy formation at low masses; however, they are difficult to detect because of their low surface brightness. In the Local Group a handful of UDGs have been found to date, most of which are satellites of the Milky Way and M31, and only two are isolated galaxies. It is unclear whether so few UDGs are expected. We address this by studying the population of UDGs formed in hydrodynamic constrained simulations of the Local Group from the HESTIA suite. For a Local Group with a total enclosed mass M LG( < 2.5 Mpc) = 8 × 1012 M⊙, we predict that there are 12 ± 3 isolated UDGs (68% confidence) with stellar masses 106 ≤ M */M⊙ < 109, and effective radii R e ≥ 1.5 kpc, within 2.5 Mpc of the Local Group, of which (68% confidence) are detectable in the footprint of the Sloan Digital Sky Survey (SDSS). Accounting for survey incompleteness, we find that almost the entire population of UDGs in the Local Group field would be observable in a future all-sky survey with a depth similar to the SDSS, the Dark Energy Survey, or the Legacy Survey of Space and Time. Our results suggest that there is a population of UDGs in the Local Group awaiting discovery.

Sex differences in hippocampal-dependent memory and the hippocampal lipidome in adolescent rats raised on diets with or without DHA

Recent studies suggest the effects of DHA supplementation on human memory may differ between females and males during infancy, adolescence, and early adulthood, but the underlying mechanisms are not clear. As a result, this study sought to examine the spatial memory and brain lipidomic profiles in female and male adolescent rats with or without a DHA-enriched diet that began perinatally with the supplementation of dams. Spatial learning and memory were examined in adolescent rats using the Morris Water Maze beginning at 6 weeks of age and animals were sacrificed at 7 weeks of age to permit isolation of brain tissue and blood samples. Behavioral testing showed that there was a significant diet x sex interaction for two key measures of spatial memory (distance to zone and time spent in the correct quadrant during the probe test), with female rats benefiting the most from DHA supplementation. Lipidomic analyses suggest levels of arachidonic acid (ARA) and n-6 docosapentaenoic acid (DPA) containing phospholipid species were lower in the hippocampus of DHA supplemented compared with control animals, and principal component analyses revealed a potential dietary treatment effect for hippocampal PUFA. Females fed DHA had slightly more PE P-18:0_22:6 and maintained levels of PE 18:0_20:4 in the hippocampus in contrast with males fed DHA. Understanding how DHA supplementation during the perinatal and adolescent periods changes cognitive function in a sex-specific manner has important implications for determining the dietary requirements of DHA. This study adds to previous work highlighting the importance of DHA for spatial memory and provides evidence that further research needs to consider how DHA supplementation can cause sex-specific changes.

The Combined Bearing Capacities of Anchor Chain Segment by Considering Its Actual Geometry and Roughness

The soil resistances along the embedded ground chain affect the pull-out capacity of anchor as they determine the magnitude and direction of tension at the padeye. To facilitate analyses, the chain was usually simplified as a cylindrical line. The chain segment with actual geometry, buried deeply in clayey soil, is studied using a large deformation finite element approach to overcome severe distortion of soil elements around the chain. The uniaxial resistances obtained by the large deformation analyses are verified by comparison with the existing model tests and simplified solutions, followed by presentation of the yield envelope against combined loading. Both the probe test and swipe test are used to form the yield envelopes, and their results have good consistency. The influence of roughness of chain–soil interface on the soil resistances is quantified as well. It is found that the envelope of the chain segment with actual geometry is smaller than that against the simplified cylindrical shape; therefore, the most convenient design may not be the safest option.

Effects of hydroalcoholic, methanolic, and hexane extracts of brown algae Sargassum angustifolium on scopolamine-induced memory impairment and learning deficit in rodents.

Properties of Alzheimer's disease, can be caused by several reasons and there is no definite treatment for it. We aimed to study the effect of the hydroalcoholic extract, methanolic and n-hexane fractions of brown algae Sargassum angustifolium on memory impairment in mice and rats. Hydroalcoholic extract (25, 50, 100, 200 mg/kg), methanolic (20 and 40 mg/kg) and n-hexane (40 and 60 mg/kg) fractions of S. angustifolium were administered for 21 days intraperitoneally before scopolamine injection (2 mg/kg) on day 21. Rivastigmine was administered for 3 weeks intraperitoneally as well. Then, cognitive function was evaluated by three behavioral tests: passive avoidance, object recognition, and the Morris Water Maze test. Scopolamine induced memory impairment and rivastigmine significantly reversed the memory dysfunction in all three tests. Hydroalcoholic extract and methanolic fraction significantly reversed scopolamine-induced memory impairment in passive avoidance by 64% and 55% and enhanced the recognition index in the object recognition test. In the Morris water maze test probe trial and training session, on days 3 and 4, the hydroalcoholic extract showed a significant decrease in time spent in the target quadrant and path length, respectively. Also, hydroalcoholic extract and methanolic fraction decreased escape latency time in training sessions on days 3 and 4, by 50% and 31% in comparison to scopolamine. N-hexane fractions had no significant effect on scopolamine-induced cognitive impairment. Although the n-hexane fraction wasn't effective, the administration of hydroalcoholic extract and the methanolic fraction of S. angustifolium enhanced scopolamine-induced memory impairment.

The effect of gastric bypass surgery on cognitive function of Alzheimer's disease and the role of GLP1-SGLT1 pathway

ObjectiveGastric bypass surgery has been shown to improve metabolic profiles via GLP1, which may also have cognitive benefits for Alzheimer's disease (AD) patients. However, the exact mechanism requires further investigation. MethodsRoux-en-Y gastric bypass or sham surgery was performed on APP/PS1/Tau triple transgenic mice (an AD mice model) or wild type C57BL/6 mice. Morris Water Maze (MWM) test was used to evaluate the cognitive function of mice and animal tissue samples were obtained for measurements two months after the surgery. Additionally, STC-1 intestine cells were treated with siTAS1R2 and siSGLT1, and HT22 nerve cells were treated with Aβ, siGLP1R, GLP1 and siSGLT1 in vitro to explore the role of GLP1-SGLT1 related signaling pathway in cognitive function. ResultsThe MWM test showed that bypass surgery significantly improved cognitive function in AD mice as measured by navigation and spatial probe tests. Moreover, bypass surgery reversed neurodegeneration, down-regulated hyperphosphorylation of Tau protein and Aβ deposition, improved glucose metabolism, and up-regulated the expression of GLP1, SGLT1, and TAS1R2/3 in the hippocampus. Furthermore, GLP1R silencing down-regulated SGLT1 expression, whereas SGLT1 silencing increased Tau protein deposition and exacerbated dysregulated of glucose metabolism in HT22 cells. However, RYGB did not alter the level of GLP1 secretion in the brainstem (where central GLP1 is mainly produced). Additionally, GLP1 expression was upregulated by RYGB via TAS1R2/3-SGLT1 activation sequentially in the small intestine. ConclusionRYGB surgery could improve cognition function in AD mice through facilitating glucose metabolism and reducing Tau phosphorylation and Aβ deposition in the hippocampus, mediated by peripheral serum GLP1 activation of SGLT1 in the brain. Furthermore, RYGB increased GLP1 expression through sequential activation of TAS1R2/TAS1R3 and SGLT1 in the small intestine.

Detection of changes in the hydrobiological parameters of the Oder River during the ecological disaster in July 2022 based on multi-parameter probe tests and remote sensing methods

Starting from the second half of July, hydrological conditions (low water levels and low flows) and atmospheric conditions (high temperatures, lack of precipitation) contributed to algae bloom in the Oder River basin. The mass extinction of fish in the middle and lower section of the Oder was probably the result of such environmental conditions. Because algae bloom is correlated with an increase in the content of chlorophyll in the river and on its surface, the authors focused on an analysis of changes in the chlorophyll amount in the longitudinal profile of the river. The key data was obtained by soundings carried out at an interval of about one kilometre during the research expedition, which took place on July 16–24, 2022. These data coincided with the values of the NDVI index (normalised difference vegetation index) based on 10-metre satellite images from the Sentinel 2 mission. Imagery from cloudless periods (mainly March, June, July and August) processed using the NDVI index was compared. Regularly elevated chlorophyll levels in the upstream section (occurring in each period) and temporarily elevated chlorophyll values as moving downstream were observed. This article confirms the initial conclusions of Kolada et al. (2022) that the mass fish kill in the Oder River in the summer of 2022 was conditioned by natural environmental pressure causing massive algae bloom and the release of their toxins. The article also proves that the use of satellite images for this type of analysis is the correct approach, but due to low resolution, they cannot be used as reference material. Changes in the hydrobiological parameters of the river, which are a direct indicator of the causes of the ecological disaster, are the data of the multi-parameter probe obtained two weeks before the first mass catches of dead fish.

A Fast and Efficient Calibration Method for Phased Array Antennas Using Fourier-Structured Excitation Matrix

This article presents a novel phased array antenna calibration method. Unlike conventional phased array calibration methods equipped with only one probe antenna in the far-field setup, multiple measurement probes are introduced in the proposed algorithm to significantly improve the measurement efficiency. Specifically, a novel construction method for an excitation matrix (which contains excitation coefficients for phased array elements) is proposed, where phase differences introduced by the spatial locations of the multiple probes are perfectly incorporated into the Fourier-structured excitation matrix, thereby presenting the best measurement efficiency without sacrificing the array calibration accuracy. The proposed method can offer robust array calibration results (guaranteed by the low condition number of the constructed excitation matrix with Fourier structure) and high measurement efficiency (offered by multiprobe setups). To experimentally validate the proposed algorithm, a multichannel (i.e., multiprobe) far-field measurement setup was utilized. A four-element open-ended waveguide array operating at 2.6 GHz and two-probe far-field systems were employed as the antenna under test (AUT) and multiple probes, respectively, to validate the effectiveness and robustness of the proposed phased array calibration algorithm. The proposed algorithm will be highly valuable for efficient phased array calibration, especially for future antenna systems equipped with large-scale antenna configurations.

Nondestructive Data Acquisition Methodology for IoT Devices: A Case Study on Amazon Echo Dot Version 2

The smart speaker is becoming a common part of the modern household, which usually includes an AI-powered Intelligent Voice Assistant to communicate with its users. Amazon Echo Dot is a popular smart speaker that extends the above-stated functionality by acting as a communication hub for other Internet of Things (IoT) and mobile devices within its local network. The nature and volume of data that an Echo Dot handles make it a potential source of evidence, if one is seized for a digital forensics investigation. Researchers and practitioners have explored various techniques to extract data from these IoT devices. However, traditional methods make changes to the physical device and/or its data, which is undesirable from a digital forensics perspective. The current work focuses on developing a nondestructive methodology for extracting data from IoT devices, with Amazon Echo Dot version 2 as an example, which use embedded Multimedia Card (eMMC)/embedded Multichip Package (eMCP) chips as their primary storage. We identify all in-system programming (ISP) pins using the computed tomography (CT) Scan imagery of the main printed circuit board (PCB) of the device. We created a 3-D fixture that accommodates pogo pin connectors to create contact with the already identified ISP taps on the main PCB. The 3-D Test Probe Jig can extract data from an IoT device’s memory chip using an eMMC reader. The proposed nondestructive solution is reproducible, portable, and affordable.

Surface modification of poly(ethylene terephthalate) fabric using conductive polyaniline

In this study, pure polyethylene terephthalate (PET) fabric was coated with polyaniline (PANI) doped with hydrochloric acid (HCl) by in situ chemical oxidation polymerization to form conductive PET/PANIHCl fabric. The surface morphology, chemical, structural, and electrical conductivity of the conductive PET/PANIHCl fabric are examined by field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FTIR), and a four-point probe, respectively. FE-SEM images showed that PANIHCl was successfully coated on the PET fabric. According to the four-point probe test, the electrical conductivity of pure PET and PET/PANIHCl fabrics were [Formula: see text] and [Formula: see text] S/cm, respectively. The electrical conductivity of PET/PANIHCl fabric is about 106 higher than that of pure PET fabric. The conductive PET/PANIHCl fabric can be used as antistatic and electrostatic discharge material, and even anti-electromagnetic interference material.

Cognitive and hippocampal effects of adult male mice exposure to environmentally relevant doses of phthalates

We recently showed that chronic exposure of adult male mice to environmental doses of DEHP alone or in a phthalate mixture altered blood brain barrier integrity and induced an inflammatory profile in the hippocampus. Here, we investigate whether such exposure alters hippocampus-dependent behavior and underlying cellular mechanisms. Adult C57BL/6 J male mice were continuously exposed orally to the vehicle or DEHP alone (5 or 50 μg/kg/d) or to DEHP (5 μg/kg/d) in a phthalate mixture. In the Morris water maze, males showed reduced latencies across days to find the platform in the cue and spatial reference memory tasks, regardless of their treatment group. In the probe test, DEHP-50 exposed males displayed a higher latency to find the platform quadrant. In the temporal order memory test, males exposed to DEHP alone or in a phthalate mixture were unable to discriminate between the most recently and previously seen objects. They also displayed reduced ability to show a preference for the new object in the novel object recognition test. These behavioral alterations were associated with a lowered dendritic spine density and protein levels of glutamate receptors and postsynaptic markers, and increased protein levels of the presynaptic synaptophysin in the hippocampus. Metabolomic analysis of the hippocampus indicated changes in amino acid levels including reduced tryptophan and L-kynurenine and elevated NAD + levels, respectively, a precursor, intermediate and endproduct of the kynurenine pathway of tryptophan metabolism. Interestingly, the protein amounts of the xenobiotic aryl hydrocarbon receptor, a target of this metabolic pathway, were elevated in the CA1 area. These data indicate that chronic exposure of adult male mice to environmental doses of DEHP alone or in a phthalate mixture impacted hippocampal function and structure, associated with modifications in amino acid metabolites with a potential involvement of the kynurenine pathway of tryptophan metabolism.

Validation of Fluorescence in Situ hybridization (FISH) Assay Using An Analyte-Specific Reagent in Detecting Aneuploidies of Chromosomes 13, 18, 21, X, and Y in Prenatal Diagnosis

Fluorescence &lt;em&gt;In-Situ&lt;/em&gt; hybridization (FISH) is a sensitive and highly efficient technique commonly used in routine diagnostics. Most of these tests that use analyte-specific reagents are not approved by US Food and Drug Administration (FDA) but are developed by individual test laboratories. There is an emerging demand for prenatal diagnosis of aneuploidies by FISH. Since most of these assays are laboratory-developed tests, it is essential to validate them prior to their use in diagnosis. However, validation procedures of these assays are oversight despite the presence of several validation guidelines. To validate FISH assay using analyte-specific reagents in detecting aneuploidies of chromosomes 13, 18, 21, X, and Y as per American College of Medical Genetics (ACMG) guidelines in 2016. Analyte-specific reagents supplied by Oxford Gene Technologies were used in the validation process using blood and amniotic fluid samples obtained from healthy male and female adults and fetuses respectively. The validation process includes probe localization, evaluation of assay specificity, and establishment of lower cut-off and reportable reference ranges. Probe localization indicated a 100% specificity for all probes tested. Interphase FISH on uncultured amniotic fluid demonstrated significantly high (≥95%) overall disomic signal patterns for all autosomes and sex chromosomes tested. The reportable 95% confidence interval was 94.84, 94.84, 95.24, 94.54, and 94.54 for chromosomes 13, 18, 21, X, and Y respectively. The present study illustrates an experimental design in validating laboratory-developed FISH assay using analyte-specific reagents in detecting aneuploidies of chromosomes 13, 18, 21, X, and Y as per ACMG guidelines. Test probes used in the present study are consistent with probe localization characteristics, assay specificity, and reportable reference ranges recommended by ACMG. Therefore, the FISH assay used in the present study could be recommended as a supplementary prenatal diagnostic test that can be carried out along with standard chromosomal analysis.

Inhibitory effect of quercetin-3-O-α-rhamnoside, p-coumaric acid, phloridzin and 4-O-β-glucopyranosyl-cis-coumaric acid on rats liver microsomes cytochrome P450 enzyme activities.

P-coumaric acid, phloridzin, quercetin-3-O-α-rhamnoside and 4-O-β-glucopyranosyl-cis-coumaric acid isolated in Malus micromalus Makino fruit were investigated the inhibitory activity of cytochrome CYP450 enzyme by the probe test method of rat liver microsomes in vitro, and determined the role in drug metabolism and/or toxicology. Enzymatic kinetics method was used to determine the inhibition type of these components and corresponding inhibition constants. The results demonstrated that all the 4 compounds had no significance to inhibit the activities of CYP2E1 and CYP2C11. P-coumaric acid, phloridzin and quercetin-3-O-α-rhamnoside had a weak inhibitory effect on CYP3A4, which belonged to the competitive inhibitory type with inhibitory constants of 10.56, 30.79 and 40.29μmolL-1, respectively. 4-O-β-glucopyranosyl-cis-coumaric acid had a moderate inhibitory effect on CYP3A4, which belonged to the anti-competitive inhibition type and the inhibition constant was 5.56μmolL-1. The CYP1A2 could be weakly inhibited by p-coumaric acid in the competitive type, and the inhibition constant is 25.20μmolL-1 4-O-β-glucopyranosyl-cis-coumaric acid exhibited anti-competitive inhibition of CYP1A2 with an inhibition constant of 19.91μmolL-1, and the inhibition effect was weak. The results will be useful to optimize the clinical dosage regimen and avoid drug-drug interactions when it is utilized comminating with other medicines in the clinic.

Peripheral administration of nanomicelle-encapsulated anti-Aβ oligomer fragment antibody reduces various toxic Aβ species in the brain

BackgroundAlthough a large amount of evidence has revealed that amyloid β (Aβ), especially Aβ oligomers, protofibrils, and pyroglutamated Aβs, participate primarily in the pathophysiological processes of Alzheimer’s disease, most clinical trials of anti-Aβ antibody therapy have never acquired successful efficacy in human clinical trials, partly because peripheral administration of antibody medications was unable to deliver sufficient amounts of the molecules to the brain. Recently, we developed polymeric nanomicelles capable of passing through the blood–brain barrier that function as chaperones to deliver larger amounts of heavy molecules to the brain. Herein, we aimed to evaluate the efficacy of newly developed antibody 6H4 fragments specific to Aβ oligomers encapsulated in polymeric nanomicelles on the development of Alzheimer’s disease pathology in Alzheimer’s disease model mice at the age of emergence of early Alzheimer’s disease pathology.ResultsDuring the 10-week administration of 6H4 antibody fragments in polymeric nanomicelles, a significant reduction in the amounts of various toxic Aβ species, such as Aβ oligomers, toxic Aβ conformers, and pyroglutamated Aβs in the brain was observed. In addition, immunohistochemistry indicated inhibition of diameters of Aβ plaques, Aβ-antibody immunoreactive areas, and also plaque core formation. Behavioral analysis of the mice model revealed that the 6H4 fragments-polymeric nanomicelle group was significantly better at maintaining long-term spatial reference memory in the probe and platform tests of the water maze, thereby indicating inhibition of the pathophysiological process of Alzheimer’s disease.ConclusionsThe results indicated that the strategy of reducing toxic Aβ species in early dementia owing to Alzheimer’s disease by providing sufficient antibodies in the brain may modify Alzheimer’s disease progression.

Effects of proactive interference on olfactory memory in dogs.

Proactive interference (PI) occurs when memories of past events or stimuli intrude in the present moment, causing working memory (WM) errors. These errors are often measured through WM tests such as matching-to-sample (MTS). When the repetition of individual stimuli increases, there is a greater chance of these intrusions, and thus there can be a decrease in accuracy in such tasks. In two experiments, we explored the nature of PI on dog working memory. First, we manipulated the size of the set of odors (2, 6, trial-unique) used to construct each session to maximize (2-odor set) and minimize (trial-unique) within-session proactive interference during an olfactory MTS task. Matching-to-sample accuracy decreased with greater PI. Second, we adapted procedures originally designed for pigeons and rhesus macaques to determine the locus of PI in dogs. To test for proactive interference, probe trials were inserted into MTS sessions where sample odors from earlier trials reappeared as incorrect comparisons. Incorrect responses on these probe trials indicated proactive interference. These probe tests were conducted with a 0-s or 20-s retention interval in separate sessions. We found that dogs performed worse on the matching task when the source of interference (odor stimulus) was from the immediately preceding trial compared with when they were from trials further back in the session but only for the 0-s retention interval. These results are compared with previous work examining the effects of proactive interference on working memory in other species.