Several iPSC-derived three-dimensional (3D) cultures have been generated to model Alzheimer’s disease (AD). While some AD-related phenotypes have been identified across these cultures, none of them could recapitulate multiple AD-related hallmarks in one model. To date, the transcriptomic features of these 3D models have not been compared with those of human AD brains. However, these data are crucial to understanding the pertinency of these models for studying AD-related pathomechanisms over time. We developed a 3D bioengineered model of iPSC-derived neural tissue that combines a porous scaffold composed of silk fibroin protein with an intercalated collagen hydrogel to support the growth of neurons and glial cells into complex and functional networks for an extended time, a fundamental requisite for aging studies. Cultures were generated from iPSC lines obtained from two subjects carrying the familial AD (FAD) APP London mutation, two well-studied control lines, and an isogenic control. Cultures were analyzed at 2 and 4.5 months. At both time points, an elevated Aβ42/40 ratio was detected in conditioned media from FAD cultures. However, extracellular Aβ42 deposition and enhanced neuronal excitability were observed in FAD culture only at 4.5 months, suggesting that extracellular Aβ deposition may trigger enhanced network activity. Remarkably, neuronal hyperexcitability has been described in AD patients early in the disease. Transcriptomic analysis revealed the deregulation of multiple gene sets in FAD samples. Such alterations were strikingly similar to those observed in human AD brains. These data provide evidence that our patient-derived FAD model develops time-dependent AD-related phenotypes and establishes a temporal relation among them. Furthermore, FAD iPSC-derived cultures recapitulate transcriptomic features of AD patients. Thus, our bioengineered neural tissue represents a unique tool to model AD in vitro over time.

Neural cell adhesion molecules 1 (NCAM1) and 2 (NCAM2) belong to the cell adhesion molecules of the immunoglobulin superfamily and have been shown to regulate formation, maturation, and maintenance of synapses. NCAM1 and NCAM2 undergo proteolysis, but the identity of all the proteases involved and how proteolysis is used to regulate their functions are not known. We report here that NCAM1 and NCAM2 are BACE1 substrates in vivo. NCAM1 and NCAM2 overexpressed in HEK cells were both cleaved by metalloproteinases or BACE1, and NCAM2 was also processed by gamma-secretase. We identified the BACE1 cleavage site of NCAM1 (at Glu 671) and NCAM2 (at Glu 663) using mass spectrometry and site-directed mutagenesis. Next, we assessed BACE1-mediated processing of NCAM1 and NCAM2 in the mouse brain during aging. NCAM1 and NCAM2 were cleaved in the olfactory bulb of BACE1+/+ but not BACE1-/- mice at postnatal day 10 (P10), 4 and 12 months of age. In the hippocampus, a BACE1-specific soluble fragment of NCAM1 (sNCAM1 beta) was only detected at P10. However, we observed an accumulation of full-length NCAM1 in hippocampal synaptosomes in 4-mont-hold BACE1-/- mice. We also found that polysialylated NCAM1 (PSA-NCAM1) levels were increased in BACE1-/- mice at P10 and demonstrated that BACE1 cleaves both NCAM1 and PSA-NCAM1 in vitro. In contrast, we did not find evidence for BACE1-dependent NCAM2 processing in the hippocampus at any age analyzed. In summary, our data demonstrate that BACE1 differentially processes NCAM1 and NCAM2 depending on the region of brain, subcellular localization, and age in vivo.

Axonal dystrophy, indicative of perturbed axonal transport, occurs early during Alzheimer's disease (AD) pathogenesis. Little is known about the mechanisms underlying this initial sign of the pathology. This study proves that Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) loss of function, due to Gga3 genetic deletion or a GGA3 rare variant that cosegregates with late-onset AD, disrupts the axonal trafficking of the β-site APP-cleaving enzyme 1 (BACE1) resulting in its accumulation in axonal swellings in cultured neurons and in vivo. We show that BACE pharmacological inhibition ameliorates BACE1 axonal trafficking and diminishes axonal dystrophies in Gga3 null neurons in vitro and in vivo. These data indicate that axonal accumulation of BACE1 engendered by GGA3 loss of function results in local toxicity leading to axonopathy. Gga3 deletion exacerbates axonal dystrophies in a mouse model of AD before β-amyloid (Aβ) deposition. Our study strongly supports a role for GGA3 in AD pathogenesis, where GGA3 loss of function triggers BACE1 axonal accumulation independently of extracellular Aβ, and initiates a cascade of events leading to the axonal damage distinctive of the early stage of AD.

Automatic prediction of the aesthetic quality of a photograph has been an important research problem in image processing and computer vision. While assessing the aesthetic quality of a photograph by human is highly subjective, most existing studies have considered only objective (or general) opinion of multiple viewers. In this paper, we provide a comprehensive investigation of the issue of subjectivity in aesthetic quality assessment using a large-scale database containing photos, user ratings, and user comments. First, we analyze how the mean aesthetic quality level and the level of subjectivity have evolved over time. Second, we examine the feasibility of automatic prediction of the level of subjectivity based on visual features, and identify which features are effective for the prediction. Third, we analyze the users' comments given to photos to understand the sources of subjectivity of aesthetic quality rating. Our results show that several factors are simultaneously involved in determining the level of subjectivity of a photo, but it can be predicted with reasonable accuracy. We believe that our results provide insight toward personalized aesthetic photo applications.

BACE1 is the first enzyme involved in APP processing, thus it is a strong therapeutic target candidate for Alzheimer’s disease. The observation of deleterious phenotypes in BACE1 Knock-out (KO) mouse models (germline and conditional) raised some concerns on the safety and tolerability of BACE1 inhibition. Here, we have employed a tamoxifen inducible BACE1 conditional Knock-out (cKO) mouse model to achieve a controlled partial depletion of BACE1 in adult mice. Biochemical and behavioural characterization was performed at two time points: 4–5 months (young mice) and 12–13 months (aged mice). A ~50% to ~70% BACE1 protein reduction in hippocampus and cortex, respectively, induced a significant reduction of BACE1 substrates processing and decrease of Aβx-40 levels at both ages. Hippocampal axonal guidance and peripheral nerve myelination were not affected. Aged mice displayed a CA1 long-term potentiation (LTP) deficit that was not associated with memory impairment. Our findings indicate that numerous phenotypes observed in germline BACE1 KO reflect a fundamental role of BACE1 during development while other phenotypes, observed in adult cKO, may be absent when partially rather than completely deleting BACE1. However, we demonstrated that partial depletion of BACE1 still induces CA1 LTP impairment, supporting a role of BACE1 in synaptic plasticity in adulthood.

β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in the production of amyloid beta (Aβ), the toxic peptide that accumulates in the brains of Alzheimer’s disease (AD) patients. Our previous studies have shown that the clathrin adaptor Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) plays a key role in the trafficking of BACE1 to lysosomes, where it is normally degraded. GGA3 depletion results in BACE1 stabilization both in vitro and in vivo. Moreover, levels of GGA3 are reduced and inversely related to BACE1 levels in post-mortem brains of AD patients.

Chem. Eur, J. (2007), 13, p. 2034-2043.* (73) Assignee: Postech Academy-Industry Chem. Commun., (2005), p. 5307-5309.* Foundation, Pohang (KR) J. Am. Chem. Soc., (2005), 127(50), p. 17620-17621.* c r Database CAPLUS on STN. Acc. No. 2005:984386, Akutagawa et (*) Notice: Subject to any disclaimer, the term of this al., European Journal of Inorganic Chemistry (2005), 16, p. 3271 patent is extended or adjusted under 35 3276 (CAPLUS abstract).* U.S.C. 154(b) by 35 days. Kim, Mahn-Joo; "Dynamic Kinetic Resolution of Primary Amines with a Recyclable Pd Nanocatalyst for Racemization.” Org. Lett. (21) Appl. No.: 11/840,935 9:1157-1159 (2007).

This paper proposes a single image super resolution algorithm with the aim of satisfying three desirable characteristics, namely, high quality of the produced images, adaptability to image contents and unknown blurring conditions used to generate given input images, and low computational complexity. After the given input image is up-scaled using a conventional reconstruction operator, the missing high frequency components estimated from lower resolution versions of the input image are added for improved quality and, moreover, the amount of the high frequency components to be added is adaptively determined. No computationally intensive operation is involved in the whole process, which makes the method computationally cheap. Experimental results show that the proposed method yields good subjective and objective image quality consistently across different blurring conditions and contents, and operates fast in comparison to existing state-of-the-art algorithms. In addition, it is also demonstrated that the proposed method can be used in combination with the existing algorithms in order to improve further their performance in terms of image quality.

While most of the existing work in aesthetic image quality assessment focuses on the overall (or average) opinion of users, this paper raises the issue of subjectivity (or taste) of aesthetic quality. We argue that subjectivity differs among different images, and investigate what causes such difference. We first analyze statistics of the user ratings of photos in a photo contest website, DPChallenge, in the viewpoint of average and standard deviation values of the ratings. Then, more importantly, we analyze the users' comments in order to identify sources contributing to subjectivity. When considering the importance of personalization in photo applications, we believe that our findings will be a valuable first step in the relevant future research.

Single-image super-resolution (SISR) is a technology to reconstruct a high-resolution image from a single low-resolution input image. The performance of SISR algorithms is usually evaluated by applying full-reference objective image quality assessment metrics. First, it is argued that the result of objective quality evaluation may become inconsistent with subjective quality assessment, depending on how the input low-resolution image is generated and how up-scaling during SISR is conducted. Since such inconsistency is due to subpixel-level misalignment between the original and output images, a framework is then proposed that compensates any spatial displacement between the two images and enables fair SISR performance evaluation using objective quality metrics.

An image resolution enhancement is mainly utilized as pre-processing technique for various image processing application. It requires to decrease image quality deterioration such as blurring. In this paper, we propose an image resolution enhancement algorithm using low level interpolation. In the proposed algorithm, we calculate an error using low level interpolation, estimate an error image from the calculated error. The estimated error image is added interpolated high resolution image, it become lastly reconstruction image. Our experiments obtained the average PSNR about 1dB which is improved results better than conventional method for sensitive image quality. Also, subjective image quality with edge region is more clearness. The proposed method may be helpful for applications in various multimedia systems such as image restoration.

영상 해상도 개선은 저해상도 획득 영상의 해상도를 개선하여 고해상도 영상을 생성하는 기술이다. 영상 해상도 개선을 위해서는 저해상도 획득 영상의 열화 과정에서 발생하는 손실된 화소 정보를 정확하게 추정하는 것이 중요하다. 따라서 본 논문에서는 영상 해상도 개선을 위한 다중 부족분 추정 방법을 제안한다. 제안하는 방법은 획득 영상의 부영상 집합에 알려진 열화 및 복원과정을 수행하여 서로 다른 형태의 다중 부족분을 추정하고, 추정된 부족분과 획득 영상의 보간 영상의 결합을 통해서 결과 영상을 생성하고, 디블러링을 수행하여 최종 복원 영상을 생성한다. 객관적 화질 측정 지표인 PSNR, SSIM, FSIM으로 비교한 결과 제안한 방법이 보간만을 사용하는 방법들보다 높은 값을 가지는 것을 확인하였다. 또한 결과 영상의 시각적 비교 결과 주관적 관점의 화질도 가장 뛰어난 것을 알 수 있었고, 보간만을 사용하는 방법들보다 빠른 계산시간을 가지는 것을 확인할 수 있었다. 제안하는 방법은 영상 해상도 개선을 위한 응용 환경에서 유용하게 사용될 수 있다.

영상 보간법은 영상의 크기 변환에서 나타나는 새로운 좌표의 화소의 값을 결정하는 방법이다. 영상 콘텐츠가 대용량화되면서 고속으로 개선된 결과 영상을 생성할 수 있는 영상 보간법이 요구된다. 따라서 본 논문에서는 영상 해상도 개선을 위한 고속 다중 혼합영상 보간법을 제안한다. 제안하는 방법은 입력 영상의 4개의 부영상으로부터 12개의 예상되는 부족분을 추정하고, 추정된 부족분과 입력 영상을 결합한 후 보간 함수를 거쳐서 결과 영상을 생성한다. 제안하는 방법은 비교 방법들보다 PSNR에서 최대 1.9dB, SSIM에서 최대 0.052 개선된 결과를 나타내었으며, 주관적 화질 비교에서도 우위에 있음을 실험을 통해서 알 수 있었다. 알고리즘의 동작속도 비교를 통해서 기존의 방법들보다 최소 3배 이상 빠르게 동작하는 것을 알 수 있었다. 제안하는 방법은 영상 해상도 개선을 위한 응용 환경에서 유용하게 사용될 수 있다. Image interpolation is a method of determining the value of new pixel coordinate in the process of image scaling. Recently, image contents are likely to be a large-capacity, interpolation algorithm is required to generate fast enhanced result image. In this paper, fast multiple mixed image interpolation for image resolution enhancement is proposed. The proposed method estimates expected 12 shortfalls from four sub-images of a input image, and generates the result image that is interpolated in the combination of the expected shortfalls with the input image. The experimental results demonstrate that PSNR increases maximum value of 1.9dB, SSIM increases maximum value of 0.052, and the subjective quality is superior to any other compared methods. Moreover, it is known by algorithm running time comparison that the proposed method has been at least three times faster than the compared conventional methods. The proposed method can be useful for application on image resolution enhancement.

영상의 다양한 변환 후에 나타나는 화질의 열화를 복원하기 위한 방법으로 보간법이나 초해상도 기술 등이 사용된다. 낮은 계산복잡도를 가지면서도 주관적 및 객관적 영상 향상을 위한 연구는 현재까지도 다양하게 이루어지고 있다. 본 논문에서는 개선된 자가 열화 복원 기법을 이용한 영상 향상 방법을 제안한다. 제안하는 방법에서는 개선된 자가 열화 복원 기법을 사용하여 영상의 크기 변환에서 소실된 정보를 유추하고, 유추한 정보를 영상 보간 기법과 결합하여 개선된 결과 영상을 생성한다. 실험을 통하여 제안한 방법이 비교 방법들보다 객관적 화질 지표인 PSNR에서 최대 1.8dB 향상된 결과를 나타내며, 주관적 화질에서도 우위에 있음을 확인할 수 있었다. 제안한 방법은 영상의 크기 변환이 요구되는 다양한 응용 환경에서 기반기술로 사용될 수 있다. Interpolation or super-resolution is used in order to restore degradation of image quality that appears after various transform of image. The method on subjective or objective image resolution improvement having low computation complexity has been being researched in many different ways. In this paper, image enhancement method using improved self degradation restoration(ISDR) method is proposed. The proposed method uses ISDR to estimate pixel value of missed coordinate in the process of image scaling, and combines the estimated loss information and interpolated image to generate enhanced result image. The proposed method shows that PSNR increases by 1.8dB, and subjective image quality is superior to other compared methods. The proposed method can be applied as a basis technique in variety of applications which requires image scale transform.

영상 크기 변환은 응용 환경에서의 다양한 목적을 위하여 사용되며, 변환 함수의 성능을 평가하기 위하여 처리전과 후의 두 영상의 화질을 비교한다. 변환 함수의 객관적 성능 평가를 위하여 화질 비교의 정확한 지표가 요구되며, 실제 다양한 관점에서의 접근이 이루어졌다. 하지만 영상 크기 변환 과정에서 생략되거나 새롭게 생성되는 화소들의 위치를 고려한 화질 비교 척도에 관한 연구는 거의 이루어지지 않고 있다. 따라서 본 논문에서는 영상 크기 변환에서 발생하는 화소들의 생략 및 추정 위치를 고려한 객관적 영상 화질 측정방법을 제안한다. 제안하는 방법은 기존의 영상 화질 척도를 이용하여 위치 변화를 고려한 새로운 영상화질 측정 방법을 만들고, 위치 변화에 대한 민감도를 평가하였다. 실험을 통해서 기존에 널리 사용되는 영상 화질 측정 방법이 화소들의 생략 및 추정 위치의 변화에 많은 영향을 받는 것을 알 수 있었고, 제안하는 방법이 화소들의 생략 및 추정 위치 변화를 고려한 영상 화질 표현의 객관적 척도임을 확인하였다. 제안하는 방법은 영상 복원 및 개선 함수의 성능을 평가하는 척도로서 유용하게 사용될 수 있다. Image scaling is used for a variety of real-life applications. In order to evaluate the performance of transform functions, the image quality are compared together before and after processing. For the objective evaluation of the transform functions, the exact criterion of image quality is required, and various aspects approaches are practically performed. However, few researches have been conducted on image quality measurement considering the position of pixels that are skipped or newly generated in the process of the image scaling. Therefore this paper focuses on the objective image quality measurement for positions of skipped or estimated pixels in the image scaling. The proposed method generated new image quality measure considering the positional changes using a conventional measure and evaluated sensitivity about positional changes. Through this experiments, it is observed that conventional image quality measurement is definitely affected by positional changes of a skipped and estimated pixels. It is also confirmed that the proposed method is an objective criterion to represent image quality for positional changes of skipped or estimated pixels. The proposed method can be used as a criterion to evaluate the performance of image restoration or enhancement functions.

선박 객체 검출 기술은 입력된 비디오 및 영상 데이터에서 선박 객체가 존재하는 경우 선박의 위치를 검출하는 기술로서 입력 영상의 환경 변화와 잡음의 영향에 따라서 검출 정확도의 편차가 높다. 이런 문제점을 해결하기 위하여 본 논문에서는 배경 구축 기법과 형태학적 연산 기반의 다중 선박 객체 검출 기술을 제안한다. 제안하는 방법은 배경 제거 단계, 잡음 제거 단계, 객체 기준 위치 설정 단계, 객체 재구성 단계, 다중 객체 검출 단계 등 5단계를 거쳐서 선박을 검출한다. 다양한 변수를 고려한 15가지 실험 비디오를 대상으로 한 실험을 통해서 98.7%의 검출율을 나타내었으며, 환경 변화에 강인한 검출을 수행하는 것을 확인할 수 있었다. 제안하는 방법은 해상 관제와 선박 자동 운항 기술의 기반 기술로서 유용하게 사용될 수 있다. Ship object detection is a technique to detect the existence and the location of ship when ship objects are shown on input image sequence, and there are wide variations in accuracy due to environmental changes and noise of input image. In order to solve this problem, in this paper, we propose multiple ship object detection based on background registration technique and morphology operation. The proposed method consists of the following five steps: background elimination step, noise elimination step, object standard position setting step, object restructure step, and multiple object detection steps. The experimental results show accurate and real-time ship detection for 15 different test sequences with a detection rate of 98.7%, and robustness against variable environment. The proposed method may be helpful as the base technique of sea surface monitoring or automatic ship sailing.

We used a nontransgenic cellular tauopathy model in which individual giant neurons in the lamprey CNS (ABCs) overexpress human tau isoforms cell autonomously to characterize the still poorly understood consequences of disease-associated tau processing in situ. In this model, tau colocalizes with endogenous microtubules and is nontoxic when expressed at low levels, but is misprocessed by a toxicity-associated alternative pathway when expressed above levels that saturate dendritic microtubules, causing abnormally phosphorylated, vesicle-associated tau to accumulate in ABC distal dendrites. This causes localized microtubule loss and eventually dendritic degeneration, which is preceded by tau secretion to the extracellular space. This sequence is reiterated at successively more proximal dendritic locations over time, suggesting that tau-induced dendritic degeneration is driven by distal dendritic accumulation of hyperphosphorylated, vesicle-associated tau perpetuated by localized microtubule loss. The implications for the diagnosis and treatment of human disease are discussed.

While the interneuronal propagation of neurofibrillary lesions in Alzheimer's disease and other tauopathies now appears to involve the spreading of tau-associated toxicity, little is known about its mechanism. We characterized the movement of human tau through the brain of a non-transgenic lower vertebrate tauopathy model in which full-length wild type and mutant human tau isoforms were expressed in identified neurons, thus permitting the identification and localization of EC tau sources. We describe two distinct patterns of tau spreading that correspond to tau species that lack (MTBR-) and contain (MTBR+) the tau microtubule-binding region. These patterns illustrate the production, migration and uptake of EC tau and resemble some of the extracellular tau deposits typically seen in human brain after repeated traumatic injury in cases of chronic traumatic encephalopathy (CTE). We propose that misprocessed human tau can spread between CNS neurons via a variety of non-synaptic mechanisms as well as synaptically mediated mechanisms.