Miracle-dz/UniFAR-FTUs huggingface dataset:
Highlights in BACE1 Inhibitors for Alzheimer's Disease Treatment

Alzheimer's disease (AD) is a severe neurodegenerative disorder and the most common type of dementia in the elderly. The clinical symptoms of AD include a progressive loss of memory and impairment of cognitive functions interfering with daily life activities. The main neuropathological features consist in extracellular amyloid-β (Aβ) plaque deposition and intracellular Neurofibrillary tangles (NFTs) of hyperphosphorylated Tau. Understanding the pathophysiological mechanisms that underlie neurodegeneration in AD is essential for rational design of neuroprotective agents able to prevent disease progression. According to the “Amyloid Cascade Hypothesis” the critical molecular event in the pathogenesis of AD is the accumulation of Aβ neurotoxic oligomers. Since the proteolytic processing of Amyloid Precursor Protein (APP) by β-secretase (beta-site APP cleaving enzyme 1, BACE1) is the rate-limiting step in the production of Aβ, this enzyme is considered a major therapeutic target and BACE1 inhibitors have the potential to be disease-modifying drugs for AD treatment. Therefore, intensive efforts to discover and develop inhibitors that can reach the brain and effectively inhibit BACE1 have been pursued by several groups worldwide. The aim of this review is to highlight the progress in the discovery of potent and selective small molecule BACE1 inhibitors over the past decade.
A scaling law for the lift of hovering insects

Insect hovering is one of the most fascinating acrobatic flight modes in nature, and its aerodynamics has been intensively studied, mainly through computational approaches. While the numerical analyses have revealed detailed vortical structures around flapping wings and resulting forces for specific hovering conditions, theoretical understanding of a simple unified mechanism enabling the insects to be airborne is still incomplete. Here, we construct a scaling law for the lift of hovering insects through relatively simple scaling arguments of the strength of the leading edge vortex and the momentum induced by the vortical structure. Comparison of our theory with the measurement data of 35 species of insects confirms that the scaling law captures the essential physics of lift generation of hovering insects. Our results offer a simple yet powerful guideline for biologists who seek the evolutionary direction of the shape and kinematics of insect wings, and for engineers who design flapping-based micro air vehicles.
Social Class and Parental Values

Middle-and working-class parents share a broadly common se of values-but not an identical set by any means. There appears to be a close fit between the actual workings-class situation and the values of working-class parents; between the actual middle-class situation and the values of middle-class parents. In either situation the values that seem important but problematic are the ones most likely to be accorded high priority. For the working class the "important but problematic" centers around qualities that assure respectability; for the middle class it centers around internalized standards of conduct.
Effect of Jerusalem Artichoke ( Helianthus tuberosus L . ) Supplementation in Diet on Egg Production and Quality Characteristics of Laying Hens

Three hundred and twenty-four of 24 weeks hens were used to examine the Jerusalem artichoke (Helianthus tuberosus L.) supplementation as dietary prebiotic in feed on egg production and quality characteristics of laying hens. The dietary treatments were divided into 4 groups and each group consisted of 6 replications with 18 hens. The study were divided into one control (without Jerusalem artichoke) and 2 treatment groups; I) supplementing 50 ppm of dried Jerusalem artichoke in diet and II) supplementing 100 ppm of dried Jerusalem artichoke in diet. At the end of feeding trial (8 weeks), supplementing Jerusalem artichoke in feed did not influence feed intake, final body weight, egg production, egg weight and egg mass (p>0.05), however 100 ppm of dried Jerusalem artichoke significantly increased albumen ratio, yolk:albumen ratio and albumen height of eggs (p<0.05). However, yolk weight ratio, shell weight ratio and shell eggs thickness of eggs did not influence by Jerusalem artichoke. It can be concluded that Jerusalem artichoke useful as dietary prebiotic to accomplish egg quality characteristics of laying hens. Keyword--Jerusalem artichoke, Prebiotic, Feed Additive, Feed, Egg Quality, Hens
Bromodomain protein BRD4 inhibitor JQ1 regulates potential prognostic molecules in advanced renal cell carcinoma

Sunitinib is a standard molecular-targeted drug used as a first-line treatment for metastatic clear cell renal cell carcinoma (ccRCC); however, resistance to sunitinib has become a major problem in medical practice. Recently, bromodomain containing 4 (BRD4), a member of the bromodomain family proteins, was identified as a promising therapeutic target, and its inhibitor JQ1 has been shown to have inhibitory effects in various human cancers. However, the anti-cancer effects of JQ1 in ccRCC, particularly sunitinib-resistant ccRCC, are still unclear. Here, we aimed to elucidate the anti-cancer effects of JQ1 and the mechanisms underlying BRD4 inhibition in sunitinib-sensitive and -resistant ccRCCs. Analysis of The Cancer Genome Atlas (TCGA) ccRCC cohort showed that patients with high BRD4 expression had shorter overall survival than those with low expression. JQ1 treatment significantly inhibited tumor growth of sunitinib-sensitive and -resistant ccRCC cells in part through MYC regulation. Based on RNA sequencing analyses of ccRCC cells treated with JQ1 to elucidate the mechanisms other than MYC regulation, we identified several oncogenes that may be potential therapeutic targets or prognostic markers; patients with high expression of SCG5, SPOCD1, RGS19, and ARHGAP22 had poorer overall survival than those with low expression in TCGA ccRCC cohort. Chromatin immunoprecipitation assays revealed that these oncogenes may be promising BRD4 targets, particularly in sunitinib-resistant ccRCC cells. These results identified SCG5, SPOCD1, RGS19, and ARHGAP22 as potential prognostic markers and showed that BRD4 inhibition may have applications as a potential therapeutic approach in sunitinib-sensitive and -resistant ccRCC.
Dynamics of dynamics: following the formation of a line attractor

Trained recurrent neural networks are commonly used both in neuroscience and in machine learning. Recently, several attempts were made to understand the dynamics of such trained networks. Understanding how these dynamics arise through learning, however, is an uncharted territory. Here, we study this process in a simple setting -- learning to memorize analog values, leading to the formation of a line attractor. We show that problems associated with sequential learning of different tasks also occur in this setting. Specifically, catastrophic forgetting dramatically hinders a local learning rule from converging. In contrast, we show that the FORCE algorithm avoids this issue, and analyze the underlying causes. Using these insights, we suggest steps towards a more biologically plausible version of FORCE, as well as an approach to design optimal training protocols.
Infection of Fungi and Bacteria in Brain Tissue From Elderly Persons and Patients With Alzheimer’s Disease

Alzheimer’s disease (AD) is the leading cause of dementia in elderly people. The etiology of this disease remains a matter of intensive research in many laboratories. We have advanced the idea that disseminated fungal infection contributes to the etiology of AD. Thus, we have demonstrated that fungal proteins and DNA are present in nervous tissue from AD patients. More recently, we have reported that bacterial infections can accompany these mycoses, suggesting that polymicrobial infections exist in AD brains. In the present study, we have examined fungal and bacterial infection in brain tissue from AD patients and control subjects by immunohistochemistry. In addition, we have documented the fungal and bacterial species in brain regions from AD patients and control subjects by next-generation sequencing (NGS). Our results from the analysis of ten AD patients reveal a variety of fungal and bacterial species, although some were more prominent than others. The fungal genera more prevalent in AD patients were Alternaria, Botrytis, Candida, and Malassezia. We also compared these genera with those found in elderly and younger subjects. One of the most prominent genera in control subjects was Fusarium. Principal component analysis clearly indicated that fungi from frontal cortex samples of AD brains clustered together and differed from those of equivalent control subjects. Regarding bacterial infection, the phylum Proteobacteria was the most prominent in both AD patients and controls, followed by Firmicutes, Actinobacteria, and Bacteroides. At the family level, Burkholderiaceae and Staphylococcaceae exhibited higher percentages in AD brains than in control brains. These findings could be of interest to guide targeted antimicrobial therapy for AD patients. Moreover, the variety of microbial species in each patient may constitute a basis for a better understanding of the evolution and severity of clinical symptoms in each patient.
Transient hydrographic and chemical conditions affecting microplankton populations in the coastal transition zone of the Iberian upwelling system (NW Spain) in September 1986

The coastal transition zone and adjacent continental shelf of the Iberian upwelling system was studied in September 1986, during the seasonal transition from upwelling-favored to downwellingfavored winds. The most striking features in the coastal transition zone were: (1) a poleward flow of high salinity Eastern North Atlantic Central Water (subtropical) off the Rias Baixas (Galician western coast); and (2) an anticyclonic eddy off Cape Ortega1 (Galician northern coast). Chemical and biological similarities between both structures, clearly different from the surrounding oceanic waters, suggest that the eddy was an isolated and aged parcel of water originating from the poleward flow. The continental shelf was characterized by: (1) outwelling of chlorophyll-rich waters from the four large coastal embayments (the “Rias Baixas”) in the western coast and; (2) an upwelling front off the northern coast. The coexistence of opposite hydrographic structures, as the poleward flow and the upwelling front, was the consequence of transitional wind conditions in September-October, and we hypothesized transitional conditions to be crucial for the development of the eddy. Both the poleward flow and the eddy precluded the shelf-edge exchange of microplankton populations developed over the shelf, leading to massive in situ sedimentation and subsequent nutrient mineralization over the shelf.
Myopic loss aversion and the momentum premium

We examine how myopic loss aversion is related to the momentum premium by evaluating momentum using a framework of cumulative prospect theory. We show that frequent portfolio evaluations by momentum investors provide plausible arbitrage bounds that may explain the long-run success of the strategy given momentum investors' short-termism. We explore the impact of myopia over an international sample, finding that momentum is stronger in countries that are predisposed to myopia and where the proportion of funds under delegated management is high. As investor myopia may limit investors’ ability to arbitrage away momentum returns, our results support behavioral models of momentum. Acknowledgements: The comments from Peter Brooke, Stephen Brown, Steve Easton, Robert Faff, Phil Gray, and Tom Smith have been greatly appreciated. This paper has also benefited from the comments of seminar participants at the 27 Australasian Finance and Banking Conference, Monash University and the University of Newcastle. Research funding provided by Platypus Asset Management is greatly appreciated.
Rapid seismic domain transfer: Seismic velocity inversion and modeling using deep generative neural networks

Traditional physics-based approaches to infer sub-surface properties such as full-waveform inversion or reflectivity inversion are time-consuming and computationally expensive. We present a deep-learning technique that eliminates the need for these computationally complex methods by posing the problem as one of domain transfer. Our solution is based on a deep convolutional generative adversarial network and dramatically reduces computation time. Training based on two different types of synthetic data produced a neural network that generates realistic velocity models when applied to a real dataset. The system's ability to generalize means it is robust against the inherent occurrence of velocity errors and artifacts in both training and test datasets.
Biochemical and Physiological Changes during Thermal Stress in Bovines

Thermal stress is a major cause of production losses in the dairy and beef industries. Dairy animals are more heat sensitive as average milk yield has increased. During thermal stress physiological and biochemical changes occurs in the animal body which directly or indirectly affect the production. This review clearly describes about biochemical and physiological changes occur during thermal stress in bovines.
DISCRETE COSINE TRANSFORM The Discrete Fourier Transform ( DFT )

Image coding becomes an interested issue for its extensive use in wide range of applications. This work deals with the Fast approaches of hardware implementation for Forward Discrete Cosine Transform (FDCT) and the Inverse Discrete Cosine Transform (IDCT). These approaches are normally used for image coding and decoding applications. The implemented approaches are built using hardware design with specific control parameters to speed up the processing. The implemented approach based on one dimensional Discrete Cosine Transform (1D-DCT) and fast transposing through high access memory that offer real time operation. The control system of flow of pixels is built to have two principal processing of rows and columns and the flow of coefficients comes from high speed access memory. The implementation of the system is done to achieve high speed and accurate results. The differences between the original image and the recovered image for all tested sizes are very small and it is about 10 -16.
Latent tuberculosis infection in healthcare workers at a tertiary care center

Objective: The aim of the present study was to compare the of tuberculin skin test (TST) and Quantiferon-TB gold in Tube (QTF-GIT) test in diagnosis of latent tuberculosis infection in health care workers. Methods: A total of 100 volunteers were recruited from the health care workers in our hospital. In addition to collection of descriptive data and occupational history including age, gender, occupation, duration of work, presence and number of BCG scars, also chest radiographs, QTF-GIT and TST were performed routinely in all participants. Results: Rates of positivity for TST and QTF-GIT test were 42% and 23%, respectively and there was a weak concordance between these two companion diagnostic tests (k=0.23, concordance 62.2%). In comparison to TST, sensitivity and specificity of QTF were 35.7% and 86.2%. No significant correlation was detected between presence and number of Bacillus Calmette-Guerin (BCG) scars and QTF-GIT test. In contrast, as the number of BCG scar increased in accordance with the increase in the diameter of indurations in TST. Interestingly, there was a significant correlation between TST and QTF-GIT tests. The average diameter of TST in QTF-GIT negative individuals was 11 mm, while it was 15.4 mm in QTF-GIT positive cases. Positivity of QTF-GIT was more likely as the diameter of TST indurations increased. Conclusion: We suggest that QTF-GIT test is an effective diagnostic measure for latent tuberculosis infection in countries that have high NTM prevalence and BCG vaccination ratios. However, further controlled studies on larger series are warranted to acquire more accurate results.
The Nature of Stakeholder Satisfaction with Marketing Education

The current article represents a cautionary tale in continuing emerging marketization practices as the dominant form of marketing with higher education. Specifically, a review of three important emerging literature streams (i.e., quality-of-life, service-dominant logic, and stakeholder orientation) all appear to support calls for moving beyond typical (short-term, hedonistic) measures of consumer satisfaction associated with the delivery of higher education toward satisfaction judgments based on higher-order forms of happiness (i.e., prudential and perfectionist forms of happiness such as eudaimonia). This conclusion suggests that the nature of long-term value co-creation associated with higher education should focus on quality of life and well-being. Critical to the success of moving marketing strategy of institutions of higher education in the direction asserted herein will be embracing a primary strategic marketing objective of convincing stakeholders to value long-term, eudaimonic forms of happiness and satisfaction over the current psychological, short-term, hedonistic satisfaction forms assessing today’s marketization practices. A series of propositions are offered to help guide marketers in embracing this perspective.
A comparison of business angel and venture capitalist investment procedures: An agency theory-based analysis

This paper provides a detailed comparison of the investment criteria and procedures of business angels (BAs) and venture capitalists (VCs) across the full investment process. To make the study more robust, a theoretical base is adopted (based on agency theory) to form research hypotheses which propose that BAs and VCs in the UK may use different approaches to limit potential agency risks in their investments (i.e. the risks associated with an entrepreneur's potential misuse of the investor's money). Utilizing data from 40 personal interviews and 262 questionnaire responses, this study empirically supports the main hypothesized notion that, although both investors reduce agency risks at all stages of the investment process, BAs place more emphasis on doing so ex post investment (the incomplete contracts approach), while VCs stress doing so more ex ante investment (the principal-agent approach).
Selling substitute goods to loss-averse consumers: limited availability, bargains, and rip-offs

This article derives the optimal pricing and product-availability strategies for a retailer selling two substitute goods to loss-averse consumers and shows that limited-availability sales manipulate consumers into an ex ante unfavorable purchase. The seller maximizes profits by raising the consumers' reference point through a tempting discount on a good available only in limited supply (the bargain), and cashing in with a high price on the other (the rip-off), which consumers buy if the bargain is not available to reduce their disappointment. The seller might prefer to offer a deal on the more valuable product, using it as a bait.
CNN-based thermal infrared person detection by domain adaptation

Imaging sensors capturing the surroundings of an autonomous vehicle are vital for its understanding of the environment. While thermal infrared cameras promise improved bad weather and nighttime robustness compared with standard RGB cameras, detecting objects, such as persons, in thermal infrared imagery is a tough problem because image resolution and quality is typically far lower, especially for low-cost sensors. Currently, deep learning based object detection frameworks offer an impressive performance on high-quality images. However, applying them to low-quality data in a different spectral range causes significant performance drops. This work proposes a strategy to make use of elaborate CNN-based object detector frameworks which are pre-trained on visual RGB images. Two key steps are undertaken: First, an appropriate preprocessing strategy for the IR data is suggested which transforms the IR data as close as possible to the RGB domain. This allows pre-trained RGB features to be effective on the novel domain. Second, the remaining domain gap is addressed by fine-tuning the pre-trained CNN on a limited set of thermal IR data. Different IR preprocessing options are explored, each addressing a different aspect of the domain gap between thermal IR and RGB data. Examples include dynamic range, blur or contrast. Because no preprocessing can cover all aspects alone, providing preprocessing combinations to the CNN allows addressing more than one aspect at once and further improves the results. Experiments indicate significant person detection improvements on the public KAIST dataset with the optimized preprocessing strategy.
Role of MRCP in Diagnosing Biliary Anastomotic Strictures After Liver Transplantation: A Single Tertiary Care Center Experience

Background Biliary strictures (BS) are common complication after liver transplantation. We aimed to determine the accuracy of magnetic resonance cholagiopancreatography (MRCP) in diagnosing BS in liver transplant recipients (LTRs) when compared to direct cholangiographic methods (endoscopic resonance cholagiopancreatography [ERCP] and/or percutaneous transhepatic cholangiography [PTC]). Methods Retrospective chart review of 910 LTRs (July 2008 to April 2015) was performed, and a total of 39 patients with duct-to-duct anastomosis (22 males; 56.4%; mean age, 52.8 ± 8.3 years) were included who had an MRCP followed by either ERCP and/or PTC within 4 weeks. A cholangiographic narrowing (on ERCP and/or PTC) that required balloon dilation and/or stent placement was considered a BS and was considered clinically significant if the intervention resulted in at least 30% improvement of bilirubin within 2 weeks. Sensitivity, specificity, accuracy, positive predictive values and negative predictive values of MRCP in diagnosing BS were calculated. Results Magnetic resonance cholagiopancreatography showed anastomotic BS in 17 of 39 patients, and subsequent ERCP and/or PTC revealed a total of 25 BS (positive predictive value of 0.94). Nine BS on cholangiography (ERCP, 8; PTC, 1) were not detected on earlier MRCP (sensitivity, 0.64; 95% CI, 0.45-0.82); 2 were clinically significant BS and 6 of the remaining 7 had no improvement in their liver function test with biliary intervention. Thirteen LTRs had no BS on either modality (specificity, 0.93; 95% CI, 0.66-0.99). The negative predictive value of MRCP was 0.59 for cholangiographic BS. The overall accuracy of MRCP is 0.74 (exact 95% CI, 0.58-0.87). Inclusion of age, race, and alanine aminotransferase level improved the predictive value of MRCP (area under the curve = 0.94, 95% CI: 0.86-1.00). Conclusions Magnetic resonance cholagiopancreatography has high specificity but low sensitivity in diagnosing cholangiographic BS in LTRs, although the predictive value further improved with inclusion of age, race, and alanine aminotransferase. Clinical significance of BS in LTRs not identified on MRCP is questionable because ERCP with intervention did not improve their liver function tests in the vast majority.