Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic Research of Neurodegenerative Disorders Using Patient iPSC-Based Models

Epigenetic mechanisms play a role in human disease but their involvement in pathologies from the central nervous system has been hampered by the complexity of the brain together with its unique cellular architecture and diversity. Until recently, disease targeted neural types were only available as postmortem materials after many years of disease evolution. Current in vitro systems of induced pluripotent stem cells (iPSCs) generated by cell reprogramming of somatic cells from patients have provided valuable disease models recapitulating key pathological molecular events. Yet whether cell reprogramming on itself implies a truly epigenetic reprogramming, the epigenetic mechanisms governing this process are only partially understood. Moreover, elucidating epigenetic regulation using patient-specific iPSC-derived neural models is expected to have a great impact to unravel the pathophysiology of neurodegenerative diseases and to hopefully expand future therapeutic possibilities. Here we will critically review current knowledge of epigenetic involvement in neurodegenerative disorders focusing on the potential of iPSCs as a promising tool for epigenetic research of these diseases.
Enrichment of circulating melanoma cells (CMCs) using negative selection from patients with metastatic melanoma

Circulating tumor cells have emerged as prognostic biomarkers in the treatment of metastatic cancers of epithelial origins viz., breast, colorectal and prostate. These tumors express Epithelial Cell Adhesion Molecule (EpCAM) on their cell surface which is used as an antigen for immunoaffinity capture. However, EpCAM capture technologies are of limited utility for non-epithelial cancers such as melanoma. We report a method to enrich Circulating Melanoma Cells (CMCs) that does not presuppose malignant cell characteristics. CMCs were enriched by centrifugation of blood samples from healthy (N = 10) and patient (N = 11) donors, followed by RBC lysis and immunomagnetic depletion of CD45-positive leukocytes in a specialized magnetic separator. CMCs were identified by immunocytochemistry using Melan-A or S100B as melanoma markers and enumerated using automated microscopy image analyses. Separation was optimized for maximum sensitivity and recovery of CMCs. Our results indicate large number of CMCs in Stage IV melanoma patients. Analysis of survival suggested a trend toward decreased survival with increased number of CMCs. Moreover, melanoma-associated miRs were found to be higher in CMC-enriched fractions in two patients when compared with the unseparated samples, validating this method as applicable for molecular analyses. Negative selection is a promising approach for isolation of CMCs and other EpCAM -negative CTCs, and is amenable to molecular analysis of CMCs. Further studies are required to validate its efficacy at capturing specific circulating cells for genomic analysis, and xenograft studies.
Hopping Odometry: Motion Estimation with Selective Vision

We present a two-step iterative algorithm to estimate the trajectory of a hopping rover. In the first step, a monocular scheme of visual odometry is adapted to estimate an initial portion the hopping trajectory. From this, the parameters for the ballistic motion are recovered, and the trajectory is extrapolated to predict the positions of the rover for the remainder of the hop. In the second step, we devise a scheme called “selective vision”, combining the ideas of active vision and guided search. An envelope lying between the start and end of a hop is defined, within which features most likely to be re-observed across a hop are detected and matched. Performing pose estimation on the these matched features allow the relative motion between a camera frame within the visual odometry step and a camera frame within the extrapolated trajectory to be estimated. The newly determined camera frame in the extrapolated trajectory can then be used to refine the parameters of the ballistic motion, and the trajectory can be re-extrapolated to predict future positions of the hopping rover. Following this scheme, it is possible to estimate the trajectory of a hopping rover undergoing continuous rotational motion with only one set of cameras without continuous tracking of terrain features.
Pathophysiology of Diabetic Retinopathy

Diabetes is now regarded as an epidemic, with the population of patients expected to rise to 380 million by 2025. Tragically, this will lead to approximately 4 million people around the world losing their sight from diabetic retinopathy, the leading cause of blindness in patients aged 20 to 74 years. The risk of development and progression of diabetic retinopathy is closely associated with the type and duration of diabetes, blood glucose, blood pressure, and possibly lipids. Although landmark cross-sectional studies have confirmed the strong relationship between chronic hyperglycaemia and the development and progression of diabetic retinopathy, the underlying mechanism of how hyperglycaemia causes retinal microvascular damage remains unclear. Continued research worldwide has focussed on understanding the pathogenic mechanisms with the ultimate goal to prevent DR. The aim of this paper is to introduce the multiple interconnecting biochemical pathways that have been proposed and tested as key contributors in the development of DR, namely, increased polyol pathway, activation of protein kinase C (PKC), increased expression of growth factors such as vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), haemodynamic changes, accelerated formation of advanced glycation endproducts (AGEs), oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and subclinical inflammation and capillary occlusion. New pharmacological therapies based on some of these underlying pathogenic mechanisms are also discussed.
An analytical platform for mass spectrometry-based identification and chemical analysis of RNA in ribonucleoprotein complexes

We describe here a mass spectrometry (MS)-based analytical platform of RNA, which combines direct nano-flow reversed-phase liquid chromatography (RPLC) on a spray tip column and a high-resolution LTQ-Orbitrap mass spectrometer. Operating RPLC under a very low flow rate with volatile solvents and MS in the negative mode, we could estimate highly accurate mass values sufficient to predict the nucleotide composition of a ∼21-nucleotide small interfering RNA, detect post-transcriptional modifications in yeast tRNA, and perform collision-induced dissociation/tandem MS-based structural analysis of nucleolytic fragments of RNA at a sub-femtomole level. Importantly, the method allowed the identification and chemical analysis of small RNAs in ribonucleoprotein (RNP) complex, such as the pre-spliceosomal RNP complex, which was pulled down from cultured cells with a tagged protein cofactor as bait. We have recently developed a unique genome-oriented database search engine, Ariadne, which allows tandem MS-based identification of RNAs in biological samples. Thus, the method presented here has broad potential for automated analysis of RNA; it complements conventional molecular biology-based techniques and is particularly suited for simultaneous analysis of the composition, structure, interaction, and dynamics of RNA and protein components in various cellular RNP complexes.
The effect of four medicinal plants on the performance, blood biochemical traits and ileal microflora of broiler chicks.

This study was conducted with broilers to evaluate the effects of dietary supplementation of four medicinal plants on the performance, blood lipids and microfl ora population in the ileum. Three hundred and thirty-six day- old Ross broiler chicks were used in a completely randomized study with 6 treatments and 4 replicates each. The diets were iso-caloric and iso-nitrogenous and contained 15, 3, 2 and 2 g/kg of dried cumin, peppermint, yarrow and poley herbs, respectively. Two dietary treatments were considered the negative (containing no medicinal plant or antibiotic) and positive (containing Flavomycin at 0.4 g/kg) control groups. Flavomycin and peppermint supplementation to the diet increased the FI and BWG of the broiler chickens compared to the control (P<0.01). Dietary Flavomycin signifi cantly increased body weight gain (BWG) in contrast to the other dietary treatments (P<0.05). Peppermint and cumin supplementation to the diet increased the BWG of the broiler chickens, whereas dietary poley and yarrow signifi cantly reduced the BWG and increased feed conversion ratio (FCR) when compared with broilers fed the negative control diet (P<0.05). Dietary Flavomycin and peppermint increased the concentration of triglycerides (TG), low density lipoprotein (LDL) and total cholesterol in serum (P<0.05). Addition of Flavomycin or peppermint to the diet signifi cantly reduced the ileal Bifi dobacteria and Clostridia (P<0.05). In conclusion, under the conditions of this study, peppermint improved growth performance and adding it to the diet could be an alternative to the use of antibiotics as growth promoters in poultry production.
Concurrent Use of Cigarettes and Smokeless Tobacco among US Males and Females

Background. The current study describes concurrent use of cigarettes and smokeless tobacco (CiST) among males and females and evaluates factors associated with CiST use. Methods. Cross-sectional data were drawn from the 2010 Behavioral Risk Factor Surveillance System (BRFSS). Weighted stratified analyses were performed to find associations between CiST use and sociodemographic factors by gender. CiST users were compared to three different tobacco use groups: nonusers, exclusive smokers, and exclusive ST users. Results. Younger age and heavy alcohol consumption were consistently associated with increased odds of CiST use among both males and females, and regardless of comparison group. Among males, education was inversely related to CiST use, and these findings were consistent in all three comparisons. Among women, those unable to work or out of work were more likely to be CiST users, which was consistent across comparisons. American Indian females had higher odds of CiST use than White females when nontobacco users or smokers were the comparison group. Conclusion. This study identified sociodemographic characteristics associated with CiST use, and differences in these associations among women and men. Additionally, this study highlights the need to carefully consider what comparison groups should be used to examine factors associated with CiST use.
Kava hepatotoxicity: a clinical survey and critical analysis of 26 suspected cases

Background/Aims Hepatotoxicity has been previously suspected by national regulatory agencies in 26 patients in causal relationship with the treatment by kava extracts commonly used as herbal anxiolytic drugs. Methods A quantitative causality assessment was undertaken using the system of the Council for International Organizations of Medical Sciences, scale of objective probability scoring. Results Causality was unassessable, unrelated, or excluded in 16 patients owing to lack of temporal association and causes independent of kava or comedicated drugs. Low Council for International Organizations of Medical Sciences scores additionally resulted in excluded or unlikely causality assessments (n=2), leaving a total of eight patients with various degrees of causality for kava ± comedicated drugs. Only one out of these eight patients adhered to the regulatory recommendations regarding both daily dose (≤120 mg kavapyrones) and duration of therapy (≤3 months) and experienced toxic liver injury with a probable causality for kava. In six cases with kava overdose and/or increased duration of kava treatment causality for kava was possible (n=3) and for kava together with the comedicated drug(s) possible (n=2) or probable (n=1). Conclusion Kava taken as recommended is associated with rare hepatotoxicity, whereas overdose, prolonged treatment, and comedication may carry an increased risk.
Identifying communication models in Process Networks derived from Weakly Dynamic Programs

Process Networks (PNs) is an appealing computation abstraction helping to specify an application in parallel form and realize it on parallel platforms. The key questions to be answered are how a PN can be derived and how its components can be realized efficiently on a given parallel system. In this paper we present a novel approach of communication model identification in PNs derived from nested loops programs with data-dependent control statements, which we call Weakly Dynamic Programs (WDP). Identifying communication models at compile-time allows us to select the most efficient realization of communication components in a PN. We show how our approach is seamlessly integrated into our existing procedure of automated PN derivation from WDP programs. This paper can be considered as an important complementary work that makes our automated derivation of WDPs to PNs complete.
Network-Driven Proteogenomics Unveils an Aging-Related Imbalance in the Olfactory IκBα-NFκB p65 Complex Functionality in Tg2576 Alzheimer’s Disease Mouse Model

Olfaction is often deregulated in Alzheimer’s disease (AD) patients, and is also impaired in transgenic Tg2576 AD mice, which overexpress the Swedish mutated form of human amyloid precursor protein (APP). However, little is known about the molecular mechanisms that accompany the neurodegeneration of olfactory structures in aged Tg2576 mice. For that, we have applied proteome- and transcriptome-wide approaches to probe molecular disturbances in the olfactory bulb (OB) dissected from aged Tg2576 mice (18 months of age) as compared to those of age matched wild-type (WT) littermates. Some over-represented biological functions were directly relevant to neuronal homeostasis and processes of learning, cognition, and behavior. In addition to the modulation of CAMP responsive element binding protein 1 (CREB1) and APP interactomes, an imbalance in the functionality of the IκBα-NFκB p65 complex was observed during the aging process in the OB of Tg2576 mice. At two months of age, the phosphorylated isoforms of olfactory IκBα and NFκB p65 were inversely regulated in transgenic mice. However, both phosphorylated proteins were increased at 6 months of age, while a specific drop in IκBα levels was detected in 18-month-old Tg2576 mice, suggesting a transient activation of NFκB in the OB of Tg2576 mice. Taken together, our data provide a metabolic map of olfactory alterations in aged Tg2576 mice, reflecting the progressive effect of APP overproduction and β-amyloid (Aβ) accumulation on the OB homeostasis in aged stages.
Traveling-Wave Antenna (TWA) array as a thin Multioctave Planar Phased Array (MPPA)

Multioctave Planar Phased Arrays (MPPA) have advanced rapidly since 2000. Today, MPPA technology and its market needs appear to be nearing a point of convergence. This paper reviews the history of thin MPPAs, which exclude the Vivaldi antenna type, and presents modern planar Traveling-Wave Antenna (TWA) array as a thin MPPA. The differentiating features of modern planar TWA array from other thin MPPAs, and its potential high performance and other advantages, are discussed. Certain controversies in the theory and measurement of MPPAs are also reviewed and clarified. A planar TWA array design, with SEG breadboard demonstration, is presented to show potential performance of low VSWR, high-efficiency (low loss), scan angle ≤60° off broadside, over a 6:1 bandwidth and beyond.
Antiangiogenic Effect of Deguelin on Choroidal Neovascularization

Age-related macular degeneration is the leading cause of blindness in the elderly. Choroidal neovascularization (CNV) leads to severe vision loss in patients of age-related macular degeneration. Previously, we have demonstrated that deguelin, isolated from plants in the Mundulea sericea family, is a chemopreventive agent. This study evaluates the antiangiogenic effect of deguelin on CNV. The toxicity of deguelin was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human umbilical vein endothelial cells (HUVECs) as well as histological examination and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining in the deguelin-injected retina. Antiangiogenic activity of deguelin was evaluated by in vitro tube formation assay of HUVECs and in vivo angiogenesis of chick chorioallantoic membrane (CAM). In C57BL/6 mice with laser-induced CNV, deguelin or phosphate-buffered saline was injected intravitreously. CNV lesions were examined by fluorescence angiography and vessel counting in cross-sections. Deguelin showed no effect on cell viability of HUVECs and no retinal toxicity in a concentration range of 0.01 to 1 μM. Deguelin effectively inhibited in vitro tube formation of HUVECs and in vivo angiogenesis of CAM. Interestingly, deguelin significantly reduced CNV and its leakage in mouse model of laser photocoagulation-induced CNV. Our data suggests that deguelin is a potent inhibitor of CNV and may be applied in the treatment of other vasoproliferative retinopathies such as retinopathy of prematurity and diabetic retinopathy.
White Blood Cell Counts, Leukocyte Ratios, and Eosinophils as Inflammatory Markers in Patients With Coronary Artery Disease

Inflammation is a key feature of atherosclerosis and its clinical manifestations. The leukocyte count has emerged as a marker of inflammation that is widely available in clinical practice. Since inflammation plays a key role in atherosclerosis and its end results, discovering new biomarkers of inflammation becomes important in order to help diagnostic accuracy and provide prognostic information about coronary cardiac disease. In acute coronary syndromes and percutaneous coronary intervention, elevated levels of almost all subtypes of white blood cell counts, including eosinophils, monocytes, neutrophils, and lymphocytes, and neutrophil–lymphocyte ratio and eosinophil–leukocyte ratio constitute independent predictors of adverse outcomes. Eosinophil count and eosinophil–leukocyte ratio, in particular, emerge as novel biomarkers for risk stratification in patients with coronary artery disease. Since the presence of eosinophils denotes hypersensitivity inflammation and hypersensitivity associated with Kounis syndrome, this reality is essential for elucidating the etiology of inflammation in order to consider predictive and preventive measures and to apply the appropriate therapeutic methods.
From "Selena Gomez" to "Marlon Brando": Understanding Explorative Entity Search

Consider a user who submits a search query "Shakira" having a specific search goal in mind (such as her age) but at the same time willing to explore information for other entities related to her, such as comparable singers. In previous work, a system called Spark, was developed to provide such search experience. Given a query submitted to the Yahoo search engine, Spark provides related entity suggestions for the query, exploiting, among else, public knowledge bases from the Semantic Web. We refer to this search scenario as explorative entity search. The effectiveness and efficiency of the approach has been demonstrated in previous work. The way users interact with these related entity suggestions and whether this interaction can be predicted have however not been studied. In this paper, we perform a large-scale analysis into how users interact with the entity results returned by Spark. We characterize the users, queries and sessions that appear to promote an explorative behavior. Based on this analysis, we develop a set of query and user-based features that reflect the click behavior of users and explore their effectiveness in the context of a prediction task.
2D1431 Machine Learning Lab 3: Reinforcement Learning

In this lab you will use reinforcement learning to search for a working control algorithm for a simple walking robot. We will assume that you are familiar with the basic concepts of reinforcement learning and that you have read chapter 13 in the course book Machine Learning (Mitchell, 1997). As supplementary material you may read the first four chapters of the survey on reinforcement learning by Kaelbling et al. (1996). For further reading and a detailed discussion of policy iteration and reinforcement learning, the textbook “Reinforcement Learning” is highly recommended (Sutton and Barto, 1999). Policy iteration is an algorithm which can be used to compute optimal policies given a model of the environment. Policy iteration solves problems that can be formulated as Markov decision processes, i.e. when the state transitions and reward functions are known beforehand, and utilizes the principles of dynamic programming. When the environment is unknown and only accessible by interacting with it, the agent will have to use learning to solve the problem. Temporal difference learning is a technique which resembles policy iteration but without the need for a known environment. The central idea of both policy iteration and temporal difference learning is to estimate value functions, which in turn can be used to identify the optimal policy. The value function is essential in that it makes the value of predicted future events accessible to the process which decides what to do now. Reinforcement based methods are therefore able to do a basic form of planning.
Quo vadis, medicina?

Versuch einer Jahrhundertbilanz Auch im 21. Jahrhundert wird unsere Industriegesellschaft – bei allen Übergängen in eine Informationsgesellschaft – geprägt bleiben von den drei wissenschaftlichen Modellen, die bereits im 19. Jahrhundert ihr Profil gewonnen hatten, nämlich 1. den Naturwissenschaften, verknüpft mit einer hochentwickelten Technik; 2. den Entwicklungswissenschaften mit ihrer Evolutionstheorie und den damit verbundenen Wachstumsmodellen; 3. den Sozialwissenschaften mit ihren biologistischen Staatstheorien und sozialpolitischen Versorgungsstrategien. Alle drei Modelle sind ihrer Struktur nach auf eine Ökonomie festgelegt, die keine Rücksicht nehmen darf auf ökologische Gleichgewichte und qualitative Lebensinteressen. Ungelöst blieb denn auch die Frage, wie man Rentabilität und Humanität, Menschlichkeit und Wirtschaftlichkeit zugleich wird befriedigen können.
Zernike moment based time sensitive targets detection and recognition

The ground time sensitive targets have high mobility. It is hard to use traditional template matching method to detect and recognize the targets since their attitude angles are not known. To make matters worse, the complicated background and grayscale reversal always cover the target like airplane and warship. This paper proposes a method based on 2D Zernike moment and Adaboost algorithm to detect and recognize the time sensitive targets. The experimental result indicates that the method is efficient.
Replaceable Implementations for Actor Systems

CoDE is an actor-based software framework aimed at both simplifying the development of large and distributed complex systems and guarantying an efficient execution of applications. This software framework takes advantage of a concise actor model that makes easy the development of the actor code by delegating the management of events (i.e., the reception of messages) to the execution environment. Moreover, it allows the development of scalable and efficient applications through the possibility of using different implementations of the components that drive the execution of actors. This paper introduces the software framework and shows how the performance of applications can be optimized by choosing the best combination among the alternative implementations of its components.