Miracle-dz/UniFAR-FTUs huggingface dataset:
Learning image segmentation and hierarchies by learning ultrametric distances

In this thesis I present new contributions to the fields of neuroscience and computer science. The neuroscientific contribution is a new technique for automatically reconstructing complete neural networks from densely stained 3d electron micrographs of brain tissue. The computer science contribution is a new machine learning method for image segmentation and the development of a new theory for supervised hierarchy learning based on ultrametric distance functions. It is well-known that the connectivity of neural networks in the brain can have a dramatic influence on their computational function. However, our understanding of the complete connectivity of neural circuits has been quite impoverished due to our inability to image all the connections between all the neurons in biological network. Connectomics is an emerging field in neuroscience that aims to revolutionize our understanding of the function of neural circuits by imaging and reconstructing entire neural circuits. In this thesis, I present an automated method for reconstructing neural circuitry from 3d electron micrographs of brain tissue. The cortical column, a basic unit of cortical micro-circuitry, will produce a single 3d electron micrograph measuring many 100s terabytes once imaged and contain neurites from well over 100,000 different neurons. It is estimated that tracing the neurites in such a volume by hand would take several thousand human years. Automated circuit tracing methods are thus crucial to the success of connectomics. In computer vision, the circuit reconstruction problem of tracing neurites is known as image segmentation. Segmentation is a grouping problem where image pixels belonging to the same neurite are clustered together. While many algorithms for image segmentation exist, few have parameters that can be optimized using groundtruth data to extract maximum performance on a specialized dataset. In this thesis, I present the first machine learning method to directly minimize an image segmentation error. It is based the theory of ultrametric distances and hierarchical clustering. Image segmentation is posed as the problem of learning and classifying ultrametric distances between image pixels. Ultrametric distances on point set have the special property that they correspond exactly to hierarchical clustering of the set. This special property implies hierarchical clustering can be learned by directly learning ultrametric distances. In this thesis, I develop convolutional networks as a machine learning architecture for image processing. I use this powerful pattern recognition architecture with many tens of thousands of free parameters for predicting affinity graphs and detecting object boundaries in images. When trained using …
Bioresorbable polyelectrolytes for smuggling drugs into cells

There is ample evidence that biodegradable polyelectrolyte nanocapsules are multifunctional vehicles which can smuggle drugs into cells, and release them upon endogenous activation. A large number of endogenous stimuli have already been tested in vitro, and in vivo research is escalating. Thus, the interest in the design of intelligent polyelectrolyte multilayer (PEM) drug delivery systems is clear. The need of the hour is a systematic translation of PEM-based drug delivery systems from the lab to clinical studies. Reviews on multifarious stimuli that can trigger the release of drugs from such systems already exist. This review summarizes the available literature, with emphasis on the recent progress in PEM-based drug delivery systems that are receptive in the presence of endogenous stimuli, including enzymes, glucose, glutathione, pH, and temperature, and addresses different active and passive drug targeting strategies. Insights into the current knowledge on the diversified endogenous approaches and methodological challenges may bring inspiration to resolve issues that currently bottleneck the successful implementation of polyelectrolytes into the catalog of third-generation drug delivery systems.
Clinical Approach to Diabetic Cardiomyopathy: A Review of Human Studies.

BACKGROUND Diabetic Cardiomyopathy (DC) has been defined as a distinct entity characterized by the presence of diastolic or systolic cardiac dysfunction in a diabetic patient in the absence of other causes for Cardiomyopathy, such as coronary artery disease (CAD), hypertension (HTN), or valvular heart disease. Diabetes affects every organ in the body and cardiovascular disease accounts for two-thirds of the mortality in the diabetic population. Diabetes-related heart disease occurs in the form of coronary artery disease (CAD), cardiac autonomic neuropathy or DC. The prevalence of cardiac failure is high in the diabetic population and DC is a common, but underestimated cause of heart failure in diabetes. The strong association between diabetes and heart failure has fueled intense human and animal research aimed at identifying the mechanisms underlying diabetic myocardial disease. Despite significant progress made, the precise pathogenesis of diabetic Cardiomyopathy is yet to be clearly defined. Hyperglycemia, dyslipidemia and inflammation are thought to play key roles in the generation of reactive oxygen or nitrogen species which are in turn involved. METHODS We have reviewed the up-to-date scientific literature addressing these issues. RESULTS The myocardial interstitium undergoes alterations resulting in abnormal contractile function noted in DC. In the early stages of the disease, diastolic dysfunction is the only abnormality, but systolic dysfunction supervenes in the later stages with impaired left ventricular ejection fraction. Transmitral Doppler echocardiography is usually used to assess diastolic dysfunction, but tissue Doppler Imaging and Cardiac Magnetic Resonance Imaging are being increasingly used for early detection of DC. Diabetic patients with microvascular complications show the strongest association between diabetes and Cardiomyopathy, an association that parallels the duration and severity of hyperglycemia. CONCLUSION The management of DC involves improvement in lifestyle, control of glucose and lipid abnormalities, together with treatment of hypertension and CAD, if present.
Before Virtue: Biology, Brain, Behavior, and the “Moral Sense”

ABSTRACT: Biological, brain, and behavioral sciences offer strong and growing support for the virtue ethics account of moral judgment and ethical behavior in business organizations. The acquisition of moral agency in business involves the recognition, refinement, and habituation through the processes of reflexion and reflection of a moral sense encapsulated in innate modules for compassion, hierarchy, reciprocity, purity, and affiliation adaptive for communal life both in ancestral and modern environments. The genetic and neural bases of morality exist independently of institutional frameworks and social structures. The latter not only shape moral behaviors within circumscribed limits, they also imply a plurality and compartmentalization of roles which may enable or impede the habituation of virtue. Becoming a virtuous agent entails the practical refinement of predispositions in situ as a member of a community of practitioners rather than entailing a normative ethical educational project seeking an intellectual resolution of abstract moral questions.
Apolipoprotein E Genotype and Incident Ischemic Stroke: The Atherosclerosis Risk in Communities Study

Background and Purpose— A relationship between the apolipoprotein E (apoE) genotype and ischemic stroke has been inconsistently reported. We explored this relation in the Atherosclerosis Risk in Communities Study (ARIC). Methods— The ARIC cohort involves 15 792 men and women, aged 45 to 64 years at baseline and sampled from 4 U.S. communities. Between 1987 and 2001, 498 incident ischemic strokes occurred. Results— After stratifying by race and sex and adjusting for other nonlipid risk factors, there was no significant relation between the apoE genotype and incident stroke, except in black women (hazard ratio for &egr;2 genotype relative to &egr;3/&egr;3=0.53; 95% CI, 0.28 to 0.99). Conclusions— For the most part, in this middle-aged sample, apoE was not a risk factor for incident ischemic stroke.
World Journal on Educational

The purpose of this quasi experimental study is to examine the effectiveness of Facebook in terms of pre-service teachers’ attitudes, achievements and satisfactions in comparison to traditional instruction. The sample consisted of 96 pre-service teachers studying at a public university in Turkey. Attitudes towards teaching profession scale, course satisfaction scale and students’ course grades were used as data gathering tools. One-Way ANCOVA and two t tests were used as data analysis method. The analysis showed that there were no significant differences in terms of attitudes, achievement and satisfaction between those who used facebook and who did not. The findings suggest that Facebook did not have a significant effect on pre service teachers’ attitudes, achievement and satisfaction
Predicting motor and generator maximum torque as a function of mass

There is currently no universally accepted way to predict the maximum input/output torque of electrical generators/motors as a function of the machine's mass. A new correlation is proposed for this relationship that collapses the data from machines with masses ranging over more than three orders of magnitude and torques ranging over five orders of magnitude. It is shown that, at least for machines operating below 3600 rpm, this relationship is only weakly dependent on other parameters of the machine design such as operating rpm, motor type (inductance vs. permanent magnet), operating voltage etc_ Physical arguments are given to explain the correlation and its independence from other operating parameters. This new correlation allows a system designer to have a simple one variable equation to calculate the mass of a motor or generator given a desired torque capability. Because the correlation is so predictive, it can also be used as a metric to compare different machine designs. Families of machines that have slightly higher torques than predicted by the correlation typically are “better” designs.
Reducing Power in Error Correcting Code using Genetic Algorithm

Abstract — This paper proposes a method which reduces power consumption in single-error correcting, double error-detecting checker circuits that perform memory error correction code. Power is minimized with little or no impact on area and delay, using the degrees of freedom in selecting the parity check matrix of the error correcting codes. The genetic algorithm is employed to solve the non linear power optimization problem. The method is applied to two commonly used SEC-DED codes: standard Hamming and odd column weight Hsiao codes. Experiments were performed to show the performance of the proposed method. Keywords — Error correcting codes, genetic algorithm, non-linear power optimization, Hamming code, Hsiao code.I. I NTRODUCTION S technology continues to scal e with smaller features sizes, lower power supply voltages, and higher operating frequencies, the soft error rate in logic circuits is rapidly increasing. Concurrent error detection using error correcting codes (ECCs) at the outputs of a circuit provides means to detect soft errors quickly before they have a chance to propagate and compromise the data integrity of a system. Error correcting codes are commonly used to protect against soft errors and thereby enhance system reliability and data integrity [1]. Single error correcting and double error detecting (SEC-DED) codes are generally used for this purpose. These codes are able to correct single-bit errors and detect double-bit errors in a codeword. A design criterion that has become very important in recent times is power reduction. With increasing miniaturization of devices, power has become a first-order design consideration motivating researchers to look at techniques of reducing power consumption in all components of system design. For memory ECC, power reduction is also an important consideration, since the ECC checker circuit is activated during reading and writing access to the memory. As power has become an important consideration, researchers have begun looking at methods to reduce power consumption in error detection circuitry [2-4].
Tail‐Cuff Blood Pressure Measurement without External Preheating in Awake Rats

A new photoelectric sensor capable of detecting tail pulses even in unheated rats was tested for accuracy in indirect measurements of blood pressure. This sensor proved more sensitive than a Doppler ultrasonic flowmeter because it allowed detection not only of tail pulsations without preheating but also of peak oscillations usable for estimating mean arterial pressure. After blood pressures in anesthetized rats were elevated with norepinephrine or lowered with sodium nitroprusside, systolic pressures determined with the photoelectric sensor were almost identical with those recorded concurrently from femoral catheters (r = 0.939). Cuff pressure at peak oscillations in the tail correlated better with femoral mean pressure than with femoral diastolic pressure. However, similar comparisons in awake rats with chronically implanted carotid catheters showed that, although correlation between tail-cuff and carotid systolic pressures remained significant (r = 0.962), the correlation between peak tail oscillations and either mean or diastolic pressure was not. When systolic pressures were measured indirectly once a week for 7 weeks in unheated awake rats, normotensive rats could be easily distinguished from streptozotocin-diabetic and DOCA-salt hypertensive rats. (Hypertension 4: 898–903, 1982)
Clusters of Ancestrally Related Genes That Show Paralogy in Whole or in Part Are a Major Feature of the Genomes of Humans and Other Species

Arrangements of genes along chromosomes are a product of evolutionary processes, and we can expect that preferable arrangements will prevail over the span of evolutionary time, often being reflected in the non-random clustering of structurally and/or functionally related genes. Such non-random arrangements can arise by two distinct evolutionary processes: duplications of DNA sequences that give rise to clusters of genes sharing both sequence similarity and common sequence features and the migration together of genes related by function, but not by common descent [1], [2], [3]. To provide a background for distinguishing between the two, which is important for future efforts to unravel the evolutionary processes involved, we here provide a description of the extent to which ancestrally related genes are found in proximity. Towards this purpose, we combined information from five genomic datasets, InterPro, SCOP, PANTHER, Ensembl protein families, and Ensembl gene paralogs. The results are provided in publicly available datasets (http://cgd.jax.org/datasets/clustering/paraclustering.shtml) describing the extent to which ancestrally related genes are in proximity beyond what is expected by chance (i.e. form paraclusters) in the human and nine other vertebrate genomes, as well as the D. melanogaster, C. elegans, A. thaliana, and S. cerevisiae genomes. With the exception of Saccharomyces, paraclusters are a common feature of the genomes we examined. In the human genome they are estimated to include at least 22% of all protein coding genes. Paraclusters are far more prevalent among some gene families than others, are highly species or clade specific and can evolve rapidly, sometimes in response to environmental cues. Altogether, they account for a large portion of the functional clustering previously reported in several genomes.
Motivation for alcohol becomes resistant to quinine adulteration after 3 to 4 months of intermittent alcohol self-administration.

BACKGROUND Continued consumption of alcohol despite deleterious consequences is a hallmark of alcoholism and represents a critical challenge to therapeutic intervention. Previous rat studies showed that enduring alcohol self-administration despite pairing alcohol with normally aversive stimuli was only observed after very long-term intake (>8 months). Aversion-resistant alcohol intake has been previously interpreted to indicate pathological or compulsive motivation to consume alcohol. However, given the time required to model compulsive alcohol seeking in previous studies, there is considerable interest in developing more efficient and quantitative rodent models of aversion-resistant alcohol self-administration. METHODS Outbred Wistar rats underwent 3 to 4 months or approximately 1.5 months of intermittent, home-cage, two-bottle access (IAA) to 20% alcohol (v/v) or water. Then, after brief operant training, the effect of the bitter-tasting quinine (0.1 g/l) on the motivation to seek alcohol was quantified via progressive ratio (PR). Motivation for quinine-adulterated 2% sucrose under PR was assayed in a separate cohort of 3 to 4 months IAA rats. The effects of quinine on home-cage alcohol consumption in IAA rats and rats with continuous access to alcohol were also examined. Finally, a dose-response for quinine taste preference in IAA and continuous-access animals was determined. RESULTS Motivation for alcohol after 3 to 4 months IAA, measured using an operant PR procedure, was not altered by adulteration of alcohol with 0.1 g/l quinine. In contrast, after 3 to 4 months of IAA, motivation for sucrose under PR was significantly reduced by adulteration of sucrose with 0.1 g/l quinine. In addition, motivation for alcohol after only approximately 1.5 months IAA was significantly reduced by adulteration of alcohol with 0.1 g/l quinine. Furthermore, home-cage alcohol intake by IAA rats was insensitive to quinine at concentrations (0.01, 0.03 g/l) that significantly reduced alcohol drinking in animals with continuous access to alcohol. Finally, no changes in quinine taste preference after 3 to 4 months IAA or continuous access to alcohol were observed. CONCLUSIONS We have developed a novel and technically simple hybrid operant/IAA model in which quinine-resistant motivation for alcohol is evident after an experimentally tractable period of time (3 to 4 months vs. 8 months). Quinine dramatically reduced sucrose and water intake by IAA rats, indicating that continued responding for alcohol in IAA rats despite adulteration with the normally aversive quinine might reflect maladaptive or compulsive motivation for alcohol. This model could facilitate identification of novel therapeutic interventions for pathological alcohol seeking in humans.
Genetic analysis of interactions between the somitic muscle, cartilage and tendon cell lineages during mouse development

Proper formation of the musculoskeletal system requires the coordinated development of the muscle, cartilage and tendon lineages arising from the somitic mesoderm. During early somite development, muscle and cartilage emerge from two distinct compartments, the myotome and sclerotome, in response to signals secreted from surrounding tissues. As the somite matures, the tendon lineage is established within the dorsolateral sclerotome, adjacent to and beneath the myotome. We examine interactions between the three lineages by observing tendon development in mouse mutants with genetically disrupted muscle or cartilage development. Through analysis of embryos carrying null mutations in Myf5 and Myod1, hence lacking both muscle progenitors and differentiated muscle, we identify an essential role for the specified myotome in axial tendon development, and suggest that absence of tendon formation in Myf5/Myod1 mutants results from loss of the myotomal FGF proteins, which depend upon Myf5 and Myod1 for their expression, and are required, in turn, for induction of the tendon progenitor markers. Our analysis of Sox5/Sox6 double mutants, in which the chondroprogenitors are unable to differentiate into cartilage, reveals that the two cell fates arising from the sclerotome, axial tendon and cartilage are alternative lineages, and that cartilage differentiation is required to actively repress tendon development in the dorsolateral sclerotome.
Mnt–Max to Myc–Max complex switching regulates cell cycle entry

The c-Myc oncoprotein is strongly induced during the G0 to S-phase transition and is an important regulator of cell cycle entry. In contrast to c-Myc, the putative Myc antagonist Mnt is maintained at a constant level during cell cycle entry. Mnt and Myc require interaction with Max for specific DNA binding at E-box sites, but have opposing transcriptional activities. Here, we show that c-Myc induction during cell cycle entry leads to a transient decrease in Mnt–Max complexes and a transient switch in the ratio of Mnt–Max to c-Myc–Max on shared target genes. Mnt overexpression suppressed cell cycle entry and cell proliferation, suggesting that the ratio of Mnt–Max to c-Myc–Max is critical for cell cycle entry. Furthermore, simultaneous Cre-Lox mediated deletion of Mnt and c-Myc in mouse embryo fibroblasts rescued the cell cycle entry and proliferative block caused by c-Myc ablation alone. These results demonstrate that Mnt-Myc antagonism plays a fundamental role in regulating cell cycle entry and proliferation.
The velocity dispersion and mass profile of the Milky Way

We re-analyse the velocity-dispersion profile σ(r) at radii r > 10kpc in the Galactic stellar halo, recently derived by Battaglia et al., who concluded that, for a constant velocity anisotropy of the tracers, these data rule out a flat circular-speed curve for the Milky Way. However, we demonstrate that if one makes the natural assumption that the tracer density is truncated at r t ? 160 kpc and falls off significantly more steeply than r -3.5 at r? 80 kpc, then these data are consistent with a flat circular-speed curve and a constant velocity anisotropy comparable to that observed for halo stars in the solar neighbourhood. We also consider a more detailed mass model with an exponential stellar disc and an extended non-isothermal dark-matter halo. In this two-component model, the Milky Way's virial radius and mass are r vir ≃ 200 kpc and M vir ≃ 1.5 x 10 12 M ⊙ . Still assuming the tracers' velocity anisotropy to be constant (at β ≃ 0.5), we again find good agreement with the observed σ(r), so long as the tracer density is truncated near the virial radius. These data by themselves do not allow to differentiate either between different dark-halo or total-mass models for the Milky Way, nor between different velocity-anisotropy profiles for the tracers.