Miracle-dz/UniFAR-FTUs huggingface dataset:
Current therapy of sickle cell disease.

Homozygous sickle cell disease (SCD) is an autosomal recessive genetic disease that results from the substitution of valine for glutamic acid at position 6 of the β-globin gene, leading to production of a defective form of hemoglobin, hemoglobin S (HbS). The prevalence of SCD is about 1–2% among African descendants in Europe and the United States and 4% or higher in West Africa. SCD shows broad phenotypic expression that varies greatly between regions, among patients and longitudinally in the same patient.1,2 The protean clinical features of SCD result from chronic variable intravascular hemolysis, microvascular ischemia and organ damage. Vaso-occlusion is the outcome of a dynamic combination of abnormalities in hemoglobin structure and function, red blood cell membrane integrity, erythrocyte density, endothelial activation, microvascular tone, inflammatory mediators, and coagulation. These pathophysiologic events translate into clinical manifestations that fall into four general categories: anemia and its sequelae; vaso-occlusive crises and bone marrow fat embolization syndrome; infection (from functional asplenia) and organ dysfunction. Organ damage results from a combination of hemolysis and infarction and may be manifested as stroke, retinopathy, nephropathy, liver disease or pulmonary arterial hypertension. Intravascular hemolysis in SCD causes the release of hemoglobin into the plasma. When the capacity of protective hemoglobin-scavenging mechanisms (haptoglobin and hemopexin) has been saturated, levels of cell-free hemoglobin increase in the plasma resulting in the consumption of nitric oxide (NO) by hemoglobin-mediated NO scavenging.3 In addition, arginase released by hemolyzed red cells can deplete blood plasma of arginine, the substrate for NO production by NO synthase.4 NO plays a major role in vascular homeostasis and is a critical regulator of smooth muscle relaxation and vasomotor tone, expression of endothelial adhesion molecules and platelet activation and aggregation.5 A deficiency in NO, due to its inactivation by cell-free plasma hemoglobin levels during intravascular hemolysis in SCD, may underlie complications associated with SCD.6 In this editorial, we briefly review the currently available treatments for SCD. For more detail on specific topics, the reader is directed to more extensive recent review articles as cited in the references.
A categorical manifesto

This paper tries to explain why and how category theory is useful in computing science, by giving guidelines for applying seven basic categorical concepts: category, functor, natural transformation, limit, adjoint, colimit and comma category. Some examples, intuition, and references are given for each concept, but completeness is not attempted. Some additional categorical concepts and some suggestions for further research are also mentioned. The paper concludes with some philosophical discussion.
Ruminant digestion.

Ruminants are grazing animals that possess a four-chambered polygastric stomach enabling them to digest plant forages and concentrates. Some example species would include cattle, sheep, goats, deer, giraffes and camels. The unique digestive system common to these animals is capable of breaking down plant proteins and carbohydrates which are indigestible to monogastrics. The digestive process is achieved through microbial fermentation and cud-chewing, or the process of “rumination”. This chapter will discuss the anatomy and function of rumination with respect to the bovine gastrointestinal tract.
CASES-99: a comprehensive investigation of the stable nocturnal boundary layer

Abstract The Cooperative Atmosphere-Surface Exchange Study—1999 (CASES-99) refers to a field experiment carried out in southeast Kansas during October 1999 and the subsequent program of investigation. Comprehensive data, primarily taken during the nighttime but typically including the evening and morning transition, supports data analyses, theoretical studies, and state-of-the-art numerical modeling in a concerted effort by participants to investigate four areas of scientific interest. The choice of these scientific topics is motivated by both the need to delineate physical processes that characterize the stable boundary layer, which are as yet not clearly understood, and the specific scientific goals of the investigators. Each of the scientific goals should be largely achievable with the measurements taken, as is shown with preliminary analysis within the scope of three of the four scientific goals. Underlying this effort is the fundamental motivation to eliminate deficiencies in surface layer and turbul.
A randomised pilot study to assess the efficacy of an interactive, multimedia tool of cognitive stimulation in Alzheimer’s disease

Objective: To determine the usefulness of an interactive multimedia internet-based system (IMIS) for the cognitive stimulation of Alzheimer’s disease. Methods: This is a 24-week, single-blind, randomised pilot study conducted on 46 mildly impaired patients suspected of having Alzheimer’s disease receiving stable treatment with cholinesterase inhibitors (ChEIs). The patients were divided into three groups: (1) those who received 3 weekly, 20-min sessions of IMIS in addition to 8 h/day of an integrated psychostimulation program (IPP); (2) those who received only IPP sessions; and (3) those who received only ChEI treatment. The primary outcome measure was the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog). Secondary outcome measures were: Mini-Mental State Examination (MMSE), Syndrom Kurztest, Boston Naming Test, Verbal Fluency, and the Rivermead Behavioral Memory Test story recall subtest. Results: After 12 weeks, the patients treated with both IMIS and IPP had improved outcome scores on the ADAS-Cog and MMSE, which was maintained through 24 weeks of follow-up. The patients treated with IPP alone had better outcome than those treated with ChEIs alone, but the effects were attenuated after 24 weeks. All patients had improved scores in all of the IMIS individual tasks, attaining higher levels of difficulty in all cases. Conclusion: Although both the IPP and IMIS improved cognition in patients with Alzheimer’s disease, the IMIS program provided an improvement above and beyond that seen with IPP alone, which lasted for 24 weeks.
Analysis and construction of pathogenicity island regulatory pathways in Salmonella enterica serovar Typhi

Summary Signal transduction through protein-protein interactions and protein modifications are the main mechanisms controlling many biological processes. Here we described the implementation of MedScan information extraction technology and Pathway Studio software (Ariadne Genomics Inc.) to create a Salmonella specific molecular interaction database. Using the database, we have constructed several signal transduction pathways in Salmonella enterica serovar Typhi which causes Typhoid Fever, a major health threat especially in developing countries. S. Typhi has several pathogenicity islands that control rapid switching between different phenotypes including adhesion and colonization, invasion, intracellular survival, proliferation, and biofilm formation in response to environmental changes. Understanding of the detailed mechanism for S. Typhi survival in host cells is necessary for development of efficient detection and treatment of this pathogen. The constructed pathways were validated using publically available gene expression microarray data for Salmonella.
Motor Imagery May Incorporate Trial-to-Trial Error

ABSTRACT The authors tested for 1/f noise in motor imagery (MI). Participants pointed and imagined pointing to a single target (Experiment 1), to targets of varied size (Experiment 2), and switched between pointing and grasping (Experiment 3). Experiment 1 showed comparable patterns of serial correlation in actual and imagined movement. Experiment 2 suggested increased correlation for MI and performance with increased task difficulty, perhaps reflecting adaptation to a more complex environment. Experiment 3 suggested a parallel decrease in correlation with task switching, perhaps reflecting discontinuity of mental set. Although present results do not conclusively reveal 1/f fluctuation, the emergent patterns suggest that MI could incorporate trial-to-trial error across a range of constraints.
GSTP1 hypermethylation is associated with reduced protein expression, aggressive disease and prognosis in neuroblastoma

Epigenetic modifications such as methylation of CpG islands in tumor‐suppressor gene promoter regions have been associated with tumor development in many human cancers. Using methylation specific multiplex ligation‐dependent probe amplification method, we analyzed the methylation status of 35 different genes in 16 neuroblastoma (NB) cell lines and 50 NB tumor samples (NBs), and investigated whether specific hypermethylation was associated with biological and/or clinical parameters. Among the genes found hypermethylated, the effect of GSTP1 hypermethylation on mRNA and protein expression was also explored. The median number of hypermethylated genes was higher in cell lines compared to NBs (5.5 vs. 2). For eight genes, aberrant methylation of CpG‐islands in NB was not (ESR1, PAX5, WT1, CADM1, MSH6, and CDKN2B) or very rarely (CDH13 and GSTP1) reported in literature. GSTP1 was found hypermethylated in 44% of the NB cell lines and in 33% of the stage 4‐11qLOH ‐non MYCN‐amplified high risk NBs. Hypermethylation was correlated with reduced mRNA and protein expression. In the whole NBs cohort, GSTP1 hypermethylation was less frequently detected (8%), but found to be associated with lower event‐free (EFS) and overall survival. Hypermethylation of GSTP1 showed also association with lower EFS in high risk subgroups as stage 4 and older patients (≥547 days). Our results suggest that, as in several adult cancers, aberrant methylation of GSTP1 may contribute to the carcinogenetic process in NB and could be potentially used as a new marker leading to define an ultra‐high risk subgroup. © 2011 Wiley Periodicals, Inc.
An Immunohistochemical Study of Matrix Components in Early‐Stage Vascular Canals Within Mandibular Condylar Cartilage in Midterm Human Fetuses

Matrix components of vascular canals (VCs) in human fetal mandibular condylar cartilage (15–16 weeks of gestation) were analyzed by immunohistochemistry. Prevascular canals (PVCs), consisting of spindle‐shaped cells without capillary invasion, were observed within the cartilage. Intense immunoreactivity for collagen type I, weak immunoreactivity for aggrecan and tenascin‐C, weak hyaluronan (HA) staining, and abundant argyrophilic fibers in PVCs indicated that they contain noncartilaginous fibrous connective tissues that was different from those in the perichondrium/periosteum. These structural and immunohistochemical features of PVCs are different from those of previously reported cartilage canals of the long bone. Capillaries entered the VCs from the periosteum and ascended through VCs. Following capillary invasion, loose connective tissue had formed in the lower part of VCs, and immunoreactivity for collagen types I and III, tenascin‐C, and HA staining was evident in the matrix of loose connective tissue. No chondroclasts or osteogenic cells were seen at the front of capillary invasion, although small, mononuclear tartrate‐resistant acid phosphatase (TRAP)‐positive cells were present. Meanwhile, TRAP‐positive, multinucleated chondroclasts and flattened, osteoblast‐like cells were observed in the loose connective tissue at the lower part of VCs. These results may indicate slow progress of endochondral ossification in human fetal mandibular condyle. Further, unique matrix components in PVCs/VCs, which were different from those in cartilage canals in long bone, may reflect the difference of speed of endochondral ossification in cartilage canals and human fetal mandibular condyles. Anat Rec, 298:1560–1571, 2015. © 2015 Wiley Periodicals, Inc.
Interdiffusion and thermotransport in Ni–Al liquid alloys

ABSTRACT In this paper, we present extensive self-consistent results of molecular dynamics (MD) simulations of diffusion and thermotransport properties of Ni–Al liquid alloys. We develop a new formalism that allows easy connection between results of the MD simulations and the real experiments. In addition, this formalism can be extended to the case of ternary and higher component liquid alloys. We focus on the temperature and composition dependence of the self-diffusion coefficients, interdiffusion coefficients, thermodynamic factor, Manning factor and the reduced heat of transport. The two latter quantities both represent measures of the off-diagonal Onsager phenomenological coefficients. The Manning factor and the reduced heat of transport can be related to experimentally obtainable quantities provided the thermodynamic factor is available. The simulation results for the reduced heat of transport show that for all compositions, in the presence of a temperature gradient, Ni tends to migrate to the cold end. This is in agreement with an available experimental study for a Ni21.5Al78. 5 melt (only qualitative result is available so far).
Influence Maximization with Semi-Bandit Feedback

We study a stochastic online problem of learning to influence in a social network with semi-bandit feedback, individual observations of how influenced users influence others. Our problem combines challenges of partial monitoring, because the learning agent only observes the influenced portion of the network, and combinatorial bandits, because the cardinality of the feasible set is exponential in the maximum number of influencers. We propose a computationally efficient UCB-like algorithm for solving our problem, IMLinUCB, and analyze it on forests. Our regret bounds are polynomial in all quantities of interest; reflect the structure of the network; and do not depend on inherently large quantities, such as the reciprocal of the minimum probability of being influenced and the cardinality of the action set. To the best of our knowledge, these are the first such results. IMLinUCB permits linear generalization and therefore is suitable for large-scale problems. We evaluate IMLinUCB on several synthetic problems and observe that the regret of IMLinUCB scales as suggested by our upper bounds. A special form of our problem can be viewed as a linear bandit and we match the regret bounds of LinUCB in this case.
Adaptive Role Playing Games: An Immersive Approach for Problem Based Learning

In this paper we present a general framework, called NUCLEO, for the application of socio-constructive educational approaches in higher education. The underlying pedagogical approach relies on an adaptation model in order to improve group dynamics, as this has been identified as one of the key features in the success of collaborative learning scenarios. Students’ learning strategies are analyzed considering a simplified version of Vermunt’s model for learning styles. The resulting profiles provide the basis to group students in teams where each student is assigned a role according to his/her learning strategies. The result is the formation of complementary and semi-autonomous learning teams that collaborate to achieve solutions to the problems provided by the instructor. The framework is instantiated through an online multiplayer role-playing game environment, which sets a stage for the underlying collaborative problem-based learning approach. The framework has been benchmarked in different programming courses at the Complutense University of Madrid during 2007-08 and 2008-09 academic years. This work also presents the results of these experiences.
G-Quadruplexes as Potential Therapeutic Targets for Embryonal Tumors

Embryonal tumors include a heterogeneous group of highly malignant neoplasms that primarily affect infants and children and are characterized by a high rate of mortality and treatment-related morbidity, hence improved therapies are clearly needed. G-quadruplexes are special secondary structures adopted in guanine (G)-rich DNA sequences that are often present in biologically important regions, e.g. at the end of telomeres and in the regulatory regions of oncogenes such as MYC. Owing to the significant roles that both telomeres and MYC play in cancer cell biology, G-quadruplexes have been viewed as emerging therapeutic targets in oncology and as tools for novel anticancer drug design. Several compounds that target these structures have shown promising anticancer activity in tumor xenograft models and some of them have entered Phase II clinical trials. In this review we examine approaches to DNA targeted cancer therapy, summarize the recent developments of G-quadruplex ligands as anticancer drugs and speculate on the future direction of such structures as a potential novel therapeutic strategy for embryonal tumors of the nervous system.
Otoneurologic Dysfunctions in Migraine Patients With or Without Vertigo

Objective: To evaluate the neurotologic findings in patient suffering from migraine with and without vestibular symptoms. Study Design: Comparative cross-sectional and observational study. Setting: Tertiary referral center. Background: Migraine headache is often associated with other symptoms, including dizziness, head motion intolerance, or rotational-type vertigo. The neuro-otologic examination in migrainous patients often gives unremarkable results. To date, it is not fully understood why some migraine patients complain of vestibular symptoms and some do not, and it is not yet clear whether neuro-otologic abnormalities among migraine patients are more common in patients complaining of vestibular symptoms or whether they can be considered a hallmark of migraine itself. Materials and Methods: Forty-four migrainous patients were divided into 2 groups regarding the presence (22 patients, Group 1) or absence (22 patients, Group 2) of vestibular symptoms, and the results were compared with those obtained from a control group (22 normal subjects). All the patients underwent a complete neurotologic study to verify the presence of vestibular abnormalities. Results: Neurotologic abnormalities were observed in only 34% of the total, and the incidence was very similar in the 2 groups (36.3 versus 31.8%). Central vestibular involvement was observed in 18% of Group 1 and in 18% of Group 2 patients. Peripheral vestibular involvement was demonstrated in 18% of Group 1 patients and in 16% of Group 2 patients. Conclusion: Our data seem to confirm that migraine itself can affect vestibular pathways even if patients do not complain of vestibular symptoms. Vestibular examination alone does not provide enough information for a diagnosis of migrainous vertigo. A careful clinical history is fundamental for assessing the profile of patients with migrainous vertigo.
Ochratoxins—Food Contaminants: Impact on Human Health

Ochratoxins are secondary metabolites of Aspergillus and Penicillium, that are hazardous to health through contamination of dietary foods. Ochratoxin A (OTA) remains the single most potent member of this group of mycotoxins. OTA has a long half-life in humans and is thus easily detected in serum. Dietary intake studies have confirmed link between endemic nephrotoxicity in humans to their daily household intake of OTA. OTA has been reported to contribute to endemic nephrotoxicity and carcinogenicity in humans and animals. OTA produces renal tumours, DNA adducts and chromosomal aberrations in kidneys. OTA may be embryotoxic, teratogenic, and immunotoxic only at doses higher than those causing nephrotoxicity. The incidence of endemic nephrotoxicity has been mostly reported in northeast Europe since the early fifties. Recent studies however have warned that OTA and other toxins, such as aristolochic acid, show very similar renal pathology. There is thus the need for thorough co-occurrence studies on toxin incidence.
Induced Graph Ramsey Theory

We say that a graph F strongly arrows (G, H) and write F ֌ (G, H) if for every edge-coloring of F with colors red and blue a red G or a blue H occurs as an induced subgraph of F . Induced Ramsey numbers are defined by r(G, H) = min{|V (G)| : F ֌ (G, H)}. The value of r(G, H) is finite for all graphs, and good upper bounds on induced Ramsey numbers in general, and for particular families of graphs are known. Most of these results, however, use the probabilistic method, and therefore do no yield explicit constructions. This paper provides several constructions for upper bounds on r(G, H) including r(Cn) ≤ c (log n) , r(T, Kn) ≤ |T |n |T | log |T , r(B, Cn) ≤ |B| 2⌈log , where T is a tree, B is bipartite, Kn is the complete graph on n vertices and Cn a cycle on n vertices. We also have some new upper bounds for small graphs: r(K3 + e) ≤ 21, and r (K4 − e) ≤ 46.
GABAergic activities enhance macrophage inflammatory protein‐1α release from microglia (brain macrophages) in postnatal mouse brain

Microglial cells (brain macrophages) invade the brain during embryonic and early postnatal development, migrate preferentially along fibre tracts to their final position and transform from an amoeboid to a ramified morphology. Signals by which the invading microglia communicate with other brain cells are largely unknown. Here, we studied amoeboid microglia in postnatal corpus callosum obtained from 6‐ to 8‐day‐old mice. These cells accumulated on the surface of acute brain slices. Whole‐cell patch‐clamp recordings revealed that the specific GABAA receptor agonist muscimol triggered a transient increase in conductance typical for inward rectifying potassium channels in microglia. This current increase was not mediated by microglial GABAA receptors since microglial cells removed from the slice surface no longer reacted and cultured microglia only responded when a brain slice was placed in their close vicinity. Muscimol triggered a transient increase in extracellular potassium concentration ([K+]o) in brain slices and an experimental elevation of [K+]o mimicked the muscimol response in microglial cells. Moreover, in adult brain slices, muscimol led only to a minute increase in [K+]o and microglial cells failed to respond to muscimol. In turn, an increase in [K+]o stimulated the release of chemokine macrophage inflammatory protein‐1α (MIP1‐α) from brain slices and from cultures of microglia but not astrocytes. Our observations indicate that invading microglia in early postnatal development sense GABAergic activities indirectly via sensing changes in [K+]o which results in an increase in MIP1‐α release.
Structure Inference Machines: Recurrent Neural Networks for Analyzing Relations in Group Activity Recognition

Rich semantic relations are important in a variety of visual recognition problems. As a concrete example, group activity recognition involves the interactions and relative spatial relations of a set of people in a scene. State of the art recognition methods center on deep learning approaches for training highly effective, complex classifiers for interpreting images. However, bridging the relatively low-level concepts output by these methods to interpret higher-level compositional scenes remains a challenge. Graphical models are a standard tool for this task. In this paper, we propose a method to integrate graphical models and deep neural networks into a joint framework. Instead of using a traditional inference method, we use a sequential inference modeled by a recurrent neural network. Beyond this, the appropriate structure for inference can be learned by imposing gates on edges between nodes. Empirical results on group activity recognition demonstrate the potential of this model to handle highly structured learning tasks.