Miracle-dz/UniFAR-FTUs huggingface dataset:
Discriminant Adaptive Nearest Neighbor Classification

Nearest neighbor classification expects the class conditional probabilities to be locally constant, and suffers from bias in high dimensions We propose a locally adaptive form of nearest neighbor classification to try to finesse this curse of dimensionality. We use a local linear discriminant analysis to estimate an effective metric for computing neighborhoods. We determine the local decision boundaries from centroid information, and then shrink neighborhoods in directions orthogonal to these local decision boundaries, and elongate them parallel to the boundaries. Thereafter, any neighborhood-based classifier can be employed, using the modified neighborhoods. The posterior probabilities tend to be more homogeneous in the modified neighborhoods. We also propose a method for global dimension reduction, that combines local dimension information. In a number of examples, the methods demonstrate the potential for substantial improvements over nearest neighbour classification.
School of Informatics , University of Edinburgh Institute for Adaptive and Neural Computation On the Number of Modes of a Gaussian Mixture by

We consider a problem intimately related to the creation of maxima under Gaussian blurring: the number of modes of a Gaussian mixture in D dimensions. To our knowledge, a general answer to this question is not known. We conjecture that if the components of the mixture have the same covariance matrix (or the same covariance matrix up to a scaling factor), then the number of modes cannot exceed the number of components. We demonstrate that the number of modes can exceed the number of components when the components are allowed to have arbitrary and different covariance matrices. We will review related results from scale-space theory, statistics and machine learning, including a proof of the conjecture in 1D. We present a convergent, EM-like algorithm for mode finding and compare results of searching for all modes starting from the centers of the mixture components with a brute-force search. We also discuss applications to data reconstruction and clustering.
Fanconi Anemia/Brca Pathway and Head and Neck Squamous Cell Carcinomas

DNA repair defect is one of the hallmarks of tumorigenesis, and is intimately linked to various human cancers, both inherited and sporadic (1). The two best examples are perhaps the DNA mismatch repair pathway in colorectal cancer, and the Fanconi Anemia/Brca (Fanc/Brca) pathway in head and neck squamous cell carcinomas (HNSCCs) (1). In this book chapter, I will review the updated knowledge of Fanc/Brca pathway in human cancers particularly in HNSCCs. Fanconi anemia is a rare autosomal recessive or X-linked chromosomal instability disorder, with incidence of 1 to 5 cases per millions. The affected children have multiple congenital defects, and typically develop bone marrow failure during the first decade of life. They are at the risk for developing hematological cancers with the acute myelogenous leukemia (AML) the most frequent (2). Recently studies also showed a predisposition of Fanconi anemia patients to multiple solid tumors (3, 4), particularly to HNSCCs (5). Other tumors include gynecologic SCCs, and tumors of esophagus, liver, and skin (3, 4). Since Fanconi anemia is characterized by spontaneous chromosome breakage and cellular hypersensitivity to DNA cross-linking agents, such as mitomycin C, or diepoxybutane (DEB), the DEBinduced chromosome-breakage assay is widely used as a diagnostic test for Fanconi anemia patients, and the complementation test is used to define the Fanconi anemia subtypes. Androgens, hematopoietic growth factors, or stem-cell transplantation is currently used for treating bone marrow failure in Fanconi anemia patients(2). The Fanconi anemia pathway is complex and interacts with other DNA repair pathways (6, 7). The pathway itself is regulated by so far thirteen Fanconi anemia proteins (FANCA, B, C, D1, D2, E, F, G, I, J, L, M and N). Among those proteins, eight are assembled in a nuclear ubiquitin E3 ligase complex (FANCA/B/C/E/F/G/L/M), known as the Fanconi anemia core complex, which mono-ubiquitinates FANCD2 and FANCI. The mono-ubiquitinated FANCD2/FANCI complex is targeted to chromatin, where it interacts, either directly or indirectly, with additional downstream Fanconi anemia proteins (FANCD1, FANCN, and FANCJ) (6, 7). The first evidence of the convergence of Fanconi anemia pathway with
Solubilization of Dentin Matrix Collagen in situ

The effects of the oral environment on dentin matrix collagen were studied. In the partial prostheses of 12 participants, two completely demineralized dentin specimens were mounted covered by a Dacron gauze. After an experimental period of seven weeks, the specimens were transferred to a trypsin-containing buffer for determination of the amount of denatured collagen. Subsequently, the specimens were incubated with a bacterial collagenase for assessment of the amount of collagen. After the intra-oral exposure, there was a collagen loss varying between 1 and 47 wt%. This variation might be due to differences in proteolytic activity of the colonizing microflora. After exposure to the oral environment, only about 0.5 wt% of the available collagen was trypsin-degradable. This indicates a rapid solubilization of the denatured collagen from the specimens into the oral cavity. A separate group of specimens was examined by light microscopy and transmission electron microscopy. Various degrees of breakdown could be discerned. Some experimental specimens showed loss of surface integrity and tubules heavily infected with different types of micro-organisms. The lumens of the tubules were enlarged, sometimes creating caverns as a result of the loss of the intertubular collagenous matrix.
A practical guide for the stabilization of acylghrelin in human blood collections

Objective and methods To better understand acylghrelin plasma stability, human synthetic acylghrelin was spiked into plasma and tracked by liquid chromatography tandem mass spectrometry. To investigate the best method for quantifying clinical plasma acylghrelin levels, pre‐ and postprandial human blood was collected from healthy volunteers (n = 6) using various sample collections and treatments. Plasma ghrelin levels from human blood collections were analysed by enzyme‐linked immunosorbant assay (ELISA).
Palytoxin and an Ostreopsis Toxin Extract Increase the Levels of mRNAs Encoding Inflammation-Related Proteins in Human Macrophages via p38 MAPK and NF-κB

Background Palytoxin and, likely, its analogues produced by the dinoflagellate genus Ostreopsis, represent a class of non-proteinaceous compounds displaying high toxicity in animals. Owing to the wide distribution and the poisonous effects of these toxins in humans, their chemistry and mechanism of action have generated a growing scientific interest. Depending on the exposure route, palytoxin and its Ostreopsis analogues may cause several adverse effects on human health, including acute inflammatory reactions which seem more typical of cutaneous and inhalation contact. These observations have led us to hypothesize that these toxins may activate pro-inflammatory signalling cascades. Methodology and Principal Findings Here we demonstrate that palytoxin and a semi-purified Ostreopsis cf. ovata toxin extract obtained from a cultured strain isolated in the NW Adriatic Sea and containing a putative palytoxin and all the ovatoxins so far known – including the recently identified ovatoxin-f – significantly increase the levels of mRNAs encoding inflammation-related proteins in immune cells, i.e. monocyte-derived human macrophages, as assessed by Real-Time PCR analysis. Western immunoblot and electrophoretic mobility shift assays revealed that nuclear transcription factor -κB (NF-κB) is activated in cells exposed to toxins in coincidence with reduced levels of the inhibitory protein IκB-α. Moreover, Mitogen-Activated Protein Kinases (MAPK) were phosphorylated in response to palytoxin, as also reported by others, and to the Ostreopsis toxin extract, as shown here for the first time. By using specific chemical inhibitors, the involvement of NF-κB and p38 MAPK in the toxin-induced transcription and accumulation of Cycloxigenase-2, Tumor Necrosis Factor-α, and Interleukin-8 transcripts has been demonstrated. Conclusions and Significance The identification of specific molecular targets of palytoxin and its Ostreopsis analogues, besides contributing to expand the still limited knowledge of the intracellular signalling cascades affected by these toxins, may have important implications in setting up focused pharmacological interventions, replacing currently used symptomatic treatments.
The Effect of Seasonal Variations in Airborne Particulate Matter on Asthma-Related Airway Inflammation in Mice

This study aimed to investigate the effects of winter and spring particulate matter (PM) on airway inflammation and allergies in a mouse asthma model. PM was collected during 7–28 February 2013 (winter) and during 7–28 April 2013 (spring) in Yonago, Japan. NC/Nga mice were co-sensitized using intranasal instillation of the PMs and Dermatophagoides farinae (Df) for 5 consecutive days, and were subsequently challenged using intranasal Df at 7 days after the last sensitization. At 24 h after the challenge, serum immunoglobulin levels, differential leukocyte counts, and inflammatory cytokines levels were measured in the mice’s bronchoalveolar lavage fluid (BALF). Compared to co-sensitization using spring PM and Df, winter PM and Df induced greater increases in the BALF neutrophil and eosinophil counts and total serum IgE and IgG2a levels. Furthermore, winter PM-sensitized mice exhibited higher BALF levels of interleukin-5, interleukin-13, interleukin-6, and keratinocyte-derived chemokine. Therefore, we observed seasonal variations in the effects of PM on asthma-related airway inflammation. These findings suggest that the compositions of PM vary according to season, and that it is important to evaluate PM compositions in order to understand the associations between asthma and PM.
Bridging the Knowledge Gap: towards a comprehensive mHealth Training Framework

Mobile health (mHealth) solutions can improve the efficiency and effectiveness of healthcare services delivered by Primary Healthcare (PHC) workers in rural communities in developing countries. However, a host of barriers can hinder the success of new mHealth implementations including low tech-nology literacy levels and failure to communicate the benefits of the solution for all stakeholders. This paper argues that effective training of end users and all stakeholders can remove the barriers which stem from these issues, thereby improving the likelihood of successful implementation and enabling the eventual improvement of healthcare delivery. During a visit to Nigeria, the perceptions of key stakeholders regarding IMPACT, a new mHealth solution, were explored to ascertain the training needs of all stakeholders in the healthcare ecosystem. The paper leverages data from this visit and presents IMPACTeD, a comprehensive mHealth training framework which aims to develop a collec-tive understanding of the solution among all stakeholders, while also improving the technical ability and confidence of PHC workers. The framework will be implemented and evaluated during a second visit to Nigeria. This paper contributes to the scant literature in developing countries by providing a framework which can guide the implementation of further mHealth solutions in developing nations.
Reliability in One-Repetition Maximum Performance in People with Parkinson's Disease

Strength training is an effective modality to improve muscular strength and functional performance in people with Parkinson's disease (PWP). One-repetition maximum (1-RM) is the gold standard assessment of strength; however, PWP suffer from day-to-day variations in symptom severity and performance characteristics, potentially adversely affecting the reliability of 1-RM performance. Herein, we assessed the reliability of 1-RM in PWP. Forty-six participants completed two sessions of 1-RM testing of knee extension, knee flexion, chest press, and biceps curl at least 72 hours apart. Significantly differences between testing sessions were identified for knee extension (P < 0.001), knee flexion (P = 0.042), and biceps curl (P = 0.001); however, high reliability (ICC > 0.90) was also identified between sessions. Interestingly, almost third of subjects failed to perform better on the second testing session. These findings suggest that 1-RM testing can be safely performed in PWP and that disease-related daily variability may influence 1-RM performance.
Boundaryless career and career success: the impact of emotional and social competencies

Even though, over the last two decades, the boundaryless career concept has stimulated a wide theoretical debate, scholars have recently claimed that research on the competencies that are necessary for managing a cross-boundary career is still incomplete. Similarly, the literature on emotional and social competencies has demonstrated how they predict work performance across industries and jobs but has neglected their influence in explaining the individual's mobility across boundaries and their impact on career success. This study aims to fill these gaps by examining the effects of emotional and social competencies on boundaryless career and on objective career success. By analyzing a sample of 142 managers over a period of 8 years, we found evidence that emotional competencies positively influence the propensity of an individual to undertake physical career mobility and that career advancements are related to the possession of social competencies and depend on the adoption of boundaryless career paths. This study also provides a contribution in terms of the evaluation of the emotional and social competencies demonstrated by an individual and of the operationalization of the measurement of boundaryless career paths, considering three facets of the physical mobility construct (organizational, industrial, and geographical boundaries).
Symbolic Revision of Theories with M-of-N Rules

This paper presents a major revision of the EITHER propositional theory refinement system. Two issues are discussed. First, we show how run time efficiency can be greatly improved by changing from a exhaustive scheme for computing repairs to an iterative greedy method. Second, we show how to extend EITHER to refine M-of-N rules. The resulting algorithm, NEITHER, (New EITHER), is more than an order of magnitude faster and produces significantly more accurate results with theories that fit the M-of-N format. To demonstrate the advantages of NEITHER, we present preliminary experimental results comparing it to EITHER and various other systems on refining the DNA promoter domain theory.
Efeito do tratamento térmico de envelhecimento na microestrutura e nas propriedades de impacto do aço inoxidável superaustenítico ASTM A 744 Gr. CN3MN

ASTM A 744 Gr. CN3MN superaustenitic stainless steel is employed in the manufacture of equipments designed to work in severely corrosive environments under mechanical loads. This research investigated the influence of aging heat treatments on the microstructure and impact properties of this type of material. These treatments were carried out at temperature of 900oC for different periods of time: 1.5; 12; 24; 36 and 48 hours. Impact Charpy tests were conducted at room temperature and -46°C for all heat treated samples. The microstructural analyses were carried out by optical microscopy, scanning electron microscopy and X-ray diffraction. It was concluded that as long as the steel was exposed to 900oC, the energy absorbed during impact was lower. After 1.5 hours at 900oC the impact energy dropped from 128 to 25 Joules. The samples heat treated at 900oC for 48 hours showed precipitation of some phases at the austenitic matrix: the most probable were sigma (σ), chi (χ) and M23C6 carbide.
Neither more nor less: Optimizing thread-level parallelism for GPGPUs

General-purpose graphics processing units (GPG-PUs) are at their best in accelerating computation by exploiting abundant thread-level parallelism (TLP) offered by many classes of HPC applications. To facilitate such high TLP, emerging programming models like CUDA and OpenCL allow programmers to create work abstractions in terms of smaller work units, called cooperative thread arrays (CTAs). CTAs are groups of threads and can be executed in any order, thereby providing ample opportunities for TLP. The state-of-the-art GPGPU schedulers allocate maximum possible CTAs per-core (limited by available on-chip resources) to enhance performance by exploiting TLP. However, we demonstrate in this paper that executing the maximum possible number of CTAs on a core is not always the optimal choice from the performance perspective. High number of concurrently executing threads might cause more memory requests to be issued, and create contention in the caches, network and memory, leading to long stalls at the cores. To reduce resource contention, we propose a dynamic CTA scheduling mechanism, called DYNCTA, which modulates the TLP by allocating optimal number of CTAs, based on application characteristics. To minimize resource contention, DYNCTA allocates fewer CTAs for applications suffering from high contention in the memory subsystem, compared to applications demonstrating high throughput. Simulation results on a 30-core GPGPU platform with 31 applications show that the proposed CTA scheduler provides 28% average improvement in performance compared to the existing CTA scheduler.
Community Based Case-Control Study of Rotavirus Gastroenteritis among Young Children during 2008-2010 Reveals Vast Genetic Diversity and Increased Prevalence of G9 Strains in Kolkata

Background Group A Rotaviruses are a major etiologic agent of gastroenteritis in infants and young children (<5 years) worldwide. Although rotavirus vaccines have been successfully administered in many countries, in India the introduction of rotavirus vaccine in national immunization program was approved in 2014. Since high disease burden and large number of genetic variants have been reported from low income countries including India, monitoring of rotavirus was initiated prior to implementation of the vaccine in the region. Methods A total number of 3,582 stool samples were collected from an urban slum community in Kolkata, among which 1,568 samples were obtained from children of ≤5 years of age, with moderate to severe diarrhoea and 2,014 samples were collected from age-sex matched healthy neighbourhood controls. Rotavirus positive samples were typed by multiplex semi-nested PCR and nucleotide sequencing. Circulating strains were phylogenetically analyzed. Results Among 1,568 children with diarrhoea, 395 (25.2%), and among 2,014 asymptomatic children, 42 (2%) were rotavirus positive. G1P[8] was identified as the most common strain (32%) followed by G9P[8] (16.9%), G2P[4] (13.5%) and G9P[4] (10.75%). G12 strains with combinations of P[4], P[6] and P[8] comprised 11.9% of total positive strains. The rest (<10%) were rare and uncommon strains like G1P[4], G1P[6], G2P[8] and animal-like strains G4P[6], G6P[14] and G11P[25]. The 42 rotavirus positive samples from asymptomatic children revealed common genotypes like G1, G2 and G9. Conclusion This community based case-control study showed increased predominance of genotype G9 in Kolkata. It also confirmed co-circulation of a large number of genetic variants in the community. Asymptomatic rotavirus positive children though low in number can also be a source of dispersal of infection in the community. This study provides background information to the policy makers for implementation of rotavirus vaccines in this region.
Sumatriptan: Pharmacological Basis and Clinical Results

SUMMARY Sumatriptan was the first selective serotonin (5-HT)1B/1D agonist for the acute treatment of migraine attacks. Apart from the subcutaneous and oral formulation, it is also available as nasal spray and suppository. In placebo-controlled clinical trials, sumatriptan, administered subcutaneously, orally, intranasally or rectally was significantly more effective than placebo in relieving migraine headache and in producing relief or resolution of other symptoms associated with migraine, including nausea, photophobia and phonophobia. For patients who desire particularly rapid relief that cannot be provided by a tablet form, sumatriptan injection with a 10-minute onset of action may be an appropriate choice. Patients with very severe attacks and those with vomiting may also benefit from the injection. For patients with nausea who do not wish to take tablets or who fear injections, a sumatriptan nasal spray or a suppository may be appropriate options. New triptans, zolmitriptan, rizatriptan, and naratriptan began entering the market in 1997 but in clinical practice, in particular after dose adjustments have been made, all triptans appear to be very similar with respect to efficacy and tolerability as well as safety.
Mechanisms of Inhibition and Potentiation of α4β2 Nicotinic Acetylcholine Receptors by Members of the Ly6 Protein Family*

Background: Several Ly6 proteins inhibit α4β2 nAChRs, but the underlying mechanisms and the properties of homologous modulatory proteins are not well understood. Results: Lynx2 reduces cell-surface levels of receptors, whereas Ly6g6e slows receptor desensitization. Conclusion: Ly6 proteins inhibit or potentiate α4β2 function by distinct mechanisms. Significance: Ly6 proteins greatly expand the range of properties of α4β2 nAChRs. α4β2 nicotinic acetylcholine receptors (nAChRs) are abundantly expressed throughout the central nervous system and are thought to be the primary target of nicotine, the main addictive substance in cigarette smoking. Understanding the mechanisms by which these receptors are regulated may assist in developing compounds to selectively interfere with nicotine addiction. Here we report previously unrecognized modulatory properties of members of the Ly6 protein family on α4β2 nAChRs. Using a FRET-based Ca2+ flux assay, we found that the maximum response of α4β2 receptors to agonist was strongly inhibited by Ly6h and Lynx2 but potentiated by Ly6g6e. The mechanisms underlying these opposing effects appear to be fundamentally distinct. Receptor inhibition by Lynx2 was accompanied by suppression of α4β2 expression at the cell surface, even when assays were preceded by chronic exposure of cells to an established chaperone, nicotine. Receptor inhibition by Lynx2 also was resistant to pretreatment with extracellular phospholipase C, which cleaves lipid moieties like those that attach Ly6 proteins to the plasma membrane. In contrast, potentiation of α4β2 activity by Ly6g6e was readily reversible by pretreatment with phospholipase C. Potentiation was also accompanied by slowing of receptor desensitization and an increase in peak currents. Collectively our data support roles for Lynx2 and Ly6g6e in intracellular trafficking and allosteric potentiation of α4β2 nAChRs, respectively.