Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and classification of prostate tumour tissues by FTIR

The development of prostate cancer (PCa) is not yet fully understood, but it is already recognized that it develops through pre malignant stages. Thus, the most important factor in the prevention of cancer is early detection, facilitating eradication of these premalignant cells prior to systemic invasion. There is a great clinical need for techniques that can detect these pre-malignant biochemical changes that can advance to cancer. The infrared (IR) spectroscopy is a powerful analytical tool to provide detailed information on the chemical composition of complex biological samples, such as tissues. This technique is based on the vibrations between the atoms of a molecule. The molecules absorb infrared light and give rise to distinctive spectral patterns in transmitted light. This is a non-destructive, highly sensitive and specific analytical technique that allows the identification of signals associated with prostate cancer at a biochemical level, providing an improved diagnosis of cancer and also facilitating the identification of tumors with aggressive biopotential. This dissertation is an exploratory study that intends to test the ability of the Fourier transform infrared spectroscopy (FTIR) to discriminate between control and PCa samples and to identify spectroscopic signals related to functional groups of biochemical compounds present in the malignant tissues. Prostate biopsy samples were collected from radical prostatectomy pieces of 8 patients characterized with elevated prostate specific antigen (PSA) and/or abnormal digital rectal examination (DRE). Also relevant histopathological information about the patients has been provided, including the Gleason grade and the TNM staging. PCa and control samples were analysed by FTIR and the resulting spectra were submitted to Principal Component Analysis (PCA) in the ranges 3000-2800 cm -1 , 1200-900 cm -1 and 1800-1700 cm -1 . The diagram of the factorial coordinates (scores) discriminated the spectra of PCa samples from the spectra of controls samples. The diagram of the factorial contributions (loadings) allowed the identification of spectroscopic signals associated with biochemical pathologic modifications expected in malignant tissues, mainly dysregulations in lipid metabolism, based on higher content in fatty acids and increased disorder of the chains of membrane lipids; also a lower polysaccharide (glucose) and glycogen content and an increase in the nucleic acids. In the future, further investigations would make possible the development of a universal FTIR multivariate classification model for prostate cancer.
MELK and EZH2 Cooperate to Regulate Medulloblastoma Cancer Stem-like Cell Proliferation and Differentiation

Medulloblastoma is the most common malignant brain tumor in children. Although accumulated research has suggested that cancer stem-like cells play a key role in medulloblastoma tumorigenesis, the specific molecular mechanism regarding proliferation remains elusive. Here, we reported more abundant expression of maternal embryonic leucine-zipper kinase (MELK) and enhancer of zeste homolog 2 (EZH2) in medulloblastoma stem-like cells than in neural stem cells and the interaction between the two proteins could mediate the self-renewal of sonic hedgehog subtype medulloblastoma. In human medulloblastoma, extensive nodularity and large-cell/anaplastic subgroups differed according to the staining levels of MELK and EZH2 from the other two subgroups. The proportion of MELK- or EZH2-positive staining status could be considered as a potential indicator for survival. Mechanistically, MELK bound to and phosphorylated EZH2, and its methylation was induced by EZH2 in medulloblastoma, which could regulate the proliferation of cancer stem-like cells. In xenografts, loss of MELK or EZH2 attenuated medulloblastoma stem-like cell-derived tumor growth and promoted differentiation. These findings indicate that MELK-induced phosphorylation and EZH2-mediated methylation in MELK/EZH2 pathway are essential for medulloblastoma stem-like cell-derived tumor proliferation, thereby identifying a potential therapeutic strategy for these patients. Implications: This study demonstrates that the interaction occurring between MELK and EZH2 promotes self-proliferation and stemness, thus representing an attractive therapeutic target and potential candidate for diagnosis of medulloblastoma. Mol Cancer Res; 15(9); 1275–86. ©2017 AACR.
Ecstasy and new patterns of drug use: a normal population study.

AIMS (i) To describe illegal drug use patterns in an adolescent normal population sample with special emphasis on MDMA, ecstasy; (ii) to investigate where ecstasy is introduced in a hypothesized drug use sequence, and (iii) to contrast the predictors of ecstasy use with those of other illegal substances. Special attention was given to the relationship to subcultural music preferences and house-party-going. DESIGN A school-based survey of the total cohort of adolescents enrolled in the school system in a city. PARTICIPANTS 10,812 adolescents, age 14-17 years, response rate 94.3%. SETTING Oslo, the capital and only metropolitan town in Norway. MEASUREMENTS Social class was measured by the occupation standard ISCO 88, questions were posed as regards frequency of alcohol use and alcohol intoxication, cigarette smoking and use of cannabis, amphetamines, ecstasy and heroin. Alcohol problems were measured by a shortened version of Rutgers Alcohol Problem Index (RAPI), conduct problems were measured according to the four categories of acts forming the basis of the diagnosis conduct disorder in DSM-IV, internalizing mental health problems were measured using items from Hopkins Symptoms Checklist (HCL). A number of questions were asked as regards subcultural music preferences and house-party-going. STATISTICAL MODELS: A hypothesized cumulative sequence in drug use was investigated by means of latent class analysis, and the predictors of the various patterns of drug use were estimated and compared by means of multinominal logistic regression analysis. FINDINGS The use of ecstasy was often intermingled with the use of cannabis, amphetamines and heroin, in a pattern of polydrug use. The latent class analysis revealed the following drug use sequence: (1) alcohol, (2) cigarettes, (3) cannabis, (4) amphetamines, (5) ecstasy and (6) heroin. There was no significant association between ecstasy use and parental social class or residential area of the town. All patterns of illegal drug use were highly associated with cigarette smoking, alcohol use, alcohol problems and conduct problems, whereas the associations with internalizing mental health problems were of less magnitude. Multinominal logistic regression analysis revealed that the use of ecstasy (E) was significantly more weakly associated with cigarette smoking than were the use of cannabis only (C), amphetamines (A) and the combination of ecstasy and amphetamines (A + E). The association between E and conduct problems (CP) was weaker than the association between CP and A and A + E. Finally, there were associations between E and A + E and House/Techno preferences and house-party-going, which were not found for C and A. CONCLUSIONS Ecstasy is used by adolescents who use other legal and illegal substances in a polydrug-use pattern. The substance is introduced late in a hypothesized drug use sequence. Even so, ecstasy use seems to differ from the use of, e.g. amphetamines, in that the association with smoking and conduct problems is weaker and that the associations with subcultural music preferences and house-party-going are much stronger.
Roles of the Receptor, the Ligand, and the Cell in the Signal Transduction Pathways Utilized by the Relaxin Family Peptide Receptors 1–3

The relaxin‐like peptides produce their effects by acting at four G‐protein‐coupled receptors (GPCRs) RXFP1 to 4. RXFP1 and 2 are characterized by large extracellular domains containing leucine‐rich repeats, whereas RXFP3 and 4 closely resemble small‐peptide‐liganded GPCRs. Studies with mutant RXFP1 receptors established that the final 10 amino acids of the C‐terminus and Arg752 in particular are obligatory for the second phase of cAMP signaling. Examination of the importance of cell type revealed different patterns of cAMP signaling related to the types of G‐proteins expressed in these cells. Studies of RXFP3 signaling using reporter genes revealed that both relaxin and relaxin‐3 activated the receptor but displayed different patterns of signaling. The studies suggest that the functional domains of the receptor, the cell type in which it is expressed, and the ligand used to activate the receptor all have important roles in determining the functional response observed.
The patterns of musical influence on the Last.Fm social network

One classic problem definition in social network analysis is the study of diffusion in networks, which enables us to tackle problems like favoring the adoption of positive technologies. Most of the attention has been turned to how to maximize the number of influenced nodes, but this approach misses the fact that different scenarios imply different diffusion dynamics, only slightly related to maximizing the number of nodes involved. In this paper we study the patterns of musical influence through a social network. First, we define a procedure to extract musical leaders, i.e. users who start the diffusion of new music albums through the social network. Second, we measure three different dimensions of musical influence: the Width, i.e. the ratio of neighbors influenced by a leader; the Depth, i.e. the degrees of separation from a leader to its influenced nodes; and the Strength, i.e. the intensity of the influence from a leader. We validate our results on a social network extracted from the Last.Fm music platform.
Toll-like Receptor 9 Agonist IMO Cooperates with Cetuximab in K-Ras Mutant Colorectal and Pancreatic Cancers

Purpose: K-Ras somatic mutations are a strong predictive biomarker for resistance to epidermal growth factor receptor (EGFR) inhibitors in patients with colorectal and pancreatic cancer. We previously showed that the novel Toll-like receptor 9 (TLR9) agonist immunomodulatory oligonucleotide (IMO) has a strong in vivo activity in colorectal cancer models by interfering with EGFR-related signaling and synergizing with the anti-EGFR monoclonal antibody cetuximab. Experimental Design: In the present study, we investigated, both in vitro and in vivo, the antitumor effect of IMO alone or in combination with cetuximab in subcutaneous colon and orthotopic pancreatic cancer models harboring K-Ras mutations and resistance to EGFR inhibitors. Results: We showed that IMO was able to significantly restore the sensitivity of K-Ras mutant cancer cells to cetuximab, producing a marked inhibition of cell survival and a complete suppression of mitogen—activated protein kinase phosphorylation, when used in combination with cetuximab. IMO interfered with EGFR-dependent signaling, modulating the functional interaction between TLR9 and EGFR. In vivo, IMO plus cetuximab combination caused a potent and long-lasting cooperative antitumor activity in LS174T colorectal cancer and in orthotopic AsPC1 pancreatic cancer. The capability of IMO to restore cetuximab sensitivity was further confirmed by using K-Ras mutant colorectal cancer cell models obtained through homologous recombination technology. Conclusions: We showed that IMO markedly inhibits growth of K-Ras mutant colon and pancreatic cancers in vitro and in nude mice and cooperates with cetuximab via multiple mechanisms of action. Therefore, we propose IMO plus cetuximab as a therapeutic strategy for K-Ras wild-type as well for K-Ras mutant, cetuximab-resistant colorectal and pancreatic cancers. Clin Cancer Res; 17(20); 6531–41. ©2011 AACR.
Spot Ignition of Natural Fuels by Hot Metal Particles

Author(s): Urban, James Linwood | Advisor(s): Fernandez-Pello, Carlos | Abstract: The spot ignition of combustible material by hot metal particles is an important pathway by which wildland and urban spot fires and smolders are started. Upon impact with a fuel, such as dry grass, duff, or saw dust, these particles can initiate spot fires by direct flaming or smoldering which can transition to a flame. These particles can be produced by processes such as welding, powerline interactions, fragments from bullet impacts, abrasive cutting, and pyrotechnics. There is little published work that addresses the ignition capabilities of hot metal particles landing on natural fuels. The work presented here investigates the ignition capabilities of these particles by breaking the overall spot ignition process into three distinct subprocesses: generation, simultaneous transport and thermo-chemical change of the particle, and ignition of a fuel. This dissertation will present research on these subprocesses. The first subprocess, generation, was studied through literature searches and the results are shown in Section \ref{sec:Generation} of Chapter \ref{ch:Introduction} along with background on spot fires and previous and associated literature. Then in Chapter 2 a model for the heterogeneous oxidation of iron and steel particles is presented. In Chapter 3 results are presented on the ability of hot metal particles composed of four different metals to ignite a cellulose powder fuel. Then in Chapter 4, the ability of aluminum particles to ignite six natural fuels of different compositions and morphologies was investigated. Then the ability of aluminum and stainless steel particles to ignite a smolder in a grass powder fuel was investigated through experiments and modelling in Chapter 5.
An efficient fabrication of vertically aligned carbon nanotubes on flexible aluminum foils by catalyst-supported chemical vapor deposition

An efficient and versatile growth of thin-layer carbon nanotubes on a flexible aluminum foil (for kitchen use) by catalyst-supported chemical vapor deposition is reported. The aluminum foil used in the present experiment is commercially available for kitchen use. The electron-beam vapor deposition and dip-coating have been used for preparing catalysts on the aluminum foil. Vertically aligned thin-layer CNTs with typical diameters of 2.5–6.0 nm and lengths up to 90 µm are obtained when ethanol is used in combination with Fe and Co catalyst particles at a growth temperature of around 650 °C under an Ar/H2 gas flow. Thermo-gravimetric analyses together with HR-TEM observations indicate that the purity of the CNTs synthesized by the current technique is very high.
Tactical Voting in Plurality Elections

How often will elections end in landslides? What is the probability for a head-to-head race? Analyzing ballot results from several large countries rather anomalous and yet unexplained distributions have been observed. We identify tactical voting as the driving ingredient for the anomalies and introduce a model to study its effect on plurality elections, characterized by the relative strength of the feedback from polls and the pairwise interaction between individuals in the society. With this model it becomes possible to explain the polarization of votes between two candidates, understand the small margin of victories frequently observed for different elections, and analyze the polls' impact in American, Canadian, and Brazilian ballots. Moreover, the model reproduces, quantitatively, the distribution of votes obtained in the Brazilian mayor elections with two, three, and four candidates.
Positive Aspects of Caregiving Questionnaire

Objective: The potential role of positive aspects of caregiving in enhancing caregivers’ health is an important issue. The aim of this study was to develop and validate Positive Aspects of Caregiving Questionnaire (PACQ) in caregivers of patients with dementia in Iran. Methods: Content validation process was used to content valid development. Cronbach α and intraclass correlation coefficient (ICC) were calculated as reliability indices. We used exploratory factor analysis to extract potential latent factors and evaluate the factor structure of PACQ. We assess correlation between PACQ and caregiver burden for divergent validity. For convergent validity, correlation between PACQ and self-rated health was specified. Results: Content validity indices (CVIs), internal consistency, and test–retest reliability were CVI > 0.80, α = 0.785, and ICC = 0.905, respectively. Moreover, item–total correlations confirmed good reliability of PACQ. Two factors were identified by factor analysis in this 10-item measure: patient and caregiver relationship and caregiver’s psychological well-being. Divergent validity and convergent validity were established by high negative correlation between positive aspect of caregiving (PAC) and caregiver burden along with significant positive correlation between PAC and self-rated health, respectively. While Cronbach α for the entire scale was 0.785, Cronbach αs for both of the scale components were 0.71. Conclusion: The PACQ demonstrated acceptable psychometric properties of reliability and performs well in preliminary tests of validity as a measure of positive aspects of caregiving. This measure can be used to determine the outcome of interventional programs on positive, not only negative, aspect of caregiving.
GPBA: a GPCR for bile acids and an emerging therapeutic target for disorders of digestion and sensation

Bile acids (BAs) are digestive secretions that are necessary for the emulsification and absorption of dietary fats. Given the episodic nature of BA secretion and intestinal re‐absorption, the circulating and tissue levels of BAs, like those of the gut hormones, fluctuate in fasting and fed states, and BA levels and forms are markedly affected by disease. BAs exert widespread hormonal‐like effects by activating receptors in the nucleus and at the plasma membrane. The nuclear steroid receptors mediate the genomic actions of BAs on BA, glucose and lipid homeostasis. GPBA (TGR5) is a G‐protein coupled plasma membrane receptor for BAs that mediates many of the rapid, non‐genomic actions of BAs. GPBA has been implicated in the control of glucose homeostasis, inflammation and liver functions. Recent observations have revealed an unexpected role for GPBA in the nervous system. GPBA is expressed by enteric neurons and enterochromaffin cells that control peristalsis, and GPBA mediates the prokinetic actions of BAs in the colon that have been known for millennia. GPBA is also present on primary spinal afferent and spinal neurons that are necessary for sensory transduction. BA‐induced activation of GPBA in the sensory nervous system promotes scratching behaviours and analgesia, which may contribute to the pruritus and painless jaundice that are observed in some patients with chronic cholestatic disease, where circulating BA concentrations are markedly increased. Thus, GPBA has emerged as an intriguing target for diverse metabolic, inflammatory, digestive and sensory disorders, where agonists and antagonists may be of value.
Experience Management in Communities of Practice

In this paper, we describe how Communities of Practice (CoP) can be seen as a means to realize Experience Management (EM). We start by presenting a model to guide the process of CoP formation and maintenance. This model is then extended to include methods for (1) the analysis of the different requirements of the involved parties, and (2) the design of EM support systems in CoPs that implement answers to those requirements. This framework, which is based on multi-agent concepts, enables the design of CoP support systems that incorporate the principles of collaboration and internal autonomy.
A modular design space exploration framework for multiprocessor real-time systems

Embedded system designers often face a large number of design alternatives when designing complex systems. A designer must select an alternative which satisfies application constraints (e.g. timing requirements) while optimizing system level objectives such as overall energy consumption. The size of design space is often very large giving rise to the need for systematic Design Space Exploration (DSE) methods. In this paper we address the DSE problem for real-time applications that belong to two different domains: (i) streaming applications modeled using the synchronous dataflow graphs; (ii) feedback control tasks modeled using the periodic task model. We consider a heterogeneous multiprocessor platform in which processors communicate through a predictable bus architecture. We present our DSE tool in which the DSE problem is modeled as a constraint satisfaction problem, and it is solved using a constraint programming solver. This approach provides a modular framework in which different constraints such as deadline, throughput and energy consumption can easily be plugged depending on the system being designed.
Malaria model with periodic mosquito birth and death rates

In this paper, we introduce a model of malaria, a disease that involves a complex life cycle of parasites, requiring both human and mosquito hosts. The novelty of the model is the introduction of periodic coefficients into the system of one-dimensional equations, which account for the seasonal variations (wet and dry seasons) in the mosquito birth and death rates. We define a basic reproduction number R 0 that depends on the periodic coefficients and prove that if R 0<1 then the disease becomes extinct, whereas if R 0>1 then the disease is endemic and may even be periodic.
Defunctionalizing Focusing Proofs

In previous work, the author gave a higher-order analysis of focusing proofs (in the sense of Andreoli’s search strategy), with a role for infinitary rules very similar in structure to Buchholz’s Ω-rule. Among other benefits, this “pattern-based” description of focusing simplifies the cut-elimination procedure, allowing cuts to be eliminated in a connective-generic way. However, interpreted literally, it is problematic as a representation technique for proofs, because of the difficulty of inspecting and/or exhaustively searching over these infinite objects. In the spirit of infinitary proof theory, this paper explores a view of pattern-based focusing proofs as façons de parler, describing how to compile them down to first-order derivations through defunctionalization, Reynolds’ program transformation. Our main result is a representation of pattern-based focusing in the Twelf logical framework, whose core type theory is too weak to directly encode infinitary rules—although this weakness directly enables so-called “higher-order abstract syntax” encodings. By applying the systematic defunctionalization transform, not only do we retain the benefits of the higher-order focusing analysis, but we can also take advantage of HOAS within Twelf, ultimately arriving at a proof representation with surprisingly little bureaucracy.