Miracle-dz/UniFAR-FTUs huggingface dataset:
To the memory of my mother

A Dissertation submitted for the Degree of Doctor of Philosophy To the memory of my mother Contents Preface iii 1 Introduction 1 1.1 Option pricing in discrete time 1 1.2 Option pricing in continuous time 4 1.3 The Black-Scholes model 8 1.4 Interest-rate models 9
Noninvasive in vivo MRI detection of neuritic plaques associated with iron in APP[V717I] transgenic mice, a model for Alzheimer's disease

Transgenic mice overexpressing the London mutant of human amyloid precursor protein (APP[V717I]) in neurons develop amyloid plaques in the brain, thus demonstrating the most prominent neuropathological hallmark of Alzheimer's disease. In vivo 3D T2*‐weighted MRI on these mice (24 months of age) revealed hypointense brain inclusions that affected the thalamus almost exclusively. Upon correlating these MRI observations with a panel of different histologic staining techniques, it appeared that only plaques that were positive for both thioflavin‐S and iron were visible on the MR images. Numerous thioflavin‐S‐positive plaques in the cortex that did not display iron staining remained invisible to MRI. The in vivo detection of amyloid plaques in this mouse model, using the intrinsic MRI contrast arising from the iron associated with the plaques, creates an unexpected opportunity for the noninvasive investigation of the longitudinal development of the plaques in the same animal. Thus, this work provides further research opportunities for analyzing younger APP[V717I] mouse models with the knowledge of the final outcome at 24 months of age. Magn Reson Med 53:607–613, 2005. © 2005 Wiley‐Liss, Inc.
Lifestyle and metformin treatment favorably influence lipoprotein subfraction distribution in the Diabetes Prevention Program.

CONTEXT Although intensive lifestyle change (ILS) and metformin reduce diabetes incidence in subjects with impaired glucose tolerance (IGT), their effects on lipoprotein subfractions have not been studied. OBJECTIVE The objective of the study was to characterize the effects of ILS and metformin vs placebo interventions on lipoprotein subfractions in the Diabetes Prevention Program. DESIGN This was a randomized clinical trial, testing the effects of ILS, metformin, and placebo on diabetes development in subjects with IGT. PARTICIPANTS Selected individuals with IGT randomized in the Diabetes Prevention Program participated in the study. INTERVENTIONS Interventions included randomization to metformin 850 mg or placebo twice daily or ILS aimed at a 7% weight loss using a low-fat diet with increased physical activity. MAIN OUTCOME MEASURES Lipoprotein subfraction size, density, and concentration measured by magnetic resonance and density gradient ultracentrifugation at baseline and 1 year were measured. RESULTS ILS decreased large and buoyant very low-density lipoprotein, small and dense low-density lipoprotein (LDL), and small high-density lipoprotein (HDL) and raised large HDL. Metformin modestly reduced small and dense LDL and raised small and large HDL. Change in insulin resistance largely accounted for the intervention-associated decreases in large very low-density lipoprotein, whereas changes in body mass index (BMI) and adiponectin were strongly associated with changes in LDL. Baseline and a change in adiponectin were related to change in large HDL, and BMI change associated with small HDL change. The effect of metformin to increase small HDL was independent of adiponectin, BMI, and insulin resistance. CONCLUSION ILS and metformin treatment have favorable effects on lipoprotein subfractions that are primarily mediated by intervention-related changes in insulin resistance, BMI, and adiponectin. Interventions that slow the development of diabetes may also retard the progression of atherosclerosis.
Noncoding RNA Profiles in Tobacco- and Alcohol-Associated Diseases

Tobacco and alcohol are the leading environmental risk factors in the development of human diseases, such as cancer, cardiovascular disease, and liver injury. Despite the copious amount of research on this topic, by 2030, 8.3 million deaths are projected to occur worldwide due to tobacco use. The expression of noncoding RNAs, primarily microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), is modulated by tobacco and alcohol consumption. Drinking alcohol and smoking cigarettes can modulate the expression of miRNAs and lncRNAs through various signaling pathways, such as apoptosis, angiogenesis, and inflammatory pathways—primarily interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3), which seems to play a major role in the development of diseases associated with these risk factors. Since they may be predictive and prognostic biomarkers, they can be used both as predictors of the response to therapy and as a targeted therapy. Further, circulating miRNAs might be valuable noninvasive tools that can be used to examine diseases that are related to the use of tobacco and alcohol. This review discusses the function of noncoding RNAs in cancer and other human tobacco- and alcohol-associated diseases.
Ground-Dwelling Arthropod Communities of a Sky Island Mountain Range in Southeastern Arizona, USA: Obtaining a Baseline for Assessing the Effects of Climate Change

The few studies that have addressed past effects of climate change on species distributions have mostly focused on plants due to the rarity of historical faunal baselines. However, hyperdiverse groups like Arthropoda are vital to monitor in order to understand climate change impacts on biodiversity. This is the first investigation of ground-dwelling arthropod (GDA) assemblages along the full elevation gradient of a mountain range in the Madrean Sky Island Region, establishing a baseline for monitoring future changes in GDA biodiversity. To determine how GDA assemblages relate to elevation, season, abiotic variables, and corresponding biomes, GDA were collected for two weeks in both spring (May) and summer (September) 2011 in the Santa Catalina Mountains, Arizona, using pitfall traps at 66 sites in six distinct upland (non-riparian/non-wet canyon) biomes. Four arthropod taxa: (1) beetles (Coleoptera), (2) spiders (Araneae), (3) grasshoppers and crickets (Orthoptera), and (4) millipedes and centipedes (Myriapoda) were assessed together and separately to determine if there are similar patterns across taxonomic groups. We collected 335 species of GDA: 192/3793 (species/specimens) Coleoptera, 102/1329 Araneae, 25/523 Orthoptera, and 16/697 Myriapoda. GDA assemblages differed among all biomes and between seasons. Fifty-three percent (178 species) and 76% (254 species) of all GDA species were found in only one biome and during only one season, respectively. While composition of arthropod assemblages is tied to biome and season, individual groups do not show fully concordant patterns. Seventeen percent of the GDA species occurred only in the two highest-elevation biomes (Pine and Mixed Conifer Forests). Because these high elevation biomes are most threatened by climate change and they harbor a large percentage of unique arthropod species (11–25% depending on taxon), significant loss in arthropod diversity is likely in the Santa Catalina Mountains and other isolated mountain ranges in the Southwestern US.
Linking predator risk and uncertainty to adaptive forgetting: a theoretical framework and empirical test using tadpoles

Hundreds of studies have examined how prey animals assess their risk of predation. These studies work from the basic tennet that prey need to continually balance the conflicting demands of predator avoidance with activities such as foraging and reproduction. The information that animals gain regarding local predation risk is most often learned. Yet, the concept of ‘memory’ in the context of predation remains virtually unexplored. Here, our goal was (i) to determine if the memory window associated with predator recognition is fixed or flexible and, if it is flexible, (ii) to identify which factors affect the length of this window and in which ways. We performed an experiment on larval wood frogs, Rana sylvatica, to test whether the risk posed by, and the uncertainty associated with, the predator would affect the length of the tadpoles' memory window. We found that as the risk associated with the predator increases, tadpoles retained predator-related information for longer. Moreover, if the uncertainty about predator-related information increases, then prey use this information for a shorter period. We also present a theoretical framework aiming at highlighting both intrinsic and extrinsic factors that could affect the memory window of information use by prey individuals.
IL-12 Induces Monocyte IL-18 Binding Protein Expression Via IFN-γ1

IL-18 is a Th1 cytokine that synergizes with IL-12 and IL-2 in the stimulation of lymphocyte IFN-γ production. IL-18 binding protein (IL-18BP) is a recently discovered inhibitor of IL-18 that is distinct from the IL-1 and IL-18 receptor families. In this report we show that IL-18BPa, the IL-18BP isoform with the highest affinity for IL-18, was strongly induced by IL-12 in human PBMC. Other Th1 cytokines, including IFN-γ, IL-2, IL-15, and IL-18, were also capable of augmenting IL-18BPa expression. In contrast, IL-1α, IL-1β, TNF-α, IFN-γ-inducible protein-10, and Th2 cytokines such as IL-4 and IL-10 did not induce IL-18BPa. Although monocytes were found to be the primary source of IL-18BPa, the induction of IL-18BPa by IL-12 was mediated through IFN-γ derived predominantly from NK cells. IL-18BPa production was observed in cancer patients receiving recombinant human IL-12 and correlated with the magnitude of IFN-γ production. The IFN-γ/IL-18BPa negative feedback loop identified in this study may be capable of broadly controlling immune activation by cytokines that synergize with IL-18 to induce IFN-γ and probably plays a key role in the modulation of both innate and adaptive immunity.
Quasi-Periodic Bedding in the Sedimentary Rock Record of Mars

Widespread sedimentary rocks on Mars preserve evidence of surface conditions different from the modern cold and dry environment, although it is unknown how long conditions favorable to deposition persisted. We used 1-meter stereo topographic maps to demonstrate the presence of rhythmic bedding at several outcrops in the Arabia Terra region. Repeating beds are ∼10 meters thick, and one site contains hundreds of meters of strata bundled into larger units at a ∼10:1 thickness ratio. This repetition likely points to cyclicity in environmental conditions, possibly as a result of astronomical forcing. If deposition were forced by orbital variation, the rocks may have been deposited over tens of millions of years.
ow to make medication error reporting systems work – actors associated with their successful development and mplementation

This study explored factors associated with successful development and implementation of medication error reporting (MER) systems in different healthcare contexts. A descriptive online questionnaire comprising of structured and open-ended questions was responded to by 16 medication safety experts in 16 countries. The present paper describes the rich and multidimensional qualitative data from the experts’ narratives from open-ended questions. Several factors related to the national context of MER systems, i.e., the operational environment, were identified to impact successful development and implementation of these systems. The factors were: awareness of deficiencies in medication safety at local and national levels to justify the need for MER systems; gaining political will for the development and implementation actions together with international and governmental support; creating or reforming legislation and national regulations, guidelines and strategies to support MER; allocation of adequate human and financial resources; establishment of an organisation or centre to coordinate and lead MER; and extending systems approach and safety culture to all parts of the operational environment to facilitate openness on and learning from medication errors. In conclusion, operational environments of MER systems must be constructed to support functionality of these systems, and need to be improved in many countries. © 2015 Published by Elsevier Ireland Ltd.
Prevalence of lymphoreticular prion protein accumulation in UK tissue samples

This study aims to provide an estimate of the number of individuals in the UK who may be incubating variant Creutzfeldt‐Jakob disease and at risk of causing iatrogenic spread of the disease. Lymphoreticular accumulation of prion protein is a consistent feature of variant Creutzfeldt‐Jakob at autopsy and has also been demonstrated in the pre‐clinical phase. Immunohistochemical accumulation of prion protein in the lymphoreticular system remains the only technique that has been shown to predict neurological disease reliably in animal prion disorders. In this study, immunohistochemistry was used to demonstrate the presence of prion protein, with monoclonal antibodies KG9 and 3F4, in surgically removed tonsillectomy and appendicectomy specimens. The samples were collected from histopathology departments across the UK and anonymised prior to testing. Samples were tested from 16 703 patients (14 964 appendectomies, 1739 tonsillectomies), approximately 60% of whom were from the age group 20–29 years at operation. Twenty‐five per cent of the samples were excluded from the final analyses because they contained inadequate amounts of lymphoid tissue. Three appendicectomy samples showed lymphoreticular accumulation of prion protein, giving an estimated prevalence of 3/12 674 or 237 per million (95% CI 49–692 per million). The pattern of lymphoreticular accumulation in two of these samples was dissimilar from that seen in known cases of variant Creutzfeldt‐Jakob disease. Although it is uncertain whether immunohistochemical accumulation of prion protein in the lymphoreticular system is specific for variant Creutzfeldt‐Jakob disease, it has not been described in any other disease, including other forms of human prion disease or a range of inflammatory and infective conditions. These findings reinforce the importance of measures taken by the UK Department of Health to reduce the risk of spread of variant Creutzfeldt‐Jakob via blood products and surgical instruments, and of the urgency to proceed with large‐scale screening of fresh tonsil specimens for the presence of prion protein. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Outcomes of Pin and Plaster Versus Locking Plate in Distal Radius Intraarticular Fractures

Background Distal radius fractures are among the most prevalent fractures predictive of probable occurrence of other osteoporotic fractures. They are treated via a variety of methods, but the best treatment has not been defined yet. Objectives This study was performed to compare the results of open reduction and internal fixation with locking plates versus the pin and plaster method. Materials and Methods In this prospective study, 114 patients aged 40 to 60 years with Fernandez type III fracture referring to Imam-Reza and Mehr hospitals of Mashhad from 2009 to 2011, were selected randomly; after obtaining informed consent, they were treated with pin and plaster fixation (n = 57) or internal fixation with the volar locking plate (n = 57). They were compared at the one year follow up. Demographic features and standard radiographic indices were recorded and MAYO, DASH and SF - 36 tests were performed. Data was analyzed by SPSS software version 13, with descriptive indices, Mann-Whitney and Chi-square tests. Results SF-36 test demonstrated a better general health (P < 0.001), mental health (P = 0.006), physical functioning (P < 0.001), social functioning (P < 0.001) and energy/fatigue (P < 0.001) in LCP group. However, pain (P = 0.647) was not significantly different between the groups. Physical limitation (P < 0.001) and emotional limitation (P < 0.001) were greater in the pin and plaster group. Also, in the LCP group mean MAYO score (P < 0.001) was more than pin and plaster group. Mean DASH score was not different between the groups (P = 0.218). The rate of acceptable results of radiographic indices (P < 0.001), grip strength (P < 0.001) and range of motion in supination-pronation (P < 0.001) in LCP method were better than the pin and plaster method. Conclusions In treatment of intra-articular distal radius fractures in middle-aged patients internal fixation with locking plates may be prefered to pin and plaster as the treatment of choice.
Identifying Antimicrobial Resistance Genes with DNA Microarrays

ABSTRACT We developed and tested a glass-based microarray suitable for detecting multiple tetracycline (tet) resistance genes. Microarray probes for 17 tet genes, the β-lactamase blaTEM-1 gene, and a 16S ribosomal DNA gene (Escherichia coli) were generated from known controls by PCR. The resulting products (ca. 550 bp) were applied as spots onto epoxy-silane-derivatized, Teflon-masked slides by using a robotic spotter. DNA was extracted from test strains, biotinylated, hybridized overnight to individual microarrays at 65°C, and detected with Tyramide Signal Amplification, Alexa Fluor 546, and a microarray scanner. Using a detection threshold of 3× the standard deviation, we correctly identified tet genes carried by 39 test strains. Nine additional strains were not known to harbor any genes represented on the microarray, and these strains were negative for all 17 tet probes as expected. We verified that R741a, which was originally thought to carry a novel tet gene, tet(I), actually harbored a tet(G) gene. Microarray technology has the potential for screening a large number of different antibiotic resistance genes by the relatively low-cost methods outlined in this paper.
Turing Machines with Atoms

We study Turing machines over sets with atoms, also known as nominal sets. Our main result is that deterministic machines are weaker than nondeterministic ones; in particular, P≠NP in sets with atoms. Our main construction is closely related to the Cai-Furer-Immerman graphs used in descriptive complexity theory.
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses

There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this end, we performed a comprehensive genetic analysis of 24 pancreatic cancers. We first determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. Then, we searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for ∼106 single-nucleotide polymorphisms. We found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors. Analysis of these tumors' transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the importance of these pathways and processes. Our data indicate that genetically altered core pathways and regulatory processes only become evident once the coding regions of the genome are analyzed in depth. Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis.
Discrete Bayesian Networks: The Exact Posterior Marginal Distributions

In a Bayesian network, we wish to evaluate the marginal probability of a query variable, which may be conditioned on the observed values of some evidence variables. Here we first present our "border algorithm," which converts a BN into a directed chain. For the polytrees, we then present in details, with some modifications and within the border algorithm framework, the "revised polytree algorithm" by Peot & Shachter (1991). Finally, we present our "parentless polytree method," which, coupled with the border algorithm, converts any Bayesian network into a polytree, rendering the complexity of our inferences independent of the size of network, and linear with the number of its evidence and query variables. All quantities in this paper have probabilistic interpretations.
Renal hemodynamic and excretory responses to intra-arterial infusion of peroxynitrite in anesthetized rats.

Peroxynitrite (ONOO(-)) is formed endogenously by the reaction of nitric oxide (NO) and superoxide (O(2)(-)). To examine the hypothesis that OONO(-) cause renal vasodilation at low concentrations but cause vasoconstriction at higher concentrations, we examined renal responses to intra-arterial infusion of incremental doses of OONO(-) (10, 20, and 40 microg.kg(-1). min(-1); 45 min each) in anesthetized rats. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearance. In control rats (n = 6), low dose (10 microg.kg(-1). min(-1)) of OONO(-) increased RBF by 10 +/- 3% and GFR by 15 +/- 5%. The higher doses (20 and 40 microg.kg(-1). min(-1)) mostly reversed these responses which were -7 +/- 4 and -27 +/- 7% (P < 0.05) in RBF and -0.1 +/- 4.8 and -14 +/- 12% in GFR, respectively. There were no appreciable changes in urine flow (V) and sodium excretion (U(Na)V) during OONO(-) infusion. However, in rats pretreated with NO synthase (NOS) inhibitor, l-NAME (50 microg.kg(-1). min(-1); n = 5), these doses of ONOO(-) significantly reduced RBF (-26 +/- 7, -27 +/- 6, and -44 +/- 3%) and GFR (-21 +/- 6, -25 +/- 8, and -32 +/- 12%) with variable increases in V or U(Na)V. Long-term infusion of OONO(-) (10 microg.kg(-1). min(-1) for 75 min) in another set of control rats (n = 5) also showed similar vasodilator and hyperfiltration responses. These data indicate that ONOO(-) acts as an oxidant at high concentration but provides renoprotective function at low concentration that depends on intact NOS activity.
Resistance training and insulin action in humans: effects of de‐training

Aerobic endurance training increases insulin action in skeletal muscle, but the effect of resistance training has not been well described. Controversy exists about whether the effect of resistance training is merely due to an increase in muscle mass. We studied the effect of cessation of resistance training in young, healthy subjects by taking muscle biopsies and measuring insulin‐mediated whole body and leg glucose uptake rates after 90 days of heavy resistance training (T) and again after 90 days of de‐training (dT). Data on leg glucose uptake were expressed relative to accurate measures of leg muscle mass by MRI scanning. Muscle strength (239 ± 43 vs. 208 ± 33 N m), quadriceps area (8463 ± 453 vs. 7763 ± 329 mm2) and glycogen content (458 ± 22 vs. 400 ± 26 mmol (kg dry weight muscle)−1) decreased, while myosin heavy chain isoform IIX increased 4‐fold in dT vs. T, respectively (all P < 0.05). GLUT4 mRNA levels and enzyme activities and mRNA levels of glycolytic, lipolytic and glyconeogenic enzymes did not change with de‐training. Likewise, capillary density did not change. Whole body glucose uptake decreased 11 % and leg glucose uptake decreased from 75 ± 11 (T) to 50 ± 6 (dT) nmol min−1 (mm muscle)−2 (P < 0.05) at maximal insulin, the latter decrease being due to decreased arterio‐femoral venous glucose extraction. The decrease was mainly due to reduced non‐oxidative glucose disposal. We have thus shown that 90 days after the termination of heavy resistance training, insulin‐mediated glucose uptake rates per unit of skeletal muscle have decreased significantly.