Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of the Immune System in Triplet Repeat Expansion Diseases

Trinucleotide repeat expansion disorders (TREDs) are a group of dominantly inherited neurological diseases caused by the expansion of unstable repeats in specific regions of the associated genes. Expansion of CAG repeat tracts in translated regions of the respective genes results in polyglutamine- (polyQ-) rich proteins that form intracellular aggregates that affect numerous cellular activities. Recent evidence suggests the involvement of an RNA toxicity component in polyQ expansion disorders, thus increasing the complexity of the pathogenic processes. Neurodegeneration, accompanied by reactive gliosis and astrocytosis is the common feature of most TREDs, which may suggest involvement of inflammation in pathogenesis. Indeed, a number of immune response markers have been observed in the blood and CNS of patients and mouse models, and the activation of these markers was even observed in the premanifest stage of the disease. Although inflammation is not an initiating factor of TREDs, growing evidence indicates that inflammatory responses involving astrocytes, microglia, and the peripheral immune system may contribute to disease progression. Herein, we review the involvement of the immune system in the pathogenesis of triplet repeat expansion diseases, with particular emphasis on polyglutamine disorders. We also present various therapeutic approaches targeting the dysregulated inflammation pathways in these diseases.
A hyperbolic location algorithm for various distributions of a Wireless Sensor Network

Intersection of hyperbolic curves defined by the Time Difference of Arrival (TDOA) is often used in Wireless Sensor Networks (WSNs) to estimate the location of sensors. This paper proposes a new algorithm of this type. The hyperbolic parametric equation and the rotation matrix are used to estimate the location of the target node and rotation, translation and intersection operations are applied. MATLAB simulations on Uniform, Beta, Weibull and Gamma distributed networks showed the optimum combinations of distribution, constant range and anchor percentage.
Quantifying the risk to life posed by hyperconcetrated flows

QUANTIFYING THE RISK TO LIFE POSED BY HYPERCONCENTRATED FLOWS (ANALISI QUANTITATIVA DEL RISCHIO PER LA VITA UMANA DA FLUSSI IPERCONCENTRATI) ING. GIOVANNA DE CHIARA Relatore: PROF. ING. LEONARDO CASCINI Correlatore: PROF. ING. SETTIMIO FERLISI Coordinatore PROF. ING. VINCENZO BELGIORNO UIVERSITY OF SAL ER NO
The Phosphatidylinositol 3‐Kinase Inhibitor Wortmannin Alters the Metabolism of the Alzheimer's Amyloid Precursor Protein

Abstract : One of the hallmarks of Alzheimer's disease is the accumulation of senile plaques in brain, extracellular lesions comprised mostly of aggregates of the amyloid β‐peptide (Aβ). Aβ is proteolytically derived from the Alzheimer's amyloid precursor protein (APP). The generation of Aβ and nonamyloidogenic derivatives of APP involves utilization of alternative processing pathways and multiple subcellular compartments. To improve our understanding of the regulation of APP processing, we investigated the effects of wortmannin, a phosphatidyl‐inositol 3‐kinase (PI3‐kinase) inhibitor, on APP processing. PI3‐kinases form a multifaceted family of enzymes that represent converging points for multiple signal transduction pathways and also act as key regulators of vesicular trafficking. In N2a neuroblastoma cells expressing either wild‐type APP or the “Swedish” familial Alzheimer's disease‐associated mutant variant of APP, wortmannin treatment resulted in decreased release of both Aβ and soluble APPα. In parallel, full‐length APP and both processed derivatives accumulated inside the cells. These effects were not present at nanomolar concentrations of wortmannin, but only at micromolar concentrations, implying the possible involvement of a recently described trans‐Golgi network (TGN)‐associated PI3‐kinase that is resistant to nanomolar concentrations of the inhibitor, but sensitive to micromolar concentrations. All effects were reversible when the drug was removed from the cell culture medium. Given the suspected site of action of this novel PI3‐kinase activity at the TGN, it is tempting to speculate that the unexpected increase in the levels of both intracellular soluble APPα and intracellular Aβ might be due to wortmannin‐induced covesiculation of APP together with its respective secretase enzymes within the TGN, leading to the execution of α‐, β‐, and γ‐secretase reactions.
Life (and limb) in the fast-lane: disposable people as infrastructure in Kampala’s boda boda industry

Motorcycle taxis, dubbed boda bodas, constitute a vital aspect of Kampala’s transportation infrastructure, yet the industry is perpetually precarious, threatened with wholesale eviction. Moreover, drivers’ lives and bodies are continually put at risk by the city’s traffic. Through a relational approach to ontology, this article asks how the boda boda industry comes into being and endures, what forms of vulnerability it entails, and what experiences, relations, and forms of urban life it produces. It argues that three forms disposability structure and arise from the industry – structural unemployment, embodied vulnerability, and infrastructural displacement. Infrastructural violence, it is argued, must be considered when describing and theorizing people as infrastructure. The article examines how boda boda drivers’ shared condition of insecurity and disposability generates intense forms of sociality, solidarity, mutual obligation, recognition, and urban vitality.
Political Participation in Mexico Offline and Through Twitter

We used survey data and collected data from the online social network Twitter between October 5, 2015 to November 9, 2015 to provide an overview related to political participation in Mexico. With the former we provided a qualitative assessment of participation by examining electoral participation, participation between regions, interest in politics and sources of political information. With Twitter data, we described the intensity of participation, we identified locations of high activity and identified movements including agencies behind them. We compare and contrast participation in Mexico to its counterpart in Twitter. We show that participation seems to be decreasing. However, participation through Twitter seems to be increasing. Our research points towards the emergence of Twitter as a significant platform in terms of political participation in Mexico. Our study analyses the impact of how different agencies related to social movements can enhance participation through Twitter. We show that emergent topics are important because they could help to explore how politics becomes of public interest. Political Participation in Mexico Offline and Through Twitter
POLITECNICO DI TORINO Repository ISTITUZIONALE Power-Gating : More Than Leakage Savings /

While CMOS technology keeps running towards the physical limit of ”nanometer” lengths, many critical design issues have already appeared in today’s technologies (65nm and 45nm). Among them, Power and Reliability are the most insidious, because they affect energy efficiency and life-time of digital systems. In this work we establish an important link between these two metrics. More specifically, we show how the most widely adopted leakage-reduction technique, that is power-gating, can go beyond its specific goal (i.e., saving leakage) by providing, per se, an effective solution to mitigate NBTI-induced aging. Based on this important property, we first present an automated methodology that allows a push-button estimation of the aging effects induced by NBTI on logic circuits (in terms of delay degradation) and SRAM memory cells (in terms of Static Noise Margin (SNM) reduction). Second, using an industrial 45nm technology, we quantify the actual capability of power-gating to further reduce the aging of CMOS devices and extend the lifetime of digital circuits.
Who Decides When The Party Doesn’t? Authoritarian Voters and the Rise of Donald Trump

ABSTRACT While the party decides theory explains the outcomes of past nomination battles for president, this year in the Republican presidential contest party insiders failed to anoint a standard bearer. Who decides when the party elites don’t? In 2016, it was America’s authoritarian voters. And their candidate of choice, Donald Trump, is anathema to party leaders. I argue that Trump’s rise is in part the result of authoritarian voters’ response to his unvarnished, us-versus-them rhetoric. The failure of Republican Party insiders to coalesce behind one candidate opened the door for Trump. Authoritarian-driven partisan polarization (Hetherington and Weiler 2009), increasing fear of real and imagined threats, and terrorist incidents abroad and at home provided the fuel for Trump’s campaign. And Trump’s message and manner ignited that fuel, propelling him to the Republican nomination for president.
Dexmedetomidine as an adjunctive analgesic to ropivacaine in pectoral nerve block in oncological breast surgery: A randomized double-blind prospective study

Background and Aims: Pectoral nerve block (Pecs) using local anesthetic (LA) agent is a newer analgesic technique for breast surgeries. This study further evaluates the effect of addition of dexmedetomidine to LA agent on total duration of analgesia and postoperative morphine consumption. Material and Methods: A total of 60 American Society of Anesthesiologist Grade I and II female patients with age ≥18 years, scheduled for oncological breast surgery, were enrolled in the study. Patients were randomized into two equal groups of 30 each. Group R (n = 30) received ultrasound (US)-guided Pecs block with 30 ml of 0.25% ropivacaine. Group RD (n = 30 patients) received US-guided Pecs block with 30 ml of ropivacaine 0.25% and dexmedetomidine 1 μ/kg body weight. Duration of analgesia and total postoperative morphine consumption was noted in 24 h period. Unpaired t-test and Chi-square test were used for statistical analysis. Results: A statistically highly significant increase in total duration of analgesia (in minutes) was recorded in Group RD as compared to Group R (469.6 ± 81.5 in Group RD and 298.2 ± 42.3 in Group R) (P = 0.000). Total postoperative morphine consumption in mg was also statistically significantly lower in Group RD as compared to Group R (14.8 ± 2.4 in Group RD and 21.6 ± 3.1 in Group R) (P = 0.000). No patient under study reported any adverse effects. Conclusion: Addition of 1 μ/kg dexmedetomidine to 0.25% ropivacaine for Pecs block increases the duration of analgesia and decreases postoperative morphine consumption.
Regulator of Calcineurin 1 (RCAN1) Facilitates Neuronal Apoptosis through Caspase-3 Activation*

Individuals with Down syndrome (DS) will inevitably develop Alzheimer disease (AD) neuropathology sometime after middle age, which may be attributable to genes triplicated in individuals with DS. The characteristics of AD neuropathology include neuritic plaques, neurofibrillary tangles, and neuronal loss in various brain regions. The mechanism underlying neurodegeneration in AD and DS remains elusive. Regulator of calcineurin 1 (RCAN1) has been implicated in the pathogenesis of DS. Our data show that RCAN1 expression is elevated in the cortex of DS and AD patients. RCAN1 expression can be activated by the stress hormone dexamethasone. A functional glucocorticoid response element was identified in the RCAN1 isoform 1 (RCAN1-1) promoter region, which is able to mediate the up-regulation of RCAN1 expression. Here we show that overexpression of RCAN1-1 in primary neurons activates caspase-9 and caspase-3 and subsequently induces neuronal apoptosis. Furthermore, we found that the neurotoxicity of RCAN1-1 is inhibited by knock-out of caspase-3 in caspase-3−/− neurons. Our study provides a novel mechanism by which RCAN1 functions as a mediator of stress- and Aβ-induced neuronal death, and overexpression of RCAN1 due to an extra copy of the RCAN1 gene on chromosome 21 contributes to AD pathogenesis in DS.
Influência da Book-Tax-Differences no Retorno Financeiro das Ações de Companhias Brasileiras Listadas na BM&FBovespa

Este estudo analisou se a proxy Book-Tax-Differences (BTD) afeta o retorno das acoes das companhias brasileiras com acoes negociadas na BM&FBovespa. Foram coletados dados anuais no periodo de 1994 a 2013 e apos o tratamento dos dados foram analisadas 136 companhias por 19 periodos anuais utilizando o CAPM e o modelo de Fama e French (1992). Os resultados encontrados sugerem que no modelo CAPM, a variavel BTD foi estatisticamente significante. Adicionalmente, verificou-se que a relacao entre a BTD e retorno da acao das companhias nao foi afetada pela adocao do Regime Tributario de Transicao (RTT). Assim, somente com base nas evidencias apontadas atraves do CAPM, sugere-se que a diferenca entre o lucro contabil e lucro tributavel apresente conteudo informacional relevante a precificacoes de acoes no mercado de capitais brasileiro, mas cabe ressaltar que as estimativas apontam baixo poder preditivo.
Genetic modulation of TLR8 response following bacterial phagocytosis

Human Toll‐like receptors (TLRs) TLR7, TLR8, and TLR9 are important immune sensors of foreign nucleic acids encountered by phagocytes. Although there is growing evidence implicating TLR7 and TLR9 in the detection of intracellular pathogenic bacteria, characterization of such a role for TLR8 is currently lacking. A recent genetic study has correlated the presence of a TLR8 single nucleotide polymorphism (SNP) (rs3764880:A>G; p.Met1Val) with the development of active tuberculosis, suggesting a role for TLR8 in the detection of phagosomal bacteria. Here we provide the first direct evidence that TLR8 sensing is activated in human monocytic cells following Helicobacter pylori phagocytosis. In addition, we show that rs3764880 fine tunes translation of the two TLR8 main isoforms, without affecting protein function. Although we show that TLR8 variant 2 (TLR8v2) is the prevalent form of TLR8 contributing to TLR8 function, we also uncover a role for the TLR8 long isoform (TLR8v1) in the positive regulation of TLR8 function in CD16+CD14+ differentiated monocytes. Thus, TLR8 sensing can be activated following bacterial phagocytosis, and rs3764880 may play a role in the modulation of TLR8‐dependent microbicidal response of infected macrophages. Hum Mutat 31:1069–1079, 2010. © 2010 Wiley‐Liss, Inc.
New BIST techniques for universal and robust testing of CMOS stuck-open faults

This paper presents three built-in self-test (BIST) schemes for robust testing of stuck-open faults in combinational FCMOS complex cells of arbitrary structure. The first method shows that all single stuck-open faults can be robustly tested by applying a universal sequence of 5/spl times/2/sup n/ vectors to the modified circuit under test (CUT), and counting the number of 1's in the output response. The second method uses the same test pattern generator (TPG), but faults are detected by a self comparison technique without the need of storing a signature. Finally, we propose a new adaptive BIST technique, where the TPG is driven by the past outputs of the CUT itself In all the cases, the TPG is universal, i.e., if does not depend on the functionality and the structure of the CUT, but does ensure robust testing. Neither any test vector, nor any fault dictionary, is required. These approaches provide simplicity, less testing time and test data, and compare favorably with earlier BIST designs for CMOS circuits.
Comparative Value of NYHA Functional Class and Quality‐of‐Life Questionnaire Scores in Assessing Heart Failure

PURPOSE To assess the relationships between New York Heart Association (NYHA) functional class, quality of life, aerobic capacity (peak oxygen uptake, &OV0312;O2), ventilatory efficiency (minute ventilation/carbon dioxide production slope, VE/&OV0312;CO2 slope), and brain natriuretic peptide (BNP) in creating a model for predicting peak &OV0312;O2. METHODS Cardiopulmonary exercise testing was performed in 62 patients. A baseline blood sample was taken to measure the N-terminal prohormone BNP (NT-proBNP). Patients also completed the Minnesota Living with Heart Failure Questionnaire (MLHF) and the Specific Activity Questionnaire (SAQ), and NYHA functional class was determined. RESULTS NYHA functional class correlated more strongly with SAQ score than with MLHF score. Peak &OV0312;O2 and VE/&OV0312;CO2 slope had stronger associations with NYHA functional class and SAQ score than with MLHF score. NT-proBNP plasma levels correlated more significantly with NYHA functional class and SAQ score (both P < .001) than with MLHF score. Using multiple linear regression analysis adjusted for age and sex, SAQ score, NT-proBNP, and etiology of heart failure had significant independent relationships with peak &OV0312;O2, explaining 63% of its variability (adjusted R2 = 0.596). CONCLUSIONS Cardiopulmonary exercise variables and plasma NT-proBNP are associated more with NYHA functional class and SAQ score than with MLHF score. When combined, SAQ score, NT-proBNP, and etiology of heart failure can satisfactorily predict peak oxygen uptake.
Fasciola hepatica: attempts to induce protection against infection in rats and mice by injection of excretory/secretory products of immature worms

SUMMARY In vitro excretory/secretory products of 4-week (immature) and 8- week-old (mature) Fasciola hepatica parasites, derived from rats, were injected together with adjuvant into naive rats and mice. Resistance to infection was assessed in rats by counting adults in the bile ducts at 9 weeks, or in mice by recording deaths after oral challenge with a high dose of viable metacercariae. Exposure of rats to excretory/secretory products of immature F. hepatica conferred a significant degree of resistance which was comparable to the level of resistance induced following oral administration of a low number of metacercariae. No protection against infection was seen in rats injected with excretory/secretory products from mature, bile duct-derived worms. In mice, no obvious mouse strain variation in susceptibility to first infection existed and hypothymic nude mice were as susceptible to infection as intact mice. As determined by protection against death, vaccination with excretory/secretory products derived from immature P. hepatica was without effect in mice. It is concluded that ‘host protective antigens’, at least for rats, were present in the excretory/secretory products of immature F. hepatica larvae.
Epidemiologic features of Campylobacter infection among cats in the upper midwestern United States.

OBJECTIVE To describe the epidemiologic features of Campylobacter infection among cats in the Minneapolis-Saint Paul metropolitan area. DESIGN Prevalence survey. ANIMALS 152 cats examined at 3 private veterinary clinics and an animal humane society. PROCEDURES Fecal samples were submitted for bacterial culture for Campylobacter spp. To determine the duration of Campylobacter carriage, follow-up fecal samples were collected from cats with positive Campylobacter culture results. RESULTS Campylobacter organisms were cultured from 37 of the 152 (24%) fecal samples. Campylobacter isolates were identified as Campylobacter upsaliensis (29 cats), Campylobacter jejuni (2), and Campylobacter coli (1); species of the remaining 5 isolates could not be determined. Campylobacter organisms were isolated from 36 of the 122 (30%) cats that were < or = 1 year old but from only 1 of the 30 (3%) cats that were > 1 year old, and shedding was more common during the summer and fall months. No association between Campylobacter shedding and clinical signs of disease was identified. For 4 of 13 cats from which follow-up fecal samples were obtained, duration of Campylobacter carriage could not be determined because Campylobacter organisms were isolated from all follow-up samples. For the remaining 9 cats, median duration of Campylobacter carriage was 44 days. CONCLUSIONS AND CLINICAL RELEVANCE C. upsaliensis can commonly be isolated from the feces of overtly healthy kittens in the Midwest United States. Because carriage may be prolonged, veterinarians should encourage good hand hygiene among owners of cats, especially among owners with new kittens in their household.
Monitoring Signal Transduction in Cancer

This study targeted the development of a novel microarray tool to allow rapid determination of the expression levels of 58 different tyrosine kinase (tk) genes in small tumor samples. The goals were to define a reference probe for multi-sample comparison and to investigate the variability and reproducibility of the image acquisition and RT-PCR procedures. The small number of tk genes on our arrays enabled us to define a reference probe by artificially mixing all genes on the arrays. Such a probe provided contrast reference for comparative hybridization of control and sample DNA and enabled cross-comparison of more than two samples against one another. Comparison of signals generated from multiple scanning eliminated the concern of photo bleaching and scanner intrinsic noise. Tests performed with breast, thyroid, and prostate cancer samples yielded distinctive patterns and suggest the feasibility of our approach. Repeated experiments indicated reproducibility of such arrays. Up- or downregulated genes identified by this rapid screening are now being investigated with techniques such as in situ hybridization. (J Histochem Cytochem 49:1057–1058, 2001)
A comparison of position‐specific score matrices based on sequence and structure alignments

Sequence comparison methods based on position‐specific score matrices (PSSMs) have proven a useful tool for recognition of the divergent members of a protein family and for annotation of functional sites. Here we investigate one of the factors that affects overall performance of PSSMs in a PSI‐BLAST search, the algorithm used to construct the seed alignment upon which the PSSM is based. We compare PSSMs based on alignments constructed by global sequence similarity (ClustalW and ClustalW‐pairwise), local sequence similarity (BLAST), and local structure similarity (VAST). To assess performance with respect to identification of conserved functional or structural sites, we examine the accuracy of the three‐dimensional molecular models predicted by PSSM‐sequence alignments. Using the known structures of those sequences as the standard of truth, we find that model accuracy varies with the algorithm used for seed alignment construction in the pattern local‐structure (VAST) > local‐sequence (BLAST) > global‐sequence (ClustalW). Using structural similarity of query and database proteins as the standard of truth, we find that PSSM recognition sensitivity depends primarily on the diversity of the sequences included in the alignment, with an optimum around 30–50% average pairwise identity. We discuss these observations, and suggest a strategy for constructing seed alignments that optimize PSSM‐sequence alignment accuracy and recognition sensitivity.
Bureaucratic Migration Politics: German Support for Common EU Policies on Labour Migration

As a macrostructure, this article uses a bureaucratic politics framework to understand the preference formation of the German federal government on liberalising economic migration policies. This allows unpacking the process of preference formation and linking it to a number of causal factors, which, by influencing the costs and benefits distribution of the relevant actors, shape the position of the government. The article argues that the misfit between the existing national regulations for economic migration and European-level policies has to be zero – otherwise the economic and political adaptation costs for the actors involved are too high. A heated national debate on immigration is negatively related to governmental support for such measures, as the political costs of support skyrocket. Conversely, if the decision-making process happens bureaucratically, this helps to attain governmental support, as the political costs of doing so are kept minimal.