Miracle-dz/UniFAR-FTUs huggingface dataset:
Myeloperoxidase-derived Hypochlorous Acid Antagonizes the Oxidative Stress-mediated Activation of Iron Regulatory Protein 1*

Hypochlorous acid (HOCl) is a highly reactive product generated by the myeloperoxidase reaction during the oxidative burst of activated neutrophils, which is implicated in many bactericidal and cytotoxic responses. Recent evidence suggests that HOCl may also play a role in the modulation of redox sensitive signaling pathways. The short half-life of HOCl and the requirement for a continuous presence of H2O2 as a substrate for its myeloperoxidase-catalyzed generation make the study of HOCl-mediated responses very difficult. We describe here an enzymatic model consisting of glucose/glucose oxidase, catalase, and myeloperoxidase (GOX/CAT/MPO) that allows the controlled generation of both HOCl and H2O2 and thus, mimics the oxidative burst of activated neutrophils. By employing this model we show that HOCl prevents the H2O2-mediated activation of iron regulatory protein 1 (IRP1), a central post-transcriptional regulator of mammalian iron metabolism. Activated IRP1 binds to ®iron-responsive elements” (IREs) within the mRNAs encoding proteins of iron metabolism and thereby controls their translation or stability. The inhibitory effect of HOCl is not a result of a direct modification of IRP1 by this oxidant. Kinetics experiments provide evidence that HOCl intervenes with the signaling cascade, which results in the activation of IRP1. We further demonstrate that HOCl antagonizes the H2O2-mediated increase in the levels of transferrin receptor, which is a downstream target of IRP1. Our findings suggest that HOCl can modulate signaling pathways in a concerted action with H2O2. The GOX/CAT/MPO system provides a valuable tool for studying the regulatory function of HOCl.
ASB2α, an E3 Ubiquitin Ligase Specificity Subunit, Regulates Cell Spreading and Triggers Proteasomal Degradation of Filamins by Targeting the Filamin Calponin Homology 1 Domain*

Background: The E3 ubiquitin ligase ASB2α triggers proteasomal degradation of filamins and regulates cell spreading and differentiation. Results: ASB2α targets filamin's calponin homology 1 (CH1) domain, and mutations in CH1 render filamin ASB2α-resistant. Conclusion: ASB2α-resistant filamins protect cells from ASB2α-mediated inhibition of spreading. Significance: ASB2α exerts its effect on cell spreading via targeted degradation of filamins. Filamins are actin-binding and cross-linking proteins that organize the actin cytoskeleton and anchor transmembrane proteins to the cytoskeleton and scaffold signaling pathways. During hematopoietic cell differentiation, transient expression of ASB2α, the specificity subunit of an E3-ubiquitin ligase complex, triggers acute proteasomal degradation of filamins. This led to the proposal that ASB2α regulates hematopoietic cell differentiation by modulating cell adhesion, spreading, and actin remodeling through targeted degradation of filamins. Here, we show that the calponin homology domain 1 (CH1), within the filamin A (FLNa) actin-binding domain, is the minimal fragment sufficient for ASB2α-mediated degradation. Combining an in-depth flow cytometry analysis with mutagenesis of lysine residues within CH1, we find that arginine substitution at each of a cluster of three lysines (Lys-42, Lys-43, and Lys-135) renders FLNa resistant to ASB2α-mediated degradation without altering ASB2α binding. These lysines lie within previously predicted actin-binding sites, and the ASB2α-resistant filamin mutant is defective in targeting to F-actin-rich structures in cells. However, by swapping CH1 with that of α-actinin1, which is resistant to ASB2α-mediated degradation, we generated an ASB2α-resistant chimeric FLNa with normal subcellular localization. Notably, this chimera fully rescues the impaired cell spreading induced by ASB2α expression. Our data therefore reveal ubiquitin acceptor sites in FLNa and establish that ASB2α-mediated effects on cell spreading are due to loss of filamins.
Genetic Validation of Aminoacyl-tRNA Synthetases as Drug Targets in Trypanosoma brucei

ABSTRACT Human African trypanosomiasis (HAT) is an important public health threat in sub-Saharan Africa. Current drugs are unsatisfactory, and new drugs are being sought. Few validated enzyme targets are available to support drug discovery efforts, so our goal was to obtain essentiality data on genes with proven utility as drug targets. Aminoacyl-tRNA synthetases (aaRSs) are known drug targets for bacterial and fungal pathogens and are required for protein synthesis. Here we survey the essentiality of eight Trypanosoma brucei aaRSs by RNA interference (RNAi) gene expression knockdown, covering an enzyme from each major aaRS class: valyl-tRNA synthetase (ValRS) (class Ia), tryptophanyl-tRNA synthetase (TrpRS-1) (class Ib), arginyl-tRNA synthetase (ArgRS) (class Ic), glutamyl-tRNA synthetase (GluRS) (class 1c), threonyl-tRNA synthetase (ThrRS) (class IIa), asparaginyl-tRNA synthetase (AsnRS) (class IIb), and phenylalanyl-tRNA synthetase (α and β) (PheRS) (class IIc). Knockdown of mRNA encoding these enzymes in T. brucei mammalian stage parasites showed that all were essential for parasite growth and survival in vitro. The reduced expression resulted in growth, morphological, cell cycle, and DNA content abnormalities. ThrRS was characterized in greater detail, showing that the purified recombinant enzyme displayed ThrRS activity and that the protein localized to both the cytosol and mitochondrion. Borrelidin, a known inhibitor of ThrRS, was an inhibitor of T. brucei ThrRS and showed antitrypanosomal activity. The data show that aaRSs are essential for T. brucei survival and are likely to be excellent targets for drug discovery efforts.
Does Mindfulness Meditation Improve Anxiety and Mood Symptoms? A Review of the Controlled Research

Objective: To review the impact of mindfulness-based stress reduction (MBSR) on symptoms of anxiety and depression in a range of clinical populations. Method: Our review included any study that was published in a peer-reviewed journal, used a control group, and reported outcomes related to changes in depression and anxiety. We extracted the following key variables from each of the 15 studies identified: anxiety or depression outcomes after the MBSR program, measurement of compliance with MBSR instructions, type of control group included, type of clinical population studied, and length of follow-up. We also summarized modifications to the MBSR program. Results: Measures of depression and anxiety were included as outcome variables for a broad range of medical and emotional disorders. Evidence for a beneficial effect of MBSR on depression and anxiety was equivocal. When active control groups were used, MBSR did not show an effect on depression and anxiety. Adherence to the MBSR program was infrequently assessed. Where it was assessed, the relation between practising mindfulness and changes in depression and anxiety was equivocal. Conclusions: MBSR does not have a reliable effect on depression and anxiety.
E-commerce and the market structure of the recorded music industry

ABSTRACT In this article, we study the impact of the development of e-commerce on the concentration of the recorded music industry in France, for the period 2003–2010. First, we find that over the whole period, CD sales, measured at the distributor level, are less concentrated online than offline. Second, we find that sales concentration online has increased between the early period of e-commerce (2003–2006) and the later period (2007–2010).
Older Adults' Perceptions of Supporting Factors of Trust in a Robot Care Provider

The older adult population is increasing worldwide, leading to an increased need for care providers. An insufficient number of professional caregivers will lead to a demand for robot care providers to mitigate this need. Trust is an essential element for older adults and robot care providers to work effectively. Trust is context dependent. Therefore, we need to understand what older adults would need to trust robot care providers, in this specific home-care context. This mixed methods study explored what older adults, who currently receive assistance from caregivers, perceive as supporting trust in robot care providers within four common home-care tasks: bathing, transferring, medication assistance, and household tasks. Older adults reported three main dimensions that support trust: professional skills, personal traits, and communication. Each of these had subthemes including those identified in prior human-robot trust literature such as ability, reliability, and safety. In addition, new dimensions perceived to impact trust emerged such as the robot’s benevolence, the material of the robot, and the companionability of the robot. The results from this study demonstrate that the older adult-robot care provider context has unique dimensions related to trust that should be considered when designing robots for home-care tasks.
Osteitis condensans ilii in differential diagnosis of patients with chronic low back pain: a review of the literature

Osteitis condensans ilii (OCI) is a benign pathology causing chronic back and hip pain. Although the definitive cause is uncertain, mechanical stress is a significant factor in the development of the disease. Bilateral involvement of the sacroiliac joint is typical. We describe a case of unilateral OCI with unilateral sclerosis observed at radiography in a 34-year-old patient presenting with chronic back and hip pain, together with a review of the literature.
Loss of Erk3 function in mice leads to intrauterine growth restriction, pulmonary immaturity, and neonatal lethality

Extracellular signal-regulated kinase 3 (Erk3) is an atypical member of the mitogen-activated protein (MAP) kinase family. No function has yet been ascribed to this MAP kinase. Here we show that targeted disruption of the Mapk6 gene (encoding Erk3) leads to intrauterine growth restriction, associated with marked pulmonary hypoplasia, and early neonatal death during the first day of life. Around 40% of Erk3−/− neonates die within minutes after birth from acute respiratory failure. Erk3-deficient mice have normal lung-branching morphogenesis, but show delayed lung maturation characterized by decreased sacculation, atelectasis, and defective type II pneumocyte differentiation. Interestingly, in utero administration of glucocorticoid promoted fetal lung maturity and rescued differentiation of type II cells, but failed to alter the neonatal lethality. We observed that loss of Erk3 retards intrauterine growth, as reflected by a marked reduction in fetal lung, heart, and liver weights, and by low body weight at birth. Importantly, we found that insulin-like growth factor (IGF)-2 levels are decreased in the serum of Erk3-deficient mice. Our findings reveal a critical role for Erk3 in the establishment of fetal growth potential and pulmonary function in the mouse.
Pulmonary blast injury in mice: A novel model for studying blast injury in the laboratory using laser‐induced stress waves

Primary blast injury is produced by shock waves. Blast injuries to lungs are extremely critical threats to survival, but their etiology is largely undefined. The majority of animal models for these injuries use explosive or complex experimental settings, limiting the laboratory study of blast injury. The aim of this study was to establish a small‐animal model for blast injuries, using laser‐induced stress waves (LISWs) with high controllability, high reproducibility, and easy experimental settings.
Morphological Integration of the Orbital Region in a Human Ontogenetic Sample

Most studies on craniofacial morphology have focused on adult individuals, but patterns of variation are the outcome of genetic and epigenetic variables that interact throughout ontogeny. Among cranial regions, the orbits exhibit morphological variation and occupy an intermediate position between neurocranial and facial structures. The main objective of this work was to analyze postnatal ontogenetic variation and covariation in the morphology of the orbital region in a cross‐sectional series of humans from 0 to 31 years old. Landmarks and semilandmarks were digitized on the orbital rim, as well as in neighboring neural and facial structures. Data were analyzed using geometric morphometrics. Results indicated that orbital size increases during the first years of postnatal life, while the shape of the orbital aperture does not change significantly with age. In general, the pattern and magnitude of shape covariation do not vary markedly during postnatal life although some subtle shifts were documented. Additionally, the shape of the orbital aperture is more related to the anterior neurocranium than to zygomatic structures, even when the allometry is adjusted. Although we expected some influence from postnatal craniofacial growth and from some functional factors, such as mastication, on the development of the orbits, this assumption was not completely supported by our results. As a whole, our findings are in line with the prediction of an early influence of the eyes and extraocular tissues on orbital morphology, and could be interpreted in relation to processes promoting early neural development that coordinately affects orbital traits and the neurocranial skeleton. Anat Rec, 299:70–80, 2016. © 2015 Wiley Periodicals, Inc.
DOĞRUDAN SERMAYE YATIRIMLARI, TİCARİ DIŞA AÇIKLIK VE EKONOMİK BÜYÜME ARASINDAKİ İLİŞKİ: TÜRKİYE VE BRICS ÜLKELERİ ÖRNEĞİ THE RELATIONSHIP BETWEEN FOREIGN DIRECT INVESTMENT, TRADE OPENNESS AND ECONOMIC GROWTH: THE CASE OF TURKEY AND BRICS COUNTRIES

OZ: Dogrudan sermaye yatirimlari ve ekonomik buyume iliskisi gelismis ve gelismekte olan ulkeler icin tartisilan bir konudur. Bu calismanin amaci, BRICS ulkelerinde ve Turkiye'de 1982-2013 doneminde dogrudan sermaye yatirimlari, ticari disa aciklik ve ekonomik buyume arasindaki iliskiyi incelemektir. Iliskiyi incelemek amaciyla CADF birim kok testi ve Emirmahmutoglu ve Kose (2011) nedensellik testi kullanilmistir. Sonuclar ekonomik buyumeden dogrudan yabanci yatirimlara dogru tek yonlu nedensellik oldugunu gostermistir. Ayrica ekonomik buyume ve ticari disa aciklik arasinda cift yonlu nedensellik iliskisi oldugu tespit edilmistir. Dogrudan yabanci yatirimlar ve ticari disa aciklik arasinda cift yonlu nedensellik iliskisi saptanmistir. Bireysel ulke sonuclarina gore ise karma bulgular elde edilmistir. Anahtar Kelimeler: Ekonomik Buyume, Dogrudan Sermaye Yatirimlari, Ticari Disa Aciklik, Panel Nedensellik ABSTRACT: Relationship between foreign direct investment and economic growth for developed and developing countries is controversial issue. The aim of this study is to examine relationship between foreign direct investment, trade openness and economic growth in the BRICS countries and in Turkey during the period 1982-2013. CADF unit root test and Emirmahmutoglu ve Kose (2011) causality test are employed to examine the relationship. The results indicate that there is uni-directional causality running from economic growth to foreign direct investment. Besides, there is found bi-directional causality between economic growth and trade openness. There is detected bi-directional causality between foreign direct investment and trade openness. According to individual country results it is obtained mixed evidence.
Ontology-Driven Information System Design

Conventional information systems are built on top of a relational database that requires its data model to be stable. This lack of adaptability is very restrictive for systems that manipulate evolving or heterogenous knowledge. The authors of this paper faced this issue at the time of the development of an information system of structural failures. As knowledge on structural failures is very heterogeneous and dynamic, it is practically impossible to define a stable database schema ahead. The widely accepted alternative to relational databases are semantic web ontologies. However, software developers miss adequate frameworks and design methodologies in this area. This paper tries to fill the gap by proposing a methodology for designing ontology-backed software applications that make the ontology possible to evolve while being exploited by one or more applications at the same time. The methodology relies on a contract between the ontology and the application that is formally expressed in terms of integrity constraints. Violation of the contract means either that the ontology evolved in a way that is incompatible with the particular application or the application produced invalid data. In the first case, the ontology change must either be rolled back, or the application needs to be upgraded. In the second case, the user has to modify entered data to fulfill the contract. Furthermore, this paper elaborates an object ontological mapping, transaction management, and efficient querying API. A reference Java implementation of the methodology and the proof-of-concept application in the civil engineering domain is introduced at the end of the paper.
High-Extinction-Ratio Multipassband Filter With Flat-Top and Low-Dispersion

This paper proposes a novel structure to realize a high-extinction-ratio multipassband filter (HERMPF) with flat-top, low dispersion, and large passband and stopband bandwidths. Spectrum and chromatic dispersion of the HERMPF are given under ideal conditions, which show that such a filter has excellent performance. Analysis on fabrication tolerances is given as well, focusing on factors such as the length mismatch and loss which degrade the spectral and chromatic dispersion performances of HERMPF in practice. A single-cavity ring resonator is inserted into either arm of a Mach-Zehnder interferometer to form a Mach-Zehnder ring resonator interferometer (MZRRI), which is an infinite-impulse- response half-band filter with two complementary channels (even and odd channels). MZRRI is the core element of HERMPF which determines the spectral performance. A set of multicavity Gires-Tournois etalon composed of cascaded Sagnac loop mirrors is proposed as the tunable dispersion compensator and fully reflective mirror in HERMPF. The third main part of HERMPF is a 1 × 2 switch, which is used to select the even/odd channel of MZRRI. Thus, HERMPF can be used as an even/odd channel switch.
Fragility Analysis of Highway Bridges Based on Long‐Term Monitoring Data

Abstract: In the probabilistic seismic risk assessment of highway transportation networks, fragility curves are used to represent the vulnerability of a bridge. Because these networks have hundreds or thousands of bridges, it is not possible to study each bridge individually. Instead, bridges with similar properties are grouped together and are represented by the same fragility curve. However, this approach may be inadequate at times for different reasons. For instance, bridges with similar geometrical and material properties could have different age and/or could deteriorate at a different rate. Moreover, certain bridges are unique such as a cable stayed bridge or a suspension bridge. In this study, fragility curves are calculated based not only on the geometry and material properties but also on vibration data recorded by a structural health monitoring system. The fragility curves are used to track changes of the structural parameters of a bridge throughout its service life. Based on vibration data the fragility curves are updated reflecting a change in structural parameters. Fragility curves based on vibration data, whenever these are available, represent the vulnerability of a bridge with greater accuracy than fragility curves based only on the geometry and material properties. This article demonstrates the applicability of structural health monitoring to generate more reliable fragility curves. This is useful not only for bridges that are unique, which are usually the first to be instrumented, but for every instrumented bridge as well.
Viral Evolution in Response to the Broad-Based Retroviral Protease Inhibitor TL-3

ABSTRACT TL-3 is a protease inhibitor developed using the feline immunodeficiency virus protease as a model. It has been shown to efficiently inhibit replication of human, simian, and feline immunodeficiency viruses and therefore has broad-based activity. We now demonstrate that TL-3 efficiently inhibits the replication of 6 of 12 isolates with confirmed resistance mutations to known protease inhibitors. To dissect the spectrum of molecular changes in protease and viral properties associated with resistance to TL-3, a panel of chronological in vitro escape variants was generated. We have virologically and biochemically characterized mutants with one (V82A), three (M46I/F53L/V82A), or six (L24I/M46I/F53L/L63P/V77I/V82A) changes in the protease and structurally modeled the protease mutant containing six changes. Virus containing six changes was found to be 17-fold more resistant to TL-3 in cell culture than was wild-type virus but maintained similar in vitro replication kinetics compared to the wild-type virus. Analyses of enzyme activity of protease variants with one, three, and six changes indicated that these enzymes, compared to wild-type protease, retained 40, 47, and 61% activity, respectively. These results suggest that deficient protease enzymatic activity is sufficient for function, and the observed protease restoration might imply a selective advantage, at least in vitro, for increased protease activity.
Synergistic and Regulatory Effects of Orbitofrontal Cortex on Amygdala‐Dependent Appetitive Behavior

Abstract: This paper will review two avenues of our research in marmosets that have focused on the role of the orbitofrontal cortex (OFC) in amygdala‐dependent appetitive behavior. The first demonstrates the important contribution of both the OFC and the amygdala to conditioned reinforcement (CRF). The second reveals the regulatory effects of the OFC on amygdala‐dependent autonomic and behavioral arousal in appetitive conditioning. The process of CRF is one way in which an environmental cue can guide emotional behavior. As a consequence of its previous relationship with reward, a cue can take on affective value and reinforce behavior. Lesion studies in marmosets are described that show that CRF is dependent upon both the amygdala and OFC. The synergistic interactions between these structures that have been shown to underlie other aspects of reward processing are then considered with respect to CRF. The results are contrasted with those that show the importance of the OFC in suppressing positive affective responses elicited by the amygdala in response to a conditioned stimulus (CS). Specifically, it will be shown that the OFC is involved in the rapid suppression of conditioned autonomic arousal upon CS withdrawal and in the co‐ordination of conditioned autonomic and behavioral responses when adapting to changing reward contingencies. It will be argued that, overall, the OFC plays a critical role in the context‐dependent regulation of positive affective responding governed by external cues, in keeping with a role in executive control.
Skilled Immigration, Innovation, and the Wages of Native‐Born Americans

The paper examines the effects of skilled immigration on wages that can be credited to immigrants’ contribution to innovation. Using both individual and state-level datasets from the United States, we find a significant and positive effect of immigration on wages that is attributable to skilled immigrants’ contribution to innovation. Our results confirm previous findings that immigrants contribute substantially to the host economy's innovation, which is a major driver of technological progress and productivity growth. When we augment the analysis to an immigration–innovation–wages nexus, the results suggest that as the share of skilled immigrants in a particular skill group increases, the wages of both natives and immigrants in that group also get a positive boost. We also identify evidence in favor of a positive spillover effect of skilled immigrants on a state's wage level of all workers, including those who do not directly contribute to innovation.