Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of the GLT‐1 subtype of glutamate transporter in glutamate homeostasis: the GLT‐1‐preferring inhibitor WAY‐855 produces marginal neurotoxicity in the rat hippocampus

Glutamate is the major excitatory neurotransmitter in the central nervous system and is tightly regulated by cell surface transporters to avoid increases in concentration and associated neurotoxicity. Selective blockers of glutamate transporter subtypes are sparse and so knock‐out animals and antisense techniques have been used to study their specific roles. Here we used WAY‐855, a GLT‐1‐preferring blocker, to assess the role of GLT‐1 in rat hippocampus. GLT‐1 was the most abundant transporter in the hippocampus at the mRNA level. According to [3H]‐l‐glutamate uptake data, GLT‐1 was responsible for approximately 80% of the GLAST‐, GLT‐1‐, and EAAC1‐mediated uptake that occurs within dissociated hippocampal tissue, yet when this transporter was preferentially blocked for 120 h with WAY‐855 (100 µm), no significant neurotoxicity was observed in hippocampal slices. This is in stark contrast to results obtained with TBOA, a broad‐spectrum transport blocker, which, at concentrations that caused a similar inhibition of glutamate uptake (10 and 30 µm), caused substantial neuronal death when exposed to the slices for 24 h or longer. Likewise, WAY‐855, did not significantly exacerbate neurotoxicity associated with simulated ischemia, whereas TBOA did. Finally, intrahippocampal microinjection of WAY‐855 (200 and 300 nmol) in vivo resulted in marginal damage compared with TBOA (20 and 200 nmol), which killed the majority of both CA1–4 pyramidal cells and dentate gyrus granule cells. These results indicate that selective inhibition of GLT‐1 is insufficient to provoke glutamate build‐up, leading to NMDA receptor‐mediated neurotoxic effects, and suggest a prominent role of GLAST and/or EAAC1 in extracellular glutamate maintenance.
The institutional factors of strategic development and the tactical regulation of nanotechnology

The analysis of influence of institutional factors on development of technologies is carried out. The generating role of institutions in technological progress is proved. The general logic of an institutionalization of new technological way is presented on an example of nanotechnologies.Institutes are the "weak link" of the concepts and theories of the evolution of technology and technological structures. Most modern theorists of evolutionary economics are focused mainly on the study of the dynamics and forms of scientific and technological progress, especially the mechanisms of nucleation and diffusion of large "clusters" of innovation.In their turn, the institutional economists have concentrated on the analysis of factors and ways to minimize the transaction costs sustained interaction of agents and their organizations "in the high-tech world with a huge degree of specialization and division of labor other than impersonal exchange" (North 1997). In their works only relate to the institutional structure and infrastructure of innovative development, although, as noted by Nelson (2002), the concept of national and regional innovation systems is institutional in nature just on this fact is rarely emphasizes the attention of scientists. As a result, institutional forms and mechanisms of technological evolution is very poorly understood, and their analysis is based on very general ideas about the institutes and institutions.
The chitinase-like proteins breast regression protein-39 and YKL-40 regulate hyperoxia-induced acute lung injury.

RATIONALE Prolonged exposure to 100% O(2) causes hyperoxic acute lung injury (HALI), characterized by alveolar epithelial cell injury and death. We previously demonstrated that the murine chitinase-like protein, breast regression protein (BRP)-39 and its human homolog, YKL-40, inhibit cellular apoptosis. However, the regulation and roles of these molecules in hyperoxia have not been addressed. OBJECTIVES We hypothesized that BRP-39 and YKL-40 (also called chitinase-3-like 1) play important roles in the pathogenesis of HALI. METHODS We characterized the regulation of BRP-39 during HALI and the responses induced by hyperoxia in wild-type mice, BRP-39-null (-/-) mice, and BRP-39(-/-) mice in which YKL-40 was overexpressed in respiratory epithelium. We also compared the levels of tracheal aspirate YKL-40 in premature newborns with respiratory failure. MEASUREMENTS AND MAIN RESULTS These studies demonstrate that hyperoxia inhibits BRP-39 in vivo in the murine lung and in vitro in epithelial cells. They also demonstrate that BRP-39(-/-) mice have exaggerated permeability, protein leak, oxidation, inflammatory, chemokine, and epithelial apoptosis responses, and experience premature death in 100% O(2). Lastly, they demonstrate that YKL-40 ameliorates HALI, prolongs survival in 100% O(2), and rescues the exaggerated injury response in BRP-39(-/-) animals. In accord with these findings, the levels of tracheal aspirate YKL-40 were lower in premature infants treated with hyperoxia for respiratory failure who subsequently experienced bronchopulmonary dysplasia or death compared with those that did not experience these complications. CONCLUSIONS These studies demonstrate that hyperoxia inhibits BRP-39/YKL-40, and that BRP-39 and YKL-40 are critical regulators of oxidant injury, inflammation, and epithelial apoptosis in the murine and human lung.
ALTRUISM IN MENDELIAN POPULATIONS DERIVED FROM SIBLING GROUPS: THE HAYSTACK MODEL REVISITED

A group‐selection model is presented in which each group is initiated by a single fertilized female and persists for several generations before dispersal. Maynard Smith (1964) concluded that altruism could not plausibly evolve under these circumstances. I show that his conclusion is an artifact of a simplifying assumption that amounts to a worst‐case scenario for group selection. When the standard donor‐recipient equations for altruistic behavior are used in Maynard Smith's model, Mendelian populations derived from sibling groups are often more favorable for the evolution of altruism than are the sibling groups themselves. In general, long‐term and large‐scale aspects of population structure may at times be important in the evolution of altruistic and other group‐advantageous behaviors.
Substantially elevating the levels of αB‐crystallin in spinal motor neurons of mutant SOD1 mice does not significantly delay paralysis or attenuate mutant protein aggregation

There has been great interest in enhancing endogenous protein maintenance pathways such as the heat‐shock chaperone response, as it is postulated that enhancing clearance of misfolded proteins could have beneficial disease modifying effects in amyotrophic lateral sclerosis and other neurodegenerative disorders. In cultured cell models of mutant SOD1 aggregation, co‐expression of αB‐crystallin (αB‐crys) has been shown to inhibit the formation of detergent‐insoluble forms of mutant protein. Here, we describe the generation of a new line of transgenic mice that express αB‐crys at > 6‐fold the normal level in spinal cord, with robust increases in immunoreactivity throughout the spinal cord grey matter and, specifically, in spinal motor neurons. Surprisingly, spinal cords of mice expressing αB‐crys alone contained 20% more motor neurons per section than littermate controls. Raising αB‐crys by these levels in mice transgenic for either G93A or L126Z mutant SOD1 had no effect on the age at which paralysis developed. In the G93A mice, which showed the most robust degree of motor neuron loss, the number of these cells declined by the same proportion as in mice expressing the mutant SOD1 alone. In paralyzed bigenic mice, the levels of detergent‐insoluble, misfolded, mutant SOD1 were similar to those of mice expressing mutant SOD1 alone. These findings indicate that raising the levels of αB‐crys in spinal motor neurons by 6‐fold does not produce the therapeutic effects predicted by cell culture models of mutant SOD1 aggregation.
Parents' views and government rhetoric about schooling : beyond simple notions of exclusion and marginalisation

Against the background of continuing political rhetoric promising better outcomes for disadvantaged children and advocating the importance of parents’ roles, this study gave voice to a group of parents from a disadvantaged community. The author’s experiences, as a headteacher in challenging schools, of disadvantaged children’s outcomes not improving coupled with diminishing parental voice, provided the passion which drove this study. The participant parents’ children attended a non-selective secondary school within a highly selective authority in England. Through an innovative combination of a Facebook group and follow up interviews, the parents chose and discussed schooling issues which they identified as relevant to their experiences. The themes interpreted from the parents’ discussions were used to analyse government speeches in order to explore the extent to which there existed a relationship between parents’ views and government rhetoric. Interpretations of the parents’ views, and their relationship with government rhetoric, highlight three contentions which add to current discourses about disadvantaged parents’ experiences of schooling. Firstly, notions that exclusion and marginalisation cause parents’ disadvantage, do not fully explain the complexity of the participant parents’ views and their relationship with government rhetoric. Secondly, the thesis proposes the existence of two separate fields of schooling. An ambitious field which the parents consciously resist and are excluded from, and a less ambitious field focused on disadvantage, which the participant parents’ views are most aligned with. Thirdly, the existence of two separate fields of schooling is argued to evidence political intentionality, which is demonstrated by speeches adopting deterministic and less ambitious rhetoric when focused on issues of disadvantage. Finally, the thesis adopts a notion of social justice which advocates parents’ participation and roles for organic intellectuals (Gramsci, 1971), as a route to ameliorating experiences and outcomes for disadvantaged parents and children.
Burn injuries among infants and toddlers in the United States, 1997-2002.

OBJECTIVES To determine the magnitude and causes of unintentional burn injuries attributed to hot objects or substances among children aged birth to 4 years in the United States. METHODS Data were obtained from the National Hospital Ambulatory Medical Care System. RESULTS Annually, 78,000 infants and toddlers were treated in ambulatory care settings for injuries due to contact with a hot object or substance. Hot foods, curling irons, or clothing irons were the main causes of burns. CONCLUSIONS Due to the varied causes of burns, a combination of health education and product design interventions are likely necessary to prevent these injuries.
Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is a rare superficial sarcoma usually affecting the trunk, with significant risk of local recurrence. It is characterized by the presence of ring chromosomes or chromosomal translocations fusing the promoter of the collagen gene COL1A1 to the platelet‐derived growth factor β‐chain gene PDGFB, increasing the production of PDGF locally and promoting autocrine or paracrine tumor growth. Fewer than 5% of patients with DFSP develop metastatic sarcoma, with a poor subsequent prognosis. Imatinib (STI‐571) was developed as an inhibitor of the PDGF receptor tyrosine kinase and has proven clinical activity against chronic myelogenous leukemia (expressing bcr‐abl) and gastrointestinal stromal tumors (expressing c‐kit). We describe 2 patients with metastatic and unresectable metastases from DFSP treated with imatinib. After confirmation of negative CD117 status of 2 sarcomas arising from DFSP, patients were given imatinib 400 mg po qd and assessed at regular intervals for their tolerance and response to therapy. One patient had a transient response, then progressed rapidly and died of disease. Another patient showed a partial response to therapy after 2 months, with resolution of superior vena cava syndrome and shrinking of metastatic lung lesions. His response is ongoing after 6 months of therapy. These clinical data confirm findings from models of DFSP and support the use of imatinib in the rare setting of metastatic DFSP. Imatinib may be useful for patients with locally advanced DFSP, when other options for local therapy are limited. © 2002 Wiley‐Liss, Inc.
The energy dependence of lithium formate EPR dosimeters for clinical electron beams

The objective of this study was to investigate the potential of using polycrystalline lithium formate for EPR (electron paramagnetic resonance) dosimetry of clinical electron beams, with the main focus on the dose-to-water energy response. Lithium formate dosimeters were irradiated using 60Co γ-rays and 6–20 MeV electrons in a PMMA phantom to doses in the range of 3–9 Gy. A plane-parallel ion chamber was used for water-based absolute dosimetry. In addition, the electron/photon transport was simulated using the EGSnrc Monte Carlo code. From the EPR measurements, the standard deviation of single dosimeter readings was 1.2%. The experimental energy response (the lithium formate dosimeter reading per absorbed dose to water for electrons relative to that for 60Co γ rays) was nearly independent of the electron energy and on average 0.99 ± 0.03. The Monte Carlo calculated energy response was on average 0.5% higher than the experimental energy response, the difference being not significant. Simulations with water and polystyrene as irradiation media indicated that the energy response of lithium formate dosimeters was nearly independent of the phantom materials. In conclusion, lithium formate EPR dosimetry of clinical electron beams provides precise dose measurements with low dependence on the electron energy.
Composite indicators of sustainable urban mobility: Estimating the rankings frequency distribution combining multiple methodologies

ABSTRACT The contribution of this paper consists in applying several techniques to estimate a composite indicator of sustainable urban mobility for 116 Italian provincial towns, as proposed by Luzzati and Gucciardi (2015). The aim is to provide the decision-maker with a richer set of information on sustainable mobility, making explicit the impact of the techniques used on the values obtained. A set of 16 indicators with a nested structure has been selected and 33 combinations of normalization, weighting, and aggregation techniques are applied. The results are presented by city, by city groupings (size and location), and focusing on the ten largest Italian cities. It is found that small cities perform better in terms of sustainable mobility than medium or large cities. As expected, in some cases (e.g., Milan) the intervals of the results obtained are quite large, indicating that the techniques used to normalize, weight, and aggregate the indicators highly affect the performance indexes. In other cases (e.g., Rome) the results are stable across methodologies.
EFFECTS OF PROBIOTIC INTAKE ON INTESTINAL BIFIDOBACTERIA OF CELIAC PATIENTS.

BACKGROUND Healthy individuals exhibit a significantly higher concentration of faecal bifidobacteria in comparison to celiac patients. Even though there are potential benefits in probiotic usage, they have been little explored as an adjunctive therapy in celiac disease. OBJECTIVE This study aimed at the comparison of faecal bifidobacteria concentration and pH among celiac patients and healthy subjects before and after the daily intake of 100 g of yogurt containing probiotic for a thirty-day period. METHODS Feces from 17 healthy subjects and 14 celiac patients were analyzed, in which stool culture was performed for the isolation and quantification of faecal bifidobacteria. Furthermore, Gram's method was employed for the microscopic analysis of the colonies, while the identification of the Bifidobacterium genus was made through determination of the fructose-6-phosphate phosphoketolase enzyme. Faecal pH was measured using a calibrated pHmeter. RESULTS Faecal bifidobacteria concentration before probiotic consumption was significantly higher in healthy individuals (2.3x108±6.3x107 CFU/g) when compared to celiac patients (1.0x107±1.7x107 CFU/g). Faecal pH values did not show a significant difference. After the daily consumption of probiotic-containing yogurt both groups showed a significant increase in the concentration of faecal bifidobacteria, but healthy subjects presented significantly higher bifidobacteria concentrations (14.7x108±0.2x108 CFU/g) than the celiac group (0.76x108±0.1x108 CFU/g). The obtained pH values from both groups were not significantly different, being 7.28±0.518 for the celiac patients and 7.07±0.570 for healthy individuals after the probiotic intake. CONCLUSION The probiotic supplementation significantly increased the number of bifidobacteria in the feces of celiac patients, although it was not sufficient to reach the concentration found in healthy individuals prior to its consumption.
Fetal Mouse Cyp1b1 and Transplacental Carcinogenesis from Maternal Exposure to Dibenzo(a,l)pyrene

Abstract Dibenzo(a,l)pyrene (DBP) is among the most potent carcinogenic polycyclic aromatic hydrocarbons. Previously, we showed that DBP administration to pregnant mice resulted in high mortality of offspring from an aggressive T-cell lymphoma. All mice that survive to 10 months of age exhibit lung tumors with high multiplicity. Recombinant cytochrome P450 (cyp) 1b1 from mice and the homologue 1B1 in humans exhibit high activity toward the metabolic activation of DBP. Targeted disruption of the cyp1b1 gene protects against most DBP-dependent cancers. Mice heterozygous for the disrupted cyp1b1 allele were used to examine the effect of cyp1b1 gene dosage on DBP transplacental carcinogenesis. Dams were treated with 1 or 15 mg/kg of DBP or 50 mg/kg of benzo(a)pyrene. Cyp1b1-null offspring did not develop lymphoma, whereas wild-type and heterozygous siblings, born to dams given the high dose of DBP, exhibited significant mortalities between 10 and 30 weeks of age. At 10 months, all groups had lung adenomas or carcinomas [9.5%, 40.3%, 25.6%, and 100% incidences for controls, benzo(a)pyrene, 1 and 15 mg/kg DBP, respectively]. Cyp1b1 status did not alter benzo(a)pyrene-dependent carcinogenesis. At 1 mg/kg DBP, cyp1b1 status altered the incidence of lung tumors (19.0, 27.8, and 28.6% for nulls, heterozygous, and wild-type, respectively). At 15 mg/kg, tumor multiplicities in cyp1b1 wild-type (9.3) and heterozygous (9.5) offspring were nearly twice that of cyp1b1-null siblings (5.0). These data confirm that cyp1b1 bioactivation of DBP occurs in fetal target tissues, following transplacental exposure, with the thymus and lung as primary and secondary targets, respectively.
A Continuous Return Model for the Low-Volatility andLow-Beta Anomalies

This study shows that a “rational,” capital asset pricing model (CAPM) type of positive relationship between short-horizon expected arithmetic return and risk can lead to a negative long-horizon relationship between compound annual return and risk (whether risk is measured by volatility or beta). This result follows from the stochastic portfolio theory relationship that a stock’s growth rate is less than its expected arithmetic return by approximately one-half its variance of return. The negative long-horizon relationships between return mean and volatility/beta often have been noted and characterized as the low-volatility and low-beta anomalies. Thus, these characterizations may be problematic.
Optimal selection of dental implant for different bone conditions based on the mechanical response.

PURPOSE Bone quality varies from one patient to another extensively. Young's modulus may deviate up to 40% of normal bone quality, which results into alteration of bone stiffness immensely. The prime goal of this study is to design the optimum dental implant considering the mechanical response at bone implant interfaces for a patient with specific bone quality. METHOD 3D models of mandible and natural molar tooth were prepared from CT scan data, while dental implants were modelled using different diameter, length and porosity and FE analysis was carried out. Based on the variation in bone density, five different bone qualities were considered. First, failure analysis of implants, under maximum biting force of 250 N had been performed. Next, the implants that remained were selected for observation of mechanical response at bone implant interfaces under common chewing load of 120 N. RESULT Maximum Von Mises stress did not surpass the yield strength of the implant material (TiAl4V). However, factor of safety of 1.5 was considered and all but two dental implants survived the design stress or allowable stress. Under 120 N load, distribution of Von Mises stress and strain at the boneimplant interface corresponding to the rest of the implants for five bone conditions were obtained and enlisted. CONCLUSION Implants exhibiting interface strain within 1500-3000 microstrain range show the best bone remodelling and osseointegration. So, implant models having this range of interface strains were selected corresponding to the particular bone quality. A set of optimum dental implants for each of the bone qualities were predicted.
Monetary Policy and Anti‐Cyclical Bank Capital Regulation

The financial crisis of 2008–2009 revived attention given to booms and busts in bank credit, and their effects on real activity. This interest sparked two different strands of research in macro. The first one focuses on monetary policy in the context of financial frictions. The second studies capital regulation in banking. To the best of our knowledge, so far these two topics have mostly been studied in isolation from each other. Thus, we still lack an understanding of how monetary policy and bank capital regulation interact in the presence of financial fragility. This paper aims to contribute to furthering this understanding. Specifically, we ask how the monetary policy rule should look like in the presence of cyclical capital requirements. We extend the dynamic stochastic general equilibrium model with bank capital in Aliaga‐Diaz and Olivero by introducing price rigidities in the spirit of the New‐Keynesian literature. We find that: First, anti‐cyclical requirements have important stabilization properties relative to the case of constant requirements. This is true for all types of fluctuations that we study, which include those caused by productivity, preference, fiscal, monetary, and financial shocks. Second, output and consumption volatilities present in the no regulation economy can be recovered with anti‐cyclical requirements as long as the policy rate responds only slightly to credit spreads. Third, monetary policy rules that respond to credit conditions also perform better in terms of welfare. (JEL E32, E44)