pinecone/core-2020-05-10-deduplication huggingface dataset:
Quantitative determination of the antitumor alkyl ether phospholipid edelfosine by reversed-phase liquid chromatography–electrospray mass spectrometry: application to cell uptake studies and characterization of drug delivery systems

El pdf del artículo es el manuscrito revisado.Edelfosine is a synthetic alkyl ether phospholipid that represents a promising class of antitumor agents. However, analytical methods to measure these type compounds are scarce. The lack of a reliable methodology to quantify edelfosine is a major problem in ongoing and scheduled preclinical and clinical trials with this drug. We evaluated the applicability of high-performance liquid chromatography-mass spectrometry to determine edelfosine in biological samples and polymeric delivery systems. Sample pre-treatment involved polymer precipitation or cell lysis with methanol. HPLC separation was performed on an Alltima RPC18 narrow-bore column and edelfosine quantification was done by electrospray ionization mass spectrometry (ESI-MS) using positive ion mode and selected ion monitoring. Assays were linear in the tested range of 0.3-10 μg/ml. The limit of quantification was 0.3 ng/sample in both matrices, namely biological samples and polymeric delivery systems. The interassay precision ranging from 0.79 to 1.49%, with relative errors of -6.7 and 12.8%. Mean extraction recovery was 95.6%. HPLC-ESI-MS is a reliable system for edelfosine analysis and quantification in samples from different sources, combining advantages of full automation (rapidity, ease of use, no need of extensive extraction procedures) with high analytical performance and throughput. © 2004 Elsevier B.V. All rights reserved.This work was supported by grant FIS02/1199 from the Fondo de Investigación Sanitaria, grant SA-49/01 from the Junta de Castilla y León and by Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (Grant RTIC Cáncer C10/03).Peer Reviewe
Cytogenomic characterization of an unexpected 17.6 Mb 9p deletion associated to a 14.8 Mb 20p duplication in a dysmorphic patient with multiple congenital anomalies presenting a normal G-banding karyotype

We describe a female patient with developmental delay, dysmorphic features and multiple congenital anomalies who presented a normal G-banded karyotype at the 550-band resolution. Array and multiplex-ligation probe amplification (MLPA) techniques identified an unexpected large unbalanced genomic aberration: a 17.6 Mb deletion of 9p associated to a 14.8 Mb duplication of 20p. the deleted 9p genes, especially CER1 and FREM1, seem to be more relevant to the phenotype than the duplicated 20p genes. This study also shows the relevance of using molecular techniques to make an accurate diagnosis in patients with dysmorphic features and multiple anomalies suggestive of chromosome aberration, even if on G-banding their karyotype appears to be normal. Fluorescence in situ hybridization (FISH) was necessary to identify a masked balanced translocation in the patient's mother, indicating the importance of associating cytogenetic and molecular techniques in clinical genetics, given the implications for patient management and genetic counseling. (C) 2012 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Morphol & Genet, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Imaging Diag, BR-04023900 São Paulo, BrazilABC Sch Med, Div Obstet & Gynecol, Santo Andre, SP, BrazilUniv São Paulo, Dept Pathol, Cytogen Lab, LIM 03, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Imaging Diag, BR-04023900 São Paulo, BrazilFAPESP: 10/50737-1Web of Scienc
Humoral autoimmune response heterogeneity in the spectrum of primary biliary cirrhosis

To compare autoantibody features in patients with primary biliary cirrhosis (PBC) and individuals presenting antimitochondria antibodies (AMAs) but no clinical or biochemical evidence of disease.A total of 212 AMA-positive serum samples were classified into four groups: PBC (definite PBC, n = 93); PBC/autoimmune disease (AID; PBC plus other AID, n = 37); biochemically normal (BN) individuals (n = 61); and BN/AID (BN plus other AID, n = 21). Samples were tested by indirect immunofluorescence (IIF) on rat kidney (IIF-AMA) and ELISA [antibodies to pyruvate dehydrogenase E2-complex (PDC-E2), gp-210, Sp-100, and CENP-A/B]. AMA isotype was determined by IIF-AMA. Affinity of anti-PDC-E2 IgG was determined by 8 M urea-modified ELISA.High-titer IIF-AMA was more frequent in PBC and PBC/AID (57 and 70 %) than in BN and BN/AID samples (23 and 19 %) (p < 0.001). Triple isotype IIF-AMA (IgA/IgM/IgG) was more frequent in PBC and PBC/AID samples (35 and 43 %) than in BN sample (18 %; p = 0.008; p = 0.013, respectively). Anti-PDC-E2 levels were higher in PBC (mean 3.82; 95 % CI 3.36-4.29) and PBC/AID samples (3.89; 3.15-4.63) than in BN (2.43; 1.92-2.94) and BN/AID samples (2.52; 1.54-3.50) (p < 0.001). Anti-PDC-E2 avidity was higher in PBC (mean 64.5 %; 95 % CI 57.5-71.5 %) and PBC/AID samples (66.1 %; 54.4-77.8 %) than in BN samples (39.2 %; 30.9-37.5 %) (p < 0.001). PBC and PBC/AID recognized more cell domains (mitochondria, nuclear envelope, PML/sp-100 bodies, centromere) than BN (p = 0.008) and BN/AID samples (p = 0.002). Three variables were independently associated with established PBC: high-avidity anti-PDC-E2 (OR 4.121; 95 % CI 2.118-8.019); high-titer IIF-AMA (OR 4.890; 2.319-10.314); antibodies to three or more antigenic cell domains (OR 9.414; 1.924-46.060).The autoantibody profile was quantitatively and qualitatively more robust in definite PBC as compared with AMA-positive biochemically normal individuals.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Research and Development Department of Fleury Medicine and HealthConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, UNIFESP, Div Rheumatol, BR-04023900 São Paulo, BrazilFleury Med & Hlth Labs, Div Res & Dev, São Paulo, BrazilUniv São Paulo, Sch Med, Dept Gastroenterol, São Paulo, BrazilUniv São Paulo, Inst Trop, Lab Med Invest LIM 06, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Hosp Servidor Publ Estadual Francisco Morato Oliv, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Stat, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Div Rheumatol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Hosp Servidor Publ Estadual Francisco Morato Oliv, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Stat, São Paulo, BrazilFAPESP: 2009/51887-0CNPq: 476356/2008-3Web of Scienc
A fuzzy-split range control system applied to a fermentation process

In this study it was proposed the application of a fuzzy-PI controller in tandem with a split range control strategy to regulate the temperature inside a fermentation vat. Simulations were carried out using different configurations of fuzzy controllers and split range combinations for regulatory control. the performance of these control systems were compared using conventional integral of error criteria, the demand of utilities and the control effort. the proposed control system proved able to adequately regulate the temperature in all the tests. Besides, considering a similar ITAE index and using the energetically most efficient split range configuration, fuzzy-PI controller provided a reduction of approximately 84.5% in the control effort and of 6.75% in total demand of utilities by comparison to a conventional PI controller. (C) 2013 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Estadual Campinas, Sch Chem Engn, BR-13083970 Campinas, SP, BrazilFed Univ São Paulo UNIFESP, Dept Exact & Earth Sci, BR-09972270 Diadema, SP, BrazilFed Univ São Paulo UNIFESP, Dept Exact & Earth Sci, BR-09972270 Diadema, SP, BrazilWeb of Scienc
Generalisation, decision making, and embodiment effects in mental rotation: A neurorobotic architecture tested with a humanoid robot

Mental rotation, a classic experimental paradigm of cognitive psychology, tests the capacity of humans to mentally rotate a seen object to decide if it matches a target object. In recent years, mental rotation has been investigated with brain imaging techniques to identify the brain areas involved. Mental rotation has also been investigated through the development of neural-network models, used to identify the specific mechanisms that underlie its process, and with neurorobotics models to investigate its embodied nature. Current models, however, have limited capacities to relate to neuro-scientific evidence, to generalise mental rotation to new objects, to suitably represent decision making mechanisms, and to allow the study of the effects of overt gestures on mental rotation. The work presented in this study overcomes these limitations by proposing a novel neurorobotic model that has a macro-architecture constrained by knowledge held on brain, encompasses a rather general mental rotation mechanism, and incorporates a biologically plausible decision making mechanism. The model was tested using the humanoid robot iCub in tasks requiring the robot to mentally rotate 2D geometrical images appearing on a computer screen. The results show that the robot gained an enhanced capacity to generalise mental rotation to new objects and to express the possible effects of overt movements of the wrist on mental rotation. The model also represents a further step in the identification of the embodied neural mechanisms that may underlie mental rotation in humans and might also give hints to enhance robots\u27 planning capabilities
In good company:The influence of peers on industry engagement by academic scientists

Previous research on academic entrepreneurship and engagement with industry has found that the behaviour of academics is influenced by their local social context. However, we know little about the mechanisms that produce this effect. We argue that academic scientists' industry engagement is influenced significantly by the behaviour of their peers, that is, the behaviour of colleagues of similar seniority. Using insights from social psychology, we hypothesize that these peer effects are produced by the mechanism of social comparison. In an analysis of data from multiple sources for 1370 UK academic scientists and engineers, we find that peer effects are stronger for early career individuals and weaker for star scientists, suggesting the incidence of social comparison. We argue that individuals look to their immediate peers for inspiration, because they view them as an important reference group and use them as a benchmark for their own ambitions and behaviours. Our findings have important implications for how universities may encourage scientists' behaviours by paying attention to local work contexts
Social recovery and the move beyond deficit models of depression:A feminist analysis of mid-life women's self-care practices

In Australia, like other advanced liberal democracies, the adoption of a recovery orientation was hailed as a major leap forward in mental health policy and service provision. We argue that this shift in thinking about the meaning of recovery requires further analysis of the gendered dimension of self-identity and relationships with the social world. In this article we focus on how mid-life women constructed meaning about recovery through their everyday practices of self-care within the gendered context of depression. Findings from our qualitative research with 31 mid-life women identified how the recovery process was complicated by relapses into depression, with many women critically questioning the limitations of biomedical treatment options for a more relational understanding of recovery. Participant stories revealed important tacit knowledge about recovery that emphasised the process of realising and recognising capacities and self-knowledge. We identify two central themes through which women's tacit knowledge of this changing relation to self in recovery is made explicit: the disciplined self of normalised recovery, redefining recovery and depression. The findings point to the need to reconsider how both recovery discourses and gendered expectations can complicate women's experiences of moving through depression. We argue for a different conceptualisation of recovery as a social practice through which women realise opportunities to embody different 'beings and doings'. A gendered understanding of what women themselves identify is important to their well-being, can contribute to more effective recovery oriented policies based on capability rather than deficit
Elucidation of the mechanisms of action of Bacteriophage K / nano-emulsion formulations against S. aureus via measurement of particle size and zeta potential

In earlier work we have demonstrated the effect that nano-emulsions have on bacterial growth, and most importantly the enhanced bacteriophage infectivity against S. aureus in planktonic culture when phage are carried in nano-emulsions. However, the mechanisms of enhancement of the bacteriophage killing effect are not specifically understood. This work focuses on the investigation of the possible interactions between emulsion droplets and bacterial cells, between emulsion droplets and bacteriophages, and finally interactions between all three components: nano-emulsion droplets, bacteria, and bacteriophages. The first approach consists of simple calculations to determine the spatial distribution of the components, based on measurements of particle size. It was found that nano-emulsion droplets are much more numerous than bacteria or bacteriophage, and due to their size and surface area they must be covering the surface of both cells and bacteriophage particles. Stabilisation of bacteriophages due to electrostatic forces and interaction with nano-emulsion droplets is suspected, since bacteriophages may be protected against inactivation due to ‘charge shielding’. Zeta potential was measured for the individual components in the system, and for all of them combined. It was concluded that the presence of nano-emulsions could be reducing electrostatic repulsion between bacterial cells and bacteriophage, both of which are very negatively ‘charged’. Moreover, nano-emulsions lead to more favourable interaction between bacteriophages and bacteria, enhancing the anti-microbial or killing effect. These findings are relevant since the physicochemical properties of nano-emulsions (i.e. particle size distribution and zeta potential) are key in determining the efficacy of the formulation against infection in the context of responsive burn wound dressings – which is the main target for this work
Necrostatin-1 protects against reactive oxygen species (ROS)-induced hepatotoxicity in acetaminophen-induced acute liver failure

Excessive acetaminophen (APAP) use is one of the most common causes of acute liver failure. Various types of cell death in the damaged liver are linked to APAP-induced hepatotoxicity, and, of these, necrotic cell death of hepatocytes has been shown to be involved in disease pathogenesis. Until recently, necrosis was commonly considered to be a random and unregulated form of cell death; however, recent studies have identified a previously unknown form of programmed necrosis called receptor-interacting protein kinase (RIPK)-dependent necrosis (or necroptosis), which is controlled by the kinases RIPK1 and RIPK3. Although RIPK-dependent necrosis has been implicated in a variety of disease states, including atherosclerosis, myocardial organ damage, stroke, ischemia–reperfusion injury, pancreatitis, and inflammatory bowel disease. However its involvement in APAP-induced hepatocyte necrosis remains elusive. Here, we showed that RIPK1 phosphorylation, which is a hallmark of RIPK-dependent necrosis, was induced by APAP, and the expression pattern of RIPK1 and RIPK3 in the liver overlapped with that of CYP2E1, whose activity around the central vein area has been demonstrated to be critical for the development of APAP-induced hepatic injury. Moreover, a RIPK1 inhibitor ameliorated APAP-induced hepatotoxicity in an animal model, which was underscored by significant suppression of the release of hepatic enzymes and cytokine expression levels. RIPK1 inhibition decreased reactive oxygen species levels produced in APAP-injured hepatocytes, whereas CYP2E1 expression and the depletion rate of total glutathione were unaffected. Of note, RIPK1 inhibition also conferred resistance to oxidative stress in hepatocytes. These data collectively demonstrated a RIPK-dependent necrotic mechanism operates in the APAP-injured liver and inhibition of this pathway may be beneficial for APAP-induced fulminant hepatic failure
Insights into the internal dynamics of Etna volcano through discrete and continuous microgravity observations

Discrete and continuous microgravity observations have been routinely performed at Mt.
Etna since 1986 and 1998, respectively. Besides furnishing a full view of how gravity
measurements from Etna are accomplished and reduced, this paper is a collection of case
studies aimed at demonstrating the potential of microgravity studies to investigate the
plumbing system of an active volcano and detect forerunners to paroxysmal volcanic events.
As for discrete measurements, case studies relative to the 1994-96 and 2001 periods are
reported. During the first period, the observed gravity changes are interpreted within the
framework of the strombolian activity which occurred from the summit craters. Gravity
changes observed during the first 9 months of 2001 are directly related to the underground
mass redistributions who preceded, accompanied and followed the July-August 2001 flank
eruption of Etna.
As for continuous measurements, a three-year (1998-2000) sequence and a 48-hour (26-28
October 2002) sequence, both from PDN station, are presented and discussed. The first one is
maybe the longest continuous gravity sequence ever acquired at a station very close to the
summit zone of an active volcano. It allows to discover the cyclic character of a source whose
geometrical characteristics are retrieved through data from discrete measurements.
The second sequence is also likely to represent an unique item: a gravity sequence
encompassing the onset of an eruption and coming from a station only 1.5 km from the
eruptive fissures. It allows some constraints to be set on the characteristics of the intrusive
mechanism leading to the eruption
Surface evidence of active tectonics along the Pergola-Melandro fault: a critical

The Pergola-Melandro basin (southern Apennines) is characterized by a below-average release
of seismic energy within a wider earthquake-prone region. In fact, it is placed between the
maximum intensity areas of two of the most destructive earthquakes reported in the Italian seismic
catalogue: the M ≥ 7.0 Agri Valley earthquake in 1857 and the Ma = 6.9 Irpinia earthquake in 1980.
In this work, we present geomorphologic analysis, electrical resistivity surveys and field data,
including paleoseismologic evidence, that provided the first direct constraints on the presence of a
~20 km long, seismogenic fault at the western border of the Pergola-Melandro basin. We also
obtained geological information on the recent deformation history of the Pergola-Melandro fault
that indicates the occurrence of at least four surface faulting earthquakes since Late Pleistocene age.
The empirical relationships linking fault length and magnitude would assign to the Pergola-
Melandro fault an event of M ≥ 6.5. These new data have important implication on the seismic
hazard assessment of this sector of the Apennines, that also includes large cities such as Potenza,
about 20 km far from the recognized Pergola-Melandro fault, and highlight the relevance of the
geological approach in areas where the seismological records are poor. Finally, we discuss the
Pergola-Melandro fault within the regional seismotectonic context. In particular, this fault belongs
to the system of normal faults with an apenninic orientation, both NE and SW dipping, that
accommodate the NE- crustal extension taking place in the area. Nearby faults, similarly oriented
but with opposite dip, may coexist whether linked by secondary faults that act as slip transfer
structures. This complex system of active faults would be more realistic than to consider a narrow
band of faults, running along the belt axis, with an homogenous geometry and, moreover, more
consistent with the high extension rate measured by historical earthquakes and geodetic data
Etn@ref: a geodetic reference frame for Mt. Etna GPS networks

In volcanology, one of the most important instruments for scientific community interested in modelling the physical processes related to magma movements in the shallow crust is geodetic data. Since the end of the 1980s, GPS surveys and Continuous GPS stations (CGPS) have greatly improved the possibility to measure such movements with high time and space resolution. However, physical modelling requires that any external influence on the data, not directly related to the investigated quantity, must be filtered. One major tricky factor in determining a deformation field using GPS displacement vectors and velocities is the correct choice of a stable reference frame. In this work, using more than a decade of GPS measurements, we defined a local reference frame in order to refer the Mt. Etna ground deformation pattern to a rigid block. In particular, we estimated the Euler pole for the rigid block by minimizing, with a weighted least squares inversion, the adjustments to two horizontal components of GPS velocity at 13 “fiducial” sites located within 350 km around Mt. Etna. The inversion inferred an Euler pole located at 38.450° N and -107.702° E and a rotation rate of 0.263 deg/Myr
Birth-cohort trends in older-age functional disability and their relationship with socio-economic status:Evidence from a pooling of repeated cross-sectional population-based studies for the UK

We examine birth-cohort trends behind recent changes in the prevalence of functional disability in the older population living in private households in the United Kingdom (UK). By using three different socio-economic indicators available in the nationally representative cross-sectional data on older individuals interviewed between 2002 and 2012 in the Family Resource Survey (FRS) (96,733 respondents), we investigate the extent to which the overall trends have been more favourable among more advantaged than disadvantaged socioeconomic groups. Compared to the cohort of people born in 1924, successive cohorts of older men have lower odds of having at least one functional difficulty (FD), whereas no significant trend was found for women. Among people with at least one FD, however, the number of disabilities increases for each successive cohort of older women (incidence rate ratio 1.027, 95% confidence interval 1.023 to 1.031, P<0.001) and men (incidence rate ratio 1.028, 95% confidence interval 1.024 to 1.033, P<0.001). By allowing interactions between birth cohort and SES indicators, a significant increasing cohort trend in the number of reported FDs was found among older men and women at lower SES, whereas an almost stable pattern was observed at high SES. Our results suggest that the overall slightly increasing birth-cohort trend in functional difficulties observed among current cohorts of older people in the UK hides underlying increases among low SES individuals and a relative small reduction among high SES individuals. Further studies are needed to understand the causes of such trends and to propose appropriate interventions. However, if the SES differentials in trends in FDs observed in the past continue, this could have important implications for the future costs of the public system of care and support for people with care needs