julilili42/papers huggingface dataset:
Nephron Toxicity Profiling via Untargeted Metabolome Analysis Employing a High Performance Liquid Chromatography-Mass Spectrometry-based Experimental and Computational Pipeline
2015-06-10

Untargeted metabolomics has the potential to improve the predictivity of in vitro toxicity models and therefore may aid the replacement of expensive and laborious animal models. Here we describe a long term repeat dose nephrotoxicity study conducted on the human renal proximal tubular epithelial cell line, RPTEC/TERT1, treated with 10 and 35 μmol·liter(-1) of chloroacetaldehyde, a metabolite of the anti-cancer drug ifosfamide. Our study outlines the establishment of an automated and easy to use untargeted metabolomics workflow for HPLC-high resolution mass spectrometry data. Automated data analysis workflows based on open source software (OpenMS, KNIME) enabled a comprehensive and reproducible analysis of the complex and voluminous metabolomics data produced by the profiling approach. Time- and concentration-dependent responses were clearly evident in the metabolomic profiles. To obtain a more comprehensive picture of the mode of action, transcriptomics and proteomics data were also integrated. For toxicity profiling of chloroacetaldehyde, 428 and 317 metabolite features were detectable in positive and negative modes, respectively, after stringent removal of chemical noise and unstable signals. Changes upon treatment were explored using principal component analysis, and statistically significant differences were identified using linear models for microarray assays. The analysis revealed toxic effects only for the treatment with 35 μmol·liter(-1) for 3 and 14 days. The most regulated metabolites were glutathione and metabolites related to the oxidative stress response of the cells. These findings are corroborated by proteomics and transcriptomics data, which show, among other things, an activation of the Nrf2 and ATF4 pathways.
Computing Cox rings
2015-06-10

We consider modifications, for example blow ups, of Mori dream spaces and provide algorithms for investigating the effect on the Cox ring, for example verifying finite generation or computing an explicit presentation in terms of generators and relations.
Reply: The p.Ser107Leu inBICD2is a mutation ‘hot spot’ causing distal spinal muscular atrophy
2015-06-10

Sir, Thank you for the opportunity to reply to the correspondence concerning our recent publication in Brain , ‘Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2’ (Rossor et al. , 2015). We read with great interest the letter from Bansagi et al. and thank the authors for providing further evidence that p.Ser107Leu in BICD2 is a mutation ‘hot spot’. Bansagi et al. (2015) describe two unrelated families with a typical Spinal Muscular Atrophy Lower Extremity Dominant (SMALED) phenotype. In both families, affected individuals presented at birth with either toe deformities ...
Cortical correlates of perceptual decision making during tactile spatial pattern discrimination
2015-06-10

Abstract Perceptual decision making involves a distributed cortical network including areas related to sensory feature extraction, decision formation, and finally signalling the decision through a motor response. Although these processing steps are supposed to occur in sequence, the seemingly instant mapping of a perceptual decision onto a motor response renders these processes almost indistinguishable. To dissociate cortical areas related to sensory decision making from areas that prepare the subsequent motor response, we performed functional magnetic resonance imaging during a tactile spatial pattern discrimination task with interleaved immediate and delayed response conditions. Decision difficulty was manipulated parametrically by adding spatial noise to the tactile patterns, resulting in a rise in decision time with increasing noise. We assumed that areas involved in making the decision should show a variation in their activation with decision time and irrespective of whether (immediate response condition) or not (delayed response condition) a motor response could be prepared in advance. To exhibit these putative decision areas, we used response time, as was obtained in the immediate response condition, as parametric predictor for the difficulty‐dependent variations of blood oxygenation level‐dependent (BOLD)‐activity in both response conditions. BOLD activations in right (contralateral) postcentral sulcus, right intraparietal sulcus (IPS) and bilateral anterior insula (aINS) reflected this parametric modulation in both response conditions, suggesting a role of these areas in tactile decisions independent of decision‐specific motor preparation. Furthermore, a multivariate pattern analysis performed on the BOLD responses in the delayed response condition for a single difficulty level independently validated IPS and aINS as decision‐related areas. Hum Brain Mapp 36:3339–3350, 2015 . © 2015 Wiley Periodicals, Inc.
Interstitial 1p32.1p32.3 deletion in a patient with multiple congenital anomalies
2015-06-10

Interstitial deletions encompassing chromosome bands 1p32.1p32.3 are rare. Only nine unrelated patients with partially overlapping 1p32.1p32.3 deletions of variable size and position have been reported to date. We report on a 17‐month‐old boy with choanal atresia, hearing loss, urogenital anomalies, and microcephaly in whom an interstitial de novo deletion of 6.4 Mb was detected in 1p32.1p32.3 (genomic position chr1:54,668,618‐61,113,264 according to GRCh37/hg19). The deleted region harbors 31 RefSeq genes. Notable genes in the region are PCSK9 , haploinsufficiency of which caused low LDL cholesterol plasma levels in the patient, and DAB1 , which is a candidate gene for cognitive deficits, microcephaly, and cerebral abnormalities such as ventriculomegaly and agenesis of the corpus callosum. Choanal atresia, microcephaly, and severe hearing loss were previously not known to be associated with 1p32 deletions. Our reported patient thus broadens the spectrum of clinical findings in this chromosome region and further facilitates genotype‐phenotype correlations. Additional patients with overlapping deletions and/or point mutations in genes of this region need to be identified to elucidate the role of individual genes for the complex clinical manifestations. © 2015 Wiley Periodicals, Inc.
Professional mathematicians differ from controls in their spatial-numerical associations
2015-06-11

While mathematically impaired individuals have been shown to have deficits in all kinds of basic numerical representations, among them spatial-numerical associations, little is known about individuals with exceptionally high math expertise. They might have a more abstract magnitude representation or more flexible spatial associations, so that no automatic left/small and right/large spatial-numerical association is elicited. To pursue this question, we examined the Spatial Numerical Association of Response Codes (SNARC) effect in professional mathematicians which was compared to two control groups: Professionals who use advanced math in their work but are not mathematicians (mostly engineers), and matched controls. Contrarily to both control groups, Mathematicians did not reveal a SNARC effect. The group differences could not be accounted for by differences in mean response speed, response variance or intelligence or a general tendency not to show spatial-numerical associations. We propose that professional mathematicians possess more abstract and/or spatially very flexible numerical representations and therefore do not exhibit or do have a largely reduced default left-to-right spatial-numerical orientation as indexed by the SNARC effect, but we also discuss other possible accounts. We argue that this comparison with professional mathematicians also tells us about the nature of spatial-numerical associations in persons with much less mathematical expertise or knowledge.
1,2‐Azaborine: The Boron‐Nitrogen Derivative of ortho‐Benzyne
2015-06-11

Abstract The BN analogue of ortho ‐benzyne, 1,2‐azaborine, is generated by flash vacuum pyrolysis, trapped under cryogenic conditions, and studied by direct spectroscopic techniques. The parent BN aryne spontaneously binds N 2 and CO 2 , thus demonstrating its highly reactive nature. The interaction with N 2 is photochemically reversible. The CO 2 adduct of 1,2‐azaborine is a cyclic carbamate which undergoes photocleavage, thus resulting in overall CO 2 splitting.
Intransparent German number words complicate transcoding â€“ a translingual comparison with Japanese
2015-06-11

Superior early numerical competencies of children in several Asian countries have (amongst others) been attributed to the higher transparency of their number word systems. Here, we directly investigated this claim by evaluating whether Japanese children's transcoding performance when writing numbers to dictation (e.g., "twenty five" → 25) was less error prone than that of German-speaking children - both in general as well as when considering language-specific attributes of the German number word system such as the inversion property, in particular. In line with this hypothesis we observed that German-speaking children committed more transcoding errors in general than their Japanese peers. Moreover, their error pattern reflected the specific inversion intransparency of the German number-word system. Inversion errors in transcoding represented the most prominent error category in German-speaking children, but were almost absent in Japanese-speaking children. We conclude that the less transparent German number-word system complicates the acquisition of the correspondence between symbolic Arabic numbers and their respective verbal number words.
Synaptic unreliability facilitates information transmission in balanced cortical populations
2015-06-11

Synaptic unreliability is one of the major sources of biophysical noise in the brain. In the context of neural information processing, it is a central question how neural systems can afford this unreliability. Here we examine how synaptic noise affects signal transmission in cortical circuits, where excitation and inhibition are thought to be tightly balanced. Surprisingly, we find that in this balanced state synaptic response variability actually facilitates information transmission, rather than impairing it. In particular, the transmission of fast-varying signals benefits from synaptic noise, as it instantaneously increases the amount of information shared between presynaptic signal and postsynaptic current. Furthermore we show that the beneficial effect of noise is based on a very general mechanism which contrary to stochastic resonance does not reach an optimum at a finite noise level.
Blurring the boundaries between frame-based and frameless stereotaxy: feasibility study for brain biopsies performed with the use of a head-mounted robot
2015-06-12

OBJECT Frame-based stereotactic interventions are considered the gold standard for brain biopsies, but they have limitations with regard to flexibility and patient comfort because of the bulky head ring attached to the patient. Frameless image guidance systems that use scalp fiducial markers offer more flexibility and patient comfort but provide less stability and accuracy during drilling and biopsy needle positioning. Head-mounted robot-guided biopsies could provide the advantages of these 2 techniques without the downsides. The goal of this study was to evaluate the feasibility and safety of a robotic guidance device, affixed to the patient’s skull through a small mounting platform, for use in brain biopsy procedures. METHODS This was a retrospective study of 37 consecutive patients who presented with supratentorial lesions and underwent brain biopsy procedures in which a surgical guidance robot was used to determine clinical outcomes and technical procedural operability. RESULTS The portable head-mounted device was well tolerated by the patients and enabled stable drilling and needle positioning during surgery. Flexible adjustments of predefined paths and selection of new trajectories were successfully performed intraoperatively without the need for manual settings and fixations. The patients experienced no permanent deficits or infections after surgery. CONCLUSIONS The head-mounted robot-guided approach presented here combines the stability of a bone-mounted set-up with the flexibility and tolerability of frameless systems. By reducing human interference (i.e., manual parameter settings, calibrations, and adjustments), this technology might be particularly useful in neurosurgical interventions that necessitate multiple trajectories.
The Epoxyeicosatrienoic Acid Pathway Enhances Hepatic Insulin Signaling and is Repressed in Insulin-Resistant Mouse Liver*
2015-06-12

Although it is widely accepted that ectopic lipid accumulation in the liver is associated with hepatic insulin resistance, the underlying molecular mechanisms have not been well characterized.Here we employed time resolved quantitative proteomic profiling of mice fed a high fat diet to determine which pathways were affected during the transition of the liver to an insulin-resistant state. We identified several metabolic pathways underlying altered protein expression. In order to test the functional impact of a critical subset of these alterations, we focused on the epoxyeicosatrienoic acid (EET) eicosanoid pathway, whose deregulation coincided with the onset of hepatic insulin resistance. These results suggested that EETs may be positive modulators of hepatic insulin signaling. Analyzing EET activity in primary hepatocytes, we found that EETs enhance insulin signaling on the level of Akt. In contrast, EETs did not influence insulin receptor or insulin receptor substrate-1 phosphorylation. This effect was mediated through the eicosanoids, as overexpression of the deregulated enzymes in absence of arachidonic acid had no impact on insulin signaling. The stimulation of insulin signaling by EETs and depression of the pathway in insulin resistant liver suggest a likely role in hepatic insulin resistance. Our findings support therapeutic potential for inhibiting EET degradation.
LEGO music
2015-06-12

We present a multi-touch tabletop application that utilizes LEGO bricks as physical representations for musical notes to create a novel digital learning environment for musical composition principles. Our application makes use of the physical qualities that graspable objects provide and combines them with dynamic visualizations on a multi-touch screen. While the system can be used to collaboratively create melodies and harmonies, our concept specifically aims at introducing and teaching composition principles. In this paper, we illustrate the concept and the iterative process that lead to the final application design. Furthermore, we discuss findings from four composing workshops which were conducted with school children with varying levels of musical expertise.
Paleoecological and climatic implications of stable isotope results from late Pleistocene bone collagen, Ziegeleigrube Coenen, Germany
2015-06-12

Climatic and ecological conditions during Marine Oxygen Isotope Stage (MIS) 3 are complex and the impact of cold spells on the ecosystems in Central Europe still needs to be investigated thoroughly. Ziegeleigrube Coenen (ZC) is a late Pleistocene MIS 3 locality in the Lower Rhine Embayment of Germany, radiocarbon-dated to &gt; 34 14 C ka BP. The site yielded a broad spectrum of mammal species. We investigated the carbon (δ 13 C), nitrogen (δ 15 N) and sulfur (δ 34 S) isotope signatures of bone collagen, since these are valuable tools in characterizing ecological niches, environmental conditions and aspects of climate and mobility. By comparison with pre- and post-Last Glacial Maximum (LGM) sites in Central Europe we show that ZC belongs in a cold event of MIS 3 and was climatically more similar to post-LGM sites than to pre-LGM sites. However, the trophic structure resembled that of typical pre-LGM sites in Belgium. This cold event in MIS 3 changed the bottom of the foodweb, but do not seem to have had a direct impact on the occurrence of the mammalian species and their ecological distribution. Apparently the (mega-) faunal community could adapt also to harsher environmental conditions during MIS 3.
Trust Generating Security Generating Trust: An Ethical Perspective on a Secularized Discourse
2015-06-12

This text focuses on the moral character of trust. Trust is widely recognized as a morally charged concept: Values are inscribed in this concept, and its practices have moral consequences. Trust needs ethical reflection to explore what values are inscribed and if the consequences are desirable or welcome and if so for whom. The first step reflects trust’s religious biography, analyzing expressions of Gottvertrauen in early modern times und drawing the line to Erik Erikson, Wolfhart Pannenberg and Konrad Lorenz. The second step considers security’s underlying religious discourses, especially with the “Schutzmantelmadonnen” (Madonna with the cloak) which provide an elaborate security technology. The idea of multiple modernities and multiple secularities explains how present some of the late middle age ideas are within modern technologies. In a third step, an ethics of trust – how to do trust and security in a just way – is mapped out with its crucial “points to consider” a field where different rationalities are present. The Coda finally rescues the reputation of the “trust and security theater” – as an ethically relevant and needed act and action.
Synthesis of Glycoconjugated Phthalonitriles for New Phthalocyanine-Based Photosensitizers
2015-06-13

GRAPHICAL ABSTRACTSynthesis of Glycoconjugated Phthalonitriles for New Phthalocyanine-Based PhotosensitizersAll authorsGöran Crucius, Michael Hanack & Thomas Zieglerhttps://doi.org/10.1080/07328303.2015.1050106Published online:01 July 2015Excellent photophysical and photochemical properties completed by magnificent take-up rates in malignant tissues attracted a great deal of interest to the application of glycosylated and glycoconjugated phthalocyanines in photodynamic therapy. In this study we describe the concise synthesis and full characterization of 16 differently 3,6-bisglycoconjugated phthalonitriles 3, 5, 6, 8, and 48–59, which are precursors for a new generation of photosensitizers, namely, nonperipheral glycoconjugated phthalocyanines. The first example for the synthesis of a nonperipheral glycoconjugated zinc phthalocyanine 60 from phthalonitrile 48 is also presented in this work.
Glucagon-to-insulin ratio is pivotal for splanchnic regulation of FGF-21 in humans
2015-06-14

Collectively, our data reveal that 1) in humans, the splanchnic bed contributes to the systemic FGF-21 levels during rest and exercise; 2) under normo-physiological conditions FGF-21 is not released from the leg; 3) a dynamic interaction of glucagon-to-insulin ratio regulates FGF-21 secretion in humans.
Patients with an extraordinarily elevated serum ferritin: think of haemophagocytic lymphohistiocytosis
2015-06-14

BACKGROUND: We retrospectively analysed charts of patients with blood ferritin level &gt;5000 μg/l. The aim of the study was to look for the likelihood of haemophagocytic lymphohistiocytosis (HLH) in these patients. METHODS: Forty-two patients demonstrated hyperferritinaemia and could be evaluated. The diagnosis of HLH was based on a recently published HScore and an earlier diagnostic algorithm. RESULTS: According to the algorithm, 20 patients fulfilled the criteria for a diagnosis of HLH. However, patients with Still’s disease have macrophage activation and, in this context, a rise in ferritin without having HLH. Fourteen patients with carcinoma, haematological malignancies or infection and hyperferritinaemia remained. Signs and symptoms were: systemic inflammatory response syndrome (SIRS 100%), fever (95%), cytopenia of ≥2 lines (70%), immunosuppression (61.5%), splenomegaly (50%), elevated liver enzymes (45%), lymphadenopathy (35%), hepatomegaly (30%). These are nonspecific parameters. Therefore HLH may be overdiagnosed. Using the HScore, only 10 patients had &gt;80% probability of having HLH. Patients demonstrating cytopenia of ≥2 cell lines had a &gt;60% mortality rate. Time to death was 13.8 days; death was most often due to multiorgan failure. CONCLUSION: HScore reflects a higher specificity than the algorithm for diagnosing HLH. The discrepancy may indicate the difficulty that a specific marker still is missing. Hyperferritinaemia was strongly associated with HLH in patients with haematological or oncological malignancies. HLH may be underdiagnosed because the majority of these patients suffer from a severe underlying disease, which easily might suggest a flare or infection. In this population, hyperferritinaemia and SIRS should rise suspicion because mortality in HLH is high.
Barriers to Physical Activity in Adolescents
2015-06-15

During adolescence, physical activity (PA) decreases with potentially serious, long-term consequences for physical and mental health. Although barriers have been identified as an important PA correlate in adults, research on adolescents’ PA barriers is lacking. Thus reliable, valid scales to measure adolescents’ PA barriers are needed. We present two studies describing a broad range of PA barriers relevant to adolescents with a multidimensional approach. In Study 1, 124 adolescents (age range = 12 – 24 years) reported their most important PA barriers. Two independent coders categorized those barriers. The most frequent PA barriers were incorporated in a multidimensional questionnaire. In Study 2, 598 adolescents (age range = 13 – 21 years) completed this questionnaire and reported their current PA, intention, self-efficacy, and negative outcome expectations. Seven PA barrier dimensions (leisure activities, lack of motivation, screen-based sedentary behavior, depressed mood, physical health, school workload, and preconditions) were confirmed in factor analyses. A multidimensional approach to measuring PA barriers in adolescents is reliable and valid. The current studies provide the basis for developing individually tailored interventions to increase PA in adolescents.
In Vivo MRS of Lipids in Adipose Tissue, Bone Marrow, and Liver
2015-06-15

For a long time, adipose tissue attracted little interest for in vivo studies using magnetic resonance, as it seemed not to be directly involved in most diseases. The past few years have revealed significant correlations between the distribution and composition of adipose tissue in the body and the development of metabolic diseases. In addition, fatty components in parenchymal organs such as liver, pancreas, and musculature (the so-called ectopic fat) have attracted growing interest in medical research. T1-weighted and fat selective imaging provides a reliable overview of the distribution of adipose tissue in various body parts. Modern fat selective imaging also reveals fat concentrations in liver and other organs, detectable at lipid concentrations of about 2% by volume. The crucial role of localized 1H-MRS today is in the assessment of the composition of storage fat, especially for determining the proportions of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA). Another advantage of localized 1H spectroscopy over MRI techniques is its sensitivity to low fractions of lipids in parenchymal organs. This feature paves the way to short-term noninvasive interventional studies (nutrition, exercise, or medication), using MRS to monitor their effects on lipid concentrations. Sensitive measurements of small shifts of fat and water portions in hematopoietic red bone marrow by 1H-MRS might also help in the staging of blood disorders and in the monitoring of related treatment. Keywords: 1H localized spectroscopy; adipose tissue; adipose tissue composition; obesity; visceral adipose tissue; bone marrow; leukemia; stem cell transplantation; liver steatosis; non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH)