julilili42/papers huggingface dataset:
Binding Modes of Reverse Fosmidomycin Analogs toward the Antimalarial Target IspC
2014-09-25

1-Deoxy-d-xylulose 5-phosphate reductoisomerase of Plasmodium falciparum (PfIspC, PfDxr), believed to be the rate-limiting enzyme of the nonmevalonate pathway of isoprenoid biosynthesis (MEP pathway), is a clinically validated antimalarial target. The enzyme is efficiently inhibited by the natural product fosmidomycin. To gain new insights into the structure activity relationships of reverse fosmidomycin analogs, several reverse analogs of fosmidomycin were synthesized and biologically evaluated. The 4-methoxyphenyl substituted derivative 2c showed potent inhibition of PfIspC as well as of P. falciparum growth and was more than one order of magnitude more active than fosmidomycin. The binding modes of three new derivatives in complex with PfIspC, reduced nicotinamide adenine dinucleotide phosphate, and Mg(2+) were determined by X-ray structure analysis. Notably, PfIspC selectively binds the S-enantiomers of the study compounds.
Structures and Intriguing Conformational Behavior of 1- and 2-Naphthalenesulfonamides As Determined by Gas-Phase Electron Diffraction and Computational Methods
2014-09-25

The saturated vapors of 1- and 2-naphthalenesulfonamides (1-NaphSA and 2-NaphSA) were studied by the gas-phase electron diffraction/mass-spectrometric method at 413(9) and 431(9) K. According to quantum chemical calculations (DFT/B3LYP and MP2 with cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ basis set) 1-NaphSA possesses four conformers with different orientations of the SO2NH2 fragment relative to the naphthalene frame and eclipsed or staggered orientation of the N-H and S═O bonds, whereas 2-NaphSA possesses only two conformers with different orientations of the N-H and S═O bonds. It was experimentally established that vapors over 1-NaphSA and 2-NaphSA exist predominantly (up to 75 mol %) of low-energy conformers of C1 symmetry in which the C-S-N planes deviate from perpendicular orientation relative to the naphthalene skeleton with near eclipsed orientation of the N-H and S═O bonds of the SO2NH2 fragment. The following geometrical parameters (Å and degrees) of the dominant conformers were derived: r(h1)(C-H) = 1.089(4), r(h1)(C-C)av = 1.411(3), r(h1)(C-S) = 1.761(10), r(h1)(S-O)av = 1.425(3), r(h1)(S-N) = 1.666(10), ∠C-C1-C = 119.8(2), ∠C1-S-N = 104.5(22), C9-C1-S-N = 69.5(30) for 1-NaphSA; r(h1)(C-H) = 1.083(5), r(h1)(C-C)av = 1.411(3), r(h1)(C-S) = 1.780(7), r(h1)(S-O)av = 1.427(4), r(h1)(S-N) = 1.668(6), ∠C-C2-C = 123.0(3), ∠C2-S-N = 103.6(19), C1-C2-S-N = 110(10) for 2-NaphSA. The connection between nonequivalence of the C-C bonds in the naphthalene frame and spatial orientation of the substituents SO2NH2 is discussed. Transition states between conformers and enantiomers were determined.
Light modulated activity of root alkaline/neutral invertase involves the interaction with 14‐3‐3 proteins
2014-09-26

Summary Alkaline/neutral invertases ( A / N ‐Invs) are now recognized as essential proteins in plant life. They catalyze the irreversible breakdown of sucrose into glucose and fructose and thus supply the cells with energy as well as signaling molecules. In this study we report on a mechanism that affects the activity of the cytosolic invertase A t CINV 1 ( A t‐ A / N ‐ I nv G or AT 1 G 35580). We demonstrate that S er547 at the extreme C ‐terminus of the A t CINV 1 protein is a substrate of calcium‐dependent kinases ( CPK 3 and 21) and that phosphorylation creates a high‐affinity binding site for 14‐3‐3 proteins. The invertase as such has basal activity, but we provide evidence that interaction with 14‐3‐3 proteins enhances its activity. The analysis of three quadruple 14‐3‐3 mutants generated from six T ‐ DNA insertion mutants of the non‐epsilon family shows both specificity as well as redundancy for this function of 14‐3‐3 proteins. The strong reduction in hexose levels in the roots of one 14‐3‐3 quadruple mutant plant is in line with the activating function of 14‐3‐3 proteins. The physiological relevance of this mechanism that affects A / N ‐invertase activity is underscored by the light‐induced activation and is another example of the central role of 14‐3‐3 proteins in mediating dark/light signaling. The nature of the light‐induced signal that travels from the shoot to root and the question whether this signal is transmitted via cytosolic C a ++ changes that activate calcium‐dependent kinases, await further study.
Consequences of the New UK Tax Exemption System: Evidence from Micro-level Data
2014-09-26

Journal Article Consequences of the New UK Tax Exemption System: Evidence from Micro‐level Data Get access Peter Egger, Peter Egger ETH Zürich, CEPR, CESifo, University of Nottingham and Oxford University Centre for Business Taxation (OUCBT) Search for other works by this author on: Oxford Academic Google Scholar Valeria Merlo, Valeria Merlo University of Tübingen and CESifo Search for other works by this author on: Oxford Academic Google Scholar Martin Ruf, Martin Ruf University of Tübingen and NoCeT Search for other works by this author on: Oxford Academic Google Scholar Georg Wamser Georg Wamser University of Tübingen, CESifo and NoCeT Search for other works by this author on: Oxford Academic Google Scholar The Economic Journal, Volume 125, Issue 589, 1 December 2015, Pages 1764–1789, https://doi.org/10.1111/ecoj.12190 Published: 23 January 2015
Chemical Recognition of Oxidation-Specific Epitopes in Low-Density Lipoproteins by a Nanoparticle Based Concept for Trapping, Enrichment, and Liquid Chromatography–Tandem Mass Spectrometry Analysis of Oxidative Stress Biomarkers
2014-09-26

Monitoring bioactive oxidized phospholipids (OxPLs), such as 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-(9'-oxononanoyl)-sn-glycero-3-phosphocholine (PONPC), is of major interest as they play a crucial role in a variety of age related diseases, e.g., in the development and progression of atherosclerosis. Since they are in low abundance in samples like oxidized low-density lipoproteins (OxLDL) and human plasma, respectively, their analysis as risk biomarkers requires the combination of an efficient selective sample preparation with highly sensitive detection methods, such as liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). In this study, a nanoparticle-based strategy for successful trapping and enrichment of aldehyde-containing oxidized phospholipids is presented. The concept involves a derivatization step with a bifunctional reagent containing both a hydrazide group for hydrazone formation with carbonyl-containing PLs and a thiol moiety for subsequent trapping on GNPs. After washing, the trapped analytes are quantitatively released from the nanoparticles' surface by transimination with hydroxylamine. The released oxime-derivatives of the carbonylated-OxPLs are subsequently analyzed by LC-ESI-MS/MS in the selected reaction monitoring scan mode. Several parameters of this workflow were optimized. With the optimized nanoparticle-based extraction and enrichment step, very clean extracts of these biomarkers can be obtained and the detection limits can be significantly decreased from 2.76 and 2.65 nM for PONPC and POVPC, respectively, to 0.17 and 0.44 nM. The applicability of this nanoparticle-based sample preparation concept was demonstrated by successful extraction of oxidized phospholipids from biological samples, such as human plasma, MDA-modified LDL and Cu(2+)-oxidized LDL.
Patterns and Correlates of Expressed Emotion, Perceived Criticism, and Rearing Style in First Admitted Early-Onset Schizophrenia Spectrum Disorders
2014-09-26

The aim of this study was to assess patterns and correlates of family variables in 31 adolescents treated for their first episode of a schizophrenia spectrum disorder (early-onset schizophrenia [EOS]). Expressed emotion, perceived criticism, and rearing style were assessed. Potential correlates were patient psychopathology, premorbid adjustment, illness duration, quality of life (QoL), sociodemographic variables, patient and caregiver "illness concept," and caregiver personality traits and support. Families were rated as critical more frequently by patients than raters (55% vs. 13%). Perceived criticism was associated with worse QoL in relationship with parents and peers. An adverse rearing style was associated with a negative illness concept in patients, particularly with less trust in their physician. Future research should examine perceived criticism as a predictor of relapse and indicator of adolescents with EOS who need extended support and treatment. Rearing style should be carefully observed because of its link with patients' illness concept and, potentially, to service engagement and medication adherence.
ANTI-NATURE IN NATURE ITSELF
2014-09-26

Nature and civilization are often regarded in opposition to each other. However, civilization employs technologies and is based on laws of nature. Also, the historical world is a result of the development of the natural world. An “anti-nature” must thus be contained somewhere within nature. The idea of “anti-nature” is neither alien to the Eastern nor to the Western traditional concepts of nature. The philosophy of Lao Zi never embraces mere naturalism. Lao Zi has observed that things in the world are not always “so on their own” but rather in the mode of anti-nature. Anti-nature in nature itself does not become expressive until Christian theology, in which the origin of evil is reflected upon. The last part of the paper begins with one Buddhist thought expressed in the Diamond Sutra: “The world is not the world that is named the world.” Through naming of a thing, this thing is objectified or substantialized, and an objectified thing is not the thing itself. This self is “śūnya”, a non-world, which is what the world is. This non-world (as well nature) is first and foremost concealed by ego-consciousness that tends to objectify the things. Ego-consciousness as this anti-nature tends to conceal this non-nature, and begins to act in the form of technology. The radical way of solving the problems caused by this “anti-nature” must begin with gaining an insight into the nature of ourselves as well as the nature of technology.
The Internal/External Frame of Reference Model of Self-Concept and Achievement Relations
2014-09-27

The internal/external frame of reference (I/E) model and dimensional comparison theory posit paradoxical relations between achievement (ACH) and self-concept (SC) in mathematics (M) and verbal (V) domains; ACH in each domain positively affects SC in the matching domain (e.g., MACH to MSC) but negatively in the nonmatching domain (e.g., MACH to VSC). This substantive-methodological synergy based on latent variable models of Trends in International Mathematics and Science Study (TIMSS) data supports the generalizability of these predictions in relation to: mathematics and science domains, intrinsic motivation as well as self-concept, and age and nationality, based on nationally representative matched samples of fourth- and eighth-grade students from three Middle Eastern Islamic, five Western, and four Asian countries ( N=117,321 students) with important theoretical, developmental, cross-cultural, and methodological implications.
Tumour volume reduction after neoadjuvant chemotherapy impacts outcome in localised embryonal rhabdomyosarcoma
2014-09-27

Background Response (tumour volume reduction) to induction chemotherapy has been used to stratify secondary local and systemic treatment of Intergroup Rhabdomyosarcoma Study Group III (IRSG‐III) embryonal rhabdomyosarcoma (RME) in consecutive CWS‐trials. To evaluate its actual impact we studied response‐related treatment and outcomes. Procedure Patients with IRSG‐III RME &lt;21 years and non‐response (NR, &lt;33% volume reduction) in five consecutive CWS‐trials were analysed and compared with partial responders (PAR, ≥33% reduction). The NR was reviewed and sub‐classified as Objective Response (OR, &lt;0%–33% reduction) or Stable/Progressive Disease (SPD). Results Fifty‐nine of 529 patients had NR (n = 34 OR, n = 25 SPD). Primary risk‐factors including age, tumour size, and TN‐classification did not differ between NR and PAR groups but NR had more patients with unfavourable sites comparatively ( P = 0.04). There were no differences in primary risk‐factors between OR and SPD. Significant factors associated with poor outcome in multivariate analysis were NR, TN‐classification, age &gt;10 years, tumour size &gt;5 cm and therapy in older trials. After response assessment n = 24 NR continued to receive induction chemotherapy, n = 32 received other combinations and n = 3 no further chemotherapy. Forty‐two non‐responders were irradiated, and the tumours were completely resected in n = 20. After a median follow‐up of 8 years, 34 NR are alive. Seventeen of 21 failures leading to disease‐related deaths were locoregional. The five‐year overall survival rate (OS) was 76 ± 4% for PAR, 79 ± 14% for OR, but only 40 ± 19% for SPD ( P &lt; 0.001). Conclusion Response to induction chemotherapy appears to be an important surrogate marker of poor outcome in patients with SPD largely due to ineffective local control. Pediatr Blood Cancer 2015;62:16–23. © 2014 Wiley Periodicals, Inc.
Genetic Analysis of Leucin-Rich Repeat Kinase 2 (LRRK2) G2019S Mutation in a Sample of Egyptian Patients with Parkinson's Disease, a Pilot Study
2014-09-27

This work was carried out in collaboration between all authors. Authors ESED suggested the idea of the study, shared in the study design, participated in the practical genomic part and wrote the paper. Author EMK managed the clinical part of the study, interpreted the clinical data. Author MSK managed DNA extraction from patients and interpretation of the results. Author TG participated in the practical genomic part, interpretation of the results. All authors read and approved the final manuscript.
Dysregulated serum response factor triggers formation of hepatocellular carcinoma
2014-09-29

The ubiquitously expressed transcriptional regulator serum response factor (SRF) is controlled by both Ras/MAPK (mitogen‐activated protein kinase) and Rho/actin signaling pathways, which are frequently activated in hepatocellular carcinoma (HCC). We generated SRF‐VP16iHep mice, which conditionally express constitutively active SRF‐VP16 in hepatocytes, thereby controlling subsets of both Ras/MAPK‐ and Rho/actin‐stimulated target genes. All SRF‐VP16iHep mice develop hyperproliferative liver nodules that progresses to lethal HCC. Some murine (m)HCCs acquire Ctnnb1 mutations equivalent to those in human (h)HCC. The resulting transcript signatures mirror those of a distinct subgroup of hHCCs, with shared activation of oncofetal genes including Igf2 , correlating with CpG hypomethylation at the imprinted Igf2/H19 locus. Conclusion: SRF‐VP16iHep mHCC reveal convergent Ras/MAPK and Rho/actin signaling as a highly oncogenic driver mechanism for hepatocarcinogenesis. This suggests simultaneous inhibition of Ras/MAPK and Rho/actin signaling as a treatment strategy in hHCC therapy. (H epatology 2015;61:979–989)
ERGO: A pilot study of ketogenic diet in recurrent glioblastoma
2014-09-29

After the publication of the article, the authors noted that they had made an error regarding certain data in the Results section. On page 1848 the sentence 'Thirteen of these received no salvage treatment' should be replaced by 'Nine of these stopped the diet'. The previous statement was erroneously inserted. We apologize for the mistake and possible misunderstanding. [the original article was published in the International Journal of Oncology 44: 1843-1852, 2014 DOI: 10.3892/ijo.2014.2382].
Visual SLAM for Autonomous MAVs with Dual Cameras
2014-09-29

This paper extends a monocular visual simultane- ous localization and mapping (SLAM) system to utilize two cameras with non-overlap in their respective field of views (FOVs). We achieve using it to enable autonomous navigation of a micro aerial vehicle (MAV) in unknown environments. The methodology behind this system can easily be extended to multi-camera rigs, if the onboard computation capability allows this. We analyze the iterative optimizations for pose tracking and map refinement of the SLAM system in multi- camera cases. This ensures the soundness and accuracy of each optimization update. Our method is more resistant to tracking failure than conventional monocular visual SLAM systems, especially when MAVs fly in complex environments. It also brings more flexibility to configurations of multiple cameras used onboard of MAVs. We demonstrate its e ciency with both autonomous flight and manual flight of a MAV. The results are evaluated by comparisons with ground truth data provided by an external tracking system.
Reproduction Number
2014-09-29

Abstract The basic reproduction number (or ratio) is the expected number of secondary cases of an infection, which one typical case could generate during its infectious period in a completely susceptible population. It is the most important theoretical concept in communicable disease epidemiology.
Global Transcriptional Start Site Mapping Using Differential RNA Sequencing Reveals Novel Antisense RNAs in Escherichia coli
2014-09-30

ABSTRACT While the model organism Escherichia coli has been the subject of intense study for decades, the full complement of its RNAs is only now being examined. Here we describe a survey of the E. coli transcriptome carried out using a differential RNA sequencing (dRNA-seq) approach, which can distinguish between primary and processed transcripts, and an automated prediction algorithm for transcriptional start sites (TSS). With the criterion of expression under at least one of three growth conditions examined, we predicted 14,868 TSS candidates, including 5,574 internal to annotated genes (iTSS) and 5,495 TSS corresponding to potential antisense RNAs (asRNAs). We examined expression of 14 candidate asRNAs by Northern analysis using RNA from wild-type E. coli and from strains defective for RNases III and E, two RNases reported to be involved in asRNA processing. Interestingly, nine asRNAs detected as distinct bands by Northern analysis were differentially affected by the rnc and rne mutations. We also compared our asRNA candidates with previously published asRNA annotations from RNA-seq data and discuss the challenges associated with these cross-comparisons. Our global transcriptional start site map represents a valuable resource for identification of transcription start sites, promoters, and novel transcripts in E. coli and is easily accessible, together with the cDNA coverage plots, in an online genome browser.
Guidelines for the standardization of preanalytic variables for blood‐based biomarker studies in Alzheimer's disease research
2014-09-30

Abstract The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood‐based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement provides (1) a synopsis of selected preanalytical methods utilized in many international AD cohort studies, (2) initial draft guidelines/SOPs for preanalytical methods, and (3) a list of required methodological information and protocols to be made available for publications in the field to foster cross‐validation across cohorts and laboratories.
Effect of Fluorescent Dyes on In Vitro -Differentiated, Late-Stage Plasmodium falciparum Gametocytes
2014-09-30

ABSTRACT Plasmodium falciparum gametocytes are not associated with clinical symptoms, but they are responsible for transmitting the pathogen to mosquitoes. Therefore, gametocytocidal interventions are important for malaria control and resistance containment. Currently available drugs and vaccines are not well suited for that purpose. Several dyes have potent antimicrobial activity, but their use against gametocytes has not been investigated systematically. The gametocytocidal activity of nine synthetic dyes and four control compounds was tested against stage V gametocytes of the laboratory strain 3D7 and three clinical isolates of P. falciparum with a bioluminescence assay. Five of the fluorescent dyes had submicromolar 50% inhibitory concentration (IC 50 ) values against mature gametocytes. Three mitochondrial dyes, MitoRed, dihexyloxacarbocyanine iodide (DiOC6), and rhodamine B, were highly active (IC 50 s &lt; 200 nM). MitoRed showed the highest activity against gametocytes, with IC 50 s of 70 nM against 3D7 and 120 to 210 nM against clinical isolates. All compounds were more active against the laboratory strain 3D7 than against clinical isolates. In particular, the endoperoxides artesunate and dihydroartemisinin showed a 10-fold higher activity against 3D7 than against clinical isolates. In contrast to all clinically used antimalarials, several fluorescent dyes had surprisingly high in vitro activity against late-stage gametocytes. Since they also act against asexual blood stages, they shall be considered starting points for the development of new antimalarial lead compounds.
Structure of a new chloroauric acid
2014-09-30

The new tetrachloroaurate ethanol hydrate HAuCl 4 ·0.65C 2 H 5 OH·1.35H 2 O was prepared from chloroauric acid trihydrate in ethanol. The compound crystallizes in the triclinic space group P \\bar 1 (No. 2). The [AuCl 4 ] − units in the structure have approximately square-planar symmetry, forming chains parallel to the crystallographic b -axis direction.
Differential impact of allelic ratio and insertion site in FLT3-ITD–positive AML with respect to allogeneic transplantation
2014-10-01

Key Points In FLT3-ITD–positive AML, high allelic ratio and ITD insertion site in TKD1 predict for low complete remission rates and poor survival. In FLT3-ITD–positive AML, allogeneic HSCT in first CR outweighs the negative impact of high allelic ratio on survival.
Prediction of placebo responses: a systematic review of the literature
2014-10-01

While results are heterogeneous, some congruence of predictors can be identified. PRs mainly appear to be moderated by expectations of how the symptom might change after treatment, or expectations of how symptom repetition can be coped with. It is suggested to include the listed constructs in future research. Furthermore, a closer look at variables moderating symptom change in control groups seems warranted.