julilili42/papers huggingface dataset:
Regulation of the human endogenous retroviral Syncytin‐1 and cell–cell fusion by the nuclear hormone receptors PPARγ/RXRα in placentogenesis
2012-03-05

Abstract Cytotrophoblast (CT) cell fusion into a syncytiotrophoblast is obligatory for placentation and mediated by the human endogenous retrovirus (HERV)‐W envelope gene Syncytin‐1. Abnormal placentation is associated with preeclampsia (PE), HELLP and intrauterine growth restriction (IUGR). In placentogenesis, the MAP‐kinase p38α regulates PPARγ/RXRα signaling and target genes, like leptin, resistin, ABCG2, and hCG. The aim of this study was to analyze PPARγ/RXRα signaling and target gene regulation using primary CT cultures, the trophoblastic cell line BeWo and placental tissues from patients with normal and abnormal placentation. CT from four different human control placentae and BeWo cells demonstrated that Syncytin‐1, other signaling members and CT cell fusions were regulated with PPARγ/RXRα activators troglitazone and 9‐ cis retinoic acid, via protein kinase A and p38α inhibition. Significant discordant regulations between CTs and BeWo were found. Two PPARγ/RXRα‐response‐elements from upstream regulatory elements and the 5′LTR of HERV‐W were confirmed with DNA‐protein binding assays using nuclear extracts and recombinant PPARγ/RXRα proteins. These promoter elements were validated with luciferase assays in the presence of PPARγ/RXRα modulators. Furthermore, troglitazone or 9‐ cis retinoic acid treatment of siRNA‐PPARγ and siRNA‐RXRα transfected BeWo cells proved the requirement of these proteins for Syncytin‐1 regulation. Thirty primary abnormal placentae from PE, HELLP and IUGR patients compared to 10 controls showed significant deregulation of leptin RNA and protein, p38α, phospho‐p38α, PPARγ, ABCG2, INSL4 and Syncytin‐1. Our study characterized PPARγ/RXRα signaling in human CT and cell fusions identifying Syncytin‐1 as a new target gene. Based on these results, a disturbed PPARγ/RXRα pathway could contribute to pathological human pregnancies. J. Cell. Biochem. 113: 2383–2396, 2012. © 2012 Wiley Periodicals, Inc.
Differential Contribution of the Repeats to Heparin Binding of HBHA, a Major Adhesin of Mycobacterium tuberculosis
2012-03-05

Mycobacterial HBHA undergoes structural adaptation upon interaction with GAGs, which is likely involved in binding specificities of the adhesin, and mycobacterial pathogens may use HBD polymorphisms for host or organ specificity. Further studies will aim at decoding the complementarity between HBD repeats and HS sequence.
Time Course and Pattern of Metastasis of Cutaneous Melanoma Differ between Men and Women
2012-03-06

Both, the pattern of metastatic spread with more locoregional metastasis in women, and the time course with retracted metastasis in women contributed to the more favorable outcome of women. Furthermore, the total rate of metastasis is increased in men. Interestingly, there is also a much more favorable long term survival of women after development of distant metastasis. It remains a matter of debate and of future research, whether hormonal or immunologic factors may be responsible for these sex differences.
Immunization with L. sigmodontis Microfilariae Reduces Peripheral Microfilaraemia after Challenge Infection by Inhibition of Filarial Embryogenesis
2012-03-06

Our results present a tool to understand the immunological basis of vaccine induced protection in order to develop a microfilariae-based vaccine that reduces adult worm burden and prevents microfilaraemia, a powerful weapon to stop transmission of filariasis.
The Axonal Guidance Receptor Neogenin Promotes Acute Inflammation
2012-03-06

Neuronal guidance proteins (NGP) were originally described in the context of axonal growth and migration. Yet recent work has demonstrated that NGPs also serve as guidance cues for immune competent cells. A crucial target receptor for NGPs during embryonic development is the neogenin receptor, however its role during acute inflammation is unknown. We report here that neogenin is abundantly expressed outside the nervous system and that animals with endogenous repression of neogenin (Neo1(-/-)) demonstrate attenuated changes of acute inflammation. Studies using functional inhibition of neogenin resulted in a significant attenuation of inflammatory peritonitis. In studies employing bone marrow chimeric animals we found the hematopoietic presence of Neo1(-/-) to be responsible for the attenuated inflammatory response. Taken together our studies suggest that the guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response and further define mechanisms shared between the nervous and the immune system.
Tautomeric and Conformational Properties of Benzoylacetone, CH3–C(O)–CH2–C(O)–C6H5: Gas-Phase Electron Diffraction and Quantum Chemical Study
2012-03-06

Tautomeric and structural properties of benzoylacetone, CH(3)-C(O)-CH(2)-C(O)-C(6)H(5), have been studied by gas-phase electron diffraction (GED) and quantum chemical calculations (B3LYP and MP2 approximation with different basis sets up to aug-cc-pVTZ). Analysis of GED intensities resulted in the presence of 100% enol tautomer at 331(5) K. The existence of two possible enol conformers in about equal amounts is confirmed by both GED and quantum chemical results. In both conformers the enol ring possesses C(s) symmetry with a strongly asymmetric hydrogen bond. The experimental geometric parameters are reproduced very closely by the B3LYP/cc-pVTZ method.
Probability Distribution of Precipitation Extremes for Weather Index–Based Insurance in the Zhujiang River Basin, South China
2012-03-07

Abstract In a changing climate, understanding the frequency of weather extremes is crucial to improving the management of the associated risks. The concept of weather index–based insurance is introduced as a new approach in weather risk adaptation. It can decrease the vulnerability to precipitation extremes that cause floods and economic losses in the Zhujiang River basin. The probability of precipitation extremes is a key input and the probability distribution of annual precipitation extremes is analyzed with four distribution functions [gamma 3, generalized extreme value (GEV), generalized Pareto, and Wakeby]. Three goodness-of-fit tests (Kolmogorov–Smirnov, Anderson–Darling, and Chi Squared) are applied to the distribution functions for annual time series (1961–2007) of 192 meteorological stations. The results show that maximum precipitation and 5-day-maximum precipitation are best described by the Wakeby distribution. On a basin scale, the GEV is the most reliable and robust distribution for estimating precipitation indexes for an index-based insurance program in the Zhujiang River basin. However, each station has to be analyzed individually as GEV is not always the best-fitting distribution function. Based on the distribution functions, spatiotemporal characteristics of return periods for maximum precipitation and 5-day-maximum precipitation are determined. The return levels of the 25- and 50-yr return periods show similar spatial pattern: they are higher in the southeast and lower in the southwest of the basin. This spatial distribution is in line with the annual averages. The statistical distribution of precipitation indexes delivers important information for a theoretical weather index–based insurance program.
Discus (Canaridiscus) laurisilvae sp. nov., a species from the laurel forest of La Gomera, Canary Islands (Gastropoda: Pulmonata: Discidae)
2012-03-07

A new endemic land snail species of the family Discidae, Atlantica (Canaridiscus) saproxylophaga Alonso, G. Holyoak &amp; Yanes 2011, was recently described from La Gomera, Canary Islands (in Yanes et al. 2011). According to Rähle &amp; Allgaier (2011) it is provisorily considered as belonging to the genus Discus. This species lives in the laurel forest and has the largest shell of all the Discidae hitherto known from Macaronesia. In the same habitat where D. saproxylophagus lives, we found individuals of similar size belonging to a second species of the taxon Canaridiscus. These two species show clear differences with respect to both shell morphology and genital anatomy, as described herein.
Probiotic E.faecalis — adjuvant therapy in children with recurrent rhinosinusitis
2012-03-08

Abstract Sinusitis is a frequent complication of respiratory tract infections. Probiotics are perceived to be useful in infections, allergies, and inflammations. Our prospective trial stratified 204 children with recurrent rhinosinusitis by age (2–11 years, 54m:64f; 12–18 years, 39m:47f) and assigned them to standard treatment (antibiotics, anticongestants) or additional 60 days Symbioflor-1 (SF1; Enterococcus faecalis 1.5–4.5x107 CFU). The number of sinusitis episodes was lower in SF1-treated patients (2.52±0.91) than among controls (3.27±1.36; p=0.01). Mean duration of the first sinusitis episode was 11.9±8.6 days with SF1, whereas it was 16.1±12.9 days in the younger controls (p=0.023) and 9.86±5.05 days in the elder controls (n.s.). Duration of subsequent sinusitis episodes was also shorter in SF1 patients (15.2±13.6 days) compared with controls (22.7±14.8 days; p=0.030). No adverse events were observed. Probiotic Enterococcus faecalis adjuvant to conventional therapy can reduce the number and duration of rhinosinusitis episodes in children and adolescents.
Identification of immunogenic microbial patterns takes the fast lane
2012-03-08

Innate immunity to microbial infection is an inherent feature of all multicellular eukaryotes. In contrast to jawed vertebrates, which, in addition to innate defenses, also possess noninheritable mechanisms of adaptive immunity, antimicrobial defenses of lower metazoans and plants are germline-encoded. Plants use a bipartite immune system to cope with infection (1). The evolutionarily older branch is based on recognition of common microbe-associated molecular patterns (MAMPs) by plant pattern recognition receptors (PRRs) or upon recognition by PRR-type receptors of host-derived damage-associated molecular patterns that are produced by deleterious microbial enzymatic activities or toxins (2). This type of plant immunity is referred to as MAMP-triggered immunity (MTI), and is equivalent to metazoan innate immunity. A second, evolutionarily younger, layer of plant immunity is referred to as effector-triggered immunity, which is based on the recognition of the presence or activities of microbial pathovar-specific effector proteins by cognate plant immune receptors (3).
{nBuMg(OR)}2 und {Mg(OR)2}2 (R = 2, 4, 6‐tBu3C6H2) – sterisch überfrachtete Magnesiumalkoholate
2012-03-08

Abstract Reaction of 2, 4, 6‐tri‐ tert ‐butylphenol ( 1 ) with di‐ n ‐butylmagnesium in the molar ratio 1:1 allows the synthesis of {( n Bu)Mg( μ ‐O R ) 2 Mg( n Bu)} ( 2 ) ( R = 2, 4, 6‐ t Bu 3 C 6 H 2 ), which reacts with excess 1 to give the homoleptic alcoholate complex {( R O)Mg(μ‐O R ) 2 Mg(O R )} ( 3 ) ( R = 2, 4, 6‐ t Bu 3 C 6 H 2 ). The structures of 2 and 3 were determined by X‐ray crystallography.
Faculty Opinions recommendation of In vivo electroporation restores the low effectiveness of DNA vaccination against HER-2/neu in aging.
2012-03-09

Experimental evidence has been provided that cancer vaccines are less effective at older age than in young adults. In this study, we evaluated the possibility to recover the low effectiveness of DNA immunization against HER-2/neu increasing plasmid uptake by cells from old mice through electroporation with the aim to enhance the activation of specific immune responses. Young and old Balb/c mice received two immunizations with a pCMV-ECDTM DNA plasmid using plasmid intramuscular injection followed by electroporation (IM + E) or plasmid intramuscular injection alone (IM), and successively, they were challenged with syngeneic HER-2/neu overexpressing TUBO cells. Young mice were completely protected whereas less than 60% protection was observed in old mice after IM immunization. IM + E immunization completely protected old mice against a TUBO cell challenge. The protection was associated with increased transgene expression in the site of immunization and with the induction of both humoral and cell-mediated immunity in old mice. We conclude that the effectiveness of anticancer DNA vaccination in old ages may be improved increasing plasmid uptake and transgene expression through electroporation, suggesting the relevant role of the first steps of the immunization process in the success of cancer vaccines at older age. PMID: 21922332
Leukemia-initiating cells of patient-derived acute lymphoblastic leukemia xenografts are sensitive toward TRAIL
2012-03-10

Abstract Cancer stem cells represent the most important target cells for antitumor therapy. TRAIL (TNF-related apoptosis-inducing ligand) is a potential anticancer agent that induces apoptosis in a wide variety of tumor cells, but its ability to target cancer stem cells is currently unknown. Here we investigated whether TRAIL targets leukemia-initiating cells. Limiting dilution transplantation assays were performed on xenografts from pediatric patients with precursor B-cell acute lymphoblastic leukemia (pre-B ALL) in NSG mice. In vitro treatment of xenograft cells with TRAIL significantly reduced and delayed their engraftment and procrastinated animal death from leukemia. Systemic TRAIL treatment of mice injected with patient-derived pre-B ALL xenograft cells abrogated leukemia in 3 of 5 mice in 1 sample. In conclusion, our data suggest that TRAIL targets leukemia-initiating cells derived from pre-B ALL xenografts in vitro and in vivo, and hence constitutes an attractive candidate drug for treatment of ALL.
Linking environmental processes to the in situ functioning of microorganisms by high‐resolution secondary ion mass spectrometry (NanoSIMS) and scanning transmission X‐ray microscopy (STXM)
2012-03-12

Summary Environmental microbiology research increasingly focuses on the single microbial cell as the defining entity that drives environmental processes. The interactions of individual microbial cells with each other, the environment and with higher organisms shape microbial communities and control the functioning of whole ecosystems. A single‐cell view of microorganisms in their natural environment requires analytical tools that measure both cell function and chemical speciation at the submicrometre scale. Here we review the technical capabilities and limitations of high‐resolution secondary ion mass spectrometry (NanoSIMS) and scanning transmission (soft) X‐ray microscopy (STXM) and give examples of their applications. Whereas NanoSIMS can be combined with isotope‐labelling, thereby localizing the distribution of cellular activities (e.g. carbon/nitrogen fixation/turnover), STXM provides information on the location and chemical speciation of metabolites and products of redox reactions. We propose the combined use of both techniques and discuss the technical challenges of their joint application. Both techniques have the potential to enhance our understanding of cellular mechanisms and activities that contribute to microbially mediated processes, such as the biogeochemical cycling of elements, the transformation of contaminants and the precipitation of mineral phases.
Effectiveness of IV Cannulation Skills Laboratory Training and Its Transfer into Clinical Practice: A Randomized, Controlled Trial
2012-03-12

Transfer of IV cannulation-related skills acquired in a skills laboratory is superior to bedside teaching when rated by independent video raters by means of IPPI and BC. It enables students to perform IV cannulation more professionally on volunteer students acting as patients.
B3N3 Borazine Substitution in Hexa‐peri‐Hexabenzocoronene: Computational Analysis and Scholl Reaction of Hexaphenylborazine
2012-03-12

Abstract The doping of graphene molecules by borazine (B 3 N 3 ) units may modify the electronic properties favorably. Therefore, the influence of the substitution of the central benzene ring of hexa‐ peri ‐hexabenzocoronene (HBC, C 42 H 18 ) by an isoelectronic B 3 N 3 ring resulting in C 36 B 3 N 3 H 18 (B3N3HBC) is investigated by computational methods. For comparison, the isoelectronic and isosteric all‐B/N molecule B 21 N 21 H 18 (termed BN) and its carbon derivative C 6 B 18 N 18 H 18 (C6BN), obtained by substitution of a central B 3 N 3 by a C 6 ring, are also studied. The substitution of C 6 in the HBC molecule by a B 3 N 3 unit results in a significant change of the computed IR vibrational spectrum between 1400 and 1600 cm −1 due to the polarity of the borazine core. The properties of the BN molecule resemble those of hexagonal boron nitride, and substitution of the central B 3 N 3 ring by C 6 changes the computed IR vibrational spectrum only slightly. The allowed transitions to excited states associated with large oscillator strengths shift to higher energy upon going from HBC to B3N3HBC, but to lower energy upon going from BN to C6BN. The possibility of synthesis of B3N3HBC from hexaphenylborazine (HPB) using the Scholl reaction (CuCl 2 /AlCl 3 in CS 2 ) is investigated. Rather than the desired B3N3HBC an insoluble and X‐ray amorphous polymer P is obtained. Its analysis by IR and 11 B magic angle spinning NMR spectroscopy reveals the presence of borazine units. The changes in the 11 B quadrupolar coupling constant C Q , asymmetry parameter η , and isotropic chemical shift δ iso ( 11 B) with respect to HPB are in agreement with a structural model that includes B3N3HBC‐derived monomeric units in polymer P. This indicates that both intra‐ and intermolecular cyclodehydrogenation reactions take place during the Scholl reaction of HPB.
Studying Language Change Using Price Equation and Pólya-urn Dynamics
2012-03-12

Language change takes place primarily via diffusion of linguistic variants in a population of individuals. Identifying selective pressures on this process is important not only to construe and predict changes, but also to inform theories of evolutionary dynamics of socio-cultural factors. In this paper, we advocate the Price equation from evolutionary biology and the Pólya-urn dynamics from contagion studies as efficient ways to discover selective pressures. Using the Price equation to process the simulation results of a computer model that follows the Pólya-urn dynamics, we analyze theoretically a variety of factors that could affect language change, including variant prestige, transmission error, individual influence and preference, and social structure. Among these factors, variant prestige is identified as the sole selective pressure, whereas others help modulate the degree of diffusion only if variant prestige is involved. This multidisciplinary study discerns the primary and complementary roles of linguistic, individual learning, and socio-cultural factors in language change, and offers insight into empirical studies of language change.
Hierarchical propagation of geometric constraints for full-custom physical design of ICs
2012-03-12

In industrial environments, full-custom layout design of analog and mixed-signal ICs is done hierarchically. In order to increase design efficiency, cell layouts are reused in the design hierarchy. Constraints forming relations between instances in different hierarchical contexts are of critical importance. While implementing a cell layout, these constraints have to be available in the cell's context. In this paper, a general definition of hierarchical constraints for a constraint-driven design flow is given. Furthermore it is shown, how top-down declared constraints can be propagated into another hierarchical context. Only by propagation they become visible and verifiable for bottom-up cell design. The feasibility of our proposed methodology is shown by applying it to a modular Smart Power IC of the automotive industry.
Beyond CMOS: benchmarking for future technologies
2012-03-12

The interaction between the design and the technology research communities working in nanoelectronics, and especially in the Beyond CMOS area, is characterised by a diversity of terminologies, modi operandi and the absence of a consensus on main priorities. We present the findings of the EU project NANO-TEC to date, in the quest to bring together these communities for the benefit of a stronger European Research Area. Through this, we present a summary of technology trends and a preliminary benchmarking analysis for a subset of these as an example of the project work. We summarise relevant design issues concerning these technologies and conclude with recommendations to bridge this design-technology gap.
Prognostic Value of Three Different Methods of MGMT Promoter Methylation Analysis in a Prospective Trial on Newly Diagnosed Glioblastoma
2012-03-13

Hypermethylation in the promoter region of the MGMT gene encoding the DNA repair protein O(6)-methylguanine-DNA methyltransferase is among the most important prognostic factors for patients with glioblastoma and predicts response to treatment with alkylating agents like temozolomide. Hence, the MGMT status is widely determined in most clinical trials and frequently requested in routine diagnostics of glioblastoma. Since various different techniques are available for MGMT promoter methylation analysis, a generally accepted consensus as to the most suitable diagnostic method remains an unmet need. Here, we assessed methylation-specific polymerase chain reaction (MSP) as a qualitative and semi-quantitative method, pyrosequencing (PSQ) as a quantitative method, and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a semi-quantitative method in a series of 35 formalin-fixed, paraffin-embedded glioblastoma tissues derived from patients treated in a prospective clinical phase II trial that tested up-front chemoradiotherapy with dose-intensified temozolomide (UKT-05). Our goal was to determine which of these three diagnostic methods provides the most accurate prediction of progression-free survival (PFS). The MGMT promoter methylation status was assessable by each method in almost all cases (n = 33/35 for MSP; n = 35/35 for PSQ; n = 34/35 for MS-MLPA). We were able to calculate significant cut-points for the continuous methylation signals at each CpG site analysed by PSQ (range, 11.5 to 44.9%) and at one CpG site assessed by MS-MLPA (3.6%) indicating that a dichotomisation of continuous methylation data as a prerequisite for comparative survival analyses is feasible. Our results show that, unlike MS-MLPA, MSP and PSQ provide a significant improvement of predicting PFS compared with established clinical prognostic factors alone (likelihood ratio tests: p<0.001). Conclusively, taking into consideration prognostic value, cost effectiveness and ease of use, we recommend pyrosequencing for analyses of MGMT promoter methylation in high-throughput settings and MSP for clinical routine diagnostics with low sample numbers.