julilili42/papers huggingface dataset:
Tools for the analysis of dose optimization: III. Pointwise sensitivity and perturbation analysis
2008-10-20

The major challenge in intensity-modulated radiotherapy planning is to find the right balance between tumor control and normal tissue sparing. The most desirable solution is never physically feasible, and a compromise has to be found. One possible way to approach this problem is constrained optimization. In this context, it is worthwhile to quantitatively predict the impact of adjustments of the constraints on the optimum dose distribution. This has been dealt with in regard to cost functions in a previous paper. The aim of the present paper is to introduce spatial resolution to this formalism. Our method reveals the active constraints in a target subvolume that was previously selected by the practitioner for its insufficient dose. This is useful if a multitude of constraints can be the cause of a cold spot. The response of the optimal dose distribution to an adjustment of constraints (perturbation) is predicted. We conclude with a clinical example.
Bimolecular Fluorescence Complementation (BiFC) to Study Protein-protein Interactions in Living Plant Cells
2008-10-21

Dynamic networks of protein-protein interactions regulate numerous cellular processes and determine the ability of cells to respond appropriately to environmental stimuli. However, the study of protein complex formation in living plant cells has remained experimentally difficult and time-consuming and requires sophisticated technical equipment. In this report, we describe a bimolecular fluorescence complementation (BiFC) technique for visualization of protein-protein interactions in plant cells. This approach is based on the formation of a fluorescent complex by two non-fluorescent fragments of the yellow fluorescent protein (YFP) brought together by the association of interacting proteins fused to these fragments. We present the BiFC vectors currently available for the transient and stable transformation of plant cells and provide a detailed protocol for the successful use of BiFC in plants.
Sex-related differences in foot shape
2008-10-21

The purpose of the study was to investigate sex-related differences in foot morphology. In total, 847 subjects were scanned using a 3-D-footscanner. Three different analysis methods were used: (1) comparisons were made for absolute foot measures within 250-270 mm foot length (FL); (2) and for averaged measures (% FL) across all sizes; (3) the feet were then classified using a cluster analysis. Within 250-270 mm FL, male feet were wider and higher (mean differences (MD) 1.3-5.9 mm). No relevant sex-related differences could be found in the comparison of averaged measures (MD 0.3-0.6% FL). Foot types were categorised into voluminous, flat-pointed and slender. Shorter feet were more often voluminous, longer feet were more likely to be narrow and flat. However, the definition of 'short' and 'long' was sex-related; thus, allometry of foot measures was different. For shoe design, measures should be derived for each size and sex separately. Different foot types should be considered to account for the variety in foot shape. Improper footwear can cause foot pain and deformity. Therefore, knowledge of sex-related differences in foot measures is important to assist proper shoe fit in both men and women. The present study supplements the field of knowledge within this context with recommendations for the manufacturing of shoes.
The Determination of Protein-protein Interactions by the Mating-based Split-ubiquitin system (mbSUS)
2008-10-21

Dynamic and reversible protein-protein interactions have a pivotal function in all living cells. For instance, protein-protein interactions are involved in the assembly and regulation of multimeric enzymes and transcription factors, various signal response pathways, intracellular sorting and movement of proteins and membrane vesicles, cell-to-cell protein transport, and many others. Here we provide a detailed protocol for the mating-based split-ubiquitin system (mbSUS), which is a sensitive and user-friendly alternative to the classical yeast two-hybrid system in particular. mbSUS relies on the ubiquitin-degradation pathway as a sensor for protein-protein interactions. Thus, mbSUS is predominantly suitable for the determination of full-length proteins localized in the cytoplasm and in or at membrane compartments, without the need for their truncation and nuclear mislocation. In addition, we present a set of Gateway compatible mbSUS vectors that allow the rapid generation of constructs for fast and efficient interaction studies. An additional vector is introduced that allows the extension of mbSUS for the analysis of oligomeric protein complex formation and competition assays in vivo. In summary, mbSUS provides an additional versatile tool for protein-protein interaction studies, which is complementary to in planta assays such as BiFC and FRET.
Analysis of Plant Regulatory DNA Sequences by Transient Protoplast Assays and Computer Aided Sequence Evaluation
2008-10-21

The orchestrated regulation of hundreds of genes responding in a temporal, spatial, and conditional expression is in part mediated by the transient binding of transcription factors to their specific DNA motifs. The analysis of these cis-regulatory DNA sequences is still a challenging task. Therefore, the combination of the transient protoplast expression assay with computer aided sequence analysis is a preferred method for regulatory sequence analysis. The protocols given here describe the use of a reporter gene plasmid to investigate the effects of a transiently co-expressed transcription factor gene in planta. As a number of bioinformatic analysis tools for cis-elements are publicly available, we suggest a workflow for the electronic analysis of promoter sequences. This is in particular difficult, as most analysis programs have not been developed for the investigation of single sequences. We provide insight into bioinformatics tools that investigate cis-element presence, their distribution, and implications for further functional analyses.
Examining Protein Stability and Its Relevance for Plant Growth and Development
2008-10-21

Eukaryotes control many aspects of growth and development such as cell cycle progression and gene expression through the selective degradation of regulatory proteins by way of the 26S proteasome. Generally, proteasomal degradation requires the poly-ubiquitylation of degradation targets by E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, and E3 ubiquitin ligases. Specificity is brought to the process by E3 ubiquitin ligases, which engage in direct interactions with the degradation substrate to bring it into the proximity of the E2 enzyme. The abundance of genes encoding E3 ligase subunits in plant genomes invites the hypothesis that protein degradation plays an important role in the control of many plant growth processes, and it is therefore not surprising that proteasomal degradation has already been implicated in several important response pathways. However, most of the genes with a predicted role in the ubiquitin-proteasome pathway still remain to be characterized and the identity of their degradation substrates needs to be revealed. In this chapter, we give an overview of the ubiquitin-proteasome system and the pathway proteins that have been examined in Arabidopsis to date. We review the methods required to identify and characterize the proteins that play a role in protein degradation or that are the target for proteasomal degradation.
Analysis of Plant Regulatory DNA sequences by the Yeast-One-Hybrid Assay
2008-10-21

Regulatory DNA sequences harbor the essential information to control specific gene expression changes and integrate information derived from upstream signaling cascades. This regulatory potential is mediated by direct binding of proteins, e.g., transcription factors, to defined stretches of DNA motifs in regulatory regions. The analysis of these DNA regions, at which several signaling pathways could merge to orchestrate gene expression, is still a challenging task. To date, the combination of functional approaches in the laboratory and computer aided sequence evaluation is frequently used for regulatory sequence analysis. The yeast-one-hybrid method is a possible approach to test for direct binding of plant proteins to DNA in a heterologous system. Moreover, it is the most frequently used method for the identification of DNA-binding proteins targeting a given DNA sequence by screening a cDNA library.
Predicting the Claims-Development-Result in the Chain-Ladder Method for Correlated Run-Off Portfolios
2008-10-21

In the present paper we analyse how the estimators from Merz u. Wuthrich (2007) could be generalised to the case of N correlated run-off triangles. The simultaneous view on N correlated subportfolios is motivated by the fact, that in practice a run-off portfolio often has to be divided in subportfolios, so that the homogeneity assumption of the claims reserving method on each subportfolio is satisfied. We derive an explicit formula for the process-variance, the estimation-error and the prediction error made by the forecast for the claims development result with the Chain-Ladder method. We illustrate the results by an example.
Limits on an Energy Dependence of the Speed of Light from a Flare of the Active Galaxy PKS 2155-304
2008-10-22

In the past few decades, several models have predicted an energy dependence of the speed of light in the context of quantum gravity. For cosmological sources such as active galaxies, this minuscule effect can add up to measurable photon-energy dependent time lags. In this Letter a search for such time lags during the High Energy Stereoscopic System observations of the exceptional very high energy flare of the active galaxy PKS 2155-304 on 28 July 2006 is presented. Since no significant time lag is found, lower limits on the energy scale of speed of light modifications are derived.
Interferon‐γ down‐regulates NKG2D ligand expression and impairs the NKG2D‐mediated cytolysis of MHC class I‐deficient melanoma by natural killer cells
2008-10-22

Abstract NKG2D operates as an activating receptor on natural killer (NK) cells and costimulates the effector function of αβ CD8 + T cells. Ligands of NKG2D, the MHC class I chain‐related (MIC) and UL16 binding protein (ULBP) molecules, are expressed on a variety of human tumors, including melanoma. Recent studies in mice demonstrated that NKG2D mediates tumor immune surveillance, suggesting that antitumor immunity in humans could be enhanced by therapeutic manipulation of NKG2D ligand (NKG2DL) expression. However, signals and mechanisms regulating NKG2DL expression still need to be elucidated. Here, we asked whether the proinflammatory cytokine Interferon‐γ (IFN‐γ) affects NKG2DL expression in melanoma. Cell lines, established from MHC class I‐negative and ‐positive melanoma metastases, predominantly expressed MICA and ULBP2 molecules on their surface. Upon IFN‐γ treatment, expression of MICA, in some cases, also of ULBP2 decreased. Besides melanoma, this observation was made also for glioma cells. Down‐regulation of NKG2DL surface expression was dependent on the cytokine dose and the duration of treatment, but was neither due to an intracellular retention of the molecules nor to an increased shedding of ligands from the tumor cell surface. Instead, quantitative RT‐PCR revealed a decrease of MICA‐specific mRNA levels upon IFN‐γ treatment and siRNA experiments pointed to an involvement of STAT‐1 in this process. Importantly, IFN‐γ‐treated MHC class I‐negative melanoma cells were less susceptible to NKG2D‐mediated NK cell cytotoxicity. Our study suggests that IFN‐γ, by down‐regulating ligand expression, might facilitate escape of MHC class I‐negative melanoma cells from NKG2D‐mediated killing by NK cells. © 2008 Wiley‐Liss, Inc.
Salt stress affects xylem differentiation of grey poplar (Populus × canescens)
2008-10-22

In this study the impact of salt stress on the physiology and wood structure of the salt-sensitive Populus x canescens was investigated. Two weeks of salt stress altered wood anatomy significantly. The xylem differentiation zone was reduced and the resulting vessels exhibited reduced lumina. To understand this phenomenon, ion composition, levels of corresponding transcripts and of the stress hormone ABA were analysed. With increasing sodium and chloride concentrations, a general reduction of potassium was found in roots and shoots, but not in leaves. Consequently, the corresponding K+ channel transcripts in roots favoured K+ release. The overall osmolarity in leaves was up to fourfold higher than in roots or shoots. Therefore, adjustment of the K+/Na+ balance seemed not to be required in leaves. Sodium increased gradually from roots to shoots and then to leaves indicating that sodium storage took place first in roots, then in shoots, and finally in leaves to protect photosynthesis from salt effects as long as possible. Since leaf abscisic acid levels markedly increased, stomatal closure seemed to limit CO2 uptake. As a consequence, diminished nutrient supply to the cambium in combination with lowered shoot K+ content led to decreased vessel lumina, and a reduction of the radial cambium was observed. Thus, xylem differentiation was curtailed and the development of full size vessels was impaired.
Gliding dislocations in Bi2Te3 materials
2008-10-22

Abstract In Bi 2 Te 3 , dislocations were found with an uniquely high mobility at room temperature. The gliding dislocations were analysed and their effect on the thermoelectric properties is discussed. The glide of dislocations was induced by heating with a focused electron beam at 120 keV, external stresses were not applied. The dislocations were bowed out in the glide direction and were only pinned at the surface of the samples. Stereomicroscopy combined with image simulations yielded basal plane dislocations with a density of 10 9 cm –2 and Burgers vectors of type 〈110〉. Video sequences showing the glide of single dislocations and groups of dislocations were recorded. Isolated dislocations showed a high mobility in ±〈110〉 direction at a velocity of 10–100 nm s –1 . Dislocation dipoles were pinned and did not glide. Dislocations equidistantly arranged within the same glide plane showed a collective movement. Dislocations piled up in different glide planes were fixed and acted as barriers for gliding dislocations. The motion of dislocations was attributed to residual shear stresses of about 10 MPa, and their glide directions depended on the sign of the Burgers vector. Attractive and repulsive forces of dislocations directly visualise the forces due to the elastic strain fields of other dislocations. The relevance of phonon scattering on dislocations in Bi 2 Te 3 , particularly due to their high mobility and density, was confirmed by two inspections: (i) Dislocations decrease the lattice thermal conductivity due to phonon scattering on the elastic strain field. The phonon mean free path was estimated to about 800 μm at 3 K and agreed with published data. (ii) The dislocation resonance theory of Granato and Lücke predicts an interaction between phonons and dislocations acting as oscillating strings. The attenuation of ultrasound was estimated and was compared with published data. (© 2009 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Calendar calculating in savants with autism and healthy calendar calculators
2008-10-22

Background Calendar calculation is the ability to quickly name the day that a given date falls on. Previous research has suggested that savant calendar calculation is based on rote memory and the use of rule-based arithmetic skills. The objective of this study was to identify the cognitive processes that distinguish calendar calculation in savant individuals from healthy calendar calculators. Method Savant calendar calculators with autism (ACC, n =3), healthy calendar calculators (HCC, n =3), non-savant subjects with autism ( n =6) and healthy calendar calculator laymen ( n =18) were included in the study. All participants calculated dates of the present (current month). In addition, ACC and HCC also calculated dates of the past and future 50 years. Results ACC showed shorter reaction times and fewer errors than HCC and non-savant subjects with autism, and significantly fewer errors than healthy calendar calculator laymen when calculating dates of the present. Moreover, ACC performed faster and more accurate than HCC regarding past dates. However, no differences between ACC and HCC were detected for future date calculation. Conclusions The findings may imply distinct calendar calculation strategies in ACC and HCC, with HCC relying on calendar regularities for all types of dates and an involvement of (rote) memory in ACC when processing dates of the past and the present.
Brachial plexus lesions: 10 Years of experience in a center for microsurgery in Germany
2008-10-22

Abstract Aim: Brachial plexus lesions are commonly associated with complete or partial plegia of affected muscles even after microsurgical treatment. This study provides an overview of strategies and outcomes of 42 patients operated in a center for peripheral nerve surgery in Germany. Methods: Postsurgically, the patients were followed up and examined for strength in various muscle groups by applying a standard clinical classification (M0–M5). Sensitivity was estimated by differentiation between blunt and sharp touch. The patients were asked via questionnaire about their postsurgical daily life. Most of the patients received a grafting procedure using the sural nerve. Different microsurgical techniques were applied according to the underlying pathology: Intercostal nerve transfer, end‐to‐side coaptation, and direct grafting to different recipient nerves. Results: Only the 27 patients, who had a follow‐up time of at least 36 months, presented a measurable function in the affected extremity. Elbow‐flexion was restored in 15 cases. Triceps function was reconstructed in 7 patients of 27. One patient was able to move digits toward the palm without completing a full fist. Ten patients were able to flex the wrist and 4 could extend it. Conclusion: The results were estimated as acceptable for biceps reconstruction but poor for the other muscle groups. Some treatment strategies, which are presently under frequent discussion (contralateral C7‐transfer, banked autografts, Oberlin procedure), were not applied. However, some of these techniques may provide a key to improve the results. © 2008 Wiley‐Liss, Inc. Microsurgery, 2009.
High‐performance liquid chromatography/mass spectrometric identification of dibenzylbutyrolactone‐type lignans: insights into electrospray ionization tandem mass spectrometric fragmentation of lign‐7‐eno‐9,9′‐lactones and application to the lignans of Linum usitatissimum L. (Common Flax)
2008-10-22

Abstract In continuation of our studies into the mass spectrometric detection of natural lignans and their identification in complex mixtures such as crude plant extracts, the electrospray ionization tandem mass spectrometric (ESI‐MS/MS) fragmentation of Δ 7,8 ‐unsaturated dibenzylbutyrolactone‐type lignans (lign‐7‐eno‐9,9′‐lactones) was studied in detail. It is demonstrated that the characteristic fragmentation allows unambiguous identification including distinction between constitutional isomers. These lignans containing an α , β ‐unsaturated lactone structure exist as equilibrium mixtures of E‐ and Z‐ isomers indistinguishable by mass spectrometry, but it is shown that chromatographic retention time can be used to distinguish between the isomeric forms. Based on these observations, re‐analysis of the dichloromethane extract obtained from flowering aerial parts of Linum usitatissimum L. by high‐performance liquid chromatography (HPLC)/ESI‐MS/MS led to the identification of eighteen lignans of these types (five lignano‐ and one lignenolactone previously reported along with five further lignano‐ as well as seven lignenolactones hitherto unreported for this plant). The simultaneous identification of eighteen different lignans in the complex matrix of a crude plant extract by a single analysis demonstrates the potential of this method, which will certainly lead to new insights into the lignan composition and metabolism of different Linum species and many other plants. Copyright © 2008 John Wiley &amp; Sons, Ltd.
Age‐dependent gene expression profile and protein expression in a transgenic rat model of Huntington's disease
2008-10-22

Abstract Polyglutamine‐induced changes in gene expression have been demonstrated by using several mouse models of Huntington's disease (HD), which express extreme numbers of CAG repeats. We have recently developed a transgenic rat model of HD carrying a truncated huntingtin fragment with 51 CAG repeats, which is in the range seen in adult HD patients. For further evaluation, we have performed microarray analyses on whole brains of transgenic rats at 3 and 12 months of age and correlated it with protein expression by Western blot analysis. We found that genes functionally associated with gene expression and behavior were differently regulated already at 3 months of age, whereas at 12 months of age especially genes related to neurological diseases and cell‐to‐cell signaling and interaction were dysregulated. A detailed analysis of canonical pathways revealed that at 3 months of age genes in calcium signaling and synaptic long term potentation pathways were altered, while at 12 months of age, additionally, expression level of many genes implicated in Huntington's disease signaling, were changed.
Receptor-Like Kinase ACR4 Restricts Formative Cell Divisions in the Arabidopsis Root
2008-10-23

During the development of multicellular organisms, organogenesis and pattern formation depend on formative divisions to specify and maintain pools of stem cells. In higher plants, these activities are essential to shape the final root architecture because the functioning of root apical meristems and the de novo formation of lateral roots entirely rely on it. We used transcript profiling on sorted pericycle cells undergoing lateral root initiation to identify the receptor-like kinase ACR4 of Arabidopsis as a key factor both in promoting formative cell divisions in the pericycle and in constraining the number of these divisions once organogenesis has been started. In the root tip meristem, ACR4 shows a similar action by controlling cell proliferation activity in the columella cell lineage. Thus, ACR4 function reveals a common mechanism of formative cell division control in the main root tip meristem and during lateral root initiation.
Association of the FTO rs9939609 Single Nucleotide Polymorphism With C‐reactive Protein Levels
2008-10-23

Adipose tissue is a key factor determining C‐reactive protein (CRP) plasma levels. Variation at the fat‐mass and obesity‐associated (FTO) gene locus has been reported to be associated with increased body fat. We investigated whether the FTO rs9939609 T&gt;A single nucleotide polymorphism might alter CRP levels in a population‐based sample of 2,415 participants from a large prospective cohort study. Genotype/phenotype relationships were studied by linear trend analysis stratified by sex. The rs9939609 A‐allele was significantly associated with CRP levels in both genders (men, +21%, P = 0.002; women, +14%, P = 0.01 per A‐allele). The association was attenuated, but remained statistically significant after additional adjustment for BMI, waist‐to‐hip ratio, and other potential confounding factors (men, +14%, P = 0.03; women, +12%, P = 0.02; per A‐allele). Similar results were obtained when subjects with CRP levels higher then 10 mg/l were excluded. Our data provide preliminary evidence that the FTO rs9939609 T&gt;A polymorphism contributes to variation in plasma CRP levels independently of obesity indices.