julilili42/papers huggingface dataset:
A 16-Residue Peptide Fragment of Macrophage Migration Inhibitory Factor, MIF-(50–65), Exhibits Redox Activity and Has MIF-like Biological Functions
2003-08-29

Macrophage migration inhibitory factor (MIF) is a cytokine that participates in the host inflammatory response. A Cys-Xaa-Xaa-Cys (CXXC)-based thiol-protein oxidoreductase activity of MIF is associated with certain biological functions. Peptides spanning the CXXC region of thiol-protein oxidoreductases retain some biochemical properties of the full-length protein. We report on the characterization of CXXC-spanning MIF-(50-65) and its serine variant, C57S/C60S-MIF-(50-65). Following disulfide-mediated cyclization, MIF-(50-65) adapted a beta-turn conformation comparable with that of beta-turn-containing cyclo-57,60-[Asp57,Dap60]MIF-(50-65). MIF-(50-65) had a redox potential E'0 of -0.258 V and formed mixed disulfides with glutathione and cysteine. MIF-(50-65) but not C57S/C60S-MIF-(50-65) had oxidoreductase activity in vitro. Intriguingly, MIF-(50-65) exhibited MIF-like cellular activities. The peptide but not its variant had glucocorticoid overriding and proliferation-enhancing activity and stimulated ERK1/2 phosphorylation. MIF-(50-65) and its variant bound to the MIF-binding protein JAB1 and enhanced cellular levels of p27Kip1. As the peptide and its variant were endocytosed at similar efficiency, sequence 50-65 appears sufficient for the JAB1-related effects of MIF, whereas other activities require CXXC. Cyclo-57,60-[Asp57,Dap60]MIF-(50-65) activated ERK1/2, indicating that CXXC-dependent disulfide and beta-turn formation is associated with an activity-inducing conformation. We conclude that CXXC and sequence 50-65 are critical for the activities of MIF. MIF-(50-65) is a surprisingly short sequence with MIF-like functions that could be an excellent molecular template for MIF therapeutics.
In Vivo Reconstitution of the FhuA Transport Protein ofEscherichia coliK-12
2003-08-29

ABSTRACT The FhuA protein in the outer membrane of Escherichia coli actively transports ferrichrome and the antibiotics albomycin and rifamycin CGP 4832 and serves as a receptor for the phages T1, T5, and φ80 and for colicin M and microcin J25. The crystal structure reveals a β-barrel with a globular domain, the cork, which closes the channel formed by the barrel. Genetic deletion of the cork resulted in a β-barrel that displays no FhuA activity. A functional FhuA was obtained by cosynthesis of separately encoded cork and the β-barrel domain, each endowed with a signal sequence, which showed that complementation occurs after secretion of the fragments across the cytoplasmic membrane. Inactive complete mutant FhuA and an FhuA fragment containing 357 N-proximal amino acid residues complemented the separately synthesized wild-type β-barrel to form an active FhuA. Previous claims that the β-barrel is functional as transporter and receptor resulted from complementation by inactive complete FhuA and the 357-residue fragment. No complementation was observed between the wild-type cork and complete but inactive FhuA carrying cork mutations that excluded the exchange of cork domains. The data indicate that active FhuA is reconstituted extracytoplasmically by insertion of separately synthesized cork or cork from complete FhuA into the β-barrel, and they suggest that in wild-type FhuA the β-barrel is formed prior to the insertion of the cork.
Help Seeking and Help Design in Interactive Learning Environments
2003-09-01

Many interactive learning environments (ILEs) offer on-demand help, intended to positively influence learning. Recent studies report evidence that although effective help-seeking behavior in ILEs is related to better learning outcomes, learners are not using help facilities effectively. This selective review (a) examines theoretical perspectives on the role of on-demand help in ILEs, (b) reviews literature on the relations between help seeking and learning in ILEs, and (c) identifies reasons for the lack of effective help use. We review the effect of system-related factors, of student-related factors, and of interactions between these factors. The interaction between metacognitive skills and cognitive factors is important for appropriate help seeking, as are a potentially large space of system-related factors as well as interactions among learner- and system-related factors. We suggest directions for future research.
Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells
2003-09-01

IL-12 p40–related cytokines such as IL-12 p35/p40 heterodimer and IL-23 (p19/p40) are potent regulators of adaptive immune responses. Little is known, however, about the transcriptional regulation of the p40 gene in vivo. In an attempt toward this goal, we have generated transgenic mice expressing firefly luciferase under the control of the IL-12 p40 promoter. High constitutive transgene expression was found in the small intestine only, whereas little reporter gene activity was observed in other tissues. Within the small bowel, constitutive promoter activity was restricted to the terminal ileum and associated with high expression of p40 mRNA as well as p40 and IL-23 p19/p40 proteins. The cells constitutively producing IL-12 p40 were identified as CD8α and CD11b double-negative CD11c+ lamina propria dendritic cells (LPDCs) that represent a major cell population in the lamina propria of the small intestine, but not in the colon. FISH directly demonstrated the uptake of bacteria by a subset of LPDCs in the terminal ileum that was associated with p40 expression. Furthermore, little or no p40 protein expression in LPDCs was found in the terminal ileum of germfree mice, indicating a key role of the intestinal flora for constitutive p40 expression. In addition, analysis of transgenic mice with a mutated NF-κB target site in the p40 promoter showed a critical role of NF-κB for constitutive transgene expression. Our data reveal important functional differences between the mucosal immune systems of the small and large bowel in healthy mice and suggest that the high bacterial load in the terminal ileum activates p40 gene transcription in LPDCs through NF-κB. These data suggest a predisposition of the terminal ileum to develop chronic inflammatory responses through IL-23 and thus may provide a molecular explanation for the preferential clinical manifestation of Crohn disease in this part of the gut.
Radioprotection of Normal Tissue to Improve Radiotherapy: The Effect of the Bowman Birk Protease Inhibitor
2003-09-01

Specific radioprotection of normal tissue represents a promising approach to improve radiotherapy. The ultimate feature of a normal tissue selective radioprotector is that tumor tissue is excluded from protection. Radioprotectors of the current generation, such as Ethyol, are not explicit normal tissue specific. In contrast, the Bowman Birk protease inhibitor, which is known to prevent in vitro and in vivo radiation-induced carcinogenesis, was found to be normal tissue specific. Moreover, the molecular restrictions for this specificity were identified. The radioprotective effect is dependent upon the presence of a functional wt. TP53. Since a high amount of tumors have lost TP53 function during tumor development, the clinical application of BBI to protect normal tissue from radiation damage would effectively improve the therapeutic outcome of radiation therapy. We succeeded to identify stimulation of DNA-repair mechanisms, such as nucleotide excision repair (NER) and nonhomologous end joining (NHEJ), as molecular mode of action. These results are in good agreement with the observations that BBI concomitantly exhibits anticarcinogenic effect and radioprotective effects. Taken together, BBI is recommended as a radioprotector for normal tissue expressing wild type TP53 during treatment of tumors characterized by a mutant TP53.
Professional Careers of the German Olympic Athletes
2003-09-01

Successful careers in top-performance sports demand large amounts of time and personal resources and normally they take a course parallel to the period of educational and professional qualification. Regarding careers of former top-performance athletes, the question arises as to how far the engagement in top-performance sports has an influence on the professional career path. This article aims to categorize the professional careers of top-performance athletes and to connect them with the subjective ratings of the respondents. This will be carried out by means of objective life-course data of former Olympic athletes. The theoretical approach is based on recent conceptions of life-course research and of professional socialization research. In a postal inquiry of 616 successful German Olympic athletes (male and female) the sports and professional careers were recorded retrospectively. The results show that former top-performance athletes generally have higher educational qualifications and professional positions than the German population. But as there are big differences with regard to the individual career patterns, a typology of professional careers seems to be practical. For that purpose, a classification typology of professional careers was developed using cluster analysis. The engagement in sports rather favours the professional career in its course.
Membrane Targeted Anticancer Drugs: Potent Inducers of Apoptosis and Putative Radiosensitisers
2003-09-01

In the last two decades, cellular membranes have been identified as novel targets for antineoplastic drugs. Two classes of synthetic phospholipid analogues: the alkyllysophospholipids (ALP) with the prototypical 1-O-Octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (Et-18-OCH3, Edelfosine), as well as the alkylphosphocholines (APC) with the prototypical hexadecylphosphocholine (HePC, Miltefosine), have been identified targeting cellular membranes and exerting potent antineoplastic effects in cell culture and animal models. In contrast to most of the chemotherapeutic agents in clinical use, APC and ALP primarily interfere with cellular membranes without direct interaction with the DNA. They modulate membrane permeability and fluidity, membrane lipid composition, metabolism of phospholipids and proliferation signal transduction. Interestingly, similar to DNA-damaging drugs, ALP and APC induce apoptotic cell death. Furthermore, combination experiments with cytotoxic drugs or radiation revealed a synergistic effect in leukaemic and brain tumour cell lines. These findings together with the observations that ALP and APC selectively kill malignant cells, that they lack bone marrow toxicity and even exert growth stimulatory effects on hematopoietic progenitor cells make ALP and APC a promising tool for novel approaches in cancer chemotherapy. In this contribution, novel findings on the mechanism of action, apoptotic signalling pathways and putative radiosensitising effects of ALP and APC were reviewed, with a special focus on erucylphosphocholine (ErPC), the prototype of the novel intravenously applicable APC derivatives.
The Emerging Dialogue Between Psychoanalysis and Neuroscience: Neuroimaging Perspectives
2003-09-01

Current progress in the cognitive neurosciences is highly relevant to the development of psychoanalytic theory and practice. Neuroscience is today becoming mature enough to provide empirical biological approaches for the investigation of psychoanalytic models and observations. The current state of functional neuroimaging techniques is reviewed, selected paradigms and findings relevant to psychotherapy research are presented, and ways to pursue the dialogue between psychoanalysts and neuroscientists are discussed, as are some related obstacles and pitfalls. The emerging dialogue between psychoanalysts and neuroscientists may help not only to reestablish a solid position of psychodynamic theory and treatment in contemporary medicine, but also to bridge the division between “psychological” and “somatic” treatments, and gain important insights into the mind-brain relationship.
Morphological pathways in the evolution of Early and Middle Devonian ammonoids
2003-09-01

The principal conch parameters—whorl expansion rate, whorl overlap rate, umbilical width, and whorl thickness—of Early and Middle Devonian ammonoids have been extensively investigated. Stratophenetic analyses show long-term trends in the transformations of these characters over long periods of time, but sudden and rapid reversals can also be observed. On the basis of these four quantifiable conch parameters and supplementary qualitative characters, ten ammonoid morphs were distinguished. Reconstruction of the evolutionary history of these morphs reflects the existence of two major phylogenetic lineages, both already visible in Early Devonian faunas. The agoniatitid lineage is characterized by slow character development and leads to the Frasnian gephuroceratids; the anarcestid lineage displays rapid morphological evolution that leads to the late Givetian pharciceratids as well as the Middle and Late Devonian tornoceratids. Morphological evolution is interpreted as partly limited by geometrical and physical constraints.
Solid State Metathesis Reactions in Various Applications
2003-09-01

Abstract Solid state metathesis reactions have been studied in fused silica tubes, by differential thermal analysis, and by X‐ray powder diffraction. A selection of reactions between metal (La, Nb, and Ni) chlorides and lithium nitride or lithium acetylide were investigated to get more insight into reaction pathways and intermediate reaction stages that may be adopted on course of the formation of metal nitrides or carbides. Intermediate compounds are considered to be important because they can control the reactivity of a system. Such compounds were traced by changing the molar ratios of reaction partners away from the salt‐balanced binary metal nitride or carbide target compositions. New preparative perspectives are discovered when metal chlorides were reacted with lithium nitridoborate or lithium cyanamide. Due to their reductive nature towards several d‐block metal chlorides, (BN 2 ) 3‐ and (CN 2 ) 2‐ react to form metals or metal nitrides plus X‐ray amorphous BN, and probably C 3 N 4 . With lanthanum chloride they can react to form nitridoborates and nitridocarbonates. The metathesis reaction between lithium cyanamide and cyanuric chloride (C 3 N 3 Cl 3 ) instead of metal chloride was studied for the synthesis of C 3 N 4 .
Frequency and Phenotypic Variability of the GAG Deletion of the DYT1 Gene in an Unselected Group of Patients With Dystonia
2003-09-01

Our data underline the wide range of phenotypic variability of the DYT1 mutation. A priori prediction of the mutation carrier status in dystonic patients and genetic counseling of affected families with respect to the clinical manifestation may prove difficult.
Fibronectin and laminin increase resistance to ionizing radiation and the cytotoxic drug Ukrain®in human tumour and normal cellsin vitro
2003-09-01

The data corroborate the findings of other groups that cell adhesion-mediated resistance to either single or combined drug and radiation exposure is tightly correlated to specific ECM proteins. By demonstrating a strong modulatory impact of FN and LA on the radiosensitivity-modifying activity of the drug Ukrain, the set findings are also highly important for the assessment of drug and radiation effects within in vitro cytotoxicity studies. The data give the first mechanistic insights into specific FN- and LA-modulated cellular resistance mechanisms as well as into the important role for beta1-integrins using the unique cytotoxic and radiosensitivity-modifying drug Ukrain.
Radiation therapy alone in early stage non‐small cell lung cancer
2003-09-01

Abstract Among the patients with early stage (I/II) non‐small cell lung cancer (NSCLC), there are those who, due to medical comorbidities, advanced age, or refusal, never undergo surgery. For them, exclusive radiation therapy (RT) has been the treatment of choice, achieving median survival times of 30 months and 5‐year survival of up to 42%. Doses of ≥65 Gy with standard fractionation (or its radiobiological equivalent when altered fractionation is used) are necessary for long‐lasting local control of the disease, with smaller tumors having a more favorable prognosis. The issue of elective nodal irradiation (ENI) remains controversial, since failure patterns identified local failure as the predominant pattern. None of the potential pretreatment patient‐ and tumor‐related prognostic factors has been shown to clearly influence survival. Toxicity is generally mild to moderate, although high doses (e.g., 80 Gy) may carry a risk for an excessive rate of side effects. Conformal treatment and consideration of comorbidities such as altered lung function may be essential, since simultaneous supportive treatment of acute sequelae (mainly acute esophagitis) is necessary. RT is an effective treatment modality in technically operable, but medically inoperable patients with early stage NSCLC and offers a long‐lasting cure. Semin. Surg. Oncol. 21:91–97, 2003. © 2003 Wiley‐Liss, Inc.
Evolution of bimodal accretion flows
2003-09-01

We consider time-dependent models for rotating accretion flows onto black holes, where a transition takes place from an outer cooling-dominated disc to a radiatively inefficient flow in the inner region. In order to allow for a transition of this type we solve the energy equation, both, for the gas and for the radiation field, including a radiative cooling flux and a turbulent convective heat flux directed along the negative entropy gradient. The transition region is found to be highly variable, and a corresponding variation expected for the associated total luminosity. In particular, rapid oscillations of the transition radius are present on a timescale comparable with the local Keplerian rotation time. These oscillations are accompanied by a quasi-periodic modulation of the mass flux at the outer edge of the advection-dominated accretion flow (ADAF). We speculate about the relevance for the high-frequency QPO phenomenon.
Light and Electron Microscopic Study on the Mycorrhizae of Sporophytes of Botrychium virginianum ‐ Arbuscular Structure Resembling Fossil Forms
2003-09-01

Abstract: The mycorrhizal structures of the sporophyte of the strictly protected fern Botrychium virginianum were studied by light and electron microscopy. The paper presented here is the first ultrastructural study of the mycorrhiza of the sporophyte of the genus Botrychium. The fungal colonization is restricted to two to three cell layers of the root cortex. The sometimes bifurcately ramifying hyphae form coils in the host cells. Single hypha arising from the coils penetrates into neighbouring cells and form arbuscules therein. The electron micrographs show high functional activity of the arbuscules, characterized by high glycogen‐like content in the hyphae, a thin layer of filamentous matrix material in the interface between fungus and root cell, frequent cell organelles in the cytoplasm and lack of starch in the host cells containing arbuscules. The main distinctive feature of the mycorrhizae of Botrychium virginianum is the morphology of the arbuscules, which differs not only from the common fine‐branched arbuscules, but also from the special structures reported previously from Ophioglossaceae. The robust, lobe‐like branching arbuscules most resemble arbuscule structures found in Triassic fossils.
Family trees of continuous-time birth-and-death processes
2003-09-01

We consider a stochastic graph generated by a continuous-time birth-and-death process with exponentially distributed waiting times. The vertices are the living particles, directed edges go from mothers to daughters. The size and the structure of the connected components are investigated. Furthermore, the number of connected components is determined.
Real‐Time Caustics
2003-09-01

Abstract We present a new algorithm to render caustics. The algorithm discretizes the specular surfaces into samplepoints. Each of the sample points is treated as a pinhole camera that projects an image of the incoming lightonto the diffuse receiver surfaces. Anti‐aliasing is performed by considering the local surface curvature at thesample points to filter the projected images. The algorithm can be implemented using programmable texturemapping hardware. It allows to render caustics in fully dynamic scenes in real‐time on current PC hardware. Categories and Subject Descriptors: I.3.3 [Computer Graphics]: Picture/Image Generation — Display Algorithms;I.3.7 [Computer Graphics]: Three‐Dimensional Graphics and Realism
Hypoxic Radiosensitizers and Hypoxic Cytotoxins in Radiation Oncology
2003-09-01

Tumor hypoxia is a major constraint for the tumor treatment by radiotherapy. The efficacy of ionizing radiation directly relies on adequate oxygen tensions. Furthermore, hypoxia is related to malignant progression, increased invasion, angiogenesis and an increased risk of metastases formation. Two different types of strategies can be used to overcome the problem of hypoxia-mediated radioresistance. The first strategy encompasses a variety of different methods to improve the tumor oxygenation during radiotherapy. The second strategy tries to target hypoxia as a relatively unique feature of tumor tissue by means of drugs, which are activated under hypoxic conditions and act as hypoxic radiosensitizers or hypoxic cytotoxins. This article reviews in brief the clinical experience with different generations of hypoxic radiosensitizers and hypoxic cytotoxins, which have been applied in combination with primary radiotherapy during the last three decades.
Characterization of Genomic Variants inCSH1andGH2, Two Candidate Genes for Silver-Russell Syndrome in 17q24-q25
2003-09-01

Silver-Russell syndrome (SRS) is a syndrome of severe pre- and postnatal growth retardation and typical dysmorphic features. Rare chromosomal aberrations have been reported in SRS; among these are two balanced translocations involving 17q24-q25. Recently, we described a patient with a paternally inherited heterozygous deletion of the chorionic somatomammotropin hormone 1 (CSH1) gene. The CSH1 gene is member of the growth hormone (GH) gene cluster on 17q, which consists of two growth hormone genes and three CSH genes. Genomic alterations in the GH cluster are well known, causing different phenotypes depending on the size of the deletion and the genes involved. By screening 63 SRS cases with marker D17S254, we have detected 2 further patients with a heterozygous deletion in the GH cluster. Quantitative analysis using restriction assays confirmed these findings. Additionally, in a cohort of 17 patients with isolated intrauterine and postnatal growth retardation, we detected a further patient to be carrier of a CSH1 deletion. Screening of 141 unrelated controls revealed hemizygosity in one person for which data on growth were not available. We additionally analyzed our cohort of SRS patients for mutations in CSH1 and its 3' neighbour GH2. However, analyses failed to reveal any pathogenic mutation. While the central role of GH1 in human growth is well established, the physiological roles of CSH1 and other components of the cluster are unclear. The increased prevalence of hemizygosity of CSH1 in our population in comparison to controls indicates a role for CSH1 haploinsufficiency in the etiology of growth retardation. Investigation of CSH1 deletions in further SRS and growth retarded patients will enable us to establish under which circumstances haploinsufficiency of CSH1 is likely to result in clinical changes.