Showing papers by "University of Münster published in 2008"

Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer

Abstract: Purpose Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. In this study, we compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC. Patients and Methods Analysis of a prospectively collected clinical database was performed. We included 1,118 patients who received neoadjuvant chemotherapy at M.D. Anderson Cancer Center for stage I-III breast cancer from 1985 to 2004 and for whom complete receptor information were available. Clinical and pathologic parameters, pathologic complete response rates (pCR), survival measurements, and organ-specific relapse rates were compared between patients with TNBC and non-TNBC. Results Two hundred fifty-five patients (23%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates (22% v 11%; P = .034), but decreased 3-year progression-free survival rates (P < .0001) and 3-yea...

Heterocyclic Carbenes: Synthesis and Coordination Chemistry

Abstract: The chemistry of heterocyclic carbenes has experienced a rapid development over the last years. In addition to the imidazolin-2-ylidenes, a large number of cyclic diaminocarbenes with different ring sizes have been described. Aside from diaminocarbenes, P-heterocyclic carbenes, and derivatives with only one, or even no heteroatom within the carbene ring are known. New methods for the synthesis of complexes with N-heterocyclic carbene ligands such as the oxidative addition or the metal atom template controlled cyclization of β-functionalized isocyanides have been developed recently. This review summarizes the new developments regarding the synthesis of N-heterocyclic carbenes and their metal complexes.

Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.

Abstract: The time to progression among patients receiving bortezomib plus melphalan– prednisone (bortezomib group) was 24.0 months, as compared with 16.6 months among those receiving melphalan–prednisone alone (control group) (hazard ratio for the bortezomib group, 0.48; P<0.001). The proportions of patients with a partial response or better were 71% in the bortezomib group and 35% in the control group; complete-response rates were 30% and 4%, respectively (P<0.001). The median duration of the response was 19.9 months in the bortezomib group and 13.1 months in the control group. The hazard ratio for overall survival was 0.61 for the bortezomib group (P = 0.008). Adverse events were consistent with established profiles of toxic events associated with bortezomib and melphalan–prednisone. Grade 3 events occurred in a higher proportion of patients in the bortezomib group than in the control group (53% vs. 44%, P = 0.02), but there were no significant differences in grade 4 events (28% and 27%, respectively) or treatment-related deaths (1% and 2%). Conclusions Bortezomib plus melphalan–prednisone was superior to melphalan–prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.)

The ALICE experiment at the CERN LHC

Abstract: ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.

Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60)

Abstract: Summary Background Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is used to treat patients with non-Hodgkin lymphoma. Interval decrease from 3 weeks of treatment (CHOP-21) to 2 weeks (CHOP-14), and addition of rituximab to CHOP-21 (R-CHOP-21) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma (DLBCL). This randomised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14. Methods 1222 elderly patients (aged 61–80 years) were randomly assigned to six or eight cycles of CHOP-14 with or without rituximab. Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement. The primary endpoint was event-free survival; secondary endpoints were response, progression during treatment, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat. The trial is registered on National Cancer Institute website, number NCT00052936 and as EU-20243. Findings 3-year event-free survival was 47·2% after six cycles of CHOP-14 (95% CI 41·2–53·3), 53·0% (47·0–59·1) after eight cycles of CHOP-14, 66·5% (60·9–72·0) after six cycles of R-CHOP-14, and 63·1% (57·4–68·8) after eight cycles of R-CHOP-14. Compared with six cycles of CHOP-14, the improvement in 3-year event-free survival was 5·8% (−2·8–14·4) for eight cycles of CHOP-14, 19·3% (11·1–27·5) for six cycles of R-CHOP-14, and 15·9% (7·6–24·2) for eight cycles of R-CHOP-14. 3-year overall survival was 67·7% (62·0–73·5) for six cycles of CHOP-14, 66·0% (60·1–71·9) for eight cycles of CHOP-14, 78·1% (73·2–83·0) for six cycles of R-CHOP-14, and 72·5% (67·1–77·9) for eight cycles of R-CHOP-14. Compared with treatment with six cycles of CHOP-14, overall survival improved by −1·7% (−10·0–6·6) after eight cycles of CHOP-14, 10·4% (2·8–18·0) after six cycles of R-CHOP-14, and 4·8% (−3·1–12·7) after eight cycles of R-CHOP-14. In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference, and adjusting for known prognostic factors, all three intensified regimens improved 3-year event-free survival (eight cycles of CHOP-14: RR [relative risk] 0·76 [0·60–0·95], p=0·0172; six cycles of R-CHOP-14: RR 0·51 [0·40–0·65], p Interpretation Six cycles of R-CHOP-14 significantly improved event-free, progression-free, and overall survival over six cycles of CHOP-14 treatment. Response-adapted addition of chemotherapy beyond six cycles, though widely practiced, is not justified. Of the four regimens assessed in this study, six cycles of R-CHOP-14 is the preferred treatment for elderly patients, with which other approaches should be compared.

Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations

Abstract: Demographic data clearly demonstrate that the percentage of the population in the older age group is increasing. Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. Cross-sectional and longitudinal data indicate that the testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adult (age 20–30 years) men (1–4). The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment of hypogonadal men on multiple target organs and the recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. This has been comprehensively reviewed and summarized by the Institute of Medicine in ‘Testosterone and Aging: Clinical Research Directions’ (5). Long-term data on the effects of testosterone treatment in the older population are limited mainly to effects on body composition and bone mass (6–11). Key questions of the effects of testosterone on patient reported outcomes and functional benefits that may retard physical or mental frailty of the elderly or improve the quality of life are not yet available. Specific risk data on the prostate and cardiovascular systems are needed.

The Growth Mechanisms of Macroscopic Bodies in Protoplanetary Disks

Abstract: The formation of planetesimals, the kilometer-sized planetary precursors, is still a puzzling process. Considerable progress has been made over the past years in the physical description of the first stages of planetesimal formation, owing to extensive laboratory work. This review examines the experimental achievements and puts them into the context of the dust processes in protoplanetary disks. It has become clear that planetesimal formation starts with the growth of fractal dust aggregates, followed by compaction processes. As the dust-aggregate sizes increase, the mean collision velocity also increases, leading to the stalling of the growth and possibly to fragmentation, once the dust aggregates have reached decimeter sizes. A multitude of hypotheses for the further growth have been proposed, such as very sticky materials, secondary collision processes, enhanced growth at the snow line, or cumulative dust effects with gravitational instability. We will also critically review these ideas.

Do Special Noncovalent π–π Stacking Interactions Really Exist?

Abstract: Noncovalent interactions play an increasingly important role in modern chemical research, and are nowadays considered as cornerstones in supramolecular chemistry, materials science, and even biochemistry. When unsaturated organic groups are involved in noncovalent interactions, the terms “p–p stacking”, or more generally “p–p interactions” are often used. As noted recently, this classification has a quite mysterious flavor. For larger structures, p–p stacking is a phenomenon that is theoretically not well understood, although some progress has been made. From many studies of the benzene dimer and other complexes involving phenyl rings, it can be concluded that the p orbitals do not function as in conventional overlapdriven covalent bonding, although this is not common knowledge. The prototypical benzene dimer is nowadays considered a typical van der Waals complex in which the long-range dispersion interactions (dominant R 6 dependence of the interaction energy on interfragment distance) play the major role. As a consequence, the dimer is unbound at uncorrelated Hartree–Fock and many density functional theory (DFT) levels. This more sophisticated view is increasingly replacing Hunter6s model of p–p interactions, which (over)emphasises the mainly quadrupole–quadrupole electrostatic component of the interaction in benzene-type systems (see Ref. [13] for recent theoretical work on polar psystems). Because van der Waals complexes are formed by almost all neutral, closed-shell molecules, which are considered exclusively herein, what should be so special about the interaction between stacked aromatic units compared to, for example, saturated (hydrogenated) rings of about the same size. This mainly energetic difference is termed herein the p–p stacking effect (PSE). For example, benzene and cyclohexane both exist as fluids at room temperature, which indicates similar intermolecular interactions. According to accurate CCSD(T) computations, the stacked (parallel-displaced, PD) benzene dimer has an even smaller binding energy than the pentane dimer ( 2.8 vs. 3.9 kcalmol ), 14] which has the same number of electrons. These observations seem to be incompatible with the assumption of special p–p interactions. On the other hand, it is known that larger polycyclic aromatic hydrocarbons (PAHs) behave differently to large alkanes; for example, PAHs become increasingly insoluble in common organic solvents with increasing size. Thus the magnitude of the intermolecular interactions and possibly also their fundamental character is more strongly size-dependent in aromatic systems than in saturated systems. The clarification of this matter, and the question as to whether the term “p–p interaction” makes sense from a theoretical point of view, is the central topic of the work presented herein. The linear condensed acenes, from benzene (number of rings n= 1) to tetracene (n= 4), and the corresponding perhydrogenated ring systems (all trans–all anti stereoisomers) were used as models. Homo-dimers of stacked (aromatic with Ci, except for the PD benzene dimer, which has C2h symmetry, and saturated with C2h symmetry) and T-shaped orientation (aromatic only, C2v) are investigated. The Tshaped forms are important in the crystal packing of aromatic molecules, as analyzed in detail by Desiraju and Gavezzotti. For saturated dimers, no well-defined T-shaped structures could be found. Energy-minimized dimer structures for n= 1 and n= 4 are shown as an example in Figure 1.

Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein

Abstract: Accumulation of myeloid-derived suppressor cells (MDSCs) associated with inhibition of dendritic cell (DC) differentiation is one of the major immunological abnormalities in cancer and leads to suppression of antitumor immune responses. The molecular mechanism of this phenomenon remains unclear. We report here that STAT3-inducible up-regulation of the myeloid-related protein S100A9 enhances MDSC production in cancer. Mice lacking this protein mounted potent antitumor immune responses and rejected implanted tumors. This effect was reversed by administration of wild-type MDSCs from tumor-bearing mice to S100A9-null mice. Overexpression of S100A9 in cultured embryonic stem cells or transgenic mice inhibited the differentiation of DCs and macrophages and induced accumulation of MDSCs. This study demonstrates that tumor-induced up-regulation of S100A9 protein is critically important for accumulation of MDSCs and reveals a novel molecular mechanism of immunological abnormalities in cancer.

Spin-density-wave anomaly at 140 K in the ternary iron arsenide BaFe 2 As 2

Abstract: The ternary iron arsenide ${\text{BaFe}}_{2}{\text{As}}_{2}$, with the tetragonal ${\text{ThCr}}_{2}{\text{Si}}_{2}$-type structure, exhibits a spin-density-wave (SDW) anomaly at 140 K, very similar to LaFeAsO, which is the parent compound of the iron arsenide superconductors. ${\text{BaFe}}_{2}{\text{As}}_{2}$ is a poor Pauli-paramagnetic metal and undergoes a structural and magnetic phase transition at 140 K, accompanied by strong anomalies in the specific heat, electrical resistance, and magnetic susceptibility. In the course of this transition, the space-group symmetry changes from tetragonal $(I4/mmm)$ to orthorhombic $(Fmmm)$. $^{57}\text{F}\text{e}$ M\"ossbauer spectroscopy experiments show a single signal at room temperature and full hyperfine field splitting below the phase-transition temperature (5.2 T at 77 K). Our results suggest that ${\text{BaFe}}_{2}{\text{As}}_{2}$ can serve as a parent compound for oxygen-free iron arsenide superconductors.

The Content Analysis of Media Frames: Toward Improving Reliability and Validity

Abstract: The main purpose of this study was to shed light on methodological problems in the content analysis of media frames After a review of 5 common methods, we will present an alternative procedure that aims at improving reliability and validity Based on the definition of frames advanced by R M Entman (1993), we propose that previously defined frame elements systematically group together in a specific way This pattern of frame elements can be identified across several texts by means of cluster analysis The proposed method is demonstrated with data on the coverage of the issue of biotechnology in The New York Times It is concluded that the proposed method yields better results in terms of reliability and validity compared to previous methods

Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses

Abstract: Bacterial infection often results in the formation of tissue abscesses, which represent the primary site of interaction between invading bacteria and the innate immune system. We identify the host protein calprotectin as a neutrophil-dependent factor expressed inside Staphylococcus aureus abscesses. Neutrophil-derived calprotectin inhibited S. aureus growth through chelation of nutrient Mn2+ and Zn2+: an activity that results in reprogramming of the bacterial transcriptome. The abscesses of mice lacking calprotectin were enriched in metal, and staphylococcal proliferation was enhanced in these metal-rich abscesses. These results demonstrate that calprotectin is a critical factor in the innate immune response to infection and define metal chelation as a strategy for inhibiting microbial growth inside abscessed tissue.

Components of fostering self-regulated learning among students. A meta-analysis on intervention studies at primary and secondary school level

Abstract: Due to new standards in fostering life-long learning at school, research has increasingly dealt with the promotion of self-regulated learning, resulting in a large number of intervention studies conducted at primary and secondary school. The current study aimed at investigating the impact of various training characteristics on the training outcomes, regarding academic performance, strategy use and motivation of students. Two meta-analyses were conducted separately, one for primary and one for secondary school level to allow for comparisons between both school levels. The meta-analyses included 49 studies conducted with primary school students and 35 studies conducted with secondary school students; analyzing 357 effect sizes altogether. The potential effects of training characteristics were investigated by means of meta-analytic multiple regression analyses. The average effect size was 0.69. For both school levels, effect sizes were higher when the training was conducted by researchers instead of regular teachers. Moreover, interventions attained higher effects when conducted in the scope of mathematics than in reading/writing or other subjects. Self-regulated learning can be fostered effectively at both primary and secondary school level. However, the theoretical background on which the training programme is based, as well as the type of instructed strategy led to differential effects at both school levels.

Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells.

Abstract: Chronic inflammation is a complex process that promotes carcinogenesis and tumor progression; however, the mechanisms by which specific inflammatory mediators contribute to tumor growth remain unclear. We and others recently demonstrated that the inflammatory mediators IL-1β, IL-6, and PGE2 induce accumulation of myeloid-derived suppressor cells (MDSC) in tumor-bearing individuals. MDSC impair tumor immunity and thereby facilitate carcinogenesis and tumor progression by inhibiting T and NK cell activation, and by polarizing immunity toward a tumor-promoting type 2 phenotype. We now show that this population of immature myeloid cells induced by a given tumor share a common phenotype regardless of their in vivo location (bone marrow, spleen, blood, or tumor site), and that Gr1highCD11bhighF4/80−CD80+IL4Rα+/−Arginase+ MDSC are induced by the proinflammatory proteins S100A8/A9. S100A8/A9 proteins bind to carboxylated N-glycans expressed on the receptor for advanced glycation end-products and other cell surface glycoprotein receptors on MDSC, signal through the NF-κB pathway, and promote MDSC migration. MDSC also synthesize and secrete S100A8/A9 proteins that accumulate in the serum of tumor-bearing mice, and in vivo blocking of S100A8/A9 binding to MDSC using an anti-carboxylated glycan Ab reduces MDSC levels in blood and secondary lymphoid organs in mice with metastatic disease. Therefore, the S100 family of inflammatory mediators serves as an autocrine feedback loop that sustains accumulation of MDSC. Since S100A8/A9 activation of MDSC is through the NF-κB signaling pathway, drugs that target this pathway may reduce MDSC levels and be useful therapeutic agents in conjunction with active immunotherapy in cancer patients.

Digital holographic microscopy for live cell applications and technical inspection

Abstract: Digital holographic microscopy enables a quantitative phase contrast metrology that is suitable for the investigation of reflective surfaces as well as for the marker-free analysis of living cells. The digital holographic feature of (subsequent) numerical focus adjustment makes possible applications for multifocus imaging. An overview of digital holographic microscopy methods is described. Applications of digital holographic microscopy are demonstrated by results obtained from livings cells and engineered surfaces.

Surveying sterically demanding N-heterocyclic carbene ligands with restricted flexibility for palladium-catalyzed cross-coupling reactions.

Abstract: N-Heterocyclic carbenes (NHCs), especially monodentate ones, have become the ligand of choice for many transition-metal-catalyzed transformations. They generally form highly stable complexes, have strong σ-donor character, and have a unique shape that can be used to generate sterically demanding ligands. In this Account, we survey recent developments in the design and synthesis of some sterically demanding NHCs with a particularly strong influence on the metal’s coordination sphere. We show the successful and insightful application of these ligands in transition-metal catalysis. First, we discuss methods for determining and classifying the electronic and steric properties of NHCs. In addition, we present data on the most important NHC ligands. The selective variation of either electronic or steric parameters of NHCs, and therefore of the catalyst, allows for the optimization of the reaction. Thus, we prepared several series of differentially substituted NHC derivatives. However, because the substituents v...

Genome analysis of the platypus reveals unique signatures of evolution

Abstract: We present a draft genome sequence of the platypus, Ornithorhynchus anatinus This monotreme exhibits a fascinating combination of reptilian and mammalian characters For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles Analysis of the first monotreme genome aligned these features with genetic innovations We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation

Ferruginous Conditions Dominated Later Neoproterozoic Deep-Water Chemistry

Abstract: Earth9s surface chemical environment has evolved from an early anoxic condition to the oxic state we have today. Transitional between an earlier Proterozoic world with widespread deep-water anoxia and a Phanerozoic world with large oxygen-utilizing animals, the Neoproterozoic Era [1000 to 542 million years ago (Ma)] plays a key role in this history. The details of Neoproterozoic Earth surface oxygenation, however, remain unclear. We report that through much of the later Neoproterozoic (

Multicolor bimolecular fluorescence complementation reveals simultaneous formation of alternative CBL/CIPK complexes in planta

Abstract: The specificity of intracellular signaling and developmental patterning in biological systems relies on selective interactions between different proteins in specific cellular compartments. The identification of such protein-protein interactions is essential for unraveling complex signaling and regulatory networks. Recently, bimolecular fluorescence complementation (BiFC) has emerged as a powerful technique for the efficient detection of protein interactions in their native subcellular localization. Here we report significant technical advances in the methodology of plant BiFC. We describe a series of versatile BiFC vector sets that are fully compatible with previously generated vectors. The new vectors enable the generation of both C-terminal and N-terminal fusion proteins and carry optimized fluorescent protein genes that considerably improve the sensitivity of BiFC. Using these vectors, we describe a multicolor BiFC (mcBiFC) approach for the simultaneous visualization of multiple protein interactions in the same cell. Application to a protein interaction network acting in calcium-mediated signal transduction revealed the concurrent interaction of the protein kinase CIPK24 with the calcium sensors CBL1 and CBL10 at the plasma membrane and tonoplast, respectively. We have also visualized by mcBiFC the simultaneous formation of CBL1/CIPK1 and CBL9/CIPK1 protein complexes at the plasma membrane. Thus, mcBiFC provides a useful new tool for exploring complex regulatory networks in plants.

Psoriasis is associated with increased beta-defensin genomic copy number.

Abstract: Psoriasis is a common inflammatory skin disease with a strong genetic component. We analyzed the genomic copy number polymorphism of the beta-defensin region on human chromosome 8 in 179 Dutch individuals with psoriasis and 272 controls and in 319 German individuals with psoriasis and 305 controls. Comparisons in both cohorts showed a significant association between higher genomic copy number for beta-defensin genes and risk of psoriasis.

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers

Abstract: Background: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. Methods: Published reports relevant to use of tumor markers for 5 cancer sites—testicular, prostate, colorectal, breast, and ovarian—were critically reviewed. Results: For testicular cancer, α-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are recommended for diagnosis/case finding, staging, prognosis determination, recurrence detection, and therapy monitoring. α-Fetoprotein is also recommended for differential diagnosis of nonseminomatous and seminomatous germ cell tumors. Prostate-specific antigen (PSA) is not recommended for prostate cancer screening, but may be used for detecting disease recurrence and monitoring therapy. Free PSA measurement data are useful for distinguishing malignant from benign prostatic disease when total PSA is <10 μg/L. In colorectal cancer, carcinoembryonic antigen is recommended (with some caveats) for prognosis determination, postoperative surveillance, and therapy monitoring in advanced disease. Fecal occult blood testing may be used for screening asymptomatic adults 50 years or older. For breast cancer, estrogen and progesterone receptors are mandatory for predicting response to hormone therapy, human epidermal growth factor receptor-2 measurement is mandatory for predicting response to trastuzumab, and urokinase plasminogen activator/plasminogen activator inhibitor 1 may be used for determining prognosis in lymph node–negative patients. CA15-3/BR27–29 or carcinoembryonic antigen may be used for therapy monitoring in advanced disease. CA125 is recommended (with transvaginal ultrasound) for early detection of ovarian cancer in women at high risk for this disease. CA125 is also recommended for differential diagnosis of suspicious pelvic masses in postmenopausal women, as well as for detection of recurrence, monitoring of therapy, and determination of prognosis in women with ovarian cancer. Conclusions: Implementation of these recommendations should encourage optimal use of tumor markers.

Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRIL locus on chromosome 9p

Abstract: Genome-wide association studies have identified a region on chromosome 9p that is associated with coronary artery disease (CAD). The region is also associated with type 2 diabetes (T2D), a risk factor for CAD, although different SNPs were reported to be associated to each disease in separate studies. We have undertaken a case-control study in 4251 CAD cases and 4443 controls in four European populations using previously reported ('literature') and tagging SNPs. We replicated the literature SNPs (P = 8x10(-13); OR = 1.29; 95% CI: 1.20-1.38) and showed that the strong consistent association detected by these SNPs is a consequence of a 'yin-yang' haplotype pattern spanning 53 kb. There was no evidence of additional CAD susceptibility alleles over the major risk haplotype. CAD patients without myocardial infarction (MI) showed a trend towards stronger association than MI patients. The CAD susceptibility conferred by this locus did not differ by sex, age, smoking, obesity, hypertension or diabetes. A simultaneous test of CAD and diabetes susceptibility with CAD and T2D-associated SNPs indicated that these associations were independent of each other. Moreover, this region was not associated with differences in plasma levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fibrinogen, albumin, uric acid, bilirubin or homocysteine, although the CAD-high-risk allele was paradoxically associated with lower triglyceride levels. A large antisense non-coding RNA gene (ANRIL) collocates with the high-risk haplotype, is expressed in tissues and cell types that are affected by atherosclerosis and is a prime candidate gene for the chromosome 9p CAD locus.

Singlet oxygen production in photosystem II and related protection mechanism

Abstract: High-light illumination of photosynthetic organisms stimulates the production of singlet oxygen by photosystem II (PSII) and causes photo-oxidative stress. In the PSII reaction centre, singlet oxygen is generated by the interaction of molecular oxygen with the excited triplet state of chlorophyll (Chl). The triplet Chl is formed via charge recombination of the light-induced charge pair. Changes in the midpoint potential of the primary electron donor P(680) of the primary acceptor pheophytin or of the quinone acceptor Q(A), modulate the pathway of charge recombination in PSII and influence the yield of singlet oxygen formation. The involvement of singlet oxygen in the process of photoinhibition is discussed. Singlet oxygen is efficiently quenched by beta-carotene, tocopherol or plastoquinone. If not quenched, it can trigger the up-regulation of genes, which are involved in the molecular defence response of photosynthetic organisms against photo-oxidative stress.

A generic grid interface for parallel and adaptive scientific computing. Part II: implementation and tests in DUNE

Abstract: In a companion paper (Bastian et al. 2007, this issue) we introduced an abstract definition of a parallel and adaptive hierarchical grid for scientific computing. Based on this definition we derive an efficient interface specification as a set of C++ classes. This interface separates the applications from the grid data structures. Thus, user implementations become independent of the underlying grid implementation. Modern C++ template techniques are used to provide an interface implementation without big performance losses. The implementation is realized as part of the software environment DUNE (http://dune-project.org/). Numerical tests demonstrate the flexibility and the efficiency of our approach.

Silicon/Graphite Composite Electrodes for High-Capacity Anodes: Influence of Binder Chemistry on Cycling Stability

Abstract: The binder's influence on the cycling stability of high-energy anodes for lithium-ion batteries is demonstrated. Varying the binder's nature strongly influences the composite electrode's performance on deep charging/discharging. If sodium-carboxymethylcellulose is used as binding agent, then a chemical bond between binder and silicon particles can be detected (attenuated total reflection-Fourier transform infrared spectroscopy). Consequently, a reaction mechanism that describes a condensation reaction between the binder and the silicon particles is verbalized. It is shown that, not necessarily the binder's physical flexibility, but its chemical interaction with the active masses is the major claim leading to long-lasting reversible lithium uptake/release.

Reduced basis method for finite volume approximations of parametrized linear evolution equations

Abstract: The model order reduction methodology of reduced basis (RB) techniques offers efficient treatment of parametrized partial differential equations (P2 DEs) by providing both approximate solution procedures and efficient error estimates. RB-methods have so far mainly been applied to finite element schemes for elliptic and parabolic problems. In the current study we extend the methodology to general linear evolution schemes such as finite volume schemes for parabolic and hyperbolic evolution equations. The new theoretic contributions are the formulation of a reduced basis approximation scheme for these general evolution problems and the derivation of rigorous a-posteriori error estimates in various norms. Algorithmically, an offline/online decomposition of the scheme and the error estimators is realized in case of affine parameter-dependence of the problem. This is the basis for a rapid online computation in case of multiple simulation requests. We introduce a new offline basis-generation algorithm based on our a-posteriori error estimator which combines ideas from existing approaches. Numerical experiments for an instationary convection-diffusion problem demonstrate the efficient applicability of the approach.