Showing papers by "University of Basel published in 2001"
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TL;DR: The authors report how the economic variables income, unemployment and inflation affect happiness and how institutional factors, in particular the type of democracy and the extent of government decentralization, systematically influence how satisfied individuals are with their life.
Abstract: Over the past few years, there has been a steadily increasing interest on the part of economists in happiness research. We argue that reported subjective well-being is a satisfactory empirical approximation to individual utility and that happiness research is able to contribute important insights for economics. We report how the economic variables income, unemployment and inflation affect happiness as well as how institutional factors, in particular the type of democracy and the extent of government decentralization, systematically influence how satisfied individuals are with their life. We discuss some of the consequences for economic policy and for economic theory.
3,071 citations
TL;DR: In this article, an implementation of Grover's algorithm that uses molecular magnets was proposed, which can be used to build dense and efficient memory devices based on the Grover algorithm, in which one single crystal can serve as a storage unit of a dynamic random access memory device.
Abstract: Shor and Grover demonstrated that a quantum computer can outperform any classical computer in factoring numbers1 and in searching a database2 by exploiting the parallelism of quantum mechanics. Whereas Shor's algorithm requires both superposition and entanglement of a many-particle system3, the superposition of single-particle quantum states is sufficient for Grover's algorithm4. Recently, the latter has been successfully implemented5 using Rydberg atoms. Here we propose an implementation of Grover's algorithm that uses molecular magnets6,7,8,9,10, which are solid-state systems with a large spin; their spin eigenstates make them natural candidates for single-particle systems. We show theoretically that molecular magnets can be used to build dense and efficient memory devices based on the Grover algorithm. In particular, one single crystal can serve as a storage unit of a dynamic random access memory device. Fast electron spin resonance pulses can be used to decode and read out stored numbers of up to 105, with access times as short as 10-10 seconds. We show that our proposal should be feasible using the molecular magnets Fe8 and Mn12.
2,378 citations
TL;DR: Long-term and early-life exposure to stables and farm milk induces a strong protective effect against development of asthma, hay fever, and atopic sensitisation in children.
1,452 citations
TL;DR: This highly versatile protein folding and oligomerization motif is discussed with regard to its structural architecture and how this is related to its biological functions.
1,043 citations
TL;DR: The results confirm those previously reported on the effects of ambient particles on mortality and show that the heterogeneity found in the effect parameters among cities reflects real effect modification, which is explained by specific city characteristics.
Abstract: We present the results of the Air Pollution and Health: A European Approach 2 (APHEA2) project on short-term effects of ambient particles on mortality with emphasis on effect modification. We used daily measurements for particulate matter less than 10 microm in aerodynamic diameter (PM10) and/or black smoke from 29 European cities. We considered confounding from other pollutants as well as meteorologic and chronologic variables. We investigated several variables describing the cities' pollution, climate, population, and geography as potential effect modifiers. For the individual city analysis, generalized additive models extending Poisson regression, using a smoother to control for seasonal patterns, were applied. To provide quantitative summaries of the results and explain remaining heterogeneity, we applied second-stage regression models. The estimated increase in the daily number of deaths for all ages for a 10 microg/m3 increase in daily PM10 or black smoke concentrations was 0.6% [95% confidence interval (CI) = 0.4-0.8%], whereas for the elderly it was slightly higher. We found important effect modification for several of the variables studied. Thus, in a city with low average NO2, the estimated increase in daily mortality for an increase of 10 microg/m3 in PM10 was 0.19 (95% CI = 0.00-0.41), whereas in a city with high average NO2 it was 0.80% (95% CI = 0.67-0.93%); in a relatively cold climate the corresponding effect was 0.29% (95% CI = 0.16-0.42), whereas in a warm climate it was 0.82% (95% CI = 0.69-0.96); in a city with low standardized mortality rate it was 0.80% (95% CI = 0.65-0.95%), and in one with a high rate it was 0.43% (95% CI = 0.24-0.62). Our results confirm those previously reported on the effects of ambient particles on mortality. Furthermore, they show that the heterogeneity found in the effect parameters among cities reflects real effect modification, which is explained by specific city characteristics.
971 citations
TL;DR: Using a cell-free RNA decay system, it is demonstrated that the mammalian exosome is required for rapid degradation of ARE-containing RNAs but not for poly(A) shortening.
884 citations
TL;DR: Results indicate that omalizumab therapy safely improves asthma control in allergic asthmatics who remain symptomatic despite regular use of inhaled corticosteroids and simultaneous reduction in Corticosteroid requirement.
Abstract: The clinical benefit and steroid-sparing effect of treatment with the anti-immunoglobulin-E (IgE) antibody, omalizumab, was assessed in patients with moderate-to-severe allergic asthma. After a run-in period, 546 allergic asthmatics (aged 12-76 yrs), symptomatic despite inhaled corticosteroids (500-1,200 microg daily of beclomethasone dipropionate), were randomized to receive double-blind either placebo or omalizumab every 2 or 4 weeks (depending on body weight and serum total IgE) subcutaneously for 7 months. A constant beclomethasone dose was maintained during a 16-week stable-steroid phase and progressively reduced to the lowest dose required for asthma control over the following 8 weeks. The latter dose was maintained for the next 4 weeks. Asthma exacerbations represented the primary variable. Compared to the placebo group, the omalizumab group showed 58% fewer exacerbations per patient during the stable-steroid phase (p<0.001). During the steroid-reduction phase, there were 52% fewer exacerbations in the omalizumab group versus the placebo group (p<0.001) despite the greater reduction of the beclomethasone dosage on omalizumab (p<0.001). Treatment with omalizumab was well tolerated. The incidence of adverse events was similar in both groups. These results indicate that omalizumab therapy safely improves asthma control in allergic asthmatics who remain symptomatic despite regular use of inhaled corticosteroids and simultaneous reduction in corticosteroid requirement.
794 citations
TL;DR: It is shown experimentally that the rate of charge transfer between two guanine bases decreases with increasing separation only if the guanines are separated by no more than three base pairs; if more bridging base pairs are present, the transfer rates exhibit only a weak distance dependence.
Abstract: The function of DNA during oxidative stress and its suitability as a potential building block for molecular devices depend on long-distance transfer of electrons and holes through the molecule, yet many conflicting measurements of the efficiency of this process have been reported. It is accepted that charges are transported over long distances through a multistep hopping reaction; this 'G-hopping' involves positive charges moving between guanines (Gs), the DNA bases with the lowest ionization potential. But the mechanism fails to explain the persistence of efficient charge transfer when the guanine sites are distant, where transfer rates do not, as expected, decrease rapidly with transfer distance. Here we show experimentally that the rate of charge transfer between two guanine bases decreases with increasing separation only if the guanines are separated by no more than three base pairs; if more bridging base pairs are present, the transfer rates exhibit only a weak distance dependence. We attribute this distinct change in the distance dependence of the rate of charge transfer through DNA to a shift from coherent superexchange charge transfer (tunnelling) at short distances to a process mediated by thermally induced hopping of charges between adenine bases (A-hopping) at long distances. Our results confirm theoretical predictions of this behaviour, emphasizing that seemingly contradictory observations of a strong as well as a weak influence of distance on DNA charge transfer are readily explained by a change in the transfer mechanism.
748 citations
TL;DR: OATP-B is the third bromosulphophthalein uptake system localized at the basolateral membrane of human hepatocytes and is the first to be characterized with respect to tissue distribution and hepatocellular localization.
727 citations
TL;DR: It is concluded that available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis and has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published.
Abstract: The high prevalence of liver diseases such as chronic hepatitis and cirrhosis underscores the need for efficient and cost-effective treatments. The potential benefit of silymarin (extracted from the seeds of Silybum marianum or milk thistle) in the treatment of liver diseases remains a controversial issue. Therefore, the objective of this review is to assess the clinical efficacy and safety of silymarin by application of systematic approach. 525 references were found in the databases, of which 84 papers were retained for closer examination and 36 were deemed suitable for detailed analysis. Silymarin has metabolic and cell-regulating effects at concentrations found in clinical conditions, namely carrier-mediated regulation of cell membrane permeability, inhibition of the 5-lipoxygenase pathway, scavenging of reactive oxygen species (ROS) of the R-OH type and action on DNA-expression, for example, via suppression of nuclear factor (NF)-κB. Pooled data from case record studies involving 452 patients with Amanita phalloides poisoning show a highly significant difference in mortality in favour of silibinin [the main isomer contained in silymarin] (mortality 9.8% vs 18.3% with standard treatment; p < 0.01). The available trials in patients with toxic (e.g. solvents) or iatrogenic (e.g. antispychotic or tacrine) liver diseases, which are mostly outdated and underpowered, do not enable any valid conclusions to be drawn on the value of silymarin. The exception is an improved clinical tolerance of tacrine. In spite of some positive results in patients with acute viral hepatitis, no formally valid conclusion can be drawn regarding the value of silymarin in the treatment of these infections. Although there were no clinical end-points in the four trials considered in patients with alcoholic liver disease, histological findings were reported as improved in two out of two trials, improvement of prothrombin time was significant (two trials pooled) and liver transaminase levels were consistently lower in the silymarin-treated groups. Therefore, silymarin may be of use as an adjuvant in the therapy of alcoholic liver disease. Analysis was performed on five trials with a total of 602 patients with liver cirrhosis. The evidence shows that, compared with placebo, silymarin produces a nonsignificant reduction of total mortality by −4.2% [odds ratio (OR) 0.75 (0.5–1.1)]; but that, on the other hand, the use of silymarin leads to a significant reduction in liver-related mortality of −7% [OR: 0.54 (0.3–0.9); p < 0.01]. An individual trial reported a reduction in the numberof patients with encephalopathy of −8.7% (p = 0.06). In one study of patients with cirrhosis-related diabetes mellitus, the insulin requirement was reduced by −25% (p < 0.01). We conclude that available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis. Silymarin is has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published. This review does not aim to replace future prospective trials aiming to provide the ‘final’ evidence of the efficacy of silymarin.
650 citations
TL;DR: The authors found evidence of a statistically and economically significant relationship between relative civil-service pay and corruption in regressions based on cross-country averages, where they control for a wide array of variables.
TL;DR: It is concluded that, contrary to expectations, tissue heterogeneity did not negatively influence the predictive power of the TMA results, and TMA technology will be of substantial value in rapidly translating genomic and proteomics information to clinical applications.
Abstract: Advances in genomics and proteomics are dramatically increasing the need to evaluate large numbers of molecular targets for their diagnostic, predictive or prognostic value in clinical oncology. Conventional molecular pathology techniques are often tedious, time-consuming, and require a lot of tissue, thereby limiting both the number of tissues and the number of targets that can be evaluated. Here, we demonstrate the power of our recently described tissue microarray (TMA) technology in analyzing prognostic markers in a series of 553 breast carcinomas. Four independent TMAs were constructed by acquiring 0.6 mm biopsies from one central and from three peripheral regions of each of the formalin-fixed paraffin embedded tumors. Immunostaining of TMA sections and conventional "large" sections were performed for two well- established prognostic markers, estrogen receptor (ER) and progesterone receptor (PR), as well as for p53, another frequently examined protein for which the data on prognostic utility in breast cancer are less unequivocal. Compared with conventional large section analysis, a single sample from each tumor identified about 95% of the information for ER, 75 to 81% for PR, and 70 to 74% for p53. However, all 12 TMA analyses (three antibodies on four different arrays) yielded as significant or more significant associations with tumor-specific survival than large section analyses (p < 0.0015 for each of the 12 comparisons). A single sample from each tumor was sufficient to identify associations between molecular alterations and clinical outcome. It is concluded that, contrary to expectations, tissue heterogeneity did not negatively influence the predictive power of the TMA results. TMA technology will be of substantial value in rapidly translating genomic and proteomics information to clinical applications.
TL;DR: In this paper, an updated version of the empirically and semi-empirically calibrated B aS eL library of synthetic stellar spectra was used to calculate synthetic photometry in the (UBV) J (RI) C JHKLL ′ M, HST-WFPC2, Geneva, and Washington systems for the entire set of non-rotating Geneva stellar evolution models covering masses from 0.4-0.8 to 120-150 and metallicities (1/50 ) to 0.1 (5 ).
Abstract: We have used an updated version of the empirically and semi-empirically calibrated B aS eL library of synthetic stellar spectra of Lejeune et al.([CITE], [CITE]) and Westera et al.([CITE]) to calculate synthetic photometry in the (UBV) J (RI) C JHKLL ′ M , HST-WFPC2, Geneva, and Washington systems for the entire set of non-rotating Geneva stellar evolution models covering masses from 0.4-0.8 to 120-150 and metallicities (1/50 ) to 0.1 (5 ). The results are provided in a database which includes all individual stellar tracks and the corresponding isochrones covering ages from 103 yr to 16-20 Gyr in time steps of 0.05 dex. The database also includes a new grid of stellar tracks of very metal-poor stars () from calculated with the Geneva stellar evolution code.
TL;DR: In this article, the authors investigated the dynamical family relations and dark halo properties of 21 mostly luminous, slowly rotating, and nearly round elliptical galaxies and found that they follow a Tully-Fisher (TF) relation with marginally shallower slope than spiral galaxies.
Abstract: Based on a uniform dynamical analysis of the line-pro—le shapes of 21 mostly luminous, slowly rotating, and nearly round elliptical galaxies, we have investigated the dynamical family relations and dark halo properties of ellipticals. Our results include: (i) The circular velocity curves (CVCs) of elliptical galaxies are —at to within ^10% for (ii) Most ellipticals are moderately radially anisotropic; R Z 0.2R e . their dynamical structure is surprisingly uniform. (iii) Elliptical galaxies follow a Tully-Fisher (TF) relation with marginally shallower slope than spiral galaxies, and km s~1 for an galaxy. At
TL;DR: In correspondence analysis, some host clones, although distinguishable with neutral genetic markers, were susceptible to the same set of parasite isolates and thus probably shared resistance genes, consistent with the idea that parasites track specific host genotypes under natural conditions.
Abstract: Models of host-parasite coevolution assume the presence of genetic variation for host resistance and parasite infectivity, as well as genotype-specific interactions. We used the freshwater crustacean Daphnia magna and its bacterial microparasite Pasteuria ramosa to study genetic variation for host susceptibility and parasite infectivity within each of two populations. We sought to answer the following questions: Do host clones differ in their susceptibility to parasite isolates? Do parasite isolates differ in their ability to infect different host clones? Are there host clone-parasite isolate interactions? The analysis revealed considerable variation in both host resistance and parasite infectivity. There were significant host clone-parasite isolate interactions, such that there was no single host clone that was superior to all other clones in the resistance to every parasite isolate. Likewise, there was no parasite isolate that was superior to all other isolates in infectivity to every host clone. This form of host clone-parasite isolate interaction indicates the potential for coevolution based on frequency-dependent selection. Infection success of original host clone-parasite isolate combinations (i.e., those combinations that were isolated together) was significantly higher than infection success of novel host clone-parasite isolate combinations (i.e., those combinations that were created in the laboratory). This finding is consistent with the idea that parasites track specific host genotypes under natural conditions. In addition, correspondence analysis revealed that some host clones, although distinguishable with neutral genetic markers, were susceptible to the same set of parasite isolates and thus probably shared resistance genes.
TL;DR: In conclusion, sarcomatoid change in renal cell carcinoma portends a worse prognosis, and tumors with even a small component of sarcom atoid change may have an adverse outcome.
Abstract: Sarcomatoid renal cell carcinoma is not a distinct histologic entity and represents high-grade transformation in different subtypes of renal cell carcinoma. It is not known whether any particular histologic type has a predilection for sarcomatoid change or whether the primary histologic type of renal carcinoma undergoing sarcomatoid change affects prognosis. Of 952 consecutively histologically subtyped renal cell carcinomas, the incidence of sarcomatoid differentiation was 8% in conventional (clear cell) renal carcinoma, 3% in papillary renal carcinoma, 9% in chromophobe renal carcinoma, 29% in collecting duct carcinoma, and 11% in unclassified renal cell carcinoma. One hundred one renal cell carcinomas with sarcomatoid change were studied, and clinicopathologic parameters were correlated with outcome. The mean age of patients was 60 years (range, 33-80 years), and the male-to-female ratio was 1.6:1. The median tumor size was 9.2 cm (range, 3-25 cm). The primary histologic subtype of the carcinoma component was conventional (clear cell) renal carcinoma in 80 cases, papillary renal carcinoma in eight, chromophobe renal carcinoma in seven, collecting duct carcinoma in two, and unclassified renal cell carcinoma in four. The sarcomatoid component resembled fibrosarcoma in 54 cases, malignant fibrous histiocytoma in 44, undifferentiated sarcoma (not otherwise specified) in three with focal rhabdomyosarcomatous component in two of them. The spindled elements accounted for 1% to 99% of the sampled tumor (median, 40%; mean 45%). The histologic grade of the spindled elements was intermediate to high in 92 cases and low in nine cases. Most cases were TNM stages III and IV (seven stage I, six stage II, 63 stage III, and 25 stage IV). Follow-up was available in 88 patients; 61 (69%) patients died of disease and had a median survival time of 19 months. Distant metastases, most frequently to the lungs, were documented in 51 (66%) of 77 patients who had available clinical information regarding distant metastasis. The disease-specific survival rate was 22% and 13% after 5 and 10 years, respectively, compared with a cohort of renal cell carcinomas without sarcomatoid change with a 5-and 10-year disease-specific survival of 79% and 76%, respectively. Kaplan-Meier survival analysis showed that tumors with high TNM stage (p = 0.0027), at least 50% sarcomatoid component (p = 0.0453), and angiolymphatic invasion (p = 0.0282) were associated with decreased survival rates. The primary histologic subtype of the carcinoma component and the type and grade of the sarcomatoid component did not affect survival. In a Cox proportional hazard regression model, TNM stage appeared to be the only significant variable in predicting outcome among renal cell carcinomas with sarcomatoid change (p = 0.018; risk ratio, 6.984 and 8.439). Compared with a cohort of renal cell carcinomas without sarcomatoid change, sarcomatoid tumors tended to present at a more advanced stage (p = 0.0001). Also, when adjusted for stage, necrosis, and tumor size, patients with tumors with sarcomatoid differentiation had a worse prognosis than did patients with tumors without sarcomatoid change (p = 0.0001). In conclusion, sarcomatoid change in renal cell carcinoma portends a worse prognosis. Because tumors with even a small component of sarcomatoid change may have an adverse outcome, this finding, when present, should be noted in the surgical pathology report.
TL;DR: In this paper, a chemical sensor based on a microfabricated array of eight silicon cantilevers actuated at their resonance-frequency and functionalized by polymer coatings is presented.
Abstract: We present a chemical sensor based on a microfabricated array of eight silicon cantilevers actuated at their resonance-frequency and functionalized by polymer coatings. The operating principle relies on transduction of chemical or physical processes into a mechanical response. After exposure to analyte vapor, analyte molecules diffuse into the cantilever coating, which begins to swell. Jointly with the mass increase, a change of interfacial stress between coating and cantilever occurs, resulting in a bending of the cantilevers. Our setup allows the simultaneous detection of cantilever oscillation and bending of eight cantilevers by time-multiplexed optical beam deflection readout. The ac component of the cantilever response is demodulated, and the cantilever resonance-frequency is tracked by a custom-built phase-locked loop. By filtering out the ac component (oscillation), the dc signal (bending) is extracted, yielding information on mass as well as surface stress changes simultaneously. Detection results of water, primary alcohols, alkanes and perfumes are presented.
TL;DR: The results provide evidence that growth factors during chondrocyte expansion not only influence cell proliferation and differentiation, but also the cell potential to redifferentiate and respond to regulatory molecules upon transfer into a 3D environment.
Abstract: Adult human articular chondrocytes were expanded in a medium with 10% serum (CTR) or further supplemented with different mitogens (i.e., EGF, PDGFbb, FGF-2, TGF beta 1, or FGF-2/TGF beta 1). Cells were then induced to redifferentiate in 3D pellets using serum-supplemented medium (SSM), serum-free medium (SFM), or SFM supplemented with factors inducing differentiation of chondroprogenitor cells (i.e., TGF beta 1 and/or dexamethasone). All factors tested during expansion enhanced chondrocyte proliferation and dedifferentiation, as assessed by the mRNA ratios of collagen type II to type I (CII/CI) and aggrecan to versican (Agg/Ver), using real-time PCR. FGF-2/TGF beta 1-expanded chondrocytes displayed the lowest doubling times, CII/CI and Agg/Ver ratios, averaging, respectively, 50, 0.2 and 15% of CTR-expanded cells. Redifferentiation in pellets was more efficient in SFM than SSM only for EGF-, PDGFbb- or FGF-2-expanded chondrocytes. Upon supplementation of SFM with TGF beta and dexamethasone (SFM TD), CII/CI ratios decreased 4.4-fold for EGF- and PDGFbb-expanded chondrocytes, but increased 96-fold for FGF-2/TGF beta 1-expanded cells. Chondrocytes expanded with FGF-2/TGF beta 1 and redifferentiated in SFM TD expressed the largest mRNA amounts of CII and aggrecan and generated cartilaginous tissues with the highest accumulation of glycosaminoglycans and collagen type II. Our results provide evidence that growth factors during chondrocyte expansion not only influence cell proliferation and differentiation, but also the cell potential to redifferentiate and respond to regulatory molecules upon transfer into a 3D environment.
TL;DR: Strong intranuclear immunostaining of the vitamin D receptor was detected in human muscle cells, the first in situ detection of the receptor in human skeletal muscle, and further research is needed in order to evaluate whether vitamin D3 receptor expression in human skeletons is age-dependent and varies between different muscles.
Abstract: Growing evidence suggests that intracellular vitamin D receptors are present in skeletal muscle tissue mediating vitamin D hormone response. The aim of the work reported here was to investigate the in situ expression of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Intraoperative periarticular muscle biopsies were taken from 20 female orthopaedic patients (17 middle-aged and elderly patients receiving total hip arthroplasty due to osteoarthritis of the hip or an osteoporotic hip fracture and 3 young patients who received back surgery). The immunohistological distribution of the vitamin D3 receptor was investigated using a monoclonal rat antibody to the receptor (Clone Nr. 9A7). The receptor-positive nuclei were quantified by counting 500 nuclei per biopsy. Strong intranuclear immunostaining of the vitamin D receptor was detected in human muscle cells. Biopsies of hip patients had significantly fewer receptor-positive nuclei compared to those of back surgery patients (Mann-Whitney U-test: p = 0.0025). VDR expression (number of antigen-positive nuclei) was significantly correlated with age (coefficient of correlation = 0.46; p = 0.005), but not with 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D levels. The data clearly demonstrate presence of nuclear 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle. To our knowledge this is the first in situ detection of the receptor in human skeletal muscle. The difference in the expression of the receptor between hip and spinal muscle biopsies might be explained by age or location. Further research is needed in order to evaluate whether vitamin D3 receptor expression in human skeletal muscle is age-dependent and varies between different muscles.
TL;DR: In this article, the rapid proton capture process of hydrogen burning on the surface of an accreting neutron star with an updated reaction network was studied, and it was shown that the process ends in a closed SnSbTe cycle.
Abstract: We calculate the rapid proton ( rp) capture process of hydrogen burning on the surface of an accreting neutron star with an updated reaction network that extends up to Xe, far beyond previous work. In both steady-state nuclear burning appropriate for rapidly accreting neutron stars (such as the magnetic polar caps of accreting x-ray pulsars) and unstable burning of type I x-ray bursts, we find that the rp process ends in a closed SnSbTe cycle. This prevents the synthesis of elements heavier than Te and has important consequences for x-ray burst profiles, the composition of accreting neutron stars, and potentially galactic nucleosynthesis of light p nuclei.
TL;DR: The authors presented evidence that spillovers through bank lending, as opposed to trade linkages and country characteristics, can help explain contagion, finding evidence in favor of a common lender effect in the Mexican, Thai, and Russian crises, after controlling for the degree of trade competition and macroeconomic fundamentals.
TL;DR: Tissue microarray technology allows a massive acceleration of studies correlating molecular in situ findings with clinico‐pathological information, and will lead to a significant acceleration of the transition of basic research findings into clinical applications.
Abstract: Tissue microarray (TMA) technology allows a massive acceleration of studies correlating molecular in situ findings with clinico-pathological information. In this technique, cylindrical tissue samples are taken from up to 1000 different archival tissue blocks and subsequently placed into one empty ‘recipient’ paraffin block. Sections from TMA blocks can be used for all different types of in situ tissue analyses including immunohistochemistry and in situ hybridization. Multiple studies have demonstrated that findings obtained on TMAs are highly representative of their donor tissues, despite the small size of the individual specimens (diameter 0.6 mm). It is anticipated that TMAs will soon become a widely used tool for all types of tissue-based research. The availability of TMAs containing highly characterized tissues will enable every researcher to perform studies involving thousands of tumours rapidly. Therefore, TMAs will lead to a significant acceleration of the transition of basic research findings into clinical applications. Copyright © 2001 John Wiley & Sons, Ltd.
TL;DR: Evidence from observational trials and 1 randomized clinical trial indicate that a subset of patients can be successfully treated with retention of the implant and susceptibility of the microorganism to an effective orally available antimicrobial agent.
Abstract: Orthopedic implants have revolutionized treatment of bone fractures and noninfectious joint arthritis. Today, the risk for orthopedic device-related infection (ODRI) is <1%-2%. However, the absolute number of patients with infection continuously increases as the number of patients requiring such implants grows. Treatment of ODRIs most frequently includes long-term antimicrobial treatment and removal of the implant. Recent evidence from observational trials and 1 randomized clinical trial indicate that a subset of patients can be successfully treated with retention of the implant. Patients eligible for such a treatment must meet the following criteria: acute infection defined as signs and symptoms lasting <14-28 days, an unambiguous diagnosis based on histopathology and microbiology, a stable implant, and susceptibility of the microorganism to an effective orally available antimicrobial agent.
TL;DR: In this article, the authors characterize and classify quantum correlations in two-fermion systems having $2K$ single-particle states and give a necessary and sufficient condition for a state to have a Slater number 1.
Abstract: We characterize and classify quantum correlations in two-fermion systems having $2K$ single-particle states. For pure states we introduce the Slater decomposition and rank (in analogy to Schmidt decomposition and rank); i.e., we decompose the state into a combination of elementary Slater determinants formed by pairs of mutually orthogonal single-particle states. Mixed states can be characterized by their Slater number which is the minimal Slater rank required to generate them. For $K=2$ we give a necessary and sufficient condition for a state to have a Slater number 1. We introduce a correlation measure for mixed states which can be evaluated analytically for $K=2.$ For higher $K,$ we provide a method of constructing and optimizing Slater number witnesses, i.e., operators that detect Slater numbers for some states.
TL;DR: In this article, it was shown that the two fls2 mutant alleles, flg2-24 and flg22-17, which were shown previously to confer insensitivity to flg 22, also cause impaired flagellin binding.
Abstract: In Arabidopsis, activation of defense responses by flagellin is triggered by the specific recognition of the most conserved domain of flagellin, represented by the peptide flg22, in a process involving the FLS2 gene, which encodes a leucine-rich repeat serine/threonine protein kinase. We show here that the two fls2 mutant alleles, fls2-24 and fls2-17, which were shown previously to confer insensitivity to flg22, also cause impaired flagellin binding. These features are rescued when a functional FLS2 gene is expressed as a transgene in each of the fls2 mutant plants, indicating that FLS2 is necessary for flagellin binding. The point mutation of the fls2-17 allele lies in the kinase domain. A kinase carrying this missense mutation lacked autophosphorylation activity when expressed in Escherichia coli. This indicates that kinase activity is required for binding and probably affects the stability of the flagellin receptor complex. We further show that overexpression of the kinase-associated protein phosphatase (KAPP) in Arabidopsis results in plants that are insensitive to flagellin treatment, and we show reduced flg22 binding in these plants. Furthermore, using the yeast two-hybrid system, we show physical interaction of KAPP with the kinase domain of FLS2. These results suggest that KAPP functions as a negative regulator of the FLS2 signal transduction pathway and that the phosphorylation of FLS2 is necessary for proper binding and signaling of the flagellin receptor complex.
TL;DR: In this article, a spin-entangler for electrons based on an s-wave superconductor coupled to two quantum dots, each of which is coupled to normal Fermi leads, is proposed.
Abstract: We propose and analyze a spin-entangler for electrons based on an s-wave superconductor coupled to two quantum dots, each of which is coupled to normal Fermi leads We show that in the presence of a voltage bias and in the Coulomb blockade regime two correlated electrons provided by the Andreev process can coherently tunnel from the superconductor via different dots into different leads The spin singlet coming from the Cooper pair remains preserved in this process, and the setup provides a source of mobile and nonlocal spin-entangled electrons The transport current is calculated and shown to be dominated by a two-particle Breit-Wigner resonance that allows the injection of two spin-entangled electrons into different leads at exactly the same orbital energy, which is a crucial requirement for the detection of spin entanglement via noise measurements The coherent tunneling of both electrons into the same lead is suppressed by the on-site Coulomb repulsion and/or the superconducting gap, while the tunneling into different leads is suppressed through the initial separation of the tunneling electrons In the regime of interest the particle-hole excitations of the leads are shown to be negligible The Aharonov-Bohm oscillations in the current are shown to contain single- and two-electron periods with amplitudes that both vanish with increasing Coulomb repulsion albeit differently fast
TL;DR: In this paper, the stellar core collapse, bounce, and postbounce evolution of a star in a self-consistent general relativistic spherically symmetric simulation based on Boltzmann neutrino transport was reported.
Abstract: We report on the stellar core collapse, bounce, and postbounce evolution of a $13 {\mathrm{M}}_{\ensuremath{\bigodot}}$ star in a self-consistent general relativistic spherically symmetric simulation based on Boltzmann neutrino transport. We conclude that approximations to exact neutrino transport and the omission of general relativistic effects were not alone responsible for the failure of numerous preceding attempts to model supernova explosions in spherical symmetry. Compared to simulations in Newtonian gravity, the general relativistic simulation results in a smaller shock radius. We however argue that the higher neutrino luminosities and rms energies in the general relativistic case could lead to a larger supernova explosion energy.
TL;DR: The authors' results provide evidence that gene patterns related to chondrocyte differentiation discriminate between CTR and OA human cartilage with higher sensitivity than single ECM genes.
TL;DR: Recent findings suggest that this domain serves as a diffusion barrier and also as a local cell-shape sensor and what is known about the organization of the septin cortex and its regulation during the cell cycle is reviewed.
TL;DR: The measured site-dependent attractive short-range force is in good agreement with first-principles calculations of an incipient covalent bond in an analogous model system, demonstrating the ability of atomic force microscopy to provide quantitative, atomic-scale information on surface chemical reactions.
Abstract: We report direct force measurements of the formation of a chemical bond. The experiments were performed using a low-temperature atomic force microscope, a silicon tip, and a silicon (111) 7×7 surface. The measured site-dependent attractive short-range force, which attains a maximum value of 2.1 nanonewtons, is in good agreement with first-principles calculations of an incipient covalent bond in an analogous model system. The resolution was sufficient to distinguish differences in the interaction potential between inequivalent adatoms, demonstrating the ability of atomic force microscopy to provide quantitative, atomic-scale information on surface chemical reactivity.