Lymphotoxin is an autocrine growth factor for Epstein-Barr virus-infected B cell lines.

Because human lymphotoxin (LT) was originally isolated from a lymphoblastoid cell line, we investigated the role of this molecule in three newly established Epstein-Barr virus (EBV)-infected human B cell lines. These lines were derived from acute lymphoblastic leukemia (Z-6), myelodysplastic syndrome (Z-43), and acute myelogenous leukemia (Z-55) patients who had a prior EBV infection. Each lymphoblastoid cell line had a karyotype that was different from that of the original parent leukemic cells, and all expressed B cell, but not T cell or myeloid surface markers. In all three lines, rearranged immunoglobulin heavy chain joining region (JH) bands were found, and the presence of EBV DNA was confirmed by Southern blotting. Z-6, Z-43, and Z-55 cell lines constitutively produced 192, 48, and 78 U/ml LT, respectively, as assessed by a cytotoxicity assay and antibody neutralization. Levels of tumor necrosis factor (TNF) were undetectable. Scatchard analysis revealed that all the cell lines expressed high-affinity TNF/LT receptors with receptor densities of 4197, 1258, and 1209 sites/cell on Z-6, Z-43, and Z-55, respectively. Furthermore, labeled TNF binding could be reversed by both unlabeled TNF, as well as by LT. Studies with p60 and p80 receptor-specific antibodies revealed that the three lines expressed primarily the p80 form of the TNF receptor. When studied in a clonogenic assay, exogenous LT stimulated proliferation of all three cell lines in a dose-dependent fashion at concentrations ranging from 25 to 500 U/ml. Similar results were obtained with [3H]TdR incorporation. Monoclonal anti-LT neutralizing antibodies at concentrations of 25-500 U/ml inhibited cellular multiplication in a dose-dependent manner. It is interesting that in spite of a common receptor, TNF (1,000 U/ml) had no direct effect on Z-55 cell growth, whereas it partially reversed the stimulatory effect of exogenous LT. In addition, TNF inhibited Z-6 and Z-43 cell proliferation, and its suppressive effect was reversed by exogenous LT. Both p80 and p60 forms of soluble TNF receptors suppressed the lymphoblastoid cell line proliferation and their inhibitory effect was partially reversed by LT. Our data suggest that (a) LT is an autocrine growth factor for EBV-transformed lymphoblastoid B cell lines; and (b) anti-LT antibodies, soluble TNF/LT receptors, and TNF itself can suppress the growth of lymphoblastoid cells, probably by modulating or competing with LT.(ABSTRACT TRUNCATED AT 400 WORDS

Tbx1 and Brn4 regulate retinoic acid metabolic genes during cochlear morphogenesis

<p>Abstract</p> <p>Background</p> <p>In vertebrates, the inner ear is comprised of the cochlea and vestibular system, which develop from the otic vesicle. This process is regulated via inductive interactions from surrounding tissues. <it>Tbx1</it>, the gene responsible for velo-cardio-facial syndrome/DiGeorge syndrome in humans, is required for ear development in mice. <it>Tbx1 </it>is expressed in the otic epithelium and adjacent periotic mesenchyme (POM), and both of these domains are required for inner ear formation. To study the function of <it>Tbx1 </it>in the POM, we have conditionally inactivated <it>Tbx1 </it>in the mesoderm while keeping expression in the otic vesicle intact.</p> <p>Results</p> <p>Conditional mutants (<it>TCre-KO</it>) displayed malformed inner ears, including a hypoplastic otic vesicle and a severely shortened cochlear duct, indicating that <it>Tbx1 </it>expression in the POM is necessary for proper inner ear formation. Expression of the mesenchyme marker <it>Brn4 </it>was also lost in the <it>TCre-KO</it>. <it>Brn4</it>^-;<it>Tbx1</it>^+/-embryos displayed defects in growth of the distal cochlea. To identify a potential signal from the POM to the otic epithelium, expression of retinoic acid (RA) catabolizing genes was examined in both mutants. <it>Cyp26a1 </it>expression was altered in the <it>TCre-KO</it>, while <it>Cyp26c1 </it>showed reduced expression in both <it>TCre-KO </it>and <it>Brn4</it>^-;<it>Tbx1</it>^+/-embryos.</p> <p>Conclusion</p> <p>These results indicate that <it>Tbx1 </it>expression in the POM regulates cochlear outgrowth potentially via control of local retinoic acid activity.</p

Soft X-ray emission lines of Fe XV in solar flare observations and the Chandra spectrum of Capella

Recent calculations of atomic data for Fe XV have been used to generate theoretical line ratios involving n = 3-4 transitions in the soft X-ray spectral region (52-83 A), for a wide range of electron temperatures and densities applicable to solar and stellar coronal plasmas. A comparison of these with solar flare observations from a rocket-borne spectrograph (XSST) reveals generally good agreement between theory and experiment. In particular, the 82.76 A emission line in the XSST spectrum is identified, for the first time to our knowledge in an astrophysical source. Most of the Fe XV transitions which are blended have had the species responsible clearly identified, although there remain a few instances where this has not been possible. The line ratio calculations are also compared with a co-added spectrum of Capella obtained with the Chandra satellite, which is probably the highest signal-to-noise observation achieved for a stellar source in the 25-175 A soft X-ray region. Good agreement is found between theory and experiment, indicating that the Fe XV lines are reliably detected in Chandra spectra, and hence may be employed as diagnostics to determine the temperature and/or density of the emitting plasma. However the line blending in the Chandra data is such that individual emission lines are difficult to measure accurately, and fluxes may only be reliably determined via detailed profile fitting of the observations. The co-added Capella spectrum is made available to hopefully encourage further exploration of the soft X-ray region in astronomical sources.Comment: 27 pages, 10 figures, Astrophysical Journal, in pres

Evolution of Fluctuation in relativistic heavy-ion collisions

We have studied the time evolution of the fluctuations in the net baryon number for different initial conditions and space time evolution scenarios. We observe that the fluctuations at the freeze-out depend crucially on the equation of state (EOS) of the system and for realistic EOS the initial fluctuation is substantially dissipated at the freeze-out stage. At SPS energies the fluctuations in net baryon number at the freeze-out stage for quark gluon plasma and hadronic initial state is close to the Poissonian noise for ideal as well as for EOS obtained by including heavier hadronic degrees of freedom. For EOS obtained from the parametrization of lattice QCD results the fluctuation is larger than Poissonian noise. It is also observed that at RHIC energies the fluctuations at the freeze-out point deviates from the Poissonian noise for ideal as well as realistic equation of state, indicating presence of dynamical fluctuations.Comment: 9 pages and 6 figures (Major modifications done

Event-by-Event Fluctuations of Particle Ratios in Heavy-Ion Collisions

We study event-by-event dynamical fluctuations of various particle ratios at different energies. We assume that particle production in final state is due to chemical equilibrium processes. We compare results from resonance gas model with available experimental data. At SPS energies, the model can very well reproduce the experimentally measured fluctuations. We make predictions for dynamical fluctuations of strangeness and non-strangeness particle ratios. We found that the energy-dependence is non-monotonic. Furthermore, we found that fluctuations strongly depend on particle ratios.Comment: 6 pages, 2 figure, 1 tabl

Effects of neo-adjuvant chemotherapy for oesophago-gastric cancer on neuro-muscular gastric function

Delayed gastric emptying symptoms are often reported after chemotherapy. This study aims to characterise the effects of chemotherapy on gastric neuro-muscular function. Patients undergoing elective surgery for oesophago-gastric cancer were recruited. Acetylcholinesterase, nNOS, ghrelin receptor and motilin expressions were studied in gastric sections from patients receiving no chemotherapy (n = 3) or oesophageal (n = 2) or gastric (n = 2) chemotherapy. A scoring system quantified staining intensity (0–3; no staining to strong). Stomach sections were separately suspended in tissue baths for electrical field stimulation (EFS) and exposure to erythromycin or carbachol; three patients had no chemotherapy; four completed cisplatin-based chemotherapy within 6 weeks prior to surgery. AChE expression was markedly decreased after chemotherapy (scores 2.3 ± 0.7, 0.5 ± 0.2 and 0 ± 0 in non-chemotherapy, oesophageal- and gastric-chemotherapy groups (p < 0.03 each) respectively. Ghrelin receptor and motilin expression tended to increase (ghrelin: 0.7 ± 0.4 vs 2.0 ± 0.4 and 1.2 ± 0.2 respectively; p = 0.04 and p = 0.2; motilin: 0.7 ± 0.5 vs 2.2 ± 0.5 and 2.0 ± 0.7; p = 0.06 and p = 0.16). Maximal contraction to carbachol was 3.7 ± 0.7 g and 1.9 ± 0.8 g (longitudinal muscle) and 3.4 ± 0.4 g and 1.6 ± 0.6 (circular) in non-chemotherapy and chemotherapy tissues respectively (p < 0.05 each). There were loss of AChE and reduction in contractility to carbachol. The tendency for ghrelin receptors to increase suggests an attempt to upregulate compensating systems. Our study offers a mechanism by which chemotherapy markedly alters neuro-muscular gastric function

The Effects of Quantum Entropy on the Bag Constant

The effects of quantum entropy on the bag constant are studied at low temperatures and small chemical potentials. The inclusion of the quantum entropy of the quarks in the equation of state provides the hadronic bag with an additional heat which causes a decrease in the effective latent heat inside the bag. We have considered two types of baryonic bags, $\Delta$ and $\Omega^-$. In both cases we have found that the bag constant without the quantum entropy almost does not change with the temperature and the quark chemical potential. The contribution from the quantum entropy to the equation of state clearly decreases the value of the bag constant.Comment: 7 pages, 2 figures (two parts each

Efficient clustering of web-derived data sets

Many data sets derived from the web are large, high-dimensional, sparse and have a Zipfian distribution of both classes and features. On such data sets, current scalable clustering methods such as streaming clustering suffer from fragmentation. where large classes are incorrectly divided into many smaller clusters. and computational efficiency drops significantly. We present a new clustering algorithm based on connected components that addresses these issues and so works well oil web-type data

Flexible provisioning of Web service workflows

Web services promise to revolutionise the way computational resources and business processes are offered and invoked in open, distributed systems, such as the Internet. These services are described using machine-readable meta-data, which enables consumer applications to automatically discover and provision suitable services for their workflows at run-time. However, current approaches have typically assumed service descriptions are accurate and deterministic, and so have neglected to account for the fact that services in these open systems are inherently unreliable and uncertain. Specifically, network failures, software bugs and competition for services may regularly lead to execution delays or even service failures. To address this problem, the process of provisioning services needs to be performed in a more flexible manner than has so far been considered, in order to proactively deal with failures and to recover workflows that have partially failed. To this end, we devise and present a heuristic strategy that varies the provisioning of services according to their predicted performance. Using simulation, we then benchmark our algorithm and show that it leads to a 700% improvement in average utility, while successfully completing up to eight times as many workflows as approaches that do not consider service failures