172 research outputs found
Enzymatic Sialylation of Synthetic Multivalent Scaffolds: From 3′-Sialyllactose Glycomacromolecules to Novel Neoglycosides
Sialoglycans play a key role in many biological recognition processes and sialylated conjugates of various types have successfully been applied, e.g., as antivirals or in antitumor therapy. A key feature for high affinity binding of such conjugates is the multivalent presentation of sialoglycans which often possess synthetic challenges. Here, the combination is described of solid phase polymer synthesis and enzymatic sialylation yielding 3′-sialyllactose-presenting precision glycomacromolecules. CMP-Neu5Ac synthetase from Neisseria meningitidis (NmCSS) and sialyltransferase from Pasteurella multocida (PmST1) are combined in a one-pot reaction giving access to sequence-defined sialylated macromolecules. Surprisingly, when employing Tris(hydroxymethyl)aminomethane (Tris) as a buffer, formation of significant amounts of α-linked Tris-sialoside is observed as a side reaction. Further exploring and exploiting this unusual sialylation reaction, different neoglycosidic structures are synthesized showing that PmST1 can be used to derive both, sialylation on natural carbohydrates as well as on synthetic hydroxylated scaffolds
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DNA methylation-based classification of central nervous system tumours.
Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology
Study of Z Boson Pair Production in e+e- Collisions at LEP at \sqrt{s}=189 GeV
The pair production of Z bosons is studied using the data collected by the L3
detector at LEP in 1998 in e+e- collisions at a centre-of-mass energy of 189
GeV. All the visible final states are considered and the cross section of this
process is measured to be 0.74 +0.15 -0.14 (stat.) +/- 0.04 (syst.) pb. Final
states containing b quarks are enhanced by a dedicated selection and their
production cross section is found to be 0.18 +0.09 -0.07 (stat.) +/- 0.02
(syst.) pb. Both results are in agreement with the Standard Model predictions.
Limits on anomalous couplings between neutral gauge bosons are derived from
these measurements
Direct Observation of Longitudinally Polarised W Bosons
The three different helicity states of W bosons, produced in the reaction
e+e- -> W+W- -> l nu q q~ are studied using leptonic and hadronic W decays at
sqrt{s}=183GeV and 189GeV. The W polarisation is also measured as a function of
the scattering angle between the W- and the direction of the e- beam. The
analysis demonstrates that W bosons are produced with all three helicities, the
longitudinal and the two transverse states. Combining the results from the two
center-of-mass energies and with leptonic and hadronic W decays, the fraction
of longitudinally polarised W bosons is measured to be 0.261 +/- 0.051(stat.)
+/- 0.016(syst.) in agreement with the expectation from the Standard Model
Search for Scalar Leptons in e+e- collisions at \sqrt{s}=189 GeV
We report the result of a search for scalar leptons in e+e- collisions at 189
GeV centre-of-mass energy at LEP. No evidence for such particles is found in a
data sample of 176 pb^{-1}. Improved upper limits are set on the production
cross sections for these new particles. New exclusion contours in the parameter
space of the Minimal Supersymmetric Standard Model are derived, as well as new
lower limits on the masses of these supersymmetric particles. Under the
assumptions of common gaugino and scalar masses at the GUT scale, we set an
absolute lower limit on the mass of the lightest scalar electron of 65.5 Ge
Search for a Higgs Boson Decaying into Two Photons at LEP
A Higgs particle produced in association with a Z boson and decaying into two
photons is searched for in the data collected by the L3 experiment at LEP. All
possible decay modes of the Z boson are investigated. No signal is observed in
447.5 pb^-1 of data recorded at centre-of-mass energies up to 209 GeV. Limits
on the branching fraction of the Higgs boson decay into two photons as a
function of the Higgs mass are derived. A lower limit on the mass of a
fermiophobic Higgs boson is set at 105.4 GeV at 95% confidence level
K0s K0s Final State in Two-Photon Collisions and Implications for Glueballs
The K0s K0s final state in two-photon collisions is studied with the L3
detector at LEP. The mass spectrum is dominated by the formation of the
f_2'(1525) tensor meson in the helicity-two state with a two-photon width times
the branching ratio into K Kbar of 76 +- 6 +- 11 eV. A clear signal for the
formation of the f_J(1710) is observed and it is found to be dominated by the
spin-two helicity-two state. No resonance is observed in the mass region around
2.2 GeV and an upper limit of 1.4 eV at 95% C.L. is derived for the two-photon
width times the branching ratio into K0s K0s for the glueball candidate
xi(2230)
Formation of the in Two-Photon Collisions at LEP
The two-photon width of the meson has been
measured with the L3 detector at LEP. The is studied in the decay
modes , KK, KK,
KK, , , and
using an integrated luminosity of 140 pb at GeV and
of 52 pb at GeV. The result is
(BR) keV. The dependence of the cross section is studied for
GeV. It is found to be better described by a Vector Meson
Dominance model form factor with a J-pole than with a -pole. In addition,
a signal of events is observed at the mass. Upper limits
for the two-photon widths of the , , and are also
given
Study of Z Boson Pair Production in e^+e^- Interactions at \sqrt{s}=192 - 202 GeV
The cross section for the production of Z boson pairs is measured using the
data collected by the L3 detector at LEP in 1999 in e^+e^- collisions at
centre-of-mass energies ranging from 192 GeV up to 202 GeV. Events in all the
visible final states are selected, measuring the cross section of this process.
The special case of final states containing b quarks is also investigated. All
results are in agreement with the Standard Model predictions
Role of AMP-Activated Protein Kinase on Steroid Hormone Biosynthesis in Adrenal NCI-H295R Cells
Regulation of human androgen biosynthesis is poorly understood. However, detailed knowledge is needed to eventually solve disorders with androgen dysbalance. We showed that starvation growth conditions shift steroidogenesis of human adrenal NCI-H295R cells towards androgen production attributable to decreased HSD3B2 expression and activity and increased CYP17A1 phosphorylation and 17,20-lyase activity. Generally, starvation induces stress and energy deprivation that need to be counteracted to maintain proper cell functions. AMP-activated protein kinase (AMPK) is a master energy sensor that regulates cellular energy balance. AMPK regulates steroidogenesis in the gonad. Therefore, we investigated whether AMPK is also a regulator of adrenal steroidogenesis. We hypothesized that starvation uses AMPK signaling to enhance androgen production in NCI-H295R cells. We found that AMPK subunits are expressed in NCI-H295 cells, normal adrenal tissue and human as well as pig ovary cells. Starvation growth conditions decreased phosphorylation, but not activity of AMPK in NCI-H295 cells. In contrast, the AMPK activator 5-aminoimidazole-4-carboxamide (AICAR) increased AMPKα phosphorylation and increased CYP17A1-17,20 lyase activity. Compound C (an AMPK inhibitor), directly inhibited CYP17A1 activities and can therefore not be used for AMPK signaling studies in steroidogenesis. HSD3B2 activity was neither altered by AICAR nor compound C. Starvation did not affect mitochondrial respiratory chain function in NCI-H295R cells suggesting that there is no indirect energy effect on AMPK through this avenue. In summary, starvation-mediated increase of androgen production in NCI-H295 cells does not seem to be mediated by AMPK signaling. But AMPK activation can enhance androgen production through a specific increase in CYP17A1-17,20 lyase activity
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