1,199 research outputs found
Microbial degradation of furanic compounds: biochemistry, genetics, and impact
Microbial metabolism of furanic compounds, especially furfural and 5-hydroxymethylfurfural (HMF), is rapidly gaining interest in the scientific community. This interest can largely be attributed to the occurrence of toxic furanic aldehydes in lignocellulosic hydrolysates. However, these compounds are also widespread in nature and in human processed foods, and are produced in industry. Although several microorganisms are known to degrade furanic compounds, the variety of species is limited mostly to Gram-negative aerobic bacteria, with a few notable exceptions. Furanic aldehydes are highly toxic to microorganisms, which have evolved a wide variety of defense mechanisms, such as the oxidation and/or reduction to the furanic alcohol and acid forms. These oxidation/reduction reactions constitute the initial steps of the biological pathways for furfural and HMF degradation. Furfural degradation proceeds via 2-furoic acid, which is metabolized to the primary intermediate 2-oxoglutarate. HMF is converted, via 2,5-furandicarboxylic acid, into 2-furoic acid. The enzymes in these HMF/furfural degradation pathways are encoded by eight hmf genes, organized in two distinct clusters in Cupriavidus basilensis HMF14. The organization of the five genes of the furfural degradation cluster is highly conserved among microorganisms capable of degrading furfural, while the three genes constituting the initial HMF degradation route are organized in a highly diverse manner. The genetic and biochemical characterization of the microbial metabolism of furanic compounds holds great promises for industrial applications such as the biodetoxifcation of lignocellulosic hydrolysates and the production of value-added compounds such as 2,5-furandicarboxylic acid
C1 compounds as auxiliary substrate for engineered Pseudomonas putida S12
The solvent-tolerant bacterium Pseudomonas putida S12 was engineered to efficiently utilize the C1 compounds methanol and formaldehyde as auxiliary substrate. The hps and phi genes of Bacillus brevis, encoding two key steps of the ribulose monophosphate (RuMP) pathway, were introduced to construct a pathway for the metabolism of the toxic methanol oxidation intermediate formaldehyde. This approach resulted in a remarkably increased biomass yield on the primary substrate glucose when cultured in C-limited chemostats fed with a mixture of glucose and formaldehyde. With increasing relative formaldehyde feed concentrations, the biomass yield increased from 35% (C-mol biomass/C-mol glucose) without formaldehyde to 91% at 60% relative formaldehyde concentration. The RuMP-pathway expressing strain was also capable of growing to higher relative formaldehyde concentrations than the control strain. The presence of an endogenous methanol oxidizing enzyme activity in P. putida S12 allowed the replacement of formaldehyde with the less toxic methanol, resulting in an 84% (C-mol/C-mol) biomass yield. Thus, by introducing two enzymes of the RuMP pathway, co-utilization of the cheap and renewable substrate methanol was achieved, making an important contribution to the efficient use of P. putida S12 as a bioconversion platform host
A randomized, phase III trial of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in first-line treatment of metastatic colorectal cancer: The AIO KRK 0110 Trial/ML22011 Trial
<p>Abstract</p> <p>Background</p> <p>Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question whether this statement holds true also for bevacizumab-based first-line treatment including escalation- and de-escalation strategies.</p> <p>Methods/Design</p> <p>The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m<sup>2 </sup>bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m<sup>2 </sup>BID for 14d (d1-14), irinotecan 200 mg/m<sup>2 </sup>(d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumour tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are overall response rate (ORR), overall survival, progression-free survival, safety and quality of life.</p> <p>Conclusion</p> <p>The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT01249638">NCT01249638</a></p> <p>EudraCT-No.: 2009-013099-38</p
Observation of two new baryon resonances
Two structures are observed close to the kinematic threshold in the mass spectrum in a sample of proton-proton collision data, corresponding
to an integrated luminosity of 3.0 fb recorded by the LHCb experiment.
In the quark model, two baryonic resonances with quark content are
expected in this mass region: the spin-parity and
states, denoted and .
Interpreting the structures as these resonances, we measure the mass
differences and the width of the heavier state to be
MeV,
MeV,
MeV, where the first and second
uncertainties are statistical and systematic, respectively. The width of the
lighter state is consistent with zero, and we place an upper limit of
MeV at 95% confidence level. Relative
production rates of these states are also reported.Comment: 17 pages, 2 figure
Observation of associated production of a boson with a meson in the~forward region
A search for associated production of a boson with an open charm meson is
presented using a data sample, corresponding to an integrated luminosity of
of proton--proton collisions at a centre-of-mass energy
of 7\,TeV, collected by the LHCb experiment. %% Seven candidate events for
associated production of a boson with a meson and four candidate
events for a boson with a meson are observed with a combined
significance of 5.1standard deviations. The production cross-sections in the
forward region are measured to be where the first uncertainty is statistical and the
second systematic.Comment: 18 pages, 2 figure
Measurements of the , , meson and baryon lifetimes
Measurements of -hadron lifetimes are reported using collision data,
corresponding to an integrated luminosity of 1.0fb, collected by the
LHCb detector at a centre-of-mass energy of Tev. Using the exclusive decays
, , ,
and the average decay
times in these modes are measured to be = 0.004 0.003 ps, =
0.006 0.004 ps, = 0.013
0.005 ps, = 0.027
0.006 ps and = 0.011
0.005 ps, where the first uncertainty is statistical and the second is
systematic. These represent the most precise lifetime measurements in these
decay modes. In addition, ratios of these lifetimes, and the ratio of the
decay-width difference, , to the average width, , in
the system, , are
reported. All quantities are found to be consistent with Standard Model
expectations.Comment: 28 pages, 4 figures. Updated reference
Evidence for the strangeness-changing weak decay
Using a collision data sample corresponding to an integrated luminosity
of 3.0~fb, collected by the LHCb detector, we present the first search
for the strangeness-changing weak decay . No
hadron decay of this type has been seen before. A signal for this decay,
corresponding to a significance of 3.2 standard deviations, is reported. The
relative rate is measured to be
, where and
are the and fragmentation
fractions, and is the branching
fraction. Assuming is bounded between 0.1 and
0.3, the branching fraction would lie
in the range from to .Comment: 7 pages, 2 figures, All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm
Observation of the decay
The decay is observed for the first
time, using proton-proton collisions collected with the LHCb detector
corresponding to an integrated luminosity of 3fb. A signal yield of
decays is reported with a significance of 6.2 standard deviations.
The ratio of the branching fraction of \B_c \rightarrow J/\psi K^+ K^- \pi^+
decays to that of decays is measured to be
, where the first uncertainty is statistical and the
second is systematic.Comment: 18 pages, 2 figure
Measurement of the mass and lifetime of the baryon
A proton-proton collision data sample, corresponding to an integrated
luminosity of 3 fb collected by LHCb at and 8 TeV, is used
to reconstruct , decays. Using the , decay mode for calibration, the lifetime ratio and absolute
lifetime of the baryon are measured to be \begin{align*}
\frac{\tau_{\Omega_b^-}}{\tau_{\Xi_b^-}} &= 1.11\pm0.16\pm0.03, \\
\tau_{\Omega_b^-} &= 1.78\pm0.26\pm0.05\pm0.06~{\rm ps}, \end{align*} where the
uncertainties are statistical, systematic and from the calibration mode (for
only). A measurement is also made of the mass difference,
, and the corresponding mass, which
yields \begin{align*} m_{\Omega_b^-}-m_{\Xi_b^-} &= 247.4\pm3.2\pm0.5~{\rm
MeV}/c^2, \\ m_{\Omega_b^-} &= 6045.1\pm3.2\pm 0.5\pm0.6~{\rm MeV}/c^2.
\end{align*} These results are consistent with previous measurements.Comment: 11 pages, 5 figures, All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-008.htm
Precision measurement of violation in decays
The time-dependent asymmetry in decays is
measured using collision data, corresponding to an integrated luminosity
of fb, collected with the LHCb detector at centre-of-mass energies
of and TeV. In a sample of 96 000 decays, the
-violating phase is measured, as well as the decay widths
and of the light and heavy mass eigenstates of the
system. The values obtained are rad, ps, andps, where the first uncertainty is
statistical and the second systematic. These are the most precise single
measurements of those quantities to date. A combined analysis with decays gives rad. All
measurements are in agreement with the Standard Model predictions. For the
first time the phase is measured independently for each polarisation
state of the system and shows no evidence for polarisation
dependence.Comment: 6 figure
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