36 research outputs found
Long-term follow-up of cytogenetically normal CEBPA-mutated AML
Background: The aim of this study was to analyze the long-term survival of AML patients with CEBPA mutations. Patients and methods: We investigated 88 AML patients with a median age of 61 years and (1) cytogenetically normal AML (CN-AML), (2) monoallelic (moCEBPA) or biallelic (biCEBPA) CEBPA mutation, and (3) intensive induction treatment. 60/88 patients have been described previously with a shorter follow-up. Results: Median follow-up time was 9.8 years (95% CI: 9.4-10.1 years) compared to 3.2 and 5.2 years in our former analyses. Patients with biCEBPA mutations survived significantly longer compared to those with moCEBPA (median overall survival (OS) 9.6 years vs. 1.7 years, p = 0.008). Patients <= 60 years and biCEBPA mutations showed a favorable prognosis with a 10-year OS rate of 81%. Both, bi- and moCEBPA-mutated groups had a low early death (d60) rate of 7% and 9%, respectively. Complete remission (CR) rates for biCEBPA and moCEBPA mutated patients were 82% vs. 70% (p = 0.17). biCEBPA mutated patients showed a longer relapse free survival (RFS) (median RFS 9.4 years vs. 1.5 years, p = 0.021) and a lower cumulative incidence of relapse (CIR) compared to moCEBPA-mutated patients. These differences in OS and RFS were confirmed after adjustment for known clinical and molecular prognostic factors. Conclusions: In this long-term observation we confirmed the favorable prognostic outcome of patients with biCEBPA mutations compared to moCEBPA-mutated CN-AML. The high probability of OS (81%) in younger patients is helpful to guide intensity of postremission therapy
Structure-based discovery of opioid analgesics with reduced side effects
Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioidsâwhich include fatal respiratory depressionâare thought to be mediated by ÎŒ-opioid-receptor (ÎŒOR) signalling through the ÎČ-arrestin pathway or by actions at other receptors. Conversely, G-protein ÎŒOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the ÎŒOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21âa potent Gi activator with exceptional selectivity for ÎŒOR and minimal ÎČ-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle ÎŒOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids
Prevalence of human papillomavirus infection in women in Benin, West Africa
<p>Abstract</p> <p>Background</p> <p>Cervical cancer ranks as the first most frequent cancer among women in Benin. The major cause of cervical cancer now recognized is persistent infection of Human Papillomavirus (HPV). In Benin there is a lack of screening programs for prevention of cervical cancer and little information exists regarding HPV genotype distribution.</p> <p>Methods</p> <p>Cervical cells from 725 women were examined for the presence of viral DNA by means of a polymerase chain reaction (PCR) multiplex-based assay with the amplification of a fragment of L1 region and of E6/E7 region of the HPV genome, and of abnormal cytology by Papanicolaou method. The association between HPV status and Pap test reports was evaluated. Socio-demographic and reproductive characteristics were also related.</p> <p>Results</p> <p>A total of 18 different HPV types were identified, with a prevalence of 33.2% overall, and 52% and 26.7% among women with and without cervical lesions, respectively. Multiple HPV infections were observed in 40.2% of HPV-infected women. In the HPV-testing group, the odds ratio for the detection of abnormal cytology was 2.98 (95% CI, 1.83-4.84) for HPV positive in comparison to HPV negative women. High risk types were involved in 88% of infections, most notably HPV-59, HPV-35, HPV-16, HPV-18, HPV-58 and HPV-45. In multiple infections of women with cytological abnormalities HPV-45 predominated.</p> <p>Conclusions</p> <p>This study provides the first estimates of the prevalence of HPV and type-specific distribution among women from Benin and demonstrates that the epidemiology of HPV infection in Benin is different from that of other world regions. Specific area vaccinations may be needed to prevent cervical cancer and the other HPV-related diseases.</p
First Direct Observation of Collider Neutrinos with FASER at the LHC
We report the first direct observation of neutrino interactions at a particle
collider experiment. Neutrino candidate events are identified in a 13.6 TeV
center-of-mass energy collision data set of 35.4 fb using the
active electronic components of the FASER detector at the Large Hadron
Collider. The candidates are required to have a track propagating through the
entire length of the FASER detector and be consistent with a muon neutrino
charged-current interaction. We infer neutrino interactions
with a significance of 16 standard deviations above the background-only
hypothesis. These events are consistent with the characteristics expected from
neutrino interactions in terms of secondary particle production and spatial
distribution, and they imply the observation of both neutrinos and
anti-neutrinos with an incident neutrino energy of significantly above 200 GeV.Comment: Submitted to PRL on March 24 202
A communal catalogue reveals Earth's multiscale microbial diversity
Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe
A communal catalogue reveals Earthâs multiscale microbial diversity
Our growing awareness of the microbial worldâs importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earthâs microbial diversity
Fertigungskonzepte fĂŒr Paneele mit Omega-Stringern (OMEGA)
Omega-Stringer bieten hinsichtlich fertigungstechnisch und unter strukturmechanischen
gesichtspunkten vorteilhafte Eigenschaften fĂŒr Leichtbaukonstruktionen. Deren Anwendung hat
sich daher in Luftfahrzeugen etabliert, muss aber noch in einen robusten Fertigungspropzess
ĂŒberfĂŒhrt werden. Im sogenannten Co-Bonding-Verfahren werden ausgehĂ€rtete Stringer auf eine
Prepreq-Schale verklebt. Bei der ProzessfĂŒhrung im Autoklav sind dabei spezielle
StĂŒtzkernprofile zum Druckaufbau zwischen Stringer und Haut erforderlich, die aus
gewichtsgrĂŒnden aus der Struktur entfernt werden mĂŒssen. HierfĂŒr wurden kosteneffiziente Lösungen gefunden und auf ihre Prozesssicherheit und MaterialvertrĂ€glichkeit hin untersucht. Die
Geometrie der StĂŒtzkerne wurde anhand von Laborversuchen analysiert und optimiert. Zur
Charakterisierung der Eigenschaften möglicher Kernmaterialien wurden werkstofftechnische und
mechanische PrĂŒfungen durchgefĂŒhrt. Die Validierung der Prozesstauglichkeit der Konzepte ist in GroĂversuchen erfolgt