A retroelement modifies pre-mRNA splicing: the murine Glrbspa allele is a splicing signal polymorphism amplified by long interspersed nuclear element insertion

The glycine receptor-deficient mutant mouse spastic carries a full-length long interspersed nuclear element (LINE1) retrotransposon in intron 6 of the glycine receptor β subunit gene, Glrb(spa). The mutation arose in the C57BL/6J strain and is associated with skipping of exon 6 or a combination of the exons 5 and 6, thus resulting in a translational frameshift within the coding regions of the GlyR β subunit. The effect of the Glrb(spa) LINE1 insertion on pre-mRNA splicing was studied using a minigene approach. Sequence comparison as well as motif prediction and mutational analysis revealed that in addition to the LINE1 insertion the inactivation of an exonic splicing enhancer (ESE) within exon 6 is required for skipping of exon 6. Reconstitution of the ESE by substitution of a single residue was sufficient to prevent exon skipping. In addition to the ESE, two regions within the 5′ and 3′ UTR of the LINE1 were shown to be critical determinants for exon skipping, indicating that LINE1 acts as efficient modifier of subtle endogenous splicing phenotypes. Thus, the spastic allele of the murine glycine receptor β subunit gene is a two-hit mutation, where the hypomorphic alteration in an ESE is amplified by the insertion of a LINE1 element in the adjacent intron. Conversely, the LINE1 effect on splicing may be modulated by individual polymorphisms, depending on the insertional environment within the host genome

Rescue bedside laparotomy in the intensive care unit in patients too unstable for transport to the operating room

INTRODUCTION: The prognoses of critically ill patients with a requirement for emergency laparotomy and severe respiratory and/or hemodynamic instability precluding transport to the operating room (OR) are often fatal without surgery. Attempting emergency surgery at the bedside might equally result in an adverse outcome. However, risk factors and predictors that could support clinical decision making have not been identified so far. This study describes the clinical characteristics, indicative pathophysiology and outcomes in patients undergoing resuscitative laparotomy in the intensive care unit (ICU). METHODS: This was a retrospective observational study of all critically ill adult patients undergoing resuscitative laparotomy in the ICUs of a German university hospital from January 2005 to July 2013. Clinical characteristics, risk factors, and treatments were compared between survivors and non-survivors. The primary endpoint was 28-day survival. RESULTS: A total of 41 patients with a median age of 64 (21 to 83) were included. The most frequent reasons for ICU admission were sepsis, pneumonia, and pancreatic surgery. All patients were mechanically ventilated, receiving vasopressors, and were in multiple organ failure. Twenty-nine patients (70.7%) were on renal replacement therapy and two patients (4.9%) on extracorporeal membrane oxygenation. The main reasons for surgery were suspected intra-abdominal bleeding (39.0%), suspected intestinal ischemia (24.4%) or abdominal compartment syndrome (24.4%). Twenty-eight-day, ICU and hospital mortalities were 75.6%, 80.5%, and 82.9%, respectively. In six out of ten patients (60%) who survived surgery for more than 28 days, bedside laparotomy was rated as a life-saving procedure by an interdisciplinary group of the investigators. CONCLUSIONS: These findings suggest that in selected critically ill patients with a vital indication for emergency laparotomy and severe cardiopulmonary instability precluding transport to the OR, a bedside resuscitative laparotomy in the ICU can be considered as a rescue procedure, even though very high mortality is to be expected

Unsupervised real-world knowledge extraction via disentangled variational autoencoders for photon diagnostics

We present real-world data processing on measured electron time-of-flight data via neural networks. Specifically, the use of disentangled variational autoencoders on data from a diagnostic instrument for online wavelength monitoring at the free electron laser FLASH in Hamburg. Without a-priori knowledge the network is able to find representations of single-shot FEL spectra, which have a low signal-to-noise ratio. This reveals, in a directly human-interpretable way, crucial information about the photon properties. The central photon energy and the intensity as well as very detector-specific features are identified. The network is also capable of data cleaning, i.e. denoising, as well as the removal of artefacts. In the reconstruction, this allows for identification of signatures with very low intensity which are hardly recognisable in the raw data. In this particular case, the network enhances the quality of the diagnostic analysis at FLASH. However, this unsupervised method also has the potential to improve the analysis of other similar types of spectroscopy data

Technische und methodische Grundlagen der THG-Bilanzierung von Bioethanol: Handreichung

Seit dem 1. Januar 2015 ist die Bemessungsgrundlage für die Erfüllung der Biokraftstoffquote nach BImSchG (§ 37) vom Energiegehalt der Kraftstoffe auf eine Verpflichtung zur Treibhausgas (THG)-Minderung umgestellt worden. Diese Maßnahme soll einen wirksamen und quantifizierbaren Beitrag zur Verringerung der Treibhausgasemissionen des Verkehrssektors leisten. Konsequenterweise haben die Biokraftstoffe die besten Marktchancen, die als Ergebnis der Nachhaltigkeitszertifizierung gemäß der Biokraftstoff-Nachhaltigkeitsverordnung (Biokraft-NachV) die beste THG-Bilanz ausweisen. Die Treibhausgasminderungseffizienz wird damit – in einem globalisierten Biomasserohstoff- und Biokraftstoffmarkt – neben dem Preis für die gesamte Warenkette zum wesentlichen Wettbewerbsfaktor. Ab 2015 ist daher zu erwarten, dass die Verwendung der so genannten Standardwerte aus dem Anhang der Biokraft-NachV stark abnimmt und vorwiegend individuell berechnete THG-Bilanzen im Rahmen der Zertifizierung erstellt werden

Technische und methodische Grundlagen der THg-Bilanzierung von Biodiesel: Handreichung

Seit dem 1. Januar 2015 ist die Bemessungsgrundlage für die Erfüllung der Biokraftstoffquote nach BImSchG (§ 37) vom Energiegehalt der Kraftstoffe auf eine Verpflichtung zur Treibhausgas (THG)-Minderung umgestellt worden. Diese Maßnahme soll einen wirksamen und quantifizierbaren Beitrag zur Verringerung der Treibhausgasemissionen des Verkehrssektors leisten. Konsequenterweise haben die Biokraftstoffe die besten Marktchancen, die als Ergebnis der Nachhaltigkeitszertifizierung gemäß der Biokraftstoff-Nachhaltigkeitsverordnung (Biokraft-NachV) die beste THG-Bilanz ausweisen. Die Treibhausgasminderungseffizienz wird damit – in einem globalisierten Biomasserohstoff- und Biokraftstoffmarkt – neben dem Preis für die gesamte Warenkette zum wesentlichen Wettbewerbsfaktor. Ab 2015 ist daher zu erwarten, dass die Verwendung der Standardwerte aus dem Anhang der Biokraft-NachV stark abnimmt und vorwiegend individuell berechnete THGBilanzen im Rahmen der Zertifizierung erstellt werden

FLASH free-electron laser single-shot temporal diagnostic: terahertz-field-driven streaking

We report on the commissioning of a terahertz (THz) field driven streak camera installed at the free-electron laser FLASH at DESY in Hamburg, being able to deliver the photon pulse duration as well as the arrival time information with around 10 fs resolution for each single XUV FEL pulse. Pulse durations between 300 fs and <15 fs have been measured for different FLASH FEL settings. A comparison between the XUV pulse arrival time and the FEL electron bunch arrival time measured at the FLASH linac section - exhibit a correlation width of 20 fs rms, thus demonstrating the excellent operation stability of FLASH. In addition, the THz streaking setup was operated simultaneously to an alternative method to determine the FEL pulse duration based on spectral analysis. FLASH pulse duration, derived from simple spectral analysis, are in good agreement with that from THz streaking measurement