A structural perspective of the role of IP6 in immature and mature retroviral assembly

The small cellular molecule inositol hexakisphosphate (IP6) has been known for ~20 years to promote the in vitro assembly of HIV-1 into immature virus-like particles. However, the molecular details underlying this effect have been determined only recently, with the identification of the IP6 binding site in the immature Gag lattice. IP6 also promotes formation of the mature capsid protein (CA) lattice via a second IP6 binding site, and enhances core stability, creating a favorable environment for reverse transcription. IP6 also enhances assembly of other retroviruses, from both the Lentivirus and the Alpharetrovirus genera. These findings suggest that IP6 may have a conserved function throughout the family Retroviridae. Here, we discuss the different steps in the viral life cycle that are influenced by IP6, and describe in detail how IP6 interacts with the immature and mature lattices of different retroviruses

In silico assessment of a novel single-molecule protein fingerprinting method employing fragmentation and nanopore detection

Summary: The identification of proteins at the single-molecule level would open exciting new venues in biological research and disease diagnostics. Previously, we proposed a nanopore-based method for protein identification called chop-n-drop fingerprinting, in which the fragmentation pattern induced and measured by a proteasome-nanopore construct is used to identify single proteins. In the simulation study presented here, we show that 97.1% of human proteome constituents are uniquely identified under close to ideal measuring circumstances, using a simple alignment-based classification method. We show that our method is robust against experimental error, as 69.4% can still be identified if the resolution is twice as low as currently attainable, and 10% of proteasome restriction sites and protein fragments are randomly ignored. Based on these results and our experimental proof of concept, we argue that chop-n-drop fingerprinting has the potential to make cost-effective single-molecule protein identification feasible in the near future

Estimating the impact of Global Navigation Satellite System horizontal delay gradients in variational data assimilation

We developed operators to assimilate Global Navigation Satellite System (GNSS) Zenith Total Delays (ZTDs) and horizontal delay gradients into a numerical weather model. In this study we experiment with refractivity fields derived from the Global Forecast System (GFS) available with a horizontal resolution of 0.5 degrees. We begin our investigations with simulated observations. In essence, we extract the tropospheric parameters from the GFS analysis, add noise to mimic observation errors and assimilate the simulated observations into the GFS 24h forecast valid at the same time. We consider three scenarios: (1) the assimilation of ZTDs (2) the assimilation of horizontal delay gradients and (3) the assimilation of both ZTDs and horizontal delay gradients. The impact is measured by utilizing the refractivity fields. We find that the assimilation of the horizontal delay gradients in addition to the ZTDs improves the refractivity field around 800 hPa. When we consider a single station there is a clear improvement when horizontal delay gradients are assimilated in addition to the ZTDs because the horizontal delay gradients contain information that is not contained in the ZTDs. On the other hand, when we consider a dense station network there is not a significant improvement when horizontal delay gradients are assimilated in addition to the ZTDs because the horizontal delay gradients do not contain information that is not already contained in the ZTDs. Finally, we replace simulated by real observations, that is, tropospheric parameters from a Precise Point Positioning solution provided with the G-Nut/Tefnut software, in order to show that the GFS 24h forecast is indeed improved when GNSS horizontal delay gradients are assimilated in addition to GNSS ZTDs; for the considered station (Potsdam, Germany) and period (June and July, 2017) we find an improvement in the retrieved refractivity of up to 4%.Web of Science111art. no. 4

A methodology to compute GPS slant total delays in a numerical weather model

A numerical algorithm based on Fermat's Principle was developed to simulate the propagation of Global Positioning System (GPS) radio signals in the refractivity field of a numerical weather model. The unique in the proposed algorithm is that the ray-trajectory automatically involves the location of the ground-based receiver and the satellite, i.e. the posed two-point boundary value problem is solved by an implicit finite difference scheme. This feature of the algorithm allows the fast and accurate computation of the signal travel-time delay, referred to as Slant Total Delay (STD), between a satellite and a ground-based receiver. We provide a technical description of the algorithm and estimate the uncertainty of STDs due to simplifying assumptions in the algorithm and due to the uncertainty of the refractivity field. In a first application, we compare STDs retrieved from GPS phase-observations at the German Research Centre for Geosciences Potsdam (GFZ STDs) with STDs derived from the European Center for Medium-Range Weather Forecasts analyses (ECMWF STDs). The statistical comparison for one month (August 2007) for a large and continuously operating network of ground-based receivers in Germany indicates good agreement between GFZ STDs and ECMWF STDs; the standard deviation is 0.5% and the mean deviation is 0.1%

Outcome and Quality of Life in Patients Treated for Abdominal Aortic Aneurysms: A Single Center Experience

Background: Durability of protection and long-term quality of life (QoL) are critical outcome parameters of abdominal aortic aneurysm (AAA) repair. The aim of the present study was to compare results of endovascular and open aneurysm repair (EVAR and OR) with adjusted standard populations, including stratification for urgency of presentation. Methods: Retrospective analysis of prospectively collected data of 401 consecutive patients presenting with AAA between January 1998 and December 2002. Cross-sectional follow up was 58±29months. Patients were grouped into three cohorts: elective EVAR (n=68), elective OR (n=244), and emergency OR (including symptomatic and ruptured AAA, n=89). Endpoints were perioperative (i.e., 30days or in-hospital) and late mortality rates, as well as long-term QoL as assessed by the Short Form health survey questionnaire (SF-36). Results: Mean age was lower in the elective OR cohort (66±10years) than in the EVAR cohort (72±7years; p<.05). Perioperative mortality rates were 4.4%, 0.4%, and 10.1%, for the EVAR, elective OR, and emergency OR cohorts, respectively (p<.05). Corresponding cumulative survival rates after 4years were 67%, 89%, and 69%, respectively. Long-term QoL SF-36 scores were in all cohorts similar to age- and gender-adjusted standard populations, which score between 85 and 115: 99.6±35.8 (EVAR), 101.3±32.4 (elective OR), and 100.4±36.5 (emergency OR). Conclusions: Long-term QoL is not permanently impaired after AAA repair, but returns in long-term survivors to what would be expected in a standard population. In this respect, differences were found neither between EVAR and OR, nor between elective and emergency repair. Perioperative mortality rates were highest in patients undergoing emergency OR. The outlook for such patients after the perioperative period, however, was similar to that for patients undergoing elective repai

Persistent sensitivity disorders at the radial artery and saphenous vein graft harvest sites: a neglected side effect of coronary artery bypass grafting procedures

Objective: The use of radial artery conduits in coronary artery bypass grafting (CABG) surgery is associated with improved long-term patency and patient survival rates as compared with saphenous vein conduits. Despite increasing popularity, relative incidence of local harvest-site complications and subjective perception of adverse long-term sequelae remain poorly described. Methods: To allow for direct comparison, we investigated a consecutive series of patients in whom both the radial artery and the saphenous vein had been harvested for isolated CABG during a 36-month period. Patients were identified from a prospective database that collects baseline clinical information. The patients' own perceptions were assessed by a standardized direct telephone survey regarding any persistent functional impairment from their arm and leg operation sites. Results: Out of 1756 CABG patients during the study period, 168 (10%) were eligible (78% men, median age: 60.1 ± 9.6 years, range: 29.6-82.4 years). Of these, 123 (73%) could be contacted and interviewed at a median follow-up time of 2.5 ± 0.9 years. Surgical wound complications at harvest sites (arms and legs) had occurred in 3% and 12%, respectively, and persistent symptoms (arms and legs) were self-reported as follows: chronic pain (5% and 8%), numbness (32% and 34%) and paresthesia/dysesthesia (14% and 7%). Overall, 39% of the patients reported persistent discomfort at the arm and 39% at the leg. Both sites were simultaneously affected in 21% (P = n.s., paired testing). Logistic regression modeling showed that patients with adverse long-term sequelae were younger (P < 0.005), had a higher body mass index (P < 0.05) and a lower EuroSCORE (P < 0.001) at the time of operation (EuroSCORE, European System for Cardiac Operative Risk Evaluation). Perioperative wound complications, however, did not predict persistence of symptoms. Conclusions: Persistent harvest-site discomfort occurs with astonishing frequency after CABG surgery and affects arms and legs equally. Although usually considered a minor complication, long-term limitation to quality of life may be substantial, particularly in younger and relatively healthy patients. Thus, harvest-site discomfort clearly belongs to the list of possible post-CABG complications of which patients need to be awar

Chirurgische und interventionelle Behandlung der chronisch-kritischen Beinischämie

Die chronisch-kritische Beinischämie (CLI) ist die schwerste Form der peripher-arteriellen Verschlusskrankheit und geht mit einem erhöhten Risiko für letale kardiovaskuläre Ereignisse einher. Die meisten Patienten überleben aber die ersten Jahre nach Diagnosestellung und sind für den Erhalt ihrer Selbständigkeit auf eine nachhaltige Verbesserung der Beindurchblutung angewiesen. Dieser CME-Artikel fasst die chirurgischen und endovaskulären Optionen zur Revaskularisierung zusammen und geht auf deren Nachhaltigkeit bei CLI ein. Grenzen der verfügbaren Evidenz werden aufgezeigt. Sie beruhen vor allem auf dem Fehlen einer einheitlichen Definition des Behandlungserfolges. Ein klinisch orientierter Lösungsvorschlag wird diskutiert, der helfen könnte, die verschiedenen Behandlungsindikationen zu schärfen. Da sich aber nur die wenigsten Patienten gleich gut für verschiedene Verfahren eignen, werden CLI-Patienten auch in Zukunft am besten in einem interdisziplinär arbeitenden Team betreut sein.Chronic critical limb ischemia (CLI) represents the most severe form of peripheral arterial occlusive disease and is associated with an increased risk for fatal cardiovascular events. However, most patients survive the first years after diagnosis and, to remain independent, depend on durable improvement of limb perfusion. This CME article summarizes the various surgical and endovascular options of revascularization in the context of CLI and discusses their durability. Available evidence is limited which is mainly due to a lack of a generally accepted outcome definition of clinical treatment success. A recently proposed clinically driven measure of success is discussed and how its use could improve definition of specific indications. As only few patients are clinically equally suitable for various treatment options, CLI patients will certainly remain to be managed best within interdisciplinary teams with close collaboration between surgeons and interventionalists

Benchmark campaign and case study episode in central Europe for development and assessment of advanced GNSS tropospheric models and products

Initial objectives and design of the Benchmark campaign organized within the European COST Action ES1206 (2013–2017) are described in the paper. This campaign has aimed to support the development and validation of advanced Global Navigation Satellite System (GNSS) tropospheric products, in particular high-resolution and ultra-fast zenith total delays (ZTDs) and tropospheric gradients derived from a dense permanent network. A complex data set was collected for the 8-week period when several extreme heavy precipitation episodes occurred in central Europe which caused severe river floods in this area. An initial processing of data sets from GNSS products and numerical weather models (NWMs) provided independently estimated reference parameters – zenith tropospheric delays and tropospheric horizontal gradients. Their provision gave an overview about the product similarities and complementarities, and thus a potential for improvements of a synergy in their optimal exploitations in future. Reference GNSS and NWM results were intercompared and visually analysed using animated maps. ZTDs from two reference GNSS solutions compared to global ERA-Interim reanalysis resulted in accuracy at the 10 mm level in terms of the root mean square (rms) with a negligible overall bias, comparisons to Global Forecast System (GFS) forecasts showed accuracy at the 12 mm level with the overall bias of −5 mm and, finally, comparisons to mesoscale ALADIN-CZ forecast resulted in accuracy at the 8 mm level with a negligible total bias. The comparison of horizontal tropospheric gradients from GNSS and NWM data demonstrated a very good agreement among independent solutions with negligible biases and an accuracy of about 0.5 mm. Visual comparisons of maps of zenith wet delays and tropospheric horizontal gradients showed very promising results for future exploitations of advanced GNSS tropospheric products in meteorological applications, such as severe weather event monitoring and weather nowcasting. The GNSS products revealed a capability of providing more detailed structures in atmosphere than the state-of-the-art numerical weather models are able to capture. In an initial study on the contribution of hydrometeors (e.g. cloud water, ice or snow) to GNSS signal delays during severe weather, the effect reached up to 17 mm, and it was suggested that hydrometeors should be carefully accounted for within the functional model. The reference products will be further exploited in various specific studies using the Benchmark data set. It is thus going to play a key role in these highly interdisciplinary developments towards better mutual benefits from advanced GNSS and meteorological products.Web of Science973008298

Thoracic endovascular aortic repair: impact of urgency on outcome and quality of life

Objectives: Endovascular repair of the descending thoracic aorta is a very promising technique in elective and, particularly, emergency situations. This study assessed the impact of urgency of the procedure on outcome and mid-term quality of life in surviving patients. Methods: Post hoc analysis of prospectively collected data of 58 consecutive patients (January 2001-December 2005) with surgical pathologies of the descending thoracic aorta treated by endovascular means. Six patients were excluded due to recent operations on the ascending aorta before thoracic endovascular repair. The remaining patients (n=52) were 69±10 years old, and 43 were men (83%). Twenty-seven had been treated electively, and 25 for emergency indications. Reasons for emergency were acute type B aortic dissections with or without malperfusion syndrome in 14, and aortic ruptures in 11 cases. Follow-up was 29±16 months. Endpoints were perioperative and late morbidity and mortality rates and long-term quality of life as assessed by the short form health survey (SF-36) and Hospital Anxiety and Depression Scale questionnaires. Results: Cohorts were comparable regarding age, sex, cardiovascular risk factors, and comorbidities. Perioperative mortality was somewhat higher in emergency cases (12% vs 4%, p=0.34). Paraplegia occurred in one patient in each cohort (4%). Overall quality of life after two and a half years was similar in both treatment cohorts: 72 (58-124) after emergency, and 85 (61-105) after elective endovascular aortic repair (p=0.98). Normal scores range from 85 to 115. Anxiety and depression scores were in the normal range and comparable. Conclusions: Thoracic endovascular aortic repair is an excellent and safe treatment option for the diseased descending aorta, particularly in emergency situations. Early morbidity and mortality rates can be kept very low. Mid-term quality of life was not affected by the urgency of the procedure. Similarly, mid-term anxiety and depression scores were not increased after emergency situation