Hydraulic Transport Across Hydrophilic and Hydrophobic Nanopores: Flow Experiments with Water and n-Hexane

We experimentally explore pressure-driven flow of water and n-hexane across nanoporous silica (Vycor glass monoliths with 7 or 10 nm pore diameters, respectively) as a function of temperature and surface functionalization (native and silanized glass surfaces). Hydraulic flow rates are measured by applying hydrostatic pressures via inert gases (argon and helium, pressurized up to 70 bar) on the upstream side in a capacitor-based membrane permeability setup. For the native, hydrophilic silica walls, the measured hydraulic permeabilities can be quantitatively accounted for by bulk fluidity provided we assume a sticking boundary layer, i.e. a negative velocity slip length of molecular dimensions. The thickness of this boundary layer is discussed with regard to previous capillarity-driven flow experiments (spontaneous imbibition) and with regard to velocity slippage at the pore walls resulting from dissolved gas. Water flow across the silanized, hydrophobic nanopores is blocked up to a hydrostatic pressure of at least 70 bar. The absence of a sticking boundary layer quantitatively accounts for an enhanced n-hexane permeability in the hydrophobic compared to the hydrophilic nanopores.Comment: 15 pages, 7 figures, in press, Physical Review E 201

Optimierung der Astaxanthin-Synthese in Synechococcus sp. PCC7002 unter Zuhilfenahme synthetischer Biologie

Weil fossile Rohstoffe endlich sind und deren Nutzung negativ auf den immer schneller voranschreitenden Klimawandel wirkt, ist es wichtig Alternativen zu finden. Eine derzeit schon genutzte Lösung stellen Produktionslinien gestützt auf Mikroorganismen dar. Diese benötigen jedoch Zucker für ihr Wachstum und die damit verbundene Produktion der gewünschten Güter. Zudem erzeugt der Metabolismus dieser Zellen CO2 im Unterschied zu photosynthetisch aktiven Mikroorganismen. Diese benötigen keinen Zucker für ihr Wachstum und produzieren darüber hinaus Sauerstoff. Eine klimaneutrale oder sogar klimapositive Produktion ist so möglicherweise erreichbar. Entsprechend werden Cyanobakterien derzeit intensiv erforscht. Sie sollen als Produktionsplattform für die Synthese verschiedenster Substanzen verwendet werden. Darunter sind Feinchemikalien, Medikamente oder Biotreibstoff. Jedoch scheitern viele dieser Ansätze derzeit an der zu geringen Ausbeute. Hier spielen die kostenintensive Ernte und Aufreinigung eine wichtige Rolle. Auch die Synthese von Astaxanthin ist aus diesem Grund oft nicht rentabel, obwohl die Substanz hochpreisig gehandelt wird und in der Pharma-, Lebensmittel- oder Kosmetikindustrie wegen starker antioxidativer Eigenschaften gefragt ist. Synechococcus sp. PCC7002 kann den Astaxanthin-Vorläufer β-Carotin produzieren, aber nicht Astaxanthin. Jedoch ist dieses Cyanobakterium leicht genetisch zu modifizieren und weist ein extremes Wachstum, mit einer minimalen Verdopplungszeit von 2,6 Stunden, auf. Unter Verwendung eines synthetischen Ketolase- und eines synthetischen Hydroxylase-Gens gelang die Modifizierung des Carotin-Stoffwechsels. Der Organismus war nun in der Lage Astaxanthin zu synthetisieren. Der zelluläre Gesamtgehalt an Astaxanthin wurde durch die Überexpression der intrinsischen Phytoen-Synthase weiter erhöht. Bei den Versuchen der Modifizierung des Carotinoid-Stoffwechsels zeigte sich, dass es mehr Regulationsmechanismen gibt als derzeit in der wissenschaftlichen Literatur bekannt sind. Darüber hinaus stellten sich gewisse durch die wissenschaftliche Literatur begründete Annahmen als falsch heraus. Bezüglich der Lösung des Problems der kostenintensiven Ernte und Extraktion, ermöglichte die Expression eines E. coli-ABC-Transporter den Export von Astaxanthin. Zugleich verringert dies die intrazelluläre Produktakkumulation. Auf diese Weise wurde die Synthese weiter gesteigert. Aus dem Kulturmedium können dann erhebliche Mengen Astaxanthin zurückgewonnen werden, ohne dass es einer Zerstörung der Zellen bedarf. Insgesamt ermöglichen die erzielten Erfolge, allen voran durch die erstmalige erfolgreiche Nutzung eines ABC-Transporters für den Export von Carotinoiden in photosynthetisch aktiven Mikroorganismen, eine gänzlich neue Produktionsstrategie. Der erzeugte Synechococcus sp. PCC7002-Stamm kann eine kontinuierliche Astaxanthin-Produktion gewährleisten, die ohne Ernte und Zerstörung der Zellen auskommt. Potenziell ergibt sich daraus eine klimaneutrale oder sogar klimapositive Produktionsplattform

Cardiovascular magnetic resonance risk stratification in patients with clinically suspected myocarditis

BACKGROUND: The diagnosis of myocarditis is challenging due to its varying clinical presentation. Since myocarditis can be associated with significant 5-year mortality, and postmortem data show myocarditis in almost 10% of all adults suffering sudden cardiac death, individual risk stratification for patients with suspected myocarditis is of great clinical interest. We sought to demonstrate that patients with clinically suspected myocarditis and a normal cardiovascular magnetic resonance (CMR) according to our definition have a good prognosis, independent of their clinical symptoms and other findings. METHODS: Prospective clinical long-term follow-up of consecutive patients undergoing CMR for work-up of clinically suspected myocarditis at our institution in 2007-2008. RESULTS: Follow-up was available for n = 405 patients (all-comers, 54.8% inpatients, 38% outpatient referrals from cardiologists). Median follow-up time was 1591 days. CMR diagnosis was “myocarditis” in 28.8%, “normal” in 55.6% and “other pathology” in 15.6%. Normal CMR was defined as normal left ventricular (LV) volumes and normal left ventricular ejection fraction (LV-EF) in the absence of late Gadolinium Enhancement (LGE). The overall mortality was 3.2%. There were seven cardiac deaths during follow-up, in addition one aborted SCD and two patients had appropriate internal cardioverter defibrillator (ICD) shocks – all of these occurred in patients with abnormal CMR. Kaplan-Meier analysis with log-rank test showed significant difference for major adverse cardiac events (cardiac death, sudden cardiac death (SCD), ICD discharge, aborted SCD) between patients with normal and abnormal CMR (p = 0.0003). CONCLUSION: In our unselected population of consecutive patients referred for CMR work-up of clinically suspected myocarditis, patients with normal CMR have a good prognosis independent of their clinical symptoms and other findings

Towards a Greater Diversity of Replication Studies

The replication of existing knowledge (e.g., previous study results) stands as an essential research practice across all science disciplines. Despite the importance of replication, the scarcity of replication studies is commonly criticized in business, management, and information system (IS) research. Therefore, efforts have already been made to facilitate replication research in the IS community, such as establishing conference tracks and journals focusing on publishing replication studies and providing guidelines on how and why to conduct replication research. Nonetheless, the perception of replication research remains unchanged, describing it as mundane. Therefore, in this issues and opinions article, we will explore how replication research could be made more appealing by diversifying the categories of replication studies. In this regard, we looked at replication in neuroscience, eliciting two new replication study categories: ‘transfer’ and ‘method.’ Additionally, through extensive discussion with other IS scholars, we added one more replication category, ‘comparison.’ We hope that this diversification will attract more researchers and also show the potential replication research holds

Multiparametric Cardiac Magnetic Resonance Imaging to Discriminate Endomyocardial Biopsy-Proven Chronic Myocarditis From Healed Myocarditis.

BACKGROUND Detecting ongoing inflammation in myocarditis patients has prognostic relevance, but there are limited data on the detection of chronic myocarditis and its differentiation from healed myocarditis. OBJECTIVES This study sought to assess the performance of cardiac magnetic resonance (CMR) for the detection of ongoing inflammation and the discrimination of chronic myocarditis from healed myocarditis. METHODS Consecutive patients with persistent symptoms (>30 days) suggestive of myocarditis were prospectively enrolled from a single tertiary center. All patients underwent a multiparametric 1.5-T CMR protocol including biventricular strain, T1/T2 mapping, and late gadolinium enhancement (LGE). Endomyocardial biopsy was chosen for the reference standard diagnosis. RESULTS Among 452 consecutive patients, 103 (median age: 50 years; 66 men) had evaluable CMR and cardiopathologic reference diagnosis: 53 (51%) with chronic lymphocytic myocarditis and 50 (49%) with healed myocarditis. T2 mapping as a single parameter showed the best accuracy in detecting chronic myocarditis, if abnormal in ≥3 segments (92%; 95% CI: 85-97), and provided the best discrimination from healed myocarditis, as defined by the area under the receiver-operating characteristic curve (0.87 [95% CI: 0.79-0.93]; P < 0.001), followed by radial peak systolic strain rate of the left ventricle (0.86) and the right ventricle (0.84); T1 mapping (0.64), extracellular volume fraction (0.62), and LGE (0.57). Specificity increased when T2 mapping was combined with elevation of either troponin or C-reactive protein. CONCLUSIONS A multiparametric CMR protocol allows detection of ongoing myocardial inflammation and discrimination of chronic myocarditis from healed myocarditis, with segmental T2 mapping and biventricular strain analysis showing higher diagnostic accuracy compared with T1 mapping, extracellular volume fraction, and LGE. The use of biomarkers (troponin or C-reactive protein) may improve specificity

Using Multiparametric Cardiac Magnetic Resonance to Phenotype and Differentiate Biopsy-Proven Chronic from Healed Myocarditis and Dilated Cardiomyopathy.

(1) Objectives: To discriminate biopsy-proven myocarditis (chronic vs. healed myocarditis) and to differentiate from dilated cardiomyopathy (DCM) using cardiac magnetic resonance (CMR). (2) Methods: A total of 259 consecutive patients (age 51 ± 15 years; 28% female) who underwent both endomyocardial biopsy (EMB) and CMR in the years 2008-2021 were evaluated. According to right-ventricular EMB results, patients were divided into either chronic (n = 130, 50%) or healed lymphocytic myocarditis (n = 60, 23%) or DCM (n = 69, 27%). The CMR protocol included functional, strain, and late gadolinium enhancement (LGE) imaging, T2w imaging, and T2 mapping. (3) Results: Left-ventricular ejection fraction (LV-EF) was higher, and the indexed end-diastolic volume (EDV) was lower in myocarditis patients (chronic: 42%, median 96 mL/m²; healed: 49%, 86 mL/m²) compared to the DCM patients (31%, 120 mL/m²), p &lt; 0.0001. Strain analysis demonstrated lower contractility in DCM patients vs. myocarditis patients, p &lt; 0.0001. Myocarditis patients demonstrated a higher LGE prevalence (68% chronic; 59% healed) than the DCM patients (45%), p = 0.01. Chronic myocarditis patients showed a higher myocardial edema prevalence and ratio (59%, median 1.3) than healed myocarditis (23%, 1.3) and DCM patients (13%, 1.0), p &lt; 0.0001. T2 mapping revealed elevated values more frequently in chronic (90%) than in healed (21%) myocarditis and DCM (23%), p &lt; 0.0001. T2 mapping yielded an AUC of 0.89 (sensitivity 90%, specificity 76%) in the discrimination of chronic from healed myocarditis and an AUC of 0.92 (sensitivity 86%, specificity 91%) in the discrimination of chronic myocarditis from DCM, both p &lt; 0.0001. (4) Conclusions: Multiparametric CMR imaging, including functional parameters, LGE and T2 mapping, may allow differentiation of chronic from healed myocarditis and DCM and therefore help to optimize patient management in this clinical setting

Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer

Background Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma. Methodology/Principal Findings Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes–WHSC1L1, LETM2, and FGFR1–is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition. Conclusions/Significance These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer.Novartis Pharmaceuticals CorporationAmerican Lung AssociationUniting Against Lung CancerSara Thomas Monopoli FundSeaman FoundationIndia. Dept. of BiotechnologyNational Lung Cancer Partnershi

Predictive value of cardiac magnetic resonance right ventricular longitudinal strain in patients with suspected myocarditis

BACKGROUND Recent evidence underlined the importance of right (RV) involvement in suspected myocarditis. We aim to analyze the possible incremental prognostic value from RV global longitudinal strain (GLS) by CMR. METHODS Patients referred for CMR, meeting clinical criteria for suspected myocarditis and no other cardiomyopathy were enrolled in a dual-center register cohort study. Ejection fraction (EF), GLS and tissue characteristics were assessed in both ventricles to assess their association to first major adverse cardiovascular events (MACE) including hospitalization for heart failure (HF), ventricular tachycardia (VT), recurrent myocarditis and death. RESULTS Among 659 patients (62.8% male; 48.1 ± 16.1 years), RV GLS was impaired (> - 15.4%) in 144 (21.9%) individuals, of whom 76 (58%), 108 (77.1%), 27 (18.8%) and 40 (32.8%) had impaired right ventricular ejection fraction (RVEF), impaired left ventricular ejection fraction (LVEF), RV late gadolinium enhancement (LGE) or RV edema, respectively. After a median observation time of 3.7 years, 45 (6.8%) patients were hospitalized for HF, 42 (6.4%) patients died, 33 (5%) developed VT and 16 (2.4%) had recurrent myocarditis. Impaired RV GLS was associated with MACE (HR = 1.07, 95% CI 1.04-1.10; p < 0.001), HF hospitalization (HR = 1.17, 95% CI 1.12-1.23; p < 0.001), and death (HR = 1.07, 95% CI 1.02-1.12; p = 0.004), but not with VT and recurrent myocarditis in univariate analysis. RV GLS lost its association with outcomes, when adjusted for RVEF, LVEF, LV GLS and LV LGE extent. CONCLUSION RV strain is associated with MACE, HF hospitalization and death but has neither independent nor incremental prognostic value after adjustment for RV and LV function and tissue characteristics. Therefore, assessing RV GLS in the setting of myocarditis has only limited value

Impact of long-term steroid therapy on epicardial and pericardial fat deposition: a cardiac MRI study

BACKGROUND: Increased cardiac fat has been identified as a risk factor for coronary artery disease. Metabolic syndrome is associated with increased cardiac fat deposition. Steroids are known to imitate some effects of metabolic syndrome and are frequently used in patients with rheumatic disorders. Primary aim was to evaluate the impact of long-term steroid use on cardiac fat deposition in patients with rheumatic disorders. In addition, we sought to investigate if this effect might be dose-dependent. METHODS: Patients were enrolled as follows: (1) rheumatic disorder; and (2) long-term steroid therapy, and (3) underwent cardiovascular magnetic resonance (CMR) imaging. Patients were stratified in a high-dose (>7.5 mg prednisone equivalent/day for at least 6 months) and a low-dose steroid group (<7.5 mg prednisone equivalent/day) and compared to steroid-naïve controls without rheumatic disorders. RESULTS: 122 patients were included (n = 61 steroid patients, n = 61 controls). N = 36 were classified as high-dose, n = 25 as low-dose steroid group. Steroid patients showed larger epicardial 5.7 [3.5–9.1] cm(2) and pericardial 13.0 [6.1–26.8] cm(2) areas of fat than controls 4.2 [1.3–5.8] cm(2)/6.4 [1.6–15.4] cm(2), p < 0.001, p < 0.01, respectively. High-dose steroid patients had more epi- and pericardial fat both than controls: 7.2 [4.2–11.1] cm(2) vs. 4.4 [1.0-6.0] cm(2), p < 0.001; 18.6 [8.9–38.2] cm(2) vs. 10.7 [4.7–26.8] cm(2), p < 0.05, and patients in the low-dose steroid group (p < 0.01, p < 0.001, respectively). CONCLUSION: The present data suggest increased cardiac fat deposition in steroid-treated patients with rheumatic disorders. Furthermore, this accumulation of cardiac fat seems to be dose-dependent, pointing towards a cumulative effect of steroids