Maclyn McCarty (1911-2005)

"If I have seen further, it is by standing on the shoulders of giants" (letter of Isaac Newton to Robert Hooke). This well-known sentence of Newton finds its correct meaning in biology through the work of Oswald Avery (1877-1955), Colin MacLeod (1909-1972), and Maclyn McCarty (1911-2005) that was published in 1944 in The Journal of Experimental Medicine, which showed that DNA carried genetic information. These giants of molecular biology attained scientific evidence to provide shoulders strong enough to allow Crick and Watson to build on the foundations laid down by this group to postulate, 9 years later, the double-helix model of DNA. Maclyn McCarty died in New York on January 3, 2005, at age 93. At the time of his death, he was an active editor of the above-mentioned journal, which is published by The Rockefeller University.Peer reviewe

Inquiries into Epistemologies and Ethics: Collaborative Knowledge Production in Cross-Generational Research

Die Autorinnen (Kulturanthropologinnen) erläutern die Produktivität des Zusammenspiels unterschiedlicher Wissenshorizonte und Kompetenzen in der Wissensproduktion im Rahmen von 'Studios'. Das wichtigste Prinzip ist der Austausch über die Erkenntnisse und Vorgehensweisen; im Diskurs werden Ideen formuliert, weiterentwickelt und überprüft. Die Autor*innen führen einige konkrete, erfolgreiche Projekte des Instituts auf, in denen Studierende, Nachwuchswissenschaftler*innen und Hochschullehrer*innen gemeinsam Themen erarbeitet haben. Es wird deutlich, dass sich aus dem Gesprächsbedarf und den sich daraus entwickelnden Auseinandersetzungen eine Dynamik entwickelt. Sie zeigen, dass über die Multiperspektivität die Komplexität der Forschungsgegenstände Berücksichtigung findet.The authors (cultural anthropologists) explain the efficacy of the combination of a variety of knowledge backgrounds and competences in the production of knowledge. The most important principle of the 'Studios' is the exchange of insights and procedures; ideas are being formulated, developed further and tested in discourse. The authors refer to several successful projects that have been carried out at the institute for which students, young researchers and senior researchers have concerted their input. It becomes clear that the need to communicate and the debates evolving from that develop a productive dynamism. The autors show that the multi-perspectivity and the complexity of the research objects are being addressed in these larger and heterogeneous research groups

Inquiries into Epistemologies and Ethics: Collaborative Knowledge Production in Cross-Generational Research

Die Kulturanthropologinnen Lina Franken, Lara Hansen, Samantha Lutz, Teresa Stumpf, Alejandra Tijerina García und Gertraud Koch erläutern die Produktivität des Zusammenspiels unterschiedlicher Wissenshorizonte und Kompetenzen in der Wissensproduktion im Rahmen von 'Studios'. Das wichtigste Prinzip ist der Austausch über die Erkenntnisse und Vorgehensweisen; im Diskurs werden Ideen formuliert, weiterentwickelt und überprüft. Die Autor*innen führen einige konkrete, erfolgreiche Projekte des Instituts auf, in denen Studierende, Nachwuchswissenschaftler*innen und Hochschullehrer*innen gemeinsam Themen erarbeitet haben. Es wird deutlich, dass sich aus dem Gesprächsbedarf und den sich daraus entwickelnden Auseinandersetzungen eine Dynamik entwickelt. Sie zeigen, dass über die Multiperspektivität die Komplexität der Forschungsgegenstände Berücksichtigung findet. Cultural anthropologists Lina Franken, Lara Hansen, Samantha Lutz, Teresa Stumpf, Alejandra Tijerina García and Gertraud Koch explain the efficacy of the combination of a variety of knowledge backgrounds and competences in the production of knowledge. The most important principle of the 'Studios' is the exchange of insights and procedures; ideas are being formulated, developed further and tested in discourse. The authors refer to several successful projects that have been carried out at the institute for which students, young researchers and senior researchers have concerted their input. It becomes clear that the need to communicate and the debates evolving from that develop a productive dynamism. The autors show that the multi-perspectivity and the complexity of the research objects are being addressed in these larger and heterogeneous research groups

Prognostic impact of fractional flow reserve measurements in patients with acute coronary syndromes: a subanalysis of the FLORIDA study

Randomized trials suggest benefits for fractional flow reserve (FFR)-guided vs. angiography-guided treatment strategies in well-defined and selected patient cohorts with acute coronary syndromes (ACS). The long-term prognostic value of FFR measurement in unselected all-comer ACS patients, however, remains unknown. This subanalysis of the Fractional FLOw Reserve In cardiovascular DiseAses (FLORIDA) study sought to investigate the long-term effects of FFR in the management of lesions in patients with acute coronary syndrome (ACS). FLORIDA was an observational all-comer cohort study performed in Germany, that was population-based and unselected. Patients enrolled into the anonymized InGef Research Database presenting with ACS and undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Patients were stratified into either the FFR-guided or the angiography-guided treatment arm, based on the treatment received. A matched cohort study design was used. The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiovascular events (MACE), a composite of death, non-fatal myocardial infarction (MI), and repeat revascularization. Follow-up time was 3 years. Rates of 3-year mortality were 10.2 and 14.0% in the FFR-guided and the angiography-guided treatment arms (p = 0.04), corresponding to a 27% relative risk reduction for FFR in ACS patients. Rates of MACE were similar in both arms (47.7 vs. 51.5%, p = 0.14), including similar rates of non-fatal MI (27.7 vs. 25.4%, p = 0.47) and revascularization (9.9 vs. 12.1%, p = 0.17). In this large, all-comer observational study of ACS patients, FFR-guided revascularization was associated with a lower mortality at 3 years. This finding encourages the routine use of FFR to guide lesion revascularization in patients presenting with ACS

Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone

Chronic Fatigue Syndrome (CFS) presents with symptoms of hypothyroidism, including mental and physical fatigue, poor sleep, depression, and anxiety. However, thyroid hormone (TH) profiles of elevated thyrotropin and low thyroxine (T4) are not consistently observed. Recently, autoantibodies to the Se transporter SELENOP (SELENOP-aAb) have been identified in Hashimoto's thyroiditis and shown to impair selenoprotein expression. We hypothesized that SELENOP-aAb are prevalent in CFS, and associate with reduced selenoprotein expression and impaired TH deiodination. Se status and SELENOP-aAb prevalence was compared by combining European CFS patients (n = 167) and healthy controls (n = 545) from different sources. The biomarkers total Se, glutathione peroxidase (GPx3) and SELENOP showed linear correlations across the samples without reaching saturation, indicative of Se deficiency. SELENOP-aAb prevalence was 9.6-15.6% in CFS versus 0.9-2.0% in controls, depending on cut-off for positivity. The linear correlation between Se and GPx3 activity was absent in SELENOP-aAb positive patients, suggesting impaired Se supply of kidney. A subgroup of paired control (n = 119) and CSF (n = 111) patients had been characterized for TH and biochemical parameters before. Within this subgroup, SELENOP-aAb positive patients displayed particularly low deiodinase activity (SPINA-GD index), free T3 levels, total T3 to total T4 (TT3/TT4) and free T3 to free T4 (FT3/FT4) ratios. In 24 h urine, iodine concentrations were significantly lower in SELENOP-aAb positive than in SELENOP-aAb negative patients or controls (median (IQR); 43.2 (16.0) vs. 58.9 (45.2) vs. 89.0 (54.9) & mu;g/L). The data indicate that SELENOP-aAb associate with low deiodination rate and reduced activation of TH to active T3. We conclude that a subset of CFS patients express SELENOP-aAb that disturb Se transport and reduce sele-noprotein expression in target tissues. Hereby, TH activation decreases as an acquired condition not reflected by thyrotropin and T4 in blood. This hypothesis opens new diagnostic and therapeutic options for SELENOP-aAb positive CFS, but requires clinical evidence from intervention trials

Needle Technology for Insulin Administration: A Century of Innovation

Innovations in syringe and pen needle (PN) technology over the last 100 years have led to important advances in insulin delivery for people with diabetes, paralleling the strides made in developing recombinant DNA human insulin and insulin analogs with varying onset and duration of action. In this review, the history of advances in insulin delivery is described, focusing on progress in syringe, needle, and PN technologies. The early glass and metal syringes that required sterilization by boiling have been replaced by disposable, single-use syringes or pens with clear labeling for precise insulin dosing. The early needles ranging in length from 19 to 26 mm that required manual sharpening against a whetstone have been replaced by syringe needles of 6 mm and PNs of 4 mm in length as slender as 34 gauge. Imaging studies using ultrasound and computed tomography measured the thickness of skin and subcutaneous tissue layers to show feasibility of targeted insulin administration with shorter needles. These developments, coupled with innovations in needle/PN wall and tip structure, have led to improved injection experience for people with diabetes. It is also important to acknowledge the role of injection technique education, together with these advances in injection technology, for improving clinical outcomes and patient satisfaction. With continued projected growth of diabetes prevalence, particularly in developing countries where expensive and complex insulin delivery systems may not be practical, insulin syringes and pens will continue to serve as reliable and cost-effective means of insulin delivery for people with diabetes

Analisis Optimasi Produksi Sumur Gas Lift Lapangan Awiligar dengan Perbandingan Desain Ulang dan Konversi Esp

Sumur minyak yang berproduksi akan mengalami penurunan produksi dikarenakan turunnya tekanan formasi sehingga dibutuhkan pengangkatan buatan.Sumur – sumur pada Lapangan Awiligar sebagian besar berproduksi dengan pengangkatan buatan gas lift. Lapangan Awiligar bertujuan meningkatkan produksi harian, sehingga perlu dilakukan optimasi diantaranya optimasi sumur – sumur gas lift. Sumur gas lift yang dikaji adalah Sumur M-150, Sumur – M-155, Sumur M-160, dan Sumur M-165 karena water cut yang tidak terlalu tinggi diantara sumur gas lift lainnya dan produksi yang lebih tinggi dari sumur gas lift lainnya.Optimasi dilakukan dengan perbandingan antara menambah jumlah laju injeksi gas, mendesain ulang posisi katup, dan menkonversi menjadi Electric Submersible Pump (ESP) dimana skenario terbaik dilihat dari lifting cost terkecil. Hasil skenario terbaik untuk optimasi sumur kajian adalah dengan konversi menjadi ESP dikarenakan produksi yang lebih besar dan lifting cost yang lebih rendah dari gas lift

Safety and Efficacy of Donor T Cells Engineered with Herpes Simplex Virus Thymidine-Kinase Suicide Gene (TK Cells) Given after T-Cell Depleted (TCD) Haploidentical Hematopoietic Transplantation (Haplo-HSCT): Results of a 14-Year Follow-Up in 45 Patients

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Evolution of non-thyroidal illness syndrome in acute decompensation of liver cirrhosis and acute-on-chronic liver failure

Background and aimsNon-thyroidal illness syndrome (NTIS) is frequent in critically ill patients and associated with adverse outcomes. We aimed to characterize the evolution of NTIS in patients with acute decompensation (AD) of cirrhosis and acute-on-chronic liver failure (ACLF), since NTIS is not well described in these newly defined syndromes.MethodsThyroid hormones (TH) were quantified at baseline in consecutive patients with cirrhosis. In addition, 76 inflammatory mediators were quantified by proximity extension analysis assay in a subgroup of patients. Associations between TH, cirrhosis stage, mortality and inflammation were assessed.ResultsOverall, 437 patients were included, of whom 165 (37.8%), 211 (48.3%), and 61 (14%) had compensated cirrhosis (CC), AD, and ACLF. FT3 concentrations were lower in AD versus CC, and further decreased in ACLF. Importantly, NTIS was present in 83 (39.3%) patients with AD and in 44 (72.1%) patients with ACLF (P<0.001). Yet, TSH and TSH-based indexes (TSH/FT3-ratio, thyroid index) showed an U-shaped evolution during progression of cirrhosis, suggesting a partially preserved responsiveness of the hypothalamus and pituitary in AD. Infections were associated with lower FT3 concentrations in AD, but not in ACLF. Low FT3 concentrations correlated significantly with 90-day mortality. Both, AD/ACLF and NTIS, were associated with signatures of inflammatory mediators, which were partially non-overlapping.ConclusionNTIS is frequent already in AD and therefore precedes critically illness in a subgroup of patients with decompensated cirrhosis. This might constitute a new paradigm of TH signaling in cirrhosis, offering opportunities to explore preventive effects of TH in AD