Reducing the linewidth of a diode laser below 30 Hz by stabilization to a reference cavity with finesse above 10^5

An extended cavity diode laser operating in the Littrow configuration emitting near 657 nm is stabilized via its injection current to a reference cavity with a finesse of more than 10^5 and a corresponding resonance linewidth of 14 kHz. The laser linewidth is reduced from a few MHz to a value below 30 Hz. The compact and robust setup appears ideal for a portable optical frequency standard using the Calcium intercombination line.Comment: 8 pages, 4 figures on 3 additional pages, corrected version, submitted to Optics Letter

Effects of serum and serum heat-inactivation on human bone derived osteoblast progenitor cells

Generally, heat inactivated foetal calf serum (FCS) containing media are used for the cultivation of animal and human cells. The role of serum source and serum treatment on the behaviour of cells has long been neglected. The present study was performed to investigate the effects of serum heat inactivation and serum source on trabecular bone derived progenitor cells (HBC). Furthermore, it was investigated in how far these reactions differed from those seen in bone marrow derived mesenchymal progenitor cells (HBMC) cultures. We found that HBC cultures performed differently in the presence of FCS and HS with or without heat inactivation. The reactions similar to some degree those observed in HBMC cultures. The implications of the results on cell-implant surface interaction studies are discusse

Patient-reported outcomes on empagliflozin treatment in glycogen storage disease type Ib:An international questionnaire study

In patients with glycogen storage disease type Ib (GSD Ib), quality of life is severely hampered by neutropenia and neutropenia-associated symptoms. SGLT2 inhibitors are a new treatment option and have shown improved medical outcomes in more than 120 patients so far. The aim of this international questionnaire study was to assess patient-reported outcomes of this new treatment in GSD Ib patients. Patients and caregivers of pediatric patients were invited to complete a web-based questionnaire. This was designed to evaluate treatment effects of the SGLT2 inhibitor empagliflozin on clinical symptoms and important aspects of daily life including physical performance, sleep, social and work life, traveling, socioeconomic aspects, and quality of life. The questionnaire was completed by 73 respondents from 17 different countries. The mean duration of treatment was 15 months, the cumulative treatment time was 94.8 years. More than 80% of patients reported an improved quality of life. The number of hospitalizations was reduced (66% of patients), as well as the number of days absent from school or work. Granulocyte colony-stimulating factor (G-CSF) treatment could be stopped in 49% of patients and reduced in another 42%. Clear improvement of neutropenia and all neutropenia-associated symptoms was reported by the majority of patients. Additionally, patients or caregivers reported positive effects on appetite (63%), level of activity (75%), overall well-being (96%), and sleep (63%). Empagliflozin positively impacts many aspects of daily life including work and social life and thereby significantly improves quality of life of patients and caregivers.</p

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire

Purpose: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). Methods: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. Results: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. Conclusion: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib. Keywords: GSD Ib; Glycogen storage disease type Ib; Neutropenia; SGLT2 inhibitors; SLC37A

Novel homozygous RARS2 mutation in two siblings without pontocerebellar hypoplasia - further expansion of the phenotypic spectrum.

BACKGROUND: Pontocerebellar hypoplasia type 6 (PCH6) is a mitochondrial disease caused by mutations in the RARS2 gene. RARS2 encodes mitochondrial arginyl transfer RNA synthetase, an enzyme involved in mitochondrial protein translation. A total of 27 patients from 14 families have been reported so far. Characteristic clinical features comprise neonatal lactic acidosis, severe encephalopathy, intractable seizures, feeding problems and profound developmental delay. Most patients show typical neuroradiologic abnormalities including cerebellar hypoplasia and progressive pontocerebellar atrophy. METHODS: We describe the clinical, biochemical and molecular features of 2 siblings with a novel homozygous mutation in RARS2. Both patients presented neonatally with lactic acidosis. While the older sibling had severe neurological symptoms with microcephaly, seizures and developmental delay, the younger patient was still neurologically asymptomatic at the age of 2 months. RESULTS: MRI studies in both children lacked pontocerebellar involvement. The expression of the OXPHOS complex proteins was decreased in both patients, whereas oxygen consumption was increased. CONCLUSIONS: Characteristic neuroradiological abnormalities of PCH6 such as vermis and cerebellar hypoplasia and progressive pontocerebellar atrophy may be missing in patients with RARS2 mutations. RARS2 testing should therefore also be performed in patients without pontocerebellar hypoplasia but otherwise typical clinical symptoms

Handlungsmöglichkeiten für Kommunikation und Beteiligung beim Stromnetzausbau. Ein Praxishandbuch für Abgeordnete. Abschlussbericht zum TA-Projekt »Interessenausgleich bei Infrastrukturprojekten: Handlungsoptionen für die Kommunikation und Organisation vor Ort«

Aktuell sind in Deutschland ein weitreichender Umbau und eine Erweiterung des Stromnetzes im Gang. Hierbei treten immer wieder Konflikte vor Ort auf. Bürger lehnen neue Leitungen ab, gründen Bürgerinitiativen, organisieren Protest. Die Diskussionen werden sehr engagiert und emotional geführt. Bundestagsabgeordnete nehmen als Vermittler zwischen bundespolitischen Entscheidungen und den lokalen Ansprüchen eine Schlüsselrolle ein. Einerseits erwarten die Bürger von ihnen eine klare Positionierung und eine aktive Rolle als Sachwalter ihrer Interessen. Auf der anderen Seite gehen die Betreiber der Übertragungsnetze davon aus, dass die Politik die gefassten Beschlüsse rechtfertigt und dafür einsteht, dass sie möglichst reibungslos umgesetzt werden können. Das vorliegende TAB-Hintergrundpapier stellt wissenschaftliche Erkenntnisse und Praxiserfahrungen zu Kommunikation und Beteiligung beim Netzausbau zusammenfassend dar und gibt daraus folgernd Hinweise auf Handlungsmöglichkeiten für Kommunikationsstrategien und Beteiligungsverfahren. Mitglieder des Deutschen Bundestages, in deren Wahlkreisen Netzausbauvorhaben geplant sind, sollen auf diese Weise beim Umgang mit den daraus entstehenden Interessenkollisionen und Konflikten vor Ort unterstützt werden. INHALT ZUSAMMENFASSUNG 7 I. EINLEITUNG 9 II. KOMMUNIKATION UND BETEILIGUNG BEIM INFRASTRUKTURAUSBAU VOR ORT 11 1. Kommunikation und Beteiligung – was ist das und was können sie leisten? 11 2. Die Rolle der Mitglieder des Bundestages 13 3. Bürgerfragen zum Netzausbau 15 4. Erkenntnisse zu Information und Beteiligung aus der Forschung 17 4.1 Bürgerbeteiligung und Demokratie – Konzepte und Definitionen 18 4.2 Erkenntnisse aus der Partizipationsforschung 23 4.3 Ausgewählte Methoden der Beteiligung 28 5. Erkenntnisse aus Praxisbeispielen 31 5.1 Dialog zur Westküstenleitung in Schleswig-Holstein 31 5.2 Dialog zur Leitung Dörpen/West–Niederrhein in Niedersachsen 36 5.3 Dialoge im Rahmen des BESTGRID-Projekts 39 5.4 Mediationsverfahren Umspannwerk Hagen-Garenfeld 41 5.5 Tunneldialog Schwäbisch Gmünd 42 5.6 Dialog zur Bahnstrecke Hanau–Fulda 43 5.7 Aktuelle MdB-Veranstaltungen zum Netzausbau 43 6. Fazit aus den Praxiserfahrungen mit Kommunikation und Beteiligung 51 III. HANDLUNGSMÖGLICHKEITEN FÜR MDB FÜR EINE ERFOLGREICHE KOMMUNIKATION UND BÜRGERBETEILIGUNG 55 1. Ziele und Zielgruppe 55 2. Der richtige Zeitpunkt 55 3. Vertrauen als wichtigster »weicher Faktor« 56 4. Eigene Veranstaltungen – welches Format ist geeignet? 57 5. Praktische Komponenten einer erfolgreichen Veranstaltung 60 IV. HINTERGRUNDWISSEN ZUM NETZAUSBAU 67 1. Rechtlicher Rahmen – das Planungsverfahren 67 2. Akteure und ihre Rollen 72 3. Hintergründe zu den häufigsten Fragen der Bürger 74 3.1 Gesundheitsschutz 74 3.2 Wohnumfeldschutz – Abstandsregelungen 75 3.3 Wertverlust von Grundstücken 76 3.4 Landschafts-/Ortsbild – Möglichkeiten der Verkabelung 77 3.5 Einschränkung der Bewirtschaftung 78 3.6 Bündelung/Überbündelung 78 3.7 Mitnahme/Rückbau 79 3.8 Vogelschutz 79 4. Kleiner Exkurs zur Technik des Netzausbaus 80 LITERATUR 82 1. In Auftrag gegebene Gutachten 82 2. Weitere Literatur 82 ANHANG 86 1. Tabellenverzeichnis 86 2. Abbildungsverzeichnis 8

Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare inborn error of glycogen metabolism due to mutations in SLC37A4. Besides a severe form of fasting intolerance, the disorder is usually associated with neutropenia and neutrophil dysfunction causing serious infections, inflammatory bowel disease, oral, urogenital and perianal lesions as well as impaired wound healing. Recently, SGLT2 inhibitors such as empagliflozin that reduce the plasma levels of 1,5-anhydroglucitol have been described as a new treatment option for the neutropenia and neutrophil dysfunction in patients with GSD Ib. RESULTS: We report on a 35-year-old female patient with GSD Ib who had been treated with G-CSF for neutropenia since the age of 9. She had a large chronic abdominal wound as a consequence of recurrent operations due to complications of her inflammatory bowel disease. Treatment with 20 mg empagliflozin per day resulted in normalisation of the neutrophil count and neutrophil function even after termination of G-CSF. The chronic abdominal wound that had been unchanged for 2 years before the start of empagliflozin nearly closed within 12 weeks. No side effects of empagliflozin were observed. CONCLUSION: SGLT2 inhibitors are a new and probably safe treatment option for GSD Ib-associated neutropenia and neutrophil dysfunction. We hypothesize that restoration of neutrophil function and normalisation of neutrophil apoptosis leads to improvement of wound healing and ameliorates symptoms of inflammatory bowel disease

A Search for Variations of Fundamental Constants using Atomic Fountain Clocks

Over five years we have compared the hyperfine frequencies of 133Cs and 87Rb atoms in their electronic ground state using several laser cooled 133Cs and 87Rb atomic fountains with an accuracy of ~10^{-15}. These measurements set a stringent upper bound to a possible fractional time variation of the ratio between the two frequencies : (d/dt)ln(nu_Rb/nu_Cs)=(0.2 +/- 7.0)*10^{-16} yr^{-1} (1 sigma uncertainty). The same limit applies to a possible variation of the quantity (mu_Rb/mu_Cs)*alpha^{-0.44}, which involves the ratio of nuclear magnetic moments and the fine structure constant.Comment: 4 pages, 3 figures, 1 table submitted to Phys. Rev. Let

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

A generic emergency protocol for patients with inborn errors of metabolism causing fasting intolerance:A retrospective, single-center study and the generation of www.emergencyprotocol.net

Patients with inborn errors of metabolism causing fasting intolerance can experience acute metabolic decompensations. Long‐term data on outcomes using emergency letters are lacking. This is a retrospective, observational, single‐center study of the use of emergency letters based on a generic emergency protocol in patients with hepatic glycogen storage diseases (GSD) or fatty acid oxidation disorders (FAOD). Data on hospital admissions, initial laboratory results, and serious adverse events were collected. Subsequently, the website www.emergencyprotocol.net was generated in the context of the CONNECT MetabERN eHealth project following multiple meetings, protocol revisions, and translations. Representing 470 emergency protocol years, 127 hospital admissions were documented in 54/128 (42%) patients who made use of emergency letters generated based on the generic emergency protocol. Hypoglycemia (here defined as glucose concentration 5 years. Convulsions, coma, or death was not documented. By providing basic information, emergency letters for individual patients with hepatic GSD or the main FAOD can be generated at www.emergencyprotocol.net, in nine different languages. Generic emergency protocols are safe and easy for home management by the caregivers and the first hour in‐hospital management to prevent metabolic emergencies in patients with hepatic GSD and medium‐chain Acyl CoA dehydrogenase deficiency. The website www.emergencyprotocol.net is designed to support families and healthcare providers to generate personalized emergency letters for patients with hepatic GSD and the main FAOD