Structural characterization and bioactivity profiling of the fungal peptaibiotic tolypin reveal protective effects against influenza viruses.

In a bioprospection for new antivirals, we tested nonribosomally biosynthesized polypeptide antibiotics in MDCK II cells for their actions on influenza A and B viruses (IAV/IBV). Only tolypin, a mixture of closely related 16-residue peptaibiotics from the fungus Tolypocladium inflatum IE 1897, showed promising activity. It was selected for further investigation and structural characterization by ultrahigh performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HR-MS/MS) and ultrahigh performance liquid chromatography coupled to in-source collision-induced dissociation tandem mass spectrometry (UHPLC-isCID-HR-MS/MS), revealing 12 partially co-eluting individual peptides that were fully sequenced.

Cholangiocarcinoma, sequential chemotherapy, and prognostic tests.

Introduction: Routine blood tests are prognostic tests for patients with cholangiocarcinoma. New drug regimens may produce a median overall survival of 2 years or more.

Methods: This single practice, IRB-approved, phase II trial examines prognostic tests, Kaplan-Meier survival, and univariate Cox regression analyses.

Effectiveness of an online recovery training for employees exposed to blurred boundaries between work and non-work: Bayesian analysis of a randomised controlled trial.

Background: Blurred work-non-work boundaries can have negative effects on mental health, including sleep.

Objectives: In a randomised control trial, we aimed to assess the effectiveness of an online recovery training programme designed to improve symptoms of insomnia in a working population exposed to blurred boundaries.

Methods: 128 participants with severe insomnia symptoms (Insomnia Severity Index ≥15) and working under blurred work and non-work conditions (segmentation supplies <2.

Digital cognitive behavioural therapy for insomnia reduces insomnia in nurses suffering from shift work disorder: A randomised-controlled pilot trial.

Insomnia is a primary symptom of shift work disorder, yet it remains undertreated. This randomised-controlled pilot trial examined the efficacy of a digital, guided cognitive behavioural therapy for insomnia adapted to shift work (SleepCare) in nurses with shift work disorder. The hypothesis was that SleepCare reduces insomnia severity compared with a waitlist control condition.

Who benefits from indirect prevention and treatment of depression using an online intervention for insomnia? Results from an individual-participant data meta-analysis.

Background: Major depressive disorder (MDD) is highly prevalent and burdensome for individuals and society. While there are psychological interventions able to prevent and treat MDD, uptake remains low. To overcome structural and attitudinal barriers, an indirect approach of using online insomnia interventions seems promising because insomnia is less stigmatized, predicts MDD onset, is often comorbid and can outlast MDD treatment.

Innovative spiral electrode configuration for enhancement of electrocoagulation-flotation.

The performance of electrocoagulation-flotation (ECF) process can profoundly be affected by the reactor design and electrode configuration. These may, in turn, influence the removal efficiency, flow hydrodynamic, floc formation, and flotation/settling characteristics. The present work aimed at developing a new spiral electrode configuration to enhance the ECF process.

Phase I-II study using DeltaRex-G, a tumor-targeted retrovector encoding a cyclin G1 inhibitor for metastatic carcinoma of breast.

Metastatic breast cancer is associated with a poor prognosis and therefore, innovative therapies are urgently needed. Here, we report on the results of a Phase I-II study using DeltaRex-G for chemotherapy resistant metastatic carcinoma of breast. Dose limiting toxicity; Antitumor activity.

Actionable tests and treatments for patients with gastrointestinal cancers and historically short median survival times.

Background: Patients have difficult unmet needs when standard chemotherapy produces a median survival of less than 1 year or many patients will experience severe toxicities. Blood tests can predict their survival.

Methods: Analyses evaluate predictive blood tests to identify patients who often survive 1 and 2 years.

Organic matter parameters in WWTP - a critical review and recommendations for application in activated sludge modelling.

This paper includes a comprehensive literature review of sludge composition data from wastewater treatment plants. 722 data sets from 249 sources were used to establish typical ratios between COD and solids-based parameters and to verify rule-of-thumb values, respectively. Confirmation of these typical ratios can also be accomplished by using biochemical composition data.

Tumor protein p53 mutation in archived tumor samples from a 12-year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long-term survival with DeltaRex-G: A case report and literature review.

DeltaRex-G is a replication-incompetent amphotropic murine leukemia virus-based retroviral vector that displays a collagen-matrix-targeting decapeptide on its surface envelope protein, gp70, and encodes a cytocidal 'dominant negative', i.e. a truncated construct of the executive cyclin G1 () oncogene.

Late, But Not Too Late? Postponement of First Birth Among Highly Educated US Women.

We examine the link between the postponement of parenthood and fertility outcomes among highly educated women in the USA born in 1920-1986, using data from the CPS June Supplement 1979-2016. We argue that the postponement-low fertility nexus noted in demographic and biomedical research is especially relevant for women who pursue postgraduate education because of the potential overlap of education completion, early career stages, and family formation. The results show that women with postgraduate education differ from women with college education in terms of the timing of the first birth, childlessness, and completed fertility.

Dispersion analysis of sucrose CHO single crystal.

We present the first complete dispersion analysis of a sucrose single crystal in the infrared spectral region between 4000 and 400 cm by means of an adapted generalized dispersion analysis employing the naturally grown crystal faces. The gained dielectric tensor function and the oscillator parameters were confirmed by forward calculation of reflection spectra of different orientations. Reliable growth of large-sized sucrose crystals makes it candidates for doping with photonically active materials.

The first non-helical Aib-containing hexapeptide: The crystal structure of Z-Gly-Aib-Gly-Aib-Gly-Aib-OtBu.

The synthetic peptide Z-Gly-Aib-Gly-Aib-Gly-Aib-OtBu was crystallized from a mixture of ethyl acetate and n-hexane. The crystals belong to the centrosymmetric space group Pbca. There are three molecules in the asymmetric unit.

Removing the C-terminal protecting group enlarges the crystal size: Z-(Gly-Aib)-OH·HO.

The achiral tetrapeptide monohydrate N-(benzyloxycarbonyl)glycyl-α-aminoisobutyrylglycyl-α-aminoisobutyric acid monohydrate, Z-Gly-Aib-Gly-Aib-OH·HO (Z is benzyloxycarbonyl, Aib is α-aminoisobutyric acid and Gly is glycine) or CHNO·HO, exhibits two conformations related by the symmetry operation of an inversion centre. It adopts only one of two possible intramolecular hydrogen bonds in a type I (and I') β-turn and forms a maximum of intermolecular hydrogen bonds partly mediated by water. The space group, the molecular structure and the crystal packing differ from two already described (Gly-Aib) peptides which vary only in the protecting groups.

On the geoarchaeology of Limyra (SW Anatolia)-new insights into the famous Lycian city and its environs.

Geoarchives in ancient settlement sites and their environs bear valuable information about Holocene landscape evolution and human-environment interactions. During the last six millennia, sea-level and coastline changes have had a significant impact on coastal settlements, some of which even had to be relocated. This paper reveals new insights into the spatio-temporal development of the Lycian city of Limyra.

Sequences of Tolypins, Insecticidal Efrapeptin-Type Peptaibiotics from Species of the Fungal Genus Tolypocladium.

A peptide mixture named tolypin, originally isolated from species of the fungal genus Tolypocladium, was structurally characterised and sequences compared to those reported for efrapeptins isolated from strains of Tolypocladium inflatum. Chiral amino acid analysis, direct infusion, and online HPLC electrospray ionization tandem mass spectrometry provided composition, molecular weights of peptides, and series of diagnostic fragment ions. Sequences deduced from ESI-MS revealed that tolypins C-G are identical to efrapeptins C-G.

Publisher Correction: First experimental evaluation of the alpha efficiency in coarse-grained quartz for ESR dating purposes: implications for dose rate evaluation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

First experimental evaluation of the alpha efficiency in coarse-grained quartz for ESR dating purposes: implications for dose rate evaluation.

We present the first experimental evaluation of the alpha efficiency value for electron spin resonance (ESR) dating of coarse quartz grains, which is used for the evaluation of the internal and external alpha dose rate components. Based on our results, we recommend the use of an a-value of 0.07 ± 0.

Ileal Adenocarcinoma with Liver Metastasis in Patient with Crohn's Disease: A 9-Year Survival.

Small bowel adenocarcinoma is a rare but well-known complication of Crohn's disease. The diagnosis of small bowel adenocarcinoma remains difficult since its presentation is highly variable and mimics active or obstructive Crohn's disease. The diagnosis is often delayed and typically detected only at surgery in an advanced stage with a poor prognosis.

Dispersion analysis of the orthorhombic peptide single crystal Z-(Aib)-L-Ala-OtBu.

We present a dispersion analysis of the orthorhombic peptide single crystal Z-Aib-Aib-Aib-L-Ala-OtBu (N-benzyloxycarbonyl-α-aminoisobutyryl-α-aminoisobutyryl-α-aminoisobutyryl-L-alanine tert-butyl ester, CHNO), where Z is benzyloxycarbonyl and OtBu is the tert-butylester) in the MIR spectral region by means of adapted generalized dispersion analysis, employing the naturally grown crystal faces. Based on the results we identify the orientation of the crystal axes a, b, c within the sample, and supported by a stereographic projection of the crystal, we assign the individual axes. The gained dielectric tensor function and the oscillator parameters were confirmed by forward calculation of reflection spectra of different orientations.

A Phase I-II Study Using Rexin-G Tumor-Targeted Retrovector Encoding a Dominant-Negative Cyclin G1 Inhibitor for Advanced Pancreatic Cancer.

Rexin-G is a replication-incompetent retroviral vector displaying a cryptic -binding peptide for targeting abnormal Signature () proteins in tumors and encoding a dominant-negative human cyclin G1 construct. Herein we report on the safety and antitumor activity of escalating doses of Rexin-G in gemcitabine-refractory pancreatic adenocarcinoma, with one 10-year survivor. For the safety analysis (n = 20), treatment-related grade 1 adverse events included fatigue (n = 6), chills (n = 2), and headache (n = 1), with no organ damage and no DLT.

Crystal structures of -Gly-Aib-O·0.5Ca·HO and -Gly-Aib-OH.

Both deprotonated and neutral achiral title dipeptides assume similar structures of two conformations, which are related by a unit-cell inversion centre. Two mol-ecules of both conformations of the metal-free neutral dipeptide are linked by two hydrogen bonds, while two mol-ecules of both conformations of the ionized form coordinate a calcium ion in calcium(II) bis-[2-(2-{[(benz-yl-oxy)carbon-yl]amino}-acetamido)-2-methyl-propano-ate] monohydrate, 0.5Ca·CHNO·0.

The crystal structure of the lipoaminopeptaibol helioferin, an antibiotic peptide from Mycogone rosea.

The crystal structure of the natural nonapeptide antibiotic helioferin has been determined and refined to 0.9 Å resolution. Helioferin consists of helioferin A and B, which contain 2-(2'-aminopropyl)aminoethanol (Apae) and 2-[(2'-aminopropyl)methylamino]ethanol (Amae) at their respective alkanolamine termini.