O- vs. N-protonation of 1-dimethylaminonaphthalene-8-ketones: formation of a peri N–C bond or a hydrogen bond to the pi-electron density of a carbonyl group

X-ray crystallography and solid-state NMR measurements show that protonation of a series of 1-dimethylaminonaphthalene-8-ketones leads either to O protonation with formation of a long N–C bond (1.637–1.669 Å) between peri groups, or to N protonation and formation of a hydrogen bond to the π surface of the carbonyl group, the latter occurring for the larger ketone groups (C(O)R, R = t-butyl and phenyl). Solid state 15N MAS NMR studies clearly differentiate the two series, with the former yielding significantly more deshielded resonances. This is accurately corroborated by DFT calculation of the relevant chemical shift parameters. In the parent ketones X-ray crystallography shows that the nitrogen lone pair is directed towards the carbonyl group in all cases

Hysteretic thermal spin-crossover in heteroleptic Fe(II) complexes using alkyl chain substituted 2,2’-dipyridylamine ligands

The alkyl chain carrying ligands N,N-di(pyridin-2-yl)butanamide (LC4) and N,N-di(pyridin-2-yl)decanamide (LC10) were combined with NCS− co-ligands to form the neutral heteroleptic Fe(II) complexes trans-[FeII(LC4)2(NCS)2] (1C4) and trans-[FeII(LC10)2(NCS)2] (1C10). Variable temperature crystallographic studies revealed that 1C4 is in the orthorhombic space group Pna21 between 85–200 K whereas 1C10 is in the monoclinic space group P21/c between 85–140 K. The average Fe–N bond lengths suggest that at 85 K 1C4 contains LS Fe(II) centres; however, the ca. 0.18 Å increase in the average Fe–N bond lengths between 85 and 120 K suggests a spin-transition to the HS state occurs within this temperature interval. 1C10 contains LS Fe(II) centres between 85 and 105 K. Upon warming from 105 to 140 K the average Fe–N bond lengths increase by ca. 0.19 Å, which suggests a spin-transition to the HS state. Solid-state magnetic susceptibility measurements showed that 1C4 undergoes semi-abrupt spin-crossover with T1/2 = 127.5 K and a thermal hysteresis of ca. 13 K whereas, 1C10 undergoes an abrupt spin-crossover with T1/2 = 119.0 K, and is also accompanied by thermal hysteresis of ca. 4 K. The crystallographic and magnetic data show that the length of the complex's alkyl chain substituents can have a large impact on the structure of the crystal lattice as well as a subtle effect on the T1/2 value for thermal spin-crossover

A CTP-Dependent Archaeal Riboflavin Kinase Forms a Bridge in the Evolution of Cradle-Loop Barrels

SummaryProteins of the cradle-loop barrel metafold are formed by duplication of a conserved βαβ-element, suggesting a common evolutionary origin from an ancestral group of nucleic acid-binding proteins. The basal fold within this metafold, the RIFT barrel, is also found in a wide range of enzymes, whose homologous relationship with the nucleic acid-binding group is unclear. We have characterized a protein family that is intermediate in sequence and structure between the basal group of cradle-loop barrels and one family of RIFT-barrel enzymes, the riboflavin kinases. We report the structure, substrate-binding mode, and catalytic activity for one of these proteins, Methanocaldococcus jannaschii Mj0056, which is an archaeal riboflavin kinase. Mj0056 is unusual in utilizing CTP rather than ATP as the donor nucleotide, and sequence conservation in the relevant residues suggests that this is a general feature of archaeal riboflavin kinases

Dielectric nanoantenna as an efficient and ultracompact demultiplexer for surface waves

Nanoantennas for highly efficient excitation and manipulation of surface waves at nanoscale are key elements of compact photonic circuits. However, previously implemented designs employ plasmonic nanoantennas with high Ohmic losses, relatively low spectral resolution, and complicated lithographically made architectures. Here we propose an ultracompact and simple dielectric nanoantenna (silicon nanosphere) allowing for both directional launching of surface plasmon polaritons on a thin gold film and their demultiplexing with a high spectral resolution. We show experimentally that mutual interference of magnetic and electric dipole moments supported by the dielectric nanoantenna results in opposite propagation of the excited surface waves whose wavelengths differ by less than 50 nm in the optical range. Broadband reconfigurability of the nanoantennas operational range is achieved simply by varying the diameter of the silicon sphere. Moreover, despite subwavelength size ($<\lambda/3$) of the proposed nanoantennas, they demonstrate highly efficient and directional launching of surface waves both in the forward and backward directions with the measured front-to-back ratio having a contrast of almost two orders of magnitude within a 50 nm spectral band. Our lithography-free design has great potential as highly efficient, low-cost, and ultracompact demultiplexer for advanced photonic circuits.Comment: added relevant references; fixed typos in Supplementary eq. 8,9,1

Statistical uncertainty of changes in winter storms over the North Atlantic and Europe in an ensemble of transient climate simulations

Winter storms are among the most important natural hazards affecting Europe. We quantify changes in storm frequency and intensity over the North Atlantic and Europe under future climate scenarios in terms of return periods (RPs) considering uncertainties due to both sampling and methodology. RPs of North Atlantic storms' minimum central pressure (CP) and maximum vorticity (VOR) remain unchanged by 2100 for both the A1B and A2 scenarios compared to the present climate. Whereas shortened RPs for VOR of all intensities are detected for the area between British Isles/North-Sea/western Europe as early as 2040. However, the changes in storm VOR RP may be unrealistically large: a present day 50 (20) year event becomes approximately a 9 (5.5) year event in both A1B and A2 scenarios by 2100. The detected shortened RPs of storms implies a higher risk of occurrence of damaging wind events over Europe

SimShiftDB; local conformational restraints derived from chemical shift similarity searches on a large synthetic database

We present SimShiftDB, a new program to extract conformational data from protein chemical shifts using structural alignments. The alignments are obtained in searches of a large database containing 13,000 structures and corresponding back-calculated chemical shifts. SimShiftDB makes use of chemical shift data to provide accurate results even in the case of low sequence similarity, and with even coverage of the conformational search space. We compare SimShiftDB to HHSearch, a state-of-the-art sequence-based search tool, and to TALOS, the current standard tool for the task. We show that for a significant fraction of the predicted similarities, SimShiftDB outperforms the other two methods. Particularly, the high coverage afforded by the larger database often allows predictions to be made for residues not involved in canonical secondary structure, where TALOS predictions are both less frequent and more error prone. Thus SimShiftDB can be seen as a complement to currently available methods

Acute skin toxicity associated with a 1-week schedule of whole breast radiotherapy compared with a standard 3-week regimen delivered in the UK FAST-Forward Trial

BACKGROUND AND PURPOSE: FAST-Forward is a phase 3 clinical trial testing a 1-week course of whole breast radiotherapy against the UK standard 3-week regimen after primary surgery for early breast cancer. Two acute skin toxicity substudies were undertaken to test the safety of the test schedules with respect to early skin reactions. MATERIAL AND METHODS: Patients were randomly allocated to 40Gy/15 fractions (F)/3-weeks, 27Gy/5F/1-week or 26Gy/5F/1-week. Acute breast skin reactions were graded using RTOG (first substudy) and CTCAE criteria v4.03 (second substudy) weekly during treatment and for 4weeks after treatment ended. Primary endpoint was the proportion of patients within each treatment group with grade ⩾3 toxicity (RTOG and CTCAE, respectively) at any time from the start of radiotherapy to 4weeks after completion. RESULTS: 190 and 162 patients were recruited. In the first substudy, evaluable patients with grade 3 RTOG toxicity were: 40Gy/15F 6/44 (13.6%); 27Gy/5F 5/51 (9.8%); 26Gy/5F 3/52 (5.8%). In the second substudy, evaluable patients with grade 3 CTCAE toxicity were: 40Gy/15F 0/43; 27Gy/5F 1/41 (2.4%); 26Gy/5F 0/53. CONCLUSIONS: Acute breast skin reactions with two 1-week schedules of whole breast radiotherapy under test in FAST-Forward were mild

The B-MaP-C study: Breast cancer management pathways during the COVID-19 pandemic. Study protocol.

Introduction: Approximately 55,000 women in the United Kingdom are diagnosed with new breast cancer annually. Since emerging in December 2019, SARS-CoV-2 (coronavirus disease 2019, COVID-19) has become a global pandemic, affecting healthcare delivery worldwide. In response to the pandemic, multiple guidelines were issued to assist with rationalising breast cancer care. The primary aim of the B-MaP-C study is to audit and describe breast cancer management of patients newly diagnosed with breast cancer during the COVID-19 pandemic against pre-COVID-19 management practice in the UK. The implications of changes to management will be determined and the impact of a COVID-19 diagnosis on the patient's breast cancer management will be determined. Methods and analysis: This is a multi-centre collaborative audit of consecutive breast cancer patients undergoing treatment decisions during the acute and recovery phases of the COVID-19 pandemic. All patients with newly diagnosed primary breast cancer, whose treatment was decided in a multidisciplinary meeting from the 16th March 2020, are eligible for inclusion. Ethics and dissemination: As this is an audit ethical approval is not required. Each participating centre is required to register the study locally and obtain local governance approvals prior to commencement of data collection. Local audit data will be available to individual participating units for governance purposes. The results of the data analysis will be submitted for publication, as well as disseminated via the ABS newsletter and a webinar. All data will be presented at national and international conferences, circumstances permitting. Registration details: Each participating centre received local governance audit registration

Eveningness is associated with poor sleep quality and negative affect in obsessive-compulsive disorder

Background: Obsessive–compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive behaviors that severely encumber daily functioning. OCD patients seem to exhibit sleep disturbances, especially delayed bedtimes that reflect disrupted circadian rhythmicity. Morningness–eveningness is a fundamental factor reflecting individual variations in diurnal preferences related to sleep and waking activities. Eveningness reflecting a delayed sleep–wake timing has repeatedly been associated with sleep problems and negative affect (NA). Therefore, the aim of this study was to examine the associations between morningness–eveningness, sleep complaints, and symptom severity in OCD patients and compared with a mixed psychiatric control group.  Materials and methods: The data of 49 OCD and 49 mixed psychiatric inpatients (with unipolar depression and anxiety disorders) were analyzed. Patients completed questionnaires regarding morningness–eveningness, sleep quality, nightmare frequency, depression, anxiety, and affective states. Obsessive and compulsive symptom severity was also assessed within the OCD group by clinician-rated scales.  Results: Eveningness preference was associated with impaired sleep quality and higher NA in OCD patients. In addition, impaired sleep quality showed a moderate correlation with anxiety and strong correlations with depressive symptoms and NA. Interestingly, in the mixed psychiatric group, eveningness was not linked to NA, and sleep quality also showed weaker associations with depressive symptoms and NA. Within the OCD group, eveningness preference was predictive of poorer sleep quality regardless the influence of depressive symptoms.  Conclusion: Our findings suggest that eveningness and sleep complaints are predictive of affective dysfunctions, and should be carefully considered in the evaluation and treatment of OCD patients

Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism

© 2015 Wiley Periodicals, Inc. Acknowledgement Grant sponsor: State of Lower Saxony-Israel Research Cooperation; Grant number: ZN2035; Grant sponsor:German Research Council; Grant number: SFB/TRR43 and FOR1336; Grant sponsor: Parkinson UK; Grant number: K-1001; Grant sponsor: ProFutura Program (University of Gottingen); Grant sponsor: Else Kroner Fresenius Stiftung;Grant number: A69/2010; Grant sponsor: DFG; Grant number: WE 3547/4–1; Grant sponsor: US National Multiple Sclerosis Society; Grant numbers: NMSS; PP 1660. The authors thank Elke Pralle, Susanne Kiecke and Caroline Jaß (University of Gottingen) for excellent technical assistance.Peer reviewedPostprin