Polarised neutron scattering from dynamic polarised nuclei 1972-2022.

With the inauguration of the small-angle instrument D11 of the Institute Laue-Langevin (ILL) in September 1972 neutron scattering revolutionized methods of contrast variation. Very soon D11 was oversubscribed by proposals relying on isotopic substitution of hydrogen isotopes. At the same time in Oxford first experiments of polarised neutron diffraction from dynamic polarised protons in lanthanum magnesium nitrate crystals demonstrated the great utility of this approach. In the early eighties a new type of polarised target material led to a boom of contrast variation by nuclear polarisation. The new samples of frozen solutions of macromolecules lent themselves to small-angle scattering. Often in collaboration with research centres of High Energy Physics various groups in Europe and Japan started experiments of polarized neutron scattering from dynamic polarised protons. Techniques of NMR and EPR considerably enlarged the spectrum of nuclear contrast variation. This is shown with time-resolved polarised neutron scattering from dynamic polarized proton spins of a free radical and of tyrosyl doped catalase using D22 at the ILL.

Modified pyridine-triazole and 2,2'-bipyrimidine ligands generating robust titanium complexes constructed around a TiO4N2 core.

The synthesis and characterisation of novel chelate nitrogen ligands with phasmidic tails (pyridine-triazole ligand 1b; 2,2'-bipyrimidine ligands 2b and 3b) as well as their titanium(IV) coordination complexes are reported. The analogous ligands 1a, 2a and 3a with methoxy substituents instead of the tails were also synthesized, together with titanium complexes that could be crystallographically characterised. A good agreement is noticed between analytical data of the complexes in solution (NMR) and in the solid state (X-ray diffraction). The complexes are overall robust on phases like alumina or silica, so that they could be characterised by TLC and sometimes chromatographied. Supramolecular architectures were generated from an equimolar solution of titanium(IV) isopropoxide, ligand 1a and a polyphenol ligand 5-H4, leading to a double-stranded helicate characterised by MS, NMR and crystallography, which was then converted into a trinuclear complex as shown by MS and NMR DOSY data. The liquid-crystalline behaviour of the ligands 1b, 2b and 3b incorporating the long alkyl tails and that of the complexes derived from these ligands have been investigated.

A robust Ti(iv)-based mesogen constructed around a TiO4N2 core.

Stable complexes [Ti(1a)(2)2] and [Ti(1b)(2)2], where 2 is the 6,6'-diphenyl-2,2'-biphenolato ligand and 1a and 1b ligands are 2,2'-bipyrimidine derivatives, are synthesized. The complex [Ti(1b)(2)2] containing a diimine ligand substituted with long alkyl chains (C16) exhibits a liquid crystal behaviour. This property and self-assembling in the crystalline state are explained by the particular molecular conformation of the complexes.

Immunogenicity of oncolytic vaccinia viruses JX-GFP and TG6002 in a human melanoma in vitro model: studying immunogenic cell death, dendritic cell maturation and interaction with cytotoxic T lymphocytes.

Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP) and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) or transforming 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). We compared their properties to kill tumor cells and induce an immunogenic type of cell death in a human melanoma cell model using SK29-MEL melanoma cells. Their influence on human immune cells, specifically regarding the activation of dendritic cells (DCs) and the interaction with the autologous cytotoxic T lymphocyte (CTL) clone, was investigated. Melanoma cells were infected with either JX-GFP or TG6002 alone or in combination with 5-FC and 5-FU. The influence of viral infection on cell viability followed a time- and multiplicity of infection dependent manner. Combination of virus treatment with 5-FU resulted in stronger reduction of cell viability. TG6002 in combination with 5-FC did not significantly strengthen the reduction of cell viability in this setting. Expression of calreticulin and high mobility group 1 protein (HMGB1), markers of immunogenic cell death (ICD), could be detected after viral infection. Accordingly, DC maturation was noted after viral oncolysis. DCs presented stronger expression of activation and maturation markers. The autologous CTL clone IVSB expressed the activation marker CD69, but viral treatment failed to enhance cytotoxicity marker. In summary, vaccinia viruses JX-GFP and TG6002 lyse melanoma cells and induce additional immunostimulatory effects to promote antitumor immune response. Further investigation in vivo is needed to consolidate the data.

What motivates men to offer sperm donation via the internet?

To investigate why men offer sperm donation via the internet, a questionnaire was disseminated via 39 Dutch-language websites thought to be visited by potential sperm donors. Nine internet donors completed the survey, men who typically knew the women they were donating to. Their responses were compared with those of a control group of 35 general sperm bank donors who were recruited using flyers in Dutch sperm banks, and who were typically unaware of the identity of the eventual recipients. The findings shed light on the motives and attitudes of internet donors. Both groups of donors indicated that their primary motivation for donating was altruism (>80% of all respondents). However, internet donors had a more pronounced desire to procreate than sperm bank donors (6 out of 9, i.e. 66 vs. 22%, respectively) and more often felt that they had good genes they wished to pass on (5 out of 9, i.e. 55 vs. 31%, respectively). The main reason internet donors gave for donating via the internet was that they wanted to know the prospective parents and be kept up to date on the progress of the offspring conceived from their donations. This distinguishes them significantly from sperm bank donors. A further finding was that they were not prompted to avoid the formal donation circuit for which, by law in the Netherlands, pregnancies resulting from donations have to be registered in a central database. This study is subject to several, in some cases inevitable, limitations, but it provides an interesting starting point that future studies can seek to confirm and extend.

Polarized proton spin density images the tyrosyl radical locations in bovine liver catalase.

A tyrosyl radical, as part of the amino acid chain of bovine liver catalase, supports dynamic proton spin polarization (DNP). Finding the position of the tyrosyl radical within the macromolecule relies on the accumulation of proton polarization close to it, which is readily observed by polarized neutron scattering. The nuclear scattering amplitude due to the polarization of protons less than 10 Šdistant from the tyrosyl radical is ten times larger than the amplitude of magnetic neutron scattering from an unpaired polarized electron of the same radical. The direction of DNP was inverted every 5 s, and the initial evolution of the intensity of polarized neutron scattering after each inversion was used to identify those tyrosines which have assumed a radical state. Three radical sites, all of them close to the molecular centre and the haem, appear to be equally possible. Among these is tyr-369, the radical state of which had previously been proven by electron paramagnetic resonance.

Inside the bulk of magnetic nanocomposites: I am not what I am.

An unexpected and not always easily discernible feature in the picture of magnetic neutron scattering is widening the outlook on micromagnetic architecture [Mettus & Michels (2015). J. Appl. Cryst.48, 1437-1450].

Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)†.

BACKGROUND: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, ß = 0.8) 379 events had to be observed in the bevacizumab arms. RESULTS: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. CONCLUSIONS: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. CLINICAL TRIAL NUMBER: NCT 00567554, www.clinicaltrials.gov.

[New context for the Individual Healthcare Professions Act (BIG law)]. / Nieuwe context voor de wet BIG.

In 2013 the Dutch Individual Healthcare Professions Act (known as the BIG law) was evaluated for the second time. The research showed that patients have limited awareness of the registration of healthcare professionals and that the system of reserved procedures is almost unknown. On the other hand, healthcare institutions (especially hospitals) frequently check the register, as do healthcare insurance companies when contracting institutions. Knowledge of the reserved procedures system is moderate amongst professionals too, while the organisation of care is to a great extent based on this system. Since the change of system in 2006 quality assurance in professional practice has been much more rooted in the internal structure of care; in this way, the BIG law did not go the way the legislator intended. According to the researchers, this has not prevented the BIG law from still playing an essential function. Indeed, the BIG law has not reached its final destination, but it may reach its goal via another route.

Photophysical, amplified spontaneous emission and charge transport properties of oligofluorene derivatives in thin films.

We investigate the photophysical and amplified spontaneous emission properties of a series of monodisperse solution-processable oligofluorenes functionalized with hexyl chains at the C9 position of each fluorene unit. Thin films of these oligofluorenes are then used in organic field-effect transistors and their charge transport properties are examined. We have particularly focused our attention on the influence of oligofluorene length on the absorption and steady-state fluorescence spectra, on the HOMO/LUMO energy levels, on the photoluminescence lifetime and quantum yield as well as on the amplified spontaneous emission properties and the charge carrier mobilities. Differential scanning calorimetry and X-ray diffraction measurements demonstrate that, among all oligofluorene derivatives used in this study, only the structure and morphology of the pentafluorene film is significantly modified by a thermal treatment above the glass transition temperature, resulting in a 9 nm blue-shift of the fluorescence spectrum without significant changes in the photoluminescence quantum yield and in the amplified spontaneous emission threshold. In parallel, hole field-effect mobility is significantly increased from 8.6 × 10(-7) to 3.8 × 10(-5) cm(2) V(-1) s(-1) upon thermal treatment, due to an increase of crystallinity. This study provides useful insights into the morphological control of oligofluorene thin films and how it affects their photophysical and charge transport properties. Moreover, we provide evidence that, because of the low threshold, the tunability of the amplified spontaneous emission and the photostability of the films, these oligofluorenes are promising candidates for organic solid-state laser applications.

Puckering stick-slip friction induced by a sliding nanoscale contact.

An atomic force microscope reveals that the sliding of a nanotip on a graphite surface occurs through a nanoscale stick-slip mechanism. The angle between the sliding direction and a stiff crystallographic axis determines the periodicity of the slip events defining domains of various friction properties. The experimental data are interpreted using the reaction rate theory, with the energy barrier driven by a local deformation of the surface and a thermally activated relaxation.

Damping in yttrium iron garnet nanoscale films capped by platinum.

Strong damping enhancement in nm-thick yttrium iron garnet (YIG) films due to Pt capping layers was observed. This damping is substantially larger than the expected damping due to conventional spin pumping, is accompanied by a shift in the ferromagnetic resonance field, and can be suppressed by the use of a Cu spacer in between the YIG and Pt films. The data indicate that such damping may originate from the ferromagnetic ordering in Pt atomic layers near the YIG/Pt interface and the dynamic exchange coupling between the ordered Pt spins and the spins in the YIG film.

[Mental incompetence and representation; a thematic evaluation of legislation]. / Wilsonbekwaamheid en vertegenwoordiging: een thematische wetsevaluatie.

OBJECTIVE: To assess how the laws pertaining to the mentally incompetent and their guardians relate to each other and how these topics are handled in daily practice. DESIGN: Structured interviews. METHOD: We administered a questionnaire to healthcare providers and patient guardians in four sectors: care for mentally disabled, nursing home care, psychiatry and intensive care. The topics discussed during the interviews were mental incompetence, advance directives, representation, resistance, and complaint and conflict resolution. For further exploration of the results, we presented these to focus groups in three sectors. We received written comments from several experts of the intensive care sector. RESULTS: Most healthcare providers' initial assumption was that the assessment of mental competence should be more thorough when the treatment is more drastic. The healthcare providers were unenlightened on matters concerning the tasks and authority of patient guardians. This sometimes created tension when their opinions deviated from those of the guardians. It was notable that guardians of mentally incompetent patients in intensive care perceived themselves to be most informed. There is indeed frequent consultation with relatives or guardians in the intensive care unit; however, they are hardly ever asked to participate in decision making. CONCLUSION: There is much ambiguousness on issues relating to mental incompetence and representation among healthcare providers. According to the legislation, reconstructing the will of the patient or client is paramount. Guardians should be involved in establishing mental incompetence and in decisions about treatment, care and research. Advance directives also play an important role. This study has resulted in recommendations on legislation, self-regulation and daily practice.

Dispersion and localization of electronic states at a ferrocene/Cu(111) interface.

Low-temperature scanning tunneling microscopy and spectroscopy combined with first-principles simulations reveal a nondissociative physisorption of ferrocene molecules on a Cu(111) surface, giving rise to ordered molecular layers. At the interface, a 2D-like electronic band is found, which shows an identical dispersion as the Cu(111) Shockley surface-state band. Subsequent deposition of Cu atoms forms charged organometallic compounds that localize interface-state electrons.

Spin pumping at the magnetic insulator (YIG)/normal metal (Au) interfaces.

Spin injection across the ferrimagnetic insulator (YIG)/normal metal (Au) interface was studied by ferromagnetic resonance. The spin mixing conductance was determined by comparing the Gilbert damping in bare YIG films with those covered by a Au/Fe/Au structure. The Fe layer in Au/Fe/Au acted as a spin sink as displayed by an increased Gilbert damping parameter α compared to that in the bare YIG. In particular, for the 9.0 nm YIG/2.0 nm Au/4.3 nm Fe/6.1 nm Au structure, the YIG and Fe films were coupled by an interlayer exchange coupling, and the exchange coupled YIG exhibited an increased Gilbert damping compared to the bare YIG. This relationship between static and dynamic coupling provides direct evidence for spin pumping. The transfer of spin momentum across the YIG interface is surprisingly efficient with the spin mixing conductance g(↑↓) ≃ 1.2 × 10(14) cm(-2).

Control of the transition temperatures of metallomesogens by specific interface design: application to Mn12 single molecule magnets.

Reaction of the Single Molecule Magnet [Mn(12)O(12)(CH(3)CO(2))(16)(H(2)O)(4)] (Mn(12)) with mesogenic dendritic ligands Li (i = 4, 5) quantitatively yields functional clusters [Mn(12)O(12)(Li-H)(16)(H(2)O)(4)] (i = 4, 5) that self-organize into a thermotropic SmA-type liquid crystalline phase. The perturbation of the molecular interface by methylation of the terminal mesogenic cyanobiphenyl groups induces a significant decrease of the clearing temperature without affecting the magnetic properties and the supramolecular organization of the Mn(12)-based clusters.

A prospective multicenter phase II study of oral and i.v. vinorelbine plus trastuzumab as first-line therapy in HER2-overexpressing metastatic breast cancer.

BACKGROUND: To evaluate the efficacy and safety of oral and i.v. vinorelbine plus trastuzumab as first-line regimen in a patient-convenient application for human epidermal growth factor receptor 2 (HER2)-overexpressing patients with metastatic breast cancer. PATIENTS AND METHODS: Forty-two women were enrolled in a multicenter study. The patients received i.v. vinorelbine at a dose of 25 mg/m(2) on day 1 followed by oral vinorelbine at a dose of 60 mg/m(2) on days 8 and 15 in a 3-week cycle. Standard dose trastuzumab was given at 3-week intervals. RESULTS: Complete response was observed in 7 patients (18.9%) and partial response in 19 patients (51.4%), for an overall response rate of 70.3% [95% confidence interval (CI) 53.0-84.1]. The disease control rate reached 91.9% (95% CI 78.1-98.3). The median time to progression was 9.3 months, while median overall survival reached 35.6 months. Hematological and non-hematological toxic effects were acceptable with grade 3-4 leukopenia of 14% and neutropenia of 38%; cardiac toxicity did not reach the level of clinical relevance. CONCLUSION: The combination of i.v. and oral vinorelbine plus trastuzumab demonstrates high activity and good tolerability in first-line treatment of HER2-overexpressing metastatic breast cancer. In addition, it offers convenience for the patients with only one i.v. treatment every 3 weeks.

Engineering negative differential conductance with the Cu(111) surface state.

Low-temperature scanning tunneling microscopy and spectroscopy are employed to investigate electron tunneling from a C60-terminated tip into a Cu(111) surface. Tunneling between a C60 orbital and the Shockley surface states of copper is shown to produce negative differential conductance (NDC) contrary to conventional expectations. NDC can be tuned through barrier thickness or C60 orientation up to complete extinction. The orientation dependence of NDC is a result of a symmetry matching between the molecular tip and the surface states.

[Process and outcome quality of the German Paediatric Surveillance Unit (ESPED)]. / Evaluation der Prozess- und Ergebnisqualität der Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (ESPED).

UNLABELLED: The German paediatric surveillance unit (ESPED) was founded in 1992 with the objective to generate incidence data and to describe symptoms, diagnostic procedures, therapy and prevention for rare paediatric diseases requiring in hospital treatment. Every month the ESPED office sends a mailing card to the heads of all paediatric departments asking for the incident diagnosis of up to 12 conditions. In 2007 about 96% of the cards are returned. Each condition is represented by a principal investigator. Up till now surveillance of 52 conditions has been performed. Reports on the mailing card prompt immediate mailing of the full questionnaire. For 43 conditions the return rates were in the range of 70-100% and for 7 conditions <70% (unknown 2). The highest return rates were achieved if the principal investigator was supported by staff comprising at least two persons or if the mailing of the questionnaire was handled by the ESPED office. The scientific impact of the ESPED System was assessed by the impact factors of the journals, in which the respective ESPED studies were published. By August 31 (st) 2008 the investigators of 38 studies reported up to 7 publications per conditions surveyed. A total of 104 publications was reported: 27 of these appeared in journals without an impact factor. Among the 77 other publications 10 appeared in journals with an impact factor >10. CONCLUSION: Surveillance in ESPED has contributed significantly to high quality research on rare conditions in children.