Dendrimer-aktivierte Chipmatrix für die Herstellung von Nukleinsäure- und Protein-Microarrays

Für die Herstellung von Microarrays durch Immobilisierung bioorganischer Sondenmoleküle, wie DNA-Fragmente oder Proteine, mittels automatisierter Dispenser- oder Plottersysteme werden modifizierte Oberflächen benötigt, die eine physikalische oder chemische Bindung zum Biomolekül ausbilden können. Als Trägermaterial für die Herstellung von Microarrays hat sich aufgrund seiner hohen mechanischen und chemischen Stabilität, sowie seiner geringen Eigenfluoreszenz Glas bewährt. Damit Biochip-basierte Analysen reproduzierbar und mit hoher Nachweisempfindlichkeit durchgeführt werden können, ist es unabdingbar, daß die Modifikation einerseits homogen über die gesamte Chipoberfläche verläuft und andererseits eine hohe Dichte aktiver Kopplungsstellen für das Sondenmolekül bereitstellt. Desweiteren ist es wünschenswert, daß einmal eingesetzte Microarrays durch Regeneration wiederverwendet werden können. Zur Zeit gängige Verfahren, wie z. B. das UV-induzierte Crosslinking an amino-funktionalisierte oder polyamidbeschichtete Trägersysteme, sowie die Chemisorption thiolierter Verbindungen an Gold weisen diesbezüglich erhebliche Defizite auf. Verbesserte Eigenschaften lassen sich erzielen, wenn die Immobilisierung kovalent über ein Linkersystem zwischen Trägermaterial und Biomolekül erfolgt. Wir berichten hier über ein Modifikationsverfahren, das durch den Aufbau einer dendritischen Polymerschicht eine hocheffiziente, kovalente Immobilisierung von Sondenmolekülen erlaubt

Precise Neutron Magnetic Form Factors

Precise data on the neutron magnetic form factor G_{mn} have been obtained with measurements of the ratio of cross sections of D(e,e'n) and D(e,e'p) up to momentum transfers of Q^2 = 0.9 (GeV/c)^2. Data with typical uncertainties of 1.5% are presented. These data allow for the first time to extract a precise value of the magnetic radius of the neutron.Comment: 10 pages, 2 figures, submitted to Physics Letters

A Measurement of the Electric Form Factor of the Neutron through d⃗(e⃗,e′n)p\vec{d}(\vec{e},e'n)p at Q2=0.5Q^2 = 0.5 (GeV/c)2^2

We report the first measurement of the neutron electric form factor $G_E^n$ via $\vec{d}(\vec{e},e'n)p$ using a solid polarized target. $G_E^n$ was determined from the beam-target asymmetry in the scattering of longitudinally polarized electrons from polarized deuterated ammonia, $^{15}$ND$_3$. The measurement was performed in Hall C at Thomas Jefferson National Accelerator Facility (TJNAF) in quasi free kinematics with the target polarization perpendicular to the momentum transfer. The electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle segmented detector. We find $G_E^n = 0.04632\pm0.00616 (stat.) \pm0.00341 (syst.)$ at $Q^2 = 0.495$ (GeV/c)$^2$.Comment: Latex2e 5 pages, 3 figure

IVF for premature ovarian failure: first reported births using oocytes donated from a twin sister

BACKGROUND: Premature ovarian failure (POF) remains a clinically challenging entity because in vitro fertilisation (IVF) with donor oocytes is currently the only treatment known to be effective. METHODS: A 33 year-old nulligravid patient with a normal karyotype was diagnosed with POF; she had a history of failed fertility treatments and had an elevated serum FSH (42 mIU/ml). Oocytes donated by her dizygotic twin sister were used for IVF. The donor had already completed a successful pregnancy herself and subsequently produced a total of 10 oocytes after a combined FSH/LH superovulation regime. These eggs were fertilised with sperm from the recipient\u27s husband via intracytoplasmic injection and two fresh embryos were transferred to the recipient on day three. RESULTS: A healthy twin pregnancy resulted from IVF; two boys were delivered by caesarean section at 39 weeks\u27 gestation. Additionally, four embryos were cryopreserved for the recipient\u27s future use. The sister-donor achieved another natural pregnancy six months after oocyte retrieval, resulting in a healthy singleton delivery. CONCLUSION: POF is believed to affect approximately 1% of reproductive age females, and POF patients with a sister who can be an oocyte donor for IVF are rare. Most such IVF patients will conceive from treatment using oocytes from an anonymous oocyte donor. This is the first report of births following sister-donor oocyte IVF in Ireland. Indeed, while sister-donor IVF has been successfully undertaken by IVF units elsewhere, this is the only known case where oocyte donation involved twin sisters. As with all types of donor gamete therapy, pre-treatment counselling is important in the circumstance of sister oocyte donation

Measurement of the asymmetries in 3He→ \overrightarrow{\sf He}(¯e, e′p)d and 3He→ \overrightarrow{\sf He}(¯e, e′p)np

Abstract.: The electron target asymmetries A || and A⊥ with target spin parallel and perpendicular to the momentum transfer \ensuremath{\boldsymbol{q}} were measured for both the two- and three-body breakup of 3He in the 3 $\overrightarrow{\rm He}$ (¯e, e'p)-reaction. Polarized electrons were scattered off polarized 3He in the quasielastic regime in parallel kinematics with the scattered electron and the knocked-out proton detected using the Three-Spectrometer Facility at MAMI. The results are compared to Faddeev calculations which take into account Final-State Interactions as well as Meson Exchange Currents. The experiment confirms the prediction of a large effect of Final-State Interactions in the asymmetry of the three-body breakup and of an almost negligible one for the two-body breaku

A controlled trial of rivaroxaban after transcatheter aortic-valve replacement

Background: whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. Methods: we randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. Results: after a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). Conclusions: in patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.)

Can Echocardiographic Findings Predict Falls in Older Persons?

Background. The European and American guidelines state the need for echocardiography in patients with syncope. 50% of older adults with syncope present with a fall. Nonetheless, up to now no data have been published addressing echocardiographic abnormalities in older fallers. Method and Findings. In order to determine the association between echocardiographic abnormalities and falls in older adults, we performed a prospective cohort study, in which 215 new consecutive referrals (age 77.4 SD 6.0) of a geriatric outpatient clinic of a Dutch university hospital were included. During the previous year, 139 had experienced a fall. At baseline, all patients underwent routine two-dimensional and Doppler echocardiography. Falls were recorded during a three-month follow-up. Multivariate adjustment for compounders was performed with a Cox proportional hazards model. 557 patients (26%) fell at least once during follow-up. The adjusted hazard ratio of a fall during follow-up was 135 (95% Cl, 1.08-1.71) for pulmonary hypertension, 1.66 (95% Cl, 1.01 to 2.89) for 4-initial regurgitation, 2.41 (95% Cl, 1.32 to 4.37) for tricuspid regurgitation and 1.76 (95% Cl, 1.03 to 3.01) for pulmonary regurgitation. For aoitic regurgitation the risk of a fall was also increased, but non-significantly. (hazard ratio, 1.57 [95% Cl 0.85 to 2.92]). Trend analysis of the severity of the difterent regurgitations showed a significant relationship for mitral, tricuspid and pulmonary valve regurgitation and pulmonary hypertension. Conclusions. Echo(Dopler)cardiography can be useful in order to identify risk indicators for falling. Presence of pulmonary hypertension or regurgitation of mitral, tricuspid or pulmonary valves was associated with a higher fall risk. Our study indicates that the diagnostic work-up for falls in older adults might be improved by adding an echo(Doppler)cardiogram in selected groups

Tetrabenzoporphyrin and -mono-, - Cis -di- and tetrabenzotriazaporphyrin derivatives: Electrochemical and spectroscopic implications of meso CH Group replacement with nitrogen

Nonperipherally hexyl-substituted metal-free tetrabenzoporphyrin (2H-TBP, 1a) tetrabenzomonoazaporphyrin (2H-TBMAP, 2a), tetrabenzo-cis-diazaporphyrin (2H-TBDAP, 3a), tetrabenzotriazaporphyrin (2H-TBTAP, 4a), and phthalocyanine (2H-Pc, 5a), as well as their copper complexes (1b-5b), were synthesized. As the number of meso nitrogen atoms increases from zero to four, Îmax of the Q-band absorption peak becomes red-shifted by almost 100 nm, and extinction coefficients increased at least threefold. Simultaneously the blue-shifted Soret (UV) band substantially decreased in intensity. These changes were related to the relative electron-density of each macrocycle expressed as the group electronegativity sum of all meso N and CH atom groups, âχR. X-ray photoelectron spectroscopy differentiated between the three different types of macrocyclic nitrogen atoms (the Ninner, (NH)inner, and Nmeso) in the metal-free complexes. Binding energies of the Nmeso and Ninner,Cu atoms in copper chelates could not be resolved. Copper insertion lowered especially the cathodic redox potentials, while all four observed redox processes occurred at larger potentials as the number of meso nitrogens increased. Computational chemical methods using density functional theory confirmed 1b to exhibit a Cu(II) reduction prior to ring-based reductions, while for 2b, Cu(II) reduction is the first reductive step only if the nonperipheral substituents are hydrogen. When they are methyl groups, it is the second reduction process; when they are ethyl, propyl, or hexyl, it becomes the third reductive process. Spectro-electrochemical measurements showed redox processes were associated with a substantial change in intensity of at least two main absorbances (the Q and Soret bands) in the UV spectra of these compounds