Localized functionalization of single nanopores

We demonstrate the localization of chemical functionality at the entrance of single nanopores for the first time by using the controlled growth of an oxide ring. Nanopores were fabricated by Focused Ion Beam machining on silicon platforms, locally derivatized by ion beam assisted oxide deposition, and further functionalized with DNA probes via silane chemistry. Ionic current recorded through single nanopores at various stages of the fabrication process demonstrated that the apertures can be locally functionalized with DNA probes. Future applications for this functional platform include the selective detection of biological organisms and molecules by ionic current blockade measurements

Novel Methods for Binding Disparate Materials

This project was intended to advance the science of surface bonding in order to provide the functionality demanded by target fabrication requirements, as well as similar needs in other fields of importance to LLNL. We have developed and demonstrated a very powerful capability, i.e. 'single molecule force spectroscopy', that allows the strength of individual chemical bonds to be measured. This project focused on long chain molecules that are covalently bound to surfaces on one end and have complementary reactive groups that have the potential for bridging between surfaces. In biological systems, long chain tethers provide the mechanism for adhesion between dissimilar surfaces, e.g. bacteria adhesion to cells, and were found useful for developing the methodology. Polymer tethers offer the means to bridge across finite surface roughness and have the potential of forming thin, well-characterized bonds on a variety of surfaces

Application of a physically based model to forecast shallow landslides at a regional scale

<p>In this work, we apply a physically based model, namely the HIRESSS (HIgh REsolution Slope Stability Simulator) model, to forecast the occurrence of shallow landslides at the regional scale. HIRESSS is a physically based distributed slope stability simulator for analyzing shallow landslide triggering conditions during a rainfall event. The modeling software is made up of two parts: hydrological and geotechnical. The hydrological model is based on an analytical solution from an approximated form of the Richards equation, while the geotechnical stability model is based on an infinite slope model that takes the unsaturated soil condition into account. The test area is a portion of the Aosta Valley region, located in the northwest of the Alpine mountain chain. The geomorphology of the region is characterized by steep slopes with elevations ranging from 400 m a.s.l. on the Dora Baltea River's floodplain to 4810 m a.s.l. at Mont Blanc. In the study area, the mean annual precipitation is about 800–900 mm. These features make the territory very prone to landslides, mainly shallow rapid landslides and rockfalls. In order to apply the model and to increase its reliability, an in-depth study of the geotechnical and hydrological properties of hillslopes controlling shallow landslide formation was conducted. In particular, two campaigns of on site measurements and laboratory experiments were performed using 12 survey points. The data collected contributed to the generation of an input map of parameters for the HIRESSS model. In order to consider the effect of vegetation on slope stability, the soil reinforcement due to the presence of roots was also taken into account; this was done based on vegetation maps and literature values of root cohesion. The model was applied using back analysis for two past events that affected the Aosta Valley region between 2008 and 2009, triggering several fast shallow landslides. The validation of the results, carried out using a database of past landslides, provided good results and a good prediction accuracy for the HIRESSS model from both a temporal and spatial point of view.</p

Nonlinearly Additive Forces in Multivalent Ligand Binding to a Single Protein Revealed with Force Spectroscopy

We present evidence of multivalent interactions between a single protein molecule and multiple carbohydrates at a pH where the protein can bind four ligands. The evidence is based not only on measurements of the force required to rupture the bonds formed between ConcanavalinA (ConA) and {alpha}-D-mannose, but also on an analysis of the polymer-extension force curves to infer the polymer architecture that binds the protein to the cantilever and the ligands to the substrate. We find that although the rupture forces for multiple carbohydrate connections to a single protein are larger than the rupture force for a single connection, they do not scale additively with increasing number. Specifically, the most common rupture forces are approximately 46, 66, and 85 pN, which we argue corresponds to 1, 2, and 3 ligands being pulled simultaneously from a single protein as corroborated by an analysis of the linkage architecture. As in our previous work polymer tethers allow us to discriminate between specific and non-specific binding. We analyze the binding configuration (i.e. serial versus parallel connections) through fitting the polymer stretching data with modified Worm-Like Chain (WLC) models that predict how the effective stiffness of the tethers is affected by multiple connections. This analysis establishes that the forces we measure are due to single proteins interacting with multiple ligands, the first force spectroscopy study that establishes single-molecule multivalent binding unambiguously

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study

Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity

Parametrical optomechanical oscillations in phoxonic whispering gallery mode resonators

We report on the experimental and theoretical analysis of parametrical optomechanical oscillations in hollow spherical phoxonic whispering gallery mode resonators due to radiation pressure. The optically excited acoustic eigenmodes of the phoxonic cavity oscillate regeneratively leading to parametric oscillation instabilities

The Macroeconomic Effects of the Euro Area's Fiscal Consolidation 2011-2013: A Simulation-Based Approach

We simulate the Euro Area's fiscal consolidation between 2011 and 2013 by employing two DSGE models used by the ECB and the European Commission, respectively. The cumulative multiplier amounts to 0.7 and 1.0 in the baseline, but increases to 1.3 with a reasonably calibrated financial accelerator and a crisis-related increase of the share of liquidity constrained households. In the latter scenario, fiscal consolidation would be largely responsible for the decline in the output gap from 2011-2013. Postponing the fiscal consolidation to a period of unconstrained monetary policy (until after the economic recovery) would have avoided most of these losses.Wir simulieren die Haushaltskonsolidierung im Euroraum im Zeitraum 2011 bis 2013 mit Hilfe von zwei DSGE Modellen der EZB und der Europäischen Kommission. Der kumulative Multiplikator beträgt 0.7 bzw. 1.0 in der Basislinie, steigt aber auf 1.3, wenn die Modelle um einen plausibel kalibrierter Finanzakzelerator erweitert und der Anteil liquiditätsbeschränkter Haushalte krisenbedingt erhöht wird. Im letzteren Szenario trägt die Haushaltskonsolidierung die maßgebliche Verantwortung für die Verschlechterung der Produktionslücke im Zeitraum 2011 bis 2013. Wäre die Haushaltskonsolidierung erst in einer Phase mit uneingeschränktem geldpolitischen Handlungsspielraum vorgenommen worden (d.h. nach der Erholung der Wirtschaft) hätte der Großteil der BIP-Verluste verhindert werden können

Combining scanning probe microscopy and x-ray spectroscopy

A new versatile tool, combining Shear Force Microscopy and X-Ray Spectroscopy was designed and constructed to obtain simultaneously surface topography and chemical mapping. Using a sharp optical fiber as microscope probe, it is possible to collect locally the visible luminescence of the sample. Results of tests on ZnO and on ZnWO4 thin layers are in perfect agreement with that obtained with other conventional techniques. Twin images obtained by simultaneous acquisition in near field of surface topography and of local visible light emitted by the sample under X-Ray irradiation in synchrotron environment are shown. Replacing the optical fibre by an X-ray capillary, it is possible to collect local X-ray fluorescence of the sample. Preliminary results on Co-Ti sample analysis are presented

Induction chemotherapy followed by concurrent standard radiotherapy and daily low-dose cisplatin in locally advanced non-small-cell lung cancer

Both induction chemotherapy and concurrent low-dose cisplatin have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study was designed to investigate activity and feasibility of a novel chemoradiation regimen consisting of induction chemotherapy followed by standard radiotherapy and concurrent daily low-dose cisplatin. Previously untreated patients with histologically/cytologically proven unresectable stage IIIA/B NSCLC were eligible. Induction chemotherapy consisted of vinblastine 5 mg m−2 intravenously (i.v.) on days 1, 8, 15, 22 and 29, and cisplatin 100 mg m−2 i.v. on days 1 and 22 followed by continuous radiotherapy (60 Gy in 30 fractions) given concurrently with daily cisplatin at a dose of 5 mg m−2 i.v. Thirty-two patients were enrolled. Major toxicity during induction chemotherapy was haematological: grade III–IV leukopenia was observed in 31% and grade II anaemia in 16% of the patients. The most common severe toxicity during concurrent chemoradiation consisted of grade III leukopenia (21% of the patients); grade III oesophagitis occurred in only two patients and pulmonary toxicity in one patient who died of this complication. Eighteen of 32 patients (56%, 95% CI 38–73%) had a major response (11 partial response, seven complete response). With a median follow-up of 38.4 months, the median survival was 12.5 months and the actuarial survival rates at 1, 2 and 3 years were 52%, 26% and 19% respectively. The median event-free survival was 8.3 months with a probability of 40%, 23% and 20% at 1, 2 and 3 years respectively. Induction chemotherapy followed by concurrent daily low-dose cisplatin and thoracic irradiation, in patients with locally advanced NSCLC, is active and feasible with minimal non-haematological toxicity. Long-term survival results are promising and appear to be similar to those of more toxic chemoradiation regimens, warranting further testing of this novel chemoradiation strategy. © 1999 Cancer Research Campaig