Surface-hopping dynamics and decoherence with quantum equilibrium structure

In open quantum systems decoherence occurs through interaction of a quantum subsystem with its environment. The computation of expectation values requires a knowledge of the quantum dynamics of operators and sampling from initial states of the density matrix describing the subsystem and bath. We consider situations where the quantum evolution can be approximated by quantum-classical Liouville dynamics and examine the circumstances under which the evolution can be reduced to surface-hopping dynamics, where the evolution consists of trajectory segments evolving exclusively on single adiabatic surfaces, with probabilistic hops between these surfaces. The justification for the reduction depends on the validity of a Markovian approximation on a bath averaged memory kernel that accounts for quantum coherence in the system. We show that such a reduction is often possible when initial sampling is from either the quantum or classical bath initial distributions. If the average is taken only over the quantum dispersion that broadens the classical distribution, then such a reduction is not always possible.Comment: 11, pages, 8 figure

The conduction pathway of potassium channels is water free under physiological conditions.

Ion conduction through potassium channels is a fundamental process of life. On the basis of crystallographic data, it was originally proposed that potassium ions and water molecules are transported through the selectivity filter in an alternating arrangement, suggesting a "water-mediated" knock-on mechanism. Later on, this view was challenged by results from molecular dynamics simulations that revealed a "direct" knock-on mechanism where ions are in direct contact. Using solid-state nuclear magnetic resonance techniques tailored to characterize the interaction between water molecules and the ion channel, we show here that the selectivity filter of a potassium channel is free of water under physiological conditions. Our results are fully consistent with the direct knock-on mechanism of ion conduction but contradict the previously proposed water-mediated knock-on mechanism

Fifth-order susceptibility unveils growth of thermodynamic amorphous order in glass-formers

Glasses are ubiquitous in daily life and technology. However the microscopic mechanisms generating this state of matter remain subject to debate: Glasses are considered either as merely hyper-viscous liquids or as resulting from a genuine thermodynamic phase transition towards a rigid state. We show that third- and fifth-order susceptibilities provide a definite answer to this longstanding controversy. Performing the corresponding high-precision nonlinear dielectric experiments for supercooled glycerol and propylene carbonate, we find strong support for theories based upon thermodynamic amorphous order. Moreover, when lowering temperature, we find that the growing transient domains are compact - that is their fractal dimension d_f = 3. The glass transition may thus represent a class of critical phenomena different from canonical second-order phase transitions for which d_f < 3.Comment: 9 pages, 3 figure

Development and application of the modelling system J2000-S for the EU-water framework directive

The scientific sound definition of measures to achieve the goals of the EU water framework directive (WFD) acquires spatially distributed analyses of the water and substance dynamics in meso- to macro-scale catchments. For this purpose, modelling tools or systems are needed which are robust and fast enough to be applied on such scales, but which are also able to simulate the impact of changes on single fields or small areas of a specific land use in the catchment. &lt;br&gt;&lt;br&gt; To face these challenges, we combined the fully-distributed hydrological model J2000 with the nitrogen transport routines of the Soil Water Assessment Tool SWAT model, which are normally applied in a semi-distributive approach. With this combination, we could extend the quantitative focus of J2000 with qualitative processes and could overcome the semi-distributed limitation of SWAT. For the implementation and combination of the components, we used the Jena Adaptable Modelling System JAMS (Kralisch and Krause, 2006) which helped tremendously in the relatively rapid and easy development of the new resultant model J2000-S (J2000-Substance). &lt;br&gt;&lt;br&gt; The modelling system was applied in the upper Gera watershed, located in Thuringia, Germany. The catchment has an area of 844 km&lt;sup&gt;2&lt;/sup&gt; and includes three of the typical landscape forms of Thuringia. The application showed, that the new modelling system was able to reproduce the daily hydrological as well as the nitrogen dynamics with a sufficient quality. The paper will describe the results of the new model and compare them with the results obtained with the original semi-distributed application of SWAT

Emerging concepts in pancreatic cancer medicine: targeting the tumor stroma

Pancreatic ductal adenocarcinoma is a stroma-rich and highly challenging cancer to treat. Over recent years, it has become increasingly evident that the complex network of soluble cytokines, growth factors, proteases, and components of the extracellular matrix collaboratively interact within the tumor microenvironment, sustaining and driving cancer cell proliferation, invasion, and early metastasis. More recently, the tumor microenvironment has also been appreciated to mediate therapeutic resistance in pancreatic ductal adenocarcinoma, thus opening numerous avenues for novel therapeutic explorations. Inert and soluble components of the tumor stroma have been targeted in order to break down the extracellular matrix scaffold, relieve vessel compression, and increase drug delivery to hypovascular tumors. Moreover, targeting of antiapoptotic, immunosuppressive, and pro-proliferative effects of the tumor stroma provides novel vantage points of attack. This review focuses on current and future developments in pancreatic cancer medicine, with a particular emphasis on biophysical and biochemical approaches that target the tumor microenvironment

Gearing motion in cogwheel pairs of molecular rotors: weak-coupling limit

Variable-​temp. (VT) crystal structures, VT 1H spin-​lattice relaxation in static crystals, and DFT modeling of the rotational barriers of BCP rotators in cryst. arrays of a rod-​like mol. contg. two 1,​3-​bis(ethynyl)​bicyclo[1.1.1]​pentane (BCP) units demonstrate that a correlated gearing motion occurs in the limit of a weak coupling between two rotors in a pair

Surface Grafting of Poly(L-glutamates). 2. Helix Orientation

In this paper the average helix orientation of surface-grafted poly(γ-benzyl L-glutamate) (PBLG), poly(γ-methyl L-glutamate) (PMLG), and poly(γ-methyl L-glutamate)-co-(γ-n-stearyl L-glutamate) (PMLGSLG 70/30) was investigated by means of FT-IR transmission spectroscopy. The theoretical relation between the average tilt angle (θ) and the absorption peak areas of three different backbone amide bands could be calculated because their transition dipole moment directions with respect to the helix axis were known. From the normalized absorptions, the average tilt angles of grafted helices of PBLG, PMLG, and PMLGSLG 70/30 were determined. The somewhat larger average angle of PMLG helices of 35 ± 5° with respect to the substrate compared to the value of 32 ± 5° of PBLG was due to the higher grafting density of PMLG. Because of the smaller helix diameter as a result of the smaller size of the methyl side group, more PMLG helices grew on the same surface area. Sterical hindrance and unfavorable polar interactions between unidirectional aligned helices forced the PMLG helices in a more upright arrangement. The even more perpendicular orientation of PMLGSLG 70/30 (48 ± 6°) could be the result of incorporation of mainly γ-methyl L-glutamate N-carboxyanhydride (MLG-NCA) monomers during the initiation step. Incorporation of the much larger γ-n-stearyl L-glutamate N-carboxyanhydride (SLG-NCA) monomers afterward lead to enlarged angles with respect to the substrate. Due to swelling, a pronounced change in helix orientation of grafted PMLGSLG 70/30 in n-hexadecane was observed, resulting in an almost perpendicular helix orientation.

Effect of interchain coupling on conducting polymer luminescence: excimers in derivatives of poly(phenylene vinylene)

Optical excitation of a chain in a polymer film may result in formation of an excimer, a superposition of on-chain excitons and charge-transfer excitons on the originally excited chain and a neighboring chain. The excimer emission is red-shifted compared to that of an on-chain exciton by an amount depending on the interchain coupling $t_\perp$. Setting up the excimer wavefunction and calculating the red shift, we determine average $t_\perp$ values, referred to a monomer, of 0.52 eV and 0.16 eV for poly(2,5-hexyloxy $p$-phenylene cyanovinylene), CN-PPV, and poly[2-methoxy, 5-(2'-ethyl-hexyloxy)-1, 4 p-phenylene vinylene], MEH-PPV, respectively, and use them to determine the effect of interchain distance on the emission.Comment: 10 pages, RevTeX, 1 PS figure, replaced version of cond-mat/9707095, accepted for publication in Phys. Rev. B, Rapid Communicatio

Length of Variable Numbers of Tandem Repeats in the Carboxyl Ester Lipase (CEL) Gene May Confer Susceptibility to Alcoholic Liver Cirrhosis but Not Alcoholic Chronic Pancreatitis

Background Carboxyl-ester lipase (CEL) contributes to fatty acid ethyl ester metabolism, which is implicated in alcoholic pancreatitis. The CEL gene harbours a variable number of tandem repeats (VNTR) region in exon 11. Variation in this VNTR has been linked to monogenic pancreatic disease, while conflicting results were reported for chronic pancreatitis (CP). Here, we aimed to investigate a potential association of CEL VNTR lengths with alcoholic CP. Methods Overall, 395 alcoholic CP patients, 218 patients with alcoholic liver cirrhosis (ALC) serving as controls with a comparable amount of alcohol consumed, and 327 healthy controls from Germany and the United Kingdom (UK) were analysed by determination of fragment lengths by capillary electrophoresis. Allele frequencies and genotypes of different VNTR categories were compared between the groups. Results Twelve repeats were overrepresented in UK ACP patients (P = 0.04) compared to controls, whereas twelve repeats were enriched in German ALC compared to alcoholic CP patients (P = 0.03). Frequencies of CEL VNTR lengths of 14 and 15 repeats differed between German ALC patients and healthy controls (P = 0.03 and 0.008, respectively). However, in the genotype and pooled analysis of VNTR lengths no statistical significant association was depicted. Additionally, the 16–16 genotype as well as 16 repeats were more frequent in UK ALC than in alcoholic CP patients (P = 0.034 and 0.02, respectively). In all other calculations, including pooled German and UK data, allele frequencies and genotype distributions did not differ significantly between patients and controls or between alcoholic CP and ALC. Conclusions We did not obtain evidence that CEL VNTR lengths are associated with alcoholic CP. However, our results suggest that CEL VNTR lengths might associate with ALC, a finding that needs to be clarified in larger cohorts

Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer

Background Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer. Methods Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA. Results Ninety patients overall received treatment. The maximum tolerated dose was refametinib 50 mg twice daily plus standard gemcitabine (1000 mg/m2 weekly). The combination was well tolerated, with no pharmacokinetic interaction. Treatment-emergent toxicities included thrombocytopenia, fatigue, anemia, and edema. The objective response rate was 23% and the disease control rate was 73%. Overall response rate, disease control rate, progression-free survival, and overall survival were higher in patients without detectable KRAS mutations (48% vs. 28%, 81% vs. 69%, 8.8 vs. 5.3 months, and 18.2 vs. 6.6 months, respectively). Conclusion Refametinib plus gemcitabine was well tolerated, with a promising objective response rate, and had an acceptable safety profile and no pharmacokinetic interaction. There was a trend towards improved outcomes in patients without detectable KRAS mutations that deserves future investigation