Comments on the Quantum Potential Approach to a Class of Quantum Cosmological Models

In this comment we bring attention to the fact that when we apply the ontological interpretation of quantum mechanics, we must be sure to use it in the coordinate representation. This is particularly important when canonical tranformations that mix momenta and coordinates are present. This implies that some of the results obtained by A. B\l aut and J. Kowalski-Glikman are incorrect.Comment: 7 pages, LaTe

Quantum Potential Approach to Class of Cosmological Models

In this paper we discuss the quantum potential approach of Bohm in the context of quantum cosmological model. This approach makes it possible to convert the wavefunction of the universe to a set of equations describing the time evolution of the universe. Following Ashtekar et.\ al., we make use of quantum canonical transformation to cast a class of quantum cosmological models to a simple form in which they can be solved explicitly, and then we use the solutions do recover the time evolution.Comment: The corrected version of gr-qc/9506081, 18 pages LaTeX, to appear in Classical and Quantum Gravit

Design of an Activity-Based Probe for Human Neutrophil Elastase: Implementation of the Lossen Rearrangement To Induce Förster Resonance Energy Transfers.

Human neutrophil elastase is an important regulator of the immune response and plays a role in host defense mechanisms and further physiological processes. The uncontrolled activity of this serine protease may cause severe tissue alterations and impair inflammatory states. The design of an activity-based probe for human neutrophil elastase reported herein relies on a sulfonyloxyphthalimide moiety as a new type of warhead that is linker-connected to a coumarin fluorophore. The inhibitory potency of the activity-based probe was assessed against several serine and cysteine proteases, and the selectivity for human neutrophil elastase (Ki = 6.85 nM) was determined. The adequate fluorescent tag of the probe allowed for the in-gel fluorescence detection of human neutrophil elastase in the low nanomolar range. The coumarin moiety and the anthranilic acid function of the probe, produced in the course of a Lossen rearrangement, were part of two different Förster resonance energy transfers

The Challenges in Gravitational Wave Astronomy for Space-Based Detectors

The Gravitational Wave (GW) universe contains a wealth of sources which, with the proper treatment, will open up the universe as never before. By observing massive black hole binaries to high redshifts, we should begin to explore the formation process of seed black holes and track galactic evolution to the present day. Observations of extreme mass ratio inspirals will allow us to explore galactic centers in the local universe, as well as providing tests of General Relativity and constraining the value of Hubble's constant. The detection of compact binaries in our own galaxy may allow us to model stellar evolution in the Milky Way. Finally, the detection of cosmic (super)strings and a stochastic background would help us to constrain cosmological models. However, all of this depends on our ability to not only resolve sources and carry out parameter estimation, but also on our ability to define an optimal data analysis strategy. In this presentation, I will examine the challenges that lie ahead in GW astronomy for the ESA L3 Cosmic Vision mission, eLISA.Comment: 12 pages. Plenary presentation to appear in the Proceedings of the Sant Cugat Forum on Astrophysics, Sant Cugat, April 22-25, 201

Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4.

BACKGROUND: Gut bacteria trigger colitis in animal models and are suspected to aggravate inflammatory bowel diseases. We have recently reported that Escherichia coli accumulates in murine ileitis and exacerbates small intestinal inflammation via Toll-like receptor (TLR) signaling. METHODOLOGY AND PRINCIPAL FINDINGS: Because knowledge on shifts in the intestinal microflora during colitis is limited, we performed a global survey of the colon flora of C57BL/10 wild-type (wt), TLR2(-/-), TLR4(-/-), and TLR2/4(-/-) mice treated for seven days with 3.5% dextrane-sulfate-sodium (DSS). As compared to wt animals, TLR2(-/-), TLR4(-/-), and TLR2/4(-/-) mice displayed reduced macroscopic signs of acute colitis and the amelioration of inflammation was associated with reduced IFN-gamma levels in mesenteric lymph nodes, lower amounts of neutrophils, and less FOXP3-positive T-cells in the colon in situ. During acute colitis E. coli increased in wt and TLR-deficient mice (P<0.05), but the final numbers reached were significantly lower in TLR2(-/-), TLR4(-/-) and TLR2/4(-/-) animals, as compared to wt controls (P<0.01). Concentrations of Bacteroides/ Prevotella spp., and enterococci did not increase during colitis, but their numbers were significantly reduced in the colon of DSS-treated TLR2/4(-/-) animals (P<0.01). Numbers of lactobacilli and clostridia remained unaffected by colitis, irrespective of the TLR-genotype of mice. Culture-independent molecular analyses confirmed the microflora shifts towards enterobacteria during colitis and showed that the gut flora composition was similar in both, healthy wt and TLR-deficient animals. CONCLUSIONS AND SIGNIFICANCE: DSS-induced colitis is characterized by a shift in the intestinal microflora towards pro-inflammatory Gram-negative bacteria. Bacterial products exacerbate acute inflammation via TLR2- and TLR4-signaling and direct the recruitment of neutrophils and regulatory T-cells to intestinal sites. E. coli may serve as a biomarker for colitis severity and DSS-induced barrier damage seems to be a valuable model to further identify bacterial factors involved in maintaining intestinal homeostasis and to test therapeutic interventions based upon anti-TLR strategies

TOPBP1 missense variant Arg309Cys and breast cancer in a German hospital-based case-control study

The DNA double strand break repair gene TOPBP1 has been suggested as a breast cancer susceptibility gene and a missense variant Arg309Cys was observed at elevated frequency in familial breast cancer cases compared to healthy controls from Finland. We found the Arg309Cys allele at a 13% carrier frequency in a hospital-based series of 1064 German breast cancer patients and at a 14% carrier frequency in 1014 population controls (OR 0.89, 95%CI 0.69-1.15; p = 0.4). Arg309Cys carriers were not enriched among patients with a family history of breast cancer (OR = 0.87, 95%CI 0.53-1.43, p = 0.6) and were slightly underrepresented in patients with bilateral disease (OR = 0.49, 95%CI = 0.24-0.99; p = 0.047). In the latter group, the mean age at diagnosis was 62 years in carriers and 54 years in non-carriers (p = 0.004). We conclude that there is no evidence for the TOPBP1*Arg309Cys variant to confer an increased risk for breast cancer in the German population

Comparative prebiotic activity of mixtures of cereal grain polysaccharides

The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan. These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats. Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity. AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios. Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH). Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity. The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet. This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential

Gut health : Predictive biomarkers for preventive medicine and development of functional foods

There is an urgent need to develop and validate a series of biomarkers, which accurately measure and inform on how the human gut microbiota can affect human health. The human gut hosts a complex community of micro-organisms, with unique features in each individual. The functional role of this gut microbiota in health and disease is increasingly evident, but poorly understood. Comprehension of this ecosystem implies a significant challenge in the elucidation of interactions between all of its components, but promises a paradigm shift in preventive nutrition and medicine. Omics technologies for the first time offer tools of sufficient subtlety to tackle this challenge. However, these techniques must be allied with traditional skills of the microbial physiologist, which are in danger of being lost. Targeting these efforts at the identification of biomarkers associated with gut health will require access to a biobank from a pan-European or worldwide observation study, which would include samples taken with appropriate frequency from healthy individuals of different ages. This offers a pragmatic opportunity for a unique food and pharmaceutical industry collaboration