Structural Changes of Yellow Cameleon Domains Observed by Quantitative FRET Analysis and Polarized Fluorescence Correlation Spectroscopy

Förster resonance energy transfer (FRET) is a widely used method for monitoring interactions between or within biological macromolecules conjugated with suitable donor-acceptor pairs. Donor fluorescence lifetimes in absence and presence of acceptor molecules are often measured for the observation of FRET. However, these lifetimes may originate from interacting and noninteracting molecules, which hampers quantitative interpretation of FRET data. We describe a methodology for the detection of FRET that monitors the rise time of acceptor fluorescence on donor excitation thereby detecting only those molecules undergoing FRET. The large advantage of this method, as compared to donor fluorescence quenching method used more commonly, is that the transfer rate of FRET can be determined accurately even in cases where the FRET efficiencies approach 100% yielding highly quenched donor fluorescence. Subsequently, the relative orientation between donor and acceptor chromophores is obtained from time-dependent fluorescence anisotropy measurements carried out under identical conditions of donor excitation and acceptor detection. The FRET based calcium sensor Yellow Cameleon 3.60 (YC3.60) was used because it changes its conformation on calcium binding, thereby increasing the FRET efficiency. After mapping distances and orientation angles between the FRET moieties in YC3.60, cartoon models of this FRET sensor with and without calcium could be created. Independent support for these representations came from experiments where the hydrodynamic properties of YC3.60 under ensemble and single-molecule conditions on selective excitation of the acceptor were determined. From rotational diffusion times as found by fluorescence correlation spectroscopy and consistently by fluorescence anisotropy decay analysis it could be concluded that the open structure (without calcium) is flexible as opposed to the rather rigid closed conformation. The combination of two independent methods gives consistent results and presents a rapid and specific methodology to analyze structural and dynamical changes in a protein on ligand bindin

Burst dynamics during drainage displacements in porous media: Simulations and experiments

We investigate the burst dynamics during drainage going from low to high injection rate at various fluid viscosities. The bursts are identified as pressure drops in the pressure signal across the system. We find that the statistical distribution of pressure drops scales according to other systems exhibiting self-organized criticality. The pressure signal was calculated by a network model that properly simulates drainage displacements. We compare our results with corresponding experiments.Comment: 7 pages, 4 figures. Submitted to Europhys. Let

What Moves the Highly Skilled and Why? Comparing Turkish Nationals in Canada and Germany

Based on in-depth interviews with highly skilled and business Turkish nationals (HSBTN) in Canada and Germany, this study aims to explore why HSBTN decide to move and whether migration policy differences among the countries of destination affect recent migration motivations of HSBTN. It mainly focuses on the reasons and rationale of HSBTN and their explanations. This study argues that the high skilled and business migrants in general and HSBTN in particular move internationally as a consequence of individual-level gain beyond economic prospects. © 2016 The Authors. International Migration © 2016 IO

Preface

These proceedings contain the papers of the Third International Workshop on Recent Trends in News Informa-tion Retrieval (NewsIR\u201919) held in conjunction with the ACM SIGIR 2019 conference in Paris, France, on the25thof July 2019. Ten full papers and two short papers (one position paper and one demo paper) were selectedby the programme committee from a total of 21 submissions. Each submitted paper was reviewed by at leastthree members of an international programme committee. In addition to the selected papers, the workshopfeatures one keynote and one invited talk. The Keynote speech is given by Aron Pilhofer \u201cFrom Redlining toRobots: How newsrooms apply technology to the craft of journalism\u201d. The invited talk is given by FriedrichLindenberg \u201cMining Leaks and Open Data to Follow the Money\u201d. We would like to thank SIGIR for hostingus. Thanks also go to the keynote speakers, the program committee, the paper authors, and the participants,for without these people there would be no worksho

Acupuncture for chronic neck pain: a pilot for a randomised controlled trial

Background: Acupuncture is increasingly being used for many conditions including chronic neck pain. However the evidence remains inconclusive, indicating the need for further well-designed research. The aim of this study was to conduct a pilot randomised controlled parallel arm trial, to establish key features required for the design and implementation of a large-scale trial on acupuncture for chronic neck pain. Methods: Patients whose GPs had diagnosed neck pain were recruited from one general practice, and randomised to receive usual GP care only, or acupuncture ( up to 10 treatments over 3 months) as an adjunctive treatment to usual GP care. The primary outcome measure was the Northwick Park Neck Pain Questionnaire (NPQ) at 3 months. The primary analysis was to determine the sample size for the full scale study. Results: Of the 227 patients with neck pain identified from the GP database, 28 (12.3%) consenting patients were eligible to participate in the pilot and 24 (10.5%) were recruited to the trial. Ten patients were randomised to acupuncture, receiving an average of eight treatments from one of four acupuncturists, and 14 were randomised to usual GP care alone. The sample size for the full scale trial was calculated from a clinically meaningful difference of 5% on the NPQ and, from this pilot, an adjusted standard deviation of 15.3%. Assuming 90% power at the 5% significance level, a sample size of 229 would be required in each arm in a large-scale trial when allowing for a loss to follow-up rate of 14%. In order to achieve this sample, one would need to identify patients from databases of GP practices with a total population of 230,000 patients, or approximately 15 GP practices roughly equal in size to the one involved in this study (i.e. 15,694 patients). Conclusion: This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn will help to clarify the existing evidence base on acupuncture for neck pain

Fludarabine-Based Reduced Intensity Conditioning for Stem Cell Transplantation of Fanconi Anemia Patients from Fully Matched Related and Unrelated Donors

AbstractReduced intensity conditioning has been suggested as a desirable therapeutic modality for the treatment of patients with malignant and nonmalignant indications, but it seems particularly attractive for patients with Fanconi anemia due to their increased sensitivity to chemoradiotherapy. Between November 1996 and September 2003, 7 patients (1 male and 6 female; age range, 3-31 years; median age, 9.5) were conditioned with a fludarabine-based protocol for stem cell transplantation without radiation. In vivo T-cell depletion was accomplished with anti-thymocytic globulin or Campath-1H (alemtuzumab). Graft-versus-host disease prophylaxis consisted of low-dose cyclosporine alone. Eight transplantations were carried out for 7 patients using bone marrow, peripheral blood, and/or cord blood as sources of stem cells. All patients received transplants from HLA-A, -B, -C, and -DR matched donors, 5 from family members and 2 from matched unrelated donors. One patient did not engraft her first matched unrelated donor and underwent a second transplantation from another matched unrelated donor, after which she engrafted well. All 7 patients are alive and well, fully reconstituted with donor cells, and with 100% performance status. In conclusion, fludarabine-based preparative protocols are well tolerated, facilitate rapid engraftment with minimal toxicity, and should be considered an essential component of choice for patients with Fanconi anemia

Pipe network model for scaling of dynamic interfaces in porous media

We present a numerical study on the dynamics of imbibition fronts in porous media using a pipe network model. This model quantitatively reproduces the anomalous scaling behavior found in imbibition experiments [Phys. Rev. E {\bf 52}, 5166 (1995)]. Using simple scaling arguments, we derive a new identity among the scaling exponents in agreement with the experimental results.Comment: 13 pages, 3 figures, REVTeX, to appear in Phys. Rev. Let

Simulating temporal evolution of pressure in two-phase flow in porous media

We have simulated the temporal evolution of pressure due to capillary and viscous forces in two-phase drainage in porous media. We analyze our result in light of macroscopic flow equations for two-phase flow. We also investigate the effect of the trapped clusters on the pressure evolution and on the effective permeability of the system. We find that the capillary forces play an important role during the displacements for both fast and slow injection rates and both when the invading fluid is more or less viscous than the defending fluid. The simulations are based on a network simulator modeling two-phase drainage displacements on a two-dimensional lattice of tubes.Comment: 12 pages, LaTeX, 14 figures, Postscrip

Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.

We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57 keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9})  eV^{2}. From this, we derive an upper limit of 1.1 eV (90% confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation