Matching Items (44)
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Description

Structural studies on living cells by conventional methods are limited to low resolution because radiation damage kills cells long before the necessary dose for high resolution can be delivered. X-ray free-electron lasers circumvent this problem by outrunning key damage processes with an ultra-short and extremely bright coherent X-ray pulse. Diffraction-before-destruction

Structural studies on living cells by conventional methods are limited to low resolution because radiation damage kills cells long before the necessary dose for high resolution can be delivered. X-ray free-electron lasers circumvent this problem by outrunning key damage processes with an ultra-short and extremely bright coherent X-ray pulse. Diffraction-before-destruction experiments provide high-resolution data from cells that are alive when the femtosecond X-ray pulse traverses the sample. This paper presents two data sets from micron-sized cyanobacteria obtained at the Linac Coherent Light Source, containing a total of 199,000 diffraction patterns. Utilizing this type of diffraction data will require the development of new analysis methods and algorithms for studying structure and structural variability in large populations of cells and to create abstract models. Such studies will allow us to understand living cells and populations of cells in new ways. New X-ray lasers, like the European XFEL, will produce billions of pulses per day, and could open new areas in structural sciences.

Contributorsvan der Schot, Gijs (Author) / Svenda, Martin (Author) / Maia, Filipe R. N. C. (Author) / Hantke, Max F. (Author) / DePonte, Daniel P. (Author) / Seibert, M. Marvin (Author) / Aquila, Andrew (Author) / Schulz, Joachim (Author) / Kirian, Richard (Author) / Liang, Mengning (Author) / Stellato, Francesco (Author) / Bari, Sadia (Author) / Iwan, Bianca (Author) / Andreasson, Jakob (Author) / Timneanu, Nicusor (Author) / Bielecki, Johan (Author) / Westphal, Daniel (Author) / Nunes de Almeida, Francisca (Author) / Odic, Dusko (Author) / Hasse, Dirk (Author) / Carlsson, Gunilla H. (Author) / Larsson, Daniel S. D. (Author) / Barty, Anton (Author) / Martin, Andrew V. (Author) / Schorb, Sebastian (Author) / Bostedt, Christoph (Author) / Bozek, John D. (Author) / Carron, Sebastian (Author) / Ferguson, Ken (Author) / Rolles, Daniel (Author) / Rudenko, Artem (Author) / Epp, Sascha W. (Author) / Foucar, Lutz (Author) / Rudek, Benedikt (Author) / Erk, Benjamin (Author) / Hartmann, Robert (Author) / Kimmel, Nils (Author) / Holl, Peter (Author) / Englert, Lars (Author) / Loh, N. Duane (Author) / Chapman, Henry N. (Author) / Andersson, Inger (Author) / Hajdu, Janos (Author) / Ekeberg, Tomas (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-08-01
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Description

We describe the deposition of four datasets consisting of X-ray diffraction images acquired using serial femtosecond crystallography experiments on microcrystals of human G protein-coupled receptors, grown and delivered in lipidic cubic phase, at the Linac Coherent Light Source. The receptors are: the human serotonin receptor 2B in complex with an

We describe the deposition of four datasets consisting of X-ray diffraction images acquired using serial femtosecond crystallography experiments on microcrystals of human G protein-coupled receptors, grown and delivered in lipidic cubic phase, at the Linac Coherent Light Source. The receptors are: the human serotonin receptor 2B in complex with an agonist ergotamine, the human δ-opioid receptor in complex with a bi-functional peptide ligand DIPP-NH2, the human smoothened receptor in complex with an antagonist cyclopamine, and finally the human angiotensin II type 1 receptor in complex with the selective antagonist ZD7155. All four datasets have been deposited, with minimal processing, in an HDF5-based file format, which can be used directly for crystallographic processing with CrystFEL or other software. We have provided processing scripts and supporting files for recent versions of CrystFEL, which can be used to validate the data.

ContributorsWhite, Thomas A. (Author) / Barty, Anton (Author) / Liu, Wei (Author) / Ishchenko, Andrii (Author) / Zhang, Haitao (Author) / Gati, Cornelius (Author) / Zatsepin, Nadia (Author) / Basu, Shibom (Author) / Oberthur, Dominik (Author) / Metz, Markus (Author) / Beyerlein, Kenneth R. (Author) / Yoon, Chun Hong (Author) / Yefanov, Oleksandr M. (Author) / James, Daniel (Author) / Wang, Dingjie (Author) / Messerschmidt, Marc (Author) / Koglin, Jason E. (Author) / Boutet, Sebastien (Author) / Weierstall, Uwe (Author) / Cherezov, Vadim (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-08-01
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Description

Objective: Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored) events. We present considerations for choosing an approach, using a comparison of semi-parametric

Objective: Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored) events. We present considerations for choosing an approach, using a comparison of semi-parametric proportional hazards (PH) and fully parametric accelerated failure time (AFT) approaches for illustration.

Method: We compare PH and AFT models and procedures in their integration into mediation models and review their ability to produce coefficients that estimate causal effects. Using simulation studies modeling Weibull-distributed survival times, we compare statistical properties of mediation analyses incorporating PH and AFT approaches (employing SAS procedures PHREG and LIFEREG, respectively) under varied data conditions, some including censoring. A simulated data set illustrates the findings.

Results: AFT models integrate more easily than PH models into mediation models. Furthermore, mediation analyses incorporating LIFEREG produce coefficients that can estimate causal effects, and demonstrate superior statistical properties. Censoring introduces bias in the coefficient estimate representing the treatment effect on outcome—underestimation in LIFEREG, and overestimation in PHREG. With LIFEREG, this bias can be addressed using an alternative estimate obtained from combining other coefficients, whereas this is not possible with PHREG.

Conclusions: When Weibull assumptions are not violated, there are compelling advantages to using LIFEREG over PHREG for mediation analyses involving survival-time outcomes. Irrespective of the procedures used, the interpretation of coefficients, effects of censoring on coefficient estimates, and statistical properties should be taken into account when reporting results.

ContributorsGelfand, Lois A. (Author) / MacKinnon, David (Author) / DeRubeis, Robert J. (Author) / Baraldi, Amanda N. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-03-30
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Description

This randomized prospective trial aimed to assess the feasibility and efficacy of a team-based worksite health and safety intervention for law enforcement personnel. Four-hundred and eight subjects were enrolled and half were randomized to meet for weekly, peer-led sessions delivered from a scripted team-based health and safety curriculum. Curriculum addressed:

This randomized prospective trial aimed to assess the feasibility and efficacy of a team-based worksite health and safety intervention for law enforcement personnel. Four-hundred and eight subjects were enrolled and half were randomized to meet for weekly, peer-led sessions delivered from a scripted team-based health and safety curriculum. Curriculum addressed: exercise, nutrition, stress, sleep, body weight, injury, and other unhealthy lifestyle behaviors such as smoking and heavy alcohol use. Health and safety questionnaires administered before and after the intervention found significant improvements for increased fruit and vegetable consumption, overall healthy eating, increased sleep quantity and sleep quality, and reduced personal stress.

ContributorsKuehl, Kerry S. (Author) / Elliot, Diane L. (Author) / Goldberg, Linn (Author) / MacKinnon, David (Author) / Vila, Bryan J. (Author) / Smith, Jennifer (Author) / Miocevic, Milica (Author) / O'Rourke, Holly (Author) / Valente, Matthew (Author) / DeFrancesco, Carol (Author) / Sleigh, Adriana (Author) / McGinnis, Wendy (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-05-08