The individual-cell-based cryo-chip for the cryopreservation, manipulation and observation of spatially identifiable cells. I: Methodology

<p>Abstract</p> <p>Background</p> <p>Cryopreservation is the only widely applicable method of storing vital cells for nearly unlimited periods of time. Successful cryopreservation is essential for reproductive medicine, stem cell research, cord blood storage and related biomedical areas. The methods currently used to retrieve a specific cell or a group of individual cells with specific biological properties after cryopreservation are quite complicated and inefficient.</p> <p>Results</p> <p>The present study suggests a new approach in cryopreservation, utilizing the Individual Cell-based Cryo-Chip (i3C). The i3C is made of materials having appropriate durability for cryopreservation conditions. The core of this approach is an array of picowells, each picowell designed to maintain an individual cell during the severe conditions of the freezing - thawing cycle and accompanying treatments. More than 97% of cells were found to retain their position in the picowells throughout the entire freezing - thawing cycle and medium exchange. Thus the comparison between pre-freezing and post-thawing data can be achieved at an individual cell resolution. The intactness of cells undergoing slow freezing and thawing, while residing in the i3C, was found to be similar to that obtained with micro-vials. However, in a fast freezing protocol, the i3C was found to be far superior.</p> <p>Conclusions</p> <p>The results of the present study offer new opportunities for cryopreservation. Using the present methodology, the cryopreservation of individual identifiable cells, and their observation and retrieval, at an individual cell resolution become possible for the first time. This approach facilitates the correlation between cell characteristics before and after the freezing - thawing cycle. Thus, it is expected to significantly enhance current cryopreservation procedures for successful regenerative and reproductive medicine.</p

The effects of closeness on the election of a pairwise majority rule winner

Some studies have recently examined the effect of closeness on the probability of observing the monotonicity paradox in three-candidate elections under Scoring Elimination Rules. It has been shown that the frequency of such paradox significantly increases as elections become more closely contested. In this paper we consider the effect of closeness on one of the most studied notions in Social Choice Theory: The election of the Condorcet winner, i.e., the candidate who defeats any other opponent in pairwise majority comparisons, when she exists. To be more concrete, we use the well known concept of the Condorcet efficiency, that is, the conditional probability that a voting rule will elect the Condorcet winner, given that such a candidate exists. Our results, based on the Impartial Anonymous Culture (IAC) assumption, show that closeness has also a significant effect on the Condorcet efficiency of different voting rules in the class of Scoring and Scoring Elimination Rules

Testing the leadership and organizational change for implementation (LOCI) intervention in substance abuse treatment: A cluster randomized trial study protocol

© 2017 The Author(s). Background: Evidence-based practice (EBP) implementation represents a strategic change in organizations that requires effective leadership and alignment of leadership and organizational support across organizational levels. As such, there is a need for combining leadership development with organizational strategies to support organizational climate conducive to EBP implementation. The leadership and organizational change for implementation (LOCI) intervention includes leadership training for workgroup leaders, ongoing implementation leadership coaching, 360° assessment, and strategic planning with top and middle management regarding how they can support workgroup leaders in developing a positive EBP implementation climate. Methods: This test of the LOCI intervention will take place in conjunction with the implementation of motivational interviewing (MI) in 60 substance use disorder treatment programs in California, USA. Participants will include agency executives, 60 program leaders, and approximately 360 treatment staff. LOCI will be tested using a multiple cohort, cluster randomized trial that randomizes workgroups (i.e., programs) within agency to either LOCI or a webinar leadership training control condition in three consecutive cohorts. The LOCI intervention is 12months, and the webinar control intervention takes place in months 1, 5, and 8, for each cohort. Web-based surveys of staff and supervisors will be used to collect data on leadership, implementation climate, provider attitudes, and citizenship. Audio recordings of counseling sessions will be coded for MI fidelity. The unit of analysis will be the workgroup, randomized by site within agency and with care taken that co-located workgroups are assigned to the same condition to avoid contamination. Hierarchical linear modeling (HLM) will be used to analyze the data to account for the nested data structure. Discussion: LOCI has been developed to be a feasible and effective approach for organizations to create a positive climate and fertile context for EBP implementation. The approach seeks to cultivate and sustain both effective general and implementation leadership as well as organizational strategies and support that will remain after the study has ended. Development of a positive implementation climate for MI should result in more positive service provider attitudes and behaviors related to the use of MI and, ultimately, higher fidelity in the use of MI. Trial registration: This study is registered with Clinicaltrials.gov ( NCT03042832 ), 2 February 2017, retrospectively registered

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe

Preparation and characterization of polymer/zirconia nanocomposite antistatic coatings on plastic substrates

[[abstract]]Zirconia nanoparticles synthesized by the sol–gel method were surface modified by the coupling agent, 3-(trimethoxy silyl) propyl methacrylate (MSMA), containing C=C bonds. These particles were then UV-cured together with the hexa-functional monomer, dipentaethritol hexaacrylate (DPHA), to prepare transparent coatings that exhibited antistatic property on plastic substrates. FTIR and solid 29SiNMR were used to analyze the chemical bonds in the formed particles and coatings. Dynamic light scattering measurement of the modified ZrO2 sol indicated a relatively small particle size distribution, 1.5–20 nm, with a maximum intensity at ~5.5 nm. These particles dispersed uniformly in the organic host, poly(DPHA), as was manifested by the high resolution SEM images of the coatings. Antistatic performance of the coatings was examined based on the surface resistivity measurements. A resistivity of 7.74 × 108 Ω/□ suited to common antistatic applications could be attained for coatings containing 10% inorganic component. In addition, all of the prepared coatings were very hard with pencil hardness 7H–8H, and they attached perfectly to the PMMA substrate according to the peel test.[[incitationindex]]SCI[[booktype]]電子版[[booktype]]紙