Computation of free energy profiles with parallel adaptive dynamics

We propose a formulation of adaptive computation of free energy differences, in the ABF or nonequilibrium metadynamics spirit, using conditional distributions of samples of configurations which evolve in time. This allows to present a truly unifying framework for these methods, and to prove convergence results for certain classes of algorithms. From a numerical viewpoint, a parallel implementation of these methods is very natural, the replicas interacting through the reconstructed free energy. We show how to improve this parallel implementation by resorting to some selection mechanism on the replicas. This is illustrated by computations on a model system of conformational changes.Comment: 4 pages, 1 Figur

Concurrent Geometric Multicasting

We present MCFR, a multicasting concurrent face routing algorithm that uses geometric routing to deliver a message from source to multiple targets. We describe the algorithm's operation, prove it correct, estimate its performance bounds and evaluate its performance using simulation. Our estimate shows that MCFR is the first geometric multicast routing algorithm whose message delivery latency is independent of network size and only proportional to the distance between the source and the targets. Our simulation indicates that MCFR has significantly better reliability than existing algorithms

Immune Reactivity and Pseudoprogression or Tumor Flare in a Serially Biopsied Neuroendocrine Patient Treated with the Epigenetic Agent RRx-001.

Neuroendocrine tumors (NETs) are grouped together as a single class on the basis of histologic appearance, immunoreactivity for the neuroendocrine markers chromogranin A and synaptophysin, and potential secretion of hormones, neurotransmitters, neuromodulators and neuropeptides. Nevertheless, despite these common characteristics, NETs differ widely in terms of their natural histories: high-grade NETs are clinically aggressive and, like small cell lung cancer, which they most closely resemble, tend to respond to cisplatin and etoposide. In contrast, low-grade NETs, which as a rule progress and behave indolently, do not. In either case, the treatment strategy, apart from potentially curative surgical resection, is very poorly defined. This report describes the case of a 28-year-old white male with a diagnosis of high-grade NET of undetermined primary site metastatic to the lymph nodes, skin and paraspinal soft tissues, treated with the experimental anticancer agent RRx-001, in the context of a phase II clinical trial called TRIPLE THREAT (NCT02489903); serial sampling of tumor material through repeat biopsies demonstrated an intratumoral inflammatory response, including the amplification of infiltrating T cells, which correlated with clinical and symptomatic benefit. This case suggests that pseudoprogression or RRx-001-induced enlargement of tumor lesions, which has been previously described for several RRx-001-treated patients, is the result of tumoral lymphocyte infiltration

On how personal values and sustainability conceptions impact students’ sustainability management orientation: evidence from Germany, Indonesia, and the USA

Purpose This study develops and empirically tests a framework on how personal values and sustainability conceptions affect students’ sustainability management orientation (SMO). An understanding of this connection gives insight into the question whether students are likely to engage in sustainable business practices in their future work. Design/methodology/approach A cross-sectional and comparative research design is employed, using survey data of business students from Germany, Indonesia, and the United States (N=475). The proposed mediation models are tested by bootstrap procedures using Hayes’s (2013) PROCESS macro for SPSS. Findings Self-transcendence values translate into more nuanced sustainability conceptions since individuals with self-transcendence values are more likely to conceptualize sustainability beyond their own (narrow) self-interests. In turn, the stronger individuals’ sustainability conceptions, the higher the likelihood that they prefer sustainable management practices in their future professional working field. Research limitations/implications Implications arise for researchers to investigate the engagement of future managers with different personal value types in sustainability practices and to gain insights into values and sustainability conceptions as a learning outcome. Limitations of this research—for instance, arising from potential common method bias—are discussed. Practical implications The findings point to the need to (re-)design appointment processes for management positions in a way that allows taking into account individuals’ personal values and sustainability conceptions. This research may also help firms and higher education institutions to empower their workforce/students to develop more integrated perspectives on sustainability challenges as well as teaching methods that address students’ effective learning outcomes, e.g. their values. Originality/value The paper offers a new framework and a cross-country perspective on psychological antecedents of individuals’ sustainability management orientation as an important prerequisite for responsible behavior in the business context

Bibliometric and authorship trends over a 30 year publication history in two representative US sports medicine journals

Bibliometric studies are important to understand changes and improvement opportunities in academia. This study compared bibliometric trends for two major sports medicine/arthroscopy journals, the American Journal of Sports Medicine® (AJSM®) and Arthroscopy® over the past 30 years. Trends over time and comparisons between both journals were noted for common bibliometric variables (number of authors, references, pages, citations, and corresponding author position) as well as author gender and continental origin. Appropriate statistical analyses were performed. A p < 0.001 was considered statistically significant. One representative year per decade was used. There were 814 manuscripts from AJSM® and 650 from Arthroscopy®. For AJSM® the number of manuscripts steadily increased from 86 in 1986 to 350 in 2016; for Arthroscopy® the number of manuscripts increased from 73 in 1985/1986, to 267 in 2006, but then dropped to 229 in 2016. There were significant increases in all bibliometric variables, except for the number of citations which decreased in Arthroscopy®. There were significant differences in manuscript region of origin by journal (p = 0.000002). Arthroscopy® had a greater percentage of manuscripts from Asia than AJSM® (19.3% vs 11.5%) while AJSM® had a greater percentage from North America (70.3% vs 59.2%); both journals had similar percentages from Europe (18.2% for AJSM® and 21.6% for Arthroscopy®). For AJSM® the average percentage of female first authors was 13.3%, increasing from 4.7% in 1986 to 19.3% in 2016; the average percentage of female corresponding authors was 7.3%. For Arthroscopy®, the average percentage of female first authors was 8.1%, increasing from 2.8% in 1985/1986 to 15.7% in 2016 (p = 0.00007). In conclusion, AJSM® and Arthroscopy® showed an increase in most variables analyzed. Although Arthroscopy® is climbing at a higher rate than AJSM® for female authors, AJSM® has an overall greater percentage of female authors

Comparison of Radiation Transport Codes, HZETRN, HETC and FLUKA, Using the 1956 Webber SPE Spectrum

Protection of astronauts and instrumentation from galactic cosmic rays (GCR) and solar particle events (SPE) in the harsh environment of space is of prime importance in the design of personal shielding, spacec raft, and mission planning. Early entry of radiation constraints into the design process enables optimal shielding strategies, but demands efficient and accurate tools that can be used by design engineers in every phase of an evolving space project. The radiation transport code , HZETRN, is an efficient tool for analyzing the shielding effectiveness of materials exposed to space radiation. In this paper, HZETRN is compared to the Monte Carlo codes HETC-HEDS and FLUKA, for a shield/target configuration comprised of a 20 g/sq cm Aluminum slab in front of a 30 g/cm^2 slab of water exposed to the February 1956 SPE, as mode led by the Webber spectrum. Neutron and proton fluence spectra, as well as dose and dose equivalent values, are compared at various depths in the water target. This study shows that there are many regions where HZETRN agrees with both HETC-HEDS and FLUKA for this shield/target configuration and the SPE environment. However, there are also regions where there are appreciable differences between the three computer c odes

Lamin B1 Depletion in Senescent Cells Triggers Large-Scale Changes in Gene Expression and the Chromatin Landscape

Senescence is a stable proliferation arrest, associated with an altered secretory pathway, thought to promote tumor suppression and tissue aging. While chromatin regulation and lamin B1 down-regulation have been implicated as senescence effectors, functional interactions between them are poorly understood. We compared genome-wide Lys4 trimethylation on histone H3 (H3K4me3) and H3K27me3 distributions between proliferating and senescent human cells and found dramatic differences in senescence, including large-scale domains of H3K4me3- and H3K27me3-enriched “mesas” and H3K27me3-depleted “canyons.” Mesas form at lamin B1-associated domains (LADs) in replicative senescence and oncogene-induced senescence and overlap DNA hypomethylation regions in cancer, suggesting that pre-malignant senescent chromatin changes foreshadow epigenetic cancer changes. Hutchinson-Gilford progeria syndrome fibroblasts (mutant lamin A) also show evidence of H3K4me3 mesas, suggesting a link between premature chromatin changes and accelerated cell senescence. Canyons mostly form between LADs and are enriched in genes and enhancers. H3K27me3 loss is correlated with up-regulation of key senescence genes, indicating a link between global chromatin changes and local gene expression regulation. Lamin B1 reduction in proliferating cells triggers senescence and formation of mesas and canyons. Our data illustrate profound chromatin reorganization during senescence and suggest that lamin B1 down-regulation in senescence is a key trigger of global and local chromatin changes that impact gene expression, aging, and cancer

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

STUDY DESIGN: A multicenter, retrospective review of C5 palsy after cervical spine surgery. OBJECTIVE: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. METHODS: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ(2) tests or Fisher exact tests for categorical variables. RESULTS: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). CONCLUSION: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date

First radial velocity results from the MINiature Exoplanet Radial Velocity Array (MINERVA)

The MINiature Exoplanet Radial Velocity Array (MINERVA) is a dedicated observatory of four 0.7m robotic telescopes fiber-fed to a KiwiSpec spectrograph. The MINERVA mission is to discover super-Earths in the habitable zones of nearby stars. This can be accomplished with MINERVA's unique combination of high precision and high cadence over long time periods. In this work, we detail changes to the MINERVA facility that have occurred since our previous paper. We then describe MINERVA's robotic control software, the process by which we perform 1D spectral extraction, and our forward modeling Doppler pipeline. In the process of improving our forward modeling procedure, we found that our spectrograph's intrinsic instrumental profile is stable for at least nine months. Because of that, we characterized our instrumental profile with a time-independent, cubic spline function based on the profile in the cross dispersion direction, with which we achieved a radial velocity precision similar to using a conventional "sum-of-Gaussians" instrumental profile: 1.8 m s$^{-1}$ over 1.5 months on the RV standard star HD 122064. Therefore, we conclude that the instrumental profile need not be perfectly accurate as long as it is stable. In addition, we observed 51 Peg and our results are consistent with the literature, confirming our spectrograph and Doppler pipeline are producing accurate and precise radial velocities.Comment: 22 pages, 9 figures, submitted to PASP, Peer-Reviewed and Accepte