Miracle-dz/UniFAR-FTUs huggingface dataset:
Digital PCR quantification of MGMT methylation refines prediction of clinical benefit from alkylating agents in glioblastoma and metastatic colorectal cancer.

BACKGROUND O(6)-methyl-guanine-methyl-transferase (MGMT) silencing by promoter methylation may identify cancer patients responding to the alkylating agents dacarbazine or temozolomide. PATIENTS AND METHODS We evaluated the prognostic and predictive value of MGMT methylation testing both in tumor and cell-free circulating DNA (cfDNA) from plasma samples using an ultra-sensitive two-step digital PCR technique (methyl-BEAMing). Results were compared with two established techniques, methylation-specific PCR (MSP) and Bs-pyrosequencing. RESULTS Thresholds for MGMT methylated status for each technique were established in a training set of 98 glioblastoma (GBM) patients. The prognostic and the predictive value of MGMT methylated status was validated in a second cohort of 66 GBM patients treated with temozolomide in which methyl-BEAMing displayed a better specificity than the other techniques. Cutoff values of MGMT methylation specific for metastatic colorectal cancer (mCRC) tissue samples were established in a cohort of 60 patients treated with dacarbazine. In mCRC, both quantitative assays methyl-BEAMing and Bs-pyrosequencing outperformed MSP, providing better prediction of treatment response and improvement in progression-free survival (PFS) (P < 0.001). Ability of methyl-BEAMing to identify responding patients was validated in a cohort of 23 mCRC patients treated with temozolomide and preselected for MGMT methylated status according to MSP. In mCRC patients treated with dacarbazine, exploratory analysis of cfDNA by methyl-BEAMing showed that MGMT methylation was associated with better response and improved median PFS (P = 0.008). CONCLUSIONS Methyl-BEAMing showed high reproducibility, specificity and sensitivity and was applicable to formalin-fixed paraffin-embedded tissues and cfDNA. This study supports the quantitative assessment of MGMT methylation for clinical purposes since it could refine prediction of response to alkylating agents.
Real-time loop detection with bags of binary words

We present a method for detecting revisited places in a image sequence in real time by using efficient features. We introduce three important novelties to the bag-of-words plus geometrical checking approach. We use FAST keypoints and BRIEF descriptors, which are binary and very fast to compute (less that 20µs per point). To perform image comparisons, we make use of a bag of words that discretises the binary descriptor space and an inverse index. We also introduce the use of a direct index to take advantage of the bag of words to obtain correspondence points between two images efficiently, avoiding a matching of complexity Θ(n2). To detect loop closure candidates, we propose managing matches in groups to increase the reliability of the candidates returned by the bag of words. We present results in three real and public datasets, with 0.7–1.7 Km long trajectories. We obtain high precision and recall rates, spending 16 ms on average per image for the feature computation and the whole loop detection process in sequences with 19000 images, one order of magnitude less than other similar techniques.
Intra-fraction motion of the prostate is a random walk

A random walk model for intra-fraction motion has been proposed, where at each step the prostate moves a small amount from its current position in a random direction. Online tracking data from perineal ultrasound is used to validate or reject this model against alternatives. Intra-fraction motion of a prostate was recorded by 4D ultrasound (Elekta Clarity system) during 84 fractions of external beam radiotherapy of six patients. In total, the center of the prostate was tracked for 8 h in intervals of 4 s. Maximum likelihood model parameters were fitted to the data. The null hypothesis of a random walk was tested with the Dickey–Fuller test. The null hypothesis of stationarity was tested by the Kwiatkowski–Phillips–Schmidt–Shin test. The increase of variance in prostate position over time and the variability in motility between fractions were analyzed. Intra-fraction motion of the prostate was best described as a stochastic process with an auto-correlation coefficient of ρ = 0.92 ± 0.13. The random walk hypothesis (ρ = 1) could not be rejected (p = 0.27). The static noise hypothesis (ρ = 0) was rejected (p < 0.001). The Dickey–Fuller test rejected the null hypothesis ρ = 1 in 25% to 32% of cases. On average, the Kwiatkowski–Phillips–Schmidt–Shin test rejected the null hypothesis ρ = 0 with a probability of 93% to 96%. The variance in prostate position increased linearly over time (r2 = 0.9 ± 0.1). Variance kept increasing and did not settle at a maximum as would be expected from a stationary process. There was substantial variability in motility between fractions and patients with maximum aberrations from isocenter ranging from 0.5 mm to over 10 mm in one patient alone. In conclusion, evidence strongly suggests that intra-fraction motion of the prostate is a random walk and neither static (like inter-fraction setup errors) nor stationary (like a cyclic motion such as breathing, for example). The prostate tends to drift away from the isocenter during a fraction, and this variance increases with time, such that shorter fractions are beneficial to the problem of intra-fraction motion. As a consequence, fixed safety margins (which would over-compensate at the beginning and under-compensate at the end of a fraction) cannot optimally account for intra-fraction motion. Instead, online tracking and position correction on-the-fly should be considered as the preferred approach to counter intra-fraction motion.
Is the hidden hand an iron fist? Capitalism and civil peace, 1970-2005

There is surprisingly little empirical scholarship on the spread of capitalistic economic policies under the rubric of ‘globalization’ and domestic peace. While the classical liberals saw free markets leading to social harmony because of self-interest of individuals, who cooperate for profit, Marxists and others viewed markets as anarchical, requiring state intervention for obtaining justice and peace. The authors argue from an opportunity-cost perspective that the payoffs to rebellion are structured by how an economy is governed. Closed economies are likelier than more open ones to accumulate ‘rebellion specific capital’ because of high payoffs to organization in the shadows. Using an index of economic freedom that measures how free people are to transact in an economy, the authors find that countries more favorable to free enterprise have a reduced risk of civil war onsets, a result that is robust to the inclusion of institutional quality, per capita wealth, and sundry controls. The results hold up despite a battery of specification changes, alternative data, and testing methods. The findings do not suggest that states under conditions of capitalism lose their autonomy to provide the public good of peace, as skeptics of globalization claim. Peacemakers will do well to build institutions that reward productive investment over rent-seeking, alongside democratic institutions that ultimately gain their legitimacy on the back of good economic performance and well-functioning markets.
Non-Nuclear WldS Determines Its Neuroprotective Efficacy for Axons and Synapses In Vivo

Axon degeneration contributes widely to neurodegenerative disease but its regulation is poorly understood. The Wallerian degeneration slow (WldS) protein protects axons dose-dependently in many circumstances but is paradoxically abundant in nuclei. To test the hypothesis that WldS acts within nuclei in vivo, we redistributed it from nucleus to cytoplasm in transgenic mice. Surprisingly, instead of weakening the phenotype as expected, extranuclear WldS significantly enhanced structural and functional preservation of transected distal axons and their synapses. In contrast to native WldS mutants, distal axon stumps remained continuous and ultrastructurally intact up to 7 weeks after injury and motor nerve terminals were robustly preserved even in older mice, remaining functional for 6 d. Moreover, we detect extranuclear WldS for the first time in vivo, and higher axoplasmic levels in transgenic mice with WldS redistribution. Cytoplasmic WldS fractionated predominantly with mitochondria and microsomes. We conclude that WldS can act in one or more non-nuclear compartments to protect axons and synapses, and that molecular changes can enhance its therapeutic potential.
Smoke-Free Rules and Secondhand Smoke Exposure in Homes and Vehicles Among US Adults, 2009–2010

Introduction An increasing number of US states and localities have implemented comprehensive policies prohibiting tobacco smoking in all indoor areas of public places and worksites. However, private settings such as homes and vehicles remain a major source of exposure to secondhand smoke (SHS) for many people. This study assessed the prevalence and correlates of voluntary smoke-free rules and SHS exposure in homes and vehicles among US adults. Methods We obtained data from the 2009–2010 National Adult Tobacco Survey, a landline and cellular-telephone survey of adults aged 18 years or older residing in the 50 US states or the District of Columbia. We calculated national and state estimates of smoke-free rules and past-7-day SHS exposure in homes and vehicles and examined national estimates by sex, age, race/ethnicity, and education. Results The national prevalence of voluntary smoke-free home rules was 81.1% (state range, 67.9%–92.9%), and the prevalence of household smoke-free vehicle rules was 73.6% (state range, 58.6%–85.8%). Among nonsmokers, the prevalence of SHS exposure was 6.0% in homes (state range, 2.4%–13.0%) and 9.2% in vehicles (state range, 4.8%–13.7%). SHS exposure among nonsmokers was greatest among men, younger adults, non-Hispanic blacks, and those with a lower level of education. Conclusion Most US adults report having voluntary smoke-free home and vehicle rules; however, millions of people remain exposed to SHS in these environments. Disparities in exposure also exist among certain states and subpopulations. Efforts are needed to warn about the dangers of SHS and to promote voluntary smoke-free home and vehicle rules.
Science As Storytelling for Teaching the Nature of Science and the Science-Religion Interface

Here we describe a method for teaching the NOS called " Science as Storytelling, which was designed to directly confront na i¨ ve realist preconceptions about the NOS and replace them with more sophisticated ideas, while retaining a moderate realist perspective. It was also designed to foster a more sophisticated understanding of the science-religion interface, where occasional science-religion conflicts are seen as inevitable in cases where religious beliefs incorporate supernatural intervention in the natural world. We evaluated the program as implemented in a geology course for preservice elementary teachers at Brigham Young University, and showed that it was successful at helping students understand the tentative and creative aspects of scientific thought, and fostering more positive attitudes toward science. Our evaluation also showed that the students adopted a more irenic stance toward science-religion conflict. These results directly contradict fears that emphasizing the creative and tentative aspects of the NOS, and admitting that science and religion sometimes conflict, will cause students to reject scientific claims to an even greater degree.
Meditators and non-meditators on sustained and executive attentional performance

In order to gain a deeper understanding of the mindfulness construct and the mental health benefits associated with mindfulness-based programmes, the relation between mindfulness and its proposed core component attention was studied. Buddhist and Western mindfulness meditators were compared with non-meditators on tasks of sustained (SART) and executive (the Stroop Task) attention. Relations between self-reported mindfulness (FFMQ) and sustained and executive attention were also analysed. No significant differences were found between meditators and non-meditators either in sustained or executive attention. High scores on the FFMQ total scale and on Describe were related to fewer SART errors. High scores on Describe were also related to low Stroop interference. Mindfulness meditators may have an increased awareness of internal processes and the ability to quickly attend to them but this type of refined attentional ability does not seem to be related to performance on attention tests requiring responses to external targets.
Supervised Matrix Factorization for Cross-Modality Hashing

Matrix factorization has been recently utilized for the task of multi-modal hashing for cross-modality visual search, where basis functions are learned to map data from different modalities to the same Hamming embedding. In this paper, we propose a novel cross-modality hashing algorithm termed Supervised Matrix Factorization Hashing (SMFH) which tackles the multi-modal hashing problem with a collective non-matrix factorization across the different modalities. In particular, SMFH employs a well-designed binary code learning algorithm to preserve the similarities among multi-modal original features through a graph regularization. At the same time, semantic labels, when available, are incorporated into the learning procedure. We conjecture that all these would facilitate to preserve the most relevant information during the binary quantization process, and hence improve the retrieval accuracy. We demonstrate the superior performance of SMFH on three cross-modality visual search benchmarks, i.e., the PASCAL-Sentence, Wiki, and NUS-WIDE, with quantitative comparison to various state-of-the-art methods
Mining distance-based outliers from large databases in any metric space

Let R be a set of objects. An object o ∈ R is an outlier, if there exist less than k objects in R whose distances to o are at most r. The values of k, r, and the distance metric are provided by a user at the run time. The objective is to return all outliers with the smallest I/O cost.This paper considers a generic version of the problem, where no information is available for outlier computation, except for objects' mutual distances. We prove an upper bound for the memory consumption which permits the discovery of all outliers by scanning the dataset 3 times. The upper bound turns out to be extremely low in practice, e.g., less than 1% of R. Since the actual memory capacity of a realistic DBMS is typically larger, we develop a novel algorithm, which integrates our theoretical findings with carefully-designed heuristics that leverage the additional memory to improve I/O efficiency. Our technique reports all outliers by scanning the dataset at most twice (in some cases, even once), and significantly outperforms the existing solutions by a factor up to an order of magnitude.
Air quality improvements and health benefits from China’s clean air action since 2013

Aggressive emission control measures were taken by the Chinese government after the promulgation of the ‘Air Pollution Prevention and Control Action Plan’ in 2013. Here we evaluated the air quality and health benefits associated with this stringent policy during 2013–2015 by using surface PM2.5 concentrations estimated from a three-stage data fusion model and cause-specific integrated exposure–response functions. The population-weighted annual mean PM2.5 concentrations decreased by 21.5% over China during 2013–2015, reducing from 60.5 in 2013 to 47.5 μg m−3 in 2015. Subsequently, the national PM2.5-attributable mortality decreased from 1.22 million (95% CI: 1.05, 1.37) in 2013 to 1.10 million (95% CI: 0.95, 1.25) in 2015, which is a 9.1% reduction. The limited health benefits compared to air quality improvements are mainly due to the supralinear responses of mortality to PM2.5 over the high concentration end of the concentration–response functions. Our study affirms the effectiveness of China’s recent air quality policy; however, due to the nonlinear responses of mortality to PM2.5 variations, current policies should remain in place and more stringent measures should be implemented to protect public health.
LEARNING WITHOUT AWARENESS

Two experiments examined the learning of form-meaning connections under conditions where the relevant forms were noticed but the critical aspects of meaning were not. Miniature noun class systems were employed, and the participants were told that the choice of determiner in noun phrases depended on whether the object was “near” or “far” from the subject of the sentence. What they were not told was that the choice of determiner also depended on the animacy of the noun. Most participants remained unaware of this correlation during the training and test tasks; yet when faced with a choice between two determiners for a noun, they chose the one that was appropriate to the noun's animacy at significantly above-chance levels, even though that combination had never been encountered during training. This ability to generalize provided evidence of learning form-meaning connections without awareness. In both experiments, there was a correlation between generalization test performance and knowledge of languages that encode grammatical gender. This points to the importance of prior knowledge in implicit learning.Many thanks to Ronald Leow, Daphnée Simard, and the anonymous SSLA reviewers for their helpful comments on an earlier draft of this article.
Understanding Non-Tenure Track Faculty

This article examines the underlying assumptions brought to bear on studies of non–tenure track faculty. The authors examine the deficit views that characterize non–tenure track as other than professional. Furthermore, they explore and challenge theories brought to bear to currently understand this population and suggest other theories that may better explain research outcomes. Finally, they note the importance of grounded theories that develop out of non–tenure track faculties’ own experience rather than derive from deductive assumptions from temporary employees in business.
Modeling of waveguide-based spatial power combining systems

A modeling scheme is proposed and tested for the analysis of waveguide-based quasi-optical systems. The system is partitioned into blocks, each block is characterized by its generalized scattering matrix (GSM) which in turn are cascaded to obtain the model of the complete system. Blocks with active devices are accounted for in the GSM by means of circuit ports. The calculated and measured results for a Ka-band double layer patch array is presented. A good agreement between theory and measurement is obtained.
Surfactant Reduction in Embolism Bubble Adhesion and Endothelial Damage

Background:Surfactants may reduce the adhesion force holding bubbles to the vessel wall in gas embolism. The authors measured bubble adhesion force using excised microvessels. They assessed endothelial damage by measuring vessel reactivity and with microscopy. Methods:Microbubbles injected into arterioles resided for 5, 10, or 30 min, with intact or damaged endothelium. Perfusion was with rat serum alone (control) or with 1% Perftoran (OJSC SPC Perftoran, Moscow, Russia) or 1% Pluronic F-127 (Molecular Probes, Eugene, OR) added. Pressure across the bubble, bubble length, and bubble diameter were measured, and adhesion force per unit surface area, K = &Dgr;PD/4 l, was calculated. Vessel reactivity was assessed using topical application of phenylephrine and acetylcholine. Results:With the endothelium intact, K was higher in controls than with Perftoran at 10 and 30 min or Pluronic F-127 at 10 min (P < 0.05). With surfactant added after air perfusion to damage the endothelium, K was lower (P < 0.05) at all times for both Perftoran and Pluronic F-127. With surfactant in the perfusate before air perfusion, K was lower at 10 and 30 min for Perftoran and at 10 min for Pluronic F-127 than for controls (P < 0.05). Phenylephrine-induced vasoconstriction was identical among groups. Acetylcholine-induced vasodilatation was the same among groups with an intact endothelium but was found to be lower in controls after air perfusion that followed surfactant exposure than in either surfactant group (P < 0.05). Conclusions:Surfactants reduced bubble adhesion force and preserved basic endothelial structure and vasodilatory function despite attempts to damage the endothelium. Surfactants seem to protect the endothelium from mechanically induced injury in addition to decreasing bubble adhesion forces.
Modulation of Prion-dependent Polyglutamine Aggregation and Toxicity by Chaperone Proteins in the Yeast Model*

In yeast, aggregation and toxicity of the expanded polyglutamine fragment of human huntingtin strictly depend on the presence of the endogenous self-perpetuating aggregated proteins (prions), which contain glutamine/asparagine-rich domains. Some chaperones of the Hsp100/70/40 complex, modulating propagation of yeast prions, were also reported to influence polyglutamine aggregation in yeast, but it was not clear whether they do it directly or via affecting prions. Our data show that although some chaperone alterations indeed act on polyglutamines via curing endogenous prions, other alterations decrease size and ameliorate toxicity of polyglutamine aggregates without affecting prion propagation. Therefore, the role of yeast chaperones in polyglutamine aggregation and toxicity is not restricted only to their effects on the endogenous prions. Moreover, chaperone interactions with prion and polyglutamine aggregates appear to be of a highly specific nature. One and the same chaperone alteration, substitution A503V in the middle region of the chaperone Hsp104, exhibited opposite effects on one of the endogenous prions ([PSI+], the prion form of Sup35) and on polyglutamines, increasing aggregate size and toxicity in the former case and decreasing them in the latter case. On the other hand, different members of a single chaperone family exhibited opposite effects on one and the same type of aggregates: excess of the Hsp40 chaperone Ydj1 increased polyglutamine aggregate size and toxicity, whereas excess of the other Hsp40 chaperone, Sis1, decreased them. As many stress-defense proteins are conserved between yeast and mammals, these data shed light on possible mechanisms modulating polyglutamine aggregation and toxicity in mammalian cells.