Showing papers by "University of Colorado Boulder published in 2014"

Glove: Global Vectors for Word Representation

Abstract: Recent methods for learning vector space representations of words have succeeded in capturing fine-grained semantic and syntactic regularities using vector arithmetic, but the origin of these regularities has remained opaque. We analyze and make explicit the model properties needed for such regularities to emerge in word vectors. The result is a new global logbilinear regression model that combines the advantages of the two major model families in the literature: global matrix factorization and local context window methods. Our model efficiently leverages statistical information by training only on the nonzero elements in a word-word cooccurrence matrix, rather than on the entire sparse matrix or on individual context windows in a large corpus. The model produces a vector space with meaningful substructure, as evidenced by its performance of 75% on a recent word analogy task. It also outperforms related models on similarity tasks and named entity recognition.

Review of Particle Physics

Abstract: The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 Japers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on: Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters.

Biological insights from 108 schizophrenia-associated genetic loci

Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies

Abstract: The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.

Improved cosmological constraints from a joint analysis of the SDSS-II and SNLS supernova samples

Abstract: Aims. We present cosmological constraints from a joint analysis of type Ia supernova (SN Ia) observations obtained by the SDSS-II and SNLS collaborations. The dataset includes several low-redshift samples (z< 0.1), all three seasons from the SDSS-II (0.05

Crizotinib in ROS1-Rearranged Non–Small-Cell Lung Cancer

Abstract: BackgroundChromosomal rearrangements of the gene encoding ROS1 proto-oncogene receptor tyrosine kinase (ROS1) define a distinct molecular subgroup of non–small-cell lung cancers (NSCLCs) that may be susceptible to therapeutic ROS1 kinase inhibition. Crizotinib is a small-molecule tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and another proto-oncogene receptor tyrosine kinase, MET. MethodsWe enrolled 50 patients with advanced NSCLC who tested positive for ROS1 rearrangement in an expansion cohort of the phase 1 study of crizotinib. Patients were treated with crizotinib at the standard oral dose of 250 mg twice daily and assessed for safety, pharmacokinetics, and response to therapy. ROS1 fusion partners were identified with the use of next-generation sequencing or reverse-transcriptase–polymerase-chain-reaction assays. ResultsThe objective response rate was 72% (95% confidence interval [CI], 58 to 84), with 3 complete responses and 33 partial responses. The median duration of respon...

The default network and self-generated thought: component processes, dynamic control, and clinical relevance

Abstract: Though only a decade has elapsed since the default network (DN) was first defined as a large-scale brain system, recent years have brought great insight into the network's adaptive functions. A growing theme highlights the DN as playing a key role in internally directed or self-generated thought. Here, we synthesize recent findings from cognitive science, neuroscience, and clinical psychology to focus attention on two emerging topics as current and future directions surrounding the DN. First, we present evidence that self-generated thought is a multifaceted construct whose component processes are supported by different subsystems within the network. Second, we highlight the dynamic nature of the DN, emphasizing its interaction with executive control systems when regulating aspects of internal thought. We conclude by discussing clinical implications of disruptions to the integrity of the network, and consider disorders when thought content becomes polarized or network interactions become disrupted or imbalanced.

Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs

Abstract: Importance Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials. Objectives To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival. Design, Setting, and Participants From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival. Interventions Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies. Main Outcomes and Measures Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival. Results From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR , 122 (17%); ALK rearrangements, 57 (8%); other EGFR , 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2 ), 19 (3%); BRAF , 16 (2%); PIK3CA , 6 ( MET amplification, 5 ( NRAS , 5 ( MEK1 , 1 ( AKT1 , 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score–adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006). Conclusions and Relevance Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival. Trial Registration clinicaltrials.gov Identifier:NCT01014286.

Cognitive Reappraisal of Emotion: A Meta-Analysis of Human Neuroimaging Studies

Abstract: In recent years, an explosion of neuroimaging studies has examined cognitive reappraisal, an emotion regulation strategy that involves changing the way one thinks about a stimulus in order to change its affective impact Existing models broadly agree that reappraisal recruits frontal and parietal control regions to modulate emotional responding in the amygdala, but they offer competing visions of how this is accomplished One view holds that control regions engage ventromedial prefrontal cortex (vmPFC), an area associated with fear extinction, that in turn modulates amygdala responses An alternative view is that control regions modulate semantic representations in lateral temporal cortex that indirectly influence emotion-related responses in the amygdala Furthermore, while previous work has emphasized the amygdala, whether reappraisal influences other regions implicated in emotional responding remains unknown To resolve these questions, we performed a meta-analysis of 48 neuroimaging studies of reappraisal, most involving downregulation of negative affect Reappraisal consistently 1) activated cognitive control regions and lateral temporal cortex, but not vmPFC, and 2) modulated the bilateral amygdala, but no other brain regions This suggests that reappraisal involves the use of cognitive control to modulate semantic representations of an emotional stimulus, and these altered representations in turn attenuate activity in the amygdala

The Thiol-Michael Addition Click Reaction: A Powerful and Widely Used Tool in Materials Chemistry

Abstract: The key attribute of the thiol-Michael addition reaction that makes it a prized tool in materials science is its modular “click” nature, which allows for the implementation of this highly efficient, “green” reaction in applications that vary from small molecule synthesis to in situ polymer modifications in biological systems to the surface functionalization of material coatings. Over the past few decades, interest in the thiol-Michael addition reaction has increased dramatically, as is evidenced by the number of studies that have been dedicated to elucidating different aspects of the reaction that range from an in-depth analysis aimed at understanding the mechanistic pathways of the reaction to synthetic studies that have examined modifying molecular structures with the aim of yielding highly efficient thiol-Michael reaction monomers. This review examines the reaction mechanisms, the substrates and catalysts used in the reaction, and the subsequent implementation of the thiol-Michael reaction in materials...

The IOC consensus statement: beyond the Female Athlete Triad—Relative Energy Deficiency in Sport (RED-S)

Abstract: Protecting the health of the athlete is a goal of the International Olympic Committee (IOC). The IOC convened an expert panel to update the 2005 IOC Consensus Statement on the Female Athlete Triad. This Consensus Statement replaces the previous and provides guidelines to guide risk assessment, treatment and return-to-play decisions. The IOC expert working group introduces a broader, more comprehensive term for the condition previously known as ‘Female Athlete Triad’. The term ‘Relative Energy Deficiency in Sport’ (RED-S), points to the complexity involved and the fact that male athletes are also affected. The syndrome of RED-S refers to impaired physiological function including, but not limited to, metabolic rate, menstrual function, bone health, immunity, protein synthesis, cardiovascular health caused by relative energy deficiency. The cause of this syndrome is energy deficiency relative to the balance between dietary energy intake and energy expenditure required for health and activities of daily living, growth and sporting activities. Psychological consequences can either precede RED-S or be the result of RED-S. The clinical phenomenon is not a ‘triad’ of the three entities of energy availability, menstrual function and bone health, but rather a syndrome that affects many aspects of physiological function, health and athletic performance. This Consensus Statement also recommends practical clinical models for the management of affected athletes. The ‘Sport Risk Assessment and Return to Play Model’ categorises the syndrome into three groups and translates these classifications into clinical recommendations.

Flood risk and climate change: global and regional perspectives

Abstract: A holistic perspective on changing rainfall-driven flood risk is provided for the late 20th and early 21st centuries. Economic losses from floods have greatly increased, principally driven by the expanding exposure of assets at risk. It has not been possible to attribute rain-generated peak streamflow trends to anthropogenic climate change over the past several decades. Projected increases in the frequency and intensity of heavy rainfall, based on climate models, should contribute to increases in precipitation-generated local flooding (e.g. flash flooding and urban flooding). This article assesses the literature included in the IPCC SREX report and new literature published since, and includes an assessment of changes in flood risk in seven of the regions considered in the recent IPCC SREX report—Africa, Asia, Central and South America, Europe, North America, Oceania and Polar regions. Also considering newer publications, this article is consistent with the recent IPCC SREX assessment finding that ...

Financial Literacy, Financial Education, and Downstream Financial Behaviors

Abstract: Policy makers have embraced financial education as a necessary antidote to the increasing complexity of consumers' financial decisions over the last generation. We conduct a meta-analysis of the relationship of financial literacy and of financial education to financial behaviors in 168 papers covering 201 prior studies. We find that interventions to improve financial literacy explain only 0.1% of the variance in financial behaviors studied, with weaker effects in low-income samples. Like other education, financial education decays over time; even large interventions with many hours of instruction have negligible effects on behavior 20 months or more from the time of intervention. Correlational studies that measure financial literacy find stronger associations with financial behaviors. We conduct three empirical studies, and we find that the partial effects of financial literacy diminish dramatically when one controls for psychological traits that have been omitted in prior research or when one uses an instrument for financial literacy to control for omitted variables. Financial education as studied to date has serious limitations that have been masked by the apparently larger effects in correlational studies. We envisage a reduced role for financial education that is not elaborated or acted upon soon afterward. We suggest a real but narrower role for “just-in-time” financial education tied to specific behaviors it intends to help. We conclude with a discussion of the characteristics of behaviors that might affect the policy maker's mix of financial education, choice architecture, and regulation as tools to help consumer financial behavior. This paper was accepted by Uri Gneezy, behavioral economics.

An optical lattice clock with accuracy and stability at the 10 −18 level

Abstract: In the search for stable and accurate atomic clocks, many-atom lattice clocks have shown higher precision than clocks based on single trapped ions, but have been less accurate; here, a stable many-atom clock is demonstrated that has accuracy better than single-ion clocks. Whether for the definition of SI units, testing the laws of physics or for applications yet to be dreamt of, scientists will always want more stability and more accuracy in their atomic clocks. Many-atom lattice clocks have achieved better precision than clocks based on single trapped ions, but their accuracy has so far been relatively poor. This study from the National Institute of Standards and Technology (NIST) demonstrates a many-atom clock that achieves better accuracy than single-ion-based clocks, and at the same time reduces the required measurement time by two orders of magnitude. Based on thousands of neutral strontium atoms trapped in a laser beam, this new 'optical lattice' clock has the stability, reproducibility and accuracy that make it a prime contender for consideration as a primary standard. It would neither gain nor lose one second in about 5 billion years — although the Earth is unlikely to last that long. Progress in atomic, optical and quantum science1,2 has led to rapid improvements in atomic clocks. At the same time, atomic clock research has helped to advance the frontiers of science, affecting both fundamental and applied research. The ability to control quantum states of individual atoms and photons is central to quantum information science and precision measurement, and optical clocks based on single ions have achieved the lowest systematic uncertainty of any frequency standard3,4,5. Although many-atom lattice clocks have shown advantages in measurement precision over trapped-ion clocks6,7, their accuracy has remained 16 times worse8,9,10. Here we demonstrate a many-atom system that achieves an accuracy of 6.4 × 10−18, which is not only better than a single-ion-based clock, but also reduces the required measurement time by two orders of magnitude. By systematically evaluating all known sources of uncertainty, including in situ monitoring of the blackbody radiation environment, we improve the accuracy of optical lattice clocks by a factor of 22. This single clock has simultaneously achieved the best known performance in the key characteristics necessary for consideration as a primary standard—stability and accuracy. More stable and accurate atomic clocks will benefit a wide range of fields, such as the realization and distribution of SI units11, the search for time variation of fundamental constants12, clock-based geodesy13 and other precision tests of the fundamental laws of nature. This work also connects to the development of quantum sensors and many-body quantum state engineering14 (such as spin squeezing) to advance measurement precision beyond the standard quantum limit.

Mechanical memory and dosing influence stem cell fate.

Abstract: Mechanical cues from the local cellular microenvironment can direct cell fate. Now, experiments with human mesenchymal stem cells cultured on phototunable soft poly(ethylene glycol) hydrogels show that the cells remember past physical environments—with the transcriptional co-activators YAP and TAZ acting as a mechanical rheostat—and therefore that appropriate doses of mechanical cues can be used to manipulate the cells’ fate.

The Randolph Glacier inventory: a globally complete inventory of glaciers

Abstract: The Randolph Glacier Inventory (RGI) is a globally complete collection of digital outlines of glaciers, excluding the ice sheets, developed to meet the needs of the Fifth Assessment of the Intergovernmental Panel on Climate Change for estimates of past and future mass balance. The RGI was created with limited resources in a short period. Priority was given to completeness of coverage, but a limited, uniform set of attributes is attached to each of the � 198 000 glaciers in its latest version, 3.2. Satellite imagery from 1999-2010 provided most of the outlines. Their total extent is estimated as 726 800 � 34 000 km 2 . The uncertainty, about � 5%, is derived from careful single-glacier and basin-scale uncertainty estimates and comparisons with inventories that were not sources for the RGI. The main contributors to uncertainty are probably misinterpretation of seasonal snow cover and debris cover. These errors appear not to be normally distributed, and quantifying them reliably is an unsolved problem. Combined with digital elevation models, the RGI glacier outlines yield hypsometries that can be com- bined with atmospheric data or model outputs for analysis of the impacts of climatic change on glaciers. The RGI has already proved its value in the generation of significantly improved aggregate estimates of glacier mass changes and total volume, and thus actual and potential contributions to sea-level rise.

Financial Literacy, Financial Education and Downstream Financial Behaviors (full paper and web appendix)

Abstract: Policy makers have embraced financial education as a necessary antidote to the increasing complexity of consumers’ financial decisions over the last generation. We conduct a meta-analysis of the relationship of financial literacy and of financial education to financial behaviors in 168 papers covering 201 prior studies. We find that interventions to improve financial literacy explain only 0.1% of the variance in financial behaviors studied, with weaker effects in low-income samples. Like other education, financial education decays over time; even large interventions with many hours of instruction have negligible effects on behavior 20 months or more from the time of intervention. Correlational studies that measure financial literacy find stronger associations with financial behaviors. We conduct three empirical studies and we find that the partial effects of financial literacy diminish dramatically when one controls for psychological traits that have been omitted in prior research or when one uses an instrument for financial literacy to control for omitted variables. Financial education as studied to date has serious limitations that have been masked by the apparently larger effects in correlational studies. We envisage a reduced role for financial education that is not elaborated or acted upon soon afterward. We suggest a real but narrower role for “just in time” financial education tied to specific behaviors it intends to help. We conclude with a discussion of the characteristics of behaviors that might affect the policy maker’s mix of financial education, choice architecture, and regulation as tools to help consumer financial behavior.

The North American multimodel ensemble: Phase-1 seasonal-to-interannual prediction; phase-2 toward developing intraseasonal prediction

Abstract: The recent U.S. National Academies report, Assessment of Intraseasonal to Interannual Climate Prediction and Predictability, was unequivocal in recommending the need for the development of a North American Multimodel Ensemble (NMME) operational predictive capability. Indeed, this effort is required to meet the specific tailored regional prediction and decision support needs of a large community of climate information users. The multimodel ensemble approach has proven extremely effective at quantifying prediction uncertainty due to uncertainty in model formulation and has proven to produce better prediction quality (on average) than any single model ensemble. This multimodel approach is the basis for several international collaborative prediction research efforts and an operational European system, and there are numerous examples of how this multimodel ensemble approach yields superior forecasts compared to any single model. Based on two NOAA Climate Test bed (CTB) NMME workshops (18 February and 8 April 2...

Enzo: an adaptive mesh refinement code for astrophysics

Abstract: This paper describes the open-source code Enzo, which uses block-structured adaptive mesh refinement to provide high spatial and temporal resolution for modeling astrophysical fluid flows. The code is Cartesian, can be run in one, two, and three dimensions, and supports a wide variety of physics including hydrodynamics, ideal and non-ideal magnetohydrodynamics, N-body dynamics (and, more broadly, self-gravity of fluids and particles), primordial gas chemistry, optically thin radiative cooling of primordial and metal-enriched plasmas (as well as some optically-thick cooling models), radiation transport, cosmological expansion, and models for star formation and feedback in a cosmological context. In addition to explaining the algorithms implemented, we present solutions for a wide range of test problems, demonstrate the code's parallel performance, and discuss the Enzo collaboration's code development methodology.

Longitudinal analysis of microbial interaction between humans and the indoor environment.

Abstract: The bacteria that colonize humans and our built environments have the potential to influence our health. Microbial communities associated with seven families and their homes over 6 weeks were assessed, including three families that moved their home. Microbial communities differed substantially among homes, and the home microbiome was largely sourced from humans. The microbiota in each home were identifiable by family. Network analysis identified humans as the primary bacterial vector, and a Bayesian method significantly matched individuals to their dwellings. Draft genomes of potential human pathogens observed on a kitchen counter could be matched to the hands of occupants. After a house move, the microbial community in the new house rapidly converged on the microbial community of the occupants' former house, suggesting rapid colonization by the family's microbiota.

The Earth Microbiome project: successes and aspirations

Abstract: The Earth Microbiome Project (EMP) was launched in August 2010, with the ambitious aim of constructing a global catalogue of the uncultured microbial diversity of this planet. The primary vision of the Earth Microbiome Project, to process the microbial diversity and functional potential from approximately 200,000 environmental samples, marks it as an undertaking so massive that it was at first considered to be pure folly (as late as 2012, Jonathan Eisen was quoted in Nature as saying ‘Knight

Methane leaks from North American natural gas systems

Abstract: Natural gas (NG) is a potential “bridge fuel” during transition to a decarbonized energy system: It emits less carbon dioxide during combustion than other fossil fuels and can be used in many industries. However, because of the high global warming potential of methane (CH4, the major component of NG), climate benefits from NG use depend on system leakage rates. Some recent estimates of leakage have challenged the benefits of switching from coal to NG, a large near-term greenhouse gas (GHG) reduction opportunity ( 1 – 3 ). Also, global atmospheric CH4 concentrations are on the rise, with the causes still poorly understood ( 4 ).