The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural (...) tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index, between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility. (shrink)

Smart grids are rolling out internationally, with the United States nearing completion of a significant USD4-plus-billion federal program funded under the American Recovery and Reinvestment Act. The emergence of smart grids is widespread across developed countries. Multiple approaches to analyzing the benefits of smart grids have emerged. The goals of this white paper are to review these approaches and analyze examples of each to highlight their differences, advantages, and disadvantages. This work was conducted under the auspices of a joint U.S.-China (...) research effort, the Climate Change Working Group Implementation Plan, Smart Grid. We present comparative benefits assessments of smart grid demonstrations in the U.S. and China along with a BA of a pilot project in Europe. In the U.S., we assess projects at two sites: the University of California, Irvine campus, which consists of two distinct demonstrations: Southern California Edison’s Irvine Smart Grid Demonstration Project and the UCI campus itself; and the Navy Yard area in Philadelphia, which has been repurposed as a mixed commercial-industrial, and possibly residential, development. In China, we cover several smart-grid aspects of the Sino-Singapore Tianjin Eco-city and the Shenzhen Bay Technology and Ecology City. In Europe, we look at a BA of a pilot smart grid project in the Malagrotta area west of Rome, Italy, contributed by the Joint Research Centre of the European Commission. The Irvine sub-project BAs use the U.S. Department of Energy Smart Grid Computational Tool, which is built on methods developed by the Electric Power Research Institute. The TEC sub-project BAs apply Smart Grid Multi-Criteria Analysis developed by the State Grid Corporation of China based on the analytic hierarchy process with fuzzy logic. The B-TEC and TNY sub-project BAs are evaluated using new approaches developed by those project teams. JRC has adopted an approach similar to EPRI’s but tailored to the Malagrotta distribution grid. (shrink)

In this paper, a graph-based nonlocal total variation method is proposed for unsupervised classification of hyperspectral images. The variational problem is solved by the primal-dual hybrid gradient algorithm. By squaring the labeling function and using a stable simplex clustering routine, an unsupervised clustering method with random initialization can be implemented. The effectiveness of this proposed algorithm is illustrated on both synthetic and real-world HSI, and numerical results show that the proposed algorithm outperforms other standard unsupervised clustering methods such as spherical (...) K-means, nonnegative matrix factorization, and the graph-based Merriman-Bence-Osher scheme. (shrink)

We previously reported widespread microstructural deficits of brain white matter in alcohol-dependent individuals compared to light drinkers in a small 1.5T diffusion tensor imaging study employing tract-based spatial statistics. Using a larger dataset acquired at 4T, the present study is an extension that investigated the effects of alcohol consumption, abstinence from alcohol, and comorbid cigarette smoking on white matter microstructure.Tract-based spatial statistics were performed on 20 1-week-abstinent ALC, 52 1-month-abstinent ALC, and 30 controls. Regional measures of fractional anisotropy and mean (...) diffusivity in the significant clusters were compared by Analysis of Covariance. The metrics were correlated with substance use history and behavioral measures.1-week-abstinent ALC showed lower FA than controls in the corpus callosum, right cingulum, external capsule, and hippocampus. At 1 month of abstinence, only the FA in the body of the corpus callosum of ALC remained significantly different from controls. Some regional FA deficits correlated with more severe measures of drinking and smoking histories but only weakly with mood and impulsivity measures.White matter microstructure is abnormal during early abstinence in alcohol dependent treatment seekers and recovers into the normal range within about four weeks. The compromised white matter was related to substance use severity, mood, and impulsivity. Our findings suggest that ALC may benefit from interventions that facilitate normalization of DTI metrics to maintain abstinence, via smoking cessation, cognitive-based therapy, and perhaps pharmacology to support remyelination. (shrink)

Knowing where, when, and how much rice is planted and harvested is crucial information for understanding the effects of policy, trade, and global and technological change on food security. We developed RiceAtlas, a spatial database on the seasonal distribution of the world's rice production. It consists of data on rice planting and harvesting dates by growing season and estimates of monthly production for all rice-producing countries. Sources used for planting and harvesting dates include global and regional databases, national publications, online (...) reports, and expert knowledge. Monthly production data were estimated based on annual or seasonal production statistics, and planting and harvesting dates. RiceAtlas has 2,725 spatial units. Compared with available global crop calendars, RiceAtlas is nearly ten times more spatially detailed and has nearly seven times more spatial units, with at least two seasons of calendar data, making RiceAtlas the most comprehensive and detailed spatial database on rice calendar and production. (shrink)

The NOX family includes seven unique members that are involved in a multitude of physiological functions, including extensive interaction with UVR and the skin. NOX1 is uniquely present and activated by UVB radiation with biphasic expression of the enzyme immediately and then after a several-hour delay. Specific inhibition of both early and late NOX1 activation leads to evidence of decreased photocarcinogenesis in in vitro keratinocytes and in well-characterized mouse models in which antitumor efficacy has been shown; inhibiting only late NOX (...) activation does not exhibit such effects. These results suggest a crucial function of early NOX activation in transducing a signal for cellular protection after UVB carcinogenesis provocation. We term this an intrinsic cellular ROS priming function for quenching DNA damage and promoting survival. Evolutionally, this type of priming function may be essential for addressing various types of stimuli from adverse environments. (shrink)

The ability to represent same-different relations is an important condition for abstract thought. However, there is mixed evidence for when this ability develops, both ontogenetically and phylogenetically. Apparent success in relational reasoning may be evidence for genuine conceptual understanding or may be the result of low-level, perceptual strategies. We introduce a method to discriminate these possibilities by pitting two conditions that are perceptually matched but conceptually different: in a "fused" condition, same and different objects are joined, creating single objects that (...) have the same perceptual features as the two object pairs in the "relational" condition. However, the "fused" objects do not provide evidence for the relation 'same.' Using this method with human toddlers in a causal relational reasoning task provides evidence for genuine conceptual understanding. This novel technique offers a simple manipulation that may be applied to a variety of existing match-to-sample procedures used to assess same-different reasoning to include in future research with non-human animals across species, as well as human infants. (shrink)

Recalibration of affordance perception allows observers to adapt to changes in the body's size or abilities that alter possibilities for action. Of key interest is understanding how exploratory behaviors lead to successful recalibration. The present study was designed to test a novel hypothesis-that the same processes of exploration and recalibration should generalize between affordances that share a similar function. Most affordances for fitting the body through openings are recalibrated without feedback from practicing the action; locomotion exploration is sufficient. The present (...) study used a different fitting task, squeezing through doorways, to determine whether locomotor experience was sufficient for recalibrating to changes in body size that altered affordances. Participants were unable to recalibrate from locomotor experience, demonstrating that exploratory behaviors do not necessarily generalize between functionally similar affordances. Participants only recalibrated following action practice or after receiving feedback about judgment accuracy, suggesting that the informational requirements of the squeezing task may differ from those of other fitting tasks. Implications for affordance theory are discussed. (shrink)

The value of perfusion and diffusion-weighted MRI in differentiating histological subtypes according to the 2007 WHO glioma classification scheme and genetic subtypes according to the 2016 WHO reclassification in WHO grade II and III diffuse gliomas remains controversial. In the current study, we describe unique perfusion and diffusion MR signatures between histological and genetic glioma subtypes. Sixty-five patients with 2007 histological designations, 1p/19q status, and IDH1 mutation status were included in this study. In all patients, median relative cerebral blood volume (...) and apparent diffusion coefficient were estimated within T2 hyperintense lesions. Bootstrap hypothesis testing was used to compare subpopulations of gliomas, separated by WHO grade and 2007 or 2016 glioma classification schemes. A multivariable logistic regression model was also used to differentiate between 1p19q+ and 1p19q- WHO II-III gliomas. Neither rCBV nor ADC differed significantly between histological subtypes of pure astrocytomas and pure oligodendrogliomas. ADC was significantly different between molecular subtypes, particularly between IDHWT and IDHMUT/1p19q+. IDHMUT/1p19q+ grade III gliomas had higher median ADC; IDHWT grade III gliomas had higher rCBV with lower ADC; and IDHMUT/1p19q- had intermediate rCBV and ADC values, similar to their grade II counterparts. A multivariable logistic regression model was able to differentiate between IDHWT and IDHMUT WHO II and III gliomas with an AUC of 0.84. Within IDHMUT WHO II-III gliomas, a separate multivariable logistic regression model was able to differentiate between 1p19q+ and 1p19q- WHO II-III gliomas with an AUC of 0.80. ADC better differentiated between genetic subtypes of gliomas according to the 2016 WHO guidelines compared to the classification scheme outlined in the 2007 WHO guidelines based on histological features of the tissue. Results suggest a combination of rCBV, ADC, T2 hyperintense volume, and presence of contrast enhancement together may aid in non-invasively identifying genetic subtypes of diffuse gliomas. (shrink)

Open transcranial approaches to the anterior skull base remain an integral component of current skull base practice. Evolution of these and other techniques has resulted in revisions of standard, tried-and-true methods in attempts to improve patient outcomes and cosmesis, while still providing the best combination of surgical exposure and ergonomics.To describe a modified approach for midline tumors of the anterior skull base.We describe the anatomy and techniques of a modified extended bifrontal craniotomy for anterior skull base tumors. Case examples and (...) a postoperative 3-dimensional computed tomographic reconstruction of the craniotomy are provided.The technique has been employed with success in 3 tuberculum sellae meningiomas where the anterior limit of the tumor is several centimeters back from the inner table of the frontal bone. The mean distance from the tumor to inner table was 2.8 cm. Mean tumor dimensions were 3.0 cm, 3.5 cm, and 2.2 cm. Average operative time was 557 min. No cases had new T2/fluid-attenuated inversion recovery magnetic resonance imaging signal of the inferior frontal lobe to indicate retraction injury.The tailored extended bifrontal craniotomy for anterior skull base tumors provides adequate access to the anterior cranial fossa and has replaced our standard extended bifrontal approach. Keeping the osteotomy cut lines outside of the orbit reduces orbital swelling and mechanical disruption of conjugate eye movements in the early postoperative period, while allowing for minimal frontal lobe retraction and providing sufficient surgical exposure along the anterior skull base. (shrink)

With the addition of rituximab and other treatment advances, survival after diffuse large B-cell lymphoma has improved, but subsequent primary malignancies have emerged as an important challenge for DLBCL survivorship. We calculated standardized incidence ratios and 95% confidence intervals for SPMs among 23 879 patients who survived at least 1 year after a first primary DLBCL diagnosed during 1989-2012, compared to the general population in California. Cumulative incidence of SPMs, accounting for the competing risk of death, also was calculated. We (...) found that the incidence of acute myeloid leukaemia nearly doubled in the post-rituximab era [SIR 4·39 pre- and 8·70 post-rituximab ]. Subsequent thyroid cancer was rare pre-rituximab, but increased substantially after 2001 [0·66 vs. 2·27]. The 5-year CMI for all SPMs, AML, thyroid cancer and melanoma were greater in DLBCL patients diagnosed in the post- versus pre-rituximab period. This study provides insight into the changing pattern of SPM occurrence after the introduction of rituximab, which may elucidate the aetiology of SPMs and should guide future cancer surveillance efforts among DLBCL patients. (shrink)

We report a case of a 52-year-old man who presented to the emergency department in extremis with subsequent cardiacarrest after a motor vehicle collision. The initial trauma evaluation did not reveal asource of the hemodynamic compromise. A point-of-care ultrasound revealed severemitral regurgitation secondary to an anterolateral papillary muscle rupture. Patientunderwent successful emergent mitral valve replacement after initial resuscitativeefforts and intraaortic balloon pump placement.

A 79-year-old female called 911 for abdominal pain in her left upper quadrant with radiationthrough to her back and left shoulder for three hours. Upon arrival to the emergency departmenther physical exam was positive only for tenderness in the left upper quadrant of her abdomen.The patient denied any history of trauma but reported she “did sneeze three times” just priorto the onset of her pain. Computed tomography angiography of the abdomen and pelvis wasobtained to evaluate for vascular pathology. The radiologist (...) immediately called with concern forsplenic laceration. The general surgeon took the patient directly to the operating room whereshe underwent a splenectomy and recovered without sequelae. This is the first case report ofspontaneous splenic rupture that resulted after the act of sneezing. It is important to be aware ofthis rare clinical entity because early recognition can be life saving. (shrink)

Takotsubo cardiomyopathy, also known as apical ballooning syndrome and stress cardiomyopathy, is a transient systolic and diastolic left ventricular dysfunction with a variety of cardiac wall-motion abnormalities that is increasingly being associated with significant morbidity and mortality. Wellens’ syndrome is an electrocardiographic pattern in a pain-free patient that is indicative of critical occlusion of the left anterior descending coronary artery requiring immediate cardiac catheterization. The authors report a case of a patient presenting with electrocardiographic findings consistent with Wellens’ syndrome that (...) was later found to have Takotsubo cardiomyopathy with angiographically normal coronary arteries on cardiac catheterization after a seizure. (shrink)

Altered precipitation patterns associated with anthropogenic climate change are expected to have many effects on plants and insect pollinators, but it is unknown if effects on pollination are mediated by changes in water availability. We tested the hypothesis that impacts of climate on plant-pollinator interactions operate through changes in water availability, and specifically that such effects occur through alteration of floral attractants. We manipulated water availability in two naturally occurring Mertensia ciliata populations using water addition, water reduction and control plots (...) and measured effects on vegetative and floral traits, pollinator visitation and seed set. While most floral trait values, including corolla size and nectar, increased linearly with increasing water availability, in this bumblebee-pollinated species, pollinator visitation peaked at intermediate water levels. Visitation also peaked at an intermediate corolla length, while its relationship to corolla width varied across sites. Seed set, however, increased linearly with water. These results demonstrate the potential for changes in water availability to impact plant-pollinator interactions through pollinator responses to differences in floral attractants, and that the effects of water on pollinator visitation can be nonlinear. Plant responses to changes in resource availability may be an important mechanism by which climate change will affect species interactions. (shrink)

Clenbuterol is a beta-agonist that has been abused by fitness-oriented individuals for muscle growthand weight loss. We report a case of a 46-year-old man who presented tachycardic, hypokalemic, andhyperglycemic after injecting testosterone obtained from Brazil. He developed refractory hypotensionand was started on an esmolol infusion for suspected beta-agonist toxicity. Laboratory analysisshowed a detectable clenbuterol serum concentration. Analysis of an unopened ampule containedboldenone undecylenate, clenbuterol, and vitamin E. This case illustrates a novel exposure thatcaused beta-agonist toxicity and was treated successfully with (...) rapid-onset beta blocker. (shrink)

Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response signaling pathways would allow for selective therapeutic targeting of pathological T cells in disease contexts. Consistent with these hypotheses, we found that activated mouse and human T cells display a pronounced DDR in vitro and in vivo. Upon screening a variety of small-molecule (...) compounds, we found that potentiation of p53 or impairment of cell cycle checkpoints led to the selective elimination of activated, pathological T cells in vivo. The combination of these strategies [which we termed "p53 potentiation with checkpoint abrogation" ] displayed therapeutic benefits in preclinical disease models of hemophagocytic lymphohistiocytosis and multiple sclerosis, which are driven by foreign antigens or self-antigens, respectively. PPCA therapy targeted pathological T cells but did not compromise naive, regulatory, or quiescent memory T-cell pools, and had a modest nonimmune toxicity profile. Thus, PPCA is a therapeutic modality for selective, antigen-specific immune modulation with significant translational potential for diverse immune-mediated diseases. (shrink)

Laceration injuries comprise over 8% of all emergency department visits annually.1 Given that laceration injuries represent a significant volume of ED visits, emergency medicine physicians should be comfortable treating these injuries. We present the case of a 34-year-old male who presented to the emergency department as a trauma activation who suffered multiple injuries including complex full thickness lacerations to his face. While there are scenarios in which consulting a specialist is necessary, knowledge and application of basic wound closure principles allows (...) for many complex lacerations to be repaired by emergency medicine physicians. We provide a helpful systematic approach to evaluating and treating complex facial lacerations in the emergency department. (shrink)

The complex nature of air pollution in urban areas due to meteorological influences and mobile emissions prevents traditional monitoring techniques from obtaining measurements representative of true human exposure. Small, mobile air pollution monitors, however, are useful tools to address this complexity. The current study assessed the capability of low-cost mobile monitors to acquire useful data in a city without a monitoring network in place using a bicycle platform. The monitoring campaign resulted in 30 days of data along a 13.4km fixed (...) concentric route. Due to high sensitivities to airflow, the apparent wind velocity was accounted for throughout the route. The data were also normalized into percentiles in order to visualize spatial patterns. The highest estimated pollution levels were located near frequently busy intersections and roads; however, sensor issues resulted in lower confidence. Additional research is needed concerning the appropriate use of low-cost metal oxide sensors for citizen science applications, as measurements can be misleading if the user is unaware of sensors specifications. The average person will not have the resources necessary to deal with the out-of-the-box variations discovered in this study. The simultaneous use of several low-cost mobile platforms, rather than a single platform, as well as the use of high-end cases are recommended to create a more robust spatial analysis. The issues addressed from this research are important to understand for accurate and beneficial application of low-cost gaseous monitors for citizen science. (shrink)

Isolated pelvic DVTs are rare and difficult to diagnose, but are more common in pregnant women and carry an increased risk of embolization. Pulmonary embolism is the most common non-obstretric cause of death in pregnancy. Compression ultrasound is the first-line imaging test for suspected lower extremity DVT, but it cannot usually directly visualize or easily diagnose isolated pelvic DVT. Nonetheless, Point of Care Ultrasound may provide valuable clues to help rule in pelvic DVT and expedite initiation of anticoagulant therapy. Such (...) findings include increased venous diameter, increased resistance to compression, visible venous reflux, and blunted phasicity. This case presents an example of how these findings on POCUS led the emergency physician to make the difficult diagnosis of pelvic DVT at the bedside within seconds. (shrink)

Polymorphisms in the human leukocyte antigen class I genes can cause the rejection of pluripotent stem cell -derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus -mediated gene editing to knock in HLA-E genes at the B2M locus (...) in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers or trimers, without surface expression of HLA-A, B or C. These HLA-engineered PSCs and their differentiated derivatives are not recognized as allogeneic by CD8+ T cells, do not bind anti-HLA antibodies and are resistant to NK-mediated lysis. Our approach provides a potential source of universal donor cells for applications where the differentiated derivatives lack HLA class II expression. (shrink)

Due to their unique properties, copper-based nanopesticides are emerging in the market. Thus, understanding their effect on crop plants is very important. Metabolomics can capture a snapshot of cellular metabolic responses to a stressor. We selected maize and cucumber as model plants for exposure to different doses of Cu2 nanopesticide. GC-TOF-MS-based metabolomics was employed to determine the metabolic responses of these two species. Results revealed significant differences in metabolite profile changes between maize and cucumber. Furthermore, the Cu2 nanopesticide induced metabolic (...) reprogramming in both species, but in different manners. In maize, several intermediate metabolites of the glycolysis pathway and tricarboxylic acid cycle were up-regulated, indicating the energy metabolism was activated. In addition, the levels of aromatic compounds and their precursors were enhanced, indicating the activation of shikimate-phenylpropanoid biosynthesis in maize leaves, which is an antioxidant defense-related pathway. In cucumber, arginine and proline metabolic pathways were the most significantly altered pathway. Both species exhibited altered levels of fatty acids and polysaccharides, suggesting the cell membrane and cell wall composition may change in response to Cu2 nanopesticide. Thus, metabolomics helps to deeply understand the differential response of these plants to the same nanopesticide stressor. (shrink)

α-l-Threofuranosyl nucleic acid is an artificial genetic polymer composed of vicinal 2',3'-phosphodiester bonds linking adjacent threofuranosyl nucleosides. TNA is one of a small number of genetic polymers that are both highly resistant to nuclease digestion and capable of cross-pairing with DNA and RNA. Although an efficient method for synthesizing TNA nucleosides has been reported, very few advances have been made in the synthesis of phosphorylated TNA compounds. Here, we describe a highly efficient method for synthesizing α-l-threofuranosyl nucleoside 3'-monophosphates, 3'-phosphoroimidazolides, and (...) 3'-triphosphates bearing the four genetic bases of adenine, cytosine, thymine, and guanine. We suggest that this strategy, which provides access to grams of tNMPs, hundreds of milligrams of 2-MeImptNs, and tens of milligrams of tNTPs, will help advance the use of TNA monomers in exobiology and biotechnology applications. (shrink)

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

Given the predominant use of heat-retaining materials in urban areas, numerous studies have addressed the urban heat island mitigation potential of various "cool" options, such as vegetation and high-albedo surfaces. The influence of altered radiational properties of such surfaces affects not only the air temperature within a microclimate, but more importantly the interactions of long- and short-wave radiation fluxes with the human body. Minimal studies have assessed how cool surfaces affect thermal comfort via changes in absorbed radiation by a human (...) using real-world, rather than modeled, urban field data. The purpose of the current study is to assess the changes in the absorbed radiation by a human-a critical component of human energy budget models-based on surface type on hot summer days C). Field tests were conducted using a high-end microclimate station under predominantly clear sky conditions over ten surfaces with higher sky view factors in Lubbock, Texas. Three methods were used to measure and estimate R abs: a cylindrical radiation thermometer, a net radiometer, and a theoretical estimation model. Results over dry surfaces suggest that the use of high-albedo surfaces to reduce overall urban heat gain may not improve acute human thermal comfort in clear conditions due to increased reflected radiation. Further, the use of low-cost instrumentation, such as the CRT, shows potential in quantifying radiative heat loads within urban areas at temporal scales of 5-10 min or greater, yet further research is needed. Fine-scale radiative information in urban areas can aid in the decision-making process for urban heat mitigation using non-vegetated urban surfaces, with surface type choice is dependent on the need for short-term thermal comfort, or reducing cumulative heat gain to the urban fabric. (shrink)

© 2017, Springer-Verlag Berlin Heidelberg.Eddy covariance datasets have provided insight into climate determinants of net ecosystem productivity and evapotranspiration in natural ecosystems for decades, but most EC studies were published in serial fashion such that one study’s result became the following study’s hypothesis. This approach reflects the hypothetico-deductive process by focusing on previously derived hypotheses. A synthesis of this type of sequential inference reiterates subjective biases and may amplify past assumptions about the role, and relative importance, of controls over ecosystem (...) metabolism. Long-term EC datasets facilitate an alternative approach to synthesis: the use of inductive data-based analyses to re-examine past deductive studies of the same ecosystem. Here we examined the seasonal climate determinants of NEP and ET by analyzing a 15-year EC time-series from a subalpine forest using an ensemble of Artificial Neural Networks at the half-day time-step. We extracted relative rankings of climate drivers and driver–response relationships directly from the dataset with minimal a priori assumptions. The ANN analysis revealed temperature variables as primary climate drivers of NEP and daytime ET, when all seasons are considered, consistent with the assembly of past studies. New relations uncovered by the ANN approach include the role of soil moisture in driving daytime NEP during the snowmelt period, the nonlinear response of NEP to temperature across seasons, and the low relevance of summer rainfall for NEP or ET at the same daytime/nighttime time step. These new results offer a more complete perspective of climate–ecosystem interactions at this site than traditional deductive analyses alone. (shrink)

To design and evaluate eddy current-nulled convex optimized diffusion encoding gradient waveforms for efficient diffusion tensor imaging that is free of eddy current-induced image distortions.The EN-CODE framework was used to generate diffusion-encoding waveforms that are eddy current-compensated. The EN-CODE DTI waveform was compared with the existing eddy current-nulled twice refocused spin echo sequence as well as monopolar and non-eddy current-compensated CODE in terms of echo time and image distortions. Comparisons were made in simulations, phantom experiments, and neuro imaging in 10 (...) healthy volunteers.The EN-CODE sequence achieved eddy current compensation with a significantly shorter TE than TRSE and a slightly shorter TE than MONO. Intravoxel signal variance was lower in phantoms with EN-CODE than with MONO and not different from TRSE, indicating good robustness to eddy current-induced image distortions. Mean fractional anisotropy values in brain edges were also significantly lower with EN-CODE than with MONO ) and not different from TRSE.The EN-CODE sequence eliminated eddy current-induced image distortions in DTI with a TE comparable to MONO and substantially shorter than TRSE. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine. (shrink)

We developed a dynamic multimedia fate and transport model to predict the time-dependent accumulation of metallic engineered nanomaterials across environmental media. nanoFate considers a wider range of processes and environmental subcompartments than most previous models and considers ENM releases to compartments in a manner that reflects their different patterns of use and disposal. As an example, we simulated ten years of release of nano CeO2, CuO, TiO2, and ZnO in the San Francisco Bay area. Results show that even soluble metal (...) oxide ENMs may accumulate as nanoparticles in the environment in sufficient concentrations to exceed the minimum toxic threshold in freshwater and some soils, though this is more likely with high-production ENMs such as TiO2 and ZnO. Fluctuations in weather and release scenario may lead to circumstances where predicted ENM concentrations approach acute toxic concentrations. The fate of these ENMs is to mostly remain either aggregated or dissolved in agricultural lands receiving biosolids and in freshwater or marine sediments. Comparison to previous studies indicates the importance of some key model aspects including climatic and temporal variations, how ENMs may be released into the environment, and the effect of compartment composition on predicted concentrations. (shrink)

The collagenous extracellular matrix of skeletal muscle functions to transmit force, protect sensitive structures, and generate passive tension to resist stretch. The mechanical properties of the ECM change with age, atrophy, and neuromuscular pathologies, resulting in an increase in the relative amount of collagen and an increase in stiffness. Although numerous studies have focused on the effect of muscle fibrosis on passive muscle stiffness, few have examined how these structural changes may compromise contractile performance. Here we combine a mathematical model (...) and experimental manipulations to examine how changes in the mechanical properties of the ECM constrain the ability of muscle fibers and fascicles to radially expand and how such a constraint may limit active muscle shortening. We model the mechanical interaction between a contracting muscle and the ECM using a constant volume, pressurized, fiber-wound cylinder. Our model shows that as the proportion of a muscle cross section made up of ECM increases, the muscle's ability to expand radially is compromised, which in turn restricts muscle shortening. In our experiments, we use a physical constraint placed around the muscle to restrict radial expansion during a contraction. Our experimental results are consistent with model predictions and show that muscles restricted from radial expansion undergo less shortening and generate less mechanical work under identical loads and stimulation conditions. This work highlights the intimate mechanical interaction between contractile and connective tissue structures within skeletal muscle and shows how a deviation from a healthy, well-tuned relationship can compromise performance. (shrink)

© 2017 CERN.A measurement of the inclusive pp→tt+X production cross section in the τ+jets final state using only the hadronic decays of the τ lepton is presented. The measurement is performed using 20.2 fb-1 of proton-proton collision data recorded at a center-of-mass energy of s=8 TeV with the ATLAS detector at the Large Hadron Collider. The cross section is measured via a counting experiment by imposing a set of selection criteria on the identification and kinematic variables of the reconstructed particles (...) and jets, and on event kinematic variables and characteristics. The production cross section is measured to be σtt=239±29 pb, which is in agreement with the measurements in other final states and the theoretical predictions at this center-of-mass energy. (shrink)

The wide variety of treatment options that exist for glioblastoma, including surgery, ionizing radiation, anti-neoplastic chemotherapies, anti-angiogenic therapies, and active or passive immunotherapies, all may alter aspects of vascular permeability within the tumor and/or normal parenchyma. These alterations manifest as changes in the degree of contrast enhancement or T2-weighted signal hyperintensity on standard anatomic MRI scans, posing a potential challenge for accurate radiographic response assessment for identifying anti-tumor effects. The current review highlights the challenges that remain in differentiating true disease (...) progression from changes due to radiation therapy, including pseudoprogression and radionecrosis, as well as immune or inflammatory changes that may occur as either an undesired result of cytotoxic therapy or as a desired consequence of immunotherapies. (shrink)

© 2017, CERN for the benefit of the ATLAS collaboration.This paper presents a measurement of the polarisation of W bosons from tt¯ decays, reconstructed in events with one high-pT lepton and at least four jets. Data from pp collisions at the LHC were collected at s = 8 TeV and correspond to an integrated luminosity of 20.2 fb- 1. The angle θ∗ between the b-quark from the top quark decay and a direct W boson decay product in the W boson (...) rest frame is sensitive to the W boson polarisation. Two different W decay products are used as polarisation analysers: the charged lepton and the down-type quark for the leptonically and hadronically decaying W boson, respectively. The most precise measurement of the W boson polarisation via the distribution of cos θ∗ is obtained using the leptonic analyser and events in which at least two of the jets are tagged as b-quark jets. The fitted fractions of longitudinal, left- and right-handed polarisation states are F0=0.709±0.019, FL=0.299±0.015 and FR=-0.008±0.014, and are the most precisely measured W boson polarisation fractions to date. Limits on anomalous couplings of the Wtb vertex are set. (shrink)

© 2017 Beal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Understanding dietary patterns is vital to reducing the number of people experiencing hunger, micronutrient deficiencies, and overweight or obesity. We characterize global trends in dietary quality by estimating micronutrient density of the food supply, prevalence of inadequate intake of 14 micronutrients, and average (...) prevalence of inadequate intake of these micronutrients for all countries between 1961 and2011. Over this 50-year period, the estimated prevalence of inadequate intakes of micronutrients has declined in all regions due to increased total production of food and/or micronutrient density. This decline has been particularly strong in East and Southeast Asia and weaker in South Asia and sub-Saharan Africa. Sub-Saharan Africa is the only region where dietary micronutrient density has declined over this 50-year period. At the global level, micronutrients with the lowest levels of adequate estimated intake are calcium, iron, vitamin A, and zinc, but there are strong differences between countries and regions. Fortification has reduced the estimated prevalence of inadequate micronutrient intakes in all low-income regions, except South Asia. The food supply in many countries is still far below energy requirements, which suggests a need to increase the availability and accessibility of nutritious foods. Countries where the food energy supply is adequate show a very large variation in dietary quality, and in many of these countries people would benefit from more diverse diets with a greater proportion of micronutrient-dense foods. Dietary quality can be improved through fortification, biofortification, and agricultural diversification, as well as efforts to improve access to and use of micronutrient-dense foods and nutritional knowledge. Reducing poverty and increasing education, especially of women, are integral to sustainably addressing malnutrition. (shrink)

After the financial crisis in 2008 and amid growing concerns about climate change, interest in systemic alternatives to neoliberal capitalism is growing. This cultural shift helps explain the enthusiasm from political elites, media, and academics that greeted the launch of Evergreen Co-operative Corporation in 2009. Based in Cleveland Ohio, Evergreen is a network of worker-owned co-operatives with scalability and replicability woven into its design. But how warranted is the broad-based enthusiasm around Evergreen? Is this a model that can be replicated (...) across North America as its founders suggest? Based on site visits and stakeholder interviews, we argue that there are important limits on desires to reproduce the “Cleveland Model.” However, its ambitions for scalability and replicability position it to contribute to the important project of movement building that can facilitate the policy change needed to scale up the co-operative alternative. (shrink)

© 2017, The Author.Measurements of top quark spin observables in tt¯ events are presented based on 20.2 fb−1 of s=8 TeV proton-proton collisions recorded with the ATLAS detector at the LHC. The analysis is performed in the dilepton final state, characterised by the presence of two isolated leptons. There are 15 observables, each sensitive to a different coefficient of the spin density matrix of tt¯ production, which are measured independently. Ten of these observables are measured for the first time. All (...) of them are corrected for detector resolution and acceptance effects back to the parton and stable-particle levels. The measured values of the observables at parton level are compared to Standard Model predictions at next-to-leading order in QCD. The corrected distributions at stable-particle level are presented and the means of the distributions are compared to Monte Carlo predictions. No significant deviation from the Standard Model is observed for any observable.[Figure not available: see fulltext.]. (shrink)

© 2017, CERN for the benefit of the ATLAS collaboration.Two searches for new phenomena in final states containing a same-flavour opposite-sign lepton pair, jets, and large missing transverse momentum are presented. These searches make use of proton–proton collision data, collected during 2015 and 2016 at a centre-of-mass energy s=13 TeV by the ATLAS detector at the large hadron collider, which correspond to an integrated luminosity of 14.7fb-1. Both searches target the pair production of supersymmetric particles, squarks or gluinos, which decay (...) to final states containing a same-flavour opposite-sign lepton pair via one of two mechanisms: a leptonically decaying Z boson in the final state, leading to a peak in the dilepton invariant-mass distribution around the Z boson mass; and decays of neutralinos, yielding a kinematic endpoint in the dilepton invariant-mass spectrum. The data are found to be consistent with the Standard Model expectation. Results are interpreted in simplified models of gluino-pair production, and provide sensitivity to gluinos with masses as large as 1.70 TeV. (shrink)

Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to (...) genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50, which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1, showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. (shrink)

© 2016The W boson angular distribution in events with high transverse momentum jets is measured using data collected by the ATLAS experiment from proton–proton collisions at a centre-of-mass energy s=8 TeV at the Large Hadron Collider, corresponding to an integrated luminosity of 20.3 fb−1. The focus is on the contributions to W+jets processes from real W emission, which is achieved by studying events where a muon is observed close to a high transverse momentum jet. At small angular separations, these contributions (...) are expected to be large. Various theoretical models of this process are compared to the data in terms of the absolute cross-section and the angular distributions of the muon from the leptonic W decay. (shrink)

For transforming organizations and community health, the San Francisco Department of Public Health, Population Health Division has embraced population health lean—an innovation and performance improvement management system based on the Toyota Production System, collective impact methods, and human-centered design. We cover lean, collective impact, human-centered design, making quality decisions, building effective teams, and leading organization transformations. Our core values include humility, respect for people, teamwork, embracing challenges, genchi genbutsu, and kaizen.

© 2016 The AuthorA search for dark matter pair production in association with a Higgs boson decaying to a pair of bottom quarks is presented, using 3.2 fb−1of pp collisions at a centre-of-mass energy of 13 TeV collected by the ATLAS detector at the LHC. The decay of the Higgs boson is reconstructed as a high-momentum bb¯ system with either a pair of small-radius jets, or a single large-radius jet with substructure. The observed data are found to be consistent with (...) the expected backgrounds. Results are interpreted using a simplified model with a Z′gauge boson mediating the interaction between dark matter and the Standard Model as well as a two-Higgs-doublet model containing an additional Z′boson which decays to a Standard Model Higgs boson and a new pseudoscalar Higgs boson, the latter decaying into a pair of dark matter particles. (shrink)

© 2016 The AuthorA search is presented for new resonances decaying to a W or Z boson and a Higgs boson in the ℓ+ℓ−bb¯, ℓνbb¯, and νν¯bb¯ channels in pp collisions at s=13 TeV with the ATLAS detector at the Large Hadron Collider using a total integrated luminosity of 3.2 fb−1. The search is conducted by looking for a localized excess in the WH/ZH invariant or transverse mass distribution. No significant excess is observed, and the results are interpreted in terms (...) of constraints on a simplified model based on a phenomenological Lagrangian of heavy vector triplets. (shrink)

© 2017, The Author.Same- and opposite-sign charge asymmetries are measured in lepton+jets tt¯ events in which a b-hadron decays semileptonically to a soft muon, using data corresponding to an integrated luminosity of 20.3 fb−1 from proton-proton collisions at a centre-of-mass energy of s=√8 TeV collected with the ATLAS detector at the Large Hadron Collider at CERN. The charge asymmetries are based on the charge of the lepton from the top-quark decay and the charge of the soft muon from the semileptonic (...) decay of a b-hadron and are measured in a fiducial region corresponding to the experimental acceptance. Four CP asymmetries are measured and are found to be compatible with zero and consistent with the Standard Model.[Figure not available: see fulltext.]. (shrink)

© 2017 American Chemical Society.Food waste makes up approximately 15% of municipal solid waste generated in the United States, and 95% of food waste is ultimately landfilled. Its bioavailable carbon and nutrient content makes it a major contributor to landfill methane emissions, but also presents an important opportunity for energy recovery. This paper presents the first detailed analysis of monthly food waste generation in California at a county level, and its potential contribution to the state's energy production. Scenarios that rely (...) on excess capacity at existing anaerobic digester and solid biomass combustion facilities, and alternatives that allow for new facility construction, are developed and modeled. Potential monthly electricity generation from the conversion of gross food waste using a combination of AD and combustion varies from 420 to 700 MW, averaging 530 MW. At least 66% of gross high moisture solids and 23% of gross low moisture solids can be treated using existing county infrastructure, and this fraction increases to 99% of high moisture solids and 55% of low moisture solids if waste can be shipped anywhere within the state. Biogas flaring practices at AD facilities can reduce potential energy production by 10 to 40%.. (shrink)

© 2017 Liebschner et al.The crystallographic maps that are routinely used during the structure-solution workflow are almost always model-biased because model information is used for their calculation. As these maps are also used to validate the atomic models that result from model building and refinement, this constitutes an immediate problem: anything added to the model will manifest itself in the map and thus hinder the validation. OMIT maps are a common tool to verify the presence of atoms in the model. (...) The simplest way to compute an OMIT map is to exclude the atoms in question from the structure, update the corresponding structure factors and compute a residual map. It is then expected that if these atoms are present in the crystal structure, the electron density for the omitted atoms will be seen as positive features in this map. This, however, is complicated by the flat bulk-solvent model which is almost universally used in modern crystallographic refinement programs. This model postulates constant electron density at any voxel of the unit-cell volume that is not occupied by the atomic model. Consequently, if the density arising from the omitted atoms is weak then the bulk-solvent model may obscure it further. A possible solution to this problem is to prevent bulk solvent from entering the selected OMIT regions, which may improve the interpretative power of residual maps. This approach is called a polder map. Polder OMIT maps can be particularly useful for displaying weak densities of ligands, solvent molecules, side chains, alternative conformations and residues both in terminal regions and in loops. The tools described in this manuscript have been implemented and are available in PHENIX.Residual OMIT maps can be improved by the selective exclusion of bulk solvent from the OMIT region. (shrink)

© 2017, The Author.Ratios of top-quark pair to Z-boson cross sections measured from proton-proton collisions at the LHC centre-of-mass energies of s=13 TeV, 8 TeV, and 7 TeV are presented by the ATLAS Collaboration. Single ratios, at a given s for the two processes and at different s for each process, as well as double ratios of the two processes at different s, are evaluated. The ratios are constructed using previously published ATLAS measurements of the tt¯ and Z-boson production cross (...) sections, corrected to a common phase space where required, and a new analysis of Z → ℓ+ℓ− where ℓ = e, μ at s=13 TeV performed with data collected in 2015 with an integrated luminosity of 3.2 fb−1. Correlations of systematic uncertainties are taken into account when evaluating the uncertainties in the ratios. The correlation model is also used to evaluate the combined cross section of the Z → e+e− and the Z → μ+μ− channels for each s value. The results are compared to calculations performed at next-to-next-to-leading-order accuracy using recent sets of parton distribution functions. The data demonstrate significant power to constrain the gluon distribution function for the Bjorken-x values near 0.1 and the light-quark sea for x < 0.02.[Figure not available: see fulltext.]. (shrink)

© 2017, CERN for the benefit of the ATLAS collaboration.The production of two prompt J/ ψ mesons, each with transverse momenta pT> 8.5 GeV and rapidity |y| < 2.1, is studied using a sample of proton-proton collisions at s=8 TeV, corresponding to an integrated luminosity of 11.4 fb- 1 collected in 2012 with the ATLAS detector at the LHC. The differential cross-section, assuming unpolarised J/ ψ production, is measured as a function of the transverse momentum of the lower-pTJ/ ψ meson, (...) di-J/ ψpT and mass, the difference in rapidity between the two J/ ψ mesons, and the azimuthal angle between the two J/ ψ mesons. The fraction of prompt pair events due to double parton scattering is determined by studying kinematic correlations between the two J/ ψ mesons. The total and double parton scattering cross-sections are compared with predictions. The effective cross-section of double parton scattering is measured to be σeff= 6.3 ± 1.6 ± 1.0 mb. (shrink)

© 2016 John Wiley & Sons LtdMolecular hydrogen is an atmospheric trace gas with a large microbe-mediated soil sink, yet cycling of this compound throughout ecosystems is poorly understood. Measurements of the sources and sinks of H2 in various ecosystems are sparse, resulting in large uncertainties in the global H2 budget. Constraining the H2 cycle is critical to understanding its role in atmospheric chemistry and climate. We measured H2 fluxes at high frequency in a temperate mixed deciduous forest for 15 (...) months using a tower-based flux-gradient approach to determine both the soil-atmosphere and the net ecosystem flux of H2. We found that Harvard Forest is a net H2 sink with soils as the dominant H2 sink and aboveground canopy emissions as the dominant H2 source. Aboveground emissions of H2 were an unexpected and substantial component of the ecosystem H2 flux, reducing net ecosystem uptake by 30% of that calculated from soil uptake alone. Soil uptake was highly seasonal, positively correlated with soil temperature and negatively correlated with environmental variables relevant to diffusion into soils. Soil microbial H2 uptake was correlated with rhizosphere respiration rates, and H2 metabolism yielded up to 2% of the energy gleaned by microbes from carbon substrate respiration. Here, we elucidate key processes controlling the biosphere–atmosphere exchange of H2 and raise new questions regarding the role of aboveground biomass as a source of atmospheric H2 and mechanisms linking soil H2 and carbon cycling. Results from this study should be incorporated into modeling efforts to predict the response of the H2 soil sink to changes in anthropogenic H2 emissions and shifting soil conditions with climate and land-use change. (shrink)

© 2017 American Physical Society.Information engines can use structured environments as a resource to generate work by randomizing ordered inputs and leveraging the increased Shannon entropy to transfer energy from a thermal reservoir to a work reservoir. We give a broadly applicable expression for the work production of an information engine, generally modeled as a memoryful channel that communicates inputs to outputs as it interacts with an evolving environment. The expression establishes that an information engine must have more than one (...) memory state in order to leverage input environment correlations. To emphasize this functioning, we designed an information engine powered solely by temporal correlations and not by statistical biases, as employed by previous engines. Key to this is the engine's ability to synchronize - the engine automatically returns to a desired dynamical phase when thrown into an unwanted, dissipative phase by corruptions in the input - that is, by unanticipated environmental fluctuations. This self-correcting mechanism is robust up to a critical level of corruption, beyond which the system fails to act as an engine. We give explicit analytical expressions for both work and critical corruption level and summarize engine performance via a thermodynamic-function phase diagram over engine control parameters. The results reveal a thermodynamic mechanism based on nonergodicity that underlies error correction as it operates to support resilient engineered and biological systems. (shrink)

© 2016 The AuthorThis Letter presents a search for new resonances with mass larger than 250 GeV, decaying to a Z boson and a photon. The dataset consists of an integrated luminosity of 3.2 fb−1 of pp collisions collected at s=13 TeV with the ATLAS detector at the Large Hadron Collider. The Z bosons are identified through their decays either to charged, light, lepton pairs or to hadrons. The data are found to be consistent with the expected background in the (...) whole mass range investigated and upper limits are set on the production cross section times decay branching ratio to Zγ of a narrow scalar boson with mass between 250 GeV and 2.75 TeV. (shrink)

Childhood exposure to ultraviolet radiation is a major risk factor for the development of melanoma later in life. However, it is challenging to accurately determine personal outdoor exposure to UVR, specifically erythemally weighted UVR, due to technological constraints, variable time-activity patterns, and the influence of outdoor environmental design. To address this challenge, this study utilized mobile and stationary techniques to examine the UVEry exposures of 14 children in a schoolyard in Lubbock, TX, in spring 2016. The aims of the study (...) were to examine the influence of artificial shade on personal UVEry exposures and to assess full sun exposure ratios within the same playground microenvironment. On average, personal wrist dosimeters worn during play in the sun measured 18% of the total onsite UVEry measured by a stationary UV pyranometer. Shade was found to significantly reduce the personal UVEry exposures by 55%, UVB280-315 nm exposures by 91%, and the overall solar radiation by 84%. Substantial benefits can be garnered through focused design of children's recreational space to utilize shade-both natural and artificial-to reduce UVR exposures during play, and to extend safe outdoor stays. Finally, although the wrist is a practical location for a dosimeter, it often underestimates full exposures, particularly during physical activity. (shrink)

© 2017 The Author. Published by S. Karger AG, Basel.Small cell carcinoma of the vagina is rare, so rare in fact that the total number reported in English-language journals is less than 30. Due to this extremely low incidence, no specific treatment guidelines have been established, and most of what is clinically known is derived from a handful of single case reports. However, as befitting its highly aggressive histologic features, which are reminiscent of small cell lung cancer, first-line treatment is (...) modeled after SCLC. Herein is reported the case of a 51-year-old African-American patient with metastatic biopsy-proven small cell carcinoma of the vagina that progressed through multiple therapies: first-line cisplatin and etoposide and radiotherapy, followed by the tumor macrophage-stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per protocol preceded a mandated rechallenge with cisplatin and etoposide. RECIST v.1.1 tumor progression on both RRx-001 and cisplatin/etoposide was accompanied by central necrosis in several of the enlarged lymph nodes and hepatic metastases, which may have been evidence of pseudoprogression, accounting for her ongoing longer-than-expected survival, since the necrotic tissue may have primed the activity of the PD-1 inhibitor. The lack of response to RRx-001 is hypothesized to have correlated with sparse tumor macrophage infiltration, seen on pre- and post-treatment biopsies, since the mechanism of action of RRx-001 relates to stimulation of tumor-associated macrophages. (shrink)

© 2016 American Chemical Society.Hydrostatic pressure applied using diamond anvil cells has been widely explored to modulate physical properties of materials by tuning their lattice degree of freedom. Independently, electrical field is able to tune the electronic degree of freedom of functional materials via, for example, the field-effect transistor configuration. Combining these two orthogonal approaches would allow discovery of new physical properties and phases going beyond the known phase space. Such experiments are, however, technically challenging and have not been demonstrated. (...) Herein, we report a feasible strategy to prepare and measure FETs in a DAC by lithographically patterning the nanodevices onto the diamond culet. Multiple-terminal FETs were fabricated in the DAC using few-layer MoS2 and BN as the channel semiconductor and dielectric layer, respectively. It is found that the mobility, conductance, carrier concentration, and contact conductance of MoS2 can all be significantly enhanced with pressure. We expect that the approach could enable unprecedented ways to explore new phases and properties of materials under coupled mechano-electrostatic modulation. (shrink)

Investigations of gut microbiomes have shed light on the diversity and genetic content of these communities, and helped shape our understanding of how host-associated microorganisms influence host physiology, behavior, and health. Despite the importance of gut microbes to metazoans, our understanding of the changes in diversity and composition across the alimentary tract, and the source of the resident community are limited. Here, using community metagenomics and 16S rRNA gene sequencing, we assess microbial community diversity and coding potential in the foregut, (...) midgut, and hindgut of a juvenile Panchlora cockroach, which resides in the refuse piles of the leaf-cutter ant species Atta colombica. We found a significant shift in the microbial community structure and coding potential throughout the three gut sections of Panchlora sp., and through comparison with previously generated metagenomes of the cockroach's food source and niche, we reveal that this shift in microbial community composition is influenced by the ecosystems in which Panchlora sp. occurs. While the foregut is composed of microbes that likely originate from the symbiotic fungus gardens of the ants, the midgut and hindgut are composed of a microbial community that is likely cockroach-specific. Analogous to mammalian systems, the midgut and hindgut appear to be dominated by Firmicutes and Bacteroidetes with the capacity for polysaccharide degradation, suggesting they may assist in the degradation of dietary plant material. Our work underscores the prominence of community changes throughout gut microbiomes and highlights ecological factors that underpin the structure and function of the symbiotic microbial communities of metazoans. (shrink)

Förster resonance energy transfer is a widely used single-molecule technique for measuring nanoscale distances from changes in the non-radiative transfer of energy between donor and acceptor fluorophores. For macromolecules and complexes this observed transfer efficiency is used to infer changes in molecular conformation under differing experimental conditions. However, sometimes shifts are observed in the FRET efficiency even when there is strong experimental evidence that the molecular conformational state is unchanged. We investigate ways in which such discrepancies can arise from kinetic (...) effects. We show that significant shifts can arise from the interplay between excitation kinetics, orientation diffusion of fluorophores, separation diffusion of fluorophores, and non-emitting quenching. (shrink)

© 2017, The Author.A measurement of the ZZ production cross section in the ℓ−ℓ+ℓ′ −ℓ′ + and ℓ−ℓ+νν¯ channels in proton-proton collisions at s=8TeV at the Large Hadron Collider at CERN, using data corresponding to an integrated luminosity of 20.3 fb−1 collected by the ATLAS experiment in 2012 is presented. The fiducial cross sections for ZZ → ℓ−ℓ+ℓ′ −ℓ′ + and ZZ→ ℓ−ℓ+νν¯ are measured in selected phase-space regions. The total cross section for ZZ events produced with both Z bosons (...) in the mass range 66 to 116 GeV is measured from the combination of the two channels to be 7.3 ± 0.4 ± 0.3− 0.1− 0.2 pb, which is consistent with the Standard Model prediction of 6. 6− 0.6+ 0.7 pb. The differential cross sections in bins of various kinematic variables are presented. The differential event yield as a function of the transverse momentum of the leading Z boson is used to set limits on anomalous neutral triple gauge boson couplings in ZZ production.[Figure not available: see fulltext.]. (shrink)

© 2017, The Author.Differential cross sections are presented for the prompt and non-prompt production of the hidden-charm states X and ψ, in the decay mode J/ψπ+π−, measured using 11.4 fb−1 of pp collisions at s=8 TeV by the ATLAS detector at the LHC. The ratio of cross-sections X/ψ is also given, separately for prompt and non-prompt components, as well as the non-prompt fractions of X and ψ. Assuming independent single effective lifetimes for non-prompt X and ψ production gives RB=ℬ+any)ℬ→J/ψπ+π−)/ℬ+any)ℬ→J/ψπ+π−)=±0.08)×10−2 separating (...) short- and long-lived contributions, assuming that the short-lived component is due to Bc decays, gives RB = ± 0.11) × 10−2, with the fraction of non-prompt X produced via Bc decays for pT) > 10 GeV being ± 2 ± 5)%. The distributions of the dipion invariant mass in the X and ψ decays are also measured and compared to theoretical predictions.[Figure not available: see fulltext.]. (shrink)

Although transcriptional regulation is fundamental to understanding bacterial physiology, the targets of most bacterial transcription factors are not known. Comparative genomics has been used to identify likely targets of some of these transcription factors, but these predictions typically lack experimental support. Here, we used mutant fitness data, which measures the importance of each gene for a bacterium's growth across many conditions, to test regulatory predictions from RegPrecise, a curated collection of comparative genomics predictions. Because characterized transcription factors often have correlated (...) fitness with one of their targets, correlated fitness patterns provide support for the comparative genomics predictions. At a false discovery rate of 3%, we identified significant cofitness for at least one target of 158 TFs in 107 ortholog groups and from 24 bacteria. Thus, high-throughput genetics can be used to identify a high-confidence subset of the sequence-based regulatory predictions. (shrink)

© 2017, CERN for the benefit of the ATLAS collaboration.A measurement of the tt¯ Z and tt¯ W production cross sections in final states with either two same-charge muons, or three or four leptons is presented. The analysis uses a data sample of proton–proton collisions at s=13 TeV recorded with the ATLAS detector at the Large Hadron Collider in 2015, corresponding to a total integrated luminosity of 3.2 fb- 1. The inclusive cross sections are extracted using likelihood fits to signal (...) and control regions, resulting in σtt¯Z= 0.9 ± 0.3 pb and σtt¯W= 1.5 ± 0.8 pb, in agreement with the Standard Model predictions. (shrink)

© 2017, CERN for the benefit of the ATLAS collaboration.A measurement of the calorimeter response to isolated charged hadrons in the ATLAS detector at the LHC is presented. This measurement is performed with 3.2 nb- 1 of proton–proton collision data at s=7 TeV from 2010 and 0.1 nb- 1 of data at s=8 TeV from 2012. A number of aspects of the calorimeter response to isolated hadrons are explored. After accounting for energy deposited by neutral particles, there is a 5% (...) discrepancy in the modelling, using various sets of Geant4 hadronic physics models, of the calorimeter response to isolated charged hadrons in the central calorimeter region. The description of the response to anti-protons at low momenta is found to be improved with respect to previous analyses. The electromagnetic and hadronic calorimeters are also examined separately, and the detector simulation is found to describe the response in the hadronic calorimeter well. The jet energy scale uncertainty and correlations in scale between jets of different momenta and pseudorapidity are derived based on these studies. The uncertainty is 2–5% for jets with transverse momenta above 2 TeV, where this method provides the jet energy scale uncertainty for ATLAS. (shrink)

This paper takes international climate change law norms as a given, and instead turns to their implementation in domestic courts as one of the possible enforcement strategies for advancing the protection of the climate. The enforcement of climate change law is overviewed at the international law level and portrayed in the context of domestic courts. In order to flesh out such a proposal as the latter, the viability of procedural rights, as embodied in Principle 10 of the Rio Declaration, is (...) assessed and compared with substantive rights as a possible leverage of enforcement in the sphere of climate change law. Such leverage is pictured out within the first two judicial decisions applying international law for the protection of the climate in domestic courts, namely the Urgenda decision from the Netherlands, and the Leghari decision from Pakistan. The legacy of each of those is evaluated under the prong of judicial globalization and international climate policy. The paper argues that the interpretive techniques deployed in this strand of cases are poised to further advance international climate change law, not only on a substantive plane, but also on a procedural plane, especially with regard to the standing of individuals and NGOs. Indeed, the paper holds such a judicial turn to be a viable enforcement mechanism in the field of climate change law and policy, especially in the aftermath of the 2015 Paris Agreement. (shrink)

© 2017 Wiley Periodicals, Inc.The Sapir-Whorf hypothesis holds that human thought is shaped by language, leading speakers of different languages to think differently. This hypothesis has sparked both enthusiasm and controversy, but despite its prominence it has only occasionally been addressed in computational terms. Recent developments support a view of the Sapir-Whorf hypothesis in terms of probabilistic inference. This view may resolve some of the controversy surrounding the Sapir-Whorf hypothesis, and may help to normalize the hypothesis by linking it to (...) established principles that also explain other phenomena. On this view, effects of language on nonlinguistic cognition or perception reflect standard principles of inference under uncertainty. (shrink)

Brazil’s Ministério Público, or prosecuting agency, is a unique institution. Unlike public prosecution entities in other countries, such as federal prosecutors in the United States, the MP is the primary enforcer of Brazil’s environmental laws and initiates the vast majority of environmental public civil actions. In the United States, most environmental suits are citizen suits filed by private actors, but in Brazil, the MP files almost 96 percent of those same cases. These actions have improved compliance with environmental laws and (...) helped contribute to the MP’s reputation as an independent body, separate from the corruption known to plague other governmental bodies in Brazil. While the MP’s lawsuits have proven effective, they are adversarial in nature and preclude more cooperative means of regulation. Additionally, prosecutors within the MP feel as if they must respond to every complaint they receive, which keeps them from prioritizing the largest environmental harms. As scholars like Robert Kagan, John Scholz, and John Braithwaite have noted: a rigid, punitive style of enforcement may not be appropriate in all situations with all regulated actors. This legalistic manner of enforcement creates tension between the MP, the regulated actors, and environmental agencies; slows the enforcement process; and strains the MP’s limited resources. This paper proposes creating a second branch of the MP’s offices: a more mediative style of enforcement for less culpable actors, in line with actions that certain members of the MP’s office have already begun to take. Prosecutors within this mediative branch would go beyond judicial remedies and would collaborate with environmental agencies, government bodies, and community members to solve challenging environmental problems. This plan is already within the range of autonomy given to the MP and would allow the MP to retain its reputation as an independent, un-corruptible enforcer, while also remedying some of the problems and inefficiencies that result from the current rigid, legalistic enforcement style. (shrink)

Scholars of democratic experimentalism and new governance rightly criticize the static allocations of authority found in the American traditional federalism framework for its rigidity and potential to stifle innovation at the state and local levels. Nevertheless, this critique underappreciates the level of experimentation harbored by this framework, as witnessed in the dynamic interaction between the various levels of government. This dynamic interplay, which is very much on exhibit with respect to climate change regulation, is far from being devoid of new (...) policy innovation. It also exhibits something that, in the long run, may be just as important—the adoption, at local and regional levels, of policy innovations developed at other levels, often on a national or international scale. Hence not only do we see policy innovation arising out of traditional American federalism, but also “scale innovation.” This backdrop is important when exploring the best governance models for emerging environmental issues, the full scope of which are still poorly understood. Where does climate change adaptation fit? Does it illustrate the market failures and potential gamesmanship that have justified traditional federalism models, complete with a strong policymaking role for the federal government, or is it best addressed as a problem ripe for the multilevel governance solutions offered by collaborative models? Any attempt to answer this question must match up the problems presented by adaption to the tools and processes offered by more traditional environmental federalism and that offered by collaborative governance regimes. I argue that, as understood so far, adaptation calls for a hybrid between traditional federalism models and models suggested by democratic experimentalism and collaborative governance. Commentators uniformly predict that climate change will bring with it dynamic, complex and potentially abrupt, eco-systemic change at varying scales. Thus, for some, regulations in the service of adaptation should seek to reduce the vulnerability of ecosystems to abrupt and uncertain change and to reinforce the resiliency of such systems. This process would seem ideally suited to democratic experimentalism—a problem in need of a regulatory system that is constantly monitoring its effects and updating its requirements. But for others, adaptation will necessitate national infrastructure and regulations, which, together with needed minimum standards applicable to intrastate issues, will call for federal, state and local regulation similar to traditional federalism. I conclude that a model for a hybrid of the two—experimentalism and federalism—might be found in the cooperative federalism structure of EPA’s recent Clean Power Plan. Here, states are held accountable by the federal government to regulatory goals of their own making. Thus the Plan incorporates flexibility of experimentalism but also the minimum standards and backstop of federal regulation. (shrink)

The Migratory Bird Treaty Act protects 1,027 bird species—the vast majority of native birds in the United States and its territories—by criminalizing the taking, killing, or selling of any migratory bird or bird part.3 Beginning in the 1960s, the Fish and Wildlife Service began prosecuting industrial firms for “incidental take,” the unintentional taking or killing of migratory birds. Incidental take is a negative externality of industry: firms kill birds—a natural resource shared by all—and do not compensate for their loss. A (...) split in authority consequently arose on whether the strict liability misdemeanor of the MBTA criminalizes such unintentional killings. In response to concerns of incidental take, the FWS is now in a rulemaking process, by which it hopes to establish an incidental-take permit program, allowing firms to purchase take permits, compensate the FWS for estimated bird take, and evade or at least minimize the risk of prosecution. While the incidental-take circuit split has already received scholarly attention elsewhere, this Article tackles a larger conservation question, drawing on scholarship in the fields of emissions trading and conservation banking. This Article proposes two alternative market-based solutions to the menace of incidental take. First, the Bird Tax: a Pigouvian tax that seeks to correct the inefficient market outcome that results in uncompensated industrial and nonindustrial incidental take. Second, the North American Bird Market: a trilateral initiative building upon decades of successful environmental cooperation between Canada, the United States, and Mexico. By incentivizing clean energy, requiring industry to internalize its bird take, and promoting habitat restoration, the Bird Market is an efficient and clean theoretical solution to the menace of incidental take and the looming threat to our continent’s shared birdscape. In contrast to a comprehensive, upstream Bird Tax that targets both industrial and nonindustrial incidental take, the Bird Market would entail potentially restrictive financial and logistical costs due to its limited focus on the regulation of industrial take. As such, it is possible that the Bird Market is a mere flight of fancy—a thought experiment whose doom radiates from its very core—and nothing more. Despite these challenges, this Article’s presentation of the Market serves three other purposes. First, the Market serves as a vehicle to expose the sobering truth that the MBTA and incidental-take prosecutions are an expressive, but ultimately fruitless conservation mechanism. Second, the Market is an investigation of how to quantify and trade death with the goal of conserving life. Finally, the exposition of the Market and the critique of the MBTA is an attempt to tightrope walk the seemingly unbridgeable legal-analytical rift between the ritualized law and economics of Ronald Coase,4 and the touchy-feelythrow-your-hands-up-in-the-air neorealism of Arthur Allan Leff. Ultimately, because incidental industrial take is only a minor anthropogenic stressor, the Market will fail to achieve meaningful conservation goals for the same reasons that incidental-take prosecutions under the MBTA fail to achieve these goals. August 2016 marked the centennial of the first migratory bird treaty with Canada. One hundred years have passed, and this Article calls upon Congress to abandon its ancient conservation precepts and supplement our treaties and the MBTA with a meaningful international habitat-restoration program. (shrink)