Showing papers by "University of Wisconsin-Madison published in 2010"

Global threats to human water security and river biodiversity

Abstract: Protecting the world’s freshwater resources requires diagnosing threats over a broad range of scales, from global to local. Here we present the first worldwide synthesis to jointly consider human and biodiversity perspectives on water security using a spatial framework that quantifies multiple stressors and accounts for downstream impacts. We find that nearly 80% of the world’s population is exposed to high levels of threat to water security. Massive investment in water technology enables rich nations to offset high stressor levels without remedying their underlying causes, whereas less wealthy nations remain vulnerable. A similar lack of precautionary investment jeopardizes biodiversity, with habitats associated with 65% of continental discharge classified as moderately to highly threatened. The cumulative threat framework offers a tool for prioritizing policy and management responses to this crisis, and underscores the necessity of limiting threats at their source instead of through costly remediation of symptoms in order to assure global water security for both humans and freshwater biodiversity.

Guaranteed Minimum-Rank Solutions of Linear Matrix Equations via Nuclear Norm Minimization

Abstract: The affine rank minimization problem consists of finding a matrix of minimum rank that satisfies a given system of linear equality constraints. Such problems have appeared in the literature of a diverse set of fields including system identification and control, Euclidean embedding, and collaborative filtering. Although specific instances can often be solved with specialized algorithms, the general affine rank minimization problem is NP-hard because it contains vector cardinality minimization as a special case. In this paper, we show that if a certain restricted isometry property holds for the linear transformation defining the constraints, the minimum-rank solution can be recovered by solving a convex optimization problem, namely, the minimization of the nuclear norm over the given affine space. We present several random ensembles of equations where the restricted isometry property holds with overwhelming probability, provided the codimension of the subspace is sufficiently large. The techniques used in our analysis have strong parallels in the compressed sensing framework. We discuss how affine rank minimization generalizes this preexisting concept and outline a dictionary relating concepts from cardinality minimization to those of rank minimization. We also discuss several algorithmic approaches to minimizing the nuclear norm and illustrate our results with numerical examples.

progressiveMauve: Multiple Genome Alignment with Gene Gain, Loss and Rearrangement

Abstract: Background Multiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms.

Review of Particle Physics

Abstract: This biennial Review summarizes much of particle physics. Using data from previous editions, plus 2158 new measurements from 551 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. 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 the Standard Model, particle detectors, probability, and statistics. Among the 108 reviews are many that are new or heavily revised including those on neutrino mass, mixing, and oscillations, QCD, top quark, CKM quark-mixing matrix, V-ud & V-us, V-cb & V-ub, fragmentation functions, particle detectors for accelerator and non-accelerator physics, magnetic monopoles, cosmological parameters, and big bang cosmology.

Stereotactic Body Radiation Therapy for Inoperable Early Stage Lung Cancer

Abstract: Context Patients with early stage but medically inoperable lung cancer have a poor rate of primary tumor control (30%-40%) and a high rate of mortality (3-year survival, 20%-35%) with current management. Objective To evaluate the toxicity and efficacy of stereotactic body radiation therapy in a high-risk population of patients with early stage but medically inoperable lung cancer. Design, Setting, and Patients Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1-T2N0M0 non–small cell tumors (measuring Main Outcome Measures The primary end point was 2-year actuarial primary tumor control; secondary end points were disease-free survival (ie, primary tumor, involved lobe, regional, and disseminated recurrence), treatment-related toxicity, and overall survival. Results A total of 59 patients accrued, of which 55 were evaluable (44 patients with T1 tumors and 11 patients with T2 tumors) with a median follow-up of 34.4 months (range, 4.8-49.9 months). Only 1 patient had a primary tumor failure; the estimated 3-year primary tumor control rate was 97.6% (95% confidence interval [CI], 84.3%-99.7%). Three patients had recurrence within the involved lobe; the 3-year primary tumor and involved lobe (local) control rate was 90.6% (95% CI, 76.0%-96.5%). Two patients experienced regional failure; the local-regional control rate was 87.2% (95% CI, 71.0%-94.7%). Eleven patients experienced disseminated recurrence; the 3-year rate of disseminated failure was 22.1% (95% CI, 12.3%-37.8%). The rates for disease-free survival and overall survival at 3 years were 48.3% (95% CI, 34.4%-60.8%) and 55.8% (95% CI, 41.6%-67.9%), respectively. The median overall survival was 48.1 months (95% CI, 29.6 months to not reached). Protocol-specified treatment-related grade 3 adverse events were reported in 7 patients (12.7%; 95% CI, 9.6%-15.8%); grade 4 adverse events were reported in 2 patients (3.6%; 95% CI, 2.7%-4.5%). No grade 5 adverse events were reported. Conclusion Patients with inoperable non–small cell lung cancer who received stereotactic body radiation therapy had a survival rate of 55.8% at 3 years, high rates of local tumor control, and moderate treatment-related morbidity.

Quantum information with Rydberg atoms

Abstract: Rydberg atoms with principal quantum number $n⪢1$ have exaggerated atomic properties including dipole-dipole interactions that scale as ${n}^{4}$ and radiative lifetimes that scale as ${n}^{3}$. It was proposed a decade ago to take advantage of these properties to implement quantum gates between neutral atom qubits. The availability of a strong long-range interaction that can be coherently turned on and off is an enabling resource for a wide range of quantum information tasks stretching far beyond the original gate proposal. Rydberg enabled capabilities include long-range two-qubit gates, collective encoding of multiqubit registers, implementation of robust light-atom quantum interfaces, and the potential for simulating quantum many-body physics. The advances of the last decade are reviewed, covering both theoretical and experimental aspects of Rydberg-mediated quantum information processing.

Network traffic characteristics of data centers in the wild

Abstract: Although there is tremendous interest in designing improved networks for data centers, very little is known about the network-level traffic characteristics of data centers today. In this paper, we conduct an empirical study of the network traffic in 10 data centers belonging to three different categories, including university, enterprise campus, and cloud data centers. Our definition of cloud data centers includes not only data centers employed by large online service providers offering Internet-facing applications but also data centers used to host data-intensive (MapReduce style) applications). We collect and analyze SNMP statistics, topology and packet-level traces. We examine the range of applications deployed in these data centers and their placement, the flow-level and packet-level transmission properties of these applications, and their impact on network and link utilizations, congestion and packet drops. We describe the implications of the observed traffic patterns for data center internal traffic engineering as well as for recently proposed architectures for data center networks.

Geologically current plate motions

Abstract: SUMMARY We describe best-fitting angular velocities and MORVEL, a new closure-enforced set of angular velocities for the geologically current motions of 25 tectonic plates that collectively occupy 97 per cent of Earth's surface. Seafloor spreading rates and fault azimuths are used to determine the motions of 19 plates bordered by mid-ocean ridges, including all the major plates. Six smaller plates with little or no connection to the mid-ocean ridges are linked to MORVEL with GPS station velocities and azimuthal data. By design, almost no kinematic information is exchanged between the geologically determined and geodetically constrained subsets of the global circuit—MORVEL thus averages motion over geological intervals for all the major plates. Plate geometry changes relative to NUVEL-1A include the incorporation of Nubia, Lwandle and Somalia plates for the former Africa plate, Capricorn, Australia and Macquarie plates for the former Australia plate, and Sur and South America plates for the former South America plate. MORVEL also includes Amur, Philippine Sea, Sundaland and Yangtze plates, making it more useful than NUVEL-1A for studies of deformation in Asia and the western Pacific. Seafloor spreading rates are estimated over the past 0.78 Myr for intermediate and fast spreading centres and since 3.16 Ma for slow and ultraslow spreading centres. Rates are adjusted downward by 0.6–2.6 mm yr−1 to compensate for the several kilometre width of magnetic reversal zones. Nearly all the NUVEL-1A angular velocities differ significantly from the MORVEL angular velocities. The many new data, revised plate geometries, and correction for outward displacement thus significantly modify our knowledge of geologically current plate motions. MORVEL indicates significantly slower 0.78-Myr-average motion across the Nazca–Antarctic and Nazca–Pacific boundaries than does NUVEL-1A, consistent with a progressive slowdown in the eastward component of Nazca plate motion since 3.16 Ma. It also indicates that motions across the Caribbean–North America and Caribbean–South America plate boundaries are twice as fast as given by NUVEL-1A. Summed, least-squares differences between angular velocities estimated from GPS and those for MORVEL, NUVEL-1 and NUVEL-1A are, respectively, 260 per cent larger for NUVEL-1 and 50 per cent larger for NUVEL-1A than for MORVEL, suggesting that MORVEL more accurately describes historically current plate motions. Significant differences between geological and GPS estimates of Nazca plate motion and Arabia–Eurasia and India–Eurasia motion are reduced but not eliminated when using MORVEL instead of NUVEL-1A, possibly indicating that changes have occurred in those plate motions since 3.16 Ma. The MORVEL and GPS estimates of Pacific–North America plate motion in western North America differ by only 2.6 ± 1.7 mm yr−1, ≈25 per cent smaller than for NUVEL-1A. The remaining difference for this plate pair, assuming there are no unrecognized systematic errors and no measurable change in Pacific–North America motion over the past 1–3 Myr, indicates deformation of one or more plates in the global circuit. Tests for closure of six three-plate circuits indicate that two, Pacific–Cocos–Nazca and Sur–Nubia–Antarctic, fail closure, with respective linear velocities of non-closure of 14 ± 5 and 3 ± 1 mm yr−1 (95 per cent confidence limits) at their triple junctions. We conclude that the rigid plate approximation continues to be tremendously useful, but—absent any unrecognized systematic errors—the plates deform measurably, possibly by thermal contraction and wide plate boundaries with deformation rates near or beneath the level of noise in plate kinematic data.

Visible light photocatalysis as a greener approach to photochemical synthesis

Abstract: Light can be considered an ideal reagent for environmentally friendly, 'green' chemical synthesis; unlike many conventional reagents, light is non-toxic, generates no waste, and can be obtained from renewable sources. Nevertheless, the need for high-energy ultraviolet radiation in most organic photochemical processes has limited both the practicality and environmental benefits of photochemical synthesis on industrially relevant scales. This perspective describes recent approaches to the use of metal polypyridyl photocatalysts in synthetic organic transformations. Given the remarkable photophysical properties of these complexes, these new transformations, which use Ru(bpy)(3)(2+) and related photocatalysts, can be conducted using almost any source of visible light, including both store-bought fluorescent light bulbs and ambient sunlight. Transition metal photocatalysis thus represents a promising strategy towards the development of practical, scalable industrial processes with great environmental benefits.

High-performance lithium-ion anodes using a hierarchical bottom-up approach

Abstract: Si-based Li-ion battery anodes have recently received great attention, as they offer specific capacity an order of magnitude beyond that of conventional graphite. The applications of this transformative technology require synthesis routes capable of producing safe and easy-to-handle anode particles with low volume changes and stable performance during battery operation. Herein, we report a large-scale hierarchical bottom-up assembly route for the formation of Si on the nanoscale--containing rigid and robust spheres with irregular channels for rapid access of Li ions into the particle bulk. Large Si volume changes on Li insertion and extraction are accommodated by the particle's internal porosity. Reversible capacities over five times higher than that of the state-of-the-art anodes (1,950 mA h g(-1)) and stable performance are attained. The synthesis process is simple, low-cost, safe and broadly applicable, providing new avenues for the rational engineering of electrode materials with enhanced conductivity and power.

Call of the wild: antibiotic resistance genes in natural environments

Abstract: Antibiotic-resistant pathogens are profoundly important to human health, but the environmental reservoirs of resistance determinants are poorly understood The origins of antibiotic resistance in the environment is relevant to human health because of the increasing importance of zoonotic diseases as well as the need for predicting emerging resistant pathogens This Review explores the presence and spread of antibiotic resistance in non-agricultural, non-clinical environments and demonstrates the need for more intensive investigation on this subject

Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival.

Abstract: Summary Background Previous results from our phase 3 randomised trial showed that adding cetuximab to primary radiotherapy increased overall survival in patients with locoregionally advanced squamous-cell carcinoma of the head and neck (LASCCHN) at 3 years. Here we report the 5-year survival data, and investigate the relation between cetuximabinduced rash and survival. Methods Patients with LASCCHN of the oropharynx, hypopharynx, or larynx with measurable disease were randomly allocated in a 1:1 ratio to receive either comprehensive head and neck radiotherapy alone for 6–7 weeks or radiotherapy plus weekly doses of cetuximab: 400 mg/m² initial dose, followed by seven weekly doses at 250 mg/m². Randomisation was done with an adaptive minimisation technique to balance assignments across stratifi cation factors of Karnofsky performance score, T stage, N stage, and radiation fractionation. The trial was un-blinded. The primary endpoint was locoregional control, with a secondary endpoint of survival. Following discussions with the US Food and Drug Administration, the dataset was locked, except for queries to the sites about overall survival, before our previous report in 2006, so that an independent review could be done. Analyses were done on an intention-to-treat basis. Following completion of treatment, patients underwent physical examination and radiographic imaging every 4 months for 2 years, and then every 6 months thereafter . The trial is registered at www.ClinicalTrials.gov , number NCT00004227. Findings Patients were randomly assigned to receive radiotherapy with (n=211) or without (n=213) cetuximab, and all patients were followed for survival. Updated median overall survival for patients treated with cetuximab and radiotherapy was 49·0 months (95% CI 32·8–69·5) versus 29·3 months (20·6–41·4) in the radiotherapy-alone group (hazard ratio [HR] 0·73, 95% CI 0·56–0·95; p=0·018). 5-year overall survival was 45·6% in the cetuximab-plus-radiotherapy group and 36·4% in the radiotherapy-alone group. Additionally, for the patients treated with cetuximab, overall survival was signifi cantly improved in those who experienced an acneiform rash of at least grade 2 severity compared with patients with no rash or grade 1 rash (HR 0·49, 0·34–0·72; p=0·002). Interpretation For patients with LASCCHN, cetuximab plus radiotherapy signifi cantly improves overall survival at 5 years compared with radiotherapy alone, confi rming cetuximab plus radiotherapy as an important treatment option in this group of patients. Cetuximab-treated patients with prominent cetuximab-induced rash (grade 2 or above) have better survival than patients with no or grade 1 rash.

The NIH Roadmap Epigenomics Mapping Consortium

Abstract: The NIH Roadmap Epigenomics Mapping Consortium aims to produce a public resource of epigenomic maps for stem cells and primary ex vivo tissues selected to represent the normal counterparts of tissues and organ systems frequently involved in human disease.

Pathophysiology of Sleep Apnea

Abstract: Sleep-induced apnea and disordered breathing refers to intermittent, cyclical cessations or reductions of airflow, with or without obstructions of the upper airway (OSA). In the presence of an anat...

Genome sequencing and analysis of the model grass Brachypodium distachyon

Abstract: Three subfamilies of grasses, the Ehrhartoideae, Panicoideae and Pooideae, provide the bulk of human nutrition and are poised to become major sources of renewable energy. Here we describe the genome sequence of the wild grass Brachypodium distachyon (Brachypodium), which is, to our knowledge, the first member of the Pooideae subfamily to be sequenced. Comparison of the Brachypodium, rice and sorghum genomes shows a precise history of genome evolution across a broad diversity of the grasses, and establishes a template for analysis of the large genomes of economically important pooid grasses such as wheat. The high-quality genome sequence, coupled with ease of cultivation and transformation, small size and rapid life cycle, will help Brachypodium reach its potential as an important model system for developing new energy and food crops.

Stereotactic body radiation therapy: The report of AAPM Task Group 101

Abstract: Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy (SBRT). The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures. Additionally, suggestions for developing consistent documentation for prescribing, reporting, and recording SBRT treatment delivery is provided.

`The HSP70 chaperone machinery: J proteins as drivers of functional specificity

Abstract: Heat shock 70 kDa proteins (HSP70s) are ubiquitous molecular chaperones that function in a myriad of biological processes, modulating polypeptide folding, degradation and translocation across membranes, and protein-protein interactions. This multitude of roles is not easily reconciled with the universality of the activity of HSP70s in ATP-dependent client protein-binding and release cycles. Much of the functional diversity of the HSP70s is driven by a diverse class of cofactors: J proteins. Often, multiple J proteins function with a single HSP70. Some target HSP70 activity to clients at precise locations in cells and others bind client proteins directly, thereby delivering specific clients to HSP70 and directly determining their fate.

Use of normal tissue complication probability models in the clinic.

Abstract: The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) review summarizes the currently available three-dimensional dose/volume/outcome data to update and refine the normal tissue dose/volume tolerance guidelines provided by the classic Emami et al. paper published in 1991. A "clinician's view" on using the QUANTEC information in a responsible manner is presented along with a description of the most commonly used normal tissue complication probability (NTCP) models. A summary of organ-specific dose/volume/outcome data, based on the QUANTEC reviews, is included.

Niche conservatism as an emerging principle in ecology and conservation biology.

Abstract: The diversity of life is ultimately generated by evolution, and much attention has focused on the rapid evolution of ecological traits. Yet, the tendency for many ecological traits to instead remain similar over time [niche conservatism (NC)] has many consequences for the fundamental patterns and processes studied in ecology and conservation biology. Here, we describe the mounting evidence for the importance of NC to major topics in ecology (e.g. species richness, ecosystem function) and conservation (e.g. climate change, invasive species). We also review other areas where it may be important but has generally been overlooked, in both ecology (e.g. food webs, disease ecology, mutualistic interactions) and conservation (e.g. habitat modification). We summarize methods for testing for NC, and suggest that a commonly used and advocated method (involving a test for phylogenetic signal) is potentially problematic, and describe alternative approaches. We suggest that considering NC: (1) focuses attention on the within-species processes that cause traits to be conserved over time, (2) emphasizes connections between questions and research areas that are not obviously related (e.g. invasives, global warming, tropical richness), and (3) suggests new areas for research (e.g. why are some clades largely nocturnal? why do related species share diseases?).

Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium

Abstract: Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.

The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients

Abstract: Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesu, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Task Force 2 Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Task Force 3 Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruna, La Coruna, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Independent Reviewers Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium.

Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes

Abstract: During periods of feeding, pancreatic islets secrete insulin to maintain glucose homeostasis — a rhythmic process that is disturbed in people with diabetes. Experiments in mice now show that the pancreatic islets contain their own biological clock, which orchestrates insulin secretion during the sleep–wake cycle. The transcription factors CLOCK and BMAL1 are vital for this process, and mice with defective copies of the genes Clock and Bmal1 develop hypoinsulinaemia and diabetes. By demonstrating that a local tissue clock integrates circadian and metabolic signals in pancreatic β-cells, this work suggests that circadian analyses are crucial for deeper understanding of metabolic phenotypes, as well as for the treatment of metabolic diseases such as type 2 diabetes. Circadian rhythms control many physiological functions. During periods of feeding, pancreatic islets secrete insulin to maintain glucose homeostasis — a rhythmic process that is disturbed in people with diabetes. These authors show that pancreatic islets contain their own clock: they have self-sustained circadian oscillations of CLOCK and BMAL1 genes and proteins, which are vital for the regulation of circadian rhythms. Without this clock, a cascade of cellular failure and pathology initiates the onset of diabetes mellitus. The molecular clock maintains energy constancy by producing circadian oscillations of rate-limiting enzymes involved in tissue metabolism across the day and night1,2,3. During periods of feeding, pancreatic islets secrete insulin to maintain glucose homeostasis, and although rhythmic control of insulin release is recognized to be dysregulated in humans with diabetes4, it is not known how the circadian clock may affect this process. Here we show that pancreatic islets possess self-sustained circadian gene and protein oscillations of the transcription factors CLOCK and BMAL1. The phase of oscillation of islet genes involved in growth, glucose metabolism and insulin signalling is delayed in circadian mutant mice, and both Clock5,6 and Bmal17 (also called Arntl) mutants show impaired glucose tolerance, reduced insulin secretion and defects in size and proliferation of pancreatic islets that worsen with age. Clock disruption leads to transcriptome-wide alterations in the expression of islet genes involved in growth, survival and synaptic vesicle assembly. Notably, conditional ablation of the pancreatic clock causes diabetes mellitus due to defective β-cell function at the very latest stage of stimulus–secretion coupling. These results demonstrate a role for the β-cell clock in coordinating insulin secretion with the sleep–wake cycle, and reveal that ablation of the pancreatic clock can trigger the onset of diabetes mellitus.

Practicing Intersectionality in Sociological Research: A Critical Analysis of Inclusions, Interactions, and Institutions in the Study of Inequalities*

Abstract: In this article we ask what it means for sociologists to practice intersectionality as a theoretical and methodological approach to inequality. What are the implications for choices of subject matter and style of work? We distinguish three styles of understanding intersectionality in practice: group-centered, process-centered, and system-centered. The first, emphasizes placing multiply-marginalized groups and their perspectives at the center of the research. The second, intersectionality as a process, highlights power as relational, seeing the interactions among variables as multiplying oppressions at various points of intersection, and drawing attention to unmarked groups. Finally, seeing intersectionality as shaping the entire social system pushes analysis away from associating specific inequalities with unique institutions, instead looking for processes that are fully interactive, historically co-determining, and complex. Using several examples of recent, highly regarded qualitative studies, we draw attention to the comparative, contextual, and complex dimensions of sociological analysis that can be missing even when race, class, and gender are explicitly brought together.

An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells

Abstract: The aryl hydrocarbon receptor (AHR) has been known to cause immunosuppression after binding dioxin. It has recently been discovered that the receptor may be central to T cell differentiation into FoxP3 + regulatory T cells (Tregs) versus Th17 cells. In this paper, we demonstrate that kynurenine, the first breakdown product in the IDO-dependent tryptophan degradation pathway, activates the AHR. We furthermore show that this activation leads to AHR-dependent Treg generation. We additionally investigate the dependence of TGF-β on the AHR for optimal Treg generation, which may be secondary to the upregulation of this receptor that is seen in T cells postexposure to TGF-β. These results shed light on the relationship of IDO to the generation of Tregs, in addition to highlighting the central importance of the AHR in T cell differentiation. All tissues and cells were derived from mice.

Disturbance and landscape dynamics in a changing world

Abstract: Disturbance regimes are changing rapidly, and the consequences of such changes for ecosystems and linked social-ecological systems will be profound. This paper synthesizes current understanding of disturbance with an emphasis on fundamental contributions to contemporary landscape and ecosystem ecology, then identifies future research priorities. Studies of disturbance led to insights about heterogeneity, scale, and thresholds in space and time and catalyzed new paradigms in ecology. Because they create vegetation patterns, disturbances also establish spatial patterns of many ecosystem processes on the landscape. Drivers of global change will produce new spatial patterns, altered disturbance regimes, novel trajectories of change, and surprises. Future disturbances will continue to provide valuable opportunities for studying pattern-process interactions. Changing disturbance regimes will produce acute changes in ecosystems and ecosystem services over the short (years to decades) and long-term (centuries and beyond). Future research should address questions related to (1) disturbances as catalysts of rapid ecological change, (2) interactions among disturbances, (3) relationships between disturbance and society, especially the intersection of land use and disturbance, and (4) feedbacks from disturbance to other global drivers. Ecologists should make a renewed and concerted effort to understand and anticipate the causes and consequences of changing disturbance regimes.

Effects of medical therapies on retinopathy progression in type 2 diabetes.

Abstract: BACKGROUND We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy. METHODS In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy. RESULTS At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29). CONCLUSIONS Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.)