Showing papers by "University of Rochester published in 2011"
Katholieke Universiteit Leuven1, Oslo University Hospital2, University of Pennsylvania3, University of Rochester4, Medical College of Wisconsin5, Roswell Park Cancer Institute6, Massachusetts Institute of Technology7, Harvard University8, Wayne State University9, University of British Columbia10, University of Oslo11, Medical University of Warsaw12, University of Liège13, University of Toronto14, Polish Academy of Sciences15
TL;DR: The photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells as discussed by the authors, which can prolong survival in patients with inoperable cancers and significantly improve quality of life.
Abstract: Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. CA Cancer J Clin 2011;61:250-281. V C
3,770 citations
University of Nebraska Medical Center1, University of Manitoba2, Memorial Sloan Kettering Cancer Center3, Fred Hutchinson Cancer Research Center4, City of Hope National Medical Center5, University of Rochester6, University of Texas MD Anderson Cancer Center7, University of Minnesota8, University of Florida9
TL;DR: This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002 and developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis.
Abstract: This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.
2,664 citations
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TL;DR: Optical antennas are devices that convert freely propagating optical radiation into localized energy, and vice versa as mentioned in this paper, and hold promise for enhancing the performance and efficiency of photodetection, light emission and sensing.
Abstract: Optical antennas are devices that convert freely propagating optical radiation into localized energy, and vice versa. They enable the control and manipulation of optical fields at the nanometre scale, and hold promise for enhancing the performance and efficiency of photodetection, light emission and sensing. Although many of the properties and parameters of optical antennas are similar to their radiowave and microwave counterparts, they have important differences resulting from their small size and the resonant properties of metal nanostructures. This Review summarizes the physical properties of optical antennas, provides a summary of some of the most important recent developments in the field, discusses the potential applications and identifies the future challenges and opportunities.
2,557 citations
Harvard University1, Cincinnati Children's Hospital Medical Center2, Duke University3, University of Arkansas for Medical Sciences4, Icahn School of Medicine at Mount Sinai5, Johns Hopkins University School of Medicine6, National Institutes of Health7, University of Southampton8, St Mary's Hospital9, LSU Health Sciences Center Shreveport10, University of Rochester Medical Center11, Rutgers University12, University of California, San Diego13, Boston Children's Hospital14, University of Colorado Denver15, Oregon Health & Science University16, University of Tennessee Health Science Center17, Food and Drug Administration18, University of California, Irvine19, Scripps Health20, University of Manitoba21, Children's National Medical Center22, University of Rochester23, University of Minnesota24
TL;DR: The National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy, which include a consensus definition for food allergy.
Abstract: Food allergy is an important public health problem that affects children and adults and may be increasing in prevalence. Despite the risk of severe allergic reactions and even death, there is no current treatment for food allergy: the disease can only be managed by allergen avoidance or treatment of symptoms. The diagnosis and management of food allergy also may vary from one clinical practice setting to another. Finally, because patients frequently confuse nonallergic food reactions, such as food intolerance, with food allergies, there is an unfounded belief among the public that food allergy prevalence is higher than it truly is. In response to these concerns, the National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy. These Guidelines are intended for use by a wide variety of health care professionals, including family practice physicians, clinical specialists, and nurse practitioners. The Guidelines include a consensus definition for food allergy, discuss comorbid conditions often associated with food allergy, and focus on both IgE-mediated and non-IgE-mediated reactions to food. Topics addressed include the epidemiology, natural history, diagnosis, and management of food allergy, as well as the management of severe symptoms and anaphylaxis. These Guidelines provide 43 concise clinical recommendations and additional guidance on points of current controversy in patient management. They also identify gaps in the current scientific knowledge to be addressed through future research.
2,014 citations
TL;DR: Metabolic tracer analysis revealed a Myc-dependent metabolic pathway linking glutaminolysis to the biosynthesis of polyamines, which may represent a general mechanism for metabolic reprogramming under patho-physiological conditions.
1,632 citations
Beckman Research Institute1, City of Hope National Medical Center2, University of Rochester3, Case Western Reserve University4, Wake Forest University5, Yale Cancer Center6, Memorial Sloan Kettering Cancer Center7, State University of New York Upstate Medical University8, Georgetown University9, University of California, Davis10, Cornell University11
TL;DR: A risk stratification schema can establish the risk of chemotherapy toxicity in older adults and Geriatric assessment variables independently predicted therisk of toxicity.
Abstract: Purpose Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity. Patients and Methods Patients age 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events. Results In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P .001).
1,383 citations
TL;DR: The T2K experiment observes indications of ν (μ) → ν(e) appearance in data accumulated with 1.43×10(20) protons on target, and under this hypothesis, the probability to observe six or more candidate events is 7×10(-3), equivalent to 2.5σ significance.
Abstract: The T2K experiment observes indications of nu(mu) -> nu(mu) e appearance in data accumulated with 1.43 x 10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Delta m(23)(2)| = 2.4 x 10(-3) eV(2), sin(2)2 theta(23) = 1 and sin(2)2 theta(13) = 0, the expected number of such events is 1.5 +/- 0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7 x 10(-3), equivalent to 2.5 sigma significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2 theta(13) < 0.28(0.34) for delta(CP) = 0 and a normal (inverted) hierarchy.
1,361 citations
National Institutes of Health1, City of Hope National Medical Center2, University of Würzburg3, Bosch4, University of British Columbia5, University of Arizona6, University of Barcelona7, University of Oslo8, University of Rochester9, Oregon Health & Science University10, Cleveland Clinic11, University of Nebraska Medical Center12
TL;DR: The dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, is described and the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MyD88 mutations are supported.
Abstract: The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-κB signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-β. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations.
1,346 citations
TL;DR: The Society for Vascular Surgery and the American Venous Forum have developed clinical practice guidelines for the care of patients with varicose veins of the lower limbs and pelvis, including recommendations on the management of superficial and perforating vein incompetence in patients with associated, more advanced chronic venous diseases.
1,162 citations
TL;DR: The finding that the binding of STAU1 to m RNAs can be transactivated by lncRNAs uncovers an unexpected strategy that cells use to recruit proteins to mRNAs and mediate the decay of these mRNas.
Abstract: Staufen 1 (STAU1)-mediated messenger RNA decay (SMD) involves the degradation of translationally active mRNAs whose 3'-untranslated regions (3' UTRs) bind to STAU1, a protein that binds to double-stranded RNA. Earlier studies defined the STAU1-binding site within ADP-ribosylation factor 1 (ARF1) mRNA as a 19-base-pair stem with a 100-nucleotide apex. However, we were unable to identify comparable structures in the 3' UTRs of other targets of SMD. Here we show that STAU1-binding sites can be formed by imperfect base-pairing between an Alu element in the 3' UTR of an SMD target and another Alu element in a cytoplasmic, polyadenylated long non-coding RNA (lncRNA). An individual lncRNA can downregulate a subset of SMD targets, and distinct lncRNAs can downregulate the same SMD target. These are previously unappreciated functions of non-coding RNAs and Alu elements. Not all mRNAs that contain an Alu element in the 3' UTR are targeted for SMD even in the presence of a complementary lncRNA that targets other mRNAs for SMD. Most known trans-acting RNA effectors consist of fewer than 200 nucleotides, and these include small nucleolar RNAs and microRNAs. Our finding that the binding of STAU1 to mRNAs can be transactivated by lncRNAs uncovers an unexpected strategy that cells use to recruit proteins to mRNAs and mediate the decay of these mRNAs. We name these lncRNAs half-STAU1-binding site RNAs (1/2-sbsRNAs).
1,096 citations
TL;DR: Blood B10 cells were present in 91 patients with rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, autoimmune vesiculobullous skin disease, or multiple sclerosis, and were expanded in some cases as occurs in mice with autoimmune disease.
TL;DR: This review will help illustrate both the strengths and potential pitfalls of common mitochondrial membrane potential dyes, and highlight best-usage approaches for their efficacious application in life sciences research.
Abstract: Fluorescent probes for monitoring mitochondrial membrane potential are frequently used for assessing mitochondrial function, particularly in the context of cell fate determination in biological and biomedical research. However, valid interpretation of results obtained with such probes requires careful consideration of numerous controls, as well as possible effects of non-protonic charges on dye behavior. In this context, we provide an overview of some of the important technical considerations, controls, and parallel complementary assays that can be employed to help ensure appropriate interpretation of results, thus providing a practical usage guide for monitoring mitochondrial membrane potentials with cationic probes. In total, this review will help illustrate both the strengths and potential pitfalls of common mitochondrial membrane potential dyes, and highlight best-usage approaches for their efficacious application in life sciences research.
Harvard University1, Stanford University2, University of Washington3, University of Florida4, Boston University5, University of Colorado Denver6, University of Texas Southwestern Medical Center7, University of Rochester8, University of Pittsburgh9, University of Toronto10, University of California, San Francisco11, Washington University in St. Louis12, University of Texas Medical Branch13, Loyola University Chicago14, Rutgers University15, Princeton University16
TL;DR: It is shown that critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes that alter the status of these genes in the immune system.
Abstract: Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.
University of Nebraska Medical Center1, University of Manitoba2, Memorial Sloan Kettering Cancer Center3, Fred Hutchinson Cancer Research Center4, City of Hope National Medical Center5, University of Rochester6, University of Texas MD Anderson Cancer Center7, University of Minnesota8, University of Florida9
TL;DR: This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002 and developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis.
Abstract: This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.
University of California, Irvine1, Massachusetts Institute of Technology2, University of California, Los Angeles3, University of Pennsylvania4, University of Southern California5, National Institutes of Health6, Oregon Health & Science University7, University of Rochester8, Georgetown University9, University of Washington10, Medical University of South Carolina11, University of Lethbridge12, University of Illinois at Urbana–Champaign13, Emory University14, University of California, San Francisco15, Harvard University16, University of Michigan17, Cornell University18, University of Colorado Boulder19, Stanford University20
TL;DR: Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.
Abstract: Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.
TL;DR: In this paper, the authors demonstrate the squeezed-light enhancement of GEO600, which will be the GW observatory operated by the LIGO Scientific Collaboration in its search for GWs for the next 3-4 years.
Abstract: Around the globe several observatories are seeking the first direct detection of gravitational waves (GWs). These waves are predicted by Einstein’s general theory of relativity1 and are generated, for example, by black-hole binary systems2. Present GW detectors are Michelson-type kilometre-scale laser interferometers measuring the distance changes between mirrors suspended in vacuum. The sensitivity of these detectors at frequencies above several hundred hertz is limited by the vacuum (zero-point) fluctuations of the electromagnetic field. A quantum technology—the injection of squeezed light3—offers a solution to this problem. Here we demonstrate the squeezed-light enhancement of GEO 600, which will be the GW observatory operated by the LIGO Scientific Collaboration in its search for GWs for the next 3–4 years. GEO 600 now operates with its best ever sensitivity, which proves the usefulness of quantum entanglement and the qualification of squeezed light as a key technology for future GW astronomy4.
TL;DR: Conformational changes and reactions of Gtfs on surfaces are complex and modulate the pathogenesis of dental caries in situ, deserving further investigation.
Abstract: The importance of Streptococcus mutans in the etiology and pathogenesis of dental caries is certainly controversial, in part because excessive attention is paid to the numbers of S. mutans and acid production while the matrix within dental plaque has been neglected. S. mutans does not always dominate within plaque; many organisms are equally acidogenic and aciduric. It is also recognized that glucosyltransferases from S. mutans (Gtfs) play critical roles in the development of virulent dental plaque. Gtfs adsorb to enamel synthesizing glucans in situ, providing sites for avid colonization by microorganisms and an insoluble matrix for plaque. Gtfs also adsorb to surfaces of other oral microorganisms converting them to glucan producers. S. mutans expresses 3 genetically distinct Gtfs; each appears to play a different but overlapping role in the formation of virulent plaque. GtfC is adsorbed to enamel within pellicle whereas GtfB binds avidly to bacteria promoting tight cell clustering, and enhancing cohesion of plaque. GtfD forms a soluble, readily metabolizable polysaccharide and acts as a primer for GtfB. The behavior of soluble Gtfs does not mirror that observed with surface-adsorbed enzymes. Furthermore, the structure of polysaccharide matrix changes over time as a result of the action of mutanases and dextranases within plaque. Gtfs at distinct loci offer chemotherapeutic targets to prevent caries. Nevertheless, agents that inhibit Gtfs in solution frequently have a reduced or no effect on adsorbed enzymes. Clearly, conformational changes and reactions of Gtfs on surfaces are complex and modulate the pathogenesis of dental caries in situ, deserving further investigation.
TL;DR: Athletes’ perceptions of need satisfaction predicted positive outcomes associated with sport participation (vitality and positive affect), whereas need thwarting more consistently predicted maladaptive outcomes (disordered eating, burnout, depression, negative affect, and physical symptoms).
Abstract: Drawing from self-determination theory, three studies explored the social-environmental conditions that satisfy versus thwart psychological needs and, in turn, affect psychological functioning and well-being or ill-being. In cross-sectional Studies 1 and 2, structural equation modeling analyses supported latent factor models in which need satisfaction was predicted by athletes’ perceptions of autonomy support, and need thwarting was better predicted by coach control. Athletes’ perceptions of need satisfaction predicted positive outcomes associated with sport participation (vitality and positive affect), whereas need thwarting more consistently predicted maladaptive outcomes (disordered eating, burnout, depression, negative affect, and physical symptoms). In addition, athletes’ perceptions of psychological need thwarting were significantly associated with perturbed physiological arousal (elevated levels of secretory immunoglobulin A) prior to training. The final study involved the completion of a diary and...
TL;DR: In this article, the authors show that gene-distal enhancers are key contributors to gene expression patterns, exhibiting both sequence diversity and cell type specificity, contributing to a general model for enhancer function that involves direct enhancer-promoter contact.
TL;DR: In this article, the transverse momentum balance in dijet and γ/Z+jets events is used to measure the jet energy response in the CMS detector, as well as the transversal momentum resolution.
Abstract: Measurements of the jet energy calibration and transverse momentum resolution in CMS are presented, performed with a data sample collected in proton-proton collisions at a centre-of-mass energy of 7TeV, corresponding to an integrated luminosity of 36pb−1. The transverse momentum balance in dijet and γ/Z+jets events is used to measure the jet energy response in the CMS detector, as well as the transverse momentum resolution. The results are presented for three different methods to reconstruct jets: a calorimeter-based approach, the ``Jet-Plus-Track'' approach, which improves the measurement of calorimeter jets by exploiting the associated tracks, and the ``Particle Flow'' approach, which attempts to reconstruct individually each particle in the event, prior to the jet clustering, based on information from all relevant subdetectors
TL;DR: In this article, a sample of 824 solar and late-type stars with X-ray luminosities and rotation periods was used to study the relationship between rotation and stellar activity and derive a new estimate of the convective turnover time.
Abstract: We present a sample of 824 solar and late-type stars with X-ray luminosities and rotation periods. This is used to study the relationship between rotation and stellar activity and derive a new estimate of the convective turnover time. From an unbiased subset of this sample the power-law slope of the unsaturated regime, LX /L bolRo?, is fit as ? = ?2.70 ? 0.13. This is inconsistent with the canonical ? = ?2 slope to a confidence of 5?, and argues for an additional term in the dynamo number equation. From a simple scaling analysis this implies ??/??0.7, i.e., the differential rotation of solar-type stars gradually declines as they spin down. Supersaturation is observed for the fastest rotators in our sample and its parametric dependencies are explored. Significant correlations are found with both the corotation radius and the excess polar updraft, the latter theory providing a stronger dependence and being supported by other observations. We estimate mass-dependent empirical thresholds for saturation and supersaturation and map out three regimes of coronal emission. Late F-type stars are shown never to pass through the saturated regime, passing straight from supersaturated to unsaturated X-ray emission. The theoretical threshold for coronal stripping is shown to be significantly different from the empirical saturation threshold (Ro < 0.13), suggesting it is not responsible. Instead we suggest that a different dynamo configuration is at work in stars with saturated coronal emission. This is supported by a correlation between the empirical saturation threshold and the time when stars transition between convective and interface sequences in rotational spin-down models.
TL;DR: The present meta-analysis integrates the results from 168 empirical studies on differences between caregiving spouses, adult children, and children-in-law with regard to sociodemographic variables to arrive at a conclusion that higher levels of psychological distress among spouses are explained mostly--but not completely--byHigher levels of care provision.
Abstract: The present meta-analysis integrates the results from 168 empirical studies on differences between caregiving spouses, adult children, and children-in-law. Spouses differ from children and children-in-law significantly with regard to sociodemographic variables; also, they provide more support but report fewer care recipient behavior problems. Spouse caregivers report more depression symptoms, greater financial and physical burden, and lower levels of psychological well-being. Higher levels of psychological distress among spouses are explained mostly—but not completely—by higher levels of care provision. Few differences emerge between children and children-in-law, but children-in-law perceive the relationship with the care recipient as less positive and they report fewer uplifts of caregiving.
TL;DR: Closed-loop DBS paradigms, by modulating pathological oscillatory activity rather than the discharge rate of the BG-cortical networks, may afford more effective management of advanced PD.
TL;DR: No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances), and heart failure patients with New York Heart Association class I or II and LBBB derive substantial clinical benefit from CRT-D: a Reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias.
Abstract: Background—This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) trial. Methods and Results—Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients...
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11 Dec 2011-Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment
TL;DR: The T2K experiment as discussed by the authors is a long-baseline neutrino oscillation experiment whose main goal is to measure the last unknown lepton sector mixing angle by observing its appearance in a particle beam generated by the J-PARC accelerator.
Abstract: The T2K experiment is a long-baseline neutrino oscillation experiment Its main goal is to measure the last unknown lepton sector mixing angle {\theta}_{13} by observing {
u}_e appearance in a {
u}_{\mu} beam It also aims to make a precision measurement of the known oscillation parameters, {\Delta}m^{2}_{23} and sin^{2} 2{\theta}_{23}, via {
u}_{\mu} disappearance studies Other goals of the experiment include various neutrino cross section measurements and sterile neutrino searches The experiment uses an intense proton beam generated by the J-PARC accelerator in Tokai, Japan, and is composed of a neutrino beamline, a near detector complex (ND280), and a far detector (Super-Kamiokande) located 295 km away from J-PARC This paper provides a comprehensive review of the instrumentation aspect of the T2K experiment and a summary of the vital information for each subsystem
TL;DR: This work shows that in mammalian cells subjected to oxidative stress SIRT6 is recruited to the sites of DNA double-strand breaks (DSBs) and stimulates DSB repair, through both nonhomologous end joining and homologous recombination, thereby stimulating PARP1 poly-ADP-ribosylase activity and enhancing D SB repair under oxidative stress.
Abstract: Sirtuin 6 (SIRT6) is a mammalian homolog of the yeast Sir2 deacetylase. Mice deficient for SIRT6 exhibit genome instability. Here, we show that in mammalian cells subjected to oxidative stress SIRT6 is recruited to the sites of DNA double-strand breaks (DSBs) and stimulates DSB repair, through both nonhomologous end joining and homologous recombination. Our results indicate that SIRT6 physically associates with poly[adenosine diphosphate (ADP)-ribose] polymerase 1 (PARP1) and mono-ADP-ribosylates PARP1 on lysine residue 521, thereby stimulating PARP1 poly-ADP-ribosylase activity and enhancing DSB repair under oxidative stress.
TL;DR: A novel algorithm to reconstruct dynamic magnetic resonance imaging data from under-sampled k-t space data using the compact representation of the data in the Karhunen Louve transform (KLT) domain to exploit the correlations in the dataset.
Abstract: We introduce a novel algorithm to reconstruct dynamic magnetic resonance imaging (MRI) data from under-sampled k-t space data. In contrast to classical model based cine MRI schemes that rely on the sparsity or banded structure in Fourier space, we use the compact representation of the data in the Karhunen Louve transform (KLT) domain to exploit the correlations in the dataset. The use of the data-dependent KL transform makes our approach ideally suited to a range of dynamic imaging problems, even when the motion is not periodic. In comparison to current KLT-based methods that rely on a two-step approach to first estimate the basis functions and then use it for reconstruction, we pose the problem as a spectrally regularized matrix recovery problem. By simultaneously determining the temporal basis functions and its spatial weights from the entire measured data, the proposed scheme is capable of providing high quality reconstructions at a range of accelerations. In addition to using the compact representation in the KLT domain, we also exploit the sparsity of the data to further improve the recovery rate. Validations using numerical phantoms and in vivo cardiac perfusion MRI data demonstrate the significant improvement in performance offered by the proposed scheme over existing methods.
TL;DR: In this article, the authors studied the effect of collision centrality on the transverse momentum of PbPb collisions at the LHC with a data sample of 6.7 inverse microbarns.
Abstract: Jet production in PbPb collisions at a nucleon-nucleon center-of-mass energy of 2.76 TeV was studied with the CMS detector at the LHC, using a data sample corresponding to an integrated luminosity of 6.7 inverse microbarns. Jets are reconstructed using the energy deposited in the CMS calorimeters and studied as a function of collision centrality. With increasing collision centrality, a striking imbalance in dijet transverse momentum is observed, consistent with jet quenching. The observed effect extends from the lower cut-off used in this study (jet transverse momentum = 120 GeV/c) up to the statistical limit of the available data sample (jet transverse momentum approximately 210 GeV/c). Correlations of charged particle tracks with jets indicate that the momentum imbalance is accompanied by a softening of the fragmentation pattern of the second most energetic, away-side jet. The dijet momentum balance is recovered when integrating low transverse momentum particles distributed over a wide angular range relative to the direction of the away-side jet.
TL;DR: The initial development of a multidimensional measure designed to assess psychological need thwarting, an under-studied area of conceptual and practical importance is outlined, and suggestions are made regarding the use of the PNTS in research pertaining to the darker side of sport participation.
Abstract: Research in self-determination theory (Ryan & Deci, 2002) has shown that satisfaction of autonomy, competence, and relatedness needs in sport contexts is associated with enhanced engagement, performance, and well-being This article outlines the initial development of a multidimensional measure designed to assess psychological need thwarting, an under-studied area of conceptual and practical importance Study 1 generated a pool of items designed to tap the negative experiential state that occurs when athletes perceive their needs for autonomy, competence, and relatedness to be actively undermined Study 2 tested the factorial structure of the questionnaire using confirmatory factor analysis The supported model comprised 3 factors, which represented the hypothesized interrelated dimensions of need thwarting The model was refined and cross-validated using an independent sample in Study 3 Overall, the psychological need thwarting scale (PNTS) demonstrated good content, factorial, and predictive validity, as well as internal consistency and invariance across gender, sport type, competitive level, and competitive experience The conceptualization of psychological need thwarting is discussed, and suggestions are made regarding the use of the PNTS in research pertaining to the darker side of sport participation
TL;DR: In this article, a 3 × 2 model of achievement goals is proposed and tested, which is rooted in the definition and valence components of competence, and encompasses six goal constructs: task-approach, task-avoidance, self-approaches, selfapproaches and self-avoidances.
Abstract: In the present research, a 3 × 2 model of achievement goals is proposed and tested The model is rooted in the definition and valence components of competence, and encompasses 6 goal constructs: task-approach, task-avoidance, self-approach, self-avoidance, other-approach, and other-avoidance The results from 2 studies provided strong support for the proposed model, most notably the need to separate task-based and self-based goals Studies 1 and 2 yielded data establishing the 3 × 2 structure of achievement goals, and Study 2 documented the antecedents and consequences of each of the goals in the 3 × 2 model Terminological, conceptual, and applied issues pertaining to the 3 × 2 model are discussed