Showing papers by "University of Zurich published in 2002"
TL;DR: In this article, it was shown that negative emotions towards defectors are the proximate mechanism behind altruistic punishment and that cooperation flourishes if altruistic punishments are possible, and breaks down if it is ruled out.
Abstract: Human cooperation is an evolutionary puzzle. Unlike other creatures, people frequently cooperate with genetically unrelated strangers, often in large groups, with people they will never meet again, and when reputation gains are small or absent. These patterns of cooperation cannot be explained by the nepotistic motives associated with the evolutionary theory of kin selection and the selfish motives associated with signalling theory or the theory of reciprocal altruism. Here we show experimentally that the altruistic punishment of defectors is a key motive for the explanation of cooperation. Altruistic punishment means that individuals punish, although the punishment is costly for them and yields no material gain. We show that cooperation flourishes if altruistic punishment is possible, and breaks down if it is ruled out. The evidence indicates that negative emotions towards defectors are the proximate mechanism behind altruistic punishment. These results suggest that future study of the evolution of human cooperation should include a strong focus on explaining altruistic punishment.
4,353 citations
TL;DR: In this paper, the authors argue that reported subjective well-being is a satisfactory empirical approximation to individual utility and that happiness research is able to contribute important insights for economics, and report how the economic variables income, unemployment and inflation affect happiness as well as institutional factors, in particular the type of democracy and the extent of government decentralization, systematically influence how satisfied individuals are with their life.
Abstract: In recent years, there has been a steadily increasing interest on the part of economists in happiness research. We argue that reported subjective well-being is a satisfactory empirical approximation to individual utility and that happiness research is able to contribute important insights for economics. We report how the economic variables income, unemployment and inflation affect happiness as well as how institutional factors, in particular the type of democracy and the extent of government decentralization, systematically influence how satisfied individuals are with their life. We discuss some of the consequences for economic policy and for economic theory.
2,454 citations
TL;DR: Using standardised MRI, the symptomatic hips of patients who have impingement have significantly less concavity at the femoral head-neck junction than do normal hips, and this test may be of value in patients with loss of internal rotation for which a cause is not found.
Abstract: Impingement by prominence at the femoral head-neck junction on the anterior acetabular rim may cause early osteoarthritis. Our aim was to develop a simple method to describe concavity at this junction, and then to test it by its ability to distinguish quantitatively a group of patients with clinical evidence of impingement from asymptomatic individuals who had normal hips on examination. MR scans of 39 patients with groin pain, decreased internal rotation and a positive impingement test were compared with those of 35 asymptomatic control subjects. The waist of the femoral head-neck junction was identified on tilted axial MR scans passing through the centre of the head. The anterior margin of the waist of the femoral neck was defined and measured by an angle (alpha). In addition, the width of the femoral head-neck junction was measured at two sites. Repeated measurements showed good reproducibility among four observers. The angle alpha averaged 74.0 degrees for the patients and 42.0 degrees for the control group (p < 0.001). Significant differences were also found between the patient and control groups for the scaled width of the femoral neck at both sites. Using standardised MRI, the symptomatic hips of patients who have impingement have significantly less concavity at the femoral head-neck junction than do normal hips. This test may be of value in patients with loss of internal rotation for which a cause is not found.
1,574 citations
TL;DR: The CD4 cell count at initiation was the dominant prognostic factor in patients starting HAART, and should be taken into account in future treatment guidelines.
1,563 citations
TL;DR: There was no convincing evidence that the outcome of anorexia nervosa improved over the second half of the last century, and vomiting, bulimia, and purgative abuse, chronicity of illness, and obsessive-compulsive personality symptoms are unfavorable prognostic features.
Abstract: follow-up. Results: There were large variations in the outcome parameters across studies. Mortality estimated on the basis of both crude and standardized rates was significantly high. Among the surviving patients, less than one-half recovered on average, whereas one-third improved, and 20% remained chronically ill. The normalization of the core symptoms, involving weight, menstruation, and eating behaviors, was slightly better when each symptom was analyzed in isolation. The presence of other psychiatric disorders at follow-up was very common. Longer duration of follow-up and, less strongly, younger age at onset of illness were associated with better outcome. There was no convincing evidence that the outcome of anorexia nervosa improved over the second half of the last century. Several prognostic features were isolated, but there is conflicting evidence. Most clearly, vomiting, bulimia, and purgative abuse, chronicity of illness, and obsessive-compulsive personality symptoms are unfavorable prognostic features. Conclusions: Anorexia nervosa did not lose its relatively poor prognosis in the 20th century. Advances in etiology and treatment may improve the course of patients with anorexia nervosa in the future.
1,552 citations
TL;DR: This document update and summarize new information obtained from this research and incorporate, where appropriate, the results into the BOS criteria.
Abstract: Bronchiolitis obliterans (BO) is a major cause of allograft dysfunction in lung and heart lung transplant recipients. Clinically, progressive airflow limitation develops because of small airway obstruction. The disease has a variable course. Some patients experience rapid loss of lung function and respiratory failure. Others experience either slow progression or intermittent loss of function with long plateaus during which pulmonary function is stable. Histologic confirmation is difficult because transbronchial biopsy specimens often are not sufficiently sensitive for diagnosis. Because BO is difficult to document histologically, in 1993 a committee sponsored by the International Society for Heart and Lung Transplantation (ISHLT) proposed a clinical description of BO, termed bronchiolitis obliterans syndrome (BOS) and defined by pulmonary function changes rather than histology. Although this system does not require histologic diagnosis, it does recognize it. Transplant centers worldwide have adopted the BOS system as a descriptor of lung allograft dysfunction. This allows centers to use a common language to compare program results. In the years since publication of the BOS system, transplant scientists have studied basic and clinical aspects of lung transplant BO. In this document, we update and summarize new information obtained from this research and incorporate, where appropriate, the results into the BOS criteria. The document will include the following topics: (1) criteria for BOS, (2) BOS considerations in pediatric patients, (3) risk factors for BOS, (4) pathology of BO, (5) surrogate markers for BOS, (6) confounding factors in making a BOS diagnosis, and (7) assessment of response to treatment of BOS.
1,228 citations
TL;DR: In vitro exposure of islets from nondiabetic organ donors to high glucose levels resulted in increased production and release of IL-1beta, followed by NF-kappaB activation, Fas upregulation, DNA fragmentation, and impaired beta cell function, which implicate an inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes.
Abstract: In type 2 diabetes, chronic hyperglycemia is suggested to be detrimental to pancreatic beta cells, causing impaired insulin secretion. IL-1beta is a proinflammatory cytokine acting during the autoimmune process of type 1 diabetes. IL-1beta inhibits beta cell function and promotes Fas-triggered apoptosis in part by activating the transcription factor NF-kappaB. Recently, we have shown that increased glucose concentrations also induce Fas expression and beta cell apoptosis in human islets. The aim of the present study was to test the hypothesis that IL-1beta may mediate the deleterious effects of high glucose on human beta cells. In vitro exposure of islets from nondiabetic organ donors to high glucose levels resulted in increased production and release of IL-1beta, followed by NF-kappaB activation, Fas upregulation, DNA fragmentation, and impaired beta cell function. The IL-1 receptor antagonist protected cultured human islets from these deleterious effects. beta cells themselves were identified as the islet cellular source of glucose-induced IL-1beta. In vivo, IL-1beta-producing beta cells were observed in pancreatic sections of type 2 diabetic patients but not in nondiabetic control subjects. Similarly, IL-1beta was induced in beta cells of the gerbil Psammomys obesus during development of diabetes. Treatment of the animals with phlorizin normalized plasma glucose and prevented beta cell expression of IL-1beta. These findings implicate an inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes and identify the IL-1beta/NF-kappaB pathway as a target to preserve beta cell mass and function in this condition.
1,105 citations
TL;DR: In patients with severe, low-output heart failure, levosimendan improved haemodynamic performance more effectively than dobutamine and was accompanied by lower mortality in the levosIMendan group than in theDobutamine group for up to 180 days.
1,068 citations
TL;DR: The authors showed that monetary incentives may back-fire and reduce the performance of agents or their compliance with rules, and that these motives may generate very powerful incentives themselves, such as desire to reciprocate or the desire to avoid social disapproval.
1,054 citations
TL;DR: For example, this article showed that people are willing to punish those who behaved unfairly towards a third person or who defected in a Prisoner's Dilemma game with another person.
Abstract: This paper provides strong evidence challenging the self-interest assumption that dominates the behavioral sciences and much evolutionary thinking. The evidence indicates that many people have a tendency to voluntarily cooperate, if treated fairly, and to punish noncooperators. We call this behavioral propensity "strong reciprocity" and show empirically that it can lead to almost universal cooperation in circumstances in which purely self-interested behavior would cause a complete breakdown of cooperation. In addition, we show that people are willing to punish those who behaved unfairly towards a third person or who defected in a Prisoner's Dilemma game with a third person. This suggests that strong reciprocity is a powerful device for the enforcement of social norms involving, for example, food sharing or collective action. Strong reciprocity cannot be rationalized as an adaptive trait by the leading evolutionary theories of human cooperation (in other words, kin selection, reciprocal altruism, indirect reciprocity, and costly signaling theory). However, multilevel selection theories of cultural evolution are consistent with strong reciprocity.
1,047 citations
TL;DR: Histologic disc alterations can reliably be graded based on the proposed classification system providing a morphologic framework for more sophisticated molecular biologic analyses of factors leading to age-related disc changes.
Abstract: STUDY DESIGN A histologic study on age-related changes of the human lumbar intervertebral disc was conducted. OBJECTIVES To investigate comprehensively age-related temporospatial histologic changes in human lumbar intervertebral disc, and to develop a practicable and reliable classification system for age-related histologic disc alteration. SUMMARY OF THE BACKGROUND DATA No comprehensive microscopic analysis of age-related disc changes is available. There is no conceptual morphologic framework for classifying age-related disc changes as a reference basis for more sophisticated molecular biologic analyses of the causative factors of disc aging or premature aging (degeneration). METHODS A total of 180 complete sagittal lumbar motion segment slices obtained from 44 deceased individuals (fetal to 88 years of age) were analyzed with regard to 11 histologic variables for the intervertebral disc and endplate, respectively. In addition, 30 surgical specimens (3 regions each) were investigated with regard to five histologic variables. Based on the semiquantitative analyses of 20,250 histologic variable assessments, a classification system was developed and tested in terms of validity, practicability, and reliability. The classification system was applied to cadaveric and surgical disc specimens not included in the development of the classification system, and the scores were assessed by two additional independent raters. RESULTS A semiquantitative analyses provided clear histologic evidence for the detrimental effect of a diminished blood supply on the endplate, resulting in the tissue breakdown beginning in the nucleus pulposus and starting in the second life decade. Significant temporospatial variations in the presence and abundance of histologic disc alterations were observed across levels, regions, macroscopic degeneration grades, and age groups. A practicable classification system for age-related histologic disc alterations was developed, resulting in moderate to excellent reliability (kappa values, 0.49-0.98) depending on the histologic variable. Application of the classification system to cadaveric and surgical specimens demonstrated a significant correlation with age ( < 0.0001) and macroscopic grade of degeneration ( < 0001). However, substantial data scatter caution against reliance on traditional macroscopic disc grading and favor a histology-based classification system as a reference standard. CONCLUSIONS Histologic disc alterations can reliably be graded based on the proposed classification system providing a morphologic framework for more sophisticated molecular biologic analyses of factors leading to age-related disc changes. Diminished blood supply to the intervertebral disc in the first half of the second life decade appears to initiate tissue breakdown.
TL;DR: In this article, the authors present a new "Stakeholder view" of the firm which holds that stakeholder relationships are the ultimate sources of the wealth-creating capacity.
Abstract: This article enlarges the "extended enterprise" metaphor from its origins in manufacturing-logistics management to embrace the full range of constituencies that are vital to the survival and success of the corporation. This article presents a new "Stakeholder View" of the firm which holds that stakeholder relationships are the ultimate sources of the firm's wealth-creating capacity. According to this view, long-term business success requires a firm to develop and integrate relationships with its multiple stakeholders within a comprehensive management strategy. In order to illustrate the validity of this approach, this article describes and analyzes the evolution and impact of comprehensive stakeholder management policies in three major firms.
TL;DR: The authors show empirically that economists fail to understand fundamental economic questions when they disregard social preferences, in particular, that without taking social preferences into account, it is not possible to understand adequately (i) effects of competition on market outcomes, (ii) laws governing cooperation and collective action, effects and the determinants of material incentives, which contracts and property rights arrangements are optimal, and important forces shaping social norms and market failures.
Abstract: A substantial number of people exhibit social preferences, which means they are not solely motivated by material self-interest but also care positively or negatively for the material payoffs of relevant reference agents. We show empirically that economists fail to understand fundamental economic questions when they disregard social preferences, in particular, that without taking social preferences into account, it is not possible to understand adequately (i) effects of competition on market outcomes, (ii) laws governing cooperation and collective action, (iii) effects and the determinants of material incentives, (iv) which contracts and property rights arrangements are optimal, and (v) important forces shaping social norms and market failures.
TL;DR: Men and women hospitalised for affective disorders have elevated mortality rates from suicide and circulatory disorders and long term medication treatment lowers the suicide rates, despite the fact that it was the more severely ill who were treated.
TL;DR: The authors show empirically that economists fail to understand fundamental economic questions when they disregard social preferences, in particular, that without taking social preferences into account, it is not possible to understand adequately (i) effects of competition on market outcomes, (ii) laws governing cooperation and collective action, effects and the determinants of material incentives, which contracts and property rights arrangements are optimal, and important forces shaping social norms and market failures.
Abstract: A substantial number of people exhibit social preferences, which means they are not solely motivated by material self-interest but also care positively or negatively for the material payoffs of relevant reference agents. We show empirically that economists fail to understand fundamental economic questions when they disregard social preferences, in particular, that without taking social preferences into account, it is not possible to understand adequately (i) effects of competition on market outcomes, (ii) laws governing cooperation and collective action, (iii) effects and the determinants of material incentives, (iv) which contracts and property rights arrangements are optimal, and (v) important forces shaping social norms and market failures.
TL;DR: Here, this work focuses on the functional and anatomical differences that have been detected in musicians by modern neuroimaging methods.
Abstract: Studies of experience-driven neuroplasticity at the behavioural, ensemble, cellular and molecular levels have shown that the structure and significance of the eliciting stimulus can determine the neural changes that result. Studying such effects in humans is difficult, but professional musicians represent an ideal model in which to investigate plastic changes in the human brain. There are two advantages to studying plasticity in musicians: the complexity of the eliciting stimulus — music — and the extent of their exposure to this stimulus. Here, we focus on the functional and anatomical differences that have been detected in musicians by modern neuroimaging methods.
TL;DR: The discovery of six hominid specimens from Chad, central Africa, 2,500 km from the East African Rift Valley, suggest that the earliest members of the hominids clade were more widely distributed than has been thought, and that the divergence between the human and chimpanzee lineages was earlier than indicated by most molecular studies.
Abstract: The search for the earliest fossil evidence of the human lineage has been concentrated in East Africa. Here we report the discovery of six hominid specimens from Chad, central Africa, 2,500 km from the East African Rift Valley. The fossils include a nearly complete cranium and fragmentary lower jaws. The associated fauna suggest the fossils are between 6 and 7 million years old. The fossils display a unique mosaic of primitive and derived characters, and constitute a new genus and species of hominid. The distance from the Rift Valley, and the great antiquity of the fossils, suggest that the earliest members of the hominid clade were more widely distributed than has been thought, and that the divergence between the human and chimpanzee lineages was earlier than indicated by most molecular studies. From their initial description in 1925 1 until 1995, hominids from the Pliocene (5.3‐1.6 million years, Myr) and late Upper Miocene (,7.5‐5.3 Myr) were known only from southern and eastern Africa. This distribution led some authors to postulate an East African origin for the hominid clade (where the term ‘hominid’ refers to any member of that group more closely related to extant humans than to
TL;DR: A causal link between nutrient availability and insulin-dependent growth is established and results point to a conserved role of the neuroendocrine axis in growth control in multicellular organisms.
CERN1, Royal Holloway, University of London2, Fermilab3, University of Bonn4, University of Montpellier5, University of Michigan6, University of California, Davis7, University of California, Santa Cruz8, University of Wisconsin-Madison9, Brookhaven National Laboratory10, Stanford University11, Lawrence Berkeley National Laboratory12, University of Warsaw13, Northern Illinois University14, RWTH Aachen University15, University of Florida16, University of Antwerp17, University of Colorado Boulder18, University of Minnesota19, University of Zurich20, Austrian Academy of Sciences21, Northwestern University22, California Institute of Technology23, University of Chicago24, Argonne National Laboratory25, University of Kansas26
TL;DR: The "Snowmass Points and Slopes" (SPS) as mentioned in this paper are a set of benchmark points and parameter lines in the MSSM parameter space corresponding to different scenarios in the search for Supersymmetry at present and future experiments.
Abstract: The ”Snowmass Points and Slopes” (SPS) are a set of benchmark points and parameter lines in the MSSM parameter space corresponding to different scenarios in the search for Supersymmetry at present and future experiments. This set of benchmarks was agreed upon at the 2001 ”Snowmass Workshop on the Future of Particle Physics” as a consensus based on different existing proposals.
TL;DR: This work has shown that nature has provided various safety mechanisms for the variety of novel pols identified in the last three years, including the lesion-replicating enzymes pol zeta, pol eta, pol iota, pol kappa, and Rev1, and a group of pols called pol theta that fulfill a variety of other tasks.
Abstract: ▪ Abstract Any living cell is faced with the fundamental task of keeping the genome intact in order to develop in an organized manner, to function in a complex environment, to divide at the right time, and to die when it is appropriate. To achieve this goal, an efficient machinery is required to maintain the genetic information encoded in DNA during cell division, DNA repair, DNA recombination, and the bypassing of damage in DNA. DNA polymerases (pols) α, β, γ, δ, and ϵ are the key enzymes required to maintain the integrity of the genome under all these circumstances. In the last few years the number of known pols, including terminal transferase and telomerase, has increased to at least 19. A particular pol might have more than one functional task in a cell and a particular DNA synthetic event may require more than one pol, which suggests that nature has provided various safety mechanisms. This multi-functional feature is especially valid for the variety of novel pols identified in the last three years. T...
Northwestern University1, Harvard University2, Johns Hopkins University3, University of Zurich4, Case Western Reserve University5, Christchurch Hospital6, University of North Carolina at Chapel Hill7, Thomas Jefferson University8, Kurume University9, University of Paris10, VU University Amsterdam11, Moorfields Eye Hospital12, University of California, San Francisco13, United States Department of Veterans Affairs14, Stanford University15, University of California, Los Angeles16, Mayo Clinic17, St Thomas' Hospital18, Churchill Hospital19, University of Southern California20, National Institutes of Health21, University of Würzburg22, University of Utah23
TL;DR: Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for mucous membrane pemphigoid.
Abstract: OBJECTIVE: We aimed to develop consensus-based recommendations for streamlining medical communication among various health care professionals, to improve accuracy of diagnosis and treatment, and to facilitate future investigations for mucous membrane pemphigoid. PARTICIPANTS: Because of the highly specific nature of this group of diseases, the 26 invited participants included either international scholars in the field of mucous membrane pemphigoid or experts in cutaneous pharmacology representing the 3 medical disciplines ophthalmology, oral medicine, and dermatology. EVIDENCE: The first author (L.S.C.) conducted a literature search. Based on the information obtained, international experts who had contributed to the literature in the clinical care, diagnosis, and laboratory investigation for mucous membrane pemphigoid were invited to participate in a consensus meeting aimed at developing a consensus statement. CONSENSUS PROCESS: A consensus meeting was convened and conducted on May 10, 1999, in Chicago, Ill, to discuss the relevant issues. The first author drafted the statement based on the consensus developed at the meeting and the participants' written comments. The draft was submitted to all participants for 3 separate rounds of review, and disagreements were reconciled based on literature evidence. The third and final statement incorporated all relevant evidence obtained in the literature search and the consensus developed by the participants. The final statement was approved and endorsed by all 26 participants. CONCLUSIONS: Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for mucous membrane pemphigoid. A system of standard reporting for these patients was proposed to facilitate a uniform data collection.
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TL;DR: In this article, the authors provide a theoretical foundation for rescuing Bagehot's view and derive policy implications about banking regulation (solvency and liquidity ratios) and interventions of the Lender of Last Resort as well as on the disclosure policy of the Central Bank.
Abstract: The classical doctrine of the Lender of Last Resort, elaborated by Thornton (1802) and Bagehot (1873), asserts that the Central Bank should lend to 'illiquid but solvent' banks under certain conditions. Several authors have argued that this view is now obsolete: when interbank markets are efficient, a solvent bank cannot be illiquid. This Paper provides a possible theoretical foundation for rescuing Bagehot's view. Our theory does not rely on the multiplicity of equilibria that arises in classical models of bank runs. We build a model of banks' liquidity crises that possesses a unique Bayesian equilibrium. In this equilibrium, there is a positive probability that a solvent bank cannot find liquidity assistance in the market. We derive policy implications about banking regulation (solvency and liquidity ratios) and interventions of the Lender of Last Resort as well as on the disclosure policy of the Central Bank.
TL;DR: S100 proteins have received increasing attention due to their close association with several human diseases including cardiomyopathy, neurodegenerative disorders and cancer, and are considered having a potential as drug targets to improve therapies.
Abstract: S100 proteins regulate intracellular processes such as cell growth and motility, cell cycle regulation, transcription and differentiation. Twenty members have been identified so far, and altogether, S100 proteins represent the largest subgroup in the EF-hand Ca2+ -binding protein family. A unique feature of these proteins is that individual members are localized in specific cellular compartments from which some are able to relocate upon Ca2+ activation, transducing the Ca2+ signal in a temporal and spacial manner by interacting with different targets specific for each S100 protein. Some members are even secreted from cells exerting extracellular, cytokine-like activities partially via the surface receptor RAGE (receptor for advanced glycation endproducts) with paracrine effects e.g. on neurons, promoting their survival during development or after injury. Another important aspect is that 14 bona fide S100 genes are found in a gene cluster on human chromosome 1q21 where a number of chromosomal abnormalities occur. This results in a deregulated expression of some S100 genes associated with neoplasias. Recently, S100 proteins have received increasing attention due to their close association with several human diseases including cardiomyopathy, neurodegenerative disorders and cancer. They have also been proven to be valuable in the diagnostic of these diseases, as predictive markers of improving clinical management, outcome and survival of patients and are considered having a potential as drug targets to improve therapies.
TL;DR: Rational drug targeting to specific receptor subtypes has now become possible, and only restricted neuronal networks will be modulated by the new subtype-selective drugs.
Abstract: Classical benzodiazepine drugs are in wide clinical use as anxiolytics, hypnotics, anticonvulsants, and muscle relaxants. They act by enhancing the γ-aminobutyric acid A (GABA A ) receptor function in the central nervous system. The pharmacological relevance of the multitude of structurally diverse GABA A receptor subtypes has only recently been identified. Based on an in vivo point mutation strategy, α 1 -GABA A receptors were found to mediate sedation, anterograde amnesia, and part of the seizure protection, whereas α 2 -GABA A receptors, but not α 3 -receptors, mediate anxiolysis. Rational drug targeting to specific receptor subtypes has now become possible. Only restricted neuronal networks will be modulated by the new subtype-selective drugs. Promising new anxiolytics have already been developed. A new pharmacology of the benzodiazepine site is on the horizon.
TL;DR: Recent evidence supporting the dual, the beneficial, or the deleterious role of neuroinflammation after traumatic brain injury is reported.
Abstract: Inflammation is an important part of the pathophysiology of traumatic brain injury. Although the central nervous system differs from the other organs because of the almost complete isolation from the blood stream mediated by the blood-brain barrier, the main steps characterizing the immune activation within the brain follow a scenario similar to that in other organs. The key players in these processes are the numerous immune mediators released within minutes of the primary injury. They guide a sequence of events including expression of adhesion molecules, cellular infiltration, and additional secretion of inflammatory molecules and growth factors, resulting in either regeneration or cell death. The question is this: to what extent is inflammation beneficial for the injured brain tissue, and how does it contribute to secondary brain damage and progressive neuronal loss? This review briefly reports recent evidence supporting the dual, the beneficial, or the deleterious role of neuroinflammation after traumatic brain injury.
TL;DR: This article summarizes expertise gleaned from the first years of Internet-based experimental research and presents recommendations on what precautions have to be undertaken in Web experimental design, and which techniques have proven useful in Web experimenting.
Abstract: This article summarizes expertise gleaned from the first years of Internet-based experimental research and presents recommendations on: (1) ideal circumstances for conducting a study on the Internet; (2) what precautions have to be undertaken in Web experimental design; (3) which techniques have proven useful in Web experimenting; (4) which frequent errors and misconceptions need to be avoided; and (5) what should be reported. Procedures and solutions for typical challenges in Web experimenting are discussed. Topics covered include randomization, recruitment of samples, generalizability, dropout, experimental control, identity checks, multiple submissions, configuration errors, control of moti- vational confounding, and pre-testing. Several techniques are explained, including "warm-up," "high hurdle," password methods, "multiple site entry," randomization, and the use of incentives. The article concludes by proposing sixteen stan- dards for Internet-based experimenting.
TL;DR: This work demonstrates the production of antihydrogen atoms at very low energy by mixing trapped antiprotons and positrons in a cryogenic environment and detects the neutral anti-atoms directly when they escape the trap and annihilate, producing a characteristic signature in an imaging particle detector.
Abstract: A theoretical underpinning of the standard model of fundamental particles and interactions is CPT invariance, which requires that the laws of physics be invariant under the combined discrete operations of charge conjugation, parity and time reversal. Antimatter, the existence of which was predicted by Dirac, can be used to test the CPT theorem—experimental investigations involving comparisons of particles with antiparticles are numerous1. Cold atoms and anti-atoms, such as hydrogen and antihydrogen, could form the basis of a new precise test, as CPT invariance implies that they must have the same spectrum. Observations of antihydrogen in small quantities and at high energies have been reported at the European Organization for Nuclear Research (CERN)2 and at Fermilab3, but these experiments were not suited to precision comparison measurements. Here we demonstrate the production of antihydrogen atoms at very low energy by mixing trapped antiprotons and positrons in a cryogenic environment. The neutral anti-atoms have been detected directly when they escape the trap and annihilate, producing a characteristic signature in an imaging particle detector.
TL;DR: The results suggest that the recruitment of Pygo permits beta-catenin to transcriptionally activate Wnt target genes and raise the possibility that a deregulation of these events may play a causal role in the development of B cell malignancies.
TL;DR: The presence of p62 along with other stress proteins and ubiquitin in cytoplasmic inclusions indicates deposition as aggregates as a third line of defense against misfolded proteins in addition to refolding and degradation.
Abstract: Exposure of cells to stress, particularly oxidative stress, leads to misfolding of proteins and, if they are not refolded or degraded, to cytoplasmic protein aggregates. Protein aggregates are characteristic features of a variety of chronic toxic and degenerative diseases, such as Mallory bodies (MBs) in hepatocytes in alcoholic and non-alcoholic steatohepatitis, neurofibrillary tangles in neurons in Alzheimer's, and Lewy bodies in Parkinson's disease. Using 2D gel electrophoresis and mass spectrometry, we identified p62 as a novel MB component. p62 and cytokeratins (CKs) are major MB constituents; HSP 70, HSP 25, and ubiquitinated CKs are also present. These proteins characterize MBs as a prototype of disease-associated cytoplasmic inclusions generated by stress-induced protein misfolding. As revealed by transfection of tissue culture cells overexpressed p62 did not induce aggregation of regular CK filaments but selectively bound to misfolded and ubiquitinated CKs. The general role of p62 in the cellular response to misfolded proteins was substantiated by detection of p62 in other cytoplasmic inclusions, such as neurofibrillary tangles, Lewy bodies, Rosenthal fibers, intracytoplasmic hyaline bodies in hepatocellular carcinoma, and alpha1-antitrypsin aggregates. The presence of p62 along with other stress proteins and ubiquitin in cytoplasmic inclusions indicates deposition as aggregates as a third line of defense against misfolded proteins in addition to refolding and degradation.
TL;DR: In this paper, the theoretical potential of the knowledge gap perspective for Internet research is explored and data based on two recent Internet surveys, which demonstrate a double digital divide between well-educated, affluent, young males and less educated seem to be interested particularly in the entertainment functions of the Internet.
Abstract: Although the knowledge gap hypothesis is often mentioned in connection with the social consequences of the Information Society, there is little discussion of its theoretical background or specific empirical evidence. Therefore, this article explores the theoretical potential of the knowledge gap perspective for Internet research and presents data based on two recent Internet surveys, which demonstrate a double digital divide. Access to the Internet in Switzerland is still dominated by well-educated, affluent, young males and between 1997 and 2000 the gap between those who do and those who do not have access widened not narrowed. Furthermore, there are gaps in the use of the Internet too. More educated people use the Internet more actively and their use is more information oriented, whereas the less educated seem to be interested particularly in the entertainment functions of the Internet.