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Non-standard errors
(2021)
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.
The Kinase Chemogenomic Set (KCGS): an open science resource for kinase vulnerability identification
(2021)
We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS), current Version 1.0, is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification
(2019)
We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS) is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
Back-angle enhancements of elastic alpha -scattering cross sections have been observed for nuclei at the ends of the 1p, 2s-1d, and f7 / 2 shells. Strong reduction of this enhancement occurs if excess neutrons enter the next open major shell. The results are discussed in terms of intermediate alpha structure.
Unequivocal international guidelines regarding the diagnosis and management of patients with acute appendicitis are lacking. The aim of the consensus meeting 2015 of the EAES was to generate a European guideline based on best available evidence and expert opinions of a panel of EAES members. After a systematic review of the literature by an international group of surgical research fellows, an expert panel with extensive clinical experience in the management of appendicitis discussed statements and recommendations. Statements and recommendations with more than 70 % agreement by the experts were selected for a web survey and the consensus meeting of the EAES in Bucharest in June 2015. EAES members and attendees at the EAES meeting in Bucharest could vote on these statements and recommendations. In the case of more than 70 % agreement, the statement or recommendation was defined as supported by the scientific community. Results from both the web survey and the consensus meeting in Bucharest are presented as percentages. In total, 46 statements and recommendations were selected for the web survey and consensus meeting. More than 232 members and attendees voted on them. In 41 of 46 statements and recommendations, more than 70 % agreement was reached. All 46 statements and recommendations are presented in this paper. They comprise topics regarding the diagnostic work-up, treatment indications, procedural aspects and post-operative care. The consensus meeting produced 46 statements and recommendations on the diagnostic work-up and management of appendicitis. The majority of the EAES members supported these statements. These consensus proceedings provide additional guidance to surgeons and surgical residents providing care to patients with appendicitis.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
First results on the longitudinal asymmetry and its effect on the pseudorapidity distributions in Pb–Pb collisions at √sNN = 2.76 TeV at the Large Hadron Collider are obtained with the ALICE detector. The longitudinal asymmetry arises because of an unequal number of participating nucleons from the two colliding nuclei, and is estimated for each event by measuring the energy in the forward neutron-ZeroDegree-Calorimeters (ZNs). The effect of the longitudinal asymmetry is measured on the pseudorapidity distributions of charged particles in the regions |η| < 0.9, 2.8 < η < 5.1 and −3.7 < η < −1.7 by taking the ratio of the pseudorapidity distributions from events corresponding to different regions of asymmetry. The coefficients of a polynomial fit to the ratio characterise the effect of the asymmetry. A Monte Carlo simulation using a Glauber model for the colliding nuclei is tuned to reproduce the spectrum in the ZNs and provides a relation between the measurable longitudinal asymmetry and the shift in the rapidity (y0) of the participant zone formed by the unequal number of participating nucleons. The dependence of the coefficient of the linear term in the polynomial expansion, c1, on the mean value of y0 is investigated.
The production of the charm-strange baryon Ξc0 is measured for the first time at the LHC via its semileptonic decay into eΞ−+νe in pp collisions at s=7 TeV with the ALICE detector. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 1<pT<8 GeV/c at mid-rapidity, |y|<0.5. The transverse momentum dependence of the Ξc0 baryon production relative to the D0 meson production is compared to predictions of event generators with various tunes of the hadronisation mechanism, which are found to underestimate the measured cross-section ratio.
Azimuthally-differential femtoscopic measurements, being sensitive to spatio-temporal characteristics of the source as well as to the collective velocity fields at freeze out, provide very important information on the nature and dynamics of the system evolution. While the HBT radii oscillations relative to the second harmonic event plane measured recently reflect mostly the spatial geometry of the source, model studies have shown that the HBT radii oscillations relative to the third harmonic event plane are predominantly defined by the velocity fields. In this Letter, we present the first results on azimuthally-differential pion femtoscopy relative to the third harmonic event plane as a function of the pion pair transverse momentum kT for different collision centralities in Pb–Pb collisions at √sNN = 2.76 TeV. We find that the Rside and Rout radii, which characterize the pion source size in the directions perpendicular and parallel to the pion transverse momentum, oscillate in phase relative to the third harmonic event plane, similar to the results from 3+1D hydrodynamical calculations. The observed radii oscillations unambiguously signal a collective expansion and anisotropy in the velocity fields. A comparison of the measured radii scillations with the Blast-Wave model calculations indicate that the initial state triangularity is washedout at freeze out.
We present a measurement of azimuthal correlations between inclusive J/ψ and charged hadrons in p–Pb collisions recorded with the ALICE detector at the CERN LHC. The J/ψ are reconstructed at forward (p-going, 2.03<y<3.53) and backward (Pb-going, −4.46<y<−2.96) rapidity via their μ+μ− decay channel, while the charged hadrons are reconstructed at mid-rapidity (|η|<1.8). The correlations are expressed in terms of associated charged-hadron yields per J/ψ trigger. A rapidity gap of at least 1.5 units is required between the trigger J/ψ and the associated charged hadrons. Possible correlations due to collective effects are assessed by subtracting the associated per-trigger yields in the low-multiplicity collisions from those in the high-multiplicity collisions. After the subtraction, we observe a strong indication of remaining symmetric structures at Δφ≈0 and Δφ≈π, similar to those previously found in two-particle correlations at middle and forward rapidity. The corresponding second-order Fourier coefficient (v2) in the transverse momentum interval between 3 and 6 GeV/c is found to be positive with a significance of about 5σ. The obtained results are similar to the J/ψ v2 coefficients measured in Pb–Pb collisions at sNN=5.02 TeV, suggesting a common mechanism at the origin of the J/ψ v2.
The release of RNA-containing extracellular vesicles (EV) into the extracellular milieu has been demonstrated in a multitude of different in vitro cell systems and in a variety of body fluids. RNA-containing EV are in the limelight for their capacity to communicate genetically encoded messages to other cells, their suitability as candidate biomarkers for diseases, and their use as therapeutic agents. Although EV-RNA has attracted enormous interest from basic researchers, clinicians, and industry, we currently have limited knowledge on which mechanisms drive and regulate RNA incorporation into EV and on how RNA-encoded messages affect signalling processes in EV-targeted cells. Moreover, EV-RNA research faces various technical challenges, such as standardisation of EV isolation methods, optimisation of methodologies to isolate and characterise minute quantities of RNA found in EV, and development of approaches to demonstrate functional transfer of EV-RNA in vivo. These topics were discussed at the 2015 EV-RNA workshop of the International Society for Extracellular Vesicles. This position paper was written by the participants of the workshop not only to give an overview of the current state of knowledge in the field, but also to clarify that our incomplete knowledge – of the nature of EV(-RNA)s and of how to effectively and reliably study them – currently prohibits the implementation of gold standards in EV-RNA research. In addition, this paper creates awareness of possibilities and limitations of currently used strategies to investigate EV-RNA and calls for caution in interpretation of the obtained data.
The Birds of the Highlands of South-West Saudi Arabia and adjacent parts of the Tihama: July 2010
(2010)
The objective of the survey was to compare habitats and bird life in the Asir region, particularly Jebal Souda and the Raydah escarpment protected area of the Saudi Wildlife Commission, and adjacent regions of the tihama, with those observed in July 1987 (Jennings, et al., 1988). The two surveys were approximately the same length and equal amounts of time were spent in the highlands and on the tihama. A number of walked censuses were carried out during 2010 on Jebal Souda, using the same methodology as walked censuses in 1987, and the results are compared. Broadly speaking the comparison of censuses revealed that in 2010 there were less birds and reduced diversity on the Jebal Souda plateau, compared to 1987. However in the Raydah reserve the estimates of breeding bird populations compiled in the mid 1990s was little changed as far as could be assessed in 2010. The highland region of south-west Saudi Arabia, especially Jebal Souda, has been much developed since the 1987 survey and is now an important internal recreation and resort area. This has lead to a reduction in the region’s importance for terraced agriculture. These changes may be a contributing factor to changes in bird numbers on the plateau. Subsidiary tasks that arose during the 2010 survey were to help locate satellite tagged Bald Ibises Geronticus eremita from Syria which were transiting Saudi Arabia at the time. Secondly to search for the Asir subspecies of the Eurasian Magpie Pica pica asirensis, which is endemic to the south-west Saudi Arabia highlands, and is reported to be in decline. A separate team searching for the Bald Ibis located some individuals and one was found dead. Few Magpies were located and it seems clear that this very scarce bird has declined further in numbers in recent years. A number of interesting records of birds were obtained, especially on the tihama, where two new birds for Saudi Arabia were observed, Black-headed Heron Ardea melanocephala and Painted Snipe Rostratula benghalensis and one species, Glossy Ibis Plegadis falcinellus was found breeding for the first time in the Arabian Peninsula. Some recommendations for the protection and management of the Raydah reserve are presented. A systematic list of all birds seen is provided.
The genus Squamidium, a group of mosses with a tropical to subtropical American-African distribution, consists of two sections and seven species (prior to this study 27 species were recognized): sect. Squamidium (S. leucotrichum, S. livens, S. isocladum, S. nigricans, S. brasiliense) and sect. Macrosquamidium (S. macrocarpum and S. diversicoma). Twenty-four names are treated as syn. nov., three are provisionally excluded pending an examination of their types, and one new combination is made: Orthostichopsis pilotrichelloides (Sehnem) Allen & Crosby. Section Squamidium ist characterized by immersed capsules, stolon leaves with entire margins, and a relatively high basal membrane. Section Macrosquamidium is characterized by exserted capsules, stolon leaves with sharply recurved marginal teeth, and a relatively low basal membrane. The genus is retained in the Meteoriaceae. Within the Meteoriaceae Squamidium, is most closely related to Zelotmeteorium from which it differs only by its lack of squarrose-recurved leaves and its more well-developed alar cells. Squamidium, which in the absence of sporophytes has been confused consistently with Orthostichopsis, is separated from that genus on the basis of its lack of pseudoparaphyllia, weaker costae, lack of a distinct region of reddish cells across the leaf base, and strongly decurrent alar cells.
Background: Pythium ultimum (P. ultimum) is a ubiquitous oomycete plant pathogen responsible for a variety of diseases on a broad range of crop and ornamental species. Results: The P. ultimum genome (42.8 Mb) encodes 15,290 genes and has extensive sequence similarity and synteny with related Phytophthora species, including the potato blight pathogen Phytophthora infestans. Whole transcriptome sequencing revealed expression of 86% of genes, with detectable differential expression of suites of genes under abiotic stress and in the presence of a host. The predicted proteome includes a large repertoire of proteins involved in plant pathogen interactions although surprisingly, the P. ultimum genome does not encode any classical RXLR effectors and relatively few Crinkler genes in comparison to related phytopathogenic oomycetes. A lower number of enzymes involved in carbohydrate metabolism were present compared to Phytophthora species, with the notable absence of cutinases, suggesting a significant difference in virulence mechanisms between P. ultimum and more host specific oomycete species. Although we observed a high degree of orthology with Phytophthora genomes, there were novel features of the P. ultimum proteome including an expansion of genes involved in proteolysis and genes unique to Pythium. We identified a small gene family of cadherins, proteins involved in cell adhesion, the first report in a genome outside the metazoans. Conclusions: Access to the P. ultimum genome has revealed not only core pathogenic mechanisms within the oomycetes but also lineage specific genes associated with the alternative virulence and lifestyles found within the pythiaceous lineages compared to the Peronosporaceae.
The purpose of this study of early social-cognitive development was to assess the very young child's behaviorally expressed knowledge of people's visual-attentional acts and abilities. Boys and girls (N = 60) 1, 1 1/2, 2, 2 1/2, and 3 years of age were tested in their homes with their mothers' help. Three sorts of tasks were used: 1. Percept production. The child's task was to produce a visual percept in the other. Examples include pointing to objects ("productive pointing") and a wide variety of object-showing problems. 2. Percept deprivation. The opposite, exemplified by a variety of object-hiding problems. 3. Percept diagnosis. The child's task was to determine what the other was already visually attending to, either by looking where his or her finger was pointed ("receptive pointing") or where his eyes were directed. It was found that the majority of l-year-olds produced and comprehended pointing, and would sometimes hold out a toy to show it, but did little else. The 3-year-olds were at ceiling on virtually all tasks. At 1 1/2 years, children usually showed a picture by holding it flat so that both they and the other could see it. From 2 on, they usually turned it toward the other in the adult fashion. Very few children of any age showed egocentrically - i.e., orienting the picture so only they could see it. By age 2, the children solved what were presumably novel showing problems for them: e.g., successfully showing to another a picture pasted on the inside bottom of a hollow cube. Hiding ability emerged later than showing ability but seemed well established by age 3. The role of the other's eyes in seeing appeared to be quite well understood at least by age 2-2 1/2. As examples, children of this age took the other's hands away from her or his eyes before trying to show her something, and could usually tell where she was looking from her eye orientation alone. These age trends presumably reflect important developments in the area of social interaction and communication, as well as with respect to cognition about percepts.
Hatching asynchrony and the onset of incubation in birds revisited : when is the critical period?
(1995)
1. Birds are unique among animals in being able to influence the birthing intervals of their young through the timing of the onset incubation. However, many species hatch their young asynchronously, frequently resulting in reduced survivorship for later-hatched young. This is the Paradox of Hatching Asynchrony. 2. The Brood Reduction Hypothesis provided a resolution to the paradox by suggesting an adaptive function to the offspring mortality that results from asynchrony. Experimental tests have provided little support, and 16 alternative hypotheses have been proposed, but few have been tested. Most experimental tests have not measured important parameters such as parental effort and postfledging survival. Many have lacked adequate controls or sufficient statistical power. 3. We divide the hypotheses for hatching asynchrony into four categories based on the effects of intrinsic or extrinsic factors during a critical period of the nesting cycle which constrains reproductive success. Hatching asynchrony could be simply the consequence of the early onset of incubation during egg-laying, either as a result of physiological constraints on incubation or because parents derive fitness benefits from the protective function of early incubation. During the nestling period, hatching asynchrony could be adaptive if it allowed parents to eliminate one or more nestlings selectively, or increased parental efficiency. Alternatively, parents could manipulate the duration of the different periods of the nesting cycle to maximize benefits. 4. Because the onset of incubation generally determines hatching patterns, we encourage refocusing attention from the search for adaptive hatching patterns during the nestling period to the events surrounding the onset of incubation during egg-laying. Many factors can affect when incubation is begun, including physiology, and interactions with the environment, predators, competitors, and mates. 5. Patterns of the onset of incubation are difficult to determine and to quantify, in part because many birds begin incubating gradually, or at night. In some species, the onset of incubation varies with clutch size, but not in others. 6. The onset of incubation is the principle proximate control of hatching patterns, but other factors, such as egg size, embryonic vocalizations, and time of year may also affect hatching patterns. 7. Synchronous hatching is the primitive condition in birds, and is widespread in the lower, primarily precocial taxa. Most altricial species hatch their eggs asynchronously, although some exhibit synchrony as a secondarily derived trait. Hatching patterns show wide variation within some orders and families. 8. Patterns of the onset of incubation and hatching in a species may reflect the influence of multiplefactors. The relative importance of those factors may depend on the trade-offs associated with the potential benefits of early incubation to the survival of eggs and the potential costs to the survivor of later-hatching young associatedwith nestling size hierarchies. 9. The relative effects of multiple factors can be examined by integrating the results of empirical tests of single factors through modeling. 10. We demonstrated the use of a stochastic model by using empirical data from the House Sparrow. Results revealed the trade-offs inherent in the onset of incubation from differences in egg viability and nestling survivorship. An intermediate onset of incubation produced the greatest fledging success. 11. Other factors may be integrated into such models if they can be measured in terms of their effects on fledging success. Different factors, represented by different hypotheses, vary in how readily they may be modeled.
The ( J, T ) = (1, 1) parity doublet in 20Ne at 11.26 MeV is a good candidate to study parity violation in nuclei. However, its energy splitting is known with insufficient accuracy for quantitative estimates of parity violating effects. To improve on this unsatisfactory situation, nuclear resonance fluorescence experiments using linearly and circularly polarized γ -ray beams were used to determine the energy difference of the parity doublet E = E(1−) − E(1+) = −3.2(±0.7)stat( +0.6 −1.2)sys keV and the ratio of their integrated cross sections I (+) s,0 /I (−) s,0 = 29(±3)stat( +14 −7 )sys. Shell-model calculations predict a parityviolating matrix element having a value in the range 0.46–0.83 eV for the parity doublet. The small energy difference of the parity doublet makes 20Ne an excellent candidate to study parity violation in nuclear excitations.
Background: There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group.
Methods: The study comprised 802 women (median age 40 years, range 19–76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation.
Results: A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20–29 years compared to 6.9% in the age group 60–69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50–2.32, p < 0.001). gBRCA mutation risk was predicted to be > 10% for women diagnosed below approximately 50 years.
Conclusions: Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation.