Detection of back-to-back proton pairs in charged-current neutrino interactions with the ArgoNeuT detector in the NuMI low energy beam line

Short range nucleon-nucleon correlations in nuclei (NN SRC) carry important information on nuclear structure and dynamics. NN SRC have been extensively probed through two-nucleon knock- out reactions in both pion and electron scattering experiments. We report here on the detection of two-nucleon knock-out events from neutrino interactions and discuss their topological features as possibly involving NN SRC content in the target argon nuclei. The ArgoNeuT detector in the Main Injector neutrino beam at Fermilab has recorded a sample of 30 fully reconstructed charged current events where the leading muon is accompanied by a pair of protons at the interaction vertex, 19 of which have both protons above the Fermi momentum of the Ar nucleus. Out of these 19 events, four are found with the two protons in a strictly back-to-back high momenta configuration directly observed in the final state and can be associated to nucleon Resonance pionless mechanisms involving a pre-existing short range correlated np pair in the nucleus. Another fraction (four events) of the remaining 15 events have a reconstructed back-to-back configuration of a np pair in the initial state, a signature compatible with one-body Quasi Elastic interaction on a neutron in a SRC pair. The detection of these two subsamples of the collected (mu- + 2p) events suggests that mechanisms directly involving nucleon-nucleon SRC pairs in the nucleus are active and can be efficiently explored in neutrino-argon interactions with the LAr TPC technology.

Numerical corrections to the strong coupling effective Polyakov-line action for finite T Yang-Mills theory

We consider a three-dimensional effective theory of Polyakov lines derived previously from lattice Yang-Mills theory and QCD by means of a resummed strong coupling expansion. The effective theory is useful for investigations of the phase structure, with a sign problem mild enough to allow simulations also at finite density. In this work we present a numerical method to determine improved values for the effective couplings directly from correlators of 4d Yang-Mills theory. For values of the gauge coupling up to the vicinity of the phase transition, the dominant short range effective coupling are well described by their corresponding strong coupling series. We provide numerical results also for the longer range interactions, Polyakov lines in higher representations as well as four-point interactions, and discuss the growing significance of non-local contributions as the lattice gets finer. Within this approach the critical Yang-Mills coupling β c is reproduced to better than one percent from a one-coupling effective theory on N τ = 4 lattices while up to five couplings are needed on N τ = 8 for the same accuracy.

Mechanisms of cell competition: Themes and variations

Cell competition is the short-range elimination of slow-dividing cells through apoptosis when confronted with a faster growing population. It is based on the comparison of relative cell fitness between neighboring cells and is a striking example of tissue adaptability that could play a central role in developmental error correction and cancer progression in both Drosophila melanogaster and mammals. Cell competition has led to the discovery of multiple pathways that affect cell fitness and drive cell elimination. The diversity of these pathways could reflect unrelated phenomena, yet recent evidence suggests some common wiring and the existence of a bona fide fitness comparison pathway.

Folate Receptor Targeted Alpha-Therapy Using Terbium-149

Terbium-149 is among the most interesting therapeutic nuclides for medical applications. It decays by emission of short-range α-particles (Eα = 3.967 MeV) with a half-life of 4.12 h. The goal of this study was to investigate the anticancer efficacy of a 149Tb-labeled DOTA-folate conjugate (cm09) using folate receptor (FR)-positive cancer cells in vitro and in tumor-bearing mice. 149Tb was produced at the ISOLDE facility at CERN. Radiolabeling of cm09 with purified 149Tb resulted in a specific activity of ~1.2 MBq/nmol. In vitro assays performed with 149Tb-cm09 revealed a reduced KB cell viability in a FR-specific and activity concentration-dependent manner. Tumor-bearing mice were injected with saline only (group A) or with 149Tb-cm09 (group B: 2.2 MBq; group C: 3.0 MBq). A significant tumor growth delay was found in treated animals resulting in an increased average survival time of mice which received 149Tb-cm09 (B: 30.5 d; C: 43 d) compared to untreated controls (A: 21 d). Analysis of blood parameters revealed no signs of acute toxicity to the kidneys or liver in treated mice over the time of investigation. These results demonstrated the potential of folate-based α-radionuclide therapy in tumor-bearing mice.

Flood triggering in Switzerland: the role of daily to monthly preceding precipitation

Determining the role of different precipitation periods for peak discharge generation is crucial for both projecting future changes in flood probability and for short- and medium-range flood forecasting. In this study, catchment-averaged daily precipitation time series are analyzed prior to annual peak discharge events (floods) in Switzerland. The high number of floods considered – more than 4000 events from 101 catchments have been analyzed – allows to derive significant information about the role of antecedent precipitation for peak discharge generation. Based on the analysis of precipitation times series, a new separation of flood-related precipitation periods is proposed: (i) the period 0 to 1 day before flood days, when the maximum flood-triggering precipitation rates are generally observed, (ii) the period 2 to 3 days before flood days, when longer-lasting synoptic situations generate "significantly higher than normal" precipitation amounts, and (iii) the period from 4 days to 1 month before flood days when previous wet episodes may have already preconditioned the catchment. The novelty of this study lies in the separation of antecedent precipitation into the precursor antecedent precipitation (4 days before floods or earlier, called PRE-AP) and the short range precipitation (0 to 3 days before floods, a period when precipitation is often driven by one persistent weather situation like e.g., a stationary low-pressure system). A precise separation of "antecedent" and "peak-triggering" precipitation is not attempted. Instead, the strict definition of antecedent precipitation periods permits a direct comparison of all catchments. The precipitation accumulating 0 to 3 days before an event is the most relevant for floods in Switzerland. PRE-AP precipitation has only a weak and region-specific influence on flood probability. Floods were significantly more frequent after wet PRE-AP periods only in the Jura Mountains, in the western and eastern Swiss plateau, and at the outlet of large lakes. As a general rule, wet PRE-AP periods enhance the flood probability in catchments with gentle topography, high infiltration rates, and large storage capacity (karstic cavities, deep soils, large reservoirs). In contrast, floods were significantly less frequent after wet PRE-AP periods in glacial catchments because of reduced melt. For the majority of catchments however, no significant correlation between precipitation amounts and flood occurrences is found when the last 3 days before floods are omitted in the precipitation amounts. Moreover, the PRE-AP was not higher for extreme floods than for annual floods with a high frequency and was very close to climatology for all floods. The fact that floods are not significantly more frequent nor more intense after wet PRE-AP is a clear indicator of a short discharge memory of Pre-Alpine, Alpine and South Alpine Swiss catchments. Our study poses the question whether the impact of long-term precursory precipitation for floods in such catchments is not overestimated in the general perception. The results suggest that the consideration of a 3–4 days precipitation period should be sufficient to represent (understand, reconstruct, model, project) Swiss Alpine floods.

Interactions between short-term and long-term plasticity: shooting for a moving target

Far from being static transmission units, synapses are highly dynamical elements that change over multiple time scales depending on the history of the neural activity of both the pre- and postsynaptic neuron. Moreover, synaptic changes on different time scales interact: long-term plasticity (LTP) can modify the properties of short-term plasticity (STP) in the same synapse. Most existing theories of synaptic plasticity focus on only one of these time scales (either STP or LTP or late-LTP) and the theoretical principles underlying their interactions are thus largely unknown. Here we develop a normative model of synaptic plasticity that combines both STP and LTP and predicts specific patterns for their interactions. Recently, it has been proposed that STP arranges for the local postsynaptic membrane potential at a synapse to behave as an optimal estimator of the presynaptic membrane potential based on the incoming spikes. Here we generalize this approach by considering an optimal estimator of a non-linear function of the membrane potential and the long-term synaptic efficacy—which itself may be subject to change on a slower time scale. We find that an increase in the long-term synaptic efficacy necessitates changes in the dynamics of STP. More precisely, for a realistic non-linear function to be estimated, our model predicts that after the induction of LTP, causing long-term synaptic efficacy to increase, a depressing synapse should become even more depressing. That is, in a protocol using trains of presynaptic stimuli, as the initial EPSP becomes stronger due to LTP, subsequent EPSPs should become weakened and this weakening should be more pronounced with LTP. This form of redistribution of synaptic efficacies agrees well with electrophysiological data on synapses connecting layer 5 pyramidal neurons.

The effects of long (C20/22) and short (C18) chain omega-3 fatty acids on keel bone fractures, bone biomechanics, behavior, and egg production in free-range laying hens.

Keel fractures in the laying hen are the most critical animal welfare issue facing the egg production industry, particularly with the increased use of extensive systems in response to the 2012 EU directive banning conventional battery cages. The current study is aimed at assessing the effects of 2 omega-3 (n3) enhanced diets on bone health, production endpoints, and behavior in free-range laying hens. Data was collected from 2 experiments over 2 laying cycles, each of which compared a (n3) supplemented diet with a control diet. Experiment 1 employed a diet supplemented with a 60:40 fish oil-linseed mixture (n3:n6 to 1.35) compared with a control diet (n3:n6 to 0.11), whereas the n3 diet in Experiment 2 was supplemented with a 40:60 fish oil-linseed (n3:n6 to 0.77) compared to the control diet (n3:n6 to 0.11). The n3 enhanced diet of Experiment 1 had a higher n3:n6 ratio, and a greater proportion of n3 in the long chain (C20/22) form (0.41 LC:SC) than that of Experiment 2 (0.12 LC:SC). Although dietary treatment was successful in reducing the frequency of fractures by approximately 27% in Experiment 2, data from Experiment 1 indicated the diet actually induced a greater likelihood of fracture (odds ratio: 1.2) and had substantial production detriment. Reduced keel breakage during Experiment 2 could be related to changes in bone health as n3-supplemented birds demonstrated greater load at failure of the keel, and tibiae and humeri that were more flexible. These results support previous findings that n3-supplemented diets can reduce fracture likely by increasing bone strength, and that this can be achieved without detriment to production. However, our findings suggest diets with excessive quantities of n3, or very high levels of C20/22, may experience health and production detriments. Further research is needed to optimize the quantity and type of n3 in terms of bone health and production variables and investigate the potential associated mechanisms.

[Immunosuppressive drugs - how they work, their side effects and interactions]

The central issue in organ transplantation remains suppression of allograft rejection. Immunosuppression can be achieved by depleting lymphocytes, diverting lymphocyte traffic, or blocking lymphocyte response pathways. Immunosuppressive drugs include small-molecule drugs, depleting and nondepleting protein drugs (polyclonal and monoclonal antibodies), fusion proteins, intravenous immune globulin, and glucocorticoids. Small-molecule immunosuppressive agents include calcineurin-inhibitors (cyclosporine, tacrolimus), Target-of-Rapamycin Inhibitors (Sirolimus, Everolimus), inhibitors of nucleotide synthesis and azathioprine. The review covers the mode of action of these drugs with a special focus on belatacept, a new promising fusion protein. Different immuo-suppressive strategies mean also different safety profiles. Common side effects include the consequences of diminished immuno- response, i.e. infections and cancer (mainly involving the skin). Toxic side effects of immunosuppressive drugs range in a wide spectrum that involves almost every organ. The major interest of this toxic effects is the cardiovascular tolerance (with large differences from drug to drug), that are discussed seperately. The calcineurin- and mTOR-inhibitors are both metabolized by the CYP450 3A4 enzyme, which is also involved in the metabolism of many other drugs. The review discusses the most important interactions that in- or decreases the through level of these drugs.

Bottom-up effects of plant diversity on multitrophic interactions in a biodiversity experiment

Biodiversity is rapidly declining, and this may negatively affect ecosystem processes, including economically important ecosystem services. Previous studies have shown that biodiversity has positive effects on organisms and processes across trophic levels. However, only a few studies have so far incorporated an explicit food-web perspective. In an eight-year biodiversity experiment, we studied an unprecedented range of above- and below-ground organisms and multitrophic interactions. A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments. Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory. This was true both for abundance and species richness of organisms. Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs. Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores. Density and richness of carnivorous taxa was independent of vegetation structure. Below-ground responses to plant diversity were consistently weaker than above-ground responses. Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism. Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels. Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades.

Towards optimal treatment with growth hormone in short children and adolescents: evidence and theses

Treatment with growth hormone (GH) has become standard practice for replacement in GH-deficient children or pharmacotherapy in a variety of disorders with short stature. However, even today, the reported adult heights achieved often remain below the normal range. In addition, the treatment is expensive and may be associated with long-term risks. Thus, a discussion of the factors relevant for achieving an optimal individual outcome in terms of growth, costs, and risks is required. In the present review, the heterogenous approaches of treatment with GH are discussed, considering the parameters available for an evaluation of the short- and long-term outcomes at different stages of treatment. This discourse introduces the potential of the newly emerging prediction algorithms in comparison to other more conventional approaches for the planning and evaluation of the response to GH. In rare disorders such as those with short stature, treatment decisions cannot easily be deduced from personal experience. An interactive approach utilizing the derived experience from large cohorts for the evaluation of the individual patient and the required decision-making may facilitate the use of GH. Such an approach should also lead to avoiding unnecessary long-term treatment in unresponsive individuals.

The strategies of the Theileria parasite: a new twist in host-pathogen interactions

Theileria parasites infect and transform cells of the ruminant immune system. Continuous proliferation and survival of Theileria-transformed cells involves the well-orchestrated activation of several host-cell signalling pathways. Constitutive NF-kappa B (nuclear factor kappa B) activation is accomplished by recruiting the IKK (I kappa B kinase) complex, a central regulator of NF-kappa B pathways, to the surface of the transforming schizont, where it becomes permanently activated. Constitutive activation of the PI-3K-PKB [phosphoinositide 3-kinase-(Akt) protein kinase B] pathway is likely to be indirect and is essential for continuous proliferation. Theileria-transformed T cells express a range of anti-apoptotic proteins that can be expected to provide protection against apoptosis induced by death receptors, as well as cellular control mechanisms that are mobilised to eliminate cells that entered a cycle of uncontrolled proliferation.

Differential patterns of multisensory interactions in core and belt areas of human auditory cortex

The auditory cortex is anatomically segregated into a central core and a peripheral belt region, which exhibit differences in preference to bandpassed noise and in temporal patterns of response to acoustic stimuli. While it has been shown that visual stimuli can modify response magnitude in auditory cortex, little is known about differential patterns of multisensory interactions in core and belt. Here, we used functional magnetic resonance imaging and examined the influence of a short visual stimulus presented prior to acoustic stimulation on the spatial pattern of blood oxygen level-dependent signal response in auditory cortex. Consistent with crossmodal inhibition, the light produced a suppression of signal response in a cortical region corresponding to the core. In the surrounding areas corresponding to the belt regions, however, we found an inverse modulation with an increasing signal in centrifugal direction. Our data suggest that crossmodal effects are differentially modulated according to the hierarchical core-belt organization of auditory cortex.

Geriatric Pain Measure short form: development and initial evaluation

OBJECTIVES: To develop and evaluate a short form of the 24-item Geriatric Pain Measure (GPM) for use in community-dwelling older adults. DESIGN: Derivation and validation of a 12-item version of the GPM in a European and an independent U.S. sample of community-dwelling older adults. SETTING: Three community-dwelling sites in London, United Kingdom; Hamburg, Germany; Solothurn, Switzerland; and two ambulatory geriatrics clinics in Los Angeles, California. PARTICIPANTS: European sample: 1,059 community-dwelling older persons from three sites (London, UK; Hamburg, Germany; Solothurn, Switzerland); validation sample: 50 persons from Los Angeles, California, ambulatory geriatric clinics. MEASUREMENTS: Multidimensional questionnaire including self-reported demographic and clinical information. RESULTS: Based on item-to-total scale correlations in the European sample, 11 of 24 GPM items were selected for inclusion in the short form. One additional item (pain-related sleep problems) was included based on clinical relevance. In the validation sample, the Cronbach alpha of GPM-12 was 0.92 (individual subscale range 0.77-0.92), and the Pearson correlation coefficient (r) between GPM-12 and the original GPM was 0.98. The correlation between the GPM-12 and the McGill Pain Questionnaire was 0.63 (P<.001), similar to the correlation between the original GPM and the McGill Pain Questionnaire (Pearson r=0.63; P<.001). Exploratory factor analysis indicated that the GPM-12 covers three subfactors (pain intensity, pain with ambulation, disengagement because of pain). CONCLUSION: The GPM-12 demonstrated good validity and reliability in these European and U.S. populations of older adults. Despite its brevity, the GPM-12 captures the multidimensional nature of pain in three subscales. The self-administered GPM-12 may be useful in the clinical assessment process and management of pain and in pain-related research in older persons.

Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome in which the known susceptibility genes (DKC1, TERC, and TERT) belong to the telomere maintenance pathway; patients with DC have very short telomeres. We used multicolor flow fluorescence in situ hybridization analysis of median telomere length in total blood leukocytes, granulocytes, lymphocytes, and several lymphocyte subsets to confirm the diagnosis of DC, distinguish patients with DC from unaffected family members, identify clinically silent DC carriers, and discriminate between patients with DC and those with other bone marrow failure disorders. We defined "very short" telomeres as below the first percentile measured among 400 healthy control subjects over the entire age range. Diagnostic sensitivity and specificity of very short telomeres for DC were more than 90% for total lymphocytes, CD45RA+/CD20- naive T cells, and CD20+ B cells. Granulocyte and total leukocyte assays were not specific; CD45RA- memory T cells and CD57+ NK/NKT were not sensitive. We observed very short telomeres in a clinically normal family member who subsequently developed DC. We propose adding leukocyte subset flow fluorescence in situ hybridization telomere length measurement to the evaluation of patients and families suspected to have DC, because the correct diagnosis will substantially affect patient management.

Short-term effects of hygiene education for preschool (kindergarten) children: a clinical study

AIM: To evaluate the outcomes of short (15 minutes) oral hygiene vs. hand hygiene education for preschool children 4 weeks after these interventions. MATERIALS AND METHODS: Sixty-one preschool children (age range 4-6 years) attending four kindergarten classes participated in a 15-minute health education programme on the importance of body cleanliness for general health. In addition, specific instructions on oral hygiene were provided for two randomly selected classes (30 children), while the remaining two classes (31 children) were given instruction of hand and nail cleaning. The oral hygiene status was assessed usingthe plaque control record (PCR). The cleanliness of the hands and fingernails was determined using a hand hygiene index (HHI) and a nail hygiene index (NHI). All three parameters were assessed before the intervention as well as 4 weeks thereafter. RESULTS: Four weeks after education, the PCR had improved for all children from 79.95% to 72.35% (p < 0.001). The NHI had improved from 74.91% to 61.71% (p < 0.001). In addition, the mean PCR of the children given oral hygiene instruction decreased from 83.67% to 72.40%, while the mean PCR of the children given hand and nail cleaning instruction decreased from 76.23% to 72.29% (interaction effect 'time x type of instruction': p = 0.044). Girls' PCR improved significantly more than boys' PCR (Girls, 80.98 vs. 69.71; boys, 78.33 vs. 75.31; p = 0.021). CONCLUSIONS: The results of the study show that even a short, school-based educational intervention at an early age may affect children's oral health promotion significantly. Teachers should, therefore, be encouraged to educate children from an early age about oral hygiene promotion.