Constraining A4A_4 Leptonic Flavour Model Parameters at Colliders and Beyond

The observed pattern of mixing in the neutrino sector may be explained by the presence of a non-Abelian, discrete flavour symmetry broken into residual subgroups at low energies. Many flavour models require the presence of Standard Model singlet scalars which can promptly decay to charged leptons in a flavour-violating manner. We constrain the model parameters of a generic $A_4$ leptonic flavour model using a synergy of experimental data including limits from charged lepton flavour conversion, an 8 TeV collider analysis and constraints from the anomalous magnetic moment of the muon. The most powerful constraints derive from the MEG collaborations' limit on Br$\left(\mu\to e\gamma\right)$ and the reinterpretation of an 8 TeV ATLAS search for anomalous productions of multi-leptonic final states. We quantify the exclusionary power of each of these experiments and identify regions where the constraints from collider and MEG experimental data are complementary.Comment: v1: 28 + 9 pages, 8 figures. v2: 30 + 10 pages, 10 figures. v2 consistent with JHEP accepted version where further discussion of results and several more references were adde

Comment on 'Giving According to GARP: An Experimental Test of the Consistency of Preferences for Altruism'

We present clean experimental evidence that a methodological confound was introduced by Andreoni and Miller (2002) that leads to diametrically opposed conclusions regarding comparisons of preferences between categories of fellow human beings distinguished by gender or age. Our study is a warning not to run the Andreoni-Miller tests of the consistency of altruistic preferences on the basis of their ‘interactive’ experimental protocol, and in particular not to perform preference estimations with the purpose of said comparisons. It is more interpretable and controllable to run the traditional, standard dictator game

What Can Parents Do to Reduce Youth Obesity? An Initial Study With a Diverse Sample

The body mass index (BMI) of diverse, low-income fifth grade students (n = 36) was regressed on physical activity (Child Adolescent Activity Log), percentage dietary fat (Food Habits Questionnaire), and the Food/Activity Parenting Practices Questionnaire. The model explained 50% of the variance in student BMI, adjusted R2 = .50, F (4, 19) = 6.84, p = .001. Students accurately perceived their weight status. Students\u27 perception of parenting strategies, along with dietary fat, was significantly associated with their BMI. Parent\u27s (n = 14) BMI, not the child\u27s, was associated with the strategies they used. Three parents tested an online authoritative parenting program. Further research is needed

Sonographic Evaluation of Gastric Residual Volume during Enteral Nutrition in Critically Ill Patients Using a Miniaturized Ultrasound Device

Background: To assess the risk of aspiration, nutrient tolerance, and gastric emptying of patients in ICUs, gastric ultrasound can provide information about the gastric contents. Using established formulas, the gastric residual volume (GRV) can be calculated in a standardized way by measuring the gastric antrum. The purpose of this study was to determine the GRV in a cohort of enterally fed patients using a miniaturized ultrasound device to achieve knowledge about feasibility and the GRV over time during the ICU stay. The findings could contribute to the optimization of en teral nutrition (EN) therapy. Methods: A total of 217 ultrasound examinations with 3 measurements each (651 measurements in total) were performed twice daily (morning and evening) in a longitudinal observational study on 18 patients with EN in the interdisciplinary surgical ICU of Saarland Univer sity Medical Center. The measured values of the GRV were analyzed in relation to the clinical course, the nutrition, and other parameters. Results: Measurements could be performed without interrupting the flow of clinical care and without pausing EN. The GRV was significantly larger with sparsely auscultated bowel sounds than with normal and excited bowel sounds (p < 0.01). Furthermore, a significantly larger GRV was present when using a high-caloric/low-protein nutritional product compared to an isocaloric product (p = 0.02). The GRV at the morning and evening measurements showed no circadian rhythm. When comparing the first and last ultrasound examination of each patient, there was a tendency towards an increased GRV (p = 0.07). Conclusion: The GRV measured by miniaturized ultrasound devices can provide important information about ICU patients without restricting treatment procedures in the ICU. Measurements are possible while EN therapy is ongoing. Further studies are needed to establish gastric ultrasound as a management tool in nutrition therapy

Definition of the σW regulon of Bacillus subtilis in the absence of stress

Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses to environmental stresses. Despite intensive research, the molecular dissection of ECF sigma factor regulons has remained a major challenge due to overlaps in the ECF sigma factor-regulated genes and the stimuli that activate the different ECF sigma factors. Here we have employed tiling arrays to single out the ECF σW regulon of the Gram-positive bacterium Bacillus subtilis from the overlapping ECF σX, σY, and σM regulons. For this purpose, we profiled the transcriptome of a B. subtilis sigW mutant under non-stress conditions to select candidate genes that are strictly σW-regulated. Under these conditions, σW exhibits a basal level of activity. Subsequently, we verified the σW-dependency of candidate genes by comparing their transcript profiles to transcriptome data obtained with the parental B. subtilis strain 168 grown under 104 different conditions, including relevant stress conditions, such as salt shock. In addition, we investigated the transcriptomes of rasP or prsW mutant strains that lack the proteases involved in the degradation of the σW anti-sigma factor RsiW and subsequent activation of the σW-regulon. Taken together, our studies identify 89 genes as being strictly σW-regulated, including several genes for non-coding RNAs. The effects of rasP or prsW mutations on the expression of σW-dependent genes were relatively mild, which implies that σW-dependent transcription under non-stress conditions is not strictly related to RasP and PrsW. Lastly, we show that the pleiotropic phenotype of rasP mutant cells, which have defects in competence development, protein secretion and membrane protein production, is not mirrored in the transcript profile of these cells. This implies that RasP is not only important for transcriptional regulation via σW, but that this membrane protease also exerts other important post-transcriptional regulatory functions

Subcellular localization of the antidepressant-sensitive norepinephrine transporter

<p>Abstract</p> <p>Background</p> <p>Reuptake of synaptic norepinephrine (NE) via the antidepressant-sensitive NE transporter (NET) supports efficient noradrenergic signaling and presynaptic NE homeostasis. Limited, and somewhat contradictory, information currently describes the axonal transport and localization of NET in neurons.</p> <p>Results</p> <p>We elucidate NET localization in brain and superior cervical ganglion (SCG) neurons, aided by a new NET monoclonal antibody, subcellular immunoisolation techniques and quantitative immunofluorescence approaches. We present evidence that axonal NET extensively colocalizes with syntaxin 1A, and to a limited degree with SCAMP2 and synaptophysin. Intracellular NET in SCG axons and boutons also quantitatively segregates from the vesicular monoamine transporter 2 (VMAT2), findings corroborated by organelle isolation studies. At the surface of SCG boutons, NET resides in both lipid raft and non-lipid raft subdomains and colocalizes with syntaxin 1A.</p> <p>Conclusion</p> <p>Our findings support the hypothesis that SCG NET is segregated prior to transport from the cell body from proteins comprising large dense core vesicles. Once localized to presynaptic boutons, NET does not recycle via VMAT2-positive, small dense core vesicles. Finally, once NET reaches presynaptic plasma membranes, the transporter localizes to syntaxin 1A-rich plasma membrane domains, with a portion found in cholera toxin-demarcated lipid rafts. Our findings indicate that activity-dependent insertion of NET into the SCG plasma membrane derives from vesicles distinct from those that deliver NE. Moreover, NET is localized in presynaptic membranes in a manner that can take advantage of regulatory processes targeting lipid raft subdomains.</p

Real-Time Evaluation of Optic Nerve Sheath Diameter (ONSD) in Awake, Spontaneously Breathing Patients

(1) Background: Reliable ultrasonographic measurements of optic nerve sheath diameter (ONSD) to detect increased intracerebral pressure (ICP) has not been established in awake patients with continuous invasive ICP monitoring. Therefore, in this study, we included fully awake patients with and without raised ICP and correlated ONSD with continuously measured ICP values. (2) Methods: In a prospective study, intracranial pressure (ICP) was continuously measured in 25 patients with an intraparenchymatic P-tel probe. Ultrasonic measurements were carried out three times for each optic nerve in vertical and horizontal directions. ONSD measurements and ICP were correlated. Patients with ICP of 2.0–10.0 mmHg were compared with patients suffering from an ICP of 10.1–24.2 mmHg. (3) Results: In all patients, the ONSD vertical and horizontal measurement for both eyes correlated well with the ICP (Pearson R = 0.68–0.80). Both measurements yielded similar results (Bland-Altman: vertical bias: −0.09 mm, accuracy: ±0.66 mm; horizontal bias: −0.06 mm, accuracy: ±0.48 mm). For patients with an ICP of 2.0–10.0 mmHg compared to an ICP of 10.1–24.2, ROC (receiver operating characteristic) analyses showed that ONSD measurement accurately predicts elevated ICP (optimal cut-off value 5.05 mm, AUC of 0.91, sensitivity 92% and specificity 90%, p < 0.001). (4) Conclusions: Ultrasonographic measurement of ONSD in awake, spontaneously breathing patients provides a valuable method to evaluate patients with suspected increased ICP. Additionally, it provides a potential tool for rapid assessment of ICP at the bedside and to identify patients at risk for a poor neurological outcome

Cell-Derived Vesicles for Antibiotic Delivery-Understanding the Challenges of a Biogenic Carrier System

Recently, extracellular vesicles (EVs) sparked substantial therapeutic interest, particularly due to their ability to mediate targeted transport between tissues and cells. Yet, EVs’ technological translation as therapeutics strongly depends on better biocompatibility assessments in more complex models and elementary in vitro–in vivo correlation, and comparison of mammalian versus bacterial vesicles. With this in mind, two new types of EVs derived from human B-lymphoid cells with low immunogenicity and from non-pathogenic myxobacteria SBSr073 are introduced here. A large-scale isolation protocol to reduce plastic waste and cultivation space toward sustainable EV research is established. The biocompatibility of mammalian and bacterial EVs is comprehensively evaluated using cytokine release and endotoxin assays in vitro, and an in vivo zebrafish larvae model is applied. A complex three-dimensional human cell culture model is used to understand the spatial distribution of vesicles in epithelial and immune cells and again used zebrafish larvae to study the biodistribution in vivo. Finally, vesicles are successfully loaded with the fluoroquinolone ciprofloxacin (CPX) and showed lower toxicity in zebrafish larvae than free CPX. The loaded vesicles are then tested effectively on enteropathogenic Shigella, whose infections are currently showing increasing resistance against available antibiotics

Are elites really less fair-minded?

US power ‘elites’ are substantially less fair-minded than ‘non-elite’ general populations claims a study by Ray Fisman and coauthors [Science 349, 6254 (2015)]. This supposedly explains why US governments, run by people less fair than the citizens they represent, have been uninclined to tackle inequality. We critically replicated the study, because different experimental protocols for ‘elites’ (interactive variants) and ‘non-elites’ (standard dictator games) were used to measure preferences. We find that the protocol potpourri drove the conclusion: under standard protocols, we find no significant class differences, if any opposite ones. Our work highlights the risk of producing false positives when ex post results appear invitingly plausible