Non-standard interactions versus non-unitary lepton flavor mixing at a neutrino factory

The impact of heavy mediators on neutrino oscillations is typically described by non-standard four-fermion interactions (NSIs) or non-unitarity (NU). We focus on leptonic dimension-six effective operators which do not produce charged lepton flavor violation. These operators lead to particular correlations among neutrino production, propagation, and detection non-standard effects. We point out that these NSIs and NU phenomenologically lead, in fact, to very similar effects for a neutrino factory, for completely different fundamental reasons. We discuss how the parameters and probabilities are related in this case, and compare the sensitivities. We demonstrate that the NSIs and NU can, in principle, be distinguished for large enough effects at the example of non-standard effects in the $\mu$-$\tau$-sector, which basically corresponds to differentiating between scalars and fermions as heavy mediators as leading order effect. However, we find that a near detector at superbeams could provide very synergistic information, since the correlation between source and matter NSIs is broken for hadronic neutrino production, while NU is a fundamental effect present at any experiment.Comment: 32 pages, 5 figures. Final version published in JHEP. v3: Typo in Eq. (27) correcte

CO2-brine injectivity tests in high co2 content carbonate field, sarawak basin, offshore east Malaysia

We conducted relatively long duration core-flooding tests on three representative core samples under reservoir conditions to quantify the potential impact of flow rates on fines production/permeability change. Supercritical CO2 was injected cyclically with incremental increases in flow rate (2─14 ml/min) with live brine until a total of 7 cycles were completed. To avoid unwanted fluid-rock reaction when live brine was injected into the sample, and to mimic the in-situ geochemical conditions of the reservoir, a packed column was installed on the inflow accumulator line to pre-equilibrate the fluid before entering the core sample. The change in the gas porosity and permeability of the tested plug samples due to different mechanisms (dissolution and/or precipitation) that may occur during scCO2/live brine injection was investigated. Nuclear magnetic resonance (NMR) T2 determination, X-ray CT scans and chemical analyses of the produced brine were also conducted. Results of pre- and post-test analyses (poroperm, NMR, X-ray CT) showed no clear evidence of formation damage even after long testing cycles and only minor or no dissolution (after large injected pore volumes (PVs) ~ 200). The critical flow rates (if there is one) were higher than the maximum rates applied. Chemical analyses of the core effluent showed that the rock samples for which a pre-column was installed do not experience carbonate dissolution

Comparison of two protective lung ventilatory regimes on oxygenation during one-lung ventilation: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The efficacy of protective ventilation in acute lung injury has validated its use in the operating room for patients undergoing thoracic surgery with one-lung ventilation (OLV). The purpose of this study was to investigate the effects of two different modes of ventilation using low tidal volumes: pressure controlled ventilation (PCV) vs. volume controlled ventilation (VCV) on oxygenation and airway pressures during OLV.</p> <p>Methods</p> <p>We studied 41 patients scheduled for thoracoscopy surgery. After initial two-lung ventilation with VCV patients were randomly assigned to one of two groups. In one group OLV was started with VCV (tidal volume 6 mL/kg, PEEP 5) and after 30 minutes ventilation was switched to PCV (inspiratory pressure to provide a tidal volume of 6 mL/kg, PEEP 5) for the same time period. In the second group, ventilation modes were performed in reverse order. Airway pressures and blood gases were obtained at the end of each ventilatory mode.</p> <p>Results</p> <p>PaO₂, PaCO₂and alveolar-arterial oxygen difference did not differ between PCV and VCV. Peak airway pressure was significantly lower in PCV compared with VCV (19.9 ± 3.8 cmH₂O vs 23.1 ± 4.3 cmH₂O; p < 0.001) without any significant differences in mean and plateau pressures.</p> <p>Conclusions</p> <p>In patients with good preoperative pulmonary function undergoing thoracoscopy surgery, the use of a protective lung ventilation strategy with VCV or PCV does not affect the oxygenation. PCV was associated with lower peak airway pressures.</p

Cost of the Diet: a method and software to calculate the lowest cost of meeting recommended intakes of energy and nutrients from local foods

Background When food is available, the main obstacle to access is usually economic: people may not be able to afford a nutritious diet, even if they know what foods to eat. The Cost of the Diet method and software was developed to apply linear programming to better understand the extent to which poverty may affect people’s ability to meet their nutritional specifications. This paper describes the principles of the method; the mathematics underlying the linear programming; the parameters and assumptions on which the calculations are based; and then illustrates the output of the software using examples taken from assessments. Results The software contains five databases: the energy and nutrient content of foods; the energy and nutrient specifications of individuals; predefined groups of individuals in typical households; the portion sizes of foods; and currency conversion factors. Data are collected during a market survey to calculate the average cost of foods per 100 g while focus group discussions are used to assess local dietary habits and preferences. These data are presented to a linear programming solver within the software which selects the least expensive combination of local foods for four standard diets that meet specifications for: energy only; energy and macronutrients; energy, macronutrients and micronutrients; and energy, macronutrients and micronutrients but with constraints on the amounts per meal that are consistent with typical dietary habits. Most parameters in the software can be modified by users to examine the potential impact of a wide range of theoretical interventions. The output summarises for each diet the costs, quantity and proportion of energy and nutrient specifications provided by all the foods selected for a given individual or household by day, week, season and year. When the cost is expressed as a percentage of income, the affordability of the diet can be estimated. Conclusions The Cost of the Diet method and software could be used to inform programme design and behaviour change communication in the fields of nutrition, food security, livelihoods and social protection as well as to influence policies and advocacy debates on the financial cost of meeting energy and nutrient specifications

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Diaphragm Muscle Weakness in an Experimental Porcine Intensive Care Unit Model

In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit

Immunogenic Profiling in Mice of a HIV/AIDS Vaccine Candidate (MVA-B) Expressing Four HIV-1 Antigens and Potentiation by Specific Gene Deletions

BACKGROUND: The immune parameters of HIV/AIDS vaccine candidates that might be relevant in protection against HIV-1 infection are still undefined. The highly attenuated poxvirus strain MVA is one of the most promising vectors to be use as HIV-1 vaccine. We have previously described a recombinant MVA expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B), that induced HIV-1-specific immune responses in different animal models and gene signatures in human dendritic cells (DCs) with immunoregulatory function. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to characterize in more detail the immunogenic profile of MVA-B and to improve its immunogenicity we have generated a new vector lacking two genes (A41L and B16R), known to counteract host immune responses by blocking the action of CC-chemokines and of interleukin 1beta, respectively (referred as MVA-B DeltaA41L/DeltaB16R). A DNA prime/MVA boost immunization protocol was used to compare the adaptive and memory HIV-1 specific immune responses induced in mice by the parental MVA-B and by the double deletion mutant MVA-B DeltaA41L/DeltaB16R. Flow cytometry analysis revealed that both vectors triggered HIV-1-specific CD4(+) and CD8(+) T cells, with the CD8(+) T-cell compartment responsible for >91.9% of the total HIV-1 responses in both immunization groups. However, MVA-B DeltaA41L/DeltaB16R enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4(+) and CD8(+) T-cell immune responses. HIV-1-specific CD4(+) T-cell responses were polyfunctional and preferentially Env-specific in both immunization groups. Significantly, while MVA-B induced preferentially Env-specific CD8(+) T-cell responses, MVA-B DeltaA41L/DeltaB16R induced more GPN-specific CD8(+) T-cell responses, with an enhanced polyfunctional pattern. Both vectors were capable of producing similar levels of antibodies against Env. CONCLUSIONS/SIGNIFICANCE: These findings revealed that MVA-B and MVA-B DeltaA41L/DeltaB16R induced in mice robust, polyfunctional and durable T-cell responses to HIV-1 antigens, but the double deletion mutant showed enhanced magnitude and quality of HIV-1 adaptive and memory responses. Our observations are relevant in the immune evaluation of MVA-B and on improvements of MVA vectors as HIV-1 vaccines

Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features

<p>Abstract</p> <p>Background</p> <p>Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a pro-apoptotic member of the Bcl-2 family induced under hypoxia. Low or absent expression has recently been described in human tumors, including gastrointestinal tumors, resulting in poor prognosis. Little is known about BNIP3 expression in invasive breast cancer. The aim of the present study was to investigate the expression of BNIP3 in invasive breast cancer at the mRNA and protein level in correlation with the hypoxic response and clinicopathological features.</p> <p>Methods</p> <p>In 40 cases of invasive breast cancer, BNIP3 mRNA <it>in situ </it>hybridization was performed on frozen sections with a digoxigenin labeled anti-BNIP3 probe. Paraffin embedded sections of the same specimens were used to determine protein expression of BNIP3, Hypoxia Inducible Factor 1 alpha (HIF-1α) and its downstream targets Glucose Transporter 1 (Glut-1) and Carbonic Anhydrase (CAIX) by immunohistochemistry.</p> <p>Results</p> <p>BNIP3 mRNA was expressed in 16/40 (40%) of the cases and correlated with BNIP3 protein expression (p = 0.0218). Neither BNIP3 protein nor mRNA expression correlated with expression of HIF-1α expression or its downstream targets. Tumors which showed loss of expression of BNIP3 had significantly more often lymph node metastases (82% vs 39%, p = 0.010) and showed a higher mitotic activity index (p = 0.027). BNIP3 protein expression was often nuclear in normal breast, but cytoplasmic in tumor cells.</p> <p>Conclusion</p> <p>BNIP3 expression is lost in a significant portion of invasive breast cancers, which is correlated with poor prognostic features such as positive lymph node status and high proliferation, but not with the hypoxic response.</p

Combining dispersion modelling with synoptic patterns to understand the wind-borne transport into the UK of the bluetongue disease vector

Bluetongue, an economically important animal disease, can be spread over long distances by carriage of insect vectors (Culicoides biting midges) on the wind. The weather conditions which influence the midge’s flight are controlled by synoptic scale atmospheric circulations. A method is proposed that links wind-borne dispersion of the insects to synoptic circulation through the use of a dispersion model in combination with principal component analysis (PCA) and cluster analysis. We illustrate how to identify the main synoptic situations present during times of midge incursions into the UK from the European continent. A PCA was conducted on high-pass-filtered mean sea-level pressure data for a domain centred over north-west Europe from 2005 to 2007. A clustering algorithm applied to the PCA scores indicated the data should be divided into five classes for which averages were calculated, providing a classification of the main synoptic types present. Midge incursion events were found to mainly occur in two synoptic categories; 64.8% were associated with a pattern displaying a pressure gradient over the North Atlantic leading to moderate south-westerly flow over the UK and 17.9% of the events occurred when high pressure dominated the region leading to south-easterly or easterly winds. The winds indicated by the pressure maps generally compared well against observations from a surface station and analysis charts. This technique could be used to assess frequency and timings of incursions of virus into new areas on seasonal and decadal timescales, currently not possible with other dispersion or biological modelling methods

Orientation and dynamics of transmembrane peptides: the power of simple models

In this review we discuss recent insights obtained from well-characterized model systems into the factors that determine the orientation and tilt angles of transmembrane peptides in lipid bilayers. We will compare tilt angles of synthetic peptides with those of natural peptides and proteins, and we will discuss how tilt can be modulated by hydrophobic mismatch between the thickness of the bilayer and the length of the membrane spanning part of the peptide or protein. In particular, we will focus on results obtained on tryptophan-flanked model peptides (WALP peptides) as a case study to illustrate possible consequences of hydrophobic mismatch in molecular detail and to highlight the importance of peptide dynamics for the experimental determination of tilt angles. We will conclude with discussing some future prospects and challenges concerning the use of simple peptide/lipid model systems as a tool to understand membrane structure and function