Emergence of New Pandemic GII.4 Sydney Norovirus Strain Correlates With Escape From Herd Immunity

Background. GII.4 noroviruses are a significant source of acute gastroenteritis worldwide, causing the majority of human norovirus outbreaks. Evolution of the GII.4 major capsid protein occurs rapidly, resulting in the emergence of new strains that produce successive waves of pandemic disease. A new pandemic isolate, GII.4 2012 Sydney, largely replaced previously circulating strains in late 2012. We compare the antigenic properties of GII.4 2012 Sydney with previously circulating strains. Methods. To determine whether GII.4-2012 Sydney is antigenically different from recently circulating strains GII.4-2006 Minerva and GII.4-2009 New Orleans in previously identified blockade epitopes, we compared reactivity and blockade profiles of GII.4-2006, GII.4-2009, and GII.4-2012 virus-like particles in surrogate neutralization/blockade assays using monoclonal antibodies and human polyclonal sera. Results. Using monoclonal antibodies that map to known blockade epitopes in GII.4-2006 and GII.4-2009 and human outbreak polyclonal sera, we demonstrate either complete loss or significantly reduced reactivity and blockade of GII.4.2012 compared to GII.4-2006 and GII.4-2009. Conclusions. GII.4-2012 Sydney is antigenically different from GII.4-2006 Minerva and GII.4-2009 New Orleans in at least 2 key blockade epitopes. Viral evolution in key potential neutralization epitopes likely allowed GII.4-2012 to escape from human herd immunity and emerge as the new predominant strai

Enhancement of Heavy-Duty Engines Performance and Reliability Using Cylinder Pressure Information

Sustainability issues are becoming increasingly prominent in applications requiring the use of heavy-duty engines. Therefore, it is important to cut emissions and costs of such engines to re-duce the carbon footprint and keep the operating expenses under control. Even if for some applications a battery electric equipment is introduced, the diesel-equipped machinery is still popular, thanks to the longer operating range. In this field, the open pit mines are a good example. In fact, the Total Cost of Ownership (TCO) of the mining equipment is highly impacted by fuel consumption (engine efficiency) and reliability (service interval and en-gine life). The present work is focused on efficiency enhancements achievable through the ap-plication of a combustion control strategy based on the in-cylinder pressure information. The benefits are mainly due to two factors. First, the negative effects of injectors ageing can be com-pensated. Second, cylindrical online calibration of the control parameters enables the combus-tion system optimization. The article is divided into two parts. The first part describes the tool-chain that is designed for the real time application of the combustion control system, while the second part concerns the algorithm that would be implemented on the Engine Control Unit (ECU) to leverage the in-cylinder pressure information. The assessment of the potential benefits and feasibility of the combustion control algorithm is carried out in a Software in the Loop (SiL) environment, simulating both the developed control strategy and the engine behavior (Liebherr D98). Our goal is to validate the control algorithm through SiL simulations. The results of the validation process demonstrate the effectiveness of the control strategy: firstly, cylinder dispari-ty on IMEP (+/-2.5% in reference conditions) is virtually canceled. Secondly, MFB50 is individual-ly optimized, equalizing Pmax among the cylinders (+/-4% for the standard calibration), without exceeding the reliability threshold. In addition to this, BSFC is reduced by 1%, thanks to the ac-curate cylinder-by-cylinder calibration. Finally, ageing effects or fuel variations can be implicitly compensated, keeping optimal performance thorough engine life

Analysis of fabric evolution and metamorphic reaction progress at Lago della Vecchia-Valle d'Irogna, Sesia-Lanzo Zone, Western Alps

The Lago della Vecchia-Valle d'Irogna rocks are part of the Eclogitic Micaschists Complex (EMC) of the Sesia-Lanzo Zone, western Austroalpine domain. The 1:10,000 scale map includes metaintrusive, minor micaschist, banded gneiss, and metabasic boudins. The multiscale structural analysis reveals successive magmatic and tectono-metamorphic stages: during M0 the metaintrusive protoliths emplaced; D1 took place under eclogite-facies conditions; during D2 stage, a pervasive foliation developed under retrograde blueschist-facies conditions; D3–D4 and D5 structures developed under greenschist-facies conditions; during M6 andesitic dykes intruded. The mapped degree of fabric evolution (FE) and metamorphic transformation (MT) related to D2-foliation shows that the MT was not only controlled by bulk rock and mineral compositions, but also by FE. The development of a pervasive blueschist-facies D2-foliation is in contrast with the eclogitic dominant fabric generally recorded in the EMC. This difference suggests that FE and MT are potentially responsible for km-scale heterogeneities in the tectono-metamorphic record

Analisi della trasmissione del calore nel terreno in presenza di scambiatori integrati nelle opere di fondazione

LAUREA MAGISTRALEIl lavoro di tesi è stato focalizzato sullo studio delle fonti di energia geotermica a bassa entalpia, utilizzate per il riscaldamento e/o raffrescamento di edifici o altre strutture. Negli ultimi anni, le tecnologie utilizzate per sfruttare queste risorse stanno subendo un rapido sviluppo e una sempre maggiore diffusione, in particolare la tipologia detta "energy foundation". L'impianto consiste in un sistema di serpentine disposte nelle fondazioni della struttura nelle quali circola un fluido che, attraverso una pompa di calore, permette di estrarre calore dal terreno durante i mesi invernali e cederlo durante l'estate. Le analisi sono state svolte con approccio numerico, ricorrendo al metodo degli elementi finiti. Nella prima parte del lavoro è stato studiato il campo di temperatura che si crea nel terreno in prossimità di un edificio con piani interrati, al variare dell'altezza di falda e delle fluttuazioni stagionali della temperatura esterna. Si è sottolineata inoltre la differenza tra le condizioni di aperta campagna e quelle di ambiente urbano, dove la diffusa presenza di edifici porta ad un aumento della temperatura nel suolo. Nella seconda parte è stato analizzato l'impianto di energy foundation realizzato in un edificio realmente costruito nel comune di Tradate (VA), focalizzando l'attenzione sui principali fattori che ne regolano il funzionamento. La velocità di movimento del fluido nella serpentina ha un ruolo importante nella trasmissione del calore, poiché il regime di moto presente influenza lo scambio termico e vincola la progettazione e la gestione dell'impianto. In ultimo è stata analizzata l'influenza dell'impianto sul campo di temperatura nel terreno circostante.The thesis work focuses on the study of low enthalpy geothermal energy sources, used as heating and/or cooling systems for buildings or other structures. In the last years, the technologies used to exploit these sources are subject to rapid development and increasingly widespread diffusion, in particular with respect to the type called "energy foundation". The plant consists of a system of coils, placed in the foundation works of the structure, where a fluid flows through. This flow, due to the presence of a heat pump, enables to extract heat from the ground during winter months and release it during summer. The analysis has been performed by a numerical approach, resorting to the finite element method In the first part of the work we studied the change of temperature field created in the soil mass near a building with basements floors, with variation of the water table level and seasonal external temperature. We pointed out also the difference between countryside and urban conditions, where the widespread presence of buildings leads to an average increase of soil's temperature. In the second part we analyzed the energy foundation system created in a building under construction in the town of Tradate (VA), focusing on the main factors that regulate its efficiency. The velocity of the fluid in the coil plays a key role in the process of heat transmission, since the motion type affects the thermal exchange and constrains the design and management of the plant. Finally the influence of the presence of the plant on the temperature field in the surrounding soil has been analyzed

Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic IgG1 mAbs: complete protection of rhesus monkeys from mucosal SHIV challenge.

Although IgA is the most abundantly produced immunoglobulin in humans, its role in preventing HIV-1 acquisition, which occurs mostly via mucosal routes, remains unclear. In our passive mucosal immunizations of rhesus macaques (RMs), the anti-HIV-1 neutralizing monoclonal antibody (nmAb) HGN194, given either as dimeric IgA1 (dIgA1) or dIgA2 intrarectally (i.r.), protected 83% or 17% of the RMs against i.r. simian-human immunodeficiency virus (SHIV) challenge, respectively. Data from the RV144 trial implied that vaccine-induced plasma IgA counteracted the protective effector mechanisms of IgG1 with the same epitope specificity. We thus hypothesized that mucosal dIgA2 might diminish the protection provided by IgG1 mAbs targeting the same epitope. To test our hypothesis, we administered HGN194 IgG1 intravenously (i.v.) either alone or combined with i.r. HGN194 dIgA2. We enrolled SHIV-exposed, persistently aviremic RMs protected by previously administered nmAbs; RM anti-human IgG responses were undetectable. However, low-level SIV Gag-specific proliferative T-cell responses were found. These animals resemble HIV-exposed, uninfected humans, in which local and systemic cellular immune responses have been observed. HGN194 IgG1 and dIgA2 used alone and the combination of the two neutralized the challenge virus equally well in vitro. All RMs given only i.v. HGN194 IgG1 became infected. In contrast, all RMs given HGN194 IgG1+dIgA2 were completely protected against high-dose i.r. SHIV-1157ipEL-p challenge. These data imply that combining suboptimal defenses at the mucosal and systemic levels can completely prevent virus acquisition. Consequently, active vaccination should focus on defense-in-depth, a strategy that seeks to build up defensive fall-back positions well behind the fortified frontline.We thank Dr. J. Mascola for providing mAb VRC01, Dr. S.-L. Hu for providing SHIV-1157ip Env proteins, and Dr. W. Marasco for providing mAb Fm-6. We thank Dr. K. Rogers and K. Kinsley for TRIM5α genotype analysis, Dr. S. Lee for assistance in statistical analysis, V. Shanmuganathan for technical assistance, and Juan Esquivel for assistance with the preparation of the manuscript. This was work supported by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) UCL-VDC Grant 38637 (R.A.W.). This project was also funded in part by NIH grants P01 AI048240, R01 AI100703 and R37 AI034266 to RMR. Base grant P51 OD011132 provided support to the Yerkes National Primate Research Center. The Southwest National Primate Research Center is supported by an NIH primate center base grant (previously NCRR grant P51 RR013986; currently Office of Research Infrastructure Programs/OD P51 OD011133).This is the accepted manuscript of a paper published in Vaccine (Sholukh AM, et al., Vaccine, 2015, 33, 2086-2095, doi:10.1016/j.vaccine.2015.02.020). The final version is available at http://dx.doi.org/10.1016/j.vaccine.2015.02.02

An Anti-HIV-1 V3 Loop Antibody Fully Protects Cross-Clade and Elicits T-Cell Immunity in Macaques Mucosally Challenged with an R5 Clade C SHIV

Neutralizing antibodies have been shown to protect macaques against SHIV challenge. However, genetically diverse HIV-1 clades have evolved, and a key question left unanswered is whether neutralizing antibodies can confer cross-clade protection in vivo. The novel human monoclonal antibody HGN194 was isolated from an individual infected with an HIV-1 clade AG recombinant circulating recombinant form (CRF). HGN194 targets an epitope in the third hypervariable loop (V3) of HIV-1 gp120 and neutralizes a range of relatively neutralization-sensitive and resistant viruses. We evaluated the potential of HGN194 to protect infant rhesus monkeys against a SHIV encoding a primary CCR5-tropic HIV-1 clade C envelope. After high-dose mucosal challenge, all untreated controls became highly viremic while all HGN194-treated animals (50 mg/kg) were completely protected. When HGN194 was given at 1 mg/kg, one out of two monkeys remained aviremic, whereas the other had delayed, lower peak viremia. Interestingly, all protected monkeys given high-dose HGN194 developed Gag-specific proliferative responses of both CD4+ and CD8+ T cells. To test whether generation of the latter involved cryptic infection, we ablated CD8+ cells after HGN194 clearance. No viremia was detected in any protected monkeys, thus ruling out virus reservoirs. Thus, induction of CD8 T-cell immunity may have resulted from transient “Hit and Run” infection or cross priming via Ag-Ab-mediated cross-presentation. Together, our data identified the HGN194 epitope as protective and provide proof-of-concept that this anti-V3 loop mAb can prevent infection with sterilizing immunity after challenge with virus of a different clade, implying that V3 is a potential vaccine target

The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells

The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env-specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis across epithelial cells as much as 20-fold compared with Env-specific IgG at neutral pH or non-specific IgG at either pH. Enhanced transcytosis was observed with clinical HIV-1 isolates, including transmitted/founder strains, and was eliminated in Fc neonatal receptor (FcRn)-knockdown epithelial cells. Non-neutralizing antibodies allowed similar or less transcytosis than neutralizing antibodies. However, the ratio of total:infectious virus was higher for neutralizing antibodies, indicating that they allowed transcytosis while blocking infectivity of transcytosed virus. Immunocytochemistry revealed abundant FcRn expression in columnar epithelia lining the human endocervix and penile urethra. Acidity and Env-specific IgG enhance transcytosis of virus across epithelial cells via FcRn and could facilitate translocation of virus to susceptible target cells following sexual exposure

TAO Conceptual Design Report: A Precision Measurement of the Reactor Antineutrino Spectrum with Sub-percent Energy Resolution

The Taishan Antineutrino Observatory (TAO, also known as JUNO-TAO) is a satellite experiment of the Jiangmen Underground Neutrino Observatory (JUNO). A ton-level liquid scintillator detector will be placed at about 30 m from a core of the Taishan Nuclear Power Plant. The reactor antineutrino spectrum will be measured with sub-percent energy resolution, to provide a reference spectrum for future reactor neutrino experiments, and to provide a benchmark measurement to test nuclear databases. A spherical acrylic vessel containing 2.8 ton gadolinium-doped liquid scintillator will be viewed by 10 m^2 Silicon Photomultipliers (SiPMs) of >50% photon detection efficiency with almost full coverage. The photoelectron yield is about 4500 per MeV, an order higher than any existing large-scale liquid scintillator detectors. The detector operates at -50 degree C to lower the dark noise of SiPMs to an acceptable level. The detector will measure about 2000 reactor antineutrinos per day, and is designed to be well shielded from cosmogenic backgrounds and ambient radioactivities to have about 10% background-to-signal ratio. The experiment is expected to start operation in 2022

Hybrid solar and hydrogen energy system 0-D model for off-grid sustainable power system: A case in Italy

Off-grid solar systems are one of the most promising solutions for achieving complete grid independence. Off-grid solar systems are one of the most promising solutions for achieving complete grid independence. However, the storage of large amounts of energy produced in the summer through solar panels becomes crucial However, the storage of large amounts of energy produced in the summer through solar panels becomes crucial to reach this goal and hydrogen, as a zero-CO2 energy carrier, could play a pivotal role. This paper presents a to reach this goal and hydrogen, as a zero-CO2 energy carrier, could play a pivotal role. This paper presents a case study on the integration and simulation of solar energy and hydrogen technologies in an off-grid energy case study on the integration and simulation of solar energy and hydrogen technologies in an off-grid energy plant for a teaching buildings complex in Italy. A 0-D virtual energy plant model has been developed aimed at plant for a teaching buildings complex in Italy. A 0-D virtual energy plant model has been developed aimed at estimating the net energy production and hydrogen consumption/production rates using different inputs of estimating the net energy production and hydrogen consumption/production rates using different inputs of irradiance (monthly average, daily) and energy demand (constant and variable daily consumption levels) in the irradiance (monthly average, daily) and energy demand (constant and variable daily consumption levels) in the buildings. The outcome of the analysis identifies the most convenient configuration of the plant in terms of sizing buildings. The outcome of the analysis identifies the most convenient configuration of the plant in terms of sizing and device interactions for achieving complete grid independence, and the impact of different inputs on the plant and device interactions for achieving complete grid independence, and the impact of different inputs on the plant performance. performance