Purification and preliminary crystallographic analysis of a new Lys49-PLA2 from B-jararacussu

BjVIII is a new myotoxic Lys49-PLA2 isolated from Bothrops jararacussu venom that exhibits atypical effects on human platelet aggregation. To better understand the mode of action of BjVIII, crystallographic studies were initiated. Two crystal forms were obtained, both containing two molecules in the asymmetric unit (ASU). Synchrotron radiation diffraction data were collected to 2.0 angstrom resolution and 1.9 angstrom resolution for crystals belonging to the space group P2(1)2(1)2(1) (a = 48.4 angstrom, b = 65.3 angstrom, c = 84.3 angstrom) and space group P3(1)21 (a = b = 55.7 angstrom, c = 127.9 angstrom), respectively. Refinement is currently in progress and the refined structures are expected to shed light on the unusual platelet aggregation activity observed for BjVIII.9573675

Stochastic upscaling of hydrodynamic dispersion and retardation factor in a physically and chemically heterogeneous tropical soil

[EN] Stochastic upscaling of flow and reactive solute transport in a tropical soil is performed using real data collected in the laboratory. Upscaling of hydraulic conductivity, longitudinal hydrodynamic dispersion, and retardation factor were done using three different approaches of varying complexity. How uncertainty propagates after upscaling was also studied. The results show that upscaling must be taken into account if a good reproduction of the flow and transport behavior of a given soil is to be attained when modeled at larger than laboratory scales. The results also show that arrival time uncertainty was well reproduced after solute transport upscaling. This work represents a first demonstration of flow and reactive transport upscaling in a soil based on laboratory data. It also shows how simple upscaling methods can be incorporated into daily modeling practice using commercial flow and transport codes.The authors thank the financial support by the Brazilian National Council for Scientific and Technological Development (CNPq) (Project 401441/2014-8). The doctoral fellowship award to the first author by the Coordination of Improvement of Higher Level Personnel (CAPES) is acknowledged. The first author also thanks the international mobility grant awarded by CNPq, through the Sciences Without Borders program (Grant Number: 200597/2015-9). The international mobility grant awarded by Santander Mobility in cooperation with the University of Sao Paulo is also acknowledged. DHI-WASI is gratefully thanked for providing a FEFLOW license.Almeida De-Godoy, V.; Zuquette, L.; Gómez-Hernández, JJ. (2019). Stochastic upscaling of hydrodynamic dispersion and retardation factor in a physically and chemically heterogeneous tropical soil. Stochastic Environmental Research and Risk Assessment. 33(1):201-216. https://doi.org/10.1007/s00477-018-1624-zS201216331Ahuja LR, Naney JW, Green RE, Nielsen DR (1984) Macroporosity to characterize spatial variability of hydraulic conductivity and effects of land management. Soil Sci Soc Am J 48:699. https://doi.org/10.2136/sssaj1984.03615995004800040001xBellin A, Lawrence AE, Rubin Y (2004) Models of sub-grid variability in numerical simulations of solute transport in heterogeneous porous formations: three-dimensional flow and effect of pore-scale dispersion. Stoch Environ Res Risk Assess 18:31–38. https://doi.org/10.1007/s00477-003-0164-2Brent RP (1973) Algorithms for minimization without derivatives. Prentice Hall, Englewood CliffsBrusseau ML (1998) Non-ideal transport of reactive solutes in heterogeneous porous media: 3. model testing and data analysis using calibration versus prediction. J Hydrol 209:147–165. https://doi.org/10.1016/S0022-1694(98)00121-8Brusseau ML, Srivastava R (1999) Nonideal transport of reactive solutes in heterogeneous porous media: 4. Analysis of the cape cod natural-gradient field experiment. Water Resour Res 35:1113–1125. https://doi.org/10.1029/1998WR900019Brutsaert W (1967) Some methods of calculating unsaturated permeability. Trans ASAE 10:400–404Cadini F, De Sanctis J, Bertoli I, Zio E (2013) Upscaling of a dual-permeability Monte Carlo simulation model for contaminant transport in fractured networks by genetic algorithm parameter identification. Stoch Environ Res Risk Assess 27:505–516. https://doi.org/10.1007/s00477-012-0595-8Cambardella CA, Moorman TB, Parkin TB, Karlen DL, Novak JM, Turco RF, Konopka AE (1994) Field-scale variability of soil properties in central iowa soils. Soil Sci Soc Am J 58:1501. https://doi.org/10.2136/sssaj1994.03615995005800050033xCapilla JE, Rodrigo J, Gómez-Hernández JJ (1999) Simulation of non-Gaussian transmissivity fields honoring piezometric data and integrating soft and secondary information. Math Geol 31:907–927. https://doi.org/10.1023/A:1007580902175Cassiraga EF, Fernàndez-Garcia D, Gómez-Hernández JJ (2005) Performance assessment of solute transport upscaling methods in the context of nuclear waste disposal. Int J Rock Mech Min Sci 42:756–764. https://doi.org/10.1016/j.ijrmms.2005.03.013Corey AT (1977) Mechanics of heterogeneous fluids in porous media. Water Resources Publications, Fort Collins, CO, p 259Dagan G (1989) Flow and transport in porous formations. Springer, Berlin. https://doi.org/10.1007/978-3-642-75015-1Dagan G (2004) On application of stochastic modeling of groundwater flow and transport. Stoch Environ Res Risk Assess. https://doi.org/10.1007/s00477-004-0191-7de Azevedo AAB, Pressinotti MMN, Massoli M (1981) Sedimentological studies of the Botucatu and Pirambóia formations in the region of Santa Rita do Passa Quatro (In portuguese). Rev do Inst Geológico 2:31–38. https://doi.org/10.5935/0100-929X.19810003Deng H, Dai Z, Wolfsberg AV, Ye M, Stauffer PH, Lu Z, Kwicklis E (2013) Upscaling retardation factor in hierarchical porous media with multimodal reactive mineral facies. Chemosphere 91:248–257. https://doi.org/10.1016/j.chemosphere.2012.10.105Diersch H-JG (2014) Finite element modeling of flow, mass and heat transport in porous and fractured media. Springer, Berlin. https://doi.org/10.1007/978-3-642-38739-5Dippenaar MA (2014) Porosity reviewed: quantitative multi-disciplinary understanding, recent advances and applications in vadose zone hydrology. Geotech Geol Eng 32:1–19. https://doi.org/10.1007/s10706-013-9704-9Fagundes JRT, Zuquette LV (2011) Sorption behavior of the sandy residual unconsolidated materials from the sandstones of the Botucatu Formation, the main aquifer of Brazil. Environ Earth Sci 62:831–845. https://doi.org/10.1007/s12665-010-0570-yFenton GA, Griffiths DV (2008) Risk assessment in geotechnical engineering. Wiley, p 463Fernàndez-Garcia D, Gómez-Hernández JJ (2007) Impact of upscaling on solute transport: Traveltimes, scale dependence of dispersivity, and propagation of uncertainty. Water Resour Res. https://doi.org/10.1029/2005WR004727Fernàndez-Garcia D, Llerar-Meza G, Gómez-Hernández JJ (2009) Upscaling transport with mass transfer models: mean behavior and propagation of uncertainty. Water Resour Res. https://doi.org/10.1029/2009WR007764Feyen L, Gómez-Hernández JJ, Ribeiro PJ, Beven KJ, De Smedt F (2003a) A Bayesian approach to stochastic capture zone delineation incorporating tracer arrival times, conductivity measurements, and hydraulic head observations. Water Resour Res. https://doi.org/10.1029/2002WR001544Feyen L, Ribeiro PJ, Gómez-Hernández JJ, Beven KJ, De Smedt F (2003b) Bayesian methodology for stochastic capture zone delineation incorporating transmissivity measurements and hydraulic head observations. J Hydrol 271:156–170. https://doi.org/10.1016/S0022-1694(02)00314-1Forsythe GE, Malcolm MA, Moler CB (1976) Computer methods for mathematical computations. Prentice-Hall, Englewood Cliffs, p 259Freeze R, Cherry J (1979) Groundwater. PrenticeHall Inc, Englewood cliffs, p 604Frippiat CC, Holeyman AE (2008) A comparative review of upscaling methods for solute transport in heterogeneous porous media. J Hydrol 362:150–176. https://doi.org/10.1016/j.jhydrol.2008.08.015Fu J, Gómez-Hernández JJ (2009) Uncertainty assessment and data worth in groundwater flow and mass transport modeling using a blocking Markov chain Monte Carlo method. J Hydrol 364:328–341. https://doi.org/10.1016/j.jhydrol.2008.11.014Gelhar LW, Axness CL (1983) Three-dimensional stochastic analysis of macrodispersion in aquifers. Water Resour Res 19:161–180. https://doi.org/10.1029/WR019i001p00161Gelhar LW, Welty C, Rehfeldt KR (1992) A critical review of data on field-scale dispersion in aquifers. Water Resour Res 28:1955–1974. https://doi.org/10.1029/92WR00607Giacheti HL, Rohm SA, Nogueira JB, Cintra JCA (1993) Geotechnical properties of the Cenozoic sediment (in protuguese). In: Albiero JH, Cintra JCA (eds) Soil from the interior of São Paulo. ABMS, Sao Paulo, pp 143–175Gómez-Hernandez JJ (1990) A stochastic approach to the simulation of block conductivity fields conditional upon data measured at a smaller scale. Stanford University, StanfordGómez-Hernández JJ, Gorelick SM (1989) Effective groundwater model parameter values: influence of spatial variabiity of hydraulic conductivity, leackance, and recharge. Water Resour Res 25:405–419Gómez-Hernández JJ, Journel A (1993) Joint sequential simulation of multigaussian fields. In: Geostatistics Tróia’92. pp 85–94. https://doi.org/10.1007/978-94-011-1739-5_8Gómez-Hernández JJ, Wen X-H (1994) Probabilistic assessment of travel times in groundwater modeling. Stoch Hydrol Hydraul 8:19–55. https://doi.org/10.1007/BF01581389Gómez-Hernández JJ, Fu J, Fernandez-Garcia D (2006) Upscaling retardation factors in 2-D porous media. In: Bierkens MFP, Gehrels JC, Kovar K (eds) Calibration and reliability in groundwater modelling: from uncertainty to decision making: proceedings of the ModelCARE 2005 conference held in The Hague, The Netherlands, 6–9 June, 2005. IAHS Publication, pp 130–136Goovaerts P (1999) Geostatistics in soil science: state-of-the-art and perspectives. Geoderma 89:1–45. https://doi.org/10.1016/S0016-7061(98)00078-0Jarvis NJ (2007) A review of non-equilibrium water fl ow and solute transport in soil macropores: principles, controlling factors and consequences for water quality. Eur J Soil Sci 58:523–546. https://doi.org/10.4141/cjss2011-050Jellali S, Diamantopoulos E, Kallali H, Bennaceur S, Anane M, Jedidi N (2010) Dynamic sorption of ammonium by sandy soil in fixed bed columns: evaluation of equilibrium and non-equilibrium transport processes. J Environ Manag 91:897–905. https://doi.org/10.1016/j.jenvman.2009.11.006Journel AG, Gomez-Hernandez JJ (1993) Stochastic imaging of the wilmington clastic sequence. SPE Form Eval 8:33–40. https://doi.org/10.2118/19857-PAJournel A, Deutsch C, Desbarats A (1986) Power averaging for block effective permeability. Proc SPE Calif Reg Meet. https://doi.org/10.2118/15128-MSKronberg BI, Fyfe WS, Leonardos OH, Santos AM (1979) The chemistry of some Brazilian soils: element mobility during intense weathering. Chem Geol 24:211–229. https://doi.org/10.1016/0009-2541(79)90124-4Lake LW (1988) The origins of anisotropy (includes associated papers 18394 and 18458). J Pet Technol 40:395–396. https://doi.org/10.2118/17652-PALawrence AE, Rubin Y (2007) Block-effective macrodispersion for numerical simulations of sorbing solute transport in heterogeneous porous formations. Adv Water Resour 30:1272–1285. https://doi.org/10.1016/j.advwatres.2006.11.005Lemke LD, Barrack WA II, Abriola LM, Goovaerts P (2004) Matching solute breakthrough with deterministic and stochastic aquifer models. Groundwater 42:920–934Li L, Zhou H, Gómez-Hernández JJ (2011a) A comparative study of three-dimensional hydraulic conductivity upscaling at the macro-dispersion experiment (MADE) site, Columbus Air Force Base, Mississippi (USA). J Hydrol 404:278–293. https://doi.org/10.1016/j.jhydrol.2011.05.001Li L, Zhou H, Gómez-Hernández JJ (2011b) Transport upscaling using multi-rate mass transfer in three-dimensional highly heterogeneous porous media. Adv Water Resour 34:478–489. https://doi.org/10.1016/j.advwatres.2011.01.001Logsdon Keller KE, Moorman TB (2002) Measured and predicted solute leaching from multiple undisturbed soil columns. Soil Sci Soc Am J 66:686–695. https://doi.org/10.2136/sssaj2002.6860Lourens A, van Geer FC (2016) Uncertainty propagation of arbitrary probability density functions applied to upscaling of transmissivities. Stoch Environ Res Risk Assess 30:237–249. https://doi.org/10.1007/s00477-015-1075-8Mahapatra IC, Singh KN, Pillai KG, Bapat SR (1985) Rice soils and their management. Indian J Agron 30:R1–R41Morakinyo JA, Mackay R (2006) Geostatistical modelling of ground conditions to support the assessment of site contamination. Stoch Environ Res Risk Assess 20:106–118. https://doi.org/10.1007/s00477-005-0015-4Moslehi M, de Barros FPJ, Ebrahimi F, Sahimi M (2016) Upscaling of solute transport in disordered porous media by wavelet transformations. Adv Water Resour 96:180–189. https://doi.org/10.1016/j.advwatres.2016.07.013Osinubi KJ, Nwaiwu CM (2005) Hydraulic conductivity of compacted lateritic soil. J Geotech Geoenviron Eng 131:1034–1041. https://doi.org/10.1061/(ASCE)1090-0241(2005)131:8(1034)Remy N (2004) SGeMS: stanford geostatistical modeling software. Softw Man. https://doi.org/10.1007/978-1-4020-3610-1_89Renard P, de Marsily G (1997) Calculating equivalent permeability: a review. Adv Water Resour 20:253–278. https://doi.org/10.1016/S0309-1708(96)00050-4Robin MJL, Sudicky EA, Gillham RW, Kachanoski RG (1991) Spatial variability of strontium distribution coefficients and their correlation with hydraulic conductivity in the Canadian forces base borden aquifer. Water Resour Res 27:2619–2632. https://doi.org/10.1029/91WR01107Salamon P, Fernàndez-Garcia D, Gómez-Hernández JJ (2007) Modeling tracer transport at the MADE site: the importance of heterogeneity. Water Resour Res. https://doi.org/10.1029/2006WR005522Sánchez-Vila X, Carrera J, Girardi JP (1996) Scale effects in transmissivity. J Hydrol 183:1–22. https://doi.org/10.1016/S0022-1694(96)80031-XScheibe T, Yabusaki S (1998) Scaling of flow and transport behavior in heterogeneous groundwater systems. Adv Water Resour 22:223–238. https://doi.org/10.1016/S0309-1708(98)00014-1Selvadurai PA, Selvadurai APS (2014) On the effective permeability of a heterogeneous porous medium: the role of the geometric mean. Philos Mag 94:2318–2338. https://doi.org/10.1080/14786435.2014.913111Shackelford CD (1994) Critical concepts for column testing. J Geotech Eng 120:1804–1828. https://doi.org/10.1016/0148-9062(95)96996-OŠimůnek J, van Genuchten MT, Šejna M, Toride N, Leij FJ (1999) The STANMOD computer software for evaluating solute transport in porous media using analytical solutions of convection-dispersion equation. Riverside, CaliforniaTaskinen A, Sirviö H, Bruen M (2008) Modelling effects of spatial variability of saturated hydraulic conductivity on autocorrelated overland flow data: linear mixed model approach. Stoch Environ Res Risk Assess 22:67–82. https://doi.org/10.1007/s00477-006-0099-5Tuli A, Hopmans JW, Rolston DE, Moldrup P (2005) Comparison of air and water permeability between disturbed and undisturbed soils. Soil Sci Soc Am J 69:1361. https://doi.org/10.2136/sssaj2004.0332Tyukhova AR, Willmann M (2016) Conservative transport upscaling based on information of connectivity. Water Resour Res 52:6867–6880. https://doi.org/10.1002/2015WR018331van Genuchten MTh (1980) Determining transport parameters from solute displacement experiments. Research Report 118. U.S. Salinity Lab., Riverside, CAVanderborght J, Timmerman A, Feyen J (2000) Solute transport for steady-state and transient flow in soils with and without macropores. Soil Sci Soc Am J 64:1305–1317. https://doi.org/10.2136/sssaj2000.6441305xVanmarcke E (2010) Random fields: analysis and synthesis. World Scientific. MIT Press, Cambridge, MA, p 364Vishal V, Leung JY (2017) Statistical scale-up of 3D particle-tracking simulation for non-Fickian dispersive solute transport modeling. Environ Res Risk Assess, Stoch. https://doi.org/10.1007/s00477-017-1501-1Wen X-H, Gómez-Hernández JJ (1996) Upscaling hydraulic conductivities in heterogeneous media: an overview. J Hydrol 183:ix–xxxii. https://doi.org/10.1016/S0022-1694(96)80030-8Wen XH, Gómez-Hernández JJ (1998) Numerical modeling of macrodispersion in heterogeneous media: a comparison of multi-Gaussian and non-multi-Gaussian models. J Contam Hydrol 30:129–156. https://doi.org/10.1016/S0169-7722(97)00035-1Wen XH, Capilla JE, Deutsch CV, Gómez-Hernández JJ, Cullick AS (1999) A program to create permeability fields that honor single-phase flow rate and pressure data. Comput Geosci 25:217–230. https://doi.org/10.1016/S0098-3004(98)00126-5Wilding LP, Drees LR (1983) Spatial variability and pedology. In: Wilding LP, Smeck NE, Hall GF (eds) Pedogenesis and soil taxonomy: the soil orders. Elsevier, Amsterdam, pp 83–116Willmann M, Carrera J, Guadagnini A (2006) Block-upscaling of transport in heterogeneous aquifers. h2ogeo.upc.edu 1–7Xu Z, Meakin P (2013) Upscaling of solute transport in heterogeneous media with non-uniform flow and dispersion fields. Appl Math Model 37:8533–8542. https://doi.org/10.1016/j.apm.2013.03.070Zech A, Attinger S, Cvetkovic V, Dagan G, Dietrich P, Fiori A, Rubin Y, Teutsch G (2015) Is unique scaling of aquifer macrodispersivity supported by field data? Water Resour Res 51:7662–7679. https://doi.org/10.1002/2015WR017220Zhou H, Li L, Gómez-Hernández JJ (2010) Three-dimensional hydraulic conductivity upscaling in groundwater modeling. Comput Geosci 36:1224–1235. https://doi.org/10.1016/j.cageo.2010.03.008Zhou H, Li L, Hendricks Franssen H-J, Gómez-Hernández JJ (2012) Pattern recognition in a bimodal aquifer using the normal-score ensemble Kalman filter. Math Geosci 44:169–185. https://doi.org/10.1007/s11004-011-9372-

Total Hadronic Cross Section Data and the Froissart-Martin Bound

The energy dependence of the total hadronic cross section at high energies is investigated with focus on the recent experimental result by the TOTEM Collaboration at 7 TeV and the Froissart-Martin bound. On the basis of a class of analytical parametrization with the exponent $\gamma$ in the leading logarithm contribution as a free parameter, different variants of fits to $pp$ and $\bar{p}p$ total cross section data above 5 GeV are developed. Two ensembles are considered, the first comprising data up to 1.8 TeV, the second also including the data collected at 7 TeV. We shown that in all fit variants applied to the first ensemble the exponent is statistically consistent with $\gamma$ = 2. Applied to the second ensemble, however, the same variants yield $\gamma$'s above 2, a result already obtained in two other analysis, by U. Amaldi \textit{et al}. and by the UA4/2 Collaboration. As recently discussed by Ya. I. Azimov, this faster-than-squared-logarithm rise does not necessarily violate unitarity. Our results suggest that the energy dependence of the hadronic total cross section at high energies still constitute an open problem.Comment: 20 pages, 10 figures, introduction extended and general references added to match editorial style, to appear in the Brazilian Journal of Physic

The use and limits of ITS data in the analysis of intraspecific variation in Passiflora L. (Passifloraceae)

The discovery and characterization of informative intraspecific genetic markers is fundamental for evolutionary and conservation genetics studies. Here, we used nuclear ribosomal ITS sequences to access intraspecific genetic diversity in 23 species of the genus Passiflora L. Some degree of variation was detected in 21 of these. The Passiflora and Decaloba (DC.) Rchb. subgenera showed significant differences in the sizes of the two ITS regions and in GC content, which can be related to reproductive characteristics of species in these subgenera. Furthermore, clear geographical patterns in the spatial distribution of sequence types were identified in six species. The results indicate that ITS may be a useful tool for the evaluation of intraspecific genetic variation in Passiflora

Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study

Background Preliminary evidence suggests cancer- and chemotherapy-related autonomic nervous system (ANS) dysfunction may contribute to the increased cardiovascular (CV) morbidity- and mortality-risks in cancer survivors. However, the reliability of these findings may have been jeopardized by inconsistent participant screening and assessment methods. Therefore, good laboratory practices must be established before the presence and nature of cancer-related autonomic dysfunction can be characterized. The purpose of this study was to assess the feasibility of conducting concurrent ANS and cardiovascular evaluations in young adult cancer patients, according to the following criteria: i) identifying methodological pitfalls and proposing good laboratory practice criteria for ANS testing in cancer, and ii) providing initial physiologic evidence of autonomic perturbations in cancer patients using the composite autonomic scoring scale (CASS). Methods Thirteen patients (mixed diagnoses) were assessed immediately before and after 4 cycles of chemotherapy. Their results were compared to 12 sex- and age-matched controls. ANS function was assessed using standardized tests of resting CV (tilt-table, respiratory sinus arrhythmia and Valsalva maneuver) and sudomotor (quantitative sudomotor axon reflex test) reactivity. Cardiovascular reactivity during exercise was assessed using a modified Astrand-Ryhming cycle ergometer protocol. Our feasibility criteria addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy assessment potential, iv) test performance/tolerability, and v) identification and minimizing the influence of potentially confounding medication. T-tests and repeated measures ANOVAs were used to assess between- and within-group differences at baseline and follow-up. Results The overall success rate in achieving our feasibility criteria was 98.4 %. According to the CASS, there was evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in 18.2 % of patients at follow-up, compared to 0 % of controls at baseline or follow-up. Conclusions Results from our feasibility assessment suggest that the investigation of ANS function in young adult cancer patients undergoing chemotherapy is possible. To the best of our knowledge, this is the first study to report CASS-based evidence of ANS impairment and sudomotor dysfunction in any cancer population. Moreover, we provide evidence of cancer- and chemotherapy-related parasympathetic dysfunction – as a possible contributor to the pathogenesis of CV disease in cancer survivors

Platelet-Activating Factor Receptor Plays a Role in Lung Injury and Death Caused by Influenza A in Mice

Influenza A virus causes annual epidemics which affect millions of people worldwide. A recent Influenza pandemic brought new awareness over the health impact of the disease. It is thought that a severe inflammatory response against the virus contributes to disease severity and death. Therefore, modulating the effects of inflammatory mediators may represent a new therapy against Influenza infection. Platelet activating factor (PAF) receptor (PAFR) deficient mice were used to evaluate the role of the gene in a model of experimental infection with Influenza A/WSN/33 H1N1 or a reassortant Influenza A H3N1 subtype. The following parameters were evaluated: lethality, cell recruitment to the airways, lung pathology, viral titers and cytokine levels in lungs. The PAFR antagonist PCA4248 was also used after the onset of flu symptoms. Absence or antagonism of PAFR caused significant protection against flu-associated lethality and lung injury. Protection was correlated with decreased neutrophil recruitment, lung edema, vascular permeability and injury. There was no increase of viral load and greater recruitment of NK1.1+ cells. Antibody responses were similar in WT and PAFR-deficient mice and animals were protected from re-infection. Influenza infection induces the enzyme that synthesizes PAF, lyso-PAF acetyltransferase, an effect linked to activation of TLR7/8. Therefore, it is suggested that PAFR is a disease-associated gene and plays an important role in driving neutrophil influx and lung damage after infection of mice with two subtypes of Influenza A. Further studies should investigate whether targeting PAFR may be useful to reduce lung pathology associated with Influenza A virus infection in humans