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Abstract Perfectly incompressible materials do not exist in nature but are a useful approximation of several media which can be deformed in non-isothermal processes but undergo very small volume variations. In this paper, the linear analysis of the Darcy-Bénard problem is performed in the class of extended-quasi-thermal-incompressible fluids, introducing a factor $$\beta$$ β which describes the compressibility of the fluid and plays an essential role in the instability results. In particular, in the Oberbeck-Boussinesq approximation, a more realistic constitutive equation for the fluid density is employed in order to obtain more thermodynamically consistent instability results. The critical Rayleigh-Darcy number for the onset of convection is determined, via linear instability analysis of the conduction solution, as a function of a dimensionless parameter $$\widehat{\beta }$$ β ^ proportional to the compressibility factor $$\beta$$ β , proving that $$\widehat{\beta }$$ β ^ enhances the onset of convective motions. Article Highlights The onset of convection in fluid-saturated porous media is analyzed, taking into account fluid compressibility effect. The critical Rayleigh-Darcy number is determined in a closed algebraic form via linear instability analysis. The critical Rayleigh-Darcy number is shown to be a decreasing function of the dimensionless compressibility factor.

The paper compares the final profitability of a cointegration-based pairs trading strategy when pairs of stocks are pre-selected by means of seven different measures. Some of the measures considered have been extensively used in the pairs trading literature, while others represent a novelty in this type of application. We find that pre-selection matters, since the excess returns remarkably vary, in terms of both average and variability, depending on the metrics used. Differences in profitability by pre-selection metrics are retrieved even after considering commissions and cut rules, market impact, a stricter definition of the Spread reversion to the equilibrium and alternative cointegration tests. Besides, the pairs trading profitability is found to be heterogeneous across the different pre-selection metrics also in terms of exposure to the systematic stock-market risk factors.

Evidence assessing potential diurnal variations of platelet reactivity in patients on clopidogrel treated with elective percutaneous coronary intervention (PCI) for chronic coronary syndrome (CCS) are currently lacking. We prospectively enrolled 15 patients affected by stable coronary artery disease (CAD) previously treated with elective PCI and on clopidogrel for at least 8 days (administered at 8 a.m.). A significant heterogeneity in diurnal levels of ADP-dependent platelet aggregation was found (p = 0.0004), with a peak of platelet reactivity occurring at the 6 a.m. assessment, which resulted significantly increased compared to the afternoon (6 p.m.) evaluation (255 ± 66 vs 184 ± 67, p = 0.002). In addition, at the early-morning evaluation a considerably high proportion of patients with high platelet reactivity (53.3%) were observed. In conclusion, clopidogrel-induced platelet inhibition in patients with CCS after elective PCI follows a circadian rhythm, thus suggesting that a consistent and durable antiplatelet inhibition is often failed with standard clopidogrel administration at morning.

A reaction–diffusion system governing the prey–predator interaction with Allee effect on the predators, already introduced by the authors in a previous work is reconsidered with the aim of showing destabilization mechanisms of the biologically meaning equilibrium and detecting some aspects for the eventual oscillatory pattern formation. Extensive numerical simulations, depicting such complex dynamics, are shown. In order to complete the stability analysis of the coexistence equilibrium, a nonlinear stability result is shown.

In the present paper, double-diffusive convection, taking into account Coriolis effects, in a horizontal layer of Brinkman-anisotropic bi-disperse porous medium is analysed. Via linear instability analysis, we found that convection can set in through stationary or oscillatory motions and the critical Rayleigh numbers for the onset of stationary secondary flow (steady convection) and overstability (oscillatory convection) are determined.

Aims The potential diurnal variations of platelet reactivity in patients on clopidogrel treated with elective percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) are currently unknown. Methods and results We prospectively enrolled 15 patients with stable CAD treated PCI and on clopidogrel therapy for at least eight days. All patients received their maintenance 75-mg clopidogrel dose at 8 AM. Platelet reactivity was assessed with the Verifynow P2Y12 assay at three different time points (10 AM, 6 PM, and 6 AM). Platelet reactivity is expressed as P2Y12 reaction units (PRU) and PRU thresholds ≥208 and ≥240 were used to define high platelet reactivity (HPR). A significant heterogeneity in diurnal levels of platelet reactivity was found (P = 0.0004), with a peak occurring at the 6 AM assessment. In addition, at the 6 AM evaluation patients showed the highest prevalence of HPR (53.3% of patients with PRU ≥240, 66.7% of patients with PRU ≥208). Conclusions Platelet reactivity in patients with stable CAD treated with PCI and taking clopidogrel in the morning follows a circadian rhythm, thus suggesting that platelet inhibition may not be constant and sufficient throughout the day. Whether an evening or a bis in die administration of clopidogrel may result in a constant and more reliable antiplatelet inhibition, should be investigated in dedicated studies.

Thermal convection in a horizontally isotropic bi-disperse porous medium (BDPM) uniformly heated from below is analysed. The combined effects of uniform vertical rotation and Brinkman law on the stability of the steady state of the momentum equations in a BDPM are investigated. Linear and nonlinear stability analysis of the conduction solution is performed, and the coincidence between linear instability and nonlinear stability thresholds in the$$L^2$$L2-norm is obtained.

The onset of thermal convection in uniformly rotating bidispersive horizontal porous layer, uniformly heated from below, is analyzed. A generalized Darcy equation for the macro-phase is considered to take the Vadasz number into account. It is proved that the presence of the Vadasz number can give rise to oscillatory motion at the loss of stability of thermal conduction solution.

Background and importance Neonatal pharmacotherapy is challenging and often based on little evidence. Off label use of drugs is common practice and patients are at a high risk of medication errors and drug-related problems. Prescription-screening tools are used in geriatrics, internal medicine and pediatrics to optimize drug prescribing. Aim and objectives Our aim was to develop a prescription-screening tool specific to neonatology. Materials and methods Clinical guidelines on neonatal pharmacotherapy were identified by a literature review and synthetized into short statements. A 2-rounds Delphi consensus method was used to establish the content validity of Neocheck. The statements were submitted to a group of 23 experts in 10 Swiss neonatology centers. The level of agreement was evaluated on a 5-point Likert scale (1 being the highest level of agreement). Statements for which >65% of experts gave the statement a rating of 1 or 2 were selected at round 1. This cut off was raised to >75% at round two. Results A total of 1375 clinical guidelines were identified from the literature search. After synthesis, 158 statements were submitted to the group of 23 Swiss experts. The mean agreement rating was 1.62 (95% CI 1.55 to 1.70) during the 1st round of Delphi and 1.32 (95% CI 1.28 to 1.37) during the 2nd round. The final Neocheck tool is composed of 141 statements on 11 medical domains and 49 neonatal diseases. On average, 95% (95% CI 94%-96%) of experts either totally agreed or slightly agreed with the validated statements. Conclusion and relevance A prescription-screening tool specific to neonatalogy was developed and validated by a group of 23 Swiss experts. The impact of Neocheck on the optimization of drug use in neonates and its potential interest as a teaching tool for young physicians and clinical pharmacists need to be evaluated in the future.

This paper compares the final profitability of a cointegration-based pairs trading strategy when pairs of stocks are pre-selected using seven different measures. Pre-selection matters, since the excess returns remarkably vary, in terms of both average and variability, depending on the metrics used. Differences in profitability by pre-selection metrics are retrieved even after considering commissions and cut rules, market impact, and a stricter definition of the Spread reversion to the equilibrium. Besides, the profitability of the pairs trading strategy is also found heterogeneous across the different pre-selection metrics considered in terms of exposure to the traditional risk-factors.

A reaction–diffusion ecoepidemic model of predator–prey type with a transmissible disease spreading among the predator species only is considered. The longtime behavior of solutions is analyzed and, in particular, absorbing sets in the phase space are determined. Conditions guaranteeing the non existence of non-constant equilibria have been found. Linear and non-linear stability conditions for biologically meaningful equilibria are determined.

Via the longtime behavior of the perturbations to thermal conduction solution $$m_0$$ , the nonlinear longtime behavior of Navier–Stokes fluid mixtures filling horizontal rotating layers uniformly heated from below and salted by one salt—either from above or below—is investigated. Via the existence of $$L^2$$ -absorbing sets, it is shown that the perturbations to $$m_0$$ are ultimately bounded. The onset of steady or oscillatory convection is analyzed. Via a Linearization Principle (Rionero in Rend Lincei Mat Appl 25:1–44, 2014) it is shown that the linear theory captures completely the physics of the problem since the linear stability implies the nonlinear global asymptotic stability in the $$L^2$$ -norm.

A binary mixture saturating a horizontal porous layer, with large pores and uniformly heated from below, is considered. The instability of a vertical fluid motion (throughflow) when the layer is salted by one salt (either from above or from below) is analyzed. Ultimately boundedness of solutions is proved, via the existence of positively invariant and attractive sets (i.e. absorbing sets). The critical Rayleigh numbers at which steady or oscillatory instability occurs are recovered. Sufficient conditions guaranteeing that a secondary steady motion or a secondary oscillatory motion can be observed after the loss of stability are found. When the layer is salted from above, a condition guaranteeing the occurrence of “cold” instability is determined. Finally, the influence of the velocity module on the increasing/decreasing of the instability thresholds is investigated.

The onset of thermal convection in an electrically conducting fluid saturating a porous medium, uniformly heated from below, salted by one chemical and embedded in an external transverse magnetic field is analyzed. The critical Rayleigh thermal numbers at which steady and Hopf convection can occur, are determined. Sufficient conditions guaranteeing the effective onset of convection via steady or oscillatory state are provided.

Neonatal thrombocytopenia is a rare complication of maternal autoimmune thrombocytopenia, and no maternal predictors of its gravity and potential complications have been identified. Neonatal cerebral hemorrhage, a feared event in the setting of autoimmune thrombocytopenia, is fortunately uncommon, but it can occur in utero or in the perinatal period, with potentially serious consequences. The authors report the case of a boy born to a mother affected by autoimmune thrombocytopenia, who presented with severe thrombocytopenia at birth and developed intracranial hemorrhage despite mild maternal thrombocytopenia at delivery and a prompt preventive treatment of the newborn. Platelet count should be tested at birth in all babies born from mothers with autoimmune thrombocytopenia, irrespective of maternal platelets counts during pregnancy or at delivery, and should be closely monitored during the first days of life. Systematic early and serial cranial ultrasound might be advocated in the setting of neonatal thrombocytopenia.

The classic Brusselator model consists of four reactions involving six components A, B, D, E, X, Y. In a typical run, the final products $D$ and $E$ are removed instantly, while, the concentrations of the reactants A and B are kept constant. Then, the classic Brusselator model consisting of two equations for the intermediate X and Y is obtained. When the component B is not considered constant, it is added to the mixture and the so-called full Brusselator model is considered. In this paper, the full Brusselator model is studied. In particular, the boundedness of solutions and the effect of diffusion on the linear stability is analyzed. Moreover, sufficient conditions ensuring that the unique steady state, unstable (stable) in the ODEs system, becomes stable (unstable) in presence of diffusion, are performed and a first nonlinear stability result is obtained.

Porous horizontal layers are considered. A class of non-constant porous throughflows, 2D in vertical planes, is obtained. The global stability conditions and the "cold convection instability'' conditions are investigated.

The onset of porous convection in an electrically conducting fluid uniformly heated from below and embedded in an external transverse constant magnetic field is analysed. In particular the effect of Vadasz inertia term, measured through the Vadasz number $$V_a$$ , on the instability threshold, is investigated. For the three-dimensional perturbations and full nonlinear problem it is shown that sub-critical instabilities do not exist and the global nonlinear stability is guaranteed by the linear stability. The long-time behaviour is characterized via the existence of $$L^2$$ -absorbing sets.

Background Tuberculin skin test based on in vivo intradermal inoculation of purified protein derivative from Mycobacterium bovis (bPPD) is the diagnostic test for the control and surveillance of bovine tuberculosis (bTB). Methods Proteomic analysis was performed on different bPPD preparations from M. bovis, strain AN5. Proteins were precipitated from bPPD solutions by TCA precipitation. The proteome of bPPD preparations was investigated by bottom-up proteomics, which consisted in protein digestion and nano-LC–MS/MS analysis. Mass spectrometry analysis was performed on a Q-exactive hybrid quadrupole-Orbitrap mass spectrometer coupled online to an Easy nano-LC1000 system. Results Three hundred and fifty-six proteins were identified and quantified by at least 2 peptides (99% confidence per peptide). One hundred and ninety-eight proteins, which had not been previously described, were detected; furthermore, the proteomic profile shared 80 proteins with previous proteomes from bPPDs from the United Kingdom and Brazil and 139 protein components from bPPD from Korea. Locus name of M. bovis (Mb) with orthologs from M. tuberculosis H37Rv, comparative gene and protein length, molecular mass, functional categories, gene name and function of each protein were reported. Ninety-two T cell mycobacterial antigens responsible for delayed-type hypersensitivity were detected, fifty-two of which were not previously reported in any bPPD proteome. Data are available via ProteomeXchange with identifier PXD005920. Conclusions This study represents the highest proteome coverage of bPPD preparations to date. Since proteins perform cellular functions essential to health and/or disease, obtaining knowledge of their presence and variance is of great importance in understanding disease states and for advancing translational studies. Therefore, to better understand Mycobacterium tuberculosis complex biology during infection, survival, and persistence, the reproducible evaluation of the proteins that catalyze and control these processes is critically important. More active and more specific tuberculins would be desirable. Indeed, many antigens contained within bPPD are currently responsible for the cross-reactivity resulting in false-positive results as they are shared between non-tuberculous and tuberculous mycobacteria. Electronic supplementary material The online version of this article (doi:10.1186/s12967-017-1172-1) contains supplementary material, which is available to authorized users.

A reaction-diffusion system modeling cholera epidemic in a non-homogeneously mixed population is introduced. The interaction between population and toxigenic Vibrio cholerae concentration in contaminated water has been taken into account. The existence of biologically meaningful equilibria is investigated together with their linear and nonlinear stability. Using the data collected during the Haiti cholera epidemic, a numerical simulation is performed.

A reaction-diffusion system modeling the predation between two species is analyzed in the case in which the predators have to search, share and compete for food. The boundedness and uniqueness of the solutions is proved and conditions guaranteeing the global nonlinear asymptotic stability of the positive equilibrium point have been found. These conditions improve those ones present in the existing literature.

The instability of a vertical fluid motion (throughflow) in a binary mixture saturating a horizontal porous layer, uniformly heated from below, uniformly salted from below by one salt and permeated by an imposed uniform magnetic field H , normal to the layer, is analyzed. By employing the order-1 Galerkin weighted residuals method, the critical Rayleigh numbers for the onset of steady or oscillatory instability, have been determined.

Double convection in rotating horizontal layers filled by a Navier–Stokes fluid mixture, heated and salted from below, is investigated. Onset of linear instability – for any value of the fluid and salt Prandtl numbers Pr, P1 – either via the Routh–Hurwitz conditions or via steady or oscillatory convection, is characterized. Introducing a new field connecting the perturbation fields to the temperature and salt concentration, in the cases P 1 = 1 or Pr=1 or P 1 P r = 1 , stability conditions in algebraic closed form are obtained. Linear stability is recovered as non-linear global asymptotic stability via the Auxiliary System Method.

The onset of thermal convection in a uniformly rotating horizontal layer filled by a Navier–Stokes multi-component fluid mixture, heated from below and salted partly from above and partly from below, is investigated via the new approach named auxiliary system method Rionero (Rend Lincei Mat Appl 25:1–44, 2014). In the free–free case, via the generalization of the Rionero Linearization Principle: “Decay of linear energy for any initial data implies decay of nonlinear energy at any instant” [given in Rionero (Rend Lincei Mat Appl 25:1–44, 2014) in the absence of rotation], it is shown that conditions guaranteeing linear stability of thermal conduction solution guarantee also absence of subcritical instabilities and global exponential asymptotic nonlinear stability. The classical Benard problem is investigated via a procedure different from the celebrated one given in Chandrasekhar (Hydrodynamic and hydromagnetic stability, 1981).

The longtime behaviour of a nonautonomous, bidimensional, Lotka-Volterra-Hassell model with mutual interference is investigated. The existence of an absorbing set is shown together with global nonlinear asymptotic stability of the positive critical points.

The longtime behaviour of a nonautonomous bidimensional Hassell predator-prey model with mutual interference is investigated. The existence of an absorbing set in the phase space is shown, and necessary and sufficient conditions guaranteeing the nonlinear, global, asymptotic stability of the positive solutions have been found by using the Liapunov direct method.

Neonatal thrombocytopenia is a rare complication of maternal autoimmune thrombocytopenia, and no maternal predictors of its gravity and potential complications have been identified. Neonatal cerebral hemorrhage, a feared event in the setting of autoimmune thrombocytopenia, is fortunately uncommon, but it can occur in utero or in the perinatal period, with potentially serious consequences. The authors report the case of a boy born to a mother affected by autoimmune thrombocytopenia, who presented with severe thrombocytopenia at birth and developed intracranial hemorrhage despite mild maternal thrombocytopenia at delivery and a prompt preventive treatment of the newborn. Platelet count should be tested at birth in all babies born from mothers with autoimmune thrombocytopenia, irrespective of maternal platelets counts during pregnancy or at delivery, and should be closely monitored during the first days of life. Systematic early and serial cranial ultrasound might be advocated in the setting of neonatal thrombocytopenia.

OBJECTIVE. To determine the age-stratified risk of intrapartum and neonatal mortality as well as morbidities of clinical relevance after elective cesarean delivery (ECD).METHODS. This work was a cohort study including 56 549 prospectively recorded late-preterm and term deliveries. We analyzed the effect of cesarean delivery (CD) before the onset of labor on the following multiple neonatal outcomes before hospital discharge, compared with planned vaginal delivery (PVD) and emergency CD: mortality, birth depression, special care admission, and respiratory morbidity. We adjusted for confounders by multivariate analysis and stratified the risk according to gestational age (GA).RESULTS. Mortality and morbidities had a strong GA-related trend with the lowest incidences consistently found between 38 and 40 weeks of gestation independent of delivery mode. Compared with infants delivered via PVD, infants delivered via ECD had significantly higher rates of mortality (adjusted risk ratio [aRR]: 2.1), risk of special care admission (aRR: 1.4), and respiratory morbidity (aRR: 1.8) but not of depression at birth (aRR: 1.1). Compared with emergency CD, newborns delivered via ECD had less depression at birth (aRR: 0.6) and admission to special care (aRR: 0.8), but mortality (aRR: 0.8) and respiratory morbidity (aRR: 1.0) rates were similar.CONCLUSIONS. Gestational age–specific risk estimates are lowest between 38 and 40 weeks and should be included in the informed-consent process. The information should also be used to allow for appropriate preparation with respect to adequate staff and equipment. ECD is consistently associated with increased intrapartum and neonatal mortality, risk of admission, and respiratory morbidity compared with PVD and has no advantage over emergency CD in terms of mortality. Neonatal morbidities are lower after ECD than emergency CD only with term births. Our data provide evidence that ECD should not be performed before term.

A reaction–diffusion system modeling cholera epidemic in a non-homogeneously mixed population is introduced. The interaction between population and toxigenic Vibrio cholerae concentration in contaminated water has been taken into account. The existence of biologically meaningful equilibria is investigated together with their linear and nonlinear stability. Using the data collected during the Haiti cholera epidemic, a numerical simulation is performed.

We report the clinical, neuro-imaging, pathological and biochemical features of an Italian family in which two siblings have the Adult Polyglucosan Body Disease (APBD). APBD is a rare autosomal recessive disorder characterized by a gradually progressive involvement of both the central and peripheral nervous systems caused by the deficiency of the glycogen branching enzyme (GBE1). The two affected siblings, a 64-year-old man and his 67-year-old sister who had complained of urinary urgency and sporadic incontinence and also progressive gait difficulty for 6 and 7 years respectively, had severely impaired deep sensations on direct examination and a moderately severe symmetrical, axonal sensory-motor neuropathy on electrophysiological testing. GBE1 activity was below 25% of the normal rate in leukocytes and sural nerves. The siblings were homozygous for the novel GBE1 mutation p.N541D. All other members of the pedigree are heterozygous and manifest no symptoms, even in the very elderly. The affected siblings showed polyglucosan bodies (PBs) included within non-myelinating Schwann cells and within lymphocyte vesicles, which were positive for the autophagy markers P62 and LC3-II at immunofluorescence microscopy.

Introduction Point of care devices (POCT) are used for coagulation evaluation in adults. Reduced blood volumes and the direct use of whole blood allow studies when venous puncture is difficult, such as in newborns. Elimination of sample transport is attractive for use in emergencies and intensive care. Objective To prospectively compare neonatal coagulation parameters measured by the GEM®PCL POCT versus a central laboratory. Materials and Methods Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) were performed on whole cord blood (POCT) and plasma (central laboratory) collected from consecutive newborns at Geneva University Hospitals. Agreement was assessed with a Bland & Altman plot and intra-class correlation coefficient (ICC) in 213 newborns cord blood; intra-assay variability (repeatability) was assessed using ICC and coefficient of variation (CV). Results 189 samples were available for the agreement analysis, 24 were excluded for technical problems. The 95% limits of agreements in the Bland & Altman plot ranged from -5.6 to 11.6 and from -39.6 to 11.6 seconds for the PT and aPTT, respectively. The ICC between the two methods was 0.28 (CI 95% 0.06 to 0.47) for PT and 0.20 (CI 95% -0.06 to 0.42) for aPTT. Repeatability (ICC) on the 43 eligible samples was 0.46 (CI 95% 0.19 to 0.67) for PT and 0.52 (CI 95% 0.26 to 0.71) for aPTT. The CV was 10.6% and 12% for PT and aPTT, respectively. Conclusions In newborn cord blood, PT and aPTT measurements with the GEM®PCL POCT had poor agreement with the central laboratory and poor repeatability.

A system modeling fluid motions in horizontal porous layers, uniformly heated and salted from below, is analyzed in the case of variable thermal and solutal diffusivities. The boundedness and uniqueness of solutions are shown. A class of non-constant throughflows is found and their stability is analyzed via a new approach. Conditions of global nonlinear stability, in closed form, are obtained.

This report describes the histopathology of two hundred and fifty-three mesenchymal tumors of the urinary bladder in cattle grazing on lands rich in bracken fern. Approximately 80% were hemangiomas and angiosarcomas. Hemangioma (capillary, cavernous, and large vessels) was the most frequent mesenchymal tumor and was more common than angiosarcoma. Although the appearance of endothelial cells can vary remarkably, epithelioid angiosarcomas, often containing multinucleated cells, were the most frequent malignant vascular tumors. Hemangiopericytoma and tumors of muscle and soft connective tissue origin, alone and/or in association with tumor-like lesions, were less frequently seen. Furthermore, forty-five cases of intravascular papillary endothelial hyperplasia (IPEH), a lesion not previously reported in the urinary bladder of cattle, were also described. Bovine papillomavirus type-2 DNA was amplified in tumor samples. Forty vascular tumors were investigated by dual-labeling immunofluorescence, and, for the first time, a coexpression of E5 and platelet-derived growth factor β receptor (PDGFβR) was shown to occur. The results show that the BPV-2 E5 oncoprotein binds to the activated form of the PDGFβ receptor thus playing an important role in mesenchymal as well as epithelial carcinogenesis of the urinary bladder. Furthermore, these findings demonstrate that BPV-2 infects both epithelial and mesenchymal cells.

Non-linear stability of vertical throughflows in porous layers, uniformly heated and salted from below, is analyzed. The definitively boundedness of the solutions (existence of absorbing sets in the phase space) is proved. Conditions guaranteeing global non-linear asymptotic stability have been found. In closed form, the critical Rayleigh number has been found.

The long-time behavior of triply fluid mixtures saturating horizontal porous layers uniformly rotating around the vertical axis, according to the Brinkman law (holding for large pores), is investigated. The most destabilizing case of layers heated from below and salted from above by two salts, is considered. The ultimately boundedness of the solutions (existence of absorbing sets) is shown. A necessary and sufficient condition guaranteeing the global non-linear asymptotic L 2 -stability of the conduction solution is obtained.

Ternary fluid mixtures saturating horizontal porous layers with large pores, uniformly rotating around the vertical axis, are investigated. The layers are heated from below, salted from above and from below by two salts. The stabilizing effects of both the rotation and Brinkman terms on the conduction solution are analyzed.

BackgroundPapillomaviruses (PVs) are highly epitheliotropic as they usually establish productive infections within squamous epithelia of the skin, the anogenital tract and the oral cavity. In this study, early (E) and late (L) protein expression of bovine papillomavirus type 2 (BPV-2) in the urothelium of the urinary bladder is described in cows and water buffaloes suffering from naturally occurring papillomavirus-associated urothelial bladder tumors.Methods and findingsE5 protein, the major oncoprotein of the BPV-2, was detected in all tumors. L1 DNA was amplified by PCR, cloned and sequenced and confirmed to be L1 DNA. The major capsid protein, L1, believed to be only expressed in productive papillomavirus infection was detected by Western blot analysis. Immunohistochemical investigations confirmed the presence of L1 protein both in the cytoplasm and nuclei of cells of the neoplastic urothelium. Finally, the early protein E2, required for viral DNA replication and known to be a pivotal factor for both productive and persistent infection, was detected by Western blot and immunohistochemically. Electron microscopic investigations detected electron dense particles, the shape and size of which are consistent with submicroscopic features of viral particles, in nuclei of neoplastic urothelium.ConclusionThis study shows that both active and productive infections by BPV-2 in the urothelium of the bovine and bubaline urinary bladder can occur in vivo.