Flow modeling and structural characterization in fungal pellets.

Fungal pellets are hierarchical systems that can be found in an ample variety of applications. Modeling transport phenomena in this type of systems is a challenging but necessary task to provide knowledge-based processes that improve the outcome of their biotechnological applications. In this work, an upscaled model for total mass and momentum transport in fungal pellets is implemented and analyzed, using elements of the volume averaging and adjoint homogenization methods departing from the governing equations at the microscale in the intracellular and extracellular phases. The biomass is assumed to be composed of a non-Newtonian fluid and the organelles impervious to momentum transport are modeled as a rigid solid phase. The upscaled equations contain effective-medium coefficients, which are predicted from the solution of adjoint closure problems in a three-dimensional periodic domains representative of the microstructure. The construction of these domains was performed for Laccaria trichodermophora based on observations of actual biological structures. The upscaled model was validated with direct numerical simulations in homogeneous portions of the pellets core. It is shown that no significant differences are observed when the dolipores are open or closed to fluid flow. By comparing the predictions of the average velocity in the extracellular phase resulting from the upscaled model with those from the classical Darcy equation (i.e., assuming that the biomass is a solid phase) the contribution of the intracellular fluid phase was evidenced. This work sets the foundations for further studies dedicated to transport phenomena in this type of systems.

A chiral metal cluster triggers enantiospecific electronic transport.

Chirality is a geometric property of matter that can be present at different scales, especially at the nanoscale. Here, we investigate the manifestation of chirality in electronic transport through a molecular junction. Spinless electronic transport through a chiral molecular junction is not enantiospecific. However, when a chiral metal cluster, C3-Au34, is attached to the source electrode, a different response is obtained in spinless electronic transport between R and L systems: this indicates the crucial role of chiral clusters in triggering enantiospecific spinless electronic transport. In contrast, when an achiral metal cluster, C3v-Au34, is attached, no change in conductance occurs between enantiomeric systems. Using the non-equilibrium green's function method, we characterized this phenomenon by calculating the transmission and conductance of spin-unpolarized electrons. Our theoretical results highlight the importance of metal clusters with specific sizes and chiral structures in electronic transport and support previously published experimental results that exhibited enantiospecific scanning tunneling measurements with intrinsically chiral tips.

Obesity induces extracellular vesicle release from the endothelium as a contributor to brain damage after cerebral ischemia in rats.

OBJECTIVES: Cerebral ischemia is the most common cause of disability, the second most common cause of dementia, and the fourth most common cause of death in the developed world [Sveinsson OA, Kjartansson O, Valdimarsson EM. Heilablóðþurrð/heiladrep: Faraldsfræði, orsakir og einkenni [Cerebral ischemia/infarction - epidemiology, causes and symptoms]. Laeknabladid. 2014 May;100(5):271-9. Icelandic. doi:10.17992/lbl.2014.05.543]. Obesity has been associated with worse outcomes after ischemia in rats, triggering proinflammatory cytokine production related to the brain microvasculature. The way obesity triggers these effects remains mostly unknown. Therefore, the aim of this study was to elucidate the cellular mechanisms of damage triggered by obesity in the context of cerebral ischemia. METHODS: We used a rat model of obesity induced by a 20% high fructose diet (HFD) and evaluated peripheral alterations in plasma (lipid and cytokine profiles). Then, we performed cerebral ischemia surgery using two-vessel occlusion (2VO) and analyzed neurological/motor performance and glial activation. Next, we treated endothelial cell line cultures with glutamate in vitro to simulate an excitotoxic environment, and we added 20% plasma from obese rats. Subsequently, we isolated EVs released from endothelial cells and treated primary cultures of astrocytes with them. RESULTS: Rats fed a HFD had an increased BMI with dyslipidemia and high levels of proinflammatory cytokines. Glia from the obese rats exhibited altered morphology, suggesting hyperreactivity related to neurological and motor deficits. Plasma from obese rats induced activation of endothelial cells, increasing proinflammatory signals and releasing more EVs. Similarly, these EVs caused an increase in NF-κB and astrocyte cytotoxicity. Together, the results suggest that obesity activates proinflammatory signals in endothelial cells, resulting in the release of EVs that simultaneously contribute to astrocyte activation.

Adrenal hemorrhage and non-ST elevation myocardial infarction: an antiphospholipid syndrome dilemma.

Antiphospholipid syndrome (APS) can affect different organ systems, including the heart and adrenal glands. Despite being known for its prothrombotic characteristics, APS can have serious bleeding complications. Occasionally, thrombotic and bleeding episodes can present simultaneously in an APS patient. Whenever these events co-occur, resuming anticoagulation becomes a topic of debate. As such, we present the case of a 43-year-old male with triple positive antiphospholipid antibodies, indicating APS, who presented with chest pain. Anticoagulants were switched one month before presentation from warfarin to a direct oral anticoagulant, rivaroxaban. Non-ST elevation myocardial infarction, as well as new-onset left-sided adrenal hemorrhage, were diagnosed. The patient developed adrenal insufficiency; therefore, corticosteroids were administered, and warfarin was resumed to prevent further thrombotic episodes.

Systematic mapping review of interventions to prevent blood loss, infection and relapse in orthognathic surgery.

BACKGROUND: This systematic mapping review aims to identify, describe, and organize the currently available evidence in systematic reviews (SR) and primary studies regarding orthognathic surgery (OS) co-interventions and surgical modalities, focusing on the outcomes blood loss, infection and relapse. MATERIAL AND METHODS: A comprehensive search strategy was performed to identify all SRs, randomized controlled trials and observational studies that evaluate surgical modalities and perioperative co-interventions in OS that evaluate the outcomes blood loss, infection and relapse, regardless of language or publication date. Searches were conducted in MEDLINE, EMBASE, Epistemonikos, Lilacs, Web of Science, and CENTRAL. In addition, grey literature was screened. RESULTS: 27 SRs and 150 primary studies fulfilled the inclusion criteria, 91 from SRs, and 59 from our search strategy. Overall, the quality of the SRs was graded as "Critically low," and only two SRs were rated as "High" quality. 11 PICO questions were extracted from SRs and 31 from primary studies, which focused on osteosynthesis methods, surgical cutting devices, use of antibiotics, and induced hypotension. In addition, evidence bubble maps for each outcome were created to analyze in a visual manner the existing evidence. CONCLUSIONS: Future primary and secondary high-quality research should be addressed focused on the eight knowledge gaps identified in this mapping review. We concluded that the evidence mapping approach is a practical methodology for organizing the current evidence and identifying knowledge gaps in OS, helping to reduce research waste and canalize future efforts in developing studies for unsolved questions.

Enhanced antitumor effect of L-buthionine sulfoximine or ionizing radiation by copper complexes with 2,2´-biquinoline and sulfonamides on A549 2D and 3D lung cancer cell models.

Two ternary copper(II) complexes with 2,2'-biquinoline (BQ) and with sulfonamides: sulfamethazine (SMT) or sulfaquinoxaline (SDQ) whose formulae are Cu(SMT)(BQ)Cl and Cu(SDQ)(BQ)Cl·CH3OH, in what follows SMTCu and SDQCu, respectively, induced oxidative stress by increasing ROS level from 1.0 µM and the reduction potential of the couple GSSG/GSH2. The co-treatment with L-buthionine sulfoximine (BSO), which inhibits the production of GSH, enhanced the effect of copper complexes on tumor cell viability and on oxidative damage. Both complexes generated DNA strand breaks given by-at least partially-the oxidation of pyrimidine bases, which caused the arrest of the cell cycle in the G2/M phase. These phenomena triggered processes of apoptosis proven by activation of caspase 3 and externalization of phosphatidylserine and loss of cell integrity from 1.0 µM. The combination with BSO induced a marked increase in the apoptotic population. On the other hand, an improved cell proliferation effect was observed when combining SDQCu with a radiation dose of 2 Gy from 1.0 µM or with 6 Gy from 1.5 µM. Finally, studies in multicellular spheroids demonstrated that even though copper(II) complexes did not inhibit cell invasion in collagen gels up to 48 h of treatment at the higher concentrations, multicellular resistance outperformed several drugs currently used in cancer treatment. Overall, our results reveal an antitumor effect of both complexes in monolayer and multicellular spheroids and an improvement with the addition of BSO. However, only SDQCu was the best adjuvant of ionizing radiation treatment.

Proton Distribution Radii of

The root mean square radii of the proton density distribution in ^{16-24}O derived from measurements of charge changing cross sections with a carbon target at ∼900A MeV together with the matter radii portray thick neutron skin for ^{22-24}O despite ^{22,24}O being doubly magic. Imprints of the shell closures at N=14 and 16 are reflected in local minima of their proton radii that provide evidence for the tensor interaction causing them. The radii agree with ab initio calculations employing the chiral NNLO_{sat} interaction, though skin thickness predictions are challenged. Shell model predictions agree well with the data.

Image processing tools for the validation of CryoEM maps.

The number of maps deposited in public databases (Electron Microscopy Data Bank, EMDB) determined by cryo-electron microscopy has quickly grown in recent years. With this rapid growth, it is critical to guarantee their quality. So far, map validation has primarily focused on the agreement between maps and models. From the image processing perspective, the validation has been mostly restricted to using two half-maps and the measurement of their internal consistency. In this article, we suggest that map validation can be taken much further from the point of view of image processing if 2D classes, particles, angles, coordinates, defoci, and micrographs are also provided. We present a progressive validation scheme that qualifies a result validation status from 0 to 5 and offers three optional qualifiers (A, W, and O) that can be added. The simplest validation state is 0, while the most complete would be 5AWO. This scheme has been implemented in a website https://biocomp.cnb.csic.es/EMValidationService/ to which reconstructed maps and their ESI can be uploaded.

High fructose diet-induced obesity worsens post-ischemic brain injury in the hippocampus of female rats.

Objectives: Cerebral ischemia is caused by a reduction of the blood flow in a specific area in the brain, triggering cellular cascades in the tissue that result in neuronal death. This phenomenon leads to neurological decline in patients with stroke. The extent of the injury after stroke could be related to the condition of obesity. Thus, we aim to analyze the effect of obesity induced by a high fructose diet (HFD) on the brain after cerebral ischemia in rats.Methods: We induced the obesity model in female Wistar rats with 20% fructose in water for 11 weeks. We then performed cerebral ischemia surgery (2-vessel occlusion), carried out the neurological test 6, 24 and 48 h post-ischemia and analyzed the histological markers.Results: The HFD induced an obese phenotype without insulin resistance. The obese rats exhibited worse neurological performance at 6 h post-ischemia and showed neuronal loss and astroglial and microglial immunoreactivity changes in the caudate putamen, motor cortex, amygdala and hippocampus at 48 h post-ischemia. However, the most commonly affected area was the hippocampus, where we found an increase in interleukin 1ß in the blood vessels of the dentate gyrus, a remarkable disruption of MAP-2+ dendrites, a loss of brain-derived neurotrophic factor and the presence of PHF-tau. In conclusion, a HFD induces an obese phenotype and worsens the neuronal loss, inflammation and plasticity impairment in the hippocampus after cerebral ischemia.

Orbital Many-Body Dynamics of Bosons in the Second Bloch Band of an Optical Lattice.

We explore Josephson-like dynamics of a Bose-Einstein condensate of rubidium atoms in the second Bloch band of an optical square lattice providing a double well structure with two inequivalent, degenerate energy minima. This oscillation is a direct signature of the orbital changing collisions predicted to arise in this system in addition to the conventional on-site collisions. The observed oscillation frequency scales with the relative strength of these collisional interactions, which can be readily tuned via a distortion of the unit cell. The observations are compared to a quantum model of two single-particle modes and to a semiclassical multiband tight-binding simulation of 12×12 tubular sites of the lattice. Both models reproduce the observed oscillatory dynamics and show the correct dependence of the oscillation frequency on the ratio between the strengths of the on-site and orbital changing collision processes.

Cumulative effects of titanium dioxide nanoparticles in UASB process during wastewater treatment.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in consumer products and one of their major fate is the wastewater treatment plants. However, NPs eventually arrive to aquatic and terrestrial ecosystems via treated water and biosolids, respectively. Since low concentration of NPs is accumulating in the upflow anaerobic sludge blanket (UASB) reactors that treat wastewater and reclaim water quality, the accumulation of TiO2 NPs in these reactors may impact in their performance. In this work, the long-term effects of TiO2 NPs on the main benefits of treating wastewater by UASB reactors such as, biogas production, methane fraction in biogas and organic matter removal were evaluated. Evaluation consisted of monitoring such parameters in two identical UASB reactors, one UASB-Control (without NPs) and the experimental one (UASB-TiO2 NPs) that received wastewater with TiO2 NPs. The fate of NPs in the UASB reactor was also determined. Results indicated that biogas production increased by 8.8% due to the chronic exposure of UASB reactor to TiO2 NPs during the first 44 days of experiment. However, the methane content in the biogas had no significant differences between both UASB, ranging between 78% and 90% of methane during the experiment. The removal of organic matter in both UASB was similar and ranged 92-98% along the experimental time. This means that accumulation of TiO2 NPs did not altered the biogas production and organic matter removal. However, the content of total volatile solids (TVS) in UASB-TiO2 NPs dropped off from 137.8 g to 64.2 g in 84 days, while for control reactor that decreased from 141.6 g to 92.4 g in the same period. Hence, the increased biogas production in the UASB exposed to TiO2 was attributed to hydrolysis of the TVS in this reactor. The main fate of TiO2 NPs was the granular sludge, which accumulated up to 8.56 mg Ti/g, which represent around 99% of the Ti spiked to the reactor and the possible cause of the biomass hydrolyzation in the UASB. Disposal of UASB sludge containing NPs from may raise ecotoxicological concerns due to the use of biosolids in agricultural activities.

The influence of the correlation-covariance structure of measurement errors over uncertainties propagation in online monitoring: application to environmental indicators in SUDS.

This paper presents a methodology to assess the influence of the correlation-covariance structure of measurement errors in online monitoring over the propagation of uncertainties, applied to wet-weather environmental indicators in sustainable urban drainage systems (SUDSs). The effect of auto-correlated and heteroskedastic errors in measured time-series over the estimated probability density function (PDF) of different environmental indicators is analyzed for a wide variety of possible error structures in the data. For this purpose, multiple correlation-covariance structures are randomly generated from exploring the parametric space of a linear exponent autoregressive (LEAR) model, employing a Bayesian-based Markov Chain Monte Carlo sampling technique. Significant differences tests are proposed to identify the most correlated parameters of the correlation-covariance error model with statistics of the environmental indicator PDFs. The method is applied to total suspended solids (TSS) and chemical oxygen demand (COD) time-series recorded during 13 rainfall events at the inlet and outlet of a SUDS train (stormwater settling tank-horizontal constructed wetland). In this case, results showed that the total error in the estimation of the analyzed environmental indicators is mostly explained by standard uncertainties (flattening of the PDFs) rather than bias contributions (displacement of the PDFs). The correlation-covariance model parameters related to the temporal delimitation of hydrographs/pollutographs and the intensity of the autocorrelation showed to have the strongest influence in the propagation of measurement errors (flattening/displacement of the PDFs).

Re-examining the spectra of macromolecules. Current practice of spectral quasi B-factor flattening.

The analysis of structure factors in 3D cryo-EM Coulomb potential maps and their "enhancement" at the end of the reconstruction process is a well-established practice, normally referred to as sharpening. The aim is to increase contrast and, in this way, to help tracing the atomic model. The most common way to accomplish this enhancement is by means of the so-called B-factor correction, which applies a global filter to boost high frequencies with some dampening considerations related to noise amplification. The results are maps with a better visual aspect and a quasiflat spectrum at medium and high frequencies. This practice is so widespread that most map depositions in the Electron Microscopy Data Base (EMDB) only contain sharpened maps. Here, the use in cryoEM of global B-factor corrections is theoretically and experimentally analyzed. Results clearly illustrate that protein spectra present a falloff. Thus, spectral quasi-flattening may produce protein spectra with distortions when compared with experimental ones, this fact, combined with the practice of reporting only sharpened maps, generates a sub-optimal situation in terms of data preservation, reuse and reproducibility. Now that the field is more advanced, we put forward two suggestions: (1) to use methods which keep more faithfully the original experimental signal properties of macromolecules when "enhancing" the map, and (2) to further stress the need to deposit the original experimental maps without any postprocessing or sharpening, not only the enhanced maps. In the absence of access to these original maps data is lost, preventing their future analysis with new methods.

Evidence for a New Compact Symmetric Fission Mode in Light Thorium Isotopes.

Taking benefit of the R3B/SOFIA setup to measure the mass and the nuclear charge of both fission fragments in coincidence with the total prompt-neutron multiplicity, the scission configurations are inferred along the thorium chain, from the asymmetric fission in the heavier isotopes to the symmetric fission in the neutron-deficient thorium. Against all expectations, the symmetric scission in the light thorium isotopes shows a compact configuration, which is in total contrast to what is known in the fission of the heavier thorium isotopes and heavier actinides. This new main symmetric scission mode is characterized by a significant drop in deformation energy of the fission fragments of about 19 MeV, compared to the well-known symmetric scission in the uranium-plutonium region.

Endovascular Repair of Bilateral Internal Mammary Artery Aneurysms in a Patient with Marfan Syndrome.

BACKGROUND: True internal mammary artery aneurysms are rare but rupture has been described. CASE REPORT: A 39-year-old male patient with Marfan syndrome was diagnosed with large asymptomatic bilateral internal mammary artery aneurysms (IMAAs) on contrast-enhanced CT scan, without other arterial lesions. Both aneurysms were coil embolized, a stent graft was deployed in the left subclavian artery to cover a wide neck that precluded complete and safe embolization of the left IMAA. Reintervention on the right side was performed 5 years later due to recanalization. Eight years after the initial procedure, the patient presented with a type A aortic dissection that was successfully repaired. CONCLUSIONS: Although extremely rare, endovascular treatment should be considered to prevent rupture of internal mammary artery aneurysms.

Energy requirements and efficiency of energy utilization in growing dairy goats of different sexes.

The aim of this study was to investigate the effects of sex on the requirements for maintenance and efficiency of energy utilization in growing Saanen goats. A database from 7 comparative slaughter studies that included 238 Saanen goats was gathered to provide information for the development of prediction equations of energy requirements for maintenance and efficiency of energy utilization. The experimental design provided different levels of metabolizable energy intake (MEI) and empty body weight (EBW). The data were analyzed so that sex (e.g., intact males, castrated males, and females; n = 98, 80, and 60, respectively) was a fixed effect, and blocks nested in the studies and goat sex were random effects. For the development of linear and nonlinear equations, we used the MIXED and NLMIXED procedures in SAS (SAS Institute Inc., Cary, NC). Nonlinear regression equations were developed to predict heat production (HP, kcal/kg0.75 of EBW; dependent variable) from MEI (kcal/kg0.75 of EBW; independent variable). Using the comparative slaughter technique, the net energy requirement for maintenance (NEM) was calculated as the value of HP at MEI equal to zero. Additionally, NEM was evaluated based on the degree of maturity. The metabolizable energy requirement for maintenance was calculated as the value at which HP is equal to MEI. Efficiency of ME utilization for maintenance (km) was calculated as the ratio between NEM and the metabolizable energy requirement for maintenance. Efficiency of energy utilization for growth (kg) was assumed to be the slope of the linear regression of retained energy (RE) on MEI above the maintenance stage (model intercept equal to 0). Efficiencies of RE as protein (kp) and as fat (kf) were calculated using the multiple linear regression of MEI above the maintenance (model intercept equal to 0) on RE as protein and as fat, respectively. Sex affected NEM (75.0 ± 1.76 kcal/kg0.75 of EBW for males and 63.6 ± 2.89 kcal/kg0.75 of EBW for females) and sex did not affect km (0.63). In contrast, sex no longer affected NEM when degree of maturity was considered on its estimation. The kg was different between sexes (0.31 for castrated males and females, and 0.26 for intact males), but kp (0.21) and kf (0.80) were similar between sexes. These results may be useful for improving robustness of the energy requirement recommendations for dairy goats.

ScribeMD: Mixed-methods analysis of a pen pal program in undergraduate medical education.

Introduction: A growing emphasis on humanistic medical care has led to the development of programs to imbue more humanistic values into training physicians. The ScribeMD intra-class pen pal program is a narrative medicine tool designed to meet this need with a focus on the journey through medical education. This study intends to evaluate the efficacy of this novel program on the participants' professional identity formation (PIF), emotional intelligence development (EID), and narrative competency improvement (NCI).Methods: This program evaluation involved quantitative and qualitative survey solicitations from first and second-year medical student participants and controls. An efficacy-triangulation model was developed as a quantitative outcome-measuring tool linking objective, writing prompts, and survey data.Results: The quantitative results showed statistically significant improvements in line with the Efficacy Triangulation Model in the participant group. Qualitatively, reflective and insight-driven gains were elicited, as were notable themes of personal and community improvements.Conclusion: ScribeMD poses a unique avenue for the development of more humanistic physicians during their medical education. We recommend additional development of the Efficacy Triangulation Model as well as the program design itself. We also recommend the piloting of this program in other healthcare-education settings both with medical education and other health professions.

[Endovascular management of chronic limb ischemia. Experience in 48 procedures]. / Manejo endovascular de la isquemia crítica distal: análisis de una serie contemporánea.

BACKGROUND: Chronic limb ischemia can lead to high rates of limb loss and mortality. Open surgery is the gold standard for treatment of distal disease. Endovascular surgery should have less complications with similar outcomes. AIM: To report a cohort of patients with distal arterial disease treated with endovascular surgery at our institution. MATERIAL AND METHODS: Review of angioplasty records of patients undergoing distal lower extremity endovascular procedures between 2016 and 2019. Demographics, comorbidities, form of presentation, type of intervention, perioperative complications, and length of stay were analyzed. The primary outcomes were wound healing, reinterventions and freedom from major amputation. Secondary outcomes were overall survival and amputation-free survival. RESULTS: Forty-eight limbs of 41 patients with a mean age 75 years (78% males) were treated. Ninety-three percent had hypertension, 88% diabetes, 30% chronic kidney disease. 73% presented with major wounds. Plain balloon and drug coated balloon angioplasties were carried out in 65 and 31% of procedures respectively, with no difference in results. In 46% of the cases, only chronic total occlusions were treated. Wound healing was achieved in 85% of procedures and 90% of patients were free from amputation at one year of follow up. Complications were observed in 18% of procedures, perioperative mortality was 2% and one-year survival was 76%. CONCLUSIONS: Endovascular therapy achieves high rates of wound healing and freedom from amputation with low perioperative mortality and moderate complication rates.

Expanding functions of ADP-ribosylation in the maintenance of genome integrity.

Cell response to genotoxic stress requires a complex network of sensors and effectors from numerous signaling and repair pathways, among them the nuclear poly(ADP-ribose) polymerase 1 (PARP1) plays a central role. PARP1 is catalytically activated in the setting of DNA breaks. It uses NAD+ as a donor and catalyses the synthesis and subsequent covalent attachment of branched ADP-ribose polymers onto itself and various acceptor proteins to promote repair. Its inhibition is now considered as an efficient therapeutic strategy to potentiate the cytotoxic effect of chemotherapy and radiation or to exploit synthetic lethality in tumours with defective homologous recombination mediated repair. Still, efforts made on understanding the role of PARylation in DNA repair continues to yield novel discoveries. Over the last years, our knowledge in this field has been particularly advanced by the discovery of novel biochemical and functional properties featuring PARP1, by the characterization of the other PARP family members and by the identification of a panel of enzymes capable of erasing poly(ADP-ribose). The aim of this review is to provide an overview of these newest findings and their relevance in genome surveillance.

A robust approach to ab initio cryo-electron microscopy initial volume determination.

Structural information from macromolecules provides key insights into the way complexes perform their biological functions. The reconstruction process leading to the final three-dimensional (3D) map is iterative and requires an initial volume to prime the refinement procedure. Particle images are aligned to this first reference and subsequently a new map is calculated from these particles. The accurate determination of an ab initio initial volume is still a challenging and open problem in cryo-electron microscopy (cryo-EM). Different algorithms are available to estimate an initial volume from the dataset. Some of these methods provide multiple candidate initial maps and users looking for robustness typically run different approaches. In this case, users arbitrarily evaluate the different obtained candidate maps, as we lack robust methods to objectively assess the accuracy of initial references. This workflow is subjective and error-prone preventing implementation of high-throughput data processing procedures. In this work, we present a robust method to determine the best initial map or maps from a set of ab initio initial volumes obtained from one or multiple different approaches. The method is based on evaluating multiple small subsets of candidate initial volumes and particle images through reference-based 3D classifications. Obtained 3D classes of accurate initial maps will result majoritarian and the respective attracted particles will be aligned with high angular accuracies. We have tested the proposed approach with structurally homogeneous and heterogeneous datasets providing satisfactory results with both type of data.