Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of cadherins and plakoglobin in interendothelial adhesion under resting conditions and shear stress.

The role of cadherins and the cadherin-binding cytosolic protein plakoglobin in intercellular adhesion was studied in cultured human umbilical venous endothelial cells exposed to fluid shear stress. Extracellular Ca2+depletion (<10-7 M) caused the disappearance of both cadherins and plakoglobin from junctions, whereas the distribution of platelet endothelial cell adhesion molecule 1 (PECAM-1) remained unchanged. Cells stayed fully attached to each other for several hours in low Ca2+ but began to dissociate under flow conditions. At the time of recalcification, vascular endothelial (VE) cadherin and β-catenin became first visible at junctions, followed by plakoglobin with a delay of ∼20 min. Full fluid shear stress stability of the junctions correlated with the time course of the reappearance of plakoglobin. Inhibition of plakoglobin expression by microinjection of antisense oligonucleotides did not interfere with the junctional association of VE-cadherin, PECAM-1, and β-catenin. The plakoglobin-deficient cells remained fully attached to each other under resting conditions but began to dissociate in response to flow. Shear stress-induced junctional dissociation was also observed in cultures of plakoglobin-depleted arterial endothelial cells of the porcine pulmonary trunk. These observations show that interendothelial adhesion under hydrodynamic but not resting conditions requires the junctional location of cadherins associated with plakoglobin. β-Catenin cannot functionally compensate for the junctional loss of plakoglobin, and PECAM-1-mediated adhesion is not sufficient for monolayer integrity under flow.
Evaluation of Two Liver Treatment Strategies in a Mouse Model of Niemann–Pick-Disease Type C1

Niemann–Pick-disease type C1 (NPC1) is an autosomal-recessive cholesterol-storage disorder. Besides other symptoms, NPC1 patients develop liver dysfunction and hepatosplenomegaly. The mechanisms of hepatomegaly and alterations of lipid metabolism-related genes in NPC1 disease are still poorly understood. Here, we used an NPC1 mouse model to study an additive hepatoprotective effect of a combination of 2-hydroxypropyl-β-cyclodextrin (HPβCD), miglustat and allopregnanolone (combination therapy) with the previously established monotherapy using HPβCD. We examined transgene effects as well as treatment effects on liver morphology and hepatic lipid metabolism, focusing on hepatic cholesterol transporter genes. Livers of Npc1−/− mice showed hepatic cholesterol sequestration with consecutive liver injury, an increase of lipogenetic gene expression, e.g., HMG-CoA, a decrease of lipolytic gene expression, e.g., pparα and acox1, and a decrease of lipid transporter gene expression, e.g., acat1, abca1 and fatp2. Both, combination therapy and monotherapy, led to a reduction of hepatic lipids and an amelioration of NPC1 liver disease symptoms. Monotherapy effects were related to pparα- and acox1-associated lipolysis/β-oxidation and to fatp2-induced fatty acid transport, whereas the combination therapy additionally increased the cholesterol transport via abca1 and apoE. However, HPβCD monotherapy additionally increased cholesterol synthesis as indicated by a marked increase of the HMG-CoA and srebp-2 mRNA expression, probably as a result of increased hepatocellular proliferation.
Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets

Significance Hematogenous implant-related infections are an important clinical problem because bacteria spread from the bloodstream to a previously well-functioning implant and result in infectious complications and failure of a medical device or prosthesis. To study these infections, we developed a preclinical animal model of a Staphylococcus aureus hematogenous implant infection with the capability to monitor noninvasively and longitudinally the dissemination of the bacteria from the blood to a surgically placed orthopedic implant. Using this model, α-toxin and clumping factor A were identified as key factors that contributed to the pathogenesis of these infections by promoting biofilm formation. Finally, neutralizing antibodies against these factors provided a targeted, nonantibiotic alternative approach to help prevent these difficult-to-treat and costly infections. Infection is a major complication of implantable medical devices, which provide a scaffold for biofilm formation, thereby reducing susceptibility to antibiotics and complicating treatment. Hematogenous implant-related infections following bacteremia are particularly problematic because they can occur at any time in a previously stable implant. Herein, we developed a model of hematogenous infection in which an orthopedic titanium implant was surgically placed in the legs of mice followed 3 wk later by an i.v. exposure to Staphylococcus aureus. This procedure resulted in a marked propensity for a hematogenous implant-related infection comprised of septic arthritis, osteomyelitis, and biofilm formation on the implants in the surgical legs compared with sham-operated surgical legs without implant placement and with contralateral nonoperated normal legs. Neutralizing human monoclonal antibodies against α-toxin (AT) and clumping factor A (ClfA), especially in combination, inhibited biofilm formation in vitro and the hematogenous implant-related infection in vivo. Our findings suggest that AT and ClfA are pathogenic factors that could be therapeutically targeted against S. aureus hematogenous implant-related infections.
Antibacterial activity and biofilm inhibition by surface modified titanium alloy medical implants following application of silver, titanium dioxide and hydroxyapatite nanocoatings

Abstract One of the most common causes of implant failure is peri-implantitis, which is caused by bacterial biofilm formation on the surfaces of dental implants. Modification of the surface nanotopography has been suggested to affect bacterial adherence to implants. Silver nanoparticles are also known for their antibacterial properties. In this study, titanium alloy implants were surface modified following silver plating, anodisation and sintering techniques to create a combination of silver, titanium dioxide and hydroxyapatite (HA) nanocoatings. Their antibacterial performance was quantitatively assessed by measuring the growth of Streptococcus sanguinis, proportion of live/dead cells and lactate production by the microbes over 24 h. Application of a dual layered silver–HA nanocoating to the surface of implants successfully inhibited bacterial growth in the surrounding media (100% mortality), whereas the formation of bacterial biofilm on the implant surfaces was reduced by 97.5%. Uncoated controls and titanium dioxide nanocoatings showed no antibacterial effect. Both silver and HA nanocoatings were found to be very stable in biological fluids with material loss, as a result of dissolution, to be less than 0.07% for the silver nanocoatings after 24 h in a modified Krebs-Ringer bicarbonate buffer. No dissolution was detected for the HA nanocoatings. Thus, application of a dual layered silver–HA nanocoating to titanium alloy implants creates a surface with antibiofilm properties without compromising the HA biocompatibility required for successful osseointegration and accelerated bone healing.
Rapid growth of the US wildland-urban interface raises wildfire risk

Significance When houses are built close to forests or other types of natural vegetation, they pose two problems related to wildfires. First, there will be more wildfires due to human ignitions. Second, wildfires that occur will pose a greater risk to lives and homes, they will be hard to fight, and letting natural fires burn becomes impossible. We examined the number of houses that have been built since 1990 in the United States in or near natural vegetation, in an area known as the wildland-urban interface (WUI), and found that a large number of houses have been built there. Approximately one in three houses and one in ten hectares are now in the WUI. These WUI growth trends will exacerbate wildfire problems in the future. The wildland-urban interface (WUI) is the area where houses and wildland vegetation meet or intermingle, and where wildfire problems are most pronounced. Here we report that the WUI in the United States grew rapidly from 1990 to 2010 in terms of both number of new houses (from 30.8 to 43.4 million; 41% growth) and land area (from 581,000 to 770,000 km2; 33% growth), making it the fastest-growing land use type in the conterminous United States. The vast majority of new WUI areas were the result of new housing (97%), not related to an increase in wildland vegetation. Within the perimeter of recent wildfires (1990–2015), there were 286,000 houses in 2010, compared with 177,000 in 1990. Furthermore, WUI growth often results in more wildfire ignitions, putting more lives and houses at risk. Wildfire problems will not abate if recent housing growth trends continue.
Electronic approaches to restoration of sight

Retinal prostheses are a promising means for restoring sight to patients blinded by the gradual atrophy of photoreceptors due to retinal degeneration. They are designed to reintroduce information into the visual system by electrically stimulating surviving neurons in the retina. This review outlines the concepts and technologies behind two major approaches to retinal prosthetics: epiretinal and subretinal. We describe how the visual system responds to electrical stimulation. We highlight major differences between direct encoding of the retinal output with epiretinal stimulation, and network-mediated response with subretinal stimulation. We summarize results of pre-clinical evaluation of prosthetic visual functions in- and ex vivo, as well as the outcomes of current clinical trials of various retinal implants. We also briefly review alternative, non-electronic, approaches to restoration of sight to the blind, and conclude by suggesting some perspectives for future advancement in the field.
Micromechanical modeling and strength prediction of short fiber reinforced polymers

Abstract In this contribution, the embedding and compatibility of commonly used strength criteria in practical engineering design (e.g., Tsai-Hill) into a two-step, mean-field, homogenization approach are investigated. This approach provides the opportunity to account for the heterogeneous microstructure of a polymer composite, caused by the non-unidirectional fiber distribution due to the injection molding process. In a first step, an incremental Mori-Tanaka homogenization scheme is applied to unidirectional sub-domains. In a second step, a Voigt model is used to compute the mechanical composite behavior of an entire domain, which itself is the composition of weighted sub-domains. The chosen two-step approach allows the application of models to predict the strength after both homogenization steps. This leads to two different strength prediction strategies. The selection of certain criteria in combination with the selected level of strength prediction influences the simulation results and the number of material tests necessary for calibration. These two aspects are directly linked to engineering expenses and they are evaluated in a cost benefit analysis. To account for elasto-plasticity, a second-moment formulation is used and extended. The extension allows the direct usage of experimental matrix material data, without having to introduce a virtual matrix as commonly necessary.
Machine Speech Chain with One-shot Speaker Adaptation

In previous work, we developed a closed-loop speech chain model based on deep learning, in which the architecture enabled the automatic speech recognition (ASR) and text-to-speech synthesis (TTS) components to mutually improve their performance. This was accomplished by the two parts teaching each other using both labeled and unlabeled data. This approach could significantly improve model performance within a single-speaker speech dataset, but only a slight increase could be gained in multi-speaker tasks. Furthermore, the model is still unable to handle unseen speakers. In this paper, we present a new speech chain mechanism by integrating a speaker recognition model inside the loop. We also propose extending the capability of TTS to handle unseen speakers by implementing one-shot speaker adaptation. This enables TTS to mimic voice characteristics from one speaker to another with only a one-shot speaker sample, even from a text without any speaker information. In the speech chain loop mechanism, ASR also benefits from the ability to further learn an arbitrary speaker's characteristics from the generated speech waveform, resulting in a significant improvement in the recognition rate.
Assessment of Au-Ge Die Attachment for an Extended Junction Temperature Range in Power Applications

A eutectic Au-Ge (12 wt%) die attach system has traditionally been used in electrical characterization of SiC devices in a temperature range up to 300°C. However, only fragmentary results have been reported concerning the applicability of the system. In this paper, a eutectic Au-Ge die attach system composed of 0.3-mm-thick, 2×2 mm2 SiC dies soldered on ceramic (SiN) substrates with Ni/Au-plated Cu foil is systematically discussed on the basis of the results of storage tests at 300°C and thermal cycle tests ranging from −40°C to 300°C. Die attachments were performed at ~400°C by using a vacuum reflow soldering system. Shear testing of the samples indicated that the initial dies had very strong shear strength of more than 100 MPa. After 300°C storage for 3000 hours in air, it was found that their shear strength markedly dropped, but still maintained an average value two times larger than the JAITA standard of 6.2 MPa specified in IEC 749 for die shear strength. The test results for a thermal cycle from −40.
Blockade of neuronal nitric oxide synthase alters the baroreflex control of heart rate in the rabbit.

In previous studies we used N G-nitro-l-arginine (l-NNA) to investigate the role of nitric oxide (NO) in baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA). l-NNA increased resting mean arterial pressure (MAP), decreased HR, and did not change or slightly decreased RSNA. These changes complicated the assessment of the central effects of NO on the baroreflex control of HR and RSNA. Therefore, in the present study the effects of the relatively selective neuronal NO synthase inhibitor 7-nitroindazole (7-NI) on the baroreflex control of HR and RSNA were investigated in rabbits. Intraperitoneal injection of 7-NI (50 mg/kg) had no effect on resting HR, MAP, or RSNA. 7-NI significantly reduced the lower plateau of the HR-MAP baroreflex curve from 140 ± 4 to 125 ± 4 and from 177 ± 10 to 120 ± 9 beats/min in conscious and anesthetized preparations, respectively ( P < 0.05). In contrast, there was no significant difference in the RSNA-MAP curves before and after 7-NI administration in conscious or anesthetized preparations. These data suggest that blockade of neuronal NO synthase influences baroreflex control of HR but not of RSNA in rabbits.
Results of Type I Tympanoplasty Using Fascia with or without Cartilage Reinforcement: 10 Years’ Experience

Introduction: There remains controversy about the optimal kind of graft to repair tympanic membrane. The purpose of this study was to evaluate the anatomical and auditory outcomes of type I tympanoplasty using fascia with or without cartilage reinforcement. Materials and Methods: This retrospective cohort study was conducted from 2005 to 2015. All cases were surgically treated by a single surgeon. We excluded cases in which the etiology of chronic otitis media was cholesteatoma. According to the use of cartilage reinforcement in the posterosuperior part of the graft, patients were divided into two groups, and the results of anatomical and auditory evaluation were compared between the two groups. The anatomical outcome was grafting success and the auditory outcome was improvement of air bone gap (ABG). Results: A total of 320 patients were classified in Group A (tympanoplasty with fascia temporalis only) and 346 were in Group B (tympanoplasty with cartilage reinforcement). All patients were followed for at least 2 years. The overall success rate in the two groups was 91.6% and 93.4%, respectively (P=0.3). The most common cause of failure in the two groups was re-perforation (5.6% and 3.8%, respectively). The improvement of ABG in two groups was 18.5 dB and 3.2 dB, respectively. The difference between two groups was statistically significant (P<0.001). Conclusion: In patients with dry perforation of the tympanic membrane, the anatomical success with tympanoplasty with fascia only or with cartilage reinforcement was similar. However, hearing improvement in the fascia only group was greater than in the group undergoing cartilage reinforcement.
Pulmonary surfactant inhibits LPS-induced nitric oxide production by alveolar macrophages.

The objectives of this investigation were 1) to report that pulmonary surfactant inhibits lipopolysaccharide (LPS)-induced nitric oxide (⋅ NO) production by rat alveolar macrophages, 2) to study possible mechanisms for this effect, and 3) to determine which surfactant component(s) is responsible. ⋅ NO produced by the cells in response to LPS is due to an inducible ⋅ NO synthase (iNOS). Surfactant inhibits LPS-induced ⋅ NO formation in a concentration-dependent manner; ⋅ NO production is inhibited by ∼50 and ∼75% at surfactant levels of 100 and 200 μg phospholipid/ml, respectively. The inhibition is not due to surfactant interference with the interaction of LPS with the cells or to disruption of the formation of iNOS mRNA. Also, surfactant does not seem to reduce ⋅ NO formation by directly affecting iNOS activity or by acting as an antioxidant or radical scavenger. However, in the presence of surfactant, there is an ∼80% reduction in the amount of LPS-induced iNOS protein in the cells. LPS-induced ⋅ NO production is inhibited by Survanta, a surfactant preparation used in replacement therapy, as well as by natural surfactant. ⋅ NO formation is not affected by the major lipid components of surfactant or by two surfactant-associated proteins, surfactant protein (SP) A or SP-C. However, the hydrophobic SP-B inhibits ⋅ NO formation in a concentration-dependent manner; ⋅ NO production is inhibited by ∼50 and ∼90% at SP-B levels of 1-2 and 10 μg/ml, respectively. These results show that lung surfactant inhibits LPS-induced ⋅ NO production by alveolar macrophages, that the effect is due to a reduction in iNOS protein levels, and that the surfactant component responsible for the reduction is SP-B.
Identification of a Novel Recombinant Type 2 Porcine Reproductive and Respiratory Syndrome Virus in China

Since the emergence of NADC30-like porcine reproductive and respiratory syndrome virus (PRRSV) in China in 2013, PRRSVs have undergone rapid evolution. In this study, a novel variant of PRRSV strain (designated SCcd17) was successfully isolated from piglets with clinical signs in Sichuan Province in China in 2017, and the complete genomic sequence was determined. The genome of this new isolate was 15,015 nucleotides (nt) long, and comparative analysis revealed that SCcd17 exhibited 90.2%, 85.2%, 84.9%, and 84.0% nucleotide similarity to PRRSVs NADC30, JXA1, CH-1a, and VR-2332, respectively. Phylogenetic analysis indicated that the SCcd17 strain was classified into the NADC30-like sub-genotype, in which all the strains contained the unique discontinuous 131-amino acid deletion in nonstructural protein 2 (nsp2) when compared to VR-2332-like viruses. Notably, extensive amino acid substitutions were observed in nsp2 and a unique single amino acid deletion at position 33 of the GP5 is being described for the first time. Strikingly, recombination analysis revealed that SCcd17 was the result of recombination between the NADC30-like, JXA1-like, and VR-2332-like strains at five recombination breakpoints: nsp1α (nt 641), nsp3 (nt 5141), nsp10 (nt 9521), open reading frame 3 (ORF3) (nt 12,581), and ORF4 (nt 13,021). The genomic data of SCcd17 will be helpful for understanding the role of genomic recombination in the evolution of PRRSV.
Predictive Model based on Sentiment Analysis for Peruvian SMEs in the Sustainable Tourist Sector

In the sustainable tourist sector today, there is a wide margin of loss in small and medium-sized enterprise (SMEs) because of a poor control in logistical expenses. In other words, acquired goods are note being sold, a scenario which is very common in tourism SMEs. These SMEs buy a number of travel packages to big companies and because of the lack of demand of said packages, they expire and they become an expense, not the investment it was meant to be. To solve this problem, we propose a Predictive model based on sentiment analysis of a social networks that will help the sales decision making. Once the data of the social network is analyzed, we also propose a prediction model of tourist destinations, using this information as data source it will be able to predict the tourist interest. In addition, a case study was applied to a real Peruvian tourist enterprise showing their data before and after using the proposed model in order to validate the feasibility of
The Effect of Parasites on Host Population Density and Extinction: Experimental Epidemiology with Daphnia and Six Microparasites

Parasites have been shown to reduce host density and to induce host population extinction in some cases but not in others. Epidemiological models suggest that variable effects of parasites on individual hosts can explain this variability on the population level. Here, we aim to support this hypothesis with a specific epidemiological model using a cross‐parasite species approach. We compared the effect of six parasites on host fecundity and survival to their effects on density and risk of extinction of clonal host populations. We contrast our empirical results of population density with predictions from a deterministic model and contrast our empirical results of host and parasite extinction rates with those predicted by a stochastic model. Five horizontally transmitted microparasites (two bacteria: white bacterial disease, Pasteuria ramosa; two microsporidia: Glugoides intestinalis, Ordospora colligata; one fungus: Metschnikowiella biscuspidata); and six strains of a vertically transmitted microsporidium (Flabelliforma magnivora) of the planktonic crustacean Daphnia magna were used. In life table experiments, we quantified fecundity and survival in individual parasitized and healthy hosts and compared these with the effect of the parasites on host population density and on the likelihood of host population extinction in microcosm populations. Parasite species varied strongly in their effects on host fecundity, host survival, host density reduction, and the frequency with which they drove host populations to extinction. The fewer offspring an infected host produced, the lower the density of an infected host population. This effect on host density was relatively stronger for the vertically transmitted parasite strains than for the horizontally transmitted parasites. As predicted by the stochastic simulations, strong effects of a parasite on individual host survival and fecundity increased the risk of host population extinction. The same was true for parasite extinctions. Our results have implications for the use of microparasites in biological control programs and for the role parasites play in driving small populations to extinction.