Furthermore, it is accompanied by harmonized versions of 23 biomedical NER corpora.

HunFlair ist freely available through the Flair NLP framework (https//github.com/flairNLP/flair) under an MIT license and is compatible with all major operating systems.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.All vitamin D tests carried out for outpatients aged 18 years or older during the last 3 years at an Italian University Hospital was reviewed. The serum vitamin D concentrations measured since the Italian coronavirus diseases 2019 (COVID-19) lockdown to present did not significantly differ from the previous 2 years (78 vs. 77 nmol/l; P = 0.277), whilst the prevalence of vitamin D deficiency was found to be even marginally lower in 2020 (16.0% vs. 17.9%; P = 0.003). These results suggest that vitamin D deficiency in our province has not increased during the Italian COVID-19 outbreak or in correspondence with the nationwide lockdown.Inflammation is a hallmark in the human cervix remodelling. A possible candidate inducing the inflammatory driven ripening of the cervix is the matrix component heparan sulphate, which has been shown to be elevated in late pregnancy in the cervix and uterus. Heparin and a glycol-split low molecular weight heparin (gsHep) with low anticoagulant potency has been shown to enhance myometrial contraction and interleukin (IL)-8 production by cervical fibroblasts. The aim of this study was to investigate the mechanism by which heparin promotes cervical inflammation. Wild-type, Toll-like receptor 4 (TLR4), Myeloid differentiation primary response gene 88 (MyD88) and Interferon regulatory factor 3 (IRF3)-deficient mice were treated by deposition of gsHep into the vaginas of nonpregnant mice. To identify which cells that responded to the heparin fragments, a rhodamine fluorescent construct of gsHep was used, which initially did bind to the epithelial cells and were at later time points located in the sub-mucosa. The heparin fragments induced a strong local inflammatory response in wild-type mice shown by a rapid infiltration of neutrophils and to a lesser extent macrophages into the epithelium and the underlying extracellular matrix of the cervix. Further, a marked migration into the cervical and vaginal lumen was seen by both neutrophils and macrophages. The induced mucosal inflammation was strongly reduced in TLR4- and IRF3-deficient mice. In conclusion, our findings suggest that a TLR4/IRF3-mediated innate immune response in the cervical mucosa is induced by gsHep. This low anticoagulant heparin version, a novel TLR4 agonist, could contribute to human cervical ripening during the initiation of labour.The aim was to systematically review and meta-analyze prospective cohort studies investigating the relation between maternal dietary patterns during pregnancy with pregnancy and birth outcomes. PubMed, Scopus, and ISI Web of Science were searched from inception until October 2019 for eligible studies. Studies reporting relative risk, ORs, or incidences (for binary data) or means ± SDs or B-coefficients (for continuous outcomes) comparing the highest and lowest adherence with maternal dietary patterns were included. Dietary patterns were categorized as „healthy,” „unhealthy,” or „mixed.” No language restrictions were applied. Study-specific effect sizes with SEs for outcomes of interest were pooled using a random-effects model. Quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Sixty-six relevant publications were included. A higher maternal adherence to a healthy diet was associated with a reduced risk of gestational hypertension (14%, P less th42018089756.Healthy eating patterns, as described by dietary guidelines, typically favor whole grains, low-fat dairy, vegetables, fruit, legumes, and nuts and seeds. Nutrient-profiling (NP) models capture nutrient density of individual foods and can inform healthier food choices. Although whole grains are prominently featured in most dietary guidelines, they are not included in most NP models. Healthy foods, as identified by most NP models, are those that contain limited amounts of energy, saturated fat, total or added sugar, and sodium. As global dietary guidance turns to foods and food groups as opposed to individual nutrients, future nutrient-density metrics may need to do the same. Potential methods to incorporate whole grains into the overall concept of nutrient density and into selected NP models are outlined in this review. Incorporating whole grains into the Nutri-Score, Health Star Rating, or the Nutrient Rich Food index will require further analyses of dietary nutrient density in relation to health outcomes across diverse population subgroups. We present the rationale for how the inclusion of whole grains in NP models can assist in the implementation of dietary guidance.

Covariance-based predictions of residue contacts and inter-residue distances are an increasingly popular data type in protein bioinformatics. Here we present ConPlot, a web-based application for convenient display and analysis of contact maps and distograms. Integration of predicted contact data with other predictions is often required to facilitate inference of structural features. ConPlot can therefore use the empty space near the contact map diagonal to display multiple coloured tracks representing other sequence-based predictions. Popular file formats are natively read and bespoke data can also be flexibly displayed. This novel visualisation will enable easier interpretation of predicted contact maps.

available online at http://www.conplot.org, along with documentation and examples. Alternatively, ConPlot can be installed and used locally using the docker image from the project’s Docker Hub repository. ConPlot is licensed under the BSD 3-Clause.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

This study evaluated the potential impact of environmental factors and harvesting practices on the microbial load of macadamia nuts. Three farms located in primary macadamia nut production regions, the Mbombela (A), Barberton (B) and White River (C) areas in Mpumalanga Province, South Africa, were sampled over a 2-year period. A total of 264 irrigation water (54), soil (30), and macadamia nut (180) samples were collected and evaluated for microbial load. All water samples had mean Escherichia coli loads below 1,000 MPN/100 mL, which is the standard regulatory requirement for agricultural water considered fit for irrigation in South Africa. Mean total aerobic plate counts of nut-in-husk on-tree samples (3.91 log CFU/g; n = 60) were higher after harvesting (5.98 log CFU/g; n = 60) but were lower after dehusking (to 4.89 log CFU/g; n = 60) on nut-in-shell samples. Salmonella spp. were only detected in water samples from farm B (67%; n = 18) and farm C (15%; n = 18). Neither Listeria monocytogenes nor Salmonella spp. were detected in the soil samples. E. coli was only detected in 20% (n = 10) of soil samples collected from two farms (farms A and B). None of the E. coli isolated in this study was positive for the eae, stx1, and stx2 enterohemorrhagic E. coli virulence genes. This study provides basic data that can be used in the development of macadamia nut-specific hazard assessment tools within primary production environments.

Magnetic resonance imaging (MRI) contrast agents (CAs) have drawn increasing attention in cancer diagnosis. However, since the signals they generate are always „on” and may bring interfering background signals to the region of interest, their selectivity and sensitivity need further improvement. Herein, extremely small iron oxide nanoparticles (ESIONPs) conjugated through a disulfide bond with polyethylene glycol (PEG) that is terminally modified with folic acid (FA), namely ESIONPs-s-s-PEG-FA, were designed and synthesized to target tumor tissues and selectively activate the T2 MRI contrast effect in the reducing environment of tumor cells. Due to the breakage of disulfide bonds by the high glutathione (GSH) concentration in tumor cells, the hydrophilic PEG chains detached from the surface of ESIONPs, which led to the aggregation of ESIONPs and the activation of the T2 contrast effect. In vitro results showed that ESIONPs-s-s-PEG-FA could effectively target tumors to assemble in the reductive environment and switch from a T1 contrast agent (CA) to a T2 one. Furthermore, MRI in tumor-bearing mice also indicated the obvious targeting capacity and the „turn on” of the T2 contrast effect. In addition, the results of the biosafety assay suggest that the tumor-targeted T1/T2 switchable CA is equipped with favorable biocompatibility for cancer diagnosis.While the underlying principles of simplex optimisation are easy to understand and the small number of trial experiments involved make the approach very attractive, there are several important issues to be considered in the practical application of the method to the analytical sciences and other areas. These include the selection of suitable factor levels to set the size and position of the initial simplex, and the variation of the step sizes used to find the positions of subsequent simplexes. The possibility of accidentally finding a local maximum rather than a global maximum must also be considered.We report on charge transport across single short peptides using the Mechanically Controlled Break Junction (MCBJ) method. We record thousands of electron transport events across single-molecule junctions and with an unsupervised machine learning algorithm, we identify several classes of traces with multifarious conductance values that may correspond to different peptide conformations. Data analysis shows that very short peptides, which are more rigid, show conductance plateaus at low conductance values of about 10-3G0 and below, with G0 being the conductance quantum, whereas slightly longer, more flexible peptides also show plateaus at higher values. Fully stretched peptide chains exhibit conductance values that are of the same order as that of alkane chains of similar length. The measurements show that in the case of short peptides, different compositions and molecular lengths offer a wide range of junction conformations. Such information is crucial to understand mechanism(s) of charge transport in and across peptide-based biomolecules.A new constrained-cavity [1 + 1] Schiff-base dipyrrin macrocycle comprising an N4 donor-pocket has been synthesised by spontaneous oxidation and in situ crystallisation. Access to Fe(ii) and Zn(ii) complexes is achieved by salt elimination reactions of the lithium salt. All compounds have been characterised by NMR and UV-vis spectroscopy, X-ray crystallography, and DFT analysis.Heterogeneous non-linear poly(ethylene glycol) analogs, like poly(oligo(ethylene glycol)methyl ether methacrylate) (POEGMA), are of particular interest in the fabrication of smart biocompatible coatings as they undergo a reversible macromolecular rearrangement in response to external heat stimuli. The phase transition dynamics of POEGMA coatings in response to external temperature stimuli have been poorly investigated. The quartz crystal microbalance with dissipation (QCM-D) can be used to investigate the phase transition of these functional coatings as polymer brushes in a dynamic and noninvasive in situ measurement. POEGMA brushes with different thickness are synthesized from the surface of a QCM-D sensor following a living radical polymerization technique by varying the monomer molecular weight. Investigations on the thermoresponsive collapse and swelling of POEGMA brushes grafted from the surface of a QCM-D sensor reveal the reversible phase transition nature of these coatings. Furthermore, the potential of these smart coatings in the field of biotechnology was explored by investigating the absorption and desorption of a model drug. A pulsatile drug release profile triggered by an increase in temperature is observed from POEGMA brushes. POEGMA brushes have the potential to be utilized as polymer coatings for controlled and programable drug release.We describe highly efficient interstrand photocrosslinking of a DNA duplex containing 5-chloro-2′-deoxy-4-thiouridine (ClSdU) in one strand, proceeding via a two-step photochemical cascade, involving the formation of a thermally reversible crosslink between ClSdU and thymidine in the target strand and its subsequent conversion to a thermally stable fluorescent crosslink. These results show that ClSdU has great potential to be a valuable DNA photo-crosslinking reagent for chemical biology applications.Cases of respiratory diseases have been increasing around the world, affecting the health and quality of life of millions of people every year. Chronic respiratory diseases (CRDs) and acute respiratory infections (ARIs) are responsible for many hospital admissions and deaths, requiring sophisticated treatments that facilitate the delivery of therapeutics to specific target sites with controlled release. In this context, different nanoparticles (NPs) have been explored to match this demand, such as lipid, liposome, protein, carbon-based, polymeric, metallic, oxide, and magnetic NPs. The use of NPs as drug delivery systems can improve the efficacy of commercial drugs due to their advantages related to sustained drug release, targeting effects, and patient compliance. The current review presents an updated summary of recent advances regarding the use of NPs as drug delivery systems to treat diseases related to the respiratory tract, such as CRDs and ARIs. The latest applications presented in the literature were considered, and the opportunities and challenges of NPs in the drug delivery field are discussed.With the rapid development of rechargeable lithium-ion batteries, the search for highly efficient electrode materials has become an ever-growing need for high power density and fast charge-discharge rate to meet the future challenges of energy storage. Two-dimensional MXenes exhibit good electrical and electrochemical properties and are very attractive candidates for anode materials. In this article, we addressed ordered double-metal pristine TiVC and functionalized TiVCT2 (T = O, S, F, or OH) MXenes and investigated their electrochemical properties by using density functional theory calculations. Our results reveal that these ordered MXenes all exhibit metallic characteristics with high electronic conductivity. The diffusion barrier of a Li ion is only 15 meV on the Ti surface and 14 meV on the V surface of the pristine TiVC monolayer. However, functional group terminations markedly increase the Li ion diffusion barrier on TiVC monolayers. Among all the group functionalized TiVCT2 monolayers, the TiVCS2 monolayer exhibits the lowest diffusion barrier of a Li ion (0.191 eV on the Ti surface and 0.186 eV on the V surface). Furthermore, the open circuit voltages of Li ions on both TiVC and TiVCS2 monolayers fall in the range of 0-1.0 V, which may prevent the dendrite formation of alkali metals in the charge/discharge process. Therefore, ordered pristine TiVC and functionalized TiVCS2 monolayers should be promising candidates as anode materials for lithium-ion batteries.A supramolecular brush polymer Poly(P5-OXD) was constructed through the self-assembly of an A1/A2 disubstituted pillar[5]arene P5-OXD with a 1,3,4-oxadiazole unit and a cyanobutoxy group, exhibiting external stimuli responsiveness towards Cu2+ ions with an ON/OFF fluorescence signal output.An efficient protocol for the construction of structurally diverse 2-pyridone derivatives from imines and α,β-unsaturated acid chlorides in a single operation is reported. The target compounds, including coumarin-8-oxoprotoberbine analogues and lamellarin G isomers, were prepared via thermal cyclization of the in situ generated enamides followed by thermal dehydrogenation. The cyclization of enamides was achieved by the introduction of an electron-withdrawing group on the α-carbon of acid chlorides. This methodology allows quick access to polycyclic Pechmann dyes via rare double oxidative cyclizations of dienamides under mild conditions.A high-yielding total synthesis of daptomycin, an important clinical antibiotic, is described. Key to the development of this synthesis was the elucidation of a Camps cyclization reaction that occurs in the solid-phase when conventionally used kynurenine (Kyn) synthons, such as Fmoc-l-Kyn(Boc,CHO)-OH and Fmoc-l-Kyn(CHO,CHO)-OH, are exposed to 20% 2-methylpiperidine (2MP)/DMF. During the synthesis of daptomycin, this side reaction was accompanied by intractable peptide decomposition, which resulted in a low yield of Dap and a 4-quinolone containing peptide. The Camps cyclization was found to occur in solution when Boc-l-Kyn(Boc,CHO)-Ot-Bu and Boc-l-Kyn(CHO,CHO)-OMe were exposed to 20% 2MP/DMF giving the corresponding 4-quinolone amino acid. In contrast, Boc-l-Kyn(CHO)-OMe was stable under these conditions, demonstrating that removing one of the electron withdrawing groups from the aforementioned building blocks prevents enolization in 2MP/DMF. Hence, a new synthesis of daptomycin was developed using Fmoc-l-Kyn(Boc)-OH, which is prepared in two steps from Fmoc-l-Trp(Boc)-OH, that proceeded with an unprecedented 22% overall yield. The simplicity and efficiency of this synthesis will facilitate the preparation of analogs of daptomycin. In addition, the elucidation of this side reaction will simplify preparation of other Kyn-containing natural products via Fmoc SPPS.Recently, „water-in-salt” electrolytes have provided a huge boost to the realization of high energy density for water-based supercapacitors by broadening the electrochemical stability window. However, the high cost and low conductivity of high concentration LiTFSI greatly restrict the possibility of practical application. Herein, we adopt a new strategy to develop a low-cost and quasi-solid-state polyelectrolyte hydrogel accommodating a superhigh concentration of CH3COOK through in situ polymerization, avoiding the problem that many conventional polymers cannot accommodate ultra-high ion concentration. The polyelectrolyte hydrogel with 24 M CH3COOK exhibits a conductivity of up to 35.8 mS cm-1 and a stretchability of 950%. With advanced N-doped graphene hydrogel electrodes, the assembled supercapacitor yields a voltage window of 2.1 V with an energy density of 33.0 W h kg-1 and superior cyclability with 88.2% capacitance retention at 4 A g-1 after 6000 cycles comparable to those supercapacitors using high-cost LiTFSI salts. Besides, the supercapacitor with excellent temperature stability in the range of -20 to 70 °C can light an LED for more than one minute. The assembled flexible device with the PAAK/CMC-24 M gel film sandwiched in between demonstrates excellent bendability from 0° to 180° and shows great potential for flexible/wearable electronic devices. Our feasible approach provides a new route for assembling quasi-solid-state flexible high-energy storage devices with „water-in-salt” electrolytes.Covalent functionalization is one of the most efficient ways to tune the properties of layered materials in a highly controlled manner. However, molecular chemisorption on semiconducting transition metal dichalcogenides remains a delicate task due to the inertness of their surface. Here we perform covalent modification of bulk and single layer molybdenum disulfide (MoS2) using chemical activation of diazonium salts. A high level of control over the grafting density and yield on MoS2 basal plane can be achieved by this approach. Using scanning probe microscopies and X-ray photoelectron spectroscopy we prove the covalent functionalization of MoS2.Lithium-sulfur (Li-S) batteries with high energy density, which show great application potential in flexible electronic products, have attracted a lot of research enthusiasm. However, the low utilization of sulfur and shuttle effect limit the application of Li-S batteries. Materials with a void structure and high conductivity can be used as a sulfur host to overcome these issues. Herein, a flexible MXene-coated textile fabric electrode (MF@Ti3C2Tx/S) is designed by integrating the MXene-coated textile fabric (MF) with in situ sulfur loaded MXene nanosheets (Ti3C2Tx/S). The MF provides a flexible 3D conductive framework, which is covered with Ti3C2Tx/S nanosheets to form the layer-by-layer structure. This unique structure not only provides enough space for volume expansion to maintain the structural stability in the electrochemical process, but also promotes the physical encapsulation and chemical adsorption of lithium polysulfides (LiPSs). Consequently, the MF@Ti3C2Tx/S50 electrode exhibits a high initial capacity of 916 mA h g-1 at 1C and an ultralong-term cycling stability of 674 mA h g-1 at 1C after 1000 cycles. Furthermore, this electrode also exhibits excellent rate performance at a high energy density (290 mA h g-1 at 5C after 800 cycles). A pouch cell is prepared by using the MF@Ti3C2Tx/S50 electrode and shows excellent cycle performances at different bending angles, which indicates that this study is valuable in the field of flexible energy storage. This work provides a new concept design for flexible Li-S batteries, which have great application potential as wearable and portable electronic devices.Nickel (Ni)-rich layered oxides such as LiNi0.6Co0.2Mn0.2O2 (NCM622) represent one of the most promising candidates for next-generation high-energy lithium-ion batteries (LIBs). However, the pristine Ni-rich cathode materials usually suffer from poor structural stability during cycling. In this work, we demonstrate a simple but effective approach to improve the cycling stability of the NCM622 cathode by dry coating of ultrastable Li3V2(PO4)3-carbon (LVP-C) nanoparticles, which leads to a robust composite cathode (NCM622/LVP-C) without sacrificing the specific energy density compared with pristine NCM622. The optimal NCM622/LVP-C composite presents a high specific capacity of 162 mA h g-1 at 0.5 C and excellent cycling performance with 85.0% capacity retention after 200 cycles at 2 C, higher than that of the pristine NCM622 (67.6%). Systematic characterization confirms that the LVP-C protective layer can effectively reduce the side reactions, restrict the cation mixing of NCM622 and improve its structural stability. Moreover, the NCM622/LVP-C||graphite full cells also show a commercial-level capacity of 3.2 mA h cm-2 and much improved cycling stability compared with NCM622/LVP-C||graphite full cells, indicating the great promise for low-cost, high-capacity and long-life LIBs.In the past two decades, transition metal-catalyzed C-H functionalization followed by annulations with various coupling partners has received much attention in organic synthesis. In particular, Rh(iii) or Ir(iii) catalyzed regioselective C-H functionalization followed by the cyclization of diverse arenes with metal carbene precursors has become a highly investigated research field in recent years. The purpose of this review is to provide a comprehensive essay on the Rh(iii)/Ir(iii) catalyzed C-H functionalizations/annulations via carbene migratory insertion, focusing on the diverse metal carbene precursors with arenes/alkenes reported so far. The highlighted examples are categorized by nitrogen, oxygen, sulfur-containing heterocycles and carbocyclizations. Further, key mechanistic approaches are also briefly described.Total synthesis of natural products has greatly contributed to natural product research, organic synthesis and drug discovery and development. However, in most cases, the efficiency of total synthesis is far from sufficient for direct practical industrial application. Thus, designing a concise and efficient synthetic route with balanced efforts between building the complex skeleton and introducing functional groups is highly desirable. In this critical review, we first present an introduction of this issue and a philosophical framework that cover possible synthetic approaches. Next, we have chosen the biogenetically closely related, biologically important and synthetically extremely challenging natural products, tiglianes, daphnanes and ingenanes as the particular case for the discussion, since in the past 40 years many synthetic approaches have been reported. The successes and pitfalls included therefore serve as the basis to draw some conclusions that may inspire future development in this area.Chemotherapy mostly functions as a carrier for direct drug delivery to the tumor, which may induce secondary damage to healthy tissue cells around the tumor. To avoid this side effect, using multifunctional drugs with high cell permeability during chemotherapy is crucial to achieve significant antitumor efficacy. In this study, polyhedral oligomeric silsesquioxane-based multifunctional organic-inorganic hybrid molecules with potential for recognition, imaging, and treatment were designed and successfully synthesized through a facile and efficient one-pot reaction process. The structure and properties of the synthesized multifunctional molecules were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, mass spectrometry, fluorescence spectroscopy, cytotoxicity assay, surface tension testing, cell compatibility testing, hematoxylin and eosin staining, as well as in vivo and in vitro studies. The results demonstrated that these multifunctional molecules can be effectively used for delivering precisely-targeted imaging and therapeutic agents and exhibited considerable cell permeability. The excellent synergy between high permeability and precise targeting results in multifunctional molecules with superior diagnostic performance.We report high-efficiency quantum dot light-emitting diodes (QLEDs) with Li-doped TiO2 nanoparticles (NPs) as an alternative electron transport layer (ETL). Colloidally stable TiO2 NPs are applied as ETLs of inverted structured QLEDs and the effect of the addition of lithium (Li) to TiO2 NPs on device characteristics is studied in detail. Compared to pristine TiO2 NPs, Li-doped ones are found to be beneficial for the charge balance in the emitting layer of QLEDs mainly by means of their upshifted conduction band minimum, which in turn limits electron injection. A green QLED with 5% Li-doped TiO2 NPs produces a maximum luminance of 169 790 cd m-2, an EQE of 10.27%, and a current efficiency of 40.97 cd A-1, which indicate the best device performances to date among QLEDs with non-ZnO inorganic ETLs. These results indicate that Li-doped TiO2 NPs show great promise for use as a solution-based inorganic ETL for future QLEDs.Scalable graphene synthesis and facile large-area membrane fabrication are imperative to advance nanoporous atomically thin membranes (NATMs) for molecular separations. Although chemical vapor deposition (CVD) allows for roll-to-roll high-quality monolayer graphene synthesis, facile transfer with atomically clean interfaces to porous supports for large-area NATM fabrication remains extremely challenging. Sacrificial polymer scaffolds commonly used for graphene transfer typically leave polymer residues detrimental to membrane performance and transfers without polymer scaffolds suffer from low yield resulting in high non-selective leakage through NATMs. Here, we systematically study the factors influencing graphene NATM fabrication and report on a novel roll-to-roll manufacturing compatible isopropanol-assisted hot lamination (IHL) process that enables scalable, facile and clean transfer of CVD graphene on to polycarbonate track etched (PCTE) supports with coverage ≥99.2%, while preserving support integrity/porosity. We demonstrate fully functional centimeter-scale graphene NATMs that show record high permeances (∼2-3 orders of magnitude higher) and better selectivity than commercially available state-of-the-art polymeric dialysis membranes, specifically in the 0-1000 Da range. Our work highlights a scalable approach to fabricate graphene NATMs for practical applications and is fully compatible with roll-to-roll manufacturing processes.Cytomegalovirus (CMV) causes clinically important diseases in immune compromised and immune immature individuals. Based largely on work in the mouse model of murine (M)CMV, there is a consensus that myeloid cells are important for disseminating CMV from the site of infection. In theory, such dissemination should expose CMV to cell-mediated immunity and thus necessitate evasion of T cells and NK cells. However, this hypothesis remains untested. We constructed a recombinant MCMV encoding target sites for the hematopoietic specific miRNA miR-142-3p in the essential viral gene IE3. This virus disseminated poorly to the salivary gland following intranasal or footpad infections but not following intraperitoneal infection in C57BL/6 mice, demonstrating that dissemination by hematopoietic cells is essential for specific routes of infection. Remarkably, depletion of NK cells or T cells restored dissemination of this virus in C57BL/6 mice after intranasal infection, while dissemination occurred normally in BALB/c mice,cosal tissues depends on evasion of T cells.Bartonellae are Gram-negative facultative-intracellular pathogens that use a type-IV-secretion system (T4SS) to translocate a cocktail of Bartonella effector proteins (Beps) into host cells to modulate diverse cellular functions. BepC was initially reported to act in concert with BepF in triggering major actin cytoskeletal rearrangements that result in the internalization of a large bacterial aggregate by the so-called 'invasome’. Later, infection studies with bepC deletion mutants and ectopic expression of BepC have implicated this effector in triggering an actin-dependent cell contractility phenotype characterized by fragmentation of migrating cells due to deficient rear detachment at the trailing edge, and BepE was shown to counterbalance this remarkable phenotype. However, the molecular mechanism of how BepC triggers cytoskeletal changes and the host factors involved remained elusive. Using infection assays, we show here that T4SS-mediated transfer of BepC is sufficient to trigger stress fiber formation ia support a model in which BepC activates the RhoA/ROCK pathway by re-localization of GEF-H1 from microtubules to the plasma membrane.Bartonella T4SS effector BepC was reported to mediate internalization of big Bartonella aggregates into host cells by modulating F-actin polymerization. After that, BepC was indicated to induce host cell fragmentation, an interesting cell phenotype that is characterized by failure of rear-end retraction during cell migration, and subsequent dragging and fragmentation of cells. Here, we found that expression of BepC resulted in significant stress fiber formation and contractile cell morphology, which depended on combination of the N-terminus FIC (filamentation induced by c-AMP) domain and C-terminus BID (Bartonella intracellular delivery) domain of BepC. The FIC domain played a key role in BepC-induced stress fiber formation and cell fragmentation because deletion of FIC signature motif or mutation of two conserved amino acid residues abolished BepC-induced cell fragmentation. Immunoprecipitation confirmed the interaction of BepC with GEF-H1 (a microtubule-associated RhoA guanosine exchange factor), and siRNA-mediated depletion of GEF-H1 prevented BepC-induced stress fiber formation. Interaction with BepC caused the dissociation of GEF-H1 from microtubules and activation of RhoA to induce formation of stress fibers. The ROCK (Rho-associated protein kinase) inhibitor Y27632 completely blocked BepC effects on stress fiber formation and cell contractility. Moreover, stress fiber formation by BepC increased the stability of focal adhesions, which consequently impeded rear-edge detachment. Overall, our study revealed that BepC-induced stress fiber formation was achieved through the GEF-H1/RhoA/ROCK pathway.Gammaherpesvirus infections are ubiquitous in captive and free-ranging ruminants and are associated with a variety of clinical diseases ranging from subclinical or mild inflammatory syndromes to fatal diseases such as malignant catarrhal fever. Gammaherpesvirus infections have been fully characterized in only a few ruminant species, and the overall diversity, host range, and biologic effects of most are not known. This study investigated the presence and host distribution of gammaherpesviruses in ruminant species at two facilities, the San Diego Zoo and San Diego Zoo Safari Park. We tested antemortem (blood, nasal or oropharyngeal swabs) or postmortem (internal organs) samples from 715 healthy or diseased ruminants representing 96 species and subspecies, using a consensus-based herpesvirus PCR for a segment of the DNA polymerase (DPOL) gene. Among the 715 animals tested, 161 (22.5%) were PCR and sequencing positive for herpesvirus, while only 11 (6.83%) of the PCR positive animals showed clinical signs of malignant catarrhal fever. Forty-four DPOL genotypes were identified of which only 10 have been reported in GenBank. The data describe viral diversity within species and individuals, identify host ranges of potential new viruses, and address the proclivity and consequences of interspecies transmission during management practices in zoological parks. The discovery of new viruses with wide host ranges and presence of co-infection within individual animals also suggest that the evolutionary processes influencing Gammaherpesvirus diversity are more complex than previously recognized.Alzheimer’s disease (AD) is a devastating illness affecting over 40 million people worldwide. Intraneuronal rise of amyloid beta in its oligomeric forms (iAβOs), has been linked to the pathogenesis of AD by disrupting cytosolic Ca2+ homeostasis. However, the specific mechanisms of action are still under debate and intense effort is ongoing to improve our understanding of the crucial steps involved in the mechanisms of AβOs toxicity. We report the development of a mathematical model describing a proposed mechanism by which stimulation of Phospholipase C (PLC) by iAβO, triggers production of IP3 with consequent abnormal release of Ca2+ from the endoplasmic reticulum (ER) through activation of IP3 receptor (IP3R) Ca2+ channels. After validating the model using experimental data, we quantify the effects of intracellular rise in iAβOs on model solutions. Our model validates a dose-dependent influence of iAβOs on IP3-mediated Ca2+ signaling. We investigate Ca2+ signaling patterns for small and large iAβOs doses and study the role of various parameters on Ca2+ signals. Uncertainty quantification and partial rank correlation coefficients are used to better understand how the model behaves under various parameter regimes. Our model predicts that iAβO alter IP3R sensitivity to IP3 for large doses. Our analysis also shows that the upstream production of IP3 can influence Aβ-driven solution patterns in a dose-dependent manner. Model results illustrate and confirm the detrimental impact of iAβOs on IP3 signaling.In this paper we focus on a critical component of the city its building stock, which holds much of its socio-economic activities. In our case, the lack of a comprehensive database about their features and its limitation to a surveyed subset lead us to adopt data-driven techniques to extend our knowledge to the near-city-scale. Neural networks and random forests are applied to identify the buildings’ number of floors and construction periods’ dependencies on a set of shape features area, perimeter, and height along with the annual electricity consumption, relying a surveyed data in the city of Beirut. The predicted results are then compared with established scaling laws of urban forms, which constitutes a further consistency check and validation of our workflow.Maternal effects on offspring growth can impact survival and evolution of natural and domesticated populations. Genetic correlation estimates often support a negative relationship between direct and maternal effects. However, the genetic underpinnings whereby this antagonism operates are unclear. In pigs, sow feeding status and body composition condition piglet development and growth. We hypothesized that variants in genes impacting these traits may be causative of maternal influences that could be antagonistic to the direct effects for piglet growth. A recessive missense mutation (C>T) in the porcine leptin receptor (LEPR) gene (rs709596309) has been identified as the possible causal polymorphism for increased feed intake and fatness. Using data from a Duroc line, we show that the TT sows exerted a negative impact on the body weight of their offspring at the end of the growing period of similar extent to the positive direct effect of the TT genotype over each individual. Thus, TT pigs from TT dams were about as heavy as CC and CT (C-) pigs from C-dams, but TT pigs from C-dams were around 5% heavier than C-pigs from TT dams. In contrast, body composition was only influenced by LEPR direct effects. This antagonism is due to a higher propensity of TT pigs for self-maintenance rather than for offspring investment. We show that TT pigs consumed more feed, favored fatty acid uptake over release, and produced lighter piglets at weaning than their C-counterparts. We conclude that LEPR underlies a transgenerational mechanism for energy distribution that allocates resources to the sow or the offspring according to whether selective pressure is exerted before or after weaning.Restoration of the Florida Everglades, a substantial wetland ecosystem within the United States, is one of the largest ongoing restoration projects in the world. Decision-makers and managers within the Everglades ecosystem rely on ecological models forecasting indicator wildlife response to changes in the management of water flows within the system. One such indicator of ecosystem health, the presence of wading bird communities on the landscape, is currently assessed using three species distribution models that assume perfect detection and report output on different scales that are challenging to compare against one another. We sought to use current advancements in species distribution modeling to improve models of Everglades wading bird distribution. Using a joint species distribution model that accounted for imperfect detection, we modeled the presence of nine species of wading bird simultaneously in response to annual hydrologic conditions and landscape characteristics within the Everglades system. Our resulting model improved upon the previous model in three key ways 1) the model predicts probability of occupancy for the nine species on a scale of 0-1, making the output more intuitive and easily comparable for managers and decision-makers that must consider the responses of several species simultaneously; 2) through joint species modeling, we were able to consider rarer species within the modeling that otherwise are detected in too few numbers to fit as individual models; and 3) the model explicitly allows detection probability of species to be less than 1 which can reduce bias in the site occupancy estimates. These improvements are essential as Everglades restoration continues and managers require models that consider the impacts of water management on key indicator wildlife such as the wading bird community.

This study aimed to explore the experiences of healthcare access in a diverse sample of trans and gender diverse individuals with complex needs using qualitative methods. We recruited 12 individuals using trans community-based networks facilitated by the Gender Centre. Each individual participated in an in-depth, semi structured interview conducted by a peer interviewer. Interviews were analysed thematically.

Participants had a range of complex health needs to manage, including ongoing access to gender-affirming hormones, mental health care and sexual health care. Some also had chronic diseases. Accordingly, scheduling appointments and affording the co-payments required were major preoccupations. Most participants were not in full time work, and economic hardship proved to be a major compounding factor in issues of healthcare access, impacting on the choice of clinician or practice. Other barriers to accessing health included issues within health services, such as disrespectful attitudes, misgendering, 'dealth and social services conveniently and affordably.

These findings demonstrate a need for comprehensive wrap-around service provision for trans people with complex needs which includes a substantial peer-based component, and addresses physical and mental health and social services conveniently and affordably.The number of COVID-19 infections is key for accurately monitoring the pandemics. However, due to differential testing policies, asymptomatic individuals and limited large-scale testing availability, it is challenging to detect all cases. Seroprevalence studies aim to address this gap by retrospectively assessing the number of infections, but they can be expensive and time-intensive, limiting their use to specific population subgroups. In this paper, we propose a complementary approach that combines estimated (1) infection fatality rates (IFR) using a Bayesian melding SEIR model with (2) reported case-fatality rates (CFR) in order to indirectly estimate the fraction of people ever infected (from the total population) and detected (from the ever infected). We apply the technique to the U.S. due to their remarkable regional diversity and because they count with almost a quarter of all global confirmed cases and deaths. We obtain that the IFR varies from 1.25% (0.39-2.16%, 90% CI) in Florida, the most aged population, to 0.69% in Utah (0.21-1.30%, 90% CI), the youngest population. By September 8, 2020, we estimate that at least five states have already a fraction of people ever infected between 10% and 20% (New Jersey, New York, Massachussets, Connecticut, and District of Columbia). The state with the highest estimated fraction of people ever infected is New Jersey with 17.3% (10.0, 55.8, 90% CI). Moreover, our results indicate that with a probability of 90 percent the fraction of detected people among the ever infected since the beginning of the epidemic has been less than 50% in 15 out of the 20 states analyzed in this paper. Our approach can be a valuable tool that complements seroprevalence studies and indicates how efficient have testing policies been since the beginning of the outbreak.During reading or listening, people can generate predictions about the lexical and morphosyntactic properties of upcoming input based on available context. Psycholinguistic experiments that study predictability or control for it conventionally rely on a human-based approach and estimate predictability via the cloze task. Our study investigated an alternative corpus-based approach for estimating predictability via language predictability models. We obtained cloze and corpus-based probabilities for all words in 144 Russian sentences, correlated the two measures, and found a strong correlation between them. Importantly, we estimated how much variance in eye movements registered while reading the same sentences was explained by each of the two probabilities and whether the two probabilities explain the same variance. Along with lexical predictability (the activation of a particular word form), we analyzed morphosyntactic predictability (the activation of morphological features of words) and its effect on reading times over and above lexical predictability. We found that for predicting reading times, cloze and corpus-based measures of both lexical and morphosyntactic predictability explained the same amount of variance. However, cloze and corpus-based lexical probabilities both independently contributed to a better model fit, whereas for morphosyntactic probabilities, the contributions of cloze and corpus-based measures were interchangeable. Therefore, morphosyntactic but not lexical corpus-based probabilities can substitute for cloze probabilities in reading experiments. Our results also indicate that in languages with rich inflectional morphology, such as Russian, when people engage in prediction, they are much more successful in predicting isolated morphosyntactic features than predicting the particular lexeme and its full morphosyntactic markup.

Rabies remains endemic to the Harare Metropolitan Province of Zimbabwe, with a lack of public participations potentially contributing to the limited success in eliminating the disease. We hypothesized that rabies intervention campaigns were less successful than they could be as a result of poor understanding of the disease at the community level, and thus aimed to identify the knowledge, attitudes, and practices towards rabies in the province.

A cross-sectional survey, using a semi-structured questionnaire, was implemented between January 2017 and June 2018 across the province and data were collected from 798 respondents. Frequency distributions and logistic regressions were undertaken to determine the factors associated with the adequacy of the prevailing rabies knowledge, pet ownership characteristics and the existing preventative practices.

The results of our study suggested that the majority of the respondents (92%) had heard of rabies. However, the level of rabies knowledge could be classified as „ovince.

This study showed that the majority of the respondents lacked comprehensive knowledge about rabies, with the knowledge pertaining to health seeking behaviour and the importance of rabies vaccination being the most lacking. Additional public education relying on key messages, aimed at the different target audiences, is required in the province.Kaposi’s sarcoma-associated herpesvirus (KSHV), which belongs to the gammaherpesvirus subfamily, is associated with the pathogenesis of various tumors. Nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the polymerization of ADP-ribose units on target proteins. In KSHV-infected cells, PARP1 inhibits replication and transcription activator (RTA), a molecular switch that initiates lytic replication, through direct interaction. Thus, for efficient replication, KSHV has to overcome the molecular barrier in the form of PARP1. Previously, we have demonstrated that KSHV downregulates the expression of PARP1 through PF-8, a viral processivity factor. PF-8 induces ubiquitin-proteasome system-mediated degradation of PARP1 via direct physical association and enhances RTA transactivation activity. Here, we showed that dimerization domains of PF-8 are crucial not only for PARP1 interaction and degradation but also for enhancement of the RTA transactivation activity. PF-8 recruited CHFR for the PARP1 degradation. A knockdown of CHFR attenuated the PF-8-induced PARP1 degradation and enhancement of the RTA transactivation activity, leading to reduced KSHV lytic replication. These findings reveal a mechanism by which KSHV PF-8 recruits a cellular E3 ligase to curtail the inhibitory effect of PARP1 on KSHV lytic replication.Chapatti (unleavened flatbread) is a staple food in northern India and neighboring countries but the genetics behind its processing quality are poorly understood. To understand the genes determining chapatti quality, differentially expressed genes were selected from microarray data of contrasting chapatti cultivars. From the gene and trait association studies, a null allele of granule bound starch synthase (GBSS; Wx-B1) was found to be associated with low amylose content and good chapatti quality. For validation, near-isogenic lines (NILs) of this allele were created by marker assisted backcross (MAB) breeding. Background screening indicated 88.2 to 96.7% background recovery in 16 selected BC3F5 NILs. Processing quality and sensory evaluation of selected NILs indicated improvement in chapatti making quality. Traits that showed improvement were mouthfeel, tearing strength and softness indicating that the Wx-B1 may be one of the major genes controlling chapatti softness.A compact fabric antenna structure integrated with electromagnetic bandgap structures (EBGs) covering the desired frequency spectrum between 2.36 GHz and 2.40 GHz for Medical Body-Area Networks (MBANs), is introduced. The needs of flexible system applications, the antenna is preferably low-profile, compact, directive, and robust to the human body’s loading effect have to be satisfied. The EBGs are attractive solutions for such requirements and provide efficient performance. In contrast to earlier documented EBG backed antenna designs, the proposed EBG behaved as shielding from the antenna to the human body, reduced the size, and acted as a radiator. The EBGs reduce the frequency detuning due to the human body and decrease the back radiation, improving the antenna efficiency. The proposed antenna system has an overall dimension of 46×46×2.4 mm3. The computed and experimental results achieved a gain of 7.2 dBi, a Front to Back Ratio (FBR) of 12.2 dB, and an efficiency of 74.8%, respectively. The Specific Absorption Rate (SAR) demonstrates a reduction of more than 95% compared to the antenna without EBGs. Moreover, the antenna performance robustness to human body loading and bending is also studied experimentally. Hence, the integrated antenna-EBG is a suitable candidate for many wearable applications, including healthcare devices and related applications.[This corrects the article DOI 10.1371/journal.pone.0238748.].

Escherichia coli O157H7 (E. coli O157H7) is one of the most potent zoonotic pathogens that causes mild diarrhea and leads to hemolytic uremic syndrome or death. This study was aimed to assess the prevalence and determinants of E. coli O157H7 related to diarrhea among under-five children with acute diarrhea.

A cross-sectional study design was carried out in 2018 on 378 under-five-year children recruited randomly from hospitals in Eastern Ethiopia. Stool specimens were collected and processed using enrichment, differential and selective medium. Among isolates, E. coli O157H7 was confirmed using latex test (Oxoid, Basingstoke, Hants, England). Factors associated with E. coli O157H7 infection were identified using binary and multivariable logistic regression. Associations were reported by odds ratio with 95% confidence interval.

The prevalence of E. coli O157H7 related diarrhea was 15.3% (95%CI 11.8-19.5). The E. coli O157H7 infection was positively associated with rural residence (AOR;3.75, 95%CI1.26-11.20ed on food cooking and handling, child care, and household sanitation associated with animal manure in rural resident children are helpful in.The main cause of rainfall-induced red-bed shallow landslides is the tendency of red-bed weathered soil to expand when it meets water. However, studies on the expansion mechanism of expansive soil have not considered the effects of hydration and particle orientation. In this study, the hydration force of soil was determined according to the electric double-layer theory, the particle direction of soil was determined by analyzing images of soil obtained by scanning electron microscopy, and, finally, a microscopic model of the electrical double layer of red-bed weathered expansive soil was established in which the hydration force and soil-particle orientation were taken into account. The results showed that the expansion of red-bed weathered expansive soil is the result of hydration forces and repulsive forces in the electric double layer. The grain orientation of the soil strongly influenced the microscopic model. The unloading expansion rate of red-bed weathered expansive soil decreased with an increase in cation concentration and a decrease in pH value.