Notes

Regulation of pro-σK activation: an integral gate in Bacillus subtilis sporulation.
3% for a [Formula see text] BJ cell and 2.2% for a [Formula see text] IBC cell in comparison to PERC. For these structures further research on poly-Si structuring and screen-printing on p-type poly-Si is necessary.Biochar from sewage sludge is a low-cost sorbent that may be used for several environmental functions. This study evaluates the induced effects of pyrolysis temperature on the physicochemical characteristics of sewage sludge (SS) biochar produced at 350 (SSB350), 450 (SSB450) and 600 (SSB600), based on the metal enrichment index, metal mobility index (MMI), and potential ecological risk index (PERI) of Cd, Cu, Pb, and Zn. Increased pyrolysis temperature reduced the biochar concentration of elements that are lost as volatile compounds (C, N, H, O, and S), while the concentration of stable aromatic carbon, ash, alkalinity, some macro (Ca, Mg, P2O5, and K2O) and micronutrients (Cu and Zn), and toxic elements such as Pb and Cd increased. Increasing the pyrolysis temperature is also important in the transformation of metals from toxic and available forms into more stable potentially available and non-available forms. Based on the individual potential ecological risk index, Cd in the SS and SSB450 were in the moderate and considerable contamination ranges, respectively. For all pyrolysis temperature biochar Cd was the highest metal contributor to the PERI. Despite this, the potential ecological risk index of the SS and SSBs was graded as low.Leptospirosis is an overlooked zoonotic disease caused by pathogenic Leptospira depended on virulence of Leptospira and the host-pathogen interaction. Kidney is the major organ infected by Leptospira which causes tubulointerstitial nephritis. Leptospira outer membrane contains several virulence factors and an outer membrane protein A (OmpA) like protein (Loa22) is essential for virulence. Pull-down assays suggested that Loa22 was a potential Toll-Like Receptor 2 (TLR2) binding candidates from pathogenic Leptospira. Confocal microscopy was employed to observe the co-localization of TLR2 and Loa22-LPGN (Leptospira peptidoglycan) complexes. Atomic force microscopy (AFM), side-directed mutagenesis, and enzyme-linked immunosorbent assay (ELISA) were performed to investigate the affinity between rLoa22, LPGN, and TLR2. Real time PCR was applied to measure the cytokines expression. Downstream signal transduction components were verified by western blot to evaluate the gene regulations. Mutation of two Loa22 key residues (Asp122 and Arg143) attenuated the affinities for LPGN. rLoa22-LPGN complexes were observed to co-localize with TLR2 and provoked inflammatory responses including CXCL8/IL8, hCCL2/MCP-1, and hTNF-α. Affinity studies suggested that Loa22-LPGN complexes elevated the affinity to TLR2 as compared to Loa22 protein. Downstream signals from TLR2 including p38, ERK, and JNK were regulated under rLoa22-LPGN complexes treatments. This study identified LPGN mediates interactions between Loa22 and TLR2 and induces downstream signals to trigger inflammatory responses. rLoa22-LPGN-TLR2 complexes reveal a novel binding mechanism for the innate immune system.Structural covariance assesses similarities in gray matter between brain regions and can be applied to study networks of the brain. In this study, we explored correlations between structural covariance networks (SCNs) and cognitive impairment in Parkinson's disease patients. 101 PD patients and 58 age- and sex-matched healthy controls were enrolled in the study. For each participant, comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted. Structural brain MR images were acquired using a 3.0T whole body GE Signa MRI system. T1 structural images were preprocessed and analyzed using Statistical Parametric Mapping software (SPM12) running on Matlab R2016a for voxel-based morphometric analysis and SCN analysis. PD patients with normal cognition received follow-up neuropsychological testing at 1-year interval. Cognitive impairment in PD is associated with degeneration of the amygdala/hippocampus SCN. PD patients with dementia exhibited increased covariance over the prefrontal cortex compared to PD patients with normal cognition (PDN). PDN patients who had developed cognitive impairment at follow-up exhibited decreased gray matter volume of the amygdala/hippocampus SCN in the initial MRI. Our results support a neural network-based mechanism for cognitive impairment in PD patients. SCN analysis may reveal vulnerable networks that can be used to early predict cognitive decline in PD patients.Francisella tularensis is one of the most virulent pathogenic bacteria causing the acute human respiratory disease tularemia. While the mechanisms underlying F. tularensis pathogenesis are largely unknown, previous studies have shown that a F. novicida transposon mutant with insertions in a gene coding for a putative lysine decarboxylase was attenuated in mouse spleen, suggesting a possible role of its protein product as a virulence factor. Therefore, we set out to structurally and functionally characterize the F. novicida lysine decarboxylase, which we termed LdcF. Here, we investigate the genetic environment of ldcF as well as its evolutionary relationships with other basic AAT-fold amino acid decarboxylase superfamily members, known as key actors in bacterial adaptative stress response and polyamine biosynthesis. We determine the crystal structure of LdcF and compare it with the most thoroughly studied lysine decarboxylase, E. coli LdcI. We analyze the influence of ldcF deletion on bacterial growth under different stress conditions in dedicated growth media, as well as in infected macrophages, and demonstrate its involvement in oxidative stress resistance. Finally, our mass spectrometry-based quantitative proteomic analysis enables identification of 80 proteins with expression levels significantly affected by ldcF deletion, including several DNA repair proteins potentially involved in the diminished capacity of the F. novicida mutant to deal with oxidative stress. Taken together, we uncover an important role of LdcF in F. novicida survival in host cells through participation in oxidative stress response, thereby singling out this previously uncharacterized protein as a potential drug target.After nearly a century of vaccination and six decades of drug therapy, tuberculosis (TB) kills more people annually than any other infectious disease. Substantial challenges to disease eradication remain among vulnerable and underserved populations. The Guarani-Kaiowá people are an indigenous population in Paraguay and the Brazilian state of Mato Grosso do Sul. This community, marginalized in Brazilian society, experiences severe poverty. Like other South American indigenous populations, their TB prevalence is high, but the disease has remained largely unstudied in their communities. Herein, Mycobacterium tuberculosis isolates from local clinics were whole genome sequenced, and a population genetic framework was generated. Phylogenetics show M. tuberculosis isolates in the Guarani-Kaiowá people cluster away from selected reference strains, suggesting divergence. Most cluster in a single group, further characterized as M. tuberculosis sublineage 4.3.3. Closer analysis of SNPs showed numerous variants across the genome, including in drug resistance-associated genes, and with many unique changes fixed in each group. We report that local M. tuberculosis strains have acquired unique polymorphisms in the Guarani-Kaiowá people, and drug resistance characterization is urgently needed to inform public health to ensure proper care and avoid further evolution and spread of drug-resistant TB.Pathophysiology of retinopathy of prematurity (ROP) still presents a gap. Lately blood tests parameters of premature infants have been measured at different times of ROP, attempting to detect correlations with ROP development and progression. So far, very early post-natal biomarkers, predictive of ROP outcome, have not been detected. Our purpose is to evaluate, in the earliest post birth blood sample, the correlation between routinely dosed blood parameters and ROP outcome. 563 preterm babies, screened according to ROP guidelines, were included and classified in conformity with ET-ROP study in "Group 1" (ROP needing treatment), "Group 2" (ROP spontaneously regressed) and "noROP" group (never developed ROP). The earliest (within an hour after delivery) blood test parameters routinely dosed in each preterm infant were collected. Platelet count was decreased in Group 1 versus noROP group (p = 0.0416) and in Group 2 versus noROP group (p = 0.1093). The difference of thrombocytopenic infants among groups was statistically significant (p = 0.0071). CRP was higher in noROP versus all ROPs (p = 0.0331). First post-natal blood sample revealed a significant thrombocytopenia in ROP needing treatment, suggesting a role of platelets in the pathophysiology and progression of ROP, possibly considering it as a predictive parameter of ROP evolution.The objectives of the in vitro study were (1) to investigate the effect of combining L-arginine (Arg) and NaF on the growth of Lactobacillus rhamnosus GG (LRG); and (2) to identify an optimum synergistic concentration for the synbiotic (Arg + LRG)-fluoride (SF) therapy. 1% Arg + 2000-ppm NaF (A-SF) and 2% Arg + 2000-ppm NaF (B-SF) demonstrated antagonism against LRG (FIC > 4.0). Both XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) and WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) assays showed that A-SF and B-SF enhanced the growth of LRG when compared to 2000-ppm NaF and LRG control. Colony forming units, bacterial weight, and biofilm thickness of A-SF and B-SF were significantly higher than 2000-ppm NaF and LRG control. Biofilm imaging depicted that 2000-ppm NaF inhibited biofilm formation; while 1%/2% Arg, A-SF, and B-SF increased biofilm growth of LRG. Lactic acid formation was the lowest for 2000-ppm NaF, followed by A-SF and then B-SF. The SF buffer potential after 24 h was the highest for B-SF, and then A-SF. Biofilm pH for B-SF was closest to neutral. Fluoride, Arg and LRG bioavailability remained unaffected in B-SF. The relative gene expression for arcA, argG, and argH was significantly higher for B-SF than the respective controls. In conclusion, combining 2% Arg, 2000-ppm NaF, and LRG provides an optimum synbiotic-fluoride synergism.Avian cholera, caused by the bacterium Pasteurella multocida, is a common and important infectious disease of wild birds in North America. Between 2005 and 2012, avian cholera caused annual mortality of widely varying magnitudes in Northern common eiders (Somateria mollissima borealis) breeding at the largest colony in the Canadian Arctic, Mitivik Island, Nunavut. Although herd immunity, in which a large proportion of the population acquires immunity to the disease, has been suggested to play a role in epidemic fadeout, immunological studies exploring this hypothesis have been missing. We investigated the role of three potential drivers of fadeout of avian cholera in eiders, including immunity, prevalence of infection, and colony size. Each potential driver was examined in relation to the annual real-time reproductive number (Rt) of P. multocida, previously calculated for eiders at Mitivik Island. Each year, colony size was estimated and eiders were closely monitored, and evaluated for infection and serological status. We demonstrate that acquired immunity approximated using antibody titers to P. multocida in both sexes was likely a key driver for the epidemic fadeout. This study exemplifies the importance of herd immunity in influencing the dynamics and fadeout of epidemics in a wildlife population.This study sought to evaluate the association between newly-developed significant hypercholesterolemia within one year following living donor liver transplantation (LDLT) and long term outcomes in light of cardiovascular events and graft failure. From October 2003 to July 2017, 877 LDLT recipients were stratified according to development of significant hypercholesterolemia within one year following LDLT. The primary outcome was occurrence of a major adverse cardiac event (MACE), defined as a composite of cardiac death, myocardial infarction, and coronary revascularization after LDLT. The incidence of graft failure, defined as all-cause death or retransplantation, was also compared. A total of 113 (12.9%) recipients developed significant hypercholesterolemia within one year. The differences in incidences of cardiac related events and graft related events began emerging significantly higher in the hypercholesterolemia group after 24 months and 60 months since the LDLT, respectively. After adjustment using the inverse probability of weighting, the hazard ratio (HR) for MACE was 2.77 (95% confidence interval (CI) 1.16-6.61; p = 0.02), while that for graft failure was 3.76 (95% CI 1.97-7.17, p  less then  0.001). A significant hypercholesterolemia after LDLT may be associated with cardiac and graft-related outcome; therefore, a further study and close monitoring of cholesterol level after LDLT is needed.Historical archives refer to often recurring earthquakes along the Eastern Himalaya for which geological evidence is lacking, raising the question of whether these events ruptured the surface or remained blind, and how do they contribute to the seismic budget of the region, which is home to millions of inhabitants. We report a first mega trench excavation at Himebasti village, Arunachal Pradesh, India, and analyze it with modern geological techniques. The study includes twenty-one radiocarbon dates to limit the timing of displacement after 1445 CE, suggesting that the area was devastated in the 1697 CE event, known as Sadiya Earthquake, with a dip-slip displacement of 15.3 ± 4.6 m. Intensity prediction equations and scaling laws for earthquake rupture size allow us to constraints a magnitude of Mw 7.7-8.1 and a minimum rupture length of ~ 100 km for the 1697 CE earthquake.Afrotheria is a clade of African-origin species with striking dissimilarities in appearance and habitat. In this study, we compared whole proteome sequences of six Afrotherian species to obtain a broad viewpoint of their underlying molecular make-up, to recognize potentially unique proteomic signatures. We find that 62% of the proteomes studied here, predominantly involved in metabolism, are orthologous, while the number of homologous proteins between individual species is as high as 99.5%. Further, we find that among Afrotheria, L. africana has several orphan proteins with 112 proteins showing  less then  30% sequence identity with their homologues. Rigorous sequence searches and complementary approaches were employed to annotate 156 uncharacterized protein sequences and 28 species-specific proteins. For 122 proteins we predicted potential functional roles, 43 of which we associated with protein- and nucleic-acid binding roles. Further, we analysed domain content and variations in their combinations within Afrotheria and identified 141 unique functional domain architectures, highlighting proteins with potential for specialized functions. Finally, we discuss the potential relevance of highly represented protein families such as MAGE-B2, olfactory receptor and ribosomal proteins in L. africana and E. edwardii, respectively. Taken together, our study reports the first comparative study of the Afrotherian proteomes and highlights salient molecular features.Although mammograms play a key role in early breast cancer detection, the test is not applicable to all women, for example, women under the age of 40. The development of a noninvasive blood test with high sensitivity and accessibility will improve the effectiveness of breast cancer screening programmes. Secretory factors released from cancer cells can induce the expression of certain genes in a large number of white blood cells (WBCs). Therefore, cancer-dependent proteins in WBCs can be used as tumour markers with high sensitivity. Five proteins (LMAN1, AZI2, STAU2, MMP9 and PLOD1) from a systemic analysis of a variety of array data of breast cancer patients were subjected to immunofluorescence staining to evaluate the presence of fixed WBCs on 96-well plates from 363 healthy females and 358 female breast cancer patients. The results revealed that the average fluorescence intensity of anti-STAU2 and the percentage of STAU2-positive T and B lymphocytes in breast cancer patients (110.50 ± 23.38 and 61.87 ± 12.44, respectively) were significantly increased compared with those in healthy females (56.47 ± 32.03 and 33.02 ± 18.10, respectively) (p = 3.56 × 10-71, odds ratio = 24.59, 95% CI = 16.64-36.34). The effect of secreted molecules from breast cancer cells was proven by the increase in STAU2 intensity in PBMCs cocultured with MCF-7 and T47D cells at 48 h (p = 0.0289). The test demonstrated 98.32%, 82.96%, and 48.32% sensitivity and 56.47%, 83.47%, and 98.62% specificity in correlation with the percentage of STAU2-positive cells at 40, 53.34 and 63.38, respectively. We also demonstrated how to use the STAU2 test for the assessment of risk in women under the age of 40. STAU2 is a novel breast cancer marker that can be assessed by quantitative immunofluorescence staining of fixed WBCs that are transportable at room temperature via mail, representing a useful risk assessment tool for women without access to mammograms.Submucosal deep invasion of gastric cancer (T1b2; depth of submucosal invasion ≥ 500 μm) is a risk factor for lymph node metastasis and, thus, is one of the criteria for curative treatment. Our aim was to evaluate the specific influence of endoscopic submucosal dissection (ESD) on the prognosis of patients with T1b2 gastric cancer. This was a retrospective analysis of 248 consecutive patients, with 252 pT1b2 gastric cancer lesions, who underwent ESD prior to additional surgery (Group A, n = 101) or surgery only (Group B, n = 147). After propensity score-matching (for sex, age, tumor diameter and gross type), we compared pathological characteristics between the 2 groups and the prognosis over a follow-up period ≥ 60 months. Compared to Group B, patients in Group A were older, with a higher proportion of men. The proportion of depressed and undifferentiated type tumors was greater in Group B than A, with larger tumor size and depth of submucosal invasion as well. There was no incidence of local recurrence, but distant metastasis was identified in 5% of cases in Group A and 3% in Group B. After propensity score-matching, there were no difference in the 5-year overall survival rate between Group A and B (87.5% vs. 91.2%, respectively), nor in the 5-year disease-specific survival rate (96.3% vs. 96.4%, respectively). ESD prior to surgery for T1b2 gastric cancer did not adversely affect clinical outcomes after additional surgery.The effect of mineral dust aerosols and subsequent deposition in polar regions has historically been underestimated in climate models. Dust aerosols increase melt rates by reducing surface albedo and modifying atmospheric radiative properties. In this study 127,413 satellite images covering the Arctic and Antarctic from 2007 to 2019 were assessed for dust content using thermal infrared wavelengths. The results show a strong linear trend in which the relative spatial extent of dust (RSED) increased annually by 0.31% in the Arctic (8.5% to 12.1%) and 0.19% in the Antarctic (5.2% to 7.5%). Seasonally, the maximum aggregated average RSED occurred in the Arctic during boreal winter (11.2%), while the Antarctic peaked in austral spring (9.5%). Maximum RSED rates occurred in boreal winter/austral summer (Dec-Jan-Feb) for both polar regions. The data suggests that finer dust particles are more efficiently distributed by aeolian processes leading to higher RSED values that are not necessarily reflective of polar dust loading models.Currently, there is no appropriate treatment option for patients with sorafenib-resistant hepatocellular carcinoma (HCC). Meanwhile, pronounced anticancer activities of newly-developed mitochondria-accumulating self-assembly peptides (Mito-FF) have been demonstrated. This study intended to determine the anticancer effects of Mito-FF against sorafenib-resistant Huh7 (Huh7-R) cells. Compared to sorafenib, Mito-FF led to the generation of relatively higher amounts of mitochondrial reactive oxygen species (ROS) as well as the greater reduction in the expression of antioxidant enzymes (P  less then  0.05). Mito-FF was found to significantly promote cell apoptosis while inhibiting cell proliferation of Huh7-R cells. Mito-FF also reduces the expression of antioxidant enzymes while significantly increasing mitochondrial ROS in Huh7-R cells. The pro-apoptotic effect of Mito-FFs for Huh7-R cells is possibly caused by their up-regulation of mitochondrial ROS, which is caused by the destruction of the mitochondria of HCC cells.Transformation acoustics, as an unconventional theory, provides a powerful tool to design various kinds of acoustic devices with excellent functionalities. However, the required ideal parameters, which are prescribed by the method, are both complex and hard to implement-even using acoustic metamaterials. Furthermore, simplified parameter materials are generally favored in transformation-acoustic design due to its easier realization with artificial structures. In this letter, we propose a coordinate transformation methodology for achieving simplified parameters by tuning the impedance distribution in the geometric limit, where the transformation media parameters can be derived by setting tunable impedance functions in the original space and a combination of suitable linear or nonlinear coordinate transformation. Based on this approach, both two-dimensional acoustic cloak and concentrators are designed with different sets of simplified parameters. Numerical simulations indicate good performance of these devices with minimized scattering at higher frequencies. The proposed method provides more opportunities to realize the designed acoustic devices experimentally, and can also be used for other transformation-acoustic designs including 3D cases.This study investigated the ultrafiltration (UF) membrane fouling mechanism of intracellular organic matter (IOM) from Chlorella vulgaris (CV) and Microcystis aeruginosa (MA). Both CV- and MA-IOM caused severe membrane fouling during UF; however, there were significant differences in the membrane fouling by these two materials. Neutral hydrophilic (N-HPI) compounds were the organics that caused the most severe membrane fouling during CV-IOM filtration, whereas the MA-IOM membrane fouling was induced by mainly hydrophobic (HPO) organics. From an analysis based on Derjaguin-Landau-Verwey-Overbeek theory, it was found that the interaction energy between the membrane and foulants in the later stage of filtration was the major factor determining the efficiency of filtration for both CV-IOM and MA-IOM. The TPI organics in CV-IOM fouled the membrane to a more severe degree during the initial filtration flux; however, when the membrane surface was covered with CV-IOM foulants, the N-HPI fraction of CV-IOM caused the most severe membrane fouling because its attractive energy with the membrane was the highest. For MA-IOM, regardless of the initial filtration flux or the late stage of filtration, the HPO organics fouled the membrane to the greatest extent. An analysis of modified filtration models revealed that cake layer formation played a more important role than other fouling mechanisms during the filtration of CV-IOM and MA-IOM. This study provides a significant understanding of the membrane fouling mechanism of IOM and is beneficial for developing some strategies for membrane fouling control when treating MA and CV algae-laden waters.Biting midges are widespread around the world and play an essential role in the epidemiology of over 100 veterinary and medical diseases. For taxonomists, it is difficult to correctly identify species because of affinities among cryptic species and species complexes. In this study, species boundaries were examined for C. clastrieri and C. festivipennis and compared with six other Culicoides species. The classifiers are partial least squares discriminant analysis (PLS-DA) and sparse partial least squares discriminant analysis (sPLS-DA).The performance of the proposed method was evaluated using four models (i) geometric morphometrics applied to wings; (ii) morphological wing characters, (iii) "Full wing" (landmarks and morphological characters) and (iv) "Full model" (morphological characters-wing, head, abdomen, legs-and wing landmarks). Double cross-validation procedures were used to validate the predictive ability of PLS-DA and sPLS-DA models. The AUC (area under the ROC curve) and the balanced error rate showed that the sPLS-DA model performs better than the PLS-DA model. Our final sPLS-DA analysis on the full wing and full model, with nine and seven components respectively, managed to perfectly classify our specimens. The C. clastrieri and C. festivipennis sequences, containing both COI and 28S genes, revealed our markers' weak discrimination power, with an intraspecific and interspecific divergence of 0.4% and 0.1% respectively. Moreover, C. clastrieri and C. festivipennis are grouped in the same clade. The morphology and wing patterns of C. clastrieri and C. festivipennis can be used to clearly distinguish them. Our study confirms C. clastrieri and C. festivipennis as two distinct species. Our results show that caution should be applied when relying solely on DNA barcodes for species identification or discovery.This systematic review (SR) addressed the following common clinical question What is more effective in reducing or eliminating endotoxin in endodontic infections-single or multiple-session treatments using calcium hydroxide medications? Literature searches of Medline/PubMed, Embase, Cochrane Library, Scielo, Science Direct, Web of Knowledge, Scopus, and Google Scholar databases. Two reviewers independently assessed the eligibility for inclusion, extracted data, and evaluated the quality of the studies using the risk of bias tools. Electronic searches resulted in 358 articles, of which 32 studies were included for full-text assessment, and nine were included in this review. Meta-analysis pooling all the nine studies revealed lower levels of endotoxin for multiple-session treatment (P  less then  0.001). The sub-group analysis indicated no difference between single-session and 7 days of Ca(OH)2 medication (SMD - 0.32; P = 0.22). However, 14-days (I2 = 80.5%, P  less then  0.001) and 30-days (I2 = 78.9%, P  less then  0.01) of Ca(OH)2 medication was more effective than single-session treatment (both, p  less then  0.001). Overall, Overall, this SR provides evidence to support that multiple-session disinfection protocols with the placement of Ca(OH)2 medications are more effective in reducing the levels of endotoxin from root canal infections compared to single-session when applied for 14 and 30 days.Human parvovirus B19 (B19V) infection is not notifiable in Belarus and its most common clinical presentation erythema infectiosum (EI) is often difficult to distinguish from other exanthematous diseases. The objective of this study was to provide comprehensive data about EI epidemiology in Belarus based on the serological and molecular investigation of samples from measles and rubella discarded cases collected between 2005 and 2019. Overall, 4919 sera were investigated for IgM antibodies against B19V and the positive cases were analysed according to year, season and age. B19V DNA was amplified by PCR in a total of 238 sera from all over the country, and sequenced for phylogenetic analyses. B19V infection was confirmed in 1377 (27.8%) measles and rubella discarded cases. Two high incidence periods and a seasonal increase of EI between mid-February to mid-July were identified. Children from 4 to 6 and from 7 to 10 years of age represented the largest groups of patients (22.51% and 22.66% of all cases, respectively), followed by adults between 20 and 29 years of age (14.23%). Among the 238 B19Vs sequenced, one belonged to subgenotype 3b and 237 to subgenotype 1a with 81 (34.2%) clustering with subtypes 1a1 and 153 (64.6%) with 1a2. Three strains (1.2%) formed an additional, well-supported cluster suggesting the presence of another subtype of 1a, tentatively named 1a3. The epidemiological and molecular analyses highlighted not only the prominent role of B19V in exanthematous diseases in Belarus, but also suggested a previously underestimated diversity of subgenotype 1a sequences with a third subtype 1a3.Classification tasks are a common challenge to every field of science. To correctly interpret the results provided by a classifier, we need to know the performance indices of the classifier including its sensitivity, specificity, the most appropriate cut-off value (for continuous classifiers), etc. Typically, several studies should be conducted to find all these indices. Herein, we show that they already exist, hidden in the distribution of the variable used to classify, and can readily be harvested. An educated guess about the distribution of the variable used to classify in each class would help us to decompose the frequency distribution of the variable in population into its components-the probability density function of the variable in each class. Based on the harvested parameters, we can then calculate the performance indices of the classifier. As a case study, we applied the technique to the relative frequency distribution of prostate-specific antigen, a biomarker commonly used in medicine for the diagnosis of prostate cancer. We used nonlinear curve fitting to decompose the variable relative frequency distribution into the probability density functions of the non-diseased and diseased people. The functions were then used to determine the performance indices of the classifier. Sensitivity, specificity, the most appropriate cut-off value, and likelihood ratios were calculated. The reference range of the biomarker and the prevalence of prostate cancer for various age groups were also calculated. The indices obtained were in good agreement with the values reported in previous studies. All these were done without being aware of the real health status of the individuals studied. The method is even applicable for conditions with no definite definitions (e.g., hypertension). We believe the method has a wide range of applications in many scientific fields.Cystic fibrosis (CF) is a genetic disease characterized by CF transmembrane regulator (CFTR) dysfunction. With over 2000 CFTR variants identified, in addition to known patient to patient variability, there is a need for personalized treatment. The discovery of CFTR modulators has shown efficacy in certain CF populations, however there are still CF populations without valid therapeutic options. With evidence suggesting that single drug therapeutics are insufficient for optimal management of CF disease, there has been an increased pursuit of combinatorial therapies. Our aim was to test cyclic AMP (cAMP) modulation, through ATP Binding Cassette Transporter C4 (ABCC4) and phosphodiesterase-4 (PDE-4) inhibition, as a potential add-on therapeutic to a clinically approved CFTR modulator, VX-770, as a method for increasing CFTR activity. Human airway epithelial cells (Calu-3) were used to test the efficacy of cAMP modulation by ABCC4 and PDE-4 inhibition through a series of concentration-response studies. Our results showed that cAMP modulation, in combination with VX-770, led to an increase in CFTR activity via an increase in sensitivity when compared to treatment of VX-770 alone. Our study suggests that cAMP modulation has potential to be pursued as an add-on therapy for the optimal management of CF disease.Drosophila suzukii flies cause economic losses to fruit crops globally. Previous work shows various Drosophila species are attracted to volatile metabolites produced by individual fruit associated yeast isolates, but fruits naturally harbour a rich diversity of yeast species. Here, we report the relative attractiveness of D. suzukii to yeasts presented individually or in combinations using laboratory preference tests and field trapping data. Laboratory trials revealed four of 12 single yeast isolates were attractive to D. suzukii, of which Metschnikowia pulcherrima and Hanseniaspora uvarum were also attractive in field trials. Four out of 10 yeast combinations involving Candida zemplinina, Pichia pijperi, M. pulcherrima and H. uvarum were attractive in the laboratory. Whilst a combination of M. pulcherrima + H. uvarum trapped the greatest number of D. suzukii in the field, the efficacy of the M. pulcherrima + H. uvarum combination to trap D. suzukii was not significantly greater than traps primed with volatiles from only H. uvarum. While volatiles from isolates of M. pulcherrima and H. uvarum show promise as baits for D. suzukii, further research is needed to ascertain how and why flies are attracted to certain baits to optimise control efficacy.Despite extensive research on molecular pathways controlling the process of regeneration in model organisms, little is known about the actual initiation signals necessary to induce regeneration. Recently, the activation of ERK signaling has been shown to be required to initiate regeneration in planarians. However, how ERK signaling is activated remains unknown. Reactive Oxygen Species (ROS) are well-known early signals necessary for regeneration in several models, including planarians. Still, the probable interplay between ROS and MAPK/ERK has not yet been described. Here, by interfering with major mediators (ROS, EGFR and MAPK/ERK), we were able to identify wound-induced ROS, and specifically H2O2, as upstream cues in the activation of regeneration. Our data demonstrate new relationships between regeneration-related ROS production and MAPK/ERK activation at the earliest regeneration stages, as well as the involvement of the EGFR-signaling pathway. Our results suggest that (1) ROS and/or H2O2 have the potential to rescue regeneration after MEK-inhibition, either by H2O2-treatment or light therapy, (2) ROS and/or H2O2 are required for the activation of MAPK/ERK signaling pathway, (3) the EGFR pathway can mediate ROS production and the activation of MAPK/ERK during planarian regeneration.Parkinson's disease (PD) is an incapacitating neurodegenerative disease. Patients with PD and their caregivers may have interactive effects on each other's psychological well-being. This study aimed to assess the dyadic dynamics of resilience, fatigue, and suicidal ideation on the depression severity of PD patients and their caregivers. In total, 175 PD patients and 175 caregivers were recruited at a medical center from August 2018 to May 2020. Structural equation modeling (SEM) was used to examine the actor/partner effects on the psychological well-being of both the PD patients and their caregivers. The most common psychiatric diagnoses of both the PD patients (28.6%) and their caregivers (11.4%) were depressive disorders. The PD patients' and their caregivers' fatigue, suicidal ideation, and lack of resilience were significantly associated with the severity of their depression, respectively. Interactive effects existed between psychological well-being of individuals with PD and their caregivers. Clinicians must be aware of, and manage, these contributing factors between PD patients and their caregivers in order to prevent them from worsening each other's depression.We examined the residence time, seepage rate, and submarine groundwater discharge (SGD)-driven dissolved nutrients and organic matter in Hwasun Bay, Jeju Island, Korea during the occurrence of a typhoon, Kong-rey, using a humic fluorescent dissolved organic matter (FDOMH)-Si mass balance model. The study period spanned October 4-10, 2018. One day after the typhoon, the residence time and seepage rate were calculated to be 1 day and 0.51 m day-1, respectively, and the highest SGD-driven fluxes of chemical constituents were estimated (1.7 × 106 mol day-1 for dissolved inorganic nitrogen, 0.1 × 106 mol day-1 for dissolved inorganic phosphorus (DIP), 1.1 × 106 mol day-1 for dissolved silicon, 0.5 × 106 mol day-1 for dissolved organic carbon, 1.6 × 106 mol day-1 for dissolved organic nitrogen, 0.4 × 106 mol day-1 for particulate organic carbon, and 38 × 106 g QS day-1 for FDOMH). SGD-driven fluxes of dissolved nutrient and organic matter were over 90% of the total input fluxes in Hwasun Bay. Our results highlight the potential of using the FDOMH-Si mass balance model to effectively measure SGD within a specific area (i.e., volcanic islands) under specific weather conditions (i.e., typhoon/storm). In oligotrophic oceanic regions, SGD-driven chemical fluxes from highly permeable islands considerably contribute to coastal nutrient budgets and coastal biological production.Immunofluorescence is indispensable to monitor redistribution of proteins involved in phagosome-lysosome association pathway-relevant (P-LApr) proteins. The software digitizing the signals of these proteins in an unbiased and automated manner is generally costly and not widely available. The open-source ImageJ plugin EzColocalization, which is for co-localization analysis of reporters in cells, was not straightforward and sufficient for such analysis. We describe here the input of custom Java code in a novel tailored protocol using EzColocalization to digitize the signals of punctum-distributed P-LApr proteins co-localized with phagosomes and to calculate percentages of phagosomes engaged. We showed that SYBR Gold nucleic acid dye could visualize intracellular mycobacteria that did not express a fluorescent protein. This protocol was validated by showing that IFN-γ enhanced the co-localization of a punctum-distributed P-LApr protein (LC3) with Mycobacterium bovis BCG in the monocyte/macrophage-like RAW264.7 cells and that there was greater co-localization of LC3 with BCG than with M. tuberculosis H37Rv in bone marrow-derived macrophages (BMDMs). Although BCG and a derived strain (rBCG-PA) showed a similarly high degree co-localization with LC3 in BMDMs, in RAW264.7 cells BCG showed much less co-localization with LC3 than rBCG-PA indicating the need for caution in interpreting biological significance from studies in cell lines.Mutations in BRCA genes are the leading cause of hereditary breast cancer. Current options to prevent cancer in these high-risk patients, such as anti-estrogen drugs and radical mastectomy, are limited by lack of efficacy, undesirable toxicities, or physical and emotional challenges. We have previously shown that PARP inhibitors can significantly delay tumor development in BRCA1-deficient mice. Here, we fabricated the PARP inhibitor talazoparib (TLZ) into spacer implants (InCeT-TLZ) for localized and sustained delivery. We hypothesized that this novel formulation will provide an effective chemopreventive strategy with minimal toxicity. TLZ was released gradually over 30 days as implants degraded. InCeT-TLZ significantly decreased proliferation and increased DNA damage in the mammary glands of BRCA1-deficient mice. Notably, the number of mice that developed hyperplasia in the mammary glands was significantly lower with InCeT-TLZ treatment compared to the control group. Meanwhile, InCeT-TLZ was also better tolerated than oral TLZ, without loss of body weight or anemia. This study provides proof of concept for a novel and safe chemopreventive strategy using localized delivery of a PARP inhibitor for high-risk individuals. Future studies will directly evaluate the effects of InCeT-TLZ for preventing tumor development.Conventional and nanocrystalline MCrAlY coatings were applied by the high-velocity oxy-fuel (HVOF) deposition process. The ball-milling method was used to prepare the nanocrystalline MCrAlY powder feedstock. The microstructure examinations of the conventional and nanocrystalline powders and coatings were performed using X-ray diffraction (XRD), high-resolution field emission scanning electron microscope (FESEM) equipped with energy-dispersive X-ray spectroscopy (EDX), transmission electron microscope (TEM), and X-ray photoelectron spectroscopy (XPS). Williamson-Hall analyzing method was also used for estimation of the crystalline size and lattice strain of the as-milled powders and sprayed coatings. Owing to the investigation of the oxidation behavior, the freestanding coatings were subjected to isothermal and cyclic oxidation testing at 1000 and 1100 °C under static air. The results showed that the conventional as-sprayed MCrAlY coating had a parabolic behavior in the early stage and prolonged oxidation process. On the contrary, in the case of the nanocrystalline MCrAlY coating, the long-term oxidation behavior has deviated from parabolic to sub-parabolic rate law. Moreover, the results also exemplified that the nanocrystalline MCrAlY coating had a greater oxidation resistance following the creation of a continuous and slow-growing Al2O3 scale with a fine-grained structure. The nucleation and growth mechanisms of the oxides formed on the nanocrystalline coating have also been discussed in detail.In this paper we discussed, nitrogen oxides gas sensors are designed and simulated using the MEMS-based tool of COMSOL Multiphysics software. Pd-rGO composite films were designed and their NOx sensing characteristics were investigated in this study by comparing with/without active layers. Transition metal SnO2 deals with four different active materials i.e., Pure SnO2, SnO2-Pd, SnO2-rGO, and SnO2-Pd/rGO film was controlled by altering the active materials during the active layer deposition. The deposition of Pd/rGO active material is integrated into the SnO2 thin film. The response of the nanocomposite materials on the NOx gas sensor at a low temperature below 100 °C was significantly improved. Moreover, we investigate the optimization from different active layer response for NOx by applying power in watt and milliwatt to the interdigitated electrode on the Sn substrate. The determination is tense to finalize the suitable materials that to detect more response for nitrogen oxides i.e., Pd/rGO layer shows better performance when compared with other active layers for the sensing of nitrogen oxides is in proportion to the power in the range of 0.6-4.8 W at (1-8) Voltage range. This advanced research will enable a new class of portable NOx gas sensors to be constructed with millimeter size and microwatt power.Dendritic cells (DCs) are innate immune cells which engulf, process and present antigens to the naïve T-lymphocyte cells. However, little is known about the effect of melatonin on the DCs. The present study aimed to investigate the morphology and distribution of the DCs by transmission electron microscopy and Immunohistochemistry after melatonin administration. A total of 8 out of 15 adult ram was randomly selected to receive the melatonin implant and the remaining 7 animals received melatonin free implants. DCs showed positive immunoreactivity for CD117, S-100 protein and CD34. There is an obvious increase in the number of the positive immunoreactive cells to CD3, estrogen receptor alpha and progesterone in the treated groups. The expression of CD56 and MHCII in the DCs was abundant in the treated groups. The ultrastructure study revealed that melatonin exerts a stimulatory effect on the DCs which was associated with increment in the secretory activity of DCs. The secretory activity demarcated by an obvious increase in the number of mitochondria, cisternae of rER and a well-developed Golgi apparatus. The endosomal- lysosomal system was more developed in the treated groups. A rod-shaped Birbeck granule was demonstrated in the cytoplasm of the melatonin treated group. DCs were observed in a close contact to telocytes, T-Lymphocytes, nerve fibers and blood vessels. Taken together, melatonin administration elicits a stimulatory action on the DCs and macrophages through increasing the size, the number and the endosomal compartments which may correlate to increased immunity.The breakdown of nasal epithelial barrier occurs in allergic rhinitis (AR) patients. Impairment of cell junction molecules including tight junctions (TJs) and desmosomes plays causative roles in the pathogenesis of AR. In this study, we investigated the transcript expression levels of TJs including occludin (OCLN), claudin-3 and -7 (CLDN3 and CLDN7), desmoglein 3 (DSG3) and thymic stromal lymphopoietin (TSLP) in AR patients (n = 30) and non-allergic controls (n = 30). Nasal epithelial cells of non-allergic controls and AR patients were collected to examine their mRNA expression levels, and to correlate with clinico-demographical and environmental parameters. We demonstrated that the expression of OCLN (p = 0.009), CLDN3 (p = 0.032) or CLDN7 (p = 0.004) transcript was significantly lower in AR patients compared with non-allergic controls. No significant difference was observed in the expression of DSG3 (p = 0.750) or TSLP (p = 0.991) transcript in AR patients compared with non-allergic controls. A significant association between urban locations and lower OCLN expression (p = 0.010), or exposure to second-hand smoke with lower CLDN7 expression (p = 0.042) was found in AR patients. Interestingly, none of the TJs expression was significantly associated with having pets, frequency of changing bedsheet and housekeeping. These results suggest that defective nasal epithelial barrier in AR patients is attributable to reduced expression of OCLN and CLDN7 associated with urban locations and exposure to second-hand smoke, supporting recent findings that air pollution represents one of the causes of AR.Detection and delineation are key steps for retrieving and structuring information of the electrocardiogram (ECG), being thus crucial for numerous tasks in clinical practice. Digital signal processing (DSP) algorithms are often considered state-of-the-art for this purpose but require laborious rule readaptation for adapting to unseen morphologies. This work explores the adaptation of the the U-Net, a deep learning (DL) network employed for image segmentation, to electrocardiographic data. The model was trained using PhysioNet's QT database, a small dataset of 105 2-lead ambulatory recordings, while being independently tested for many architectural variations, comprising changes in the model's capacity (depth, width) and inference strategy (single- and multi-lead) in a fivefold cross-validation manner. This work features several regularization techniques to alleviate data scarcity, such as semi-supervised pre-training with low-quality data labels, performing ECG-based data augmentation and applying in-built model regularizers. The best performing configuration reached precisions of 90.12%, 99.14% and 98.25% and recalls of 98.73%, 99.94% and 99.88% for the P, QRS and T waves, respectively, on par with DSP-based approaches. Despite being a data-hungry technique trained on a small dataset, a U-Net based approach demonstrates to be a viable alternative for this task.Generally, the decision rule for classifying unstructured data in an artificial neural network system depends on the sequence results of an activation function determined by vector-matrix multiplication between the input bias signal and the analog synaptic weight quantity of each node in a matrix array. Although a sequence-based decision rule can efficiently extract a common feature in a large data set in a short time, it can occasionally fail to classify similar species because it does not intrinsically consider other quantitative configurations of the activation function that affect the synaptic weight update. In this work, we implemented a simple run-off election-based decision rule via an additional filter evaluation to mitigate the confusion from proximity of output activation functions, enabling the improved training and inference performance of artificial neural network system. Using the filter evaluation selected via the difference among common features of classified images, the recognition accuracy achieved for three types of shoe image data sets reached ~ 82.03%, outperforming the maximum accuracy of ~ 79.23% obtained via the sequence-based decision rule in a fully connected single layer network. This training algorithm with an independent filter can precisely supply the output class in the decision step of the fully connected network.In endometriosis, M2 MΦs are dominant in endometriotic lesions, but the actual role of M2 MΦ is unclear. CD206 positive (+) MΦ is classified in one of M2 type MΦs and are known to produce cytokines and chemokines. In the present study, we used CD206 diphtheria toxin receptor mice, which enable to deplete CD206+ cells with diphtheria toxin (DT) in an endometriosis mouse model. The depletion of CD206+ MΦ decreased the total weight of endometriotic-like lesions significantly (p  less then  0.05). In the endometriotic-like lesions in the DT group, a lower proliferation of endometriotic cells and the decrease of angiogenesis were observed. In the lesions, the mRNA levels of VEGFA and TGFβ1, angiogenic factors, in the DT group significantly decreased to approximately 50% and 30% of control, respectively. Immunohistochemical study revealed the expressions of VEGFA and an endothelial cell marker CD31 in lesions of the DT group, were dim compared to those in control. Also, the number of TGFβ1 expressing MΦ was significantly reduced compared to control. These data suggest that CD206+ MΦ promotes the formation of endometriotic-like lesions by inducing angiogenesis around the lesions.We propose an encryption-decryption framework for validating diffraction intensity volumes reconstructed using single-particle imaging (SPI) with X-ray free-electron lasers (XFELs) when the ground truth volume is absent. This conceptual framework exploits each reconstructed volumes' ability to decipher latent variables (e.g. orientations) of unseen sentinel diffraction patterns. Using this framework, we quantify novel measures of orientation disconcurrence, inconsistency, and disagreement between the decryptions by two independently reconstructed volumes. We also study how these measures can be used to define data sufficiency and its relation to spatial resolution, and the practical consequences of focusing XFEL pulses to smaller foci. This conceptual framework overcomes critical ambiguities in using Fourier Shell Correlation (FSC) as a validation measure for SPI. Finally, we show how this encryption-decryption framework naturally leads to an information-theoretic reformulation of the resolving power of XFEL-SPI, which we hope will lead to principled frameworks for experiment and instrument design.
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