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Author verification is challenging because of the diversity in writing styles. We propose an enhanced handwriting verification method that combines handcrafted and automatically extracted features. The method uses a genetic algorithm to reduce the dimensionality of the feature set. We consider offline Bangla handwriting content and evaluate the proposed method using handcrafted features with a simple logistic regression, radial basis function network, and sequential minimal optimization as well as automatically extracted features using a convolutional neural network. The handcrafted features outperform the automatically extracted ones, achieving an average verification accuracy of 94.54% for 100 writers. The handcrafted features include Radon transform, histogram of oriented gradients, local phase quantization, and local binary patterns from interwriter and intrawriter content. The genetic algorithm reduces the feature dimensionality and selects salient features using a support vector machine. The top five experimental results are obtained from the optimal feature set selected using a consensus strategy. Comparisons with other methods and features confirm the satisfactory results. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal metastatic disease associated with robust activation of the coagulation and fibrinolytic systems. However, the potential contribution of the primary fibrinolytic protease plasminogen to PDAC disease progression has remained largely undefined. Mice bearing C57Bl/6‐derived KPC (KRasG12D, TRP53R172H) tumors displayed evidence of plasmin activity in the form of high plasmin–antiplasmin complexes and high plasmin generation potential relative to mice without tumors. Notably, plasminogen‐deficient mice (Plg‐) had significantly diminished KPC tumor growth in subcutaneous and orthotopic implantation models. Moreover, the metastatic potential of KPC cells was significantly diminished in Plg‐ mice, which was linked to reduced early adhesion and/or survival of KPC tumor cells. The reduction in primary orthotopic KPC tumor growth in Plg‐ mice was associated with increased apoptosis, reduced accumulation of pro‐tumor immune cells, and increased local proinflammatory cytokine production. Elimination of fibrin(ogen), the primary proteolytic target of plasmin, did not alter KPC primary tumor growth and resulted in only a modest reduction in metastatic potential. In contrast, deficiencies in the plasminogen receptors Plg‐RKT or S100A10 in tumor cells significantly reduced tumor growth. Plg‐RKT reduction in tumor cells, but not reduced S100A10, suppressed metastatic potential in a manner that mimicked plasminogen deficiency. Finally, tumor growth was also reduced in NSG mice subcutaneously or orthotopically implanted with patient‐derived PDAC tumor cells in which circulating plasminogen was pharmacologically reduced. Collectively, these studies suggest that plasminogen promotes PDAC tumor growth and metastatic potential, in part through engaging plasminogen receptors on tumor cells. [ABSTRACT FROM AUTHOR]

Robustness, payload, and imperceptibility of audio watermarking algorithms are contradictory design issues with high‐level security of the watermark. In this study, the major issue in achieving high payload along with adequate robustness against challenging signal‐processing attacks is addressed. Moreover, a security code has been strategically used for secure transmission of data, providing tamper detection at the receiver end. The high watermark payload in this work has been achieved by using the complementary features of third‐level detailed coefficients of discrete wavelet transform where the human auditory system is not sensitive to alterations in the audio signal. To counter the watermark loss under challenging attacks at high payload, Daubechies wavelets that have an orthogonal property and provide smoother frequencies have been used, which can protect the data from loss under signal‐processing attacks. Experimental results indicate that the proposed algorithm has demonstrated adequate robustness against signal processing attacks at 4,884.1 bps. Among the evaluators, 87% have rated the proposed algorithm to be remarkable in terms of transparency. [ABSTRACT FROM AUTHOR]

Juvenile onset open angle glaucoma ( JOAG) affects patients before 40 years of age, who present with high intraocular pressure and deep steep cupping of the optic nerve head. While it was considered to be inherited in an autosomal dominant fashion, recent studies have shown an autosomal recessive pattern as well as sporadic occurrence of the disease in several families. In this review, we analyze the genetic basis of the disease along with common mutations and their association with JOAG. We also analyzed the inheritance patterns in a large group of unrelated JOAG patients ( n = 336) from Northern India wherein the prevalence of familial occurrence was assessed and segregation analysis performed, to determine the mode of inheritance. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum enolase (Pfeno) is a dimeric enzyme with multiple moonlighting functions. This enzyme is thus a potential target for antimalarial treatments. A unique feature of Pfeno is the presence of a pentapeptide insert 104EWGWS108. The functional role of tryptophan residues in this insert was investigated using site-directed mutagenesis. Replacement of these two Trp residues with alanines (or lysines) resulted in a near complete loss of enolase activity and dissociation of the normal dimeric form into monomers. Molecular modeling indicated that 340R forms π-cation bonds with the aromatic rings of 105W and 46Y. Mutation induced changes in the interactions among these three residues were presumably relayed to the inter-subunit interface via a coil formed by 46Y : 59Y, resulting in the disruption of a salt bridge between 11R : 425E and a p-cation interaction between 11R : 59Y. This led to a drop of ~ 4 kcal.mole -1 in the inter-subunit docking energy in the mutant, causing a ~ 10³ fold decrease in affinity. Partial restoration of the inter-subunit interactions led to reformation of dimers and also restored a significant fraction of the lost enzyme activity. These results suggested that the perturbations in the conformation of the surface loop containing the insert sequence were relayed to the interface region, causing dimer dissociation that, in turn, disrupted the enzyme's active site. Since Plasmodium enolase is a moonlighting protein with multiple parasite-specific functions, it is likely that these functions may map on to the highly conserved unique insert region of this protein. [ABSTRACT FROM AUTHOR]

Sphingobium sp. PNB, like other sphingomonads, has multiple ring-hydroxylating oxygenase (RHO) genes. Three different fosmid clones have been sequenced to identify the putative genes responsible for the degradation of various aromatics in this bacterial strain. Comparison of the map of the catabolic genes with that of different sphingomonads revealed a similar arrangement of gene clusters that harbors seven sets of RHO terminal components and a sole set of electron transport (ET) proteins. The presence of distinctly conserved amino acid residues in ferredoxin and in silico molecular docking analyses of ferredoxin with the well characterized terminal oxygenase components indicated the structural uniqueness of the ET component in sphingomonads. The predicted substrate specificities, derived from the phylogenetic relationship of each of the RHOs, were examined based on transformation of putative substrates and their structural homologs by the recombinant strains expressing each of the oxygenases and the sole set of available ET proteins. The RHO AhdA1bA2b was functionally characterized for the first time and was found to be capable of transforming ethylbenzene, propylbenzene, cumene, p -cymene and biphenyl, in addition to a number of polycyclic aromatic hydrocarbons. Overexpression of aromatic catabolic genes in strain PNB, revealed by real-time PCR analyses, is a way forward to understand the complex regulation of degradative genes in sphingomonads. [ABSTRACT FROM AUTHOR]

Angiogenin (ANG), a 14‐kDa pro‐angiogenic secreted protein, has been shown to play a role in cell migration and tumor invasion, which involve proteolytic cleavage of plasminogen to generate plasmin. However, the mechanism by which ANG regulates plasmin formation and cell migration was not known. Our studies here detected elevated levels of secreted and cell surface‐bound ANG in highly invasive metastatic breast cancer cells. ANG was also detected at very high levels in the tumor cells in infiltrating ductal carcinomas. By immunofluorescence and immunoprecipitation analysis, ANG was detected at the leading edges of the cell surfaces where it colocalized and interacted with members of the plasminogen activation system (PAS) such as annexin A2 (A2), calpactin (S100‐A10) and urokinase plasminogen activator receptor (uPAR). Analysis of lipid raft (LR) and non‐lipid raft (NLR) regions of the cell membranes showed the predominance of ANG, A2 and S100‐A10 in the LR regions. In contrast, uPAR was detected predominantly in the NLR fractions, suggesting that ANG interacts with uPAR at the junctions of LR and NLR regions. ANG knockdown in T47D and MDA‐MB‐231 breast cancer cell lines did not affect the cellular expression of A2, S100‐A10 and uPAR but decreased cell migration and plasmin formation. Neutralization of ANG with monoclonal antibodies similarly decreased the migration of MDA‐MB‐231 cells. In the presence of ANG, uPAR was observed to interact with uPA, which is necessary for plasmin formation. Conversely, in the absence of ANG, uPAR did not interact with uPA and FAK and Src kinases were observed to be dephosphorylated. Exogenous addition of recombinant ANG to ANG knocked down MDA‐MB‐231 cells restored FAK phosphorylation, uPAR interactions with uPA, plasmin formation as well as migration of these cells. Taken together, our results identified a novel role for ANG as a member of the uPAR interactome that facilitates the interaction of uPAR with uPA, leading to plasmin formation and cell migration necessary for tumor invasion and metastasis of breast cancer cells. Highlights: Invasive metastatic breast cancer cells have high levels of cell surface bound ANG.Cell surface ANG interacts with members of the plasminogen activation system (PAS).PAS member uPAR interacts with plasminogen receptor Annexin A2 and S100‐A10 via ANG.ANG is required for interaction between uPAR and uPA.Depletion of cell surface ANG causes inhibition of plasmin formation and cell motility. [ABSTRACT FROM AUTHOR]

Amplification of 3q26.2, found in many cancer lineages, is a frequent and early event in ovarian cancer. We previously defined the most frequent region of copy number increase at 3q26.2 to EVI1 (ecotropic viral integration site‐1) and MDS1 (myelodysplastic syndrome 1) (aka MECOM), an observation recently confirmed by the cancer genome atlas (TCGA). MECOM is increased at the DNA, RNA, and protein level and likely contributes to patient outcome. Herein, we report that EVI1 is aberrantly spliced, generating multiple variants including a Del190–515 variant (equivalent to previously reported) expressed in >90% of advanced stage serous epithelial ovarian cancers. Although EVI1Del190–515 lacks ∼70% of exon 7, it binds CtBP1 as well as SMAD3, important mediators of TGFβ signaling, similar to wild type EVI1. This contrasts with EVI1 1–268 which failed to interact with CtBP1. Interestingly, the EVI1Del190–515 splice variant preferentially localizes to PML nuclear bodies compared to wild type and EVI1Del427–515. While wild type EVI1 efficiently repressed TGFβ‐mediated AP‐1 (activator protein‐1) and plasminogen activator inhibitor‐1 (PAI‐1) promoters, EVI1Del190–515 elicited a slight increase in both promoter activities. Expression of EVI1 and EVI1Del427–515 (but not EVI1Del190–515) in OVCAR8 ovarian cancer cells increased cyclin E1 LMW expression and cell cycle progression. Furthermore, knockdown of specific EVI1 splice variants (both MDS1/EVI1 and EVI1Del190–515) markedly increased claudin‐1 mRNA and protein expression in HEY ovarian and MDA‐MB‐231 breast cancer cells. Changes in claudin‐1 were associated with alterations in specific epithelial–mesenchymal transition markers concurrent with reduced migratory potential. Collectively, EVI1 is frequently aberrantly spliced in ovarian cancer with specific forms eliciting altered functions which could potentially contribute to ovarian cancer pathophysiology. Highlights: ► Similar to wild type, EVI1Del190–515 splice variant is elevated in ovarian cancers.► EVI1Del190–515 retains binding to SMAD3/CtBP1 with increased PML co‐localization.► EVI1Del190–515 differentially modulates TGFβ‐mediated PAI‐1 promoter activity.► Wild type EVI1 and EVI1Del427–515 similarly modulate cyclin E1 in OVCAR8 cells.► siRNA targeting both MDS1/EVI1 and EVI1Del190–515 alters claudin‐1 and motility. [ABSTRACT FROM AUTHOR]

Abstract: EngA is an essential protein involved in ribosome biogenesis. It is an unique GTPase, possessing two consecutive G-domains. Using sequence and phylogenetic analysis, we found two intriguing variants among EngA homologues – one with a shorter linker joining the G-domains and another with a longer linker, which additionally possesses an extended C-terminus. Interestingly, while the former variant is mainly restricted to firmicutes, the latter is found in nonfirmicutes. Chimeric proteins with interchanged linkers and extensions were generated to gauge the importance of these elements. Ribosome interaction experiments employing the chimeric proteins suggest that a precise combination of the linker and C-terminal extension are important features regulating EngA ribosome interactions in a variant-specific manner. [Copyright &y& Elsevier]

The oil in Camelina sativa L. Crantz has a combined linolenic and linoleic acid content that is greater than 50% and a relatively low saturated FA content (∼10%). Although the FA composition has been reported, no information is available on the sterol composition of camelina oil. The derivatized plant sterols were separated and quantified with capillary GC and their identity confirmed with GC-MS. The refined camelina oil sample contained approximately 0.54 wt% unsaponifiables, and over 80% of the unsaponifiables were desmethylsterols. Perhaps the most unusual characteristic of camelina oil is its relatively high content of cholesterol, particularly for a vegetable oil, since it contains several times the cholesterol found in other “high-cholesterol” vegetable oils. Camelina oil also contains relatively large amounts of another unusual sterol, brassicasterol. The major sterols identified in the camelina oil included cholesterol (188 ppm), brassicasterol (133 ppm), campesterol (893 ppm), stigmasterol (103 ppm), sitosterol (1,884 ppm), and Δ5-avenasterol (393 ppm). [ABSTRACT FROM AUTHOR]

Walnuts ( Juglans regia L.) were collected during the 1997 harvest from 13 different cultivars of trees grown in a replicated trial in an experimental orchard at Lincoln University. Two U.S. commercial cultivars (Tehama and Vina), three European commercial cultivars (Esterhazy, G139, G120), and eight New Zealand selections (Rex, Dublin’s Glory, Meyric, Stanley, Mckinster, 150, 151, 153) were evaluated. Total lipids were analyzed for fatty acids by capillary gas chromatography, tocopherols by high-performance liquid chromatography, and oxidation stability by Rancimat. The total oil content of the nuts ranged from 64.2 to 68.9% while the stability of the oil ranged from 3.9 to 7.8 h. The oleic acid content of the oils ranged from 12.7 to 20.4% of the total fatty acids, while 18:2 content ranged from 57.0 to 62.5% and the 18:3 contents ranged from 10.7 to 16.2%. Reduced stability of the oil as measured by the Rancimat method appears to be correlated to higher levels of 18:2 in the extracted oil. The total tocopherol contents of these nuts ranged from 268.5 to 436.0 µg/g oil. γ-Tocopherol dominated the profile while α-tocopherol was only 6% of the total content. Peroxide values of the fresh oil were measured spectrophotometrically to give an indication of the overall stability. The levels of total tocopherols when combined with the level of unsaturation in the oil in a multiple regression analysis had a significant relationship ( R 2=45.2%, P<0.001) with the peroxide value in the oil. [ABSTRACT FROM AUTHOR]

Hazelnut ( Corylus avellana L.) samples were collected from six different cultivars of trees grown in an experimental orchard at Lincoln University. Three U.S. commercial cultivars (Butler, Ennis, and Barcelona), two European commerical cultivars (Tonda di Giffoni and Campanica), and one New Zealand selection (Whiteheart) were evaluated. The total oil, stability to oxidation of the oil, and fatty acid, tocopherol, and sterol composition were determined on samples of freshly extracted hazelnut oil. The total oil content of the seeds ranged from 54.6 to 63.2% while the stability of the oil, as measured by the Rancimat test ranged from 15.6 to 25.3 h. The content of the monounsaturated oleic acid in the oils ranged from 73.8 to 80.1% of the total fatty acids, while the tocopherol content ranged from 225.8 to 552.0 mg/g freshly extracted oil. The major desmethylsterols were sitosterol, ranging from 1416 to 1693 µg/g, campesterol, ranging from 78 to 114 µg/g, and Δ5-avenasterol, ranging from 110 to 170 µg/g. The oil extracted from the cultivar Whiteheart was more stable (measured by Rancimat) than the oil from all other cultivars grown at the same location and under the same conditions. Whiteheart contained higher levels of total and γ-tocopherol when compared to the other cultivars. The higher levels of tocopherol in Whiteheart help to explain the greater stability of the oil during the oxidative stress test. These results suggest that nuts from the cultivar Whiteheart could be stored longer than the other nuts tested. [ABSTRACT FROM AUTHOR]

A digital high-accuracy interface for sine--cosine shaft encoders (SCE) is proffered. The outputs of SCE vary as a sine and cosine functions of shaft angle. The proposed interface processes these outputs and renders a linear direct-digital output for 360° operating range. The interface has minimal dependence on many circuit non-idealities including the phase error of quadrature oscillator. The performance of the interface is verified using simulation and emulation-based studies. Furthermore, the interface is tested with a magneto-resistance-based SCE. Test results show that the output non-linearity remains around 0.27% for typical values of phase errors. The interface also possesses features such as low-component count, high linearity, direct-digital output etc. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have validated a strong association of atherosclerosis with the CDKN2A/B locus, a locus harboring three tumor suppressor genes: p14 ARF , p15 INK4b , and p16 INK4a . Post-GWAS functional analysis reveals that CUX is a transcriptional activator of p16 INK4a via its specific binding to a functional SNP (fSNP) rs1537371 on the atherosclerosis-associated CDKN2A/B locus, regulating endothelial senescence. In this work, we characterize SATB2, another transcription factor that specifically binds to rs1537371. We demonstrate that even though both CUX1 and SATB2 are the homeodomain transcription factors, unlike CUX1, SATB2 is a transcriptional suppressor of p16 INK4a and overexpression of SATB2 competes with CUX1 for its binding to rs1537371, which inhibits p16 INK4a and p16 INK4a -dependent cellular senescence in human endothelial cells (ECs). Surprisingly, we discovered that SATB2 expression is transcriptionally repressed by CUX1. Therefore, upregulation of CUX1 inhibits SATB2 expression, which enhances the binding of CUX1 to rs1537371 and subsequently fine-tunes p16 INK4a expression. Remarkably, we also demonstrate that IL-1β, a senescence-associated secretory phenotype (SASP) gene itself and a biomarker for atherosclerosis, induces cellular senescence also by upregulating CUX1 and/or downregulating SATB2 in human ECs. A model is proposed to reconcile our findings showing how both primary and secondary senescence are activated via the atherosclerosis-associated p16 INK4a expression., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Impaired mitochondrial autophagy (mitophagy) and NLRP3 inflammasome activation have been incriminated in the pathogenesis of T2DM. Metformin besides being an insulin sensitizer also induces autophagy; however, its effect on mitophagy and NLRP3 activation in patients with T2DM still remains elusive. Forty-five drug-naïve T2DM patients with HbA 1C 7%-9% (53-75 mmol/mol) were randomly assigned to receive either metformin, voglibose, or placebo for 3 months, and were also recommended for lifestyle intervention programme (n = 15 each). Mitochondrial oxidative stress (MOS) parameters, qPCR and immunoblotting of mitophagy-related markers (PINK1, PARKIN, MFN2, NIX, LC3-II, LAMP2), p-AMPKα (T172), and NLRP3 proteins, as well as transmission electron microscopy (TEM) for assessing mitochondrial morphology were performed in the mononuclear cells of study patients. Both metformin and voglibose showed a similar efficacy towards the reduction in HbA 1c and MOS indices. However, multivariate ANCOVA divulged that mRNA and protein expression of mitophagy markers, NLRP3 and p-AMPKα (T172), were significantly increased only with metformin therapy. Moreover, PINK1 expression displayed a significant positive association with HOMA-β indices, and TEM studies further confirmed reduced distortions in mitochondrial morphology in the metformin group only. Our observations underscore that metformin upregulates mitophagy and subsequently ameliorates the altered mitochondrial morphology and function, independent of its glucose-lowering effect. Further, restoration of normal mitochondrial phenotype may improve cellular function, including β-cells, which may prevent further worsening of hyperglycaemia in patients with T2DM., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD-1) are immune checkpoint proteins expressed in T cells. Although CTLA4 expression was found in multiple tumours including non-small cell lung cancer (NSCLC) tissues and cells, its function in tumour cells is unknown. Recently, PD-1 was found to be expressed in melanoma cells and to promote tumorigenesis. We found that CTLA4 was expressed in a subset of NSCLC cell lines and in a subgroup of cancer cells within the lung cancer tissues. We further found that in NSCLC cells, anti-CTLA4 antibody can induce PD-L1 expression, which is mediated by CTLA4 and the EGFR pathway involving phosphorylation of MEK and ERK. In CTLA4 knockout cells, EGFR knockout cells or in the presence of an EGFR tyrosine kinase inhibitor, anti-CTLA4 antibody was not able to induce PD-L1 expression in NSCLC cells. Moreover, anti-CTLA4 antibody promoted NSCLC cell proliferation in vitro and tumour growth in vivo in the absence of adaptive immunity. These results suggest that tumour cell-intrinsic CTLA4 can regulate PD-L1 expression and cell proliferation, and that anti-CTLA4 antibody, by binding to the tumour cell-intrinsic CTLA4, may result in the activation of the EGFR pathway in cancer cells., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)