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Hand foot skin reaction (HFSR) is a common dose-limiting adverse effect of multi kinase inhibitors (MKI) whose mechanism is not fully understood, and the prophylaxis is inadequate. In this pilot study, a double-blind, randomized placebo-controlled trial was conducted to evaluate the effect of topical urea in secondary prevention of sunitinib-induced HFSR in renal cell cancer patients. Out of 55 screened patients, 14 were randomized to receive topical urea or placebo for four weeks. The association of HFSR with drug levels of sunitinib and its metabolite (n-desethyl sunitinib), genetic polymorphism of VEGFR2 gene, quality of life (QOL) and biochemical markers was also assessed. The results showed that urea-based cream was not superior to placebo (P =.075). There was no change in the QOL in both the groups. Single nucleotide polymorphism was checked for two nucleotides rs1870377 and rs2305948 located in VEGFR2 gene on chromosome 4. SNP (variant T > A) at rs1870377 was associated with appearance of new HFSR as compared to the wild type, although the association was not statistically significant (OR 0.714). There was no statistically significant difference between mean plasma levels of sunitinib and N-desethyl sunitinib in urea arm as compared to placebo arm as compared to placebo. The best fit population pharmacokinetic model for sunitinib was one compartment model with first order absorption and linear elimination. The median (IQR) of population parameters calculated from the population pharmacokinetics model for Ka, V and Cl was 0.22 (0.21-0.24) h-1, 4.4 (4.09-4.47) L, 0.049 (0.042-0.12) L/hr, respectively. The study suggested that the urea-based cream was not superior to placebo in decreasing the appearance of new HFSR in renal cancer patients receiving 4:2 regimen of sunitinib. In this randomized, placebo-controlled trial, urea cream was found to be non-superior to placebo in prevention of hand-foot skin reaction with no change in QoL. SNP at rs1870377 was associated with appearance of new HFSR. There was no difference between the plasma levels of sunitinib and n-desethyl sunitinib. The best-fit popPK model was one-compartment with first-order absorption and linear elimination. [ABSTRACT FROM AUTHOR]

Ion irradiation induced recovery of defects in 3C–SiC caused by electronic energy loss (S e) in the intermediate energy regime (a few 100s of keV to a few 10s of MeV) is less explored. Towards this, separate and sequential ion irradiation of 200 keV Si+ ions and 14 MeV Si+ ions in 3C–SiC were carried out. In our earlier work, RBS/C findings demonstrated that 14 MeV Si+ ion irradiation (S e - 4.9 keV/nm) resulted in defect recovery in 3C–SiC pre-damaged with 200 keV Si+ ions [1]. The present work investigates the strain and structural evolution using High-resolution X-ray diffraction (HRXRD), Reciprocal space mapping (RSM), X-ray absorption near edge spectroscopy (XANES) and Diffuse reflectance spectroscopy (DRS), in the 3C–SiC layer as a result of ion irradiation induced defect production and recovery. HRXRD results revealed that 200 keV Si+ ion results in 4 % of strain at the projected range of ions and strain relaxation as a result of ionization-induced annealing is observed after subsequent 14 MeV Si+ ion irradiation. RSM measurements showed evidence for the formation of extended defects in sequentially ion irradiated samples. Optical characterization using DRS measurements indicates a reduction of refractive index in the ion-irradiated layer, however, for the amorphous SiC layer (ion dose: 0.6 dpa, 200 keV Si+ ion), the refractive index increased due to a reduction in mass density. Modification of refractive index in the ion irradiated layer is a result of the combination of negative change in volume effect and positive change in electronic polarizability. [Display omitted] [ABSTRACT FROM AUTHOR]

The main motive of the present study is to determine the closed form solution of the generalized Riemann Problem (GRP) for the 1-D Euler's equation for Chaplygin gas by using the Differential Constraint Method (DCM). The consistency conditions and differential constraint for the governing model is determined. Also, the compatibility condition between differential constraints and Chaplygin gas model is computed here. Further, to obtain an exact (closed form) solution of Generalized Riemann Problem (GRP), we characterize the solution for a smooth arbitrary function as initial data. Ultimately, we solve the GRP with generalized discontinuous initial data. [ABSTRACT FROM AUTHOR]

In Drug–Drug-Interaction (DDI), the task is to predict the (adverse) effect of administering two drugs simultaneously. Currently, the techniques proposed in this direction are generally based on either shallow learning paradigms like Random Decision Forest (RDF), Logistic Regression (LR), Support Vector Machines (SVM), etc., or deep Convolutional Neural Networks (CNNs). However, specific works combine traditional machine learning (ML) algorithms such as RDF, LR, SVM, and deep learning paradigms such as CNNs in a piecemeal fashion which might not be optimal. Hence, the present work proposes a framework that presents a joint end-to-end solution. We propose a Siamese-like architecture with two processing channels' networks based on deep convolutional transform learning. Common fused representations as well as channel-wise representations are learnt, in addition with the transform across them. The final representation is passed to a decision forest to give final predictions. The proposed method is thus a supervised end-to-end multi-channel fusion framework that (i) learns unique and interpretable filters in contrast with CNNs, and (ii) jointly learns and optimizes decision forest in contrast with state-of-the-art piecemeal approach. We apply this technique to identify DDIs among 1059 drugs from the DrugBank database showing superiority of our method compared to the state-of-the-art(s). • The work proposes a supervised multi-channel information fusion framework. • It is based on Deep Convolutional Transform Learning and Decision Forests. • The practical goal is to perform classification tasks on drug–drug interaction data. • It improves over the state-of-the-art methods. [ABSTRACT FROM AUTHOR]

The present paper concerns with the propagation of weak shock waves in a dusty gas governed by the quasilinear hyperbolic partial differential equations. Using the method of wavefront analysis the transport equations governing the evolution of weak discontinuities are derived. Transport equations are used to determine the shock formation distance and conditions which ensure that there will not evolve any shock. Also the influence of dust particles, ratio of specific heats and upstream flow Mach number on the shock formation distance is analyzed. • The paper concerns with the propagation of weak shock waves in a dusty gas. • Method of wavefront analysis is used to derive the transport equations. • The shock formation distance is computed from the derived transport equations. • The conditions which ensure that there will not evolve any shock is obtained. • Influence of dust particles and Mach number on the shock formation is analyzed. [ABSTRACT FROM AUTHOR]

Highlights • Effect of thermal annealing on FeCoNbB thin film having different thicknesses has been studied. • UMA gradually decreases with annealing and disappears upon annealing at 773 K. • Growth induced anisotropic tensile stresses as the possible origin of observed UMA. • Nb addition improves thermal stability, inhibits grain growth and stabilises bcc-FeCo phase. • FeCoNbB films are proposed as potential material for magnetic electrode in MTJ applications. Abstract Influence of thermal annealing on the ion beam sputtered FeCo(Nb)B quaternary alloy thin films having thickness ∼20 nm and 80 nm was investigated. Regardless of amorphous microstructure, the as-deposited films possess uniaxial magnetic anisotropy (UMA) in the film plane. Annealing at temperature ∼503 K results in amorphous to nanocrystalline phase transformation with precipitation of bcc-FeCo phase. With increasing annealing temperature, magnetic anisotropy gradually decreases and thermal annealing at 773 K results in complete disappearance of UMA. In-plane strain distribution in such nanocrystalline FeCo(Nb)B thin films was obtained by using laboratory and synchrotron X-ray diffraction (XRD) measurements. In-plane and out-of-plane X-ray diffraction measurements suggest, growth induced long range non-uniform tensile stress, as the possible origin of in-plane uniaxial magnetic anisotropy in such films. It is demonstrated that the stress distribution becomes uniform after annealing at 773 K and results in complete disappearance of magnetic anisotropy. The study further suggests that the presence of Nb in FeCoB film improves the thermal stability, inhibits grain growth and stabilizes bcc-FeCo phase up to elevated temperatures. This information is useful for magnetic tunnel junction application, where annealing of FeCoB magnetic electrode is essential. [ABSTRACT FROM AUTHOR]

The main motive of the present paper is to derive the analytical solution of the Riemann problem for magnetogasdynamic equations governing an inviscid unsteady one-dimensional flow of non-ideal polytropic gas subjected to the transverse magnetic field with infinite electrical conductivity. By using the Lax entropy condition and R–H conditions, we derive the elementary wave solutions i.e. shock wave, simple wave and contact discontinuities without any restriction on the magnitude of initial data states and discussed about their properties. Further, the density and velocity distribution in the flow field for the cases of compressive wave and rarefaction wave is discussed. Here we also compare/contrast the nature of solution in non-ideal magnetogasdynamic flow and ideal gas flow. • Solution of the Riemann Problem for non-ideal magnetogasdynamics flow is obtained. • Lax entropy and R–H conditions are used to derive elementary wave solutions. • Density and velocity profiles for 1- and 3-shock wave is presented. • Effect of non-idealness of the gas in the presence of magnetic field is analyzed. [ABSTRACT FROM AUTHOR]

Abstract Plant growth-promoting rhizobacteria (PGPR) are beneficial rhizosphere derived bacteria that have the capability to colonize plant roots and are used to enhance plant growth or suppress disease caused by various phytopathogens. The fourteen isolates were screened on the basis of in vitro antagonistic activity against the root rot pathogen Rhizoctonia solani but in the present study, we have selected, two strains of rhizobacteria (Pseudomonas aeruginosa BHU B13-398 and Bacillus subtilis BHU M) through initial screening as well as their in vitro antagonistic potential activity against the root rot pathogen Rhizoctonia solani. These isolates were then tested in vitro for their specific PGPR traits, such as phosphate solubilization, ammonia, siderophore and HCN production. Both the isolates were found to be promising agents for all the tested PGPR traits. Among the two isolates, BHU B13-398 showed highest plant growth promoting attributes. Pot experiments were conducted on mung bean to evaluate their plant growth promotion potential under the controlled green house conditions (14 h light, 10 h dark, and temperature at 27 ± 2 °C). The results revealed that both the isolates (BHU B13-398 and BHU M) enhanced the growth parameters of mung bean such as root length, shoot length, root as well as shoot fresh and dry weight, leaf area and chlorophyll content compared to uninoculated control plants. Our results clearly demonstrated that both the isolates BHU B13-398 and BHU M displayed 32.26%, 84.60% and 13.38%, 61.94%, increase in shoot length, and root length respectively, as compared to uninoculated control. Mung bean root sections inoculated with respective strains were observed through scanning electron microscopy (SEM) to validate mung bean root colonizing abilities of the strains. The SEM observation confirmed that both strains BHU B13-398 and BHU M seem to be a good root colonizer and have high population densities on the root surface. Highlights • Isolation and identification of root rot pathogen Rhizoctonia solani and rhizobacteria (Pseudomonas aeruginosa BHU B13-398 and Bacillus subtilis BHUM). • In vitro screening of rhizobacteria for antagonistic potential against Rhizoctonia solani. • The results revealed that both the isolates (BHU B13-398 and BHU M) enhanced the growth parameters of mung bean compared to uninoculated control plants. • In vitro plant growth promotion study through pot experiments and were found to frequently colonize the rhizospheric region associated with the mung bean. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) provides an effective cancer treatment option but it requires sufficient cellular oxygen concentration to exert its photosensitizing effects. Due to hypoxic nature of most tumors, widespread clinical application of PDT is restricted and warrants development of photosensitizers which can kill cancer cells in ROS independent manner. Previously, we reported significant enhancement of the anti-cancer property of coralyne in presence of ultraviolet-A (UVA) light exposure against several human carcinoma cell lines. This study aimed at unravelling molecular cascades of events in CUVA treatment ( c oralyne and UVA light)-mediated photosensitization of human skin cancer. The CUVA-treatment caused robust apoptosis of A431 cancer cells, primarily through mitochondrial and lysosomal dysfunctions. Silencing of BAX conferred a significant protection against CUVA-induced apoptosis. Both lysosomal proteases and caspase-8 activation contributed to BID cleavage. Further, our results revealed that a dual signaling axis e.g., ATR-p38 MAPK and JAK2-STAT1 pathways functioned upstream of BAX activation in apoptosis response. Moreover, transient silencing of ATR and pharmacological inhibition of p38-MAPK or JAK2 significantly abolished the effect of CUVA treatment induced BAX expression and cell death, linking the extrinsic and intrinsic pathways with the observed cell death. Our data suggest that coralyne, which is known topoisomerase-I inhibitor, may be an attractive agent for photo-chemotherapeutic treatment of human skin cancers. [ABSTRACT FROM AUTHOR]

A total of 10 species of Baylisascaris , a genus of ascaridoid nematodes, occur worldwide and 6 of them occur in the New World. Most of the Baylisascaris species have a similar life cycle with carnivorous mammals or marsupials serving as definitive hosts and a smaller prey host serving as paratenic (or intermediate) hosts. However, one species in rodents is unique in that it only has one host. Considerable research has been conducted on B. procyonis, the raccoon roundworm, as it is a well-known cause of severe to fatal neurologic disease in humans and many wildlife species. However, other Baylisascaris species could cause larva migrans but research on them is limited in comparison. In addition to concerns related to the potential impacts of larva migrans on potential paratenic hosts, there are many questions about the geographic ranges, definitive and paratenic host diversity, and general ecology of these non-raccoon Baylisascaris species. Here, we provide a comprehensive review of the current knowledge of New World Baylisascaris species, including B. columnaris of skunks, B. transfuga and B. venezuelensis of bears, B. laevis of sciurids, B. devosi of gulonids, B. melis of badgers, and B. potosis of kinkajou. Discussed are what is known regarding the morphology, host range, geographic distribution, ecoepidemiology, infection dynamics in definitive and paratenic hosts, treatment, and control of these under-studied species. Also, we discuss the currently used molecular tools used to investigate this group of parasites. Because of morphologic similarities among larval stages of sympatric Baylisascaris species, these molecular tools should provide critical insight into these poorly-understood areas, especially paratenic and definitive host diversity and the possible risk these parasites pose to the health to the former group. This, paired with traditional experimental infections, morphological analysis, and field surveys will lead to a greater understanding of this interesting and important nematode genus. [ABSTRACT FROM AUTHOR]

The DNA damage response (DDR) and epithelial-to-mesenchymal transition (EMT) are two crucial cellular programs in cancer biology. While the DDR orchestrates cell-cycle progression, DNA repair, and cell death, EMT promotes invasiveness, cellular plasticity, and intratumor heterogeneity. Therapeutic targeting of EMT transcription factors, such as ZEB1, remains challenging, but tumor-promoting DDR alterations elicit specific vulnerabilities. Using multi-omics, inhibitors, and high-content microscopy, we discover a chemoresistant ZEB1-high-expressing sub-population (ZEB1hi) with co-rewired cell-cycle progression and proficient DDR across tumor entities. ZEB1 stimulates accelerated S-phase entry via CDK6, inflicting endogenous DNA replication stress. However, DDR buildups involving constitutive MRE11-dependent fork resection allow homeostatic cycling and enrichment of ZEB1hi cells during transforming growth factor β (TGF-β)-induced EMT and chemotherapy. Thus, ZEB1 promotes G1/S transition to launch a progressive DDR benefitting stress tolerance, which concurrently manifests a targetable vulnerability in chemoresistant ZEB1hi cells. Our study thus highlights the translationally relevant intercept of the DDR and EMT. [Display omitted] • Intercellular heterogeneity in ZEB1 levels is a general feature of cancer cells • ZEB1 promotes G1/S transition via CDK6 to inflict endogenous DNA replication stress • Replication stress tolerance in ZEB1hi cells requires MRE11-engaging DDR adaptation • DDR buildups render ZEB1hi cells chemoresistant but sensitive to MRE11 inhibition ZEB1 is heterogeneously expressed in cancer cells. Characterizing sub-populations with high ZEB1 levels (ZEB1hi), Schuhwerk et al. show that ZEB1 induces G1/S transition via CDK6 to launch an adaptive MRE11-involving response promoting chemoresistance. Targeting of ZEB1hi cells by MRE11 inhibition allows chemosensitization, reinforcing the translational impact of the EMT-DDR interface. [ABSTRACT FROM AUTHOR]

Polypeptides have potential to be designed as drugs or inhibitors against the desired targets. In polypeptides, every chiral α-amino acid has enantiomeric structural possibility to become l or d amino acids and can be used as design monomer. Among the various possibilities, use of stereochemistry as a design tool has potential to determine both functional specificity and metabolic stability of the designed polypeptides. The polypeptides with mixed l , d amino acids are a class of peptidomimitics, an attractive drug like molecules and also less susceptible to proteolytic activities. Therefore in this study, a three step algorithm is proposed to design the polypeptides against desired drug targets. For this, all possible configurational isomers of mixed l , d polyleucine (Ac-Leu 8 -NHMe) structure were randomly modeled with simulated annealing molecular dynamics and the resultant library of discrete folds were scored against HIV protease as a model target. The best scored folds of mixed l , d structures were inverse optimized for sequences in situ and the resultant sequences as inhibitors were validated for conformational integrity using molecular dynamics. This study presents and validates an algorithm to design polypeptides of mixed l , d structures as drugs/inhibitors by inverse fitting them as molecular ligands against desired target. [ABSTRACT FROM AUTHOR]

Understanding the variability in intra-urban forms is essential for protecting future-proofing cities from climate volatilities. However, the classification of urban forms is costly due to its reliance on high-resolution datasets, limited in the Global South's low-income cities. Additionally, the current classifiers are constrained in characterizing urban forms in heterogeneous cities where the built environment has an isomorphic footprint but vary in urban canopy parameters. Existing methodologies have constraints on using unstructured low-resolution datasets like images and portable document formats to classify intra-urban forms. This study breaks ground by forwarding a novel end-to-end multi-channel supervised data fusion framework, GeoInFuse, to classify different urban form typologies in heterogeneous hyper-dense cities. It uses a state-of-the-art deep learning network on open-source image-based datasets to generate urban form classification. Three datasets (two for ground truth and one containing multi-dimensional urban canopy parameters) are used to demonstrate the framework. The parameters as channels were fused to generate urban form classes. Results show that the GeoInFuse could extract the heterogeneous urban form classes with 74.9. • Characterizing heterogeneous urban form in data scarce cities from open-dataset • Novel GeoInFuse framework based on deep-learning is proposed for classification. • GeoInFuse fuses unstructured open image datasets to classify urban form typologies. • Urban form types in Mumbai were reliably classified from policy variables. • GeoInFuse can be used for climate-proofing transitional cities of Global-South. [ABSTRACT FROM AUTHOR]

Arsenic (As) is a toxic metalloid contaminating the environment. The aim of this research was to find out the effect of enhanced level of As in soil on developmental ultrastructure of guard cells of stomata and glandular trichomes on leaves of Vigna radiata (mung bean) . Stomata were adversely affected. Stomatal index showed a concomitant increase with rise in As level in soil. Stomatal size was reduced and at higher concentrations of As stomatal aperture was permanently closed. Also, frequency of arrested, fused and abnormal stomata increased. Guard cells in plants exposed to As displayed much vacuolation and poor cytoplasmic differentiation. At high concentration (30 mg As kg −1 soil), loss of structural organization and disintegration of cytoplasm were observed. Cytoskeleton of guard cells is sensitive to As and stomatal structure and development suffered due to microtubular disruption and organelle disorganization. Trichome density decreased with increase in concentration of As in soil on both upper and lower leaf surfaces. In As-treated leaves, trichomes were smaller in size and displayed structural disruption. Energy dispersive X-ray microanalysis revealed that the spatial distribution of As in leaves was such that the highest concentration occurred in epidermal tissues. No As was detected in mesophyll tissue. However, presence of As was recorded in the epidermal cells and the trichomes. Arsenic storage in the trichome could be a detoxification mechanism. The findings from the present study imply that more attention needs to be paid to the role of trichomes in understanding uptake and accumulation of As in plants. [ABSTRACT FROM AUTHOR]

Abstract: We probed aromatic–protein interactions based on specificity of enrichment of protein residues across a contact-based cutoff. Thus, 155 protein–NAD+/NADP+ complexes were analyzed for enrichments within 10Å of centroids of aromatic groups of the ligand when the residues were contacted and not contacted with the aromatic ligand. Specifically, neutral-adenine and cationic-nicotinamide groups of the oxidized coenzymes evoked interest to know whether the contrast of charge or the shared aromaticity will manifest in the enrichments across the cutoff. We found that when in contact, the enrichments are highly specific for nicotinamide and adenine-aromatic structures, and thus possibly complex in the basis, but when not in contact, they are generic for charge and aromaticity of the structures, and thus possibly specific in the basis. The order of enrichments over the contacted residues is Tyr>Cys>Thr>His>Asn>Ser>Met>Ile>Phe against nicotinamide–π+ structure and Asp>Ile>Thr>His>Arg>Tyr>Gly>Val against adenine–π structure, while the order over the non-contacted residues is Trp>Gly>His>Asn>Cys>Met>Tyr>Ser>Thr>Phe against nicotinamide–π+ structure and Asn>Thr>Ser>Gly>Cys>His>Val against adenine–π structure. Neutral Trp, His, Tyr, and Phe, but not cationic Arg, are thus the non-contacted residues enriched specifically against nicotinamide–π+ structure, while Asn, Gly, Thr, Ser, and Cys are the non-contacted residues enriched generically against both the nicotinamide–π+ and adenine–π aromatic structures. By analyzing the enriched groups in their geometric specificities, we found that, the enrichments against nicotinamide cation manifest the specificity expected of cation–π interaction and against nicotinamide- and adenine-aromatic groups manifest the specificity expected of dipole–π interaction. The cutoff-based method is proven valuable in probing protein–ligand interactions in the physics involved. [Copyright &y& Elsevier]

Abstract: Background: Informed consent document plays an integral part in the process of obtaining informed consent. Although India is fast gaining repute as a preferred clinical trial destination, only few studies have evaluated the compliance of informed consent documents with the Indian Good Clinical Practice guideline. Methods: Retrospective analysis of consent documents submitted to the institutional ethics committee during the periods January 2007–July 2008 and August 2008–December 2009, for the inclusion of 14 essential information elements outlined in the Indian Good Clinical Practice guideline was carried out. Cumulative scores were given for compliance with the guideline and for vernacular translations of the consent documents. Results: Majority of the informed consent documents analyzed were for academic projects in both periods. There was marked improvement in the documents in terms of compliance with Indian GCP in the period 2008–09. The mean cumulative score for consent documents for academic projects increased significantly from 7.00±0.25 in 2007–08 to 8.57±0.16 in 2008–09. The mean score for consent documents for pharmaceutical sponsored studies also increased from 10.23±0.17 in 2007–08 to 11.31±0.32 in 2008–09. Additionally, greater number of consent documents had been translated into vernacular language in the period 2008–29. Conclusions: The increased compliance with the good clinical practice guideline and improvement in the mean cumulative scores in 2008–09 was probably the outcome of greater awareness amongst the clinical researchers within the institute. [Copyright &y& Elsevier]

Long-lasting allergen treatment is the most efficient therapy in alopecia areata (AA). The underlying mechanism is unknown. We here asked whether treatment with a contact sensitizer influences leukocyte migration such that dendritic cell (DC) migration or the recruitment of activated T-cells towards the skin become hampered. Allergen treatment of AA mice was not accompanied by a decrease in skin-infiltrating leukocytes or draining lymph node cells (LNC). However, the distribution of leukocyte subsets was changed with a dominance of monocytes in the skin and a reduced percentage of DCs in draining nodes. Chemokine and chemokine receptor expression in skin and draining nodes was strikingly increased and LNC from untreated and allergen-treated AA mice showed high migratory activity in vitro and readily homed in draining nodes and skin after intravenous injection. However, FITC labelling of the skin and subcutaneous transfer of dye-labelled DC revealed that allergen treatment created a chemokine milieu severely hampering DC migration from the skin towards the draining node. An allergic eczema-induced reduction in DC migration and antigen transfer could well contribute to insufficient T-cell activation and the recovery of hair follicle in AA and possibly be of relevance for other skin-related autoimmune diseases.Journal of Investigative Dermatology (2006) 126, 1559–1573. doi:10.1038/sj.jid.5700328; published online 4 May 2006 [ABSTRACT FROM AUTHOR]

The cutaneous sinus tract of dental origin is an uncommon but well documented condition. Its diagnosis is not always easy unless the treating clinician considers the possibility of its dental origin. Such patients may undergo multiple surgical excisions, biopsies, and antibiotic regimens, but all of them fail with the recurrence of the sinus tract. This is because the primary etiology is incorrectly diagnosed. This case report describes the treatment of four patients presenting with variable complaints of pain and purulent or hemorrhagic discharge from lesions of the face. Clinical and radiographic examination revealed carious teeth with radiolucent areas indicating chronic periradicular abscess. The teeth were restorable, so nonsurgical endodontic therapy was performed in all of them. No systemic antibiotic therapy was provided. The patients responded well, and the cutaneous lesions healed uneventfully. Improper diagnosis can lead to needless loss of teeth that can be otherwise maintained through timely and proper management. [Copyright &y& Elsevier]

This work proposes a supervised multi-channel time-series learning framework for financial stock trading. Although many deep learning models have recently been proposed in this domain, most of them treat the stock trading time-series data as 2-D image data, whereas its true nature is 1-D time-series data. Since the stock trading systems are multi-channel data, many existing techniques treating them as 1-D time-series data are not suggestive of any technique to effectively fusion the information carried by the multiple channels. To contribute towards both of these shortcomings, we propose an end-to-end supervised learning framework inspired by the previously established (unsupervised) convolution transform learning framework. Our approach consists of processing the data channels through separate 1-D convolution layers, then fusing the outputs with a series of fully-connected layers, and finally applying a softmax classification layer. The peculiarity of our framework, that we call SuperDeConFuse (SDCF), is that we remove the nonlinear activation located between the multi-channel convolution layers and the fully-connected layers, as well as the one located between the latter and the output layer. We compensate for this removal by introducing a suitable regularization on the aforementioned layer outputs and filters during the training phase. Specifically, we apply a logarithm determinant regularization on the layer filters to break symmetry and force diversity in the learnt transforms, whereas we enforce the non-negativity constraint on the layer outputs to mitigate the issue of dead neurons. This results in the effective learning of a richer set of features and filters with respect to a standard convolutional neural network. Numerical experiments confirm that the proposed model yields considerably better results than state-of-the-art deep learning techniques for the real-world problem of stock trading. • The work proposes a novel supervised learning framework, for fusion of multi-channel information. • It is based on the recently established Convolutional Transform Learning technique. • The practical goal is to perform classification tasks on stock trading financial data. • The model keeps up with the univariate and sequential nature of the time-series financial data. • It improves over the state-of-the-art methods. [ABSTRACT FROM AUTHOR]

[Display omitted] Werner (WRN) expression is epigenetically downregulated in various tumors. It is imperative to understand differential repair process in WRN-proficient and WRN-deficient cancers to find pharmacological targets for radio-sensitization of WRN-deficient cancer. In the current investigation, we showed that pharmacological inhibition of CHK1 mediated homologous recombination repair (HRR), but not non-homologous end joining (NHEJ) repair, can causes hyper-radiosensitization of WRN-deficient cancers. This was confirmed in cancer cell lines of different tissue origin (osteosarcoma, colon adenocarcinoma and melanoma) with WRN silencing and overexpression. We established that WRN-depleted cells are dependent on a critical but compromised CHK1-mediated HRR-pathway for repairing ionizing radiation (IR) induced DSBs for their survival. Mechanistically, we unraveled a new finding that the MRE11, CTIP and WRN proteins are largely responsible for resections of late and persistent DSBs. In response to IR-treatment, MRE11 and CTIP-positively and WRN-negatively regulate p38-MAPK reactivation in a CHK1-dependent manner. A degradation resistant WRN protein, mutated at serine 1141, abrogates p38-MAPK activation. We also showed that CHK1-p38-MAPK axis plays important role in RAD51 mediated HRR in WRN-silenced cells. Like CHK1 inhibition, pharmacological-inhibition of p38-MAPK also hyper-radiosensitizes WRN-depleted cells by targeting HR-pathway. Combination treatment of CHK1-inhibitor (currently under various clinical trials) and IR exhibited a strong synergy against WRN-deficient melanoma tumor in vivo. Taken together, our findings suggest that pharmacological targeting of CHK1-p38-MAPK mediated HRR is an attractive strategy for enhancing therapeutic response of radiation treatment of cancer. [ABSTRACT FROM AUTHOR]