Target Classification in Synthetic Aperture Radar Images Using Quantized Wavelet Scattering Networks.

The need to classify targets and features in high-resolution imagery is of interest in applications such as detection of landmines in ground penetrating radar and tumors in medical ultrasound images. Convolutional neural networks (CNNs) trained using extensive datasets are being investigated recently. However, large CNNs and wavelet scattering networks (WSNs), which share similar properties, have extensive memory requirements and are not readily extendable to other datasets and architectures-and especially in the context of adaptive and online learning. In this paper, we quantitatively study several quantization schemes on WSNs designed for target classification using X-band synthetic aperture radar (SAR) data and investigate their robustness to low signal-to-noise ratio (SNR) levels. A detailed study was conducted on the tradeoffs involved between the various quantization schemes and the means of maximizing classification performance for each case. Thus, the WSN-based quantization studies performed in this investigation provide a good benchmark and important guidance for the design of quantized neural networks architectures for target classification.

An endogenous DNA adduct as a prognostic biomarker for hepatocarcinogenesis and its prevention by Theaphenon E in mice.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, mainly because of its poor prognosis. A valid mechanism-based prognostic biomarker is urgently needed. γ-hydroxy-1,N2 -propanodeoxyguanosine (γ-OHPdG) is an endogenously formed mutagenic DNA adduct derived from lipid peroxidation. We examined the relationship of γ-OHPdG with hepatocarcinogenesis in two animal models and its potential role as a prognostic biomarker for recurrence in HCC patients. Bioassays were conducted in xeroderma pigmentosum group A knockout mice and diethylnitrosamine-injected mice, both prone to HCC development. γ-OHPdG levels in the livers of these animals were determined. The effects of antioxidant treatments on γ-OHPdG and hepatocarcinogenesis were examined. Using two independent sets of HCC specimens from patients, we examined the relationship between γ-OHPdG and survival or recurrence-free survival. γ-OHPdG levels in liver DNA showed an age-dependent increase and consistently correlated with HCC development in all three animal models. Theaphenon E treatment significantly decreased γ-OHPdG levels in the liver DNA of xeroderma pigmentosum group A knockout mice and remarkably reduced HCC incidence in these mice to 14% from 100% in the controls. It also effectively inhibited HCC development in the diethylnitrosamine-injected mice. Using clinical samples from two groups of patients, our study revealed that higher levels of γ-OHPdG are strongly associated with low survival (P < 0.0001) and low recurrence-free survival (P = 0.007). CONCLUSION: These results support γ-OHPdG as a mechanism-based, biologically relevant biomarker for predicting the risk of HCC and its recurrence. (Hepatology 2018;67:159-170).

Attenuation of diabetic retinopathy in rats by ellagic acid through inhibition of AGE formation.

Diabetic retinopathy (DR) is a major concern for blindness all over the world. Diabetic retinopathy is associated with thickening of basement membrane, retinal thinning, retinal detachment, and pericyte death. Advanced glycation end products (AGEs) mediate the progression of DR by stimulating the expression of RAGE and VEGF which subsequently damages the blood-retinal barrier. Employing a set of in vitro protein glycation systems, earlier we demonstrated antiglycating potential of ellagic acid (EA). In this study, we evaluated the efficacy of EA to prevent in vivo accumulation of AGE and to ameliorate retinal changes in diabetic rats. Streptozotocin-induced diabetic rats were fed either with 0.2 or 2% EA in the diet for 12 weeks. Effect of EA on retinal function was assessed with electroretinogram (ERG). At the end of the experiment, rats were scarified and retina was collected. Histology was carried out with H&E staining and immunohistochemistry. Formation of AGE product (CML) and activation of RAGE was analyzed by immunoblotting and immunohistochemistry. Expression of GFAP, VEGF, Bax and HIF-1α was assessed by qRT-PCR and immunoblotting. Dietary supplementation of EA to diabetic rats resulted in: (1) inhibition of accumulation of CML and activation of RAGE in retina, (2) attenuation of expression of GFAP, VEGF, and HIF-1α in retina, (3) attenuation of cell death by reducing proapoptic mediator Bax and (4) amelioration of retinal thickness and function. In conclusion, EA attenuated the retinal abnormalities including angiogenesis, hypoxia and cell death by inhibiting AGE-RAGE mediated cellular events.

Carboxymethyl lysine induces EMT in podocytes through transcription factor ZEB2: Implications for podocyte depletion and proteinuria in diabetes mellitus.

Advanced glycation end-products (AGEs) are implicated in the pathogenesis of diabetic nephropathy (DN). N-carboxymethyl-lysine (CML) is one of the predominant AGEs that accumulate in all renal compartments of diabetic patients. Nevertheless, the direct effect of CML on podocyte biology has not been explored. In this study, we demonstrate the induction of the transcription factor Zeb2 in podocytes upon exposure to CML through activation of NF-kB signaling cascade. Zeb2 orchestrates epithelial-mesenchymal transformation (EMT), during which cell-cell and cell-extracellular matrix interactions are feeble and enable epithelial cells to become invasive. CML treatment induced both NF-kB and Zeb2 promoter activity and suppressed E-cadherin promoter activity. Inhibition of NF-kB activity prevented CML dependent induction of Zeb2 and loss of E-cadherin. While the exposure of podocytes to CML results in increased podocyte permeability, shRNA-mediated knockdown of Zeb2 expression abrogated CML-mediated podocyte permeability. Further, in vivo findings of elevated CML levels concurrent with increased expression of ZEB2 in glomeruli and proteinuria in diabetic rats confirm that CML-mediated manifestations in the kidney under chronic diabetes conditions. These in vitro and in vivo results envisage the novel axis of NFkB-ZEB2 in podocytes playing a significant role in eliciting EMT and pathogenesis of DN.

Altered ubiquitin-proteasome system leads to neuronal cell death in a spontaneous obese rat model.

BACKGROUND: Obesity is associated with various progressive age-related diseases, including neurological disorders. However, underlying molecular basis for increased risk of neurodegeneration in obesity is unknown. A suitable animal model would immensely help in understanding the obesity-linked neurological problems. METHODS: A spontaneously developed obese rat (WNIN/Ob) which is highly vulnerable for a variety of degenerative diseases was isolated from the existing WNIN stock rats. Ultrastructure of neurons in the cerebral cortex of 12-month old obese rats was evaluated by transmission electron microscopy. qRT-PCR and immunoblotting of ubiquitin C-terminal hydrolases (UCHs), ubiquitin, proteasomal sub-units, markers of ER stress and apoptosis were performed in the cerebral cortex. Proteasome activity was assayed by fluorometric method. Immunohistochemistry was performed for mediators of apoptosis, which was further confirmed by TUNEL assay. These investigations were also carried in high-fat diet-induced obese rat model. RESULTS: Neurons in the cerebral cortex of 12-month obese rats showed swollen mitochondria, disrupted ER and degenerating axons, nucleus and finally neurons. Results showed altered UPS, existence of ER stress, up-regulation of apoptotic markers and apoptosis in the cerebral cortex of obese rats. It appears that UCHL-1 mediated apoptosis through stabilizing p53 might play a role in neuronal cell death in obese rat. Similar changes were observed in the brain of diet-induced obese WNIN rats. CONCLUSION: Altered UPS could be one of the underlying mechanisms for the neuronal cell death in obese conditions. GENERAL SIGNIFICANCE: This is the first report to highlight the role of altered UPS in neurodegeneration due to obesity.

Expression and induction of small heat shock proteins in rat heart under chronic hyperglycemic conditions.

The induction of small heat shock proteins (sHsp) is observed under various stress conditions to protect the cells and organisms from adverse events including diabetes. Diabetic cardiomyopathy is a common complication of diabetes. Therefore, in this study, we investigated the expression of sHsp under chronic hyperglycemic conditions in rat heart. Hyperglycemia was induced in WNIN rats by intraperitoneal injection of streptozotocin and maintained for a period of 12weeks. Expression of sHsp, phosphorylation and translocation of phosphoforms of Hsp27 and αB-crystallin (αBC) from cytosolic fraction to cytoskeletal fraction was analyzed. While the expression of MKBP, HspB3, αBC was found to be increased in diabetic heart, expression of Hsp20 was decreased. Chronic hyperglycemia further induced phosphorylation of αBC at S59, S45, Hsp27 at S82, p38MAPK and p44/42MAPK. However, pS59-αBC and pS82-Hsp27 were translocated from detergent-soluble to detergent-insoluble fraction under hyperglycemic conditions. Furthermore, the interaction of pS82-Hsp27 and pS59-αBC with desmin was increased under hyperglycemia. However, the interaction of αBC and pS59-αBC with Bax was impaired by chronic hyperglycemia. These results suggest up regulation of sHsp (MKBP, HspB3 and αBC), phosphorylation and translocation of Hsp27 and αBC to striated sarcomeres and impaired interaction of αBC and pS59-αBC with Bax under chronic hyperglycemia.

DAS181 treatment of severe parainfluenza type 3 pneumonia in a lung transplant recipient.

Parainfluenza virus (PIV) may cause life-threatening pneumonia in lung transplant patients and there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, to treat severe PIV type 3 pneumonia in a lung transplant patient. Treatment was well tolerated and associated with improvement in oxygenation and symptoms, along with rapid clearance of PIV. DAS181 should be systematically evaluated for treatment of PIV infection in transplant recipients.

Laryngeal injury in a coronavirus disease 2019 caregiver following voluntary cough-holding within an inappropriately sized personal protective equipment suit.

OBJECTIVE: To document laryngeal framework rupture following voluntary cough-holding as an airway complication of donning a personal protective equipment suit that was too small in size. METHODS: Clinical record and literature review, with proposition of plausible aerodynamics of the airway injury. RESULTS: Whilst carrying out his duty in the coronavirus disease ward, a resident attempted to stifle a paroxysm of cough when wearing a personal protective equipment suit that was too small with his neck flexed and restricted. There was a sudden release of pressure, intense pain and swelling in the neck with crepitus. Imaging revealed a non-displaced fracture in the lower end of the partially ossified right thyroid lamina, a cricothyroid membrane tear and subcutaneous emphysema. The symptoms resolved gradually on conservative management. CONCLUSION: This report underlines the importance of donning appropriately sized personal protective equipment and encouraging its proper use amongst coronavirus disease 2019 caregivers. Non-traumatic laryngeal injury, itself a rare event, has never been reported as a posture-related complication of wearing personal protective equipment.

Regioselective formation of acrolein-derived cyclic 1,N(2)-propanodeoxyguanosine adducts mediated by amino acids, proteins, and cell lysates.

Acrolein (Acr) is a major component in cigarette smoke and a ubiquitous environmental pollutant. It is also formed as a product of lipid peroxidation. Following ring closure via the Michael addition, Acr modifies deoxyguanosine (dG) in DNA by forming cyclic 1,N(2)-propanodeoxyguanosine adducts (OHPdG). The reactions of Acr with dG yield, depending on the direction of ring closure, two regioisomers, α- and γ-OHPdG, in approximately equal amounts. However, previous (32)P-postlabeling studies showed that the γ isomers were detected predominantly in the DNA of rodent and human tissues. Because of the potential differential biological activity of the isomeric OHPdG adducts, it is important to confirm and study the chemical basis of the regioselective formation of γ isomers in vivo. In this study, it is confirmed that γ-OHPdG adducts are indeed the major isomers formed in vivo as evidenced by a LC-MS/MS method specifically developed for Acr-derived dG adducts. Furthermore, we have shown that the formation of γ-isomers is increased in the presence of amino-containing compounds, including amino acids, proteins, and cell lysates. A product of Acr and arginine that appears to mediate the regioselective formation of γ isomers was identified, but its structure was not fully characterized due to its instability. This study demonstrates that intracellular amino-containing compounds may influence the regiochemistry of the formation of OHPdG adducts and reveals a mechanism for the preferential formation of γ-OHPdG by Acr in vivo.

Assessment of pain associated with bovine respiratory disease and its mitigation with flunixin meglumine in cattle with induced bacterial pneumonia.

Pleuritic chest pain from bacterial pneumonia is often reported in human medicine. However, studies investigating pain associated with bovine respiratory disease (BRD) are lacking. The objectives of this study were to assess if bacterial pneumonia elicits a pain response in calves with experimentally induced BRD and to determine the analgesic effects of transdermally administered flunixin. A total of 26 calves, 6-7 mo of age, with no history of BRD were enrolled into one of three treatment groups: 1) experimentally induced BRD + transdermal flunixin at 3.3 mg/kg twice, 24 h apart (BRD + FTD); 2) experimentally induced BRD + placebo (BRD + PLBO); and 3) sham induction + placebo (CNTL + PLBO). Calves induced with BRD were inoculated with Mannheimia haemolytica via bronchoalveolar lavage. Outcomes were collected from -48 to 192 h post-treatment and included serum cortisol, infrared thermography, mechanical nociceptive threshold, substance P, kinematic gait analysis, visual analog scale (VAS), clinical illness score, computerized lung score, average activity and rumination level, prostaglandin E2 metabolite, plasma serum amyloid A, and rectal temperature. Outcomes were evaluated using either a generalized logistic mixed model for categorical variables or a generalized linear mixed model for continuous variables. Right front force differed by treatment (P = 0.01). The BRD + PLBO had lower mean force applied to the right front limb (85.5 kg) compared with BRD + FTD (96.5 kg; P < 0.01). Average VAS differed by a treatment by time interaction (P = 0.01). The VAS scores differed for BRD + PLBO at -48 (3.49 mm) compared with 168 and 192 h (13.49 and 13.64 mm, respectively) (P < 0.01). Activity for BRD + PLBO was higher at -48 h (27 min/h) compared with 48, 72, 120, and 168 h (≤ 22.24 min/h; P < 0.01). Activity differed by a treatment by time interaction (P = 0.01). Activity for BRD + FTD was higher at -48 and 0 h (28.2 and 28.2 min/h, respectively) compared to 48, 72, 96, and 168 h (≤23.7 min/h; P < 0.01). Results show a combination of reduced activity levels, decreased force on the right front limb, and increased VAS pain scores all support that bacterial pneumonia in cattle is painful. Differences in right front force indicate that flunixin transdermal may attenuate certain pain biomarkers in cattle with BRD. These findings suggest that BRD is painful and analgesic drugs may improve the humane aspects of care for cattle with BRD.

Bronchoalveolar lavage for the evaluation of interstitial lung disease: is it clinically useful?

Although the application of thoracic high-resolution computed tomography (HRCT) to clinical pulmonology has revolutionised the diagnostic approach to patients with suspected interstitial lung disease (ILD), additional testing is often needed to make a confident ILD diagnosis. Bronchoalveolar lavage (BAL) can play a significant role in making an accurate and confident diagnosis of specific forms of ILD. When BAL is used in conjunction with comprehensive clinical information and HRCT, BAL nucleated immune cell patterns can frequently provide useful information for diagnostic evaluation and lessen the need to proceed to more invasive procedures, such as surgical lung biopsy. Additionally, BAL can identify confounding conditions, such as infection or malignancy. However, BAL technique, and protocols for processing and analysing BAL fluid are critically important for providing useful information. This perspective reviews the current status of using BAL as a diagnostic tool for the diagnosis of ILD.

Increase in oxidative stress at low temperature in an antarctic bacterium.

Association between cold stress and oxidative stress was demonstrated by measuring the activity of two antioxidant enzymes and the level of free radicals generated in two batches of cells of an Antarctic bacterium Pseudomonas fluorescens MTCC 667, grown at 22 and 4°C. Increase in oxidative stress in cells grown at low temperature was evidenced by increase in the activity of an enzyme and also in the amount of free radicals generated, in the cold-grown cells. The association between cold stress and oxidative stress demonstrated in this investigation bolsters the concept of interlinked stress response in bacteria.

The multidrug resistance phenotype confers immunological resistance.

Multidrug resistance (MDR), which is due, in part, to the overexpression of P-glycoprotein, confers resistance to a variety of natural product chemotherapeutic agents such as daunorubicin, vincristine, and colchicine. RV+ cells are a P-glycoprotein overexpressing variant of the HL60 myeloid leukemia cell line. In addition to classic MDR, RV+ cells displayed relative resistance to complement-mediated cytotoxicity with both immunoglobulin G and M antibodies against different cell surface antigens, but not to antibody-dependent cellular cytotoxicity and lymphokine-activated killing. Complement resistance was reversed both by treatment with verapamil and with specific monoclonal antibodies (mAbs) capable of binding to P-glycoprotein and blocking its function. To further confirm that the resistance of RV+ cells was not a consequence of the selection of the cells on vincristine, a second system involving P-glycoprotein infectants was also investigated. K562 cells infected with the MDR1 gene, which were never selected on chemotherapeutic drugs, also displayed relative resistance to complement-mediated cytotoxicity. This MDR1 infection-induced resistance was also reversed by mAbs that bind to P-glycoprotein. Therefore, the MDR phenotype as mediated by P-glycoprotein provides resistance to complement-mediated cytotoxicity. The increased intracellular pH and the decreased membrane potential due to the MDR phenotype may result in abnormal membrane attack complex function. This observation may have implications for the possible mechanisms of action of P-glycoprotein and for a possible physiologic role for P-glycoprotein in protection against complement-mediated autolysis.

Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology.

Several clinical trials have recently targeted specific pathways implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, IPF remains plagued by a median survival of 3 yrs and emphasises the need for further research with new insights and perspectives. The prevailing pathogenic hypotheses assume that either an inflammatory process or an independent epithelial/fibroblastic disorder may propagate the disease process. Based on knowledge developed with considerable scientific evidence, we provide our perspectives with an alternative point of view that IPF be considered as a neoproliferative disorder of the lung. Genetic alterations, response to growth and inhibitory signals, resistance to apoptosis, myofibroblast origin and behaviour, altered cellular communications, and intracellular signalling pathways are all fundamental pathogenic hallmarks of both IPF and cancer. The concept of IPF as a lethal malignant disorder of the lung might extend beyond the pathogenic link between these two diseases and disclose new pathogenic mechanisms leading to novel therapeutic options, adopted from cancer biology. Moreover, this vision might dawn the awareness of the public, political and scientific community of this devastating disease from an angle different from the current perception and provoke new ideas and studies to get a better understanding to control the otherwise relentless progressive disease.

Quality of life and dyspnoea in patients treated with bosentan for idiopathic pulmonary fibrosis (BUILD-1).

No therapy is known to improve health-related quality of life (HRQoL) or dyspnoea in patients with idiopathic pulmonary fibrosis. The present study investigated longitudinal changes in HRQoL and dyspnoea and explored the effects of bosentan on these end-points during the Bosentan Use in Interstitial Lung Disease (BUILD)-1 trial. In total, 154 subjects received oral bosentan (n = 71) or placebo (n = 83). Changes in HRQoL and dyspnoea from baseline to month (M) 6 and up to M12 were measured using the St George's Respiratory Questionnaire (SGRQ), 36-item short-form health survey (SF-36), Transition Dyspnoea Index and Borg dyspnoea index. Overall, minimal changes occurred in measures of HRQoL and dyspnoea among placebo-treated subjects during the study. The effects of bosentan treatment on HRQoL and dyspnoea in the all-treated population were minimal. However, in the subset of subjects who had undergone surgical lung biopsy for diagnosis of idiopathic pulmonary fibrosis, treatment effects were observed up to M12 in the impact domain of the SGRQ and the physical functioning, general health and role emotional domains of the SF-36. HRQoL and dyspnoea changed minimally during the course of the present study. Observations from exploratory analyses suggested benefits of bosentan on HRQoL among patients who had undergone surgical lung biopsy for diagnosis, and they merit further investigation.

Pirfenidone in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease without proven effective therapy. A multicentre, double-blind, placebo-controlled, randomised phase III clinical trial was conducted in Japanese patients with well-defined IPF to determine the efficacy and safety of pirfenidone, a novel antifibrotic oral agent, over 52 weeks. Of 275 patients randomised (high-dose, 1,800 mg x day(-1); low-dose, 1,200 mg x day(-1); or placebo groups in the ratio 2:1:2), 267 patients were evaluated for the efficacy of pirfenidone. Prior to unblinding, the primary end-point was revised; the change in vital capacity (VC) was assessed at week 52. Secondary end-points included the progression-free survival (PFS) time. Significant differences were observed in VC decline (primary end-point) between the placebo group (-0.16 L) and the high-dose group (-0.09 L) (p = 0.0416); differences between the two groups (p = 0.0280) were also observed in the PFS (the secondary end-point). Although photosensitivity, a well-established side-effect of pirfenidone, was the major adverse event in this study, it was mild in severity in most of the patients. Pirfenidone was relatively well tolerated in patients with IPF. Treatment with pirfenidone may decrease the rate of decline in VC and may increase the PFS time over 52 weeks. Additional studies are needed to confirm these findings.

Effects of epigallocatechin gallate, L-ascorbic acid, alpha-tocopherol, and dihydrolipoic acid on the formation of deoxyguanosine adducts derived from lipid peroxidation.

Oxidation of polyunsaturated fatty acids (PUFAs) releases alpha,beta-unsaturated aldehydes that modify deoxyguanosine (dG) to form cyclic 1,N(2)-propanodeoxyguanosine adducts. One of the major adducts detected in vivo is acrolein (Acr)-derived 1,N(2)-propanodeoxyguanosine (Acr-dG). We used a chemical model system to examine the effects of 4 antioxidants known to inhibit fatty acid oxidation on the formation of Acr-dG and 8-oxodeoxyguaonsine (8-oxodG) from the PUFA docosahexaenoic acid (DHA) under oxidative conditions. We found that epigallocatechin gallate (EGCG) and dihydrolipoic acid (DHLA) inhibit both Acr-dG and 8-oxodG formation. In contrast, ascorbic acid and alpha-tocopherol actually increase Acr-dG at high concentrations and do not show a concentration-dependant inhibition of 8-oxodG. We also studied their effects on blocking Acr-dG formation directly from Acr. EGCG and DHLA can both effectively block Acr-dG formation, but ascorbic acid and alpha-tocopherol show weak or little effect. These results highlight the complexity of antioxidant mechanisms and also reveal that EGCG and DHLA are effective at suppressing lipid peroxidation-induced Acr-dG and 8-oxodG formation as well as blocking the reaction of dG with Acr.

Bioremediation of trace cobalt from simulated spent decontamination solutions of nuclear power reactors using E. coli expressing NiCoT genes.

Removal of radioactive cobalt at trace levels (approximately nM) in the presence of large excess (10(6)-fold) of corrosion product ions of complexed Fe, Cr, and Ni in spent chemical decontamination formulations (simulated effluent) of nuclear reactors is currently done by using synthetic organic ion exchangers. A large volume of solid waste is generated due to the nonspecific nature of ion sorption. Our earlier work using various fungi and bacteria, with the aim of nuclear waste volume reduction, realized up to 30% of Co removal with specific capacities calculated up to 1 microg/g in 6-24 h. In the present study using engineered Escherichia coli expressing NiCoT genes from Rhodopseudomonas palustris CGA009 (RP) and Novosphingobium aromaticivorans F-199 (NA), we report a significant increase in the specific capacity for Co removal (12 microg/g) in 1-h exposure to simulated effluent. About 85% of Co removal was achieved in a two-cycle treatment with the cloned bacteria. Expression of NiCoT genes in the E. coli knockout mutant of NiCoT efflux gene (rcnA) was more efficient as compared to expression in wild-type E. coli MC4100, JM109 and BL21 (DE3) hosts. The viability of the E. coli strains in the formulation as well as at different doses of gamma rays exposure and the effect of gamma dose on their cobalt removal capacity are determined. The potential application scheme of the above process of bioremediation of cobalt from nuclear power reactor chemical decontamination effluents is discussed.

MICA: a multilinear ICA decomposition for natural scene modeling.

We refine the classical independent component analysis (ICA) decomposition using a multilinear expansion of the probability density function of the source statistics. In particular, we introduce a specific nonlinear system that allows us to elegantly capture the statistical dependences between the responses of the multilinear ICA (MICA) filters. The resulting multilinear probability density is analytically tractable and does not require Monte Carlo simulations to estimate the model parameters. We demonstrate the MICA model on natural image textures and envision that the new model will prove useful for analyzing nonstationarity natural images using natural scene statistics models.