Semibatch monomer addition as a general method to tune and enhance the mechanics of polymer networks via loop-defect control.

Controlling the molecular structure of amorphous cross-linked polymeric materials is a longstanding challenge. Herein, we disclose a general strategy for precise tuning of loop defects in covalent polymer gel networks. This "loop control" is achieved through a simple semibatch monomer addition protocol that can be applied to a broad range of network-forming reactions. By controlling loop defects, we demonstrate that with the same set of material precursors it is possible to tune and in several cases substantially improve network connectivity and mechanical properties (e.g., ∼600% increase in shear storage modulus). We believe that the concept of loop control via continuous reagent addition could find broad application in the synthesis of academically and industrially important cross-linked polymeric materials, such as resins and gels.

Templated Self-Assembly of a PS- Branch-PDMS Bottlebrush Copolymer.

The self-assembly of block copolymers (BCPs) with novel architectures offers tremendous opportunities in nanoscale patterning and fabrication. Here, the thin film morphology, annealing kinetics, and topographical templating of an unconventional Janus-type "PS- branch-PDMS" bottlebrush copolymer (BBCP) are described. In the Janus-type BBCP, each segment of the bottlebrush backbone connects two immiscible side chain blocks. Thin films of a Janus-type BBCP with Mn = 609 kg/mol exhibited 22 nm period cylindrical microdomains with long-range order under solvent vapor annealing, and the effects of as-cast film thickness, solvent vapor pressure, and composition of the binary mixture of solvent vapors are described. The dynamic self-assembly process was characterized using in situ grazing-incidence X-ray scattering. Templated self-assembly of the BBCP within lithographically patterned substrates was demonstrated, showing distinct pattern orientation and dimensions that differ from conventional BCPs. Self-consistent field theory is used to elucidate details of the templated self-assembly behavior within confinement.

Graft-through Synthesis and Assembly of Janus Bottlebrush Polymers from A-Branch-B Diblock Macromonomers.

We report the synthesis of Janus bottlebrush block copolymers by graft-through polymerization of branched diblock macromonomers. Self-assembly of the bottlebrushes was characterized by small-angle X-ray scattering, atomic force microscopy, and scanning electron microscopy. Phase separation and packing models of the bottlebrushes were computed, and their self-assembly behavior was corroborated experimentally in bulk and in thin films. Lamellar, hexagonal cylinder, and gyroid phases were observed and modeled. The A-branch-B Janus bottlebrush structure provides several unique advantages in the context of bottlebrush polymer assembly, including access to the first examples of gyroid phases.

Color constancy of color-deficient observers under illuminations defined by individual color discrimination ellipsoids.

We explored the color constancy mechanisms of color-deficient observers under red, green, blue, and yellow illuminations. The red and green illuminations were defined individually by the longer axis of the color discrimination ellipsoid measured by the Cambridge Colour Test. Four dichromats (3 protanopes and 1 deuteranope), two anomalous trichromats (2 deuteranomalous observers), and five color-normal observers were asked to complete the color constancy task by making a simultaneous paper match under asymmetrical illuminations in haploscopic view on a monitor. The von Kries adaptation model was applied to estimate the cone responses. The model fits showed that for all color-deficient observers under all illuminations, the adjustment of the S-cone response or blue-yellow chromatically opponent responses modeled with the simple assumption of cone deletion in a certain type (S-M, S-L or S-(L+M)) was consistent with the principle of the von Kries model. The degree of adaptation was similar to that of color-normal observers. The results indicate that the color constancy of color-deficient observers is mediated by the simplified blue-yellow color system with a von Kries-type adaptation effect, even in the case of brightness match, as well as by a possible cone-level adaptation to the S-cone when the illumination produces a strong S-cone stimulation, such as blue illumination.

Material and monetary flows of construction and demolition waste and assessment on physical and environmental properties of illegally dumped construction and demolition waste in Hanoi.

The main aim of this study is to investigate the material and monetary flows of CDW management and to characterize the distribution of illegally dumped CDW in Hanoi. Construction and demolition waste management has become a source of much concern to the urban authorities and citizens of big cities in Vietnam. It is estimated that 3000 t of CDW were generated per day from construction and demolition activities in Hanoi, but only 45% of the CDW was received at official landfills, while 55% of the CDW was disposed of elsewhere. The consequences of improper waste management are potentially alarming. The study conducted interviews to identify the material and cash flow associated with licensed and unlicensed contractors in CDW classification, transportation, treatment, and disposal, to characterize the distribution of illegally dumped CDW in two districts in Hanoi (urban and suburban districts), and to assess the composition of dumped CDW and environmental assessment of illegally dumped CDW by chemical analyses such as leaching and content tests. The study concluded that illegal dumping was performed mostly by unlicensed private companies. The illegally dumped CDW was mostly composed of mixed materials such as concrete, bricks, stones, and some hazardous materials such as asbestos and gypsum were found. The environmental concern of illegally dumped CDW was mostly dust, blockage of water ways, and inundation of increased suspended solids, whereas the heavy metal leaching concentration of all samples was below the environmental standards in Vietnam.

Emergence of layered nanoscale mesh networks through intrinsic molecular confinement self-assembly.

Block copolymer self-assembly is a powerful tool for two-dimensional nanofabrication; however, the extension of this self-assembly concept to complex three-dimensional network structures is limited. Here we report a simple method to experimentally generate three-dimensional layered mesh morphologies through intrinsic molecular confinement self-assembly. We designed triblock bottlebrush polymers with two Janus domains: one perpendicular and one parallel to the polymer backbone. The former enforces a lamellar superstructure that intrinsically confines the intralayer self-assembly of the latter, giving rise to a mesh-like monoclinic (54°) M15 network substructure with excellent long-range order, as well as a tetragonal (90°) T131 mesh. Numerical simulations show that the spatial constraints exerted on the polymer backbone drive the assembly of M15 and yield T131 in the strong segregation regime. This work demonstrates that intrinsic molecular confinement is a viable path to bottom-up assembly of new geometrical phases of soft matter, extending the capabilities of block copolymer nanofabrication.

Current state of building demolition and potential for selective dismantling in Vietnam.

In Vietnam, an increase in construction activities together with the absence of recycling-oriented demolition techniques is giving rise to an alarming generation of construction and demolition waste. This study scrutinized the current state of building demolition approaches in Hanoi, Vietnam and evaluated the potential for the selective dismantling, or deconstruction, of reinforced-concrete (RC) houses. Site observations, direct measurement, and interviews were conducted to obtain information on technical, environmental, and economic characteristics of three residential housing sites, each representing a typical current demolition technique (manual, hybrid, and mechanical demolition). A selective dismantling site is proposed based on the collected survey data and published case studies. Our findings confirmed the unsustainability of RC-building demolition practices in Hanoi, which have an average reuse/recycling rate of roughly 3%. The application of selective dismantling will boost the recycling rate to a remarkable 90%, associated with a 55% decrease in greenhouse gas emissions. Even though selective dismantling is more time-consuming and therefore more costly, it results in double the resale value and an eight-fold decrease in disposal costs. The results of a sensitivity analysis indicate that increasing the current disposal fee will significantly improve the feasibility of selective dismantling, suggesting a need for stricter disposal charging mechanisms along with other interventions such as the development of recycling facilities to promote the introduction of this building removal alternative in Vietnam.

Small bowel bleeding treated successfully with transcatheter arterial embolization with imipenem/cilastatin.

BACKGROUND: Small bowel bleeding is an uncommon cause of lower gastrointestinal bleeding, which may require different management. CASE PRESENTATION: A 37-year-old man presenting with hematochezia was promptly diagnosed with small bowel bleeding by computed tomography angiography. Transcatheter arterial embolization was carried out because the patient's hemodynamic status deteriorated. Hemostasis was achieved by embolization with imipenem/cilastatin, although superselective embolization failed. Capsule endoscopy revealed multiple ulcers and erosions. Drug-induced small bowel injury was suspected to be the cause of small bowel bleeding. CONCLUSION: Computed tomography angiography can facilitate the management of lower gastrointestinal bleeding. Considering transcatheter arterial embolization and choosing an optimal embolic agent depending on the situation are important in the management of hemodynamically unstable patients.

Secreted frizzled-related protein-5 is epigenetically downregulated and functions as a tumor suppressor in kidney cancer.

Secreted frizzled-related protein-5 (sFRP-5) has been identified as 1 of the secreted antagonists that bind Wnt protein. However, the functional significance of sFRP-5 in renal cell cancer (RCC) has not been reported. We hypothesized that sFRP-5 may be epigenetically downregulated through DNA methylation and histone modification and function as a tumor suppressor gene in RCC. Using tissue microarray and real-time RT-PCR, we found that sFRP-5 was significantly downregulated in kidney cancer tissues and cell lines, respectively. DNA bisulfite sequencing of the sFRP-5 promoter region in RCC cell lines showed it to be densely methylated, whereas there was few promoter methylation in normal kidney. The sFRP-5 expression was restored and the acetylation of H3 and H4 histones associated with the sFRP-5 promoter region were significantly increased after treatment with demethylation agent (5-Aza-dc) and histone deacetylase inhibitor (TSA). When RCC cells were transfected with the sFRP-5 gene, significant inhibition of anchorage independent colony formation and cell invasion were observed compared to controls. The sFRP-5 transfection also significantly induced apoptosis in RCC cells. In conclusion, this is the first report documenting that the sFRP-5 is downregulated by promoter methylation and histone acetylation and functions as a tumor suppressor gene by inducing apoptosis in RCC cells.

Wnt antagonist DKK1 acts as a tumor suppressor gene that induces apoptosis and inhibits proliferation in human renal cell carcinoma.

The functional significance of Wnt antagonist DKK1 has not been investigated in renal cell carcinoma (RCC). Therefore, we hypothesized that DKK1 may be a tumor suppressor gene and is epigenetically silenced, thus decreased DKK1 may cause progression of RCC. To assess the function of DKK1, we established stable DKK1 transfected cells and monitored them regarding cell viability, colony formation, apoptosis, cell cycle, and invasive capability. RCC cell lines had decreased levels of DKK1, which were increased after treatment with 5-Aza-2'-deoxycytidine and trichostatin A. In chromatin immunoprecipitation assay, the level of dimethyl H3K9 and trimethyl H3K27 was decreased after 5-Aza-2'-deoxycytidine/trichostatin A treatment in RCC cell lines. Increased methylation was also associated with higher pathological stages in primary RCC tissues. T-cell factor/lymphoid enhancer factor activity and nuclear beta-catenin expression were not changed in DKK1 transfectants. Also the expression of cyclinD1 and c-Myc was not changed in DKK1 transfectants. These results suggest that DKK1 may not be involved in the beta-catenin dependent pathway. We also evaluated the expression of various related genes. Cleaved caspase3, p53, p21 and puma expression were significantly upregulated in the DKK1 transfected cells. The population of apoptotic cells was increased in stable DKK1 cells and tumor growth suppression was also observed in nude mice with DKK1 transfected cells. In conclusion, this is the first report to show that DKK1 expression is epigenetically silenced in kidney cancer and its reexpression induces apoptosis and cell cycle arrest in RCC.

Visual Acuity Apps for Rapid Integration in Teleconsultation Services in all Resource Settings: A Review.

PURPOSE: There is a need for a simple and accurate way to assess visual acuity in telemedicine consultations in ophthalmology and other related specialties. DESIGN: We surveyed visual acuity testing apps available that allow patients to measure their own acuity, focusing on freely accessible resources suitable for all resource settings. METHODS: A systematic search was performed for visual acuity testing apps on 2 major platforms: Google Play Store (Google, CA, USA) and Apple App Store (Apple, CA, USA). RESULTS: Sixteen apps (67%) tested near vision, 5 apps (21%) tested distance vision, and 3 apps (13%) offered options for both near and distance vision testing. Of the 24 apps, 5 (21%) offered a method of calibration of optotype size. Three apps (13%) demonstrated evidence of clinical validation. Only 3 apps fulfilled our criteria for suitability for clinical practice. CONCLUSIONS: We have recommended 3 apps that may be quickly integrated into clinical practice in both ophthalmic and non-ophthalmic all resource settings.

Financial and economic evaluation of construction and demolition waste recycling in Hanoi, Vietnam.

Increasing waste generation and the absence of a formal recycling industry are exacerbating the inadequacy of Construction and Demolition Waste (CDW) management in Hanoi, Vietnam. This study assesses potential CDW recycling in Hanoi by estimating the prospective supply of and demand for CDW recycling plants and evaluating their likely costs and benefits. Supply of concrete waste was calculated based on the weight-per-construction-area method whilst demand for recycled concrete aggregates (RCA) was determined by estimating the amount of aggregates for road construction in Hanoi from 2013 to 2017. Two potential models of CDW recycling plants were considered: a stationary plant and a mobile plant, with capacities of 1,000 and 360 tons/day, respectively. Our findings reveal that demand for RCA exceeds waste concrete supply, suggesting a promising market for RCA. Positive Net Present Value and Internal Rate of Return values of the stationary plant indicate its feasibility as an investment option. Meanwhile, the introduction of mobile recycling plants might require governmental intervention to internalize recycling positive externalities. Supporting policies might include a combination of a virgin material tax, green public procurement, and quality standard development.

Uncovering of intraspecies macular heterogeneity in cynomolgus monkeys using hybrid machine learning optical coherence tomography image segmentation.

The fovea is a depression in the center of the macula and is the site of the highest visual acuity. Optical coherence tomography (OCT) has contributed considerably in elucidating the pathologic changes in the fovea and is now being considered as an accompanying imaging method in drug development, such as antivascular endothelial growth factor and its safety profiling. Because animal numbers are limited in preclinical studies and automatized image evaluation tools have not yet been routinely employed, essential reference data describing the morphologic variations in macular thickness in laboratory cynomolgus monkeys are sparse to nonexistent. A hybrid machine learning algorithm was applied for automated OCT image processing and measurements of central retina thickness and surface area values. Morphological variations and the effects of sex and geographical origin were determined. Based on our findings, the fovea parameters are specific to the geographic origin. Despite morphological similarities among cynomolgus monkeys, considerable variations in the foveolar contour, even within the same species but from different geographic origins, were found. The results of the reference database show that not only the entire retinal thickness, but also the macular subfields, should be considered when designing preclinical studies and in the interpretation of foveal data.

Waste generation, composition, and handling in building-related construction and demolition in Hanoi, Vietnam.

This study conducted a survey at 15 building construction and demolition sites in Hanoi, Vietnam in order to identify waste generation rates (WGR), composition, and current handling practices of construction and demolition waste (CDW). Waste quantification based on CDW layout, image analysis to identify CDW components, and face-to-face interviews with construction and demolition contractors to reveal CDW flows were performed. WGRs of 79.3 kg/m2 and 1,030 kg/m2 were determined in small- and large-scale construction sites, respectively, whilst WGRs at small and large demolition sites were 610 kg/m2 and 318 kg/m2. The composition analysis identified soil, concrete, and brick as the major CDW components, consistent with building structures in Vietnam. The interviews discovered that merely 10% of total CDW flows was from recycled and reused CDW. Reuse and recycling rates were most significant for metal and were lower (in descending order) for brick, concrete, and soil. These findings raise a need for aggressive and integrated strategies to promote more sustainable CDW management in the country, including the development of recycled CDW product standards, policies that facilitate recycling, and more importantly, a sustainable business model for CDW recycling, for which future evaluations of economic feasibility are of great importance.

Characterization and comparison of groundwater quality and redox conditions in the Arakawa Lowland and Musashino Upland, southern Kanto Plain of the Tokyo Metropolitan area, Japan.

Groundwater is essential for the Earth biosphere but is often contaminated by harmful chemical compounds due to both anthropogenic and natural causes. A key factor controlling the fate of harmful chemicals in groundwater is the reduction/oxidation (redox) conditions. The formation factors for the groundwater redox conditions are insufficiently understood. In this study, long-term groundwater quality beneath one of the world megacities was monitored and evaluated. We measured and compared hydrogeochemical conditions including groundwater quality (35 chemical parameters) and redox conditions of five aquifers in the Arakawa Lowland and Musashino Upland, southern Kanto Plain of the Tokyo Metropolitan area, Japan. Monitoring results suggested the following: The main origin of groundwater is precipitation in both the Lowland and Upland areas. The three aquifers in the Arakawa Lowland are likely fully separated, with one unconfined and two confined aquifers under iron reducing and methanogenic conditions, respectively. Oppositely, in the Musashino Upland, the water masses in the two aquifers are likely partly connected, under aerobic conditions, and undergoing the same groundwater recharge and flow processes under similar hydrogeological conditions. The different groundwater redox conditions observed are likely caused by the very different groundwater residence times for the Arakawa Lowland and Musashino Upland.

Identification of novel microRNA targets based on microRNA signatures in bladder cancer.

MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate protein-coding genes. To identify miRNAs that have a tumor suppressive function in bladder cancer (BC), 156 miRNAs were screened in 14 BCs, 5 normal bladder epithelium (NBE) samples and 3 BC cell lines. We identified a subset of 7 miRNAs (miR-145, miR-30a-3p, miR-133a, miR-133b, miR-195, miR-125b and miR-199a*) that were significantly downregulated in BCs. To confirm these results, 104 BCs and 31 NBEs were subjected to real-time RT-PCR-based experiments, and the expression levels of each miRNA were significantly downregulated in BCs (p < 0.0001 in all). Receiver-operating characteristic curve analysis revealed that the expression levels of these miRNAs had good sensitivity (>70%) and specificity (>75%) to distinguish BC from NBE. Our target search algorithm and gene-expression profiling in BCs (Kawakami et al., Oncol Rep 2006;16:521-31) revealed that Keratin7 (KRT7) mRNA was a common target of the downregulated miRNAs, and the mRNA expression levels of KRT7 were significantly higher in BCs than in NBEs (p = 0.0004). Spearman rank correlation analysis revealed significant inverse correlations between KRT7 mRNA expression and each downregulated miRNA (p < 0.0001 in all). Gain-of-function analysis revealed that KRT7 mRNA was significantly reduced by transfection of 3 miRNAs (miR-30-3p, miR-133a and miR-199a*) in the BC cell line (KK47). In addition, significant decreases in cell growth were observed after transfection of 3 miRNAs and si-KRT7 in KK47, suggesting that miR-30-3p, miR-133a and miR-199a* may have a tumor suppressive function through the mechanism underlying transcriptional repression of KRT7.

Restoring erectile function by antioxidant therapy in diabetic rats.

PURPOSE: Diabetes mediates an increase in reactive oxygen species that can lead to impaired endothelial function, decreased smooth muscle in the diabetic corpus cavernosum and increased apoptosis. We hypothesized that antioxidant therapy may restore erectile function by inhibiting apoptosis in diabetic rat crura. MATERIALS AND METHODS: A total of 40 male Sprague-Dawley rats were randomized to 5 groups of 8 each, including healthy controls, rats with diabetes, and rats with diabetes with the antioxidant tempol (4-hydroxytetramethyl-piperidine-1-oxyl) (Sigma-Aldrich), with insulin, and with tempol and insulin. Intracavernous pressure was measured for functional analysis. Smooth muscle and collagen fiber levels in the rat penile corpus cavernosum were assessed by hematoxylin and eosin, and Masson's trichrome staining. Endothelial cells were assessed by CD31 staining. Reactive oxygen species related genes were analyzed by cDNA microarray. We confirmed mRNA and protein expression profiles for these genes in diabetic and treated rats using real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. TUNEL assay was done to analyze apoptosis status. RESULTS: Intracavernous pressure in diabetic rats was significantly decreased vs controls. After treatment with tempol or insulin alone intracavernous pressure was significantly increased compared to that in untreated diabetic rats. In the diabetic group mean smooth muscle area significantly decreased but was restored after combined tempol and insulin. Endothelial cell area in diabetic rats significantly decreased and was not restored by any treatments. However, apoptosis was restored to normal by combined insulin and tempol. Of 84 reactive oxidative stress and antioxidant genes 32 were identified specific to diabetic rats compared to healthy controls. UCP3 expression was significantly increased in diabetic rats and normal levels were restored by all treatments. CONCLUSIONS: To our knowledge this is the first report that tempol and insulin can restore erectile function in diabetic rats by inhibiting apoptosis.

Nerve growth factor combined with vascular endothelial growth factor enhances regeneration of bladder acellular matrix graft in spinal cord injury-induced neurogenic rat bladder.

OBJECTIVE: To determine the combined effects of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) on regeneration of the bladder acellular matrix graft (BAMG) in spinal cord injury (SCI)-mediated neurogenic bladder in rats. MATERIALS AND METHODS: In all, 40 female Sprague-Dawley rats were used. At 8 weeks after spinalization surgery (neurogenic bladder), they were divided into five groups consisting of untreated controls and those whose bladders were injected with either no growth factor, NGF (2 microg/rat), VEGF (2 microg/rat) or both at partial BAMG replacement surgery. After 8 weeks, bladder function was assessed by urodynamic studies and the bladders were harvested for histological examination. Smooth muscle induction, collagen and nerve fibre regeneration were assessed immunohistochemically using antibodies to smooth muscle actin (alpha-actin), Masson's trichrome and protein gene product 9.5, respectively. RESULTS: Bladder capacity and compliance were significantly increased in all BAMG groups 8 weeks after surgery compared with that before bladder replacement surgery. Bladder capacity and compliance were much higher in the VEGF and NGF combined group than in the control, or NGF and VEGF alone groups. There was no significant difference in the residual volume ratio among all groups. CONCLUSIONS: This is the first report showing that NGF has a significant synergistic effect on the development, differentiation and functional restoration of the BAMG when administered with VEGF in neurogenic bladder. Our results indicate that NGF may be a useful cytokine for enhancing the regeneration of a functional bladder following acellular matrix grafting in a neurogenic rat model.

Aortic Thrombosis in a Patient With Malignant Disease: A Literature Review and Case Presentation.

INTRODUCTION:: Aortic mural thrombosis associated with a malignant disease is rare, and whether anticoagulation therapy or surgical treatment is the more definitive primary treatment remains uncertain. This study aims to determine the best treatment strategy for aortic thrombosis in a patient with a malignant disease. METHODS:: We reviewed medical literature using the PubMed database and present a case of aortic thrombosis due to a hypercoagulable state related to sigmoid colon adenocarcinoma. RESULTS:: Of the 18 patients from 14 articles included in this study, 13 received simple anticoagulation as a primary treatment (anticoagulation group), while 5 underwent surgical treatment (surgical treatment group). Recurrence or exacerbation of embolism was found in 2 (15.4%) of the 13 patients and in 1 (20.0%) of the 5 patients ( P = 1.0). Major complications were observed in 1 (7.7%) of the patients in the anticoagulation group and in 1 (20.0%) of the 5 patients in the surgical treatment group ( P = .49). No significant differences between the groups were found. CONCLUSIONS:: A simple anticoagulation therapy may be as effective as surgical treatment in patients with aortic thrombosis associated with malignancy.

DNA methylation and histone modifications cause silencing of Wnt antagonist gene in human renal cell carcinoma cell lines.

Secreted frizzled-related protein 2 (sFRP2) is a negative modulator of the Wingless-type (Wnt) signaling pathway, and shown to be inactivated in renal cell carcinoma (RCC). However, the molecular mechanism of silencing of sFRP2 is not fully understood. Our study was designed to elucidate the silencing mechanism of sFRP2 in RCC. Expression of sFRP2 was examined in 20 pairs of primary cancers by immunohistochemistry. Kidney cell lines (HK-2, Caki-1, Caki-2, A-498 and ACHN) were analyzed for sFRP2 expression using real-time RT-PCR and Western blotting. The methylation status at 46 CpG sites of the 2 CpG islands in the sFRP2 promoter was characterized by bisulfite DNA sequencing. Histone modifications were assessed by chromatin immunoprecipitation (ChIP) assay using antibodies against AcH3, AcH4, H3K4 and H3K9. sFRP2 was frequently repressed in primary cancers and in RCC cells. The majority of sFRP2 negative cells had a methylated promoter. Meanwhile, sFRP2 expression was repressed by a hypomethylated promoter in Caki-1 cells, and these cells had a repressive histone modification at the promoter. In Caki-1 cells, sFRP2 was reactivated by trichostatin A (TSA). Repressive histone modifications were also observed in RCC cells with hypermethylated promoters, but sFRP2 was reactivated only by 5-aza-2'-deoxycytidine (DAC) and not by TSA. However, the activation of the silenced sFRP2 gene could be achieved in all cells using a combination of DAC and TSA. This is the first report indicating that aberrant DNA methylation and histone modifications work together to silence the sFRP2 gene in RCC cells.