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Background Cancer is associated with muscle atrophy (cancer cachexia) that is linked to up to 40% of cancer‐related deaths. Oxidative stress is a critical player in the induction and progression of age‐related loss of muscle mass and weakness (sarcopenia); however, the role of oxidative stress in cancer cachexia has not been defined. The purpose of this study was to examine if elevated oxidative stress exacerbates cancer cachexia. Methods Cu/Zn superoxide dismutase knockout (Sod1KO) mice were used as an established mouse model of elevated oxidative stress. Cancer cachexia was induced by injection of one million Lewis lung carcinoma (LLC) cells or phosphate‐buffered saline (saline) into the hind flank of female wild‐type mice or Sod1KO mice at approximately 4 months of age. The tumour developed for 3 weeks. Muscle mass, contractile function, neuromuscular junction (NMJ) fragmentation, metabolic proteins, mitochondrial function, and motor neuron function were measured in wild‐type and Sod1KO saline and tumour‐bearing mice. Data were analysed by two‐way ANOVA with Tukey–Kramer post hoc test when significant F ratios were determined and α was set at 0.05. Unless otherwise noted, results in abstract are mean ±SEM. Results Muscle mass and cross‐sectional area were significantly reduced, in tumour‐bearing mice. Metabolic enzymes were dysregulated in Sod1KO mice and cancer exacerbated this phenotype. NMJ fragmentation was exacerbated in tumour‐bearing Sod1KO mice. Myofibrillar protein degradation increased in tumour‐bearing wild‐type mice (wild‐type saline, 0.00847 ± 0.00205; wildtype LLC, 0.0211 ± 0.00184) and tumour‐bearing Sod1KO mice (Sod1KO saline, 0.0180 ± 0.00118; Sod1KO LLC, 0.0490 ± 0.00132). Muscle mitochondrial oxygen consumption was reduced in tumour‐bearing mice compared with saline‐injected wild‐type mice. Mitochondrial protein degradation increased in tumour‐bearing wild‐type mice (wild‐type saline, 0.0204 ± 0.00159; wild‐type LLC, 0.167 ± 0.00157) and tumour‐bearing Sod1KO mice (Sod1KO saline, 0.0231 ± 0.00108; Sod1 KO LLC, 0.0645 ± 0.000631). Sciatic nerve conduction velocity was decreased in tumour‐bearing wild‐type mice (wild‐type saline, 38.2 ± 0.861; wild‐type LLC, 28.8 ± 0.772). Three out of eleven of the tumour‐bearing Sod1KO mice did not survive the 3‐week period following tumour implantation. Conclusions Oxidative stress does not exacerbate cancer‐induced muscle loss; however, cancer cachexia may accelerate NMJ disruption.

Cancer survivors are more susceptible to pathologies such as hypertension, liver disease, depression, and coronary artery disease when compared with individuals who have never been diagnosed with cancer. Therefore, it is important to understand how tumor burden negatively impacts nontumor-bearing tissues that may impact future disease susceptibility. We hypothesized that the energetic costs of a tumor would compromise proteostatic maintenance in other tissues. Therefore, the purpose of this study was to determine if tumor burden changes protein synthesis and proliferation rates in heart, brain, and liver. One million Lewis lung carcinoma (LLC) cells or phosphate-buffered saline (PBS, sham) were injected into the hind flank of female mice at ∼4.5 mo of age, and the tumor developed for 3 wk. Rates of proliferation and protein synthesis were measured in heart, brain, liver, and tumor tissue. Compared with sham, rates of protein synthesis (structural/nuclear, cytosolic, mitochondrial, and collagen) relative to proliferation were lower in the heart and liver of LLC mice, but higher in the brain of LLC mice. In the tumor tissue, the ratio of protein synthesis to DNA synthesis was approximately 1.0 showing that protein synthesis in the tumor was used for proliferation with little proteostatic maintenance. We further provide evidence that the differences in tissue responses may be due to energetic stress. We concluded that the decrease in proteostatic maintenance in liver, heart, and muscle might contribute to the increased risk of disease in cancer survivors. NEW & NOTEWORTHY We present data showing that simultaneously measuring protein synthesis and cell proliferation can help in the understanding of protein turnover as a proteostatic process in response to tumor burden. In some tissues, like hepatic, cardiac, and skeletal muscle, there was a decrease in the protein to DNA synthesis ratio indicating less proteostatic maintenance. In contrast, the brain maintained or even increased this protein to DNA synthesis ratio indicating more proteostatic maintenance.

Immunotherapy is known to be clinically beneficial for patients with cancer and has in many cases become the new standard of care. Because of this success, the interest in integrating nanomedicine with cancer immunotherapy has grown to further improve clinical response and toxicity profiles. However, unlike conventional systemic therapies, which are directly cytotoxic to tumour cells, cancer immunotherapy relies on the host’s immune system to generate tumouricidal effects. As such, proper design of cancer immune nanomedicine requires additional scrutiny of tumours’ intrinsic and extrinsic factors that may impact host antitumour immunity. Here, we highlight key parameters that differentiate cancer immunotherapy from conventional cytotoxic agents, and we discuss their implications for designing preclinical cancer immune nanomedicine studies. We emphasize that these factors, including intratumoural genomic heterogeneity, commensal diversity, sexual dimorphism, and biological aging, which were largely ignored in traditional cancer nanomedicine experiments, should be carefully considered and incorporated into cancer immune nanomedicine investigations in the proper context given their critical involvement in shaping the body’s antitumour immune responses.

In 2018, the PNG LNG project sustained a Mw7.5 earthquake, and ca. 300 aftershocks, epicentered directly under key facilities. Around 150 km of high-pressure gas and condensate pipelines were affected. In anticipation of such an earthquake event and due to the challenging terrain that the pipeline traverses, two design methodologies were used in specifying the pipe and welds for the onshore pipelines: strain-based design and allowable stress design with robust materials selection. The strain-based design approach was used for segments crossing faults and was the subject of IPC2014-33550 [1]. In this paper, the robust allowable stress design that was used for the remainder of the onshore pipeline route will be discussed along with the performance of the pipeline designed with this methodology when it was subjected to the earthquake. Robust allowable stress design involved the selection of line pipe and welding procedures that would reduce the risk of failure during unanticipated ground movements. Lower grade, thicker wall pipe was selected, and enhanced weld properties were specified to increase weld strength overmatch and toughness. Additionally, enhanced testing of pipe and weld properties was performed in order to enable prediction of pipeline strain capacity and assessment of fitness for service of any portion of the pipeline that experienced longitudinal plastic strains due to ground movement. These efforts enabled the pipeline to safely sustain the ground movement experienced during the earthquake and allowed safe project operations to be rapidly restored. This paper provides details of the selection of pipe grade and wall thickness and the specification of material properties for pipe and girth welds. The property distributions achieved and the impact on strain capacity are presented along with estimates of the strain experienced by the pipeline due to the earthquake. The performance of the pipeline during the earthquake illustrate the benefits of the robust allowable stress design approach for pipelines in challenging environments.

Muscle disuse results in the loss of muscular strength and size, due to an imbalance between protein synthesis (MPS) and breakdown (MPB). Protein ingestion stimulates MPS, although it is not established if protein is able to attenuate muscle loss with immobilization (IM) or influence the recovery consisting of ambulatory movement followed by resistance training (RT). Thirty men (49.9 ± 0.6 yr) underwent 14 days of unilateral leg IM, 14 days of ambulatory recovery (AR), and a further six RT sessions over 14 days. Participants were randomized to consume an additional 20 g of dairy protein or placebo with a meal during the intervention. Isometric knee extension strength was reduced following IM (−24.7 ± 2.7%), partially recovered with AR (−8.6 ± 2.6%), and fully recovered after RT (−0.6 ± 3.4%), with no effect of supplementation. Thigh muscle cross-sectional area decreased with IM (−4.1 ± 0.5%), partially recovered with AR (−2.1 ± 0.5%), and increased above baseline with RT (+2.2 ± 0.5%), with no treatment effect. Myofibrillar MPS, measured using deuterated water, was unaltered by IM, with no effect of protein. During AR, MPS was increased only with protein supplementation. Protein supplementation did not attenuate the loss of muscle size and function with disuse or potentiate recovery but enhanced myofibrillar MPS during AR. NEW & NOTEWORTHY Twenty grams of daily protein supplementation does not attenuate the loss of muscle size and function induced by 2 wk of muscle disuse or potentiate recovery in middle-age men. Average mitochondrial but not myofibrillar muscle protein synthesis was attenuated during immobilization with no effect of supplementation. Protein supplementation increased myofibrillar protein synthesis during a 2-wk period of ambulatory recovery following disuse but without group differences in phenotype recovery.

Maintenance of skeletal muscle (SkM) mass is essential for maintaining mobility and metabolic health. SkM unloading or disuse, such as extended bed rest or limb immobilization, leads to rapid SkM w...

Control of protein homeostasis is fundamental to the health and longevity of all organisms. Because the rate of protein synthesis by ribosomes is a central control point in this process, regulation, and maintenance of ribosome function could have amplified importance in the overall regulatory circuit. Indeed, ribosomal defects are commonly associated with loss of protein homeostasis, aging, and disease (1–4), whereas improved protein homeostasis, implying optimal ribosomal function, is associated with disease resistance and increased lifespan (5–7). To maintain a high-quality ribosome population within the cell, dysfunctional ribosomes are targeted for autophagic degradation. It is not known if complete degradation is the only mechanism for eukaryotic ribosome maintenance or if they might also be repaired by replacement of defective components. We used stable-isotope feeding and protein mass spectrometry to measure the kinetics of turnover of ribosomal RNA (rRNA) and 71 ribosomal proteins (r-proteins) in mice. The results indicate that exchange of individual proteins and whole ribosome degradation both contribute to ribosome maintenance in vivo. In general, peripheral r-proteins and those with more direct roles in peptide-bond formation are replaced multiple times during the lifespan of the assembled structure, presumably by exchange with a free cytoplasmic pool, whereas the majority of r-proteins are stably incorporated for the lifetime of the ribosome. Dietary signals impact the rates of both new ribosome assembly and component exchange. Signal-specific modulation of ribosomal repair and degradation could provide a mechanistic link in the frequently observed associations among diminished rates of protein synthesis, increased autophagy, and greater longevity (5, 6, 8, 9).

Department of Molecular Pathology, The University of Texas-M. D. Anderson Cancer Centre, 1515 Holcombe Blvd., Houston, Texas 77030, USA Department of Chemistry, The University of Texas-Pan American, 1201 West University Drive, Edinburg, Texas 78539, USA Department of Chemistry and Chemical Engineering, Stevens Institute of Technology, Castle Point on the Hudson, Hoboken, New Jersey 07030, USA Current Address: Vice President of Research and Education Development, Community Health Systems of South Texas, 3135 South Sugar Road, Edinburg, Texas 78539, USA E-mail: bimalbanik10@gmail.com, bimal.banik@chsst.org Manuscript received 01 October 2018, accepted 02 November 2018 Bismuth nitrate-induced microwave-mediated cleavages of O-glycosidic bond in β-lactams are achieved to afford their corresponding hydroxyl derivatives in excellent yields.

Consists of one correspondence from F. Fredrick to P. A. Mullagan [?] regarding a railroad employees.

Heterotopic ossification (HO) is a well-known complication of total hip arthroplasty (THA), especially when the direct lateral approach is used. In this study, we examined the effect of the selective COX-2 inhibitor, celecoxib, on the rates of HO after THA. A control group consisting of 108 patients that did not receive celecoxib was compared with a study group consisting of 106 patients that did receive celecoxib. We assessed the presence and grade of HO using the Brooker classification and Harris hip scores were determined pre- and postoperatively to better quantify clinical outcomes. In this retrospective study of prospectively collected data, celecoxib is associated with a significant reduction in the incidence of HO in patients undergoing THA.

One of the important functions of the wetland is the retention of catchment nutrients and improving lacustrine water quality. This study analyzed how much nutrients were retained in the Nyashishi wetland, southern part of Lake Victoria, and went further to analyze the processes which were responsible in the reduction of nutrients. Three major processes were analysed in this study, namely nutrients uptake by three macrophyte species (Eichhornia crassipes, Cyperus papyrus and Typha domingensis) dominating the Nyashishi wetland, nitrification and denitrification processes. The study demonstrated high nutrients retention especially phosphorus nutrients of which up to 98% were retained. In some occasions, particularly for nitrogen nutrients, there was 0% retention especially during wet season. In some other instances, the inflow exceeded the outflow meaning that, more nutrients were generated by the wetland itself. Among the three processes analyzed, nutrients uptaken by macrophytes were more efficient in reducing nutrients in wetland water. Biological nitrification and denitrification which are believed to be the major pathway for ammonia removal in both natural and constructed wetlands were less important in this study. Among the macrophyte species, Eichhornia crassipes demonstrated higher uptake rate than the other two species possibly due to its high turnover rate. This ability can be exploited in removing excess nutrients from runoff by frequent harvesting of the mature plants.

In order to meet the increasing worldwide energy demand, there is a need to economically develop remote oil and gas resources. Construction of pipelines is required to connect these resource locations to markets. Such pipeline routes may cross areas of large ground motions such as regions of active seismicity, discontinuous permafrost, and offshore ice gouging. All of these features can subject pipelines to significant longitudinal strains. For these conditions a strain-based design (SBD) approach may be required to maintain pipeline integrity. Welding technology is a key component of pipeline construction. Significant pipeline construction cost savings are enabled with the use of higher strength steels (X80+). Higher strengths enable reduced pipe wall thicknesses, which reduces both weight and girth welding time. However, robust welding technology for high strength SBD pipelines remains challenging. Such applications demand welds with both high strength (>120ksi) and low temperature (−15°C) toughness, combinations that are at the limits of, or beyond, existing commercial technology. This paper discusses the development of an enabling welding technology which offers a superior combination of strength and toughness properties. An iron-nickel (FeNi) martensitic weld metal with a refined mixed cellular microstructure has been developed as a promising high strength weld metal that can be applied for field pipeline construction. This paper describes how this technology has been applied to create welds for X80 strain-based pipelines requiring significant weld strength overmatch and superior ductile tearing resistance. The welding technology can also be applied to X70 grade strain-based pipelines where high toughness is required. This approach has been developed for mainline girth, tie-in girth, and girth repair welding scenarios. Welding procedures are discussed and examples of the mechanical properties achieved and calculated strain capacities are described.

Pipelines may experience significant longitudinal strains when subjected to large ground motions, such as seismic activity, landslides, etc. For these conditions, a strain-based design (SBD) approach can be used. The use of higher strength steels (like X80) for SBD approach can enable significant construction cost savings. Costs can be further reduced through the use of a double jointing process in order to reduce the amount of field welding. However, it is challenging to achieve adequate girth weld properties for SBD scenarios involving higher strength steels by using conventional double jointing processes such as submerged arc welding (SAW). Acicular ferrite interspersed in martensite (AFIM) has been previously identified as an advantageous high strength weld metal microstructure that can be applied in field pipeline construction. In this paper, a double jointing technology for X70+ SBD applications will be discussed. Excellent strength and toughness properties were achieved in double joint welds by using an optimized AFIM welding technology that included a tailored welding consumable wire and a high productivity GMAW-P weld process. Welding procedures are discussed along with mechanical properties achieved. Productivity comparisons suggest that a fully optimized GMAW-P welding process in the 1G-rolled welding position can have productivity comparable to a conventional SAW double jointing process.