ACUTE NITRATE EXPOSURE CAUSES PROTEOMIC CHANGES CONSISTENT WITH THE REGULATION OF REACTIVE OXYGEN AND NITROGEN SPECIES

Nitrate is the most common ionic form of nitrogen in aquatic ecosystems. Although nitrate is known to affect ecosystems at high levels through eutrophication, hypoxia and loss of biodiversity, it is considered to be physiologically inert to the individual aquatic organism. To test the physiological effects of nitrate on aquatic life, we exposed gill tissue of the Pacific oyster, Crassostrea gigas, to nitrate and characterized changes in protein expression, using a gel-based proteomics approach. Of the 642 protein spots detected, we found that 24 proteins (15 identified) changed expression in response to a 6-hour exposure to nitrate concentrations ranging from 0-73 mg/L, values that characterize highly contaminated surface and ground waters. Proteins changing expression included the oxidative stress proteins thioredoxin and cavortin (a member of the superoxide dismutase family) as well as proteins that are involved in G-protein signaling (Rho-GDI, ADP-ribosylation factor, G-protein ß-subunit), protein homeostasis (heat shock protein 70, prohibitin, calreticulin, and proteasome &#;-type 4 subunit), glycolysis (enolase), transport of hydrophobic molecules (lipocalin) and cytoskeletal arrangements (intermediate filaments and a gelsolin-like adseverin). The most parsimonious explanation for these changes in protein expression assumes that C. gigas reduces nitrate to nitrite and nitric oxide, which reacts with superoxide anions to form the very reactive peroxynitrite. We propose that part of the cellular response to reactive nitrogen species,phagocytic hemocytes inhibit the production of reactive oxygen species, potentially compromising the immune response of oysters to invading pathogens

Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck: role, controversy, and future directions.

BackgroundThe value of induction chemotherapy (ICT) remains under investigation despite decades of research. New advancements in the field, specifically regarding the induction regimen of choice, have reignited interest in this approach for patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Sufficient evidence has accumulated regarding the benefits and superiority of TPF (docetaxel, cisplatin, and fluorouracil) over the chemotherapy doublet cisplatin and fluorouracil. We therefore sought to collate and interpret the available data and further discuss the considerations for delivering ICT safely and optimally selecting suitable post-ICT regimens.DesignWe nonsystematically reviewed published phase III clinical trials on TPF ICT in a variety of LA SCCHN patient populations conducted between 1990 and 2017.ResultsTPF may confer survival and organ preservation benefits in a subgroup of patients with functionally inoperable or poor-prognosis LA SCCHN. Additionally, patients with operable disease or good prognosis (who are not candidates for organ preservation) may benefit from TPF induction in terms of reducing local and distant failure rates and facilitating treatment deintensification in selected populations. The safe administration of TPF requires treatment by a multidisciplinary team at an experienced institution. The management of adverse events associated with TPF and post-ICT radiotherapy-based treatment is crucial. Finally, post-ICT chemotherapy alternatives to cisplatin concurrent with radiotherapy (i.e. cetuximab or carboplatin plus radiotherapy) appear promising and must be investigated further.ConclusionsTPF is an evidence-based ICT regimen of choice in LA SCCHN and confers benefits in suitable patients when it is administered safely by an experienced multidisciplinary team and paired with the optimal post-ICT regimen, for which, however, no consensus currently exists

NASA rocket motor defects investigation. Volume 2 - Tables and figures Comprehensive report, Aug. 1966 - Jun. 1968

Static firing tests to reduce glass fiber defects and to improve field repair work on X-248 rocket motor case - Supporting tables and figure

NASA rocket motor defects investigation. Volume 3 - Appendices Comprehensive report, Aug. 1966 - Jun. 1968

Static firing tests to reduce glass fiber defects and to improve field repair work on X-248 rocket motor cases - Inspection, repair and firing dat

Effectiveness evaluation of STOL transport operations

A short-takeoff and landing (STOL) systems simulation model has been developed and implemented in a computer code (known as STOL OPS) which permits evaluation of the operation of a STOL aircraft and its avionics in a commercial airline operating environment. STOL OPS concentrated on the avionics functions of navigation, guidance, control, communication, hazard aviodance, and systems management. External world factors influencing the operation of the STOL aircraft include each airport and its geometry, air traffic at each airport, air traffic control equipment and procedures, weather (including winds and visibility), and the flight path between each airport served by the route. The development of the STOL OPS program provides NASA a set of computer programs which can be used for detailed analysis of a STOL aircraft and its avionics and permit establishment of system requirements as a function of airline mission performance goals

Privatization and Entrepreneurial Transformation

Privatization has become a popular strategy to promote economic development in developing, and developed economies. Despite its popularity, little attention has been devoted to examination of the organizational and managerial implications of privatization or to the effect of privatization on companies' ability to innovate and engage in entrepreneurial activities. this article we discuss privatization's increasing importance and present a model that links privatization to a firm's entrepreneurial activities. We conclude with a discussion of issues that we believe deserve scholars' attention in theory development and subsequent empirical examination.Publicad

Dual Goals of Trunk Restriction and Stability are Prioritized by Individuals with Chronic Low Back Pain During a Volitional Movement

Background Individuals with chronic low back pain demonstrate impaired responses to volitional and externally-generated postural perturbations that may impact stability whilst performing activities of daily living. Understanding how balance may be impaired by strategy selection is an important consideration during rehabilitation from low back pain to prevent future injurious balance loss. Research question This cross-sectional study explored the influence of an active pain episode on volitional movement patterns and stability during a sit-to-stand task in individuals with chronic low back pain compared to those with no low back pain history. Methods Thirteen participants with low back pain who were in an active flare-up and 13 without pain sat on a height-adjusted chair and performed 5 sit-to-stand movements. Sagittal plane kinematics, kinetics, and surface electromyography were used to compute neuromuscular variables across Acceleration, Transition and Deceleration phases. Stability was assessed using times to contact of body centers of mass and pressure to base of support boundaries. Independent samples t-tests were used to examine group effects, and repeated measures analyses of variance assessed within-subjects effects across movement phases. Results Individuals with low back pain tended to restrict proximal joint motions through heightened muscle activity while increasing distal joint movement and distal muscle contributions. Individuals with low back pain used a greater driving force, indicated by a longer time to contact of the center of pressure, to achieve comparable center of mass stability. Individuals with low back pain may prioritize trunk restriction and stability through the sit-to-stand movement, possibly related to fear of pain or movement. Significance The tendency for individuals with active low back pain to restrict trunk movements may require additional effort to maintain stability. Further research should examine whether trunk restriction is related to pain-related fear of movement and whether additional cognitive resources are required to maintain movement stability

A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck.

BackgroundAfatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy.Patients and methodsAn open-label, randomized, phase II trial was conducted in 43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day) or cetuximab (250 mg/m(2)/week) until disease progression or intolerable adverse events (AEs) (stage I), with optional crossover (stage II). The primary end point was tumor shrinkage before crossover assessed by investigator (IR) and independent central review (ICR).ResultsA total of 121 patients were treated (61 afatinib, 60 cetuximab) and 68 crossed over to stage II (32 and 36 respectively). In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with afatinib and 5.4%/10.1% with cetuximab (P = 0.46/0.30). Objective response rate was 16.1%/8.1% with afatinib and 6.5%/9.7% with cetuximab (IR/ICR). Comparable disease control rates were observed with afatinib (50%) and cetuximab (56.5%) by IR; similar results were seen by ICR. Most common grade ≥3 drug-related AEs (DRAEs) were rash/acne (18% versus 8.3%), diarrhea (14.8% versus 0%), and stomatitis/mucositis (11.5% versus 0%) with afatinib and cetuximab, respectively. Patients with DRAEs leading to treatment discontinuation were 23% with afatinib and 5% with cetuximab. In stage II, disease control rate (IR/ICR) was 38.9%/33.3% with afatinib and 18.8%/18.8% with cetuximab.ConclusionAfatinib showed antitumor activity comparable to cetuximab in R/M HNSCC in this exploratory phase II trial, although more patients on afatinib discontinued treatment due to AEs. Sequential EGFR/ErbB treatment with afatinib and cetuximab provided sustained clinical benefit in patients after crossover, suggesting a lack of cross-resistance