Relationship between aggregation of therapeutic proteins and agitation parameters: Acceleration and frequency.

An increase in protein aggregates during transportation should be suppressed in therapeutic protein products because the aggregates have a potential risk of immunogenicity. In this study, three protein solutions in vials were exposed to tri-axial vibration with various combinations of frequency and acceleration using a transportation test system to investigate the relationship between low g-force stresses and protein aggregate generation. The number concentration of micron aggregates detected by flow imaging analysis increased markedly when the acceleration and frequency of agitation were within a specific range, in other words, above a threshold. This threshold was common among the three protein solutions. The suppression of micron aggregate formation by adding a surfactant suggested that agitation above the threshold increased micron aggregates mainly via interface-mediated routes. Notably, agitation, including agitation below the threshold, accelerated spontaneous oligomerization (nanometer aggregate generation) of proteins in bulk solution even in the presence of the surfactant. Studies of stability against mechanical stresses (e.g., a random vibration test to simulate actual shipment, with a time-compressed setting by increasing acceleration) need to be performed and discussed with careful consideration of the threshold for generating micron aggregates.

Management of Nuisance Macromoths in Expressways through Academic-Industrial Collaboration: Light Trap Designed on the Basis of Moths' Preferences for Light Attributes.

Aggregation of flying insects such as gypsy moths at commercial light sources in summer not only has an aesthetically negative impact on public facilities but also permits the establishment of new insect populations there from the next year. Although energy-efficient light traps equipped with light-emitting diodes (LEDs) have recently been used for controlling pest insects in agriculture, there are very few maintenance-free light traps that are available on the market. Based on the results of field surveys, we fabricated a prototype light trap in which the preferences of insects for light irradiation angle and wavelength are implemented. Field experiments revealed that flying moths were attracted more to light with a narrow irradiation angle than to light with a wide irradiation angle. Moreover, there was a tendency for fewer moths to be collected when fluorescent paint was applied to the surface of the flight-interception board, indicating that a high contrast made by illumination and the background is preferred by flying moths. Taken together with our previous results, we found that the moth catch was influenced more by modification of the light design than by change in visible light wavelengths. A semi-portable light trap, named the "Kurihara trap" after the primary contributor to its development, is made of light-weight plastic and is driven by solar power. This light trap is omnidirectional and maintenance-free and is therefore suitable for deployment in the backyards of rest areas as well as at houses for long-term macromoth sampling.

Lake water phosphate reduction with advanced wastewater treatment in watershed, at Lake Hamana, Shizuoka Prefecture, Japan, from 1995 to 2016.

Lake Hamana is a semi-enclosed brackish lake amid agricultural and residential land. Monthly vertical profiles of nutrients, total phosphorus (TP), and total nitrogen (TN) at twelve sampling stations in the lake were obtained from 1995 to 2016. Freshwater samples were also obtained from five stations in the river flowing into the lake. Significant decreases were seen in phosphate, TP, and TN concentrations at most lake and all river stations. Decrease in phosphate concentration reflects reduced organic matter and nutrient load into the lake due to increased sewage coverage. Nitrate concentration significantly increased at four stations, whereas ammonium and TN concentrations significantly decreased. This could be due to inefficient nitrification/denitrification of wastewater. At all stations, the nitrogen to phosphate ratio in surface water was higher than 16 and increased significantly. Therefore, phosphate limitation could be strengthened by the decrease in phosphate and increase in nitrate concentrations in the lake.

Phase II trial of chemotherapy plus bevacizumab as second-line therapy for patients with metastatic colorectal cancer that progressed on bevacizumab with chemotherapy: the Gunma Clinical Oncology Group (GCOG) trial 001 SILK study.

OBJECTIVES: BRiTE and ARIES (observational cohort studies) provided valuable information on continued use of bevacizumab (BV) beyond progression (BBP). This trial evaluates the efficacy and safety of BBP for patients with metastatic colorectal cancer that progressed on first-line chemotherapy. METHODS: A total of 39 patients received FOLFIRI + BV (after FOLFOX + BV) or FOLFOX + BV (after FOLFIRI + BV) as protocol treatment. The primary endpoint was the response rate. Secondary endpoints were overall survival (OS), total survival from initiation of first-line treatment (TS), progression-free survival (PFS), and safety. RESULTS: All 39 treated patients were evaluated for toxic effects. Two patients did not meet all of the eligibility criteria and were excluded from efficacy analyses. The response rate was 16.2%. The disease control rate was 76%. The median PFS was 150 days (range 117-224). The median OS was 417 days (range 233-813). The median TS was 988 days (range 600-1,268). Grade 3/4 adverse events (% of patients) related to treatment were neutropenia (33%), fatigue (23%), and hypertension (18%). CONCLUSIONS: This is the first report to show the effect of BBP in patients who had progressive disease on first-line treatment including BV confirmed by RECIST criteria. This analysis suggests the possibility of prolonged survival with continued use of BV.

Process for recycling waste aluminum with generation of high-pressure hydrogen.

An innovative environmently friendly hydrolysis process for recycling waste aluminum with the generation of high-pressure hydrogen has been proposed and experimentally validated. The effect of the concentration of sodium hydroxide solution on hydrogen generation rate was the main focus of the study. In the experiments, distilled water and aluminum powder were placed in the pressure-resistance reactor made of Hastelloy, and was compressed to a desired constant water pressure using a liquid pump. The sodium hydroxide solution was supplied by liquid pump with different concentrations (from 1.0 to 5.0 mol/dm3) at a constant flow rate into the reactor by replacing the distilled water, and the rate of hydrogen generated was measured simultaneously. The liquid temperature in the reactor increased due to the exothermic reaction given by Al + OH(-) + 3H2O = 1.5H2 + Al(OH)4(-) + 415.6 kJ. Therefore, a high-pressure hydrogen was generated at room temperature by mixing waste aluminum and sodium hydroxide solution. As the hydrogen compressor used in this process consumes less energy than the conventional one, the generation of hydrogen having a pressure of almost 30 MPa was experimentally validated together with Al(OH)3, a useful byproduct.