Global gain modulation generates time-dependent urgency during perceptual choice in humans

Action Contro

Hot dry rock geothermal energy development program: Annual operating plan, fiscal year 1989

With completion of the repairs of EE-2 wellbore in FY88, the major effort in FY89 will be directed toward the remaining preparations for the Long-Term Flow Test (LTFT) now scheduled to begin in September 1990. Procurement of components and equipment and installation of the surface system will continue through this and the next fiscal year to be ready for the LTFT in September 1990. Reservoir experiments will consist of pressurization and flow tests to establish further characteristics of the Phase II reservoir, particularly operating water losses. Laboratory studies will continue work on fracture healing and complete adsorption tests for chemically-reactive tracer work. Cleaning and relining of the EE-I pond to meet New Mexico State requirements, started in FY88, will be completed. Reanalysis of seismic data and automation of seismic data techniques will continue. Monitoring for environmental information, routine operations, security, health and safety training, and reporting activities will continue. The program's objectives are: (1) To develop HDR drilling, hardware and instrumentation technology for energy extraction and conduct a successful energy extraction field experiment of the Phase II reservoir. (2) To verify that the environmental consequences of HDR development are acceptable. (3) To improve HDR technology to the point where electricity could be produced commercially from a substantial number of known hot dry rock resource sites in a cost range of 5 to 8 cents/kWh. (4) To evaluate the performance of the Fenton Hill Phase II reservoir by 1992. That performance consists of system operating characteristics, including thermal drawdown, energy output, reservoir impedance, and water consumption

Pupil diameter tracks lapses of attention

Action Contro

Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma

Background Recurrent head and neck squamous cell carcinoma (HNSCC) remains a difficult cancer to treat. Here, we describe a patient with HNSCC who had complete response to methotrexate (MTX) after progressing on multiple cytotoxic agents, cetuximab, and AMG-479 (monoclonal antibody against insulin-like growth factor-1 receptor [IGF-1R]). Methods The clinical information was collected by a retrospective medical record review under an Institutional Review Board-approved protocol. From 4 tumors and 2 normal mucosal epithelia, global gene expression, and IGF-1R and dihydrofolate reductase (DHFR) protein levels were determined. Results Effective target inhibition in the tumor was confirmed by the decreased protein levels of total and phospho-IGF-1R after treatment with AMG-479. Decreased level of DHFR and conversion of a gene expression profile associated with cetuximab-resistance to cetuximab-sensitivity were also observed. Conclusion This suggests that the combination of AMG-479 and MTX or cetuximab may be a promising therapeutic approach in refractory HNSCC

Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells

Immune checkpoint immunotherapy is a pillar of human oncology treatment with potential for non-human species. The first checkpoint immunotherapy approved for human cancers targeted the CTLA4 protein. CTLA4 can inhibit T cell activation by capturing and internalizing CD80 and CD86 from antigen presenting cells, a process called trans-endocytosis. Similarly, CD28 can capture CD80 and CD86 via trogocytosis and retain the captured ligands on the surface of the CD28-expressing cells. The wild Tasmanian devil (Sarcophilus harrisii) population has declined by 77% due to transmissible cancers that evade immune defenses despite genetic mismatches between the host and tumors. We used a live cell-based assay to demonstrate that devil CTLA4 and CD28 can capture CD80 and CD86. Mutation of evolutionarily conserved motifs in CTLA4 altered functional interactions with CD80 and CD86 in accordance with patterns observed in other species. These results suggest that checkpoint immunotherapies can be translated to evolutionarily divergent species.</p

Transverse emittance measurements on an S-band photoinjector rf electron gun

Proposed fourth generation light sources using SASE FELs to generate short pulse, coherent, X-rays require demonstration of high brightness electron sources. The Gun Test Facility (GTF) at SLAC was built to test high brightness sources for the proposed Linac Coherent Light Source at SLAC. The transverse emittance measurements are made at nearly 30 MeV by measuring the spot size on a YAG screen using the quadrupole scan technique. The emittance was measured to vary from 1 to 3.5 mm-mrad as the charge is increased from 50 to 350 pC using a laser pulse width of 2 ps FWHM. The measurements are in good agreement with simulation results using the LANL version of PARMELA.Comment: 12 pages, 4 figures, contributed to The 23rd Int. FEL Conf., Darmstadt, 20-24 Aug. 200

Rotary moulding of ceramic hollow wares

A novel processing method for the fast and economic production of hollow ceramic components has been developed by combining in-situ coagulation moulding with a modified version of the technique of rotary moulding, the latter being adapted from the polymer industry. The process was found to require a high solids content suspension, hence development work was performed in this direction though in the end a new, commercial suspension was utilised. Of the three forming routes of gel casting, direct coagulation casting and in-situ coagulation moulding, the latter was found to be the most promising for the new process of rotary moulding of ceramics. Due to the low value of clay-based ceramics, a new low cost coagulant was identified and the effect of lactone concentration and temperature on setting time determined. Following substantial optimisation work, it was found that a two-speed approach to multi-axial rotation was the most successful; medium sized cream jugs could be produced in just 7 minutes. With respect to mould materials, the porous resin normally used for pressure casting of sanitary ware was found to be the best option, though since this is quite expensive conventional plaster-of-paris moulds were found to be a suitable material to enable companies, particularly SMEs, to become familiar with the technology whilst avoiding high costs for trials. The processed articles could be successfully fired and glazed using gas-fired kilns with no sign of any black cores. Major advantages of the process include the ability to precisely calculate the amount of ceramic slip required, eliminating either slip wastage or the need to pour used slip back into the virgin material as currently happens with slip casting. In addition, since the precursor suspension has a very high solids content, the time and energy required to dry the green product and associated moulds has been considerably reduced

The transcription factor NFATc2 controls IL-6-dependent T cell activation in experimental colitis.

The nuclear factor of activated T cells (NFAT) family of transcription factors controls calcium signaling in T lymphocytes. In this study, we have identified a crucial regulatory role of the transcription factor NFATc2 in T cell-dependent experimental colitis. Similar to ulcerative colitis in humans, the expression of NFATc2 was up-regulated in oxazolone-induced chronic intestinal inflammation. Furthermore, NFATc2 deficiency suppressed colitis induced by oxazolone administration. This finding was associated with enhanced T cell apoptosis in the lamina propria and strikingly reduced production of IL-6, -13, and -17 by mucosal T lymphocytes. Further studies using knockout mice showed that IL-6, rather than IL-23 and -17, are essential for oxazolone colitis induction. Administration of hyper-IL-6 blocked the protective effects of NFATc2 deficiency in experimental colitis, suggesting that IL-6 signal transduction plays a major pathogenic role in vivo. Finally, adoptive transfer of IL-6 and wild-type T cells demonstrated that oxazolone colitis is critically dependent on IL-6 production by T cells. Collectively, these results define a unique regulatory role for NFATc2 in colitis by controlling mucosal T cell activation in an IL-6-dependent manner. NFATc2 in T cells thus emerges as a potentially new therapeutic target for inflammatory bowel diseases