A phase I study of recombinant human soluble interleukin-1 receptor (rhu IL-1R) in patients with relapsed and refractory acute myeloid leukemia

PURPOSE: The recombinant human interleukin-1 receptor (rhu IL-1R) is a soluble truncated form of the type 1 full-length membrane-bound receptor that binds IL-1 with identical affinity to that of the membrane form. As such, it may have clinical potential by sequestering IL-1, thereby preventing it from binding to its membrane-bound receptor and eliciting a biological effect. As IL-1 has been shown to regulate leukemic cell proliferation in an autocrine fashion, a phase I trial of rhu IL-1R was conducted in patients with relapsed and refractory acute myeloid leukemia (AML). METHODS: The study group comprised 11 patients who were sequentially treated on one of three dose levels, receiving a single intravenous (i.v.) bolus dose on day 1 followed by 13 days of daily subcutaneous (s.c.) injections with the option of an additional 14 days of treatment if a response of stable disease or better was achieved. Dose level 1 i.v. bolus 500 microg/m2, s.c. dose 250 microg/m2 per day (five patients); dose level 2 i.v. bolus 1000 microg/m2, s.c. dose 500 microg/m2 per day (three patients); dose level 3 i.v. bolus 2000 microg/m2, s.c. dose 1000 microg/m2 per day (three patients). Owing to limited drug availability, the study was designed to only examine these three dose levels. RESULTS: rhu IL-IR was well tolerated. There was no grade 3 or 4 non-hematological toxicity related to the study drug and the maximum tolerated dose was not reached. No IL-1R-blocking antibodies developed during the course of the study. Serum levels of IL-1beta, IL-6 and TNF were undetectable before, during and after rhu IL-IR administration. The terminal half-life after i.v. dosing was at least 7-12 h, and after s.c. dosing 2-4 days. Serum levels of rhu IL-1R up to 360- and 25-fold those of pretreatment levels were achieved after i.v. and s.c. dosing respectively. No patient had a complete, partial or minor response to treatment; four had stable disease and seven had progressive disease. CONCLUSIONS: rhu IL-1R therapy was safe but did not have any apparent antileukemic effect at the doses administered.     

Superalloy Melting in an ac Electroslag Remelt Furnace with Automatic Melt Control and rms Current Regulation

A stationary mold-ingot bottom withdrawal ac consumable electrode electroslag furnace with electrode change capability has been installed for melting superalloys at Teledyne-Allvac. The furnace, which utilizes melt voltage and rms current regulation for automatic melt control and its operation are described. The stationary mold-ingot bottom withdrawal and auto-melt control concepts have proven successful and solution hardening superalloys are in routine production with high quality and good yield. Additionally, experimental melting of the nickel base and iron base precipitation hardening superalloys (containing titanium and aluminum) is in process, and initial results look encouraging with respect to quality and chemistry control.     

Perceptual organization in schizophrenia: The processing of symmetrical configurations.

The hypothesis that the perceptual organization dysfunction of patients with poor premorbid schizophrenia is due to a deficit in global visual sensory store processing was tested by assessing their ability to process symmetrical configurations that develop early and have strong prepotent structures. Two same–different judgment tasks in which performance varies as a function of the symmetrical organization and task demands were administered to participants with good and poor premorbid schizophrenia, those with mood disorders, and normal controls. Like the other groups, poor premorbid schizophrenics' latency and error response patterns closely paralleled the a priori model of adequate processing. The results support their competence in perceptually processing symmetrical configurations and disconfirm the hypothesis that their input deficiencies represent a general deficiency in all forms of perceptual organization. The implications for specifying their early input dysfunction are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Burner rig trials with nickel- and cobalt-base alloys

Selected Ni- and Co-base alloys were hot corroded in a burner rig facility at temperatures cycled from ambient to 870 or 980°C respectively for times in excess of 3000h. A diesel fuel maintained at lw/oS and doped with sea salt to 476 ppm produced characteristic hot corrosion attack at 870°C and more classical oxidation attack at 980°C. This preliminary investigation shows that the products formed on the Ni-base alloys at 980°C were cracked and dominated by local surface protrusions (“warts”). Co-base alloys did not show these features nor were they observed following tests at the lower temperature. A small % of Y in a simple Nimonic alloy reduced the extent of scale damage but did not eliminate hot-corrosion/oxidation attack.     

Measurement of IP3 in p-i-n photodetectors and proposed performancerequirements for RF fiber-optic links

The nonlinearities generated by wide-band, high-current photodetectors are discussed in the context of the performance of an externally modulated analog radio-frequency fiber-optic link. The quantitative impart of the detector's third-order intermodulation product intercept (IP3) on the link's spur-free dynamic range is analyzed. Waveguide p-i-n photodiodes were developed to specifically address these stringent IP3 goals. The IP3 was measured using a four laser heterodyne system resulting in an IP3 of 27 dBm measured at a center frequency of 20 GHz with 20 mA of de photocurrent. The authors believe that this is the highest photodetector IP3 reported to date at these operating conditions     

FILTERED REFERENCE AND FILTERED ERROR LMS ALGORITHMS FOR ADAPTIVE FEEDFORWARD CONTROL

A unified and consistent formulation is developed for both filtered reference and filtered error forms of the instantaneous steepest decent, or LMS, algorithm when used to adapt FIR feedforward controllers. Both algorithms minimise the mean-square value of the same, output, error function. The two algorithms are first formulated for single-input single-output linear plants. It is argued that since the behaviour of the two algorithms is equivalent in the case of slow adaption, the conditions on the accuracy of the plant model for stability should also be the same in both cases. This is expressed as a bound on the unstructured multiplicative uncertainty of the plant. Filtered reference and filtered error algorithms are also derived for multiple-input multiple-output (MIMO) linear systems, although the filtered reference algorithm is found not to have a simple block diagram interpretation. In the MIMO case, the filtered error form of the algorithm can have considerable computational advantages over the filtered reference form. Finally the two algorithms are extended to the case of non-linear plants and/or controllers which are modelled as feedforward neural networks. In the non-linear case the two formulations of the LMS algorithm reduce to two forms of the widely used backpropagation algorithm.     

The active control of sound

Active control of sound results from destructive interference between the sound field of an original acoustic source and that from a controllable array of `secondary' acoustic sources. For this destructive interference to occur over an appreciable region of space the sound field of the secondary sources must match that from the primary source in both time and space. The spatial matching requirement leads to an upper frequency of applicability of active control. Active control complements conventional passive methods of sound control, which do not work well at low frequencies. Practical feedforward controllers, using a multichannel generalisation of the well known LMS adaptive algorithm, have been developed, using as many as 16 loudspeakers and 32 microphones, and applied with considerable success in the control of low-frequency propeller noise inside aircraft and low-frequency engine noise inside cars. The authors describe such systems     

Design of a 3-D fully depleted SOI computational RAM

We introduce a three-dimensional (3-D) processor-in-memory integrated circuit design that provides progressively increasing processing power as the number of stacked dies increases, while incurring no extra design effort or mask sets. Innovative techniques for processor/memory redundancy and fast global bus evaluation are described. The architecture can be augmented with a nearest-neighbor physical 3-D communications network that can substantially reduce interconnect lengths and relieve routing congestion. The test chip, with 128 Kb of memory and 512 processing elements (PEs) on two fully depleted silicon-on-insulator (SOI) dies, can achieve a peak of 170 billion-bit-operations per second at 400 MHz.