Rapid Response, Dose Assessment, and Clinical Management of a Plutonium-contaminated Puncture Wound.

Internalization of radionuclides occurs not only by inhalation, ingestion, parenteral injection (i.e., administration of radioactive material for a medical purpose), and direct transdermal absorption, but also by contaminated wounds. In June 2010, a glove-box operator at the U.S. Department of Energy's Savannah River Site sustained a puncture wound while venting canisters containing legacy materials contaminated with Pu. To indicate the canisters had been vented, a flag was inserted into the vent hole. The shaft of the flag penetrated the protective gloves worn by the operator. Initial monitoring performed with a zinc-sulfide alpha detector indicated 300 dpm at the wound site. After being cleared by radiological controls personnel, the patient was taken to the site medical facility where decontamination was attempted and diethylenetriaminepentaacetic acid (DTPA) was administered intravenously within 1.5 h of the incident. The patient was then taken to the Savannah River Site In Vivo Counting Facility where the wound was counted with a Canberra GL 2820 high-purity germanium detector, capable of quantifying contamination by detecting low-energy x rays and gamma rays. In addition to the classic 13, 17, and 20 keV photons associated with Pu, the low-yield (0.04%) 43.5 keV peak was also detected. This indicated a level of wound contamination orders of magnitude above the initial estimate of 300 dpm detected with handheld instrumentation. Trace quantities of Am were also identified via the 59.5 keV peak. A 24 h urine sample collection was begun on day 1 and continued at varying intervals for over a year. The patient underwent a punch biopsy at 3 h postincident (14,000 dpm removed) and excisional biopsies on days 1 and 9 (removal of an additional 3,200 dpm and 3,800 dpm, respectively). The initial post-DTPA urine sample analysis report indicated excretion in excess of 24,000 dpm Pu. Wound mapping was performed in an effort to determine migration from the wound site and indicated minimum local migration. In vivo counts were performed on the liver, axillary lymph nodes, supratrochlear lymph nodes, and skeleton to assess uptake and did not indicate measurable activity. Seventy-one total doses of DTPA were administered at varying frequencies for 317 d post intake. After allowing 100 d for removal of DTPA from the body, five 24 h urine samples were collected and analyzed for dose assessment by using the wound model described in National Council on Radiation Protection and Measurements Report No. 156. The total effective dose averted via physical removal of the contaminant and DTPA administration exceeded 1 Sv, demonstrating that rapid recognition of incident magnitude and prompt medical intervention are critical for dose aversion.

Cortical response tracking the conscious experience of threshold duration visual stimuli indicates visual perception is all or none.

At perceptual threshold, some stimuli are available for conscious access whereas others are not. Such threshold inputs are useful tools for investigating the events that separate conscious awareness from unconscious stimulus processing. Here, viewing unmasked, threshold-duration images was combined with recording magnetoencephalography to quantify differences among perceptual states, ranging from no awareness to ambiguity to robust perception. A four-choice scale was used to assess awareness: "didn't see" (no awareness), "couldn't identify" (awareness without identification), "unsure" (awareness with low certainty identification), and "sure" (awareness with high certainty identification). Stimulus-evoked neuromagnetic signals were grouped according to behavioral response choices. Three main cortical responses were elicited. The earliest response, peaking at ∼100 ms after stimulus presentation, showed no significant correlation with stimulus perception. A late response (∼290 ms) showed moderate correlation with stimulus awareness but could not adequately differentiate conscious access from its absence. By contrast, an intermediate response peaking at ∼240 ms was observed only for trials in which stimuli were consciously detected. That this signal was similar for all conditions in which awareness was reported is consistent with the hypothesis that conscious visual access is relatively sharply demarcated.

Membrane potential shifts caused by diffusible guidance signals direct growth-cone turning.

Plasma membrane potentials gate the ion channel conductance that controls external signal-induced neuronal functions. We found that diffusible guidance molecules caused membrane potential shifts that resulted in repulsion or attraction of Xenopus laevis spinal neuron growth cones. The repellents Sema3A and Slit2 caused hyperpolarization, and the attractants netrin-1 and BDNF caused depolarization. Clamping the growth-cone potential at the resting state prevented Sema3A-induced repulsion; depolarizing potentials converted the repulsion to attraction, whereas hyperpolarizing potentials had no effect. Sema3A increased the intracellular concentration of guanosine 3',5'-cyclic monophosphate ([cGMP]i) by soluble guanylyl cyclase, resulting in fast onset and long-lasting hyperpolarization. Pharmacological increase of [cGMP](i) caused protein kinase G (PKG)-mediated depolarization, switching Sema3A-induced repulsion to attraction. This bimodal switch required activation of either Cl(-) or Na+ channels, which, in turn, regulated the differential intracellular Ca2+ concentration increase across the growth cone. Thus, the polarity of growth-cone potential shifts imposes either attraction or repulsion, and Sema3A achieves this through cGMP signaling.

Using deeply trapped intermediates to map the cytochrome c folding landscape.

Replacement of iron with cobalt(III) selectively introduces a deep trap in the folding-energy landscape of the heme protein cytochrome c. Remarkably, neither the protein structure nor the folding thermodynamics is perturbed by this metal-ion substitution, as shown by data from spectroscopic and x-ray diffraction experiments. Through kinetics measurements, we have found parallel folding pathways involving several different misligated Co(III) species, and, as these folding intermediates persist for several hours under certain conditions, we have been able to elucidate fully their spectroscopic properties. The results, along with an analysis of the fluorescence energy-transfer kinetics during refolding, show that rapidly equilibrating populations of compact and extended polypeptide conformations are present until all molecules have reached the native structure. These measurements provide direct evidence that collapsed denatured structures are not substantially more stable than extended conformations of cytochrome c.