Response to Comment on "Late Upper Paleolithic occupation at Cooper's Ferry, Idaho, USA, ~16,000 years ago".

Manning builds an inappropriate Bayesian age model to assert that the initial occupation at Cooper's Ferry began only ~15,935 ± 75 to 15,130 ± 20 cal yr B.P., suggesting that our estimation of ~16,560 to 15,280 cal yr B.P. is unsupported. However, this analysis both ignores evidence of human occupation from the earliest undated cultural deposits and reflects a misapplication of Bayesian age-modeling techniques. Consequently, his results are unreliable.

A single source femtosecond-millisecond broadband spectrometer.

Time-resolved measurement of population dynamics extending over femtosecond to millisecond time scales typically requires a combination of transient absorption techniques involving different laser systems and detection schemes. The spectrometer design presented here facilitates transient absorption measurements over 12 decades with a single ultrafast laser system by picking pump and probe pulses independently from the laser oscillator pulse train. Unamplified pulses seed a photonic crystal fiber to a supercontinuum probe source for spectrally resolved measurements. The utility of the system is demonstrated by measuring triplet state dynamics following photoexcitation of vitamin B(6) in aqueous solution.

Magnetic fluctuations in nanosized goethite (α-FeOOH) grains.

Mössbauer spectra of antiferromagnetic goethite (α-FeOOH) particles usually show an asymmetric line broadening, which increases with increasing temperature, although the magnetic anisotropy is expected to be so large that magnetic relaxation effects should be negligible. By use of high resolution transmission electron microscopy we have studied a sample of goethite particles and have found that the particles contain many defects such as low angle grain boundaries, in accordance with previous studies of other samples of goethite particles. Such defects can result in a magnetic mismatch at the grain boundaries between nanometer-sized grains, leading to a weakened magnetic coupling between the grains. We show that the Mössbauer data of goethite can be explained by fluctuations of the sublattice magnetization directions in such weakly coupled grains. It is likely that the influence of defects such as low angle grain boundaries also plays a role with regards to the magnetic properties in other antiferromagnetic nanograin systems. We discuss the results in relation to Mössbauer studies of α-Fe(2)O(3) and α-Fe(2)O(3)/NiO nanoparticles.

On the analysis of magnetization and Mössbauer data for ferritin.

Experimental data for antiferromagnetic nanoparticles are often analyzed as if the particles were ferromagnetic. However, due to the volume dependence of the magnetization resulting from uncompensated spins, such analysis will yield erroneous results. This is demonstrated as we analyze ac and dc magnetization data as well as Mössbauer spectra obtained for ferritin. The values of the median energy barrier obtained from the different data are in very close agreement when a distribution of volumes and a volume dependence of the magnetization are taken into account. However, when the volume dependence of the magnetization is neglected, erroneous values of the anisotropy energy barrier and the attempt time τ(0) are obtained.

Orientational dynamics of hydrogen-bonded phenol.

We use femtosecond mid-infrared pump-probe spectroscopy to study the effects of hydrogen bonding on the orientational dynamics of the OD-stretch vibration of phenol-d. We study two samples: phenol-d in chloroform and phenol-d in chloroform to which we added excess acetone. For phenol-d in chloroform, we observe rotational diffusion of the OD group around the CO bond, with a correlation time of 3.7 ps. For phenol-d hydrogen bonded to acetone, the reorientation time is strongly dependent on the probe frequency, varying from 3 ps on the blue side of the spectrum to more than 30 ps on the red side. (c) 2004 American Institute of Physics.

The C. elegans glutamate receptor subunit NMR-1 is required for slow NMDA-activated currents that regulate reversal frequency during locomotion.

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor is important for synaptic plasticity and nervous system development and function. We have used genetic and electrophysiological methods to demonstrate that NMR-1, a Caenorhabditis elegans NMDA-type ionotropic glutamate receptor subunit, plays a role in the control of movement and foraging behavior. nmr-1 mutants show a lower probability of switching from forward to backward movement and a reduced ability to navigate a complex environment. Electrical recordings from the interneuron AVA show that NMDA-dependent currents are selectively disrupted in nmr-1 mutants. We also show that a slowly desensitizing variant of a non-NMDA receptor can rescue the nmr-1 mutant phenotype. We propose that NMDA receptors in C. elegans provide long-lived currents that modulate the frequency of movement reversals during foraging behavior.

North American malignant hyperthermia population: screening of the ryanodine receptor gene and identification of novel mutations.

BACKGROUND: Malignant hyperthermia (MH) is a disorder of skeletal muscle manifested as a life-threatening hypermetabolic crisis in susceptible individuals after exposure to inhalational anesthetics and depolarizing muscle relaxants. Mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1) are considered a common cause of the disorder, and, to date, more than 20 RYR1 mutations have been reported in European and Canadian families. Some studies suggest that differences may exist in the frequencies and distribution of mutations in the RYR1 gene between European and North American MH families the frequency and distribution of mutations in the RYR1 gene. METHODS: Skeletal muscle samples from 73 unrelated individuals diagnosed as MH susceptible according to the North American MH caffeine-halothane contracture test were studied. Genomic DNA of MH-susceptible patients was investigated by polymerase chain reaction-based restriction fragment length polymorphism, single-strand conformation polymorphism, and sequencing analysis. The majority of known RYR1 mutations were analyzed using the restriction fragment length polymorphism method, whereas new mutations were searched by single-strand conformation polymorphism in exons 12, 15, 39, 40, 44, 45, and 46 of the gene. RESULTS: Seven known RYR1 mutations (Arg163Cys, Gly248Arg, Arg614Cys, Val2168Met, Thr2206Met, Gly2434Arg, and Arg2454His) were detected at frequencies of 2.7, 1.4, 1.4, 1.4, 1.4, 5.5, and 4.1%, respectively. In addition, three novel amino acid substitutions (Val2214Ile, Ala2367Thr, and Asp2431Asn) were detected at frequency of 1.4% each. These 10 mutations account for 21.9% of the North American MH-susceptible population. CONCLUSION: Three novel candidate mutations in the RYR1 gene were identified in these MH patients. The frequency and distribution of RYR1 mutations observed in this North American MH population was markedly different from that previously identified in Europe. Larger-scale studies are necessary to clarify the type and frequency of mutations in RYR1 associated with MH in North American families.

Differential expression of glutamate receptor subunits in the nervous system of Caenorhabditis elegans and their regulation by the homeodomain protein UNC-42.

In almost all nervous systems, rapid excitatory synaptic communication is mediated by a diversity of ionotropic glutamate receptors. In Caenorhabditis elegans, 10 putative ionotropic glutamate receptor subunits have been identified, a surprising number for an organism with only 302 neurons. Sequence analysis of the predicted proteins identified two NMDA and eight non-NMDA receptor subunits. Here we describe the complete distribution of these subunits in the nervous system of C. elegans. Receptor subunits were found almost exclusively in interneurons and motor neurons, but no expression was detected in muscle cells. Interestingly, some neurons expressed only a single subunit, suggesting that these may form functional homomeric channels. Conversely, interneurons of the locomotory control circuit (AVA, AVB, AVD, AVE, and PVC) coexpressed up to six subunits, suggesting that these subunits interact to generate a diversity of heteromeric glutamate receptor channels that regulate various aspects of worm movement. We also show that expression of these subunits in this circuit is differentially regulated by the homeodomain protein UNC-42 and that UNC-42 is also required for axonal pathfinding of neurons in the circuit. In wild-type worms, the axons of AVA, AVD, and AVE lie in the ventral cord, whereas in unc-42 mutants, the axons are anteriorly, laterally, or dorsally displaced, and the mutant worms have sensory and locomotory defects.

Bromocriptine reduces cigarette smoking.

AIMS: Animal studies have shown that nicotine releases dopamine, a neurotransmitter implicated in drug reinforcement. We hypothesized that bromocriptine would decrease smoking behavior in humans. DESIGN: The study was conducted double blind and subjects' order of dose exposure was randomized. PARTICIPANTS: The smoking behavior of 20 heavy smokers was recorded for 5 hours after ingesting placebo or one of two doses of bromocriptine (2.50 mg, 3.75 mg) over three sessions (one dose per session). FINDINGS: There was a significant negative linear trend by dosage indicating shorter total puffing time with increasing bromocriptine dosages (p < 0.02). Other significant negative linear trends by increasing dosage include fewer number of puffs, fewer number of cigarettes smoked and mean latency to smoke after 3 hours (expected CMAX on the drug (all ps < 0.05). There was a negative significant linear trend showing decreased plasma nicotine (p < 0.02) and cotinine (p < 0.005) with increasing dosages of bromocriptine. Shiffman/Jarvik Withdrawal Scale (SJWS) cigarette craving subscale scores decreased significantly across increasing dosages (linear trend p < 0.02). There was a significant negative linear trend (p < 0.05) on the Profile of Mood States (POMS) Vigor and Depression subscales, with subjects reporting decreased vigor and depression with increasing bromocriptine doses. No other mood effects were observed. CONCLUSION: These results support the hypothesis that dopaminergic mechanisms mediate cigarette smoking reinforcement.

Density profiles of Alzheimer disease regional brain pathology for the huddinge brain bank: pattern recognition emulates and expands upon Braak staging.

Density profiles of Alzheimer's disease (AD) regional brain pathology were constructed for 249 subjects in the Huddinge Brain Bank. Counts per square millimeter for neurofibrillary tangles (NFT), diffuse plaques (DP), and neuritic plaques (NP) in 38 areas were investigated using a pattern recognition technique called GoM. The seven distributional profiles of AD neuropathology emulated and expanded upon Braak staging illustrating induction (Groups 1-3) and clinical progression (Groups 4-7). Normal aging represented limited AD changes, few NFT in the entorhinal cortex and hippocampal CA1 (Group 1). The threshold for possible AD was NFT in the subiculum (Group 2), found with DP in the neocortex. Temporal medial NFT was the threshold for probable AD (Group 4). The 'oldest-old', often demented without brain atrophy, had extensive entorhinal/CA1 NFT and cortical DP, but few cortical NFT or NP (Group 5). A second subtype 'disconnection' (Group 6) lacked AD pathology for a specific set of subcortical and cortical areas. Accumulation of NFT in first-affected areas continued through end-stage disease (Group 7), with apparent rapid transition of DP to NP in the cortex during clinical progression. The evolution of AD is a highly ordered sequential process. Pattern recognition approaches such as GoM may be useful in better defining the process.

N-methyl-DL-aspartic acid monohydrate.

The title compound, C(5)H(9)NO(4).H(2)O, has been synthesized and crystallized. It crystallizes in Cc with one molecule in the asymmetric unit. The compound is found in its zwitterionic form. D and L forms of the compound are linked in the crystal via O-H...O and N-H.O hydrogen bonds, both directly between the aspartic acid-derivative entities and to the crystal water molecule. A weak intramolecular N-H...O interaction is found. The carbon skeleton is slightly twisted with C-C-C-C = 166.83 (11) degrees. A comparison with other derivatives of aspartic acid shows only two rotamers--one with a near planar carbon skeleton and one with a significantly twisted carbon skeleton.

Nicotine blood levels and subjective craving for cigarettes.

This study examined cigarette craving and blood nicotine levels in 11 male heavy smokers who were observed during 16 h of tobacco abstinence. Subjects rated their urge to smoke on a new brief 10-item questionnaire, Urge to Smoke (UTS), Schuh and Stitzer's four-item Visual Analog Scale (SSI), and a Strength of Urge to Smoke (SUTS) item. Testing occurred: 1) after 16 h (1700 h the night before to 0900 h the next morning) of abstinence from smoking; 2) after an ad lib smoking period following the 16 h abstinence; 3) every hour during 6 hours of abstinence; 4) and finally, after the 6 h abstinence, another ad lib smoking period. Thus, subjects smoked twice in each session. Blood plasma nicotine levels were measured before, after, and every 2 h during the 6-h abstinence period for a total of six measures. Blood pressure and heart rate were measured prior to each blood draw. There was a significant negative correlation between blood nicotine levels and craving for cigarettes on all craving questionnaires (rs = -0.55 to -0.78; ps < 0.002). Carbon monoxide was shown to correlate highly with nicotine blood levels (rs = 0.83 to 0.98 across subjects; ps < 0.001). Results are consistent with the hypothesis that "urge to smoke" reflects nicotine seeking in continuing smokers.

Atoms in crystals--from experimental charge densities.

An implementation is described of R. F. W. Bader's [Atoms in Molecules: a Quantum Theory (1990). Oxford: Clarendon Press] virial fragmentation of the electron density as applied to experimentally determined electron densities. It is analogous to the PROMEGA method [Keith (1993), PhD thesis, McMaster University, Ontario, Canada]. Integrated atomic properties have been determined using the models from two recent accurate charge-density studies: methylammonium hydrogen succinate monohydrate and methylammonium hydrogen maleate.

Neuronal control of locomotion in C. elegans is modified by a dominant mutation in the GLR-1 ionotropic glutamate receptor.

How simple neuronal circuits control behavior is not well understood at the molecular or genetic level. In Caenorhabditis elegans, foraging behavior consists of long, forward movements interrupted by brief reversals. To determine how this pattern is generated and regulated, we have developed novel perturbation techniques that allow us to depolarize selected neurons in vivo using the dominant glutamate receptor mutation identified in the Lurcher mouse. Transgenic worms that expressed a mutated C. elegans glutamate receptor in interneurons that control locomotion displayed a remarkable and unexpected change in their behavior-they rapidly alternated between forward and backward coordinated movement. Our findings suggest that the gating of movement reversals is controlled in a partially distributed fashion by a small subset of interneurons and that this gating is modified by sensory input.

Individual variations of pH, buffer capacity, and concentrations of calcium and phosphate in unstimulated whole saliva.

In order to evaluate the risk of development of dental caries and/or of formation of dental calculus, salivary variables have often been used, but not with particular success. A reason for the apparent lack of association could be that the individual temporal variation of a characteristic was so substantial relative to the overall variation that it is not possible to characterize an individual by a single salivary measurement. The aim here was to examine the individual variation of pH, buffer capacity, and concentrations of calcium and phosphate and to compare it with the overall variation of the characteristics in order to shed light on the above problem. Eight weekly samples of up to 4 ml of unstimulated whole saliva were collected from 11 dental students before tooth brushing on their arrival at 8 a.m. in the dental school. Calcium was determined by atomic absorption spectroscopy, phosphate colorimetrically, and pH electrometrically. The buffer capacity was assessed by titration of the saliva sample from the pH initially observed to pH 3. It was found that within each individual the concentration of calcium and of phosphate, pH, the hydroxyapatite ion product and the buffer capacity varied considerably over the 7 weeks. The individual range frequently covered more than a third of the total range. Further, within each of the variables, single individuals could be found whose samples covered 60% or more of the overall range, whilst others covered less than 10% of the range. It was therefore concluded that, although collected at the same time of the day, pH, buffer capacity and concentrations of calcium and phosphate in unstimulated whole saliva in the single individual vary so much that characterization of individuals and of their saliva based on a single salivary analysis is unreliable and hazardous.

The single-crystal structure of the organic superconductor betaCO-(BEDT-TTF)2I3 from a powder grain.

Synchrotron radiation diffraction data have been collected at 200 K on a microscopic single crystal (dimensions 12 x 10 x 2 µm) of the title compound, where BEDT-TTF is bis(ethylenedithio)tetrathiafulvalene, C(10)H(8)S(8). The quality of the diffraction data allowed a full structure refinement and enabled the determination of structural details such as the conformations of the ethylene groups as well as the occupancy of the triiodide sites. The compound was found to be slightly iodine-deficient and better described as beta(CO)-(BEDT-TTF)(2)I(3-x) [x = 0.014 (3)]. One of the ethylene groups of the BEDT-TTF cation is disordered at this temperature and exists in two distinct conformations with occupancies which are identical within the standard uncertainty.

Imaging soft x-rays using a microchannel plate.

The GOLDHELOX Project is a student run project to construct a robotic solar telescope that will be used to take images of the sun in the soft X-ray region (171–181Å) of the spectrum. The optical system uses a microchannel plate (MCP) detector. We tested the MCP to familiarize ourselves with and verify that MCP's can be used to image soft X-rays. Soft X-rays were created by a Manson source attached to a proportional counter to determine the amount of emitted X-rays detected by the MCP. The voltages on the MCP were varied to observe responses of varying voltage differences. Most of the observations were visible observations along with images made by a 35 mm camera with a telephoto lens. We found the 1000 V difference to produce the strongest and clearest images.