Isolation and genome sequence annotation of SallyK, a newly discovered cluster EG bacteriophage infecting Microbacterium.

Discovered from soil in a flower planter in Pocatello, Idaho and using Microbacterium foliorum, SallyK is a lytic bacteriophage with a siphovirus morphology. It has a 62,883 bp-long genome with 103 putative genes. Based on gene content similarity to actinobacteriophages, SallyK is assigned to cluster EG.

Isolation and genome sequence annotation of KillerTomato, a newly discovered cluster EE bacteriophage infecting Microbacterium.

Discovered in Pocatello, Idaho, soil near a tomato garden, siphovirus KillerTomato infects Microbacterium foliorum NRRL B-24224. KillerTomato is a lytic cluster EE phage with a 17,442-bp genome and 68.6% GC content. Of 25 genes, 20 were assigned putative functions, including a putative tail assembly chaperone protein with a programmed frameshift and an endolysin.

The 1933 Long Beach Earthquake (California, USA): Ground Motions and Rupture Scenario.

We present a synoptic analysis of the ground motions from the 11 March 1933 Mw 6.4 Long Beach, California, earthquake, the largest known earthquake within the central Los Angeles Basin region. Our inferred shaking intensity pattern supports the association of the earthquake with the Newport-Inglewood fault; it further illuminates the concentration of severe damage in the town of Compton, where accounts suggest vertical ground motions exceeding 1 g. We use a broadband simulation approach to develop a rupture scenario for this earthquake, informed by the damage distribution. The predicted shaking for a 25-km-long fault matches the intensity distribution, with an indication that non-linear site response on soft sediments in some near-field regions was stronger than predicted using a simple model to account for non-linearity. Our results suggest that the concentration of damage near Compton can be explained by a combination of local site amplification, source-controlled directivity, and three-dimensional basin effects whereby energy was channeled towards the deepest part of the Los Angeles Basin.

Cardiorespiratory fitness and white matter integrity in Alzheimer's disease.

The objective of this study was to investigate the relationship between cardiorespiratory (CR) fitness and the brain's white matter tract integrity using diffusion tensor imaging (DTI) in the Alzheimer's disease (AD) population. We recruited older adults in the early stages of AD (n = 37; CDR = 0.5 and 1) and collected cross-sectional fitness and diffusion imaging data. We examined the association between CR fitness (peak oxygen consumption [VO2peak]) and fractional anisotropy (FA) in AD-related white matter tracts using two processing methodologies: a tract-of-interest approach and tract-based spatial statistic (TBSS). Subsequent diffusivity metrics (radial diffusivity [RD], mean diffusivity [MD], and axial diffusivity [A × D]) were also correlated with VO2peak. The tract-of-interest approach showed that higher VO2peak was associated with preserved white matter integrity as measured by increased FA in the right inferior fronto-occipital fasciculus (p = 0.035, r = 0.36). We did not find a significant correlation using TBSS, though there was a trend for a positive association between white matter integrity and higher VO2peak measures (p < 0.01 uncorrected). Our findings indicate that higher CR fitness levels in early AD participants may be related to preserved white matter integrity. However to draw stronger conclusions, further study on the relationship between fitness and white matter deterioration in AD is necessary.

A line scanning confocal fluorescent microscope using a CMOS rolling shutter as an adjustable aperture.

Traditional confocal microscopy uses a physical aperture barrier to prevent out-of-focus light from reaching the detector. The physical nature of a conventional aperture limits control over the system confocality. We describe a new line scanning confocal microscope that eliminates a need for a physical aperture by employing a software-controllable rolling shutter on a CMOS camera. A confocal image is obtained by synchronizing motion of the rolling shutter and the laser line scanning over a sample. Confocal resolution of this microscope is adjustable in real time and independently established for each fluorescence channel by changing the rolling shutter width. This technology has been implemented in the IN Cell Analyzer 6000 system by GE Healthcare.

Memory of pain and anxiety associated with tooth extraction.

Concerns regarding pain constitute a large component of dental anxiety, and patients with high dental anxiety are likely to have exaggerated memory and prediction of dental pain. It remains to be investigated, however, if memory of anxiety is exaggerated in a manner similar to that of pain, and if anxiety and pain assimilate in memory over time. A sample of 79 patients presenting for emergency extraction rated their anxiety and pain before, during, and two weeks after the procedure. Measures of trait dental anxiety and fear of pain also were collected. All patients exaggerated their recall of procedure pain, but only those high in trait dental anxiety exaggerated their recall of anxiety. Highly anxious patients reported more pain prior to the procedure and expected more pain; ratings of anxiety and pain for all participants assimilated over time.

Heat treatment effects on electrochemical corrosion parameters of high-Pd alloys.

This research determined the effect oxidation, as that occurs during porcelain firing, has upon the corrosion parameters of Pd-based ceramic alloys and how it may relate to Pd allergy. The 20 h open circuit potential (OCP), 20 h corrosion rate (Icorr), and anodic polarization (E-i) curves of 11 commercial Pd alloys were measured in a phosphate buffered saline solution. The alloys were divided into the following four groups based upon composition: PdGa(Ag), PdCu, PdAg, and AuPd and tested in both as-cast and oxidized conditions. In both the as-cast and oxidized conditions, the OCP of Ag-containing Pd alloys is significantly lower than non Ag-containing high-Pd alloys. The OCP of all alloys increased after oxidation. With regard to corrosion rate, the Ag-containing alloys showed a decrease in Icorr with oxidation. In contrast, three of the four non Ag-containing high-Pd (>or=74 wt%) alloys exhibited a higher Icorr. A comparison of the anodic polarization curves showed only the alloys containing larger amounts (>or=16 wt%) of Ag displayed a notable difference between as-cast and oxidized states. Oxidation as required during porcelain-fused-to-metal device preparation alters the electrochemical characteristics of the alloys studied. This alteration may be of importance with regard to their potential for Pd allergy.

Combined IV-intra-arterial thrombolysis: a color-coded duplex pilot study.

The authors compared the transcranial color-coded duplex pattern of the middle cerebral arteries (MCAs) before and after IV and combined IV-intra-arterial (IV-IA) thrombolysis in consecutive first-ever stroke patients. Patients receiving combined IV-IA thrombolysis showed greater improvement in flow signal and higher incidence of complete MCA recanalization vs those receiving IV thrombolysis, especially when the MCA was occluded or had only minimal flow.

Radioprotection in mice following oral delivery of amifostine nanoparticles.

PURPOSE: Amifostine (Ethyol) is an approved cytoprotective agent prescribed to reduce certain side-effects in the chemotherapy of ovarian or non-small cell lung cancer, or in radiation treatment of head-and-neck cancer. The usefulness of this drug is further hampered, because it is not effective when given orally. The objective of this part of the project was to evaluate the radioprotective efficacy of orally active amifostine nanoparticles. MATERIALS AND METHODS: Radioprotective efficacy was evaluated by measuring the ability of the amifostine nanoparticles (equivalent to 500 mg/Kg) to inhibit whole-body gamma irradiation -induced injury in mice. All mice received acute whole-body gamma irradiation from a Cesium-137 source and the radioprotective efficacy of the formulation was determined by measuring 30-day survival at 9 Gy, bone marrow hemopoeitic progenitor cell survival at 9 Gy and 8 Gy, and intestinal crypt cell survival at 11 Gy. RESULTS: Thirty-day survival, hemopoietic progenitor cell survival, as well as the jejunal crypt cell survival were all significantly enhanced when the mice were treated orally with the amifostine nanoparticles 1 h prior to irradiation. CONCLUSIONS: These results clearly and unequivocally demonstrate that the amifostine nanoparticles developed in our laboratory provides significant protection from acute whole-body gamma irradiation injury in mice.

The effect of coencapsulation of bovine insulin with cyclodextrins in ethylcellulose microcapsules.

Polymeric microcapsules have been widely investigated for protein delivery. Common problems include: low stability, low encapsulation efficiency, lack of uniformity, and burst release. Cyclodextrins (CDs) are known to enhance stability and solubility of proteins in solution. This research examines the effect of alpha-, beta-, and gamma-CDs on: (1) stability, (2) encapsulation, and (3) release of insulin from ethylcellulose microcapsules. All CDs improved thermal stability of insulin by lowering the enthalpy of unfolding by 16-52%. alpha- and gamma-CDs also increased the encapsulation efficiency of insulin and improved uniformity of the microcapsule formulations. Two mathematical models were proposed to account for insulin release and consisted of multiple zero order and first order input processes, and a single first order output process. All CDs decreased the initial burst release of insulin by up to 30%. This research demonstrates the potential for CDs to improve stability, uniformity, and encapsulation of proteins in microcapsule formulations.

Boston naming test short forms: a comparison of previous forms with new item response theory based forms.

Two new short forms of the Boston Naming Test (BNT) were developed using item response theory (IRT) with data from 206 elderly outpatients. We evaluated the diagnostic ability of 12 short forms among the full sample and in a sub-sample of 69 patients diagnosed with mild Alzheimer's disease (AD) either alone or in combination with vascular dementia (VD). The full BNT (reliability alpha = .90) identified 44% of the AD/VD patients as abnormal on naming. Our 30 item short form (alpha = .90) also identified 44% of the AD/VD patients as abnormal, with 93% agreement with the full BNT on abnormal AD/VD patient classifications. Our 15 item short form (alpha = .84) identified 48% of the AD/VD patients as abnormal, with 90% agreement with the full BNT's abnormal classifications. An adaptive 30/15 item version equaled the performance of the full 30 item test while requiring only 15 items for 75% of the patients with normal naming ability. This study illustrates the utility of IRT for developing neuropsychological assessment tools.

Correcting the 3MS for bias does not improve accuracy when screening for cognitive impairment or dementia.

We investigated the effects of correcting for demographic biases on the sensitivity and specificity of the Modified Mini Mental Status Exam (3MS) using a sample of English-speaking older adults (N=8901) from the Canadian Studies of Health and Aging. The sensitivity and specificity of the original 3MS were compared to the 3MS regression-adjusted for the influence of demographic variables and then to 3MS percentiles based on published normative data with age and education corrected cutoff scores. According to receiver operating characteristic curve analyses, the regression-adjusted 3MS was no more accurate than the original 3MS when screening for dementia, and it was less accurate when screening for cognitive impairment. The use of 3MS percentiles based on normative data with age and education corrected cut-off points were less accurate than the original 3MS when screening for both cognitive impairment and when screening for dementia.

Development of biodegradable microcapsules as carrier for oral controlled delivery of amifostine.

The primary objective of this project was to develop a biodegradable, orally active controlled-release formulation of amifostine. Development of such a formulation will mark an important advancement in the areas of chemoprotection and radioprotection. Biodegradable microcapsules of amifostine were prepared using poly(lactide/glycolide) (PLGA 50:50). The microcapsules were prepared by solvent evaporation technique. Amifostine-loaded microcapsules were evaluated for particle size, surface morphology, thermal characteristics, and drug release. Particle size and surface morphology were determined using scanning electron microscopy (SEM). Thermal characterization was conducted using differential scanning calorimetry (DSC). In vitro release study was performed at 37 degrees C using phosphate buffer (pH 7.4). Amifostine release was calculated by measuring the amount of drug remaining within the microcapsules at a specific sampling time. The amount of amifostine in the samples was determined by high-performance liquid chromatography (HPLC) using an electrochemical detector. The yield of microcapsules was 75%. Scanning electron microscopy pictures revealed that the particles were nearly spherical and smooth with an average size of 54 microm. Differential scanning calorimetry thermograms showed that microcapsules loaded with amifostine have a glass transition at 39.4 degrees C, and the melting endotherm of amifostine was absent. The absence of a melting endotherm for amifostine was an indication that amifostine was not in the crystalline state in the microcapsules, but rather in the form of a solid solution in PLGA. Approximately 50% amifostine was released during the first 6 hr of the in vitro release study. The drug, however, continued to release over the observed period of 12 hr during which 92% amifostine was released.

Loose but normal: a semantic association study.

An abnormal facilitation of the spreading activation within semantic networks is thought to under-lie schizophrenics' remote associations and referential ideas. In normal subjects, elevated magical ideation (MI) has also been associated with a style of thinking similar to that of schizotypal subjects. We thus wondered whether normal subjects with a higher MI score would judge "loose associations" as being more closely related than do subjects with a lower MI score. In two experiments, we investigated whether judgments of the semantic distance between stimulus words varied as a function of MI. In the first experiment, random word pairs of two word classes, animals and fruits, were presented. Subjects had to judge the semantic distance between word pairs. In the second experiment, sets of three words were presented, consisting of a pair of indirectly related, or unrelated nouns plus a third noun. Subjects had to judge the semantic distance of the third noun to the word pair The results of both experiments showed that higher MI subjects considered unrelated words as more closely associated than did lower MI subjects. We conjecture that for normal subjects high on MI "loose associations" may not be loose after all. We also note that the tendency to link uncommon, nonobvious, percepts may not only be the basis of paranormal and paranoid ideas of reference, but also a prerequisite of creative thinking.

Porous biodegradable microparticles for delivery of pentamidine.

The primary objective of this study was to develop a method for the preparation of porous biodegradable controlled release formulation of poly(lactide/glycolide) (PLGA). The model drug used for this study was pentamidine. Scanning electron microscopy pictures showed that these microparticles are highly porous and spherical in shape. A comparison of particle size reveals a similar median particle size (54-68 microm) in all six batches. The particles are all smaller than 90 microm. Differential scanning calorimetry thermograms revealed that pentamidine was mostly present in the crystalline form in the microparticles and did not dissolve in PLGA. The efficiency of encapsulation of pentamidine was higher than 58% in all six batches. The amount of drug released from these microparticles was at least 12% within the first 60 min. At least 50% of the total drug was released within the first 4 h. Drug release from these microparticles continued for up to 12 h. This faster drug dissolution was due to the highly porous surface. This highly porous surface will allow large molecules to release at a much faster rate than the regular microcapsules/microspheres.

Statistical power and effect sizes of clinical neuropsychology research.

Cohen, in a now classic paper on statistical power, reviewed articles in the 1960 issue of one psychology journal and determined that the majority of studies had less than a 50-50 chance of detecting an effect that truly exists in the population, and thus of obtaining statistically significant results. Such low statistical power, Cohen concluded, was largely due to inadequate sample sizes. Subsequent reviews of research published in other experimental psychology journals found similar results. We provide a statistical power analysis of clinical neuropsychological research by reviewing a representative sample of 66 articles from the Journal of Clinical and Experimental Neuropsychology, the Journal of the International Neuropsychology Society, and Neuropsychology. The results show inadequate power, similar to that for experimental research, when Cohen's criterion for effect size is used. However, the results are encouraging in also showing that the field of clinical neuropsychology deals with larger effect sizes than are usually observed in experimental psychology and that the reviewed clinical neuropsychology research does have adequate power to detect these larger effect sizes. This review also reveals a prevailing failure to heed Cohen's recommendations that researchers should routinely report a priori power analyses, effect sizes and confidence intervals, and conduct fewer statistical tests.

Miniaturization of a hepatitis C virus RNA polymerase assay using a -102 degrees C cooled CCD camera-based imaging system.

Innovations in detection technologies have allowed us to develop a novel assay in 1536-well plate format and assess the advantages of screen miniaturization compared with conventional high-throughput compound screening in 96- or 384-well plates. An HCV RNA polymerase assay has been miniaturized in 1536-well plates by using a new detection technology known as LEADseeker homogeneous imaging system. It uses a -102 degrees C cooled charge-coupled device (CCD) camera and newly designed scintillation proximity microparticles. The miniaturized assay used europium-doped streptavidin-coated yttrium oxide (YO(x)) or polystyrene (PS) microspheres to capture biotin-labeled [(3)H]RNA product transcripts. Beads in proximity to the radioisotope convert the emitted beta(-) particles into photons having wavelengths in the red region of the visible spectrum, optimal for detection by the CCD camera. Because the camera collects light from all wells of the plate simultaneously, 1536-well plates are imaged as rapidly as 384-well plates, on the order of 10 min per plate. The assay has a signal to background of approximately 20-fold, satisfactory for high-throughput robotics screening. The enzyme kinetics and potency of a known inhibitor were similar to those obtained from the conventional assay using scintillation proximity assay (SPA) beads and a scintillation plate counter. Furthermore, the newly developed microbeads (emitting at 610 to 620 nm) are less prone to quenching effects caused by yellow-colored compounds, than conventional SPA beads or scintillation fluid (emitting at 400 to 480 nm region). Thus, the LEADseeker imaging system is a useful new tool for miniaturization of assays for high-throughput screening.

Expression of human alpha 2-adrenergic receptors in adipose tissue of beta 3-adrenergic receptor-deficient mice promotes diet-induced obesity.

Catecholamines play an important role in controlling white adipose tissue function and development. beta- and alpha 2-adrenergic receptors (ARs) couple positively and negatively, respectively, to adenylyl cyclase and are co-expressed in human adipocytes. Previous studies have demonstrated increased adipocyte alpha 2/beta-AR balance in obesity, and it has been proposed that increased alpha 2-ARs in adipose tissue with or without decreased beta-ARs may contribute mechanistically to the development of increased fat mass. To critically test this hypothesis, adipocyte alpha 2/beta-AR balance was genetically manipulated in mice. Human alpha 2A-ARs were transgenically expressed in the adipose tissue of mice that were either homozygous (-/-) or heterozygous (+/-) for a disrupted beta 3-AR allele. Mice expressing alpha 2-ARs in fat, in the absence of beta 3-ARs (beta 3-AR -/- background), developed high fat diet-induced obesity. Strikingly, this effect was due entirely to adipocyte hyperplasia and required the presence of alpha2-ARs, the absence of beta 3-ARs, and a high fat diet. Of note, obese alpha 2-transgenic beta 3 -/- mice failed to develop insulin resistance, which may reflect the fact that expanded fat mass was due to adipocyte hyperplasia and not adipocyte hypertrophy. In summary, we have demonstrated that increased alpha 2/beta-AR balance in adipocytes promotes obesity by stimulating adipocyte hyperplasia. This study also demonstrates one way in which two genes (alpha 2 and beta 3-AR) and diet interact to influence fat mass.

Electrochemical characteristics of high-Pd alloys in relation to Pd-allergy.

OBJECTIVE: The aim of this study was to determine whether the Pd-Cu-based dental ceramic alloys possess any electrochemical characteristics distinguishable from that of other Pd-containing alloys. Of all Pd-containing alloys, this particular alloy group has been linked to frequent incidence of allergy and hypersensitivity reactions. Electrochemical corrosion may instigate these reactions. METHODS: Four groups of alloys, Pd-Cu, Pd-Ga-(with and without Ag), Pd-Ag, and Au-Pd, were evaluated by traditional corrosion measurement techniques in a phosphated buffer saline solution at 20 degrees C. The electrochemical characteristics measured were: (1) 20 h open circuit potential (OCP); (2) 20 h corrosion rate (Icorr); and (3) anodic polarization (E-i) curves. RESULTS: The OCP values (232 +/- 25 mV) of the Ag-free Pd-Ga and Pd-Cu-based alloys were higher than and distinctly different from that (144 +/- 52 mV) of the Ag-containing alloys. The Icorr values of different alloys, despite varied compositions, were indistinguishable from one another. The E-i curves of all alloys were essentially similar, with the Ag-containing (> 5 wt%) alloys showing a subtle difference in their anodic slope within 100 mV above their corrosion potentials. SIGNIFICANCE: The OCP values of Pd-Cu alloys and the Ag-free Pd-Ga alloy are comparable to that reported for pure Pd (239 +/- 21 mV), which indicates that during corrosion these alloys undergo dealloying and consequent Pd-enrichment on their surface. Such a condition is conducive to the release of allergenic Pd++ ions and offers a plausible explanation for the frequent incidence of hypersensitivity reactions associated with the Pd-Cu alloys. The OCP values in other alloys are attributed to dealloying followed by surface enrichment with Ag and/or Au and the possible formation of an insoluble AgCl surface film on the respective alloy surfaces. These events have the potential to suppress or prevent Pd++ ion release. Alloys showing these characteristics have seldom been linked to allergic reactions.

Accuracy of regression equation prediction across the range of estimated premorbid IQ.

Linear regression is often used to predict psychological criterion variables such as premorbid IQ. The prevailing method of evaluating the accuracy of prediction indicates poor accuracy for both high and low criterion values. These results have led to the conclusion that the equations are not applicable for predicting scores beyond about one standard deviation from the mean. The apparent inaccuracy at the extremes, however, is an artifact of inappropriate analysis. An alternative analysis method is described and used to re-analyze two sets of data. Empirical results show that both high and low WAIS-R IQ scores, predicted using versions of the NART, agree with actual measured IQ scores as accurately as do predicted scores near the mean. In addition, confidence intervals were only 5% larger for more extreme predicted values than for values near the mean, which would be of minor clinical consequence. The practical constraint on prediction of extreme values arises not from the regression technique, but from the limited range of the predictor variable(s). The two reviewed IQ prediction equations would, however, have adequate range for a high percentage of individuals.