Adaptation kinetics in bacterial chemotaxis

Cells of Escherichia coli, tethered to glass by a single flagellum, were subjected to constant flow of a medium containing the attractant alpha-methyl-DL-aspartate. The concentration of this chemical was varied with a programmable mixing apparatus over a range spanning the dissociation constant of the chemoreceptor at rates comparable to those experienced by cells swimming in spatial gradients. When an exponentially increasing ramp was turned on (a ramp that increases the chemoreceptor occupancy linearly), the rotational bias of the cells (the fraction of time spent spinning counterclockwise) changed rapidly to a higher stable level, which persisted for the duration of the ramp. The change in bias increased with ramp rate, i.e., with the time rate of change of chemoreceptor occupancy. This behavior can be accounted for by a model for adaptation involving proportional control, in which the flagellar motors respond to an error signal proportional to the difference between the current occupancy and the occupancy averaged over the recent past. Distributions of clockwise and counterclockwise rotation intervals were found to be exponential. This result cannot be explained by a response regular model in which transitions between rotational states are generated by threshold crossings of a regular subject to statistical fluctuation; this mechanism generates distributions with far too many long events. However, the data can be fit by a model in which transitions between rotational states are governed by first-order rate constants. The error signal acts as a bias regulator, controlling the values of these constants

Helicopter Airborne Laser Positioning System (HALPS)

The theory of operation, configuration, laboratory, and ground test results obtained with a helicopter airborne laser positioning system developed by Princeton University is presented. Unfortunately, due to time constraints, flight data could not be completed for presentation at this time. The system measures the relative position between two aircraft in three dimensions using two orthogonal fan-shaped laser beams sweeping across an array of four detectors. Specifically, the system calculates the relative range, elevation, and azimuth between an observation aircraft and a test helicopter with a high degree of accuracy. The detector array provides a wide field of view in the presence of solar interference due to compound parabolic concentrators and spectral filtering of the detector pulses. The detected pulses and their associated time delays are processed by the electronics and are sent as position errors to the helicopter pilot who repositions the aircraft as part of the closed loop system. Accuracies obtained in the laboratory at a range of 80 ft in the absence of sunlight were + or - 1 deg in elevation; +0.5 to -1.5 deg in azimuth; +0.5 to -1.0 ft in range; while elevation varied from 0 to +28 deg and the azimuth varied from 0 to + or - 45 deg. Accuracies in sunlight were approximately 40 deg (+ or - 20 deg) in direct sunlight

Coordination of flagella on filamentous cells of Escherichia coli

Video techniques were used to study the coordination of different flagella on single filamentous cells of Escherichia coli. Filamentous, nonseptate cells were produced by introducing a cell division mutation into a strain that was polyhook but otherwise wild type for chemotaxis. Markers for its flagellar motors (ordinary polyhook cells that had been fixed with glutaraldehyde) were attached with antihook antibodies. The markers were driven alternately clockwise and counterclockwise, at angular velocities comparable to those observed when wild-type cells are tethered to glass. The directions of rotation of different markers on the same cell were not correlated; reversals of the flagellar motors occurred asynchronously. The bias of the motors (the fraction of time spent spinning counterclockwise) changed with time. Variations in bias were correlated, provided that the motors were within a few micrometers of one another. Thus, although the directions of rotation of flagellar motors are not controlled by a common intracellular signal, their biases are. This signal appears to have a limited range

Automated analysis of quantitative image data using isomorphic functional mixed models, with application to proteomics data

Image data are increasingly encountered and are of growing importance in many areas of science. Much of these data are quantitative image data, which are characterized by intensities that represent some measurement of interest in the scanned images. The data typically consist of multiple images on the same domain and the goal of the research is to combine the quantitative information across images to make inference about populations or interventions. In this paper we present a unified analysis framework for the analysis of quantitative image data using a Bayesian functional mixed model approach. This framework is flexible enough to handle complex, irregular images with many local features, and can model the simultaneous effects of multiple factors on the image intensities and account for the correlation between images induced by the design. We introduce a general isomorphic modeling approach to fitting the functional mixed model, of which the wavelet-based functional mixed model is one special case. With suitable modeling choices, this approach leads to efficient calculations and can result in flexible modeling and adaptive smoothing of the salient features in the data. The proposed method has the following advantages: it can be run automatically, it produces inferential plots indicating which regions of the image are associated with each factor, it simultaneously considers the practical and statistical significance of findings, and it controls the false discovery rate.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS407 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

CHOP links endoplasmic reticulum stress to NF-κB activation in the pathogenesis of nonalcoholic steatohepatitis

Free fatty acid induction of inflammation and cell death is an important feature of nonalcoholic steatohepatitis (NASH) and has been associated with disruption of the endoplasmic reticulum and activation of the Unfolded Protein Response (UPR). Following chronic UPR activation, the transcription factor CHOP (GADD153/DDIT3) triggers cell death; however, the mechanisms linking the UPR or CHOP to hepatoceullular injury and inflammation in the pathogenesis of NASH are not well understood. Using HepG2 and primary human hepatocytes, we found that CHOP induces cell death and inflammatory responses following saturated free fatty acid exposure by activating NF-κB through a pathway involving IRAK2 expression, resulting in secretion of cytokines IL-8 and TNFα directly from hepatocytes. TNFα facilitates hepatocyte death upon exposure to saturated free fatty acids and secretion of both IL-8 and TNFα contribute to inflammation. Interestingly, CHOP/NF-κB signaling is not conserved in primary rodent hepatocytes. Our studies suggest that CHOP plays a vital role in the pathophysiology of NASH through induction of secreted factors that trigger inflammation and hepatocellular death via a signaling pathway specific to human hepatocytes

Kinematic classifications of local interacting galaxies: implications for the merger/disk classifications at high-z

The classification of galaxy mergers and isolated disks is key for understanding the relative importance of galaxy interactions and secular evolution during the assembly of galaxies. The kinematic properties of galaxies as traced by emission lines have been used to suggest the existence of a significant population of high-z star-forming galaxies consistent with isolated rotating disks. However, recent studies have cautioned that post-coalescence mergers may also display disk-like kinematics. To further investigate the robustness of merger/disk classifications based on kinematic properties, we carry out a systematic classification of 24 local (U)LIRGs spanning a range of galaxy morphologies: from isolated spiral galaxies, ongoing interacting systems, to fully merged remnants. We artificially redshift the WiFeS observations of these local (U)LIRGs to z=1.5 to make a realistic comparison with observations at high-z, and also to ensure that all galaxies have the same spatial sampling of ~900 pc. Using both kinemetry-based and visual classifications, we find that the reliability of kinematic classification shows a strong trend with the interaction stage of galaxies. Mergers with two nuclei and tidal tails have the most distinct kinematic properties compared to isolated disks, whereas a significant population of the interacting disks and merger remnants are indistinguishable from isolated disks. The high fraction of late-stage mergers showing disk-like kinematics reflects the complexity of the dynamics during galaxy interactions. However, the exact fractions of misidentified disks and mergers depend on the definition of kinematic asymmetries and the classification threshold when using kinemetry-based classifications. Our results suggest that additional indicators such as morphologies traced by stars or molecular gas are required to further constrain the merger/disk classifications at high-z.Comment: 16 pages, 5 figures, ApJ accepte

Spiritual Directors and Clinical Psychologists: A Comparison of Mental Health and Spiritual Values

We surveyed a total of 315 spiritual directors, psychologist members of the Christian Association for Psychological Studies (CAPS), and psychologist members of the American Psychological Association (APA) to determine their respective values on ten mental health themes derived from Jensen and Bergin (1988), and three spirituality scales drawn from the writings of John of the Cross. All three groups endorsed the value of expressing feelings, personal autonomy and maturity, and integrating work and leisure. CAPS psychologists and spiritual directors endorsed more than APA psychologists the values of spirituality, forgiveness, and the three John of the Cross scales. Spiritual directors reported greater endorsement of the self-awareness and growth theme than did psychodynamic psychologists who, in turn, reported greater endorsement than cognitive-behavioral psychologists. The results are examined in light of the pre-Enlightenment paradigm and value system in which spiritual direction and Christian theology are rooted

The economic implications of HLA matching in cadaveric renal transplantation.

Abstract Background: The potential economic effects of the allocation of cadaveric kidneys on the basis of tissue-matching criteria are controversial. We analyzed the economic costs associated with the transplantation of cadaveric kidneys with various numbers of HLA mismatches and examined the potential economic benefits of a local, as compared with a national, system designed to minimize HLA mismatches between donor and recipient in first cadaveric renal transplantations. Methods: All data were supplied by the U.S. Renal Data System. Data on all payments made by Medicare from 1991 through 1997 for the care of recipients of a first cadaveric renal transplant were analyzed according to the number of HLA-A, B, and DR mismatches between donor and recipient and the duration of cold ischemia before transplantation. Results: Average Medicare payments for renal-transplant recipients in the three years after transplantation increased from $60,436 per patient for fully HLA-matched kidneys (those with no HLA-A, B, or DR mismatches) to$80,807 for kidneys with six HLA mismatches between donor and recipient, a difference of 34 percent (P\u3c0.001). By three years after transplantation, the average Medicare payments were $64,119 for transplantations of kidneys with less than 12 hours of cold-ischemia time and$74,997 for those with more than 36 hours (P\u3c0.001). In simulations, the assignment of cadaveric kidneys to recipients by a method that minimized HLA mismatching within a local geographic area (i.e., within one of the approximately 50 organ-procurement organizations, which cover widely varying geographic areas) produced the largest cost savings ($4,290 per patient over a period of three years) and the largest improvements in the graft-survival rate (2.3 percent) when the potential costs of longer cold-ischemia time were considered. Conclusions: Transplantation of better-matched cadaveric kidneys could have substantial economic advantages. In our simulations, HLA-based allocation of kidneys at the local level produced the largest estimated cost savings, when the duration of cold ischemia was taken into account. No additional savings were estimated to result from a national allocation program, because the additional costs of longer cold-ischemia time were greater than the advantages of optimizing HLA matching

The Epidemiology of College Alcohol and Gambling Policies

Background: This article reports the first national assessment of patterns of drinking and gambling-related rulemaking on college campuses (e.g., punitive versus recovery oriented). Analyses relating school policies to known school rates of drinking or gambling identified potentially influential policies. These results can inform and encourage the development of guidelines, or "best practices," upon which schools can base future policy. Methods: The college policy information was collected from handbooks, Web sites and supplemental materials of 119 scientifically selected colleges included in the fourth (2001) Harvard School of Public Health College Alcohol Study (CAS). A coding instrument of 40 items measured the scope and focus of school alcohol and gambling policies. This instrument included items to measure the presence of specific policies and establish whether the policies were punitive or rehabilitative. A total of 11 coders followed a process of information extraction, coding and arbitration used successfully in other published studies to codify policy information. Results: Although all schools had a student alcohol use policy, only 26 schools (22%) had a gambling policy. Punitive and restrictive alcohol policies were most prevalent; recovery-oriented policies were present at fewer than 30% of schools. Certain alcohol and gambling policies had significant relationships with student binge drinking rates. Conclusions: The relative lack of college recovery-oriented policies suggests that schools might be overlooking the value of rehabilitative measures in reducing addictive behaviors among students. Since there are few college gambling-related policies, schools might be missing an opportunity to inform students about the dangers of excessive gambling