cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhibition of NK cell-mediated cytotoxicity by oxysterols

Abstract Some of the oxidation products of cholesterol (oxysterols) have profound effects on plasma membrane structure and function. The present studies were undertaken to determine the effects of oxysterols on NK cell-mediated cytotoxicity. When mouse spleen cells were preincubated with certain oxysterols, NK cell cytotoxicity was inhibited without loss of effector cell viability. The strongest inhibition was observed with oxysterols that are oxidized at the C-5, C-6, or C-7 positions of the sterol nucleus. Among these, 7β-hydroxycholesterol caused more inhibition than 7α-hydroxycholesterol suggesting that the spatial orientation of the hydroxyl group in the β-position results in a greater perturbation in plasma membrane structure than that oriented in the α-position, In contrast, oxysterols that are oxidized at the C-20 and C-25 positions that are located on the C-17 acyl chain had little or no inhibitory effect, suggesting that oxidation in the cholesterol nucleus which is situated closer to the phospholipid headgroups at the lipid bilayer-aqueous interface results in a more profound effect on the plasma membrane physical structure. These results suggest that the lytic function of NK cell is sensitive to alterations in the physical state of its plasma membrane induced by oxysterols.
The structure of ribonuclease derived from the clustering of its ionizable groups.

Abstract A three dimensional structure of bovine ribonuclease is proposed and illustrated based on (1) the sequence of amino acids, (2) data on the active site, (3) the interpretation of proton and chloride binding yielding six clusters of five amino acids each, and (4) chemical evidence linking together distant parts of the polypeptide backbone. The model presented is examined for consistency with the data available on ribonuclease.
A Physical and Functional Interaction between Escherichia coli FtsK and Topoisomerase IV

FtsK and topoisomerase (Topo) IV are both involved in chromosome segregation in Escherichia coli. The former protein resides at the septal ring and is required for resolution of chromosome dimers. The latter protein is the chromosomal decatenase. We have demonstrated recently that Topo IV activity is concentrated at the septal proximal regions of the nucleoids late in the cell cycle. Here we demonstrate that FtsK and Topo IV physically and functionally interact. Topo IV was recovered in immunoprecipitates of FtsK. Two-hybrid analysis and immunoblotting showed that this interaction was mediated by the ParC subunit of Topo IV. In addition, we show that the C-terminal motor domain of FtsK stimulates the decatenation activity of Topo IV but not that of DNA gyrase, the other type II topoisomerase in the cell. Topo IV and FtsK appear to cooperate in the cell as well. Rescue of a parE temperature-sensitive mutation by overproduction of DnaX, which leads to stabilization of the temperature-sensitive Topo IV, required both the C-terminal domain of FtsK and dif, whereas rescue by overproduction of Topo III, which bypasses Topo IV function, did not. The interaction between FtsK and Topo IV may provide a means for concentrating the latter enzyme at the cell center.
Monitoring county-level vaccination coverage during the 2004-2005 influenza season.

Background During the 2004–2005 influenza season, the United States faced a sudden shortage of influenza vaccine. In response, the Centers for Disease Control and Prevention (CDC) and the Advisory Committee on Immunization Practices (ACIP) recommended prioritizing vaccination for persons aged 65 and older and others at high risk. To monitor subsequent vaccination coverage, several questions about influenza vaccination were added to the ongoing Behavioral Risk Factor Surveillance System (BRFSS). This study provided real-time county-level estimates of influenza vaccination coverage from the BRFSS each month from October 2004 through January 2005. Method The methods used a variation of small area estimation procedures suitable for situations in which most small areas have few or no survey respondents, and rapid assessment is essential. Both model-based methods and nonparametric spatial-smoothing methods were used in a three-step procedure. Results The highest vaccination rates during the 2004–2005 influenza season were seen in the upper Midwest and the Southeast. Areas with the lowest vaccination rates were the intermountain West, southern California, portions of Washington and Oregon, and various areas across the Eastern United States, often coinciding with urban areas. Intrastate variations were especially pronounced in the Eastern United States, particularly in Georgia, Florida, Tennessee, Kentucky, North Carolina, Virginia, and New York. These states all had areas with low immunization rates as well as areas with high rates. Conclusions The results showed that vaccination coverage varied significantly across states and substate regions. Our findings show that this methodology can provide estimates with reasonable reliability for planning during public health emergencies.
EEG changes during open heart surgery on infants aged 6 months or less: Relationship to early neurologic morbidity☆☆☆

In a prospective study, we analyzed the intraoperative electroencephalographic (EEG) changes during open heart surgery with deep hypothermia in 66 infants aged 6 months or younger, 70% of whom were neonates. Suppression of amplitude and continuity at the nadir of temperature reduction and following rewarming, and the appearance of periodic paroxysmal activity, was compared with neurologic abnormalities before and following operation, patient characteristics, and operation variables. EEG changes disclosed no relationship to abnormal neurologic findings, age at operation, type of anesthetic, duration of cardiopulmonary bypass (CPB), duration of low-flow CPB or cooling, temperature at circulatory arrest (HCA) or low flow, or nasopharyngeal-venous return temperature differences. EEG suppression following rewarming was associated with the use of thiopentone and duration of HCA. Use of thiopentone was also related to decreased levels of alertness at the end of the first postoperative week. We could not demonstrate any association between operation variables, including duration of HCA, and postoperative neurologic findings which include abnormalities of tone, alertness, seizures, generalized pyramidal signs, choreoathetosis, and hemiparesis. Severe hypotonia before operation was associated with continuing severe hypotonia during the postoperative period. EEG changes during cooling for open heart surgery on infants appear to be physiologic, and these plus EEG suppression following HCA or low-flow CPB are not useful predictors of early neurologic morbidity.
Option and constraint generation using Work Domain Analysis

In this paper we investigate the use of Work Domain Analysis (WDA), a technique from the field of cognitive engineering, to inform the creation of options and constraints for Reinforcement Learning (RL) algorithms. The micro-world of Pac-Man, a classic arcade game, is used as a tractable and representative work domain. WDA was conducted on individuals familiar with Pac-Man and an Abstraction Hierarchy (AH), a means-ends representation of their understanding of the game, was created for each individual. The abstraction hierarchies for best performing and worst performing individuals were then combined to illustrate the differences between the different groups. Several differences between the two groups were found, and included the use of defense as well as offensive strategies by high performers versus only defense by poor performers, context sensitivity and additional goals and more sophisticated constraints by high performers. The differences were translated into an options and constraint paradigm suitable for incorporation into RL algorithms.
Afr2 regulation occurs cell-autonomously in vitro but is not conferred on episomal DNA in transient assays.

Oncofetal antigens such as alpha-fetoprotein (AFP) are expressed in regenerating liver. The level of AFP gene expression during liver regeneration is regulated by the unlinked, autosomal gene, Alpha-fetoprotein regulator 2 (Afr2). C3H/HeJ (Afr2A/A) mice express 10-fold higher levels of AFP than C57BL/6J (Afr2B/B) mice. Here we show that primary hepatocytes isolated from C3H/HeJ and C57BL/6J mice exhibit differential expression of the endogenous AFP gene, which was attributed to the Afr2 gene locus and indicative of a cellautonomous mechanism. We show that the Afr2-Response Element (ARE), between 1010 and 838 base pairs upstream of the AFP transcriptional start site, did not modulate reporter gene expression in transfection assays of Hep G2, Hep 3B, Hepa 1.6, and HeLa cell lines. Reporter gene expression in transiently transfected primary hepatocytes was also ARE-independent. Finally, gene expression from reporter constructs delivered by hydrodynamics-based transfection to the livers of C3H/HeJ and C57BL/6...
Diagnostic imaging assessment of experimental intraoral “folded film”

Abstract “Folded film” is an experimental technique of film preparation that provides diagnostic imaging of intraoral structures with one-half the radiation required to produce conventional images. In this study, folded film periapical images were compared with similar conventional D- and E-speed film images with the use of 12 criteria for diagnostic visualization. Nineteen examiners judged folded films to be slightly less diagnostic than D-speed film images and somewhat more diagnostic than E-speed films. All systems were judged adequate for diagnostic visualization of bone and teeth.
The minima of indefinite binary quadratic forms

Abstract The study of the minima of indefinite binary quadratic forms has a long history and the classical results concerning the determination of such minima are stated in terms of the continued fraction expansion of the roots. These results are recast in geometric terms. Using this, and well-known geometric properties of the modular group, some necessary and sufficient conditions for a certain class of quadratic forms to have positive unattained minima are obtained.
An ethanol biosensor can detect low-oxygen injury in modified atmosphere packages of fresh-cut produce

Abstract Improper package design or temperature abuse during handling may cause fruits and vegetables in modified-atmosphere (MA) packages to be exposed to low, injurious O 2 levels associated with the production of fermentation volatiles, quality loss and eventually product breakdown. A simple and reliable technique to detect low-O 2 injury in packaged products at an early stage would reduce the risk of supplying inferior or unsafe produce to the consumer. The formation of ethanol, a common product of fermentation, has been correlated with low-O 2 injury. A commercial ethanol biosensor, composed of a chromagen and immobilized enzymes: alcohol oxidase and peroxidase, and available as a test strip, was tested for its suitability to detect low-O 2 injury indirectly. In the presence of ethanol, the chromagen was oxidized, resulting in a color change from a dull white to a clear bluish-green. The biosensor detected 10 μl l −1 (≈1 Pa) ethanol in the gas phase at 5°C with a 15-s exposure. The human threshold for ethanol detection is 30 μl l −1 (≈3 Pa). The color change of the biosensor was closely correlated to ethanol partial pressure in MA package headspace over cut lettuce, cut broccoli, cut cauliflower, shredded cabbage and cut carrots, and to that over prepared standard ethanol solutions. The study demonstrated that the biosensor can detect gas-phase ethanol quantitatively and hence indirectly can detect low-O 2 injury in MA lightly processed cut broccoli, cut cauliflower, cut lettuce and shredded cabbage packages. The biosensor detected ethanol in cut carrot packages prior to the establishment of low-O 2 conditions. This ethanol, also detected using gas chromatography, may have been produced as a wound response to cutting.
Dynamic response of immobilized cells to pulse addition of l-valine in cyclosporin A biosynthesis

Abstract A feeding strategy for l -valine was tested in the production of cyclosporin A (Cy A), a powerful immunosuppressive secondary metabolite, in celite-immobilized cells of the fungus Tolypocladium inflatum. This system has been previously shown to have promise over conventional submerged systems. Significant increase in Cy A biosynthesis was manifested in the immobilized cells when l -valine was added at 108 h (system C) and at 156 h (system D) during the exponential growth phase. However, no clearly stimulating effect of l -valine on Cy A titre was observed when the amino acid was supplemented at hour 60 (lag phase, system B) or when the valine was present from the start (system A), where system A = 100%, system B = 113%, system C = 253%, system D = 302%. The large contribution to the enhanced production of Cy A in systems C and D may be explained by the preferential channeling of l -valine to growth during the lag phase and to secondary metabolism during the late exponential phase of the immobilized cells.
Helium momentum-space wave function and Compton profile

This paper describes an effort to develop further the work of R. McWeeny and C. A. Coulson (Proc. Phys. Soc. London, Sect. A 62, 509 (1949)) to obtain a helium-atom ground-state wave function in momentum space. In the application of Svartholm's method (N. V. Svartholm, Ph.D. thesis, University of Lund, Sweden (1945)) to the helium momentum-space integral Schroedinger equation, a Feynman-integral evaluation technique is used to start the iteration in the electron-electron interaction term. The resulting correlated momentum-space wave function is used to evaluate the helium-atom ground-state energy and Compton profile.
839 INTEGUMENTARY LOSS OF CALCIUM

The amount of integumentary calcium loss has been generally considered very small and therefore, has rarely been included in calcium metabolic studies. During our study of calcium and protein metabolism, two conditions of integumentary calcium loss were measured. The first, collected over a six-day period represented dermal loss by an ambulatory but rather sedentary man. The second was collected over a 40 minute period of strenous exercise. The daily loss of 16 subjects in 52 determination of six-day periods each was 8.7 ± 1.9 mg/m2/day. The amount was not influenced by calcium intake (0.1 to 2.3 g/day). In contrast to urinary calcium excretion, which is directly related to protein intake, there was no significant change by varing protein intake (1 to 96 g nitrogen/day). No compensatory relationship between urinary and integumentary calcium excretion was noted. During strenous exercise calcium loss increased to to 25 mg (11 to 45 mg) in 40 minutes. There was no compensatory decrease in urinary excretion on the day of strenous exercise. It was also noted that this calcium loss was not affected by general calcium balance. The amount of integumentary loss may become even greater than the urinary calcium excretion. We conclude that integumentary calcium loss probably should be considered in calcium metabolic studies.
SU‐FF‐T‐75: IG IMRT of Tumors On Convex Surfaces with Grazing Incidence Photon Therapy

Purpose: The treatment of tumors on convex surfaces with a uniform dose is a challenging problem in radiotherapy. Traditionally, surfacetumors have been treated with electron beams or a combination of electron and photonbeams with consequent problems of uniformity at regions of abutment. Grazing Incidence Photon Therapy (GIPT) can potentially provide better dose uniformity and tissue sparring than current standards of care but is typically more complex and requires exacting set‐up conditions. The advent of image guided (IG) intensity modulated radiation therapy(IMRT) provides a new opportunity to explore potential of this method for the treatment of tumors on convex surfaces. The treatment of the total scalp with GIPT is an ideal test of the potential of IGIMRT because the beams are grazing incidence throughout the treatment volume and a sensitive structure is in close and constant proximity. Method and Materials: Helical tomotherapy plans using GIPT were developed for the Rando phantom and a patient for the treatment of the total scalp. A patient plan using the Lateral Photon Electron (LPE) technique was developed for comparison. TLD measurements were made with Rando for dose verification in addition to dosimetry quality assurance. Results: The Rando plan and dosimerty demonstrate that the IMRT method using GIPT provides a clinically acceptable treatment. The patient plan shows a reduction in scalp dose non‐uniformity by 34% and improved sparing of peripheral brain by a reduction of the volume exposed to ⩾40 Gy to 17% of the LPE method. Conclusion: GIBT of the total scalp is clinically feasible when implemented with IGIMRT. It substantially improves the quality of patient care when compared to current standards of care by resolving the issue of abutting fields. This has broad implications for the treatment of tumors on convex surfaces by IGIMRT.
Probabilistic forecasting and the reshaping of flood risk management

Advances in probabilistic forecasting, notably based on ensemble prediction systems, are transforming flood risk management. Four trends shaping the assimilation of probabilistic flood forecasting into flood risk management are longer forecasting lead times, advances in decision-making aids, inclusion of probabilistic forecasting in hazard mitigation and collaboration between researchers and managers. Confronting how to use probabilistic flood forecasts to make binary management decisions for reducing flood losses requires developing institutional capacity while acknowledging flood risk estimation is one component of decision making under uncertainty in an evolving policy landscape.
Portable visible imaging spectropolarimeter for remote sensing applications

We have developed a laboratory breadboard spectropolarimetric hyperspectral imaging sensor for operation in the visible-near IR waveband to demonstrate its potential for future airborne and spaceborne systems. An existing spatially modulated imaging Fourier transform spectrometer was modified by the addition of polarization analyzer components. Images collected by the focal plane array vary spatially in one dimension and spectrally in the other. A scanning slit simulates a pushbroom scanning mode for the second spatial dimension. Polarimetric sensing is accomplished using two liquid crystal variable retarders in tandem followed by a linear polarizer. To recover the complete Stokes vector four images, each with distinct combinations of retardances, are collected for each slit position. Sample images are presented.
The supplementary effect of adding canthaxanthin to a diet containing natural sources of pigmenting compounds on the pigmentation of broilers

Synopsis Two experiments have been carried out involving 4200 broiler‐type chicks maintained on litter with six basal diets in the first study and six in the second. From the data of these studies, it can be concluded that canthaxanthin can be used effectively to augment or supplement naturally occurring xanthophylls found in yellow corn or alfalfa for the pigmentation of broilers. From the data, it would appear that it would be possible to produce any level of pigmentation desired by combining canthaxanthin with yellow corn or alfalfa or a combination of these two ingredients.
Distribution of immunoreactive met-enkephalin-Arg6-Gly7-Leu8 and leu-enkephalin in discrete regions of the rat brain

The distribution of immunoreactive (ir) leucine-enkephalin (LE) and ir-methhionine-enkephalin-Arg-Gly-Leu (ME-RGL) in 101 microdissected rat brain and spinal cord regions was determined using specific and sensitive radioimmunoassays. The highest concentrations of LE and ME-RGL were measured in globus pallidus (5190 and 4378.8 fmol/mg protein, respectively). Very high concentrations of LE and ME-RGL (750fmol/mg protein) were found in the central amygdaloid nucleus, anterior hypothalamic nucleus, lateral preoptic area, nucleus of the solitary tract (medial and commissural parts), bed nucleus of stria terminalis, dorsomedial nucleus, parabrachial nuclei, periaqueductal gray and motor hypoglossal nucleus. Very high concentrations of ME-RGL were found in 14 additional brain regions including medial preoptic area, area postrema, nucleus ambiguus, periventricular nucleus, ventromedial nucleus, interpeduncular nucleus, paraventricular, arcuate and others. High concentrations of LE (between 500 and 750 fmol/mg protein) were found in 15 brain areas, among them the periventricular nucleus, medial preoptic area, suprachiasmatic nucleus, dorsal premamillary nucleus, ventromedial nucleus, arcuate nucleus, nucleus ambiguus, locus coeruleus, substantia nigra. High concentrations of ME-RGL were measured in 13 brain areas including the suorachiasmatic nucleus, lateral septal nucleus, raphe magnus, motor facial nucleus, la ral amygdaloid nucleus, sensory trigeminal nucleus, nucleus accumbens, caudate-putamen. Moderate concentrations of LE (between 250 and 500 fmol/mg) were found in 46 brain areas such as the lateral septal nucleus, nucleus accumbens, caudate-putamen, several amygdaloid nuclei, supraoptic nucleus, the perifornical nucleus, posterior hypothalamic nucleus, red nucleus. Moderate concentrations of ME-RGL were detected in 27 areas such as the median eminence, nuclei of the reticular formation, supraoptic nucleus, red nucleus and others. Low levels of both peptides (< 250fmol/mg protein) were measured in the cortical structures, hippocampus, dentate gyrus, olfactory tubercle, dorsal septal nucleus, thalamic nuclei, habenular nuclei, cerebellum, subfornical organ. The lowest concentrations of LE and ME-RGL peptides were found in the olfactory bulb (26.3 and 27.2 fmol/mg protein, respectively).
Sublethal responses to endrin in sediment by Limnodrilus hoffmeisteri (Tubificidae), and in mixed-culture with Stylodrilus heringianus (Lumbriculidae)

Abstract Sediment reworking by Limnodrilus hoffmeisteri (Tubificidae) alone, and with Stylodrilus heringianus (Lumbriculidae) were measured in sediments dosed with endrin by monitoring the burial of a 137 cesium marker layer. Endrin concentrations ranged from 16.1 to 81 400 ng/g dry sediment weight. Alterations in reworking rates were observed at sediment concentrations two to five orders of magnitude below LC 50 values. In single species experiments with L. hoffmeisteri at low endrin concentrations, marker layer burial rate data did not suggest stimulation of reworking, as had previously been found for S. heringianus . At higher concentrations, reworking rates were equal to or slower than control rates early in experiments, followed by dramatic decreases thereafter. Reworking rates with mixed species (1:1 species ratio) suggested that the presence of S. heringianus enhanced the reworking response of L. hoffmeisteri . Post-experimental worm dry weights were inversely related to high sediment concentrations for both species. Reductions in post-experimental L. hoffmeisteri mortalities and increases in L. hoffmeisteri dry weights in mixed species tests at high endrin concentrations implied that L. hoffmeisteri benefits from the presence of S. heringianus , although the reverse was not observed. High final sediment endrin concentrations in the upper three cm implied worm mediated upward contaminant transport. Bioaccumulation factors for S. heringianus ranged from 9.7 to 43.8 and were consistently three to four times greater than bioaccumulation factors for L. hoffmeisteri (1.7 to 13.6).
A cross-validation of the Keane and Penk MMPI scales as measures of post-traumatic stress disorder.

The scores of DSM-III-diagnosed post-traumatic stress disorder (PTSD) patients (N = 116), psychiatric patients who did not meet the criteria, and normals (N = 19) on the Keane, Malloy, and Fairbank (1984) PTSD and Penk Combat scales for the MMPI were compared. The Keane scale discriminated PTSD-positive patients from normals at a substantial level of accuracy (omega 2 = .23; mean hit rate = 80.5%) and PTSD-positive from PTSD-negative patients at a more modest level (omega 2 = .09; mean hit rate = 64%). The scores of the PTSD-positive and PTSD-negative patients were considerably lower than those of Keane et al.'s (1984) samples, which suggests that local norms may be needed to facilitate their interpretation. The Penk Combat Intensity scale, which was correlated highly with the Keane scale, differentiated the PTSD-positive patients from both the normals and the PTSD-negative patients, but with less differentiating power (omega 2'S = .07 and .08). The Penk Combat Exposure scale did not separate the groups.
A structured planning and debugging environment for elementary programming

How could an appropriately structured environment facilitate the acquisition of programming skills? Significant theoretical strides are needed before human-quality performance can be expected from a computer-based programming tutor. As an intermediate step, a system has been implemented which serves primarily as an editing language and diligent clerk. However, it differs from conventional programming environments in two crucial ways: (1) it interacts with the student using a vocabulary of concepts about planning and debugging, derived from an explicit model of the design process; and (2) it actively prompts the student with a menu of design alternatives, within the overall framework of a mixed-initiative dialogue. The current system is not a tutor; but the process of implementing and testing it has been instrumental in refining our model of the design process, thereby bringing us a step closer to realizing a computer-based programming tutor.
Sequence for human argininosuccinate synthetase cDNA

The nucleotide sequence for human argininosuccinate synthetase cDNA was determined by analysis of six clones isolated from a single experiment. The sequence covered 1623 nucleotides including 76 bases of poly(A) and contained a 1236 nucleotide open reading frame encoding a protein of 46,434 daltons. In one cDNA isolate, a cloning artifact or perhaps RNA polymerase error involving addition of an A in a region of six A's within the coding sequence was documented. Single base variations in the 3' untranslated region were examined in detail since detection of DNA polymorphisms in the cDNAs could imply over-expression of both alleles at the active locus in canavanine-resistant cells, i.e. a trans-acting mechanism for enzyme overproduction. However, the sequence from five cDNAs suggested some single base artifacts, and DNA polymorphism remains uncertain. The occurrence of three tandem arginine codons in the 5' untranslated region of the cDNA suggested the possibility of an interaction of arginyl-tRNA with mRNA to regulate RNA processing or half-life as a mechanism for arginine-mediated repression.
Larval Taenia crassiceps secretes a protein with characteristics of murine interferon-γ

Previous studies have shown that excretory/secretory products of larval Taenia crassiceps have immunomodulatory activities. We report here that one of these products, termed p66, possesses activities that mimic some characteristics of murine interferon-γ (IFN-γ). Purified p66 cross-reacts with anti-murine IFN-γ on immunoblots and increases concanavalin-A-induced splenic T-cell proliferative responses of normal and chronically infected mice. It has also been shown that p66 induces enhanced IFN-γ and interleukin-10 (IL-10) production in cells from infected or normal mice. Adherent and non-adherent peritoneal exudates cells were stimulated with p66 and showed that the adherent cells were induced to produce IL-10 and that the non-adherent cells were induced to produce IFN-γ. p66 was shown as well to upregulate nitric oxide production in macrophages and two T-cell lines, IEL and YAC-1, were shown to be stimulated to produce IFN-γ and IL-10, respectively, by p66. Although the significance of p66 in immunoregulation is not known, we show here that this molecule mimics characteristics of IFN-γ.
Summary of Lessons Learned When Working With Translators and Interpreters in Research

This is a response to the articles in the special section written by Jones & Boyle, Baird, Siaki, and Sheppard.
Medical Entrepreneurism: The Current Opportunity in America

This article discusses both the current climate for entrepreneurial activity in the fields of biotechnology, health care services, and medical devices as well as key ideas in the process of successful innovation. Basic issues related to the nature of new medical ventures and its importance in the U.S. economy are discussed. A stepwise overview of the process of innovation is provided, starting from the initial idea, through the early and middle stages of growth, and on to an initial public offering or other alternative harvest strategy. The roles of financing sources in generating health care entrepreneurial activity are explored, and the advantages and disadvantages of each are discussed. The article focuses on venture capital investment because of its pivotal role in high-profile successes; however, alternative forms of financing are also covered as appropriate to each stage. In addition, critical nonfinancial issues that affect the success of new enterprises, such as intellectual property protection and the creation of management teams for young companies, are also covered. The magnitude of current investment in the domestic biomedical field is addressed, and future prospects for American medical innovation are briefly discussed.
CNS imaging findings associated with Parry–Romberg syndrome and en coup de sabre: correlation to dermatologic and neurologic abnormalities

Parry–Romberg syndrome (PRS) and en coup de sabre (ECS) are variants of morphea. Although numerous findings on central nervous system (CNS) imaging of PRS and ECS have been reported, the spectrum and frequency of CNS imaging findings and relation to cutaneous and neurologic abnormalities have not been fully characterized. We retrospectively reviewed patients younger than 50 years at our institution over a 16-year interval who had clinical diagnosis of PRS and ECS by a skin or facial subspecialist. Two neuroradiologists evaluated available imaging and characterized CNS imaging findings. Eighty-eight patients with PRS or ECS were identified (62 women [70.4 %]; mean age 28.8 years). Of the 43 patients with CNS imaging, 19 (44 %) had abnormal findings. The only finding in 1 of these 19 patients was lateral ventricle asymmetry; of the other 18, findings were bilateral in 11 (61 %), ipsilateral to the side of facial involvement in 6 (33 %), and contralateral in 1 (6 %). Sixteen patients had serial imaging examinations over an average of 632 days; 13 (81 %) had stable imaging findings, and 3 (19 %) had change over time. Of six patients with progressive cutaneous findings, five (83 %) had stable imaging findings over time. Among the 23 patients with clinical neurologic abnormality and imaging, 12 (52 %) had abnormal imaging findings. All seven patients with seizures (100 %) had abnormal imaging studies. In PRS and ECS, imaging findings often are bilateral and often do not progress, regardless of cutaneous disease activity. Findings are inconsistently associated with clinical abnormalities.
Help feature interactions in digital libraries: Influence of learning styles

Little is known about how learning styles may have an impact on users' help-seeking behaviors. In this paper, we report the results of a study investigating the effects of learning styles on help feature interactions in the digital library environment. The Felder-Silverman Index of Learning Styles was employed to measure users' four different style dimensions: Active/Reflective, Sensory/Intuitive, Visual/Verbal, and Sequential/Global. Multiple data collection methods, including questionnaires, think-aloud protocols, transaction logs, and interviews, were employed to collect data from 27 participants. Findings of this study demonstrate that learning styles influence the way that participants interact with help features of digital libraries. The results suggest that the designs of IR systems, including digital libraries, need to support different learning styles by offering different types of help features, different formats of help, and different organization and presentation of help content.
A study of numerical methods for hyperbolic conservation laws with stiff source terms

The proper modeling of nonequilibrium gas dynamics is required in certain regimes of hypersonic flow. For inviscid flow this gives a system of conservation laws coupled with source terms representing the chemistry. Often a wide range of time scales is present in the problem, leading to numerical difficulties as in stiff systems of ordinary differential equations. Stability can be achieved by using implicit methods, but other numerical difficulties are observed. The behavior of typical numerical methods on a simple advection equation with a parameter-dependent source term was studied. Two approaches to incorporate the source term were utilized: MacCormack type predictor-corrector methods with flux limiters, and splitting methods in which the fluid dynamics and chemistry are handled in separate steps. Various comparisons over a wide range of parameter values were made. In the stiff case where the solution contains discontinuities, incorrect numerical propagation speeds are observed with all of the methods considered. This phenomenon is studied and explained.
The algorithm for detecting critical conditions during anesthesia

The complexity of modern anesthesia procedures requires the development of decision support systems functioning in a smart-alarm capacity. Based on computerized anesthesia records containing hemodynamic data (heart rate, mean arterial pressure and systolic arterial pressure) and assessments made by experienced anesthesiologists reviewing printed anesthesia records, we have developed rule-based computer algorithms to detect critical conditions during surgery, such as inadequate (light) anesthesia (LA) or unstable blood pressure (lability). Our analysis indicated that a /spl ges/12% change in mean arterial blood pressure (MAP), compared with the median value of MAP over the preceding 10 minute interval, may be chosen as the criterion for detecting LA, with a sensitivity of 96% and a specificity of 91%. The best agreement between human and computer ratings of blood pressure lability (correlation coefficient 0.78) was achieved when we used the absolute value of the fractional change of the mean arterial pressure (|FCM|) between one 2-min epoch and the next 2-min epoch. We developed rule-based computer algorithms to defect critical conditions during surgery (light anesthesia or unstable blood pressure), based on computerized anesthesia records containing hemodynamic data (heart rate, mean arterial pressure and systolic arterial pressure).
Optically measuring force near the standard quantum limit

The Heisenberg uncertainty principle sets a lower bound on the noise in a force measurement based on continuously detecting a mechanical oscillator’s position. This bound, the standard quantum limit, can be reached when the oscillator subjected to the force is unperturbed by its environment and when measurement imprecision from photon shot noise is balanced against disturbance from measurement back-action. We applied an external force to the center-of-mass motion of an ultracold atom cloud in a high-finesse optical cavity and measured the resulting motion optically. When the driving force is resonant with the cloud’s oscillation frequency, we achieve a sensitivity that is a factor of 4 above the standard quantum limit and consistent with theoretical predictions given the atoms’ residual thermal disturbance and the photodetection quantum efficiency.
Multisite phosphorylation of the guanine nucleotide exchange factor Cdc24 during yeast cell polarization.

Background: Cell polarization is essential for processes such as cell migration and asymmetric cell division. A common regulator of cell polarization in most eukaryotic cells is the conserved Rho GTPase, Cdc42. In budding yeast, Cdc42 is activated by a single guanine nucleotide exchange factor, Cdc24. The mechanistic details of Cdc24 activation at the onset of yeast cell polarization are unclear. Previous studies have suggested an important role for phosphorylation of Cdc24, which may regulate activity or function of the protein, representing a key step in the symmetry breaking process. Methodology/Principal Findings: Here, we directly ask whether multisite phosphorylation of Cdc24 plays a role in its regulation. We identify through mass spectrometry analysis over thirty putative in vivo phosphorylation sites. We first focus on sites matching consensus sequences for cyclin-dependent and p21-activated kinases, two kinase families that have been previously shown to phosphorylate Cdc24. Through site-directed mutagenesis, yeast genetics, and light and fluorescence microscopy, we show that nonphosphorylatable mutations of these consensus sites do not lead to any detectable consequences on growth rate, morphology, kinetics of polarization, or localization of the mutant protein. We do, however, observe a change in the mobility shift of mutant Cdc24 proteins on SDS-PAGE, suggesting that we have indeed perturbed its phosphorylation. Finally, we show that mutation of all identified phosphorylation sites does not cause observable defects in growth rate or morphology. Conclusions/Significance: We conclude that lack of phosphorylation on Cdc24 has no overt functional consequences in budding yeast. Yeast cell polarization may be more tightly regulated by inactivation of Cdc42 by GTPase activating proteins or by alternative methods of Cdc24 regulation, such as conformational changes or oligomerization.
Compensatory Role of Inositol 5-Phosphatase INPP5B to OCRL in Primary Cilia Formation in Oculocerebrorenal Syndrome of Lowe.

Inositol phosphatases are important regulators of cell signaling, polarity, and vesicular trafficking. Mutations in OCRL, an inositol polyphosphate 5-phosphatase, result in Oculocerebrorenal syndrome of Lowe, an X-linked recessive disorder that presents with congenital cataracts, glaucoma, renal dysfunction and mental retardation. INPP5B is a paralog of OCRL and shares similar structural domains. The roles of OCRL and INPP5B in the development of cataracts and glaucoma are not understood. Using ocular tissues, this study finds low levels of INPP5B present in human trabecular meshwork but high levels in murine trabecular meshwork. In contrast, OCRL is localized in the trabecular meshwork and Schlemm’s canal endothelial cells in both human and murine eyes. In cultured human retinal pigmented epithelial cells, INPP5B was observed in the primary cilia. A functional role for INPP5B is revealed by defects in cilia formation in cells with silenced expression of INPP5B. This is further supported by the defective cilia formation in zebrafish Kupffer’s vesicles and in cilia-dependent melanosome transport assays in inpp5b morphants. Taken together, this study indicates that OCRL and INPP5B are differentially expressed in the human and murine eyes, and play compensatory roles in cilia development.
Pheochromocytoma in a Twelve-Year-Old Girl with SDHB-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome

A twelve-year-old girl presented with a history of several weeks of worsening headaches accompanied by flushing and diaphoresis. The discovery of markedly elevated blood pressure and tachycardia led the child's pediatrician to consider the diagnosis of a catecholamine-secreting tumor, and an abdominal CT scan confirmed the presence of a pheochromocytoma. The patient was found to have a mutation in the succinyl dehydrogenase B (SDHB) gene, which is causative for SDHB-related hereditary paraganglioma-pheochromocytoma syndrome. Herein, we describe her presentation and medical management and discuss the clinical implications of SDHB deficiency.
Long-Term Exercise Training Selectively Alters Serum Cytokines Involved in Fever

Long-term exercise training selectively alters serum cytokines involved in fever. Chronic exercise training has a number of effects on the immune system that may mimic the physiological response to fever. Female rats that voluntarily exercise on running wheels develop an elevated daytime core temperature after several weeks of training. It remains to be seen whether the elevation in daytime temperature involves inflammatory patterns characteristic of an infectious fever. We assessed whether chronic exercise training in the rat would alter levels of cytokines involved in fever. Female Sprague Dawley rats at 45 days of age weighing 90–110 g were divided into two groups (exercise and sedentary) and housed at an ambient temperature of 22 � C. Interleukin-1 beta (IL-1b), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-a), iron, and zinc levels were analyzed. Rats underwent 8 weeks of exercise on running wheels. Exercise led to altered levels of some key cytokines that are involved in fever. Exercise animals had significantly higher IL-1b levels and lower IL-10 levels compared to sedentary animals. Although IL-6 levels were slightly lower in the exercise animals, these levels were not significantly affected by training. TNF-a activity was similar in the two groups. Training also led to a slight increase in serum zinc and decrease in serum unsaturated iron binding capacity (UIBC). The data suggest that chronic exercise training evokes immune responses that mimic some, but not all, aspects of fever. This may explain why exercise leads to elevated daytime core temperature.
Teaching Students With Intellectual Disability to Integrate Reading Skills: Effects of Text and Text-Based Lessons

This multiple baseline study investigated the effectiveness of text-based reading lessons for students with intellectual disability (ID). Three students were selected who had not responded well to explicit and systematic reading instruction. They were provided with individual instruction in daily 45-min sessions for 14 weeks (approximately 70 sessions). All three students increased the number of words read from baseline (ranging from 5 to 20 words correct) to the final intervention session (ranging from 40 to 75 words correct), though one student’s data were less conclusive due to growth during the baseline phase. Regression discontinuity revealed the intervention caused statistically significant growth. The intervention is promising given that students with ID who initially did not respond to systematic instruction improved their ability to sound out and unitize (i.e., read with automaticity) words.
Enhancement of synaptic function in cat motoneurones during peripheral sensory regeneration.

1. Monosynaptic excitatory post-synaptic potentials (e.p.s.p.s) were recorded from medial (m.g.) and lateral gastrocnemius (l.g.) motoneurones in the cat 2-30 weeks after crushing the m.g. nerve. 2. The mean amplitudes of homonymous and heteronymous e.p.s.p.s evoked from the m.g. nerve were initially depressed (2-3 weeks after injury) and subsequently reached levels greater than normal for a period (8-12 weeks) before slowly declining to about 70% of the normal values (by week 30). 3. Monosynaptic e.p.s.p.s evoked in m.g. motoneurones from the intact l.g. nerve showed neither initial depression nor subsequent alterations following crush of the m.g. nerve. 4. By the eighth week after nerve crush, about 70% of Group I and Group II sensory fibres in the m.g. nerve responded to muscle stretch, about 15% had regenerated into the muscle but did not respond to muscle stretch, and the remainder failed to regenerate across the neuroma formed by the nerve crush. 5. Homonymous, monosynaptic e.p.s.p.s produced by impulses in single sensory fibres responding to stretch of the m.g. muscle were recorded 8 weeks after crush of the m.g. nerve. Their amplitude distribution was indistinguishable from that obtained in normal, unoperated cats. Thus, there was no evidence that functionally reinnervated sensory fibres are responsible for the enhanced phase of composite e.p.s.p.s observed during peripheral regeneration. 6. When the m.g. nerve had been sectioned and prevented from regenerating into the muscle for 8 weeks, the amplitudes of homonymous and heteronymous e.p.s.p.s evoked from the m.g. nerve were significantly smaller than those observed in control animals. Thus, there was no evidence that non-regenerating sensory fibres are responsible for the enhanced phase of composite e.p.s.p.s after nerve crush. 7. It is suggested that the sensory fibres responsible for abnormally large composite e.p.s.p.s following nerve crush are those that regenerate into the muscle but do not achieve functional reinnervation. This possibility is discussed in relation to the increase in central synaptic efficacy observed after prolonged disuse of the sensory pathway.
Making e-working work

It is estimated that by 2010 there will be 20 million full- and part-time telecommuters working in the United States. The purpose of this article is to assist employment counselors in their work with organizations in implementing e-worker programs as well as in their counseling of e-workers. The authors define e-worker, summarize the growth of e-worker programs, outline benefits and drawbacks to teleworking, discuss critical elements of a successful teleworker program, and elaborate on potential strategies for becoming a successful e-worker.
Steroid Hormone Receptors and the Nucleus

I. Introduction THE CONCEPT that steroid hormone action is mediated by interaction with specific target tissue receptor proteins has become generally well accepted. Receptors that are not bound to hormone (unoccupied receptors) were initially described as residing in cytosolic/cytoplasmic1 compartments of many systems. Biochemical and autoradiographic procedures led to this conclusion. Additional evidence established that hormone binding induces receptor transformation2 and receptor movement from the cytosolic to the nuclear compartment (translocation), where the biological response is initiated. This review summarizes the evidence for steroid receptor action in the nucleus and discusses the recent controversy that unoccupied receptors themselves may be predominantly associated with nuclear components in vivo. This summary, rather than being an exhaustive review of one or two receptor systems, emphasizes the parallel development of these concepts in multiple steroid hormone receptor systems,3 in part by r...
Mortality Rate in Patients With Diastolic Dysfunction and Normal Systolic Function

Background Diastolic dysfunction (DD) is known to be associated with increased mortality rate in the presence of impaired systolic function. However, few prognostic data exist regarding the effect of DD in patients with normal systolic function. Methods We reviewed clinical records and echocardiographic findings of consecutive patients who underwent an outpatient echocardiogram that revealed normal systolic function (ejection fraction, ≥55%) from January 1, 1996, through December 31, 2005. Diastolic function was graded using echocardiographic Doppler variables designated as normal, mild (grade I, ie, impaired relaxation pattern), moderate (grade II, ie, pseudonormal pattern), or severe (grade III, ie, restrictive filling pattern) dysfunction. Propensity analysis was performed to compare outcomes among the groups. Results A total of 36 261 patients were identified (mean [SD] age, 58.3 [15.4] years; 54.4% female) with a mean (SD) follow-up time of 6.2 (2.3) years. In 65.2% of the cohort, DD was present, with mild DD being the most prevalent type of dysfunction. A total of 5789 deaths occurred during the follow-up period. The unadjusted survival rate was worse according to the presence and degree of DD ( P P Conclusions In this single-center study of patients with normal ejection fraction who presented for outpatient echocardiography, the presence of moderate or severe DD was an independent predictor of mortality. Mild DD, although prevalent, did not affect survival rate.