cssi/SciSciGPT-SciSciNet huggingface dataset:
CpG methylation at the USF-binding site mediates cell-specific transcription of human ascorbate transporter SVCT2 exon 1a

SVCT2 (sodium-vitamin C co-transporter 2) is the major transporter mediating vitamin C uptake in most organs. Its expression is driven by two promoters (CpG-poor exon 1a promoter and CpG-rich exon 1b promoter). In the present study, we mapped discrete elements within the proximal CpG-poor promoter responsible for exon 1a transcription. We identified two E boxes for USF (upstream stimulating factor) binding and one Y box for NF-Y (nuclear factor Y) binding. We show further that NF-Y and USF bind to the exon 1a promoter in a co-operative manner, amplifying the binding of each to the promoter, and is absolutely required for the full activity of the exon 1a promoter. The analysis of the CpG site located at the upstream USF-binding site in the promoter showed a strong correlation between expression and demethylation. It was also shown that exon 1a transcription was induced in cell culture treated with the demethylating agent decitabine. The specific methylation of this CpG site impaired both the binding of USF and the formation of the functional NF-Y-USF complex as well as promoter activity, suggesting its importance for cell-specific transcription. Thus CpG methylation at the upstream USF-binding site functions in establishing and maintaining cell-specific transcription from the CpG-poor SVCT2 exon 1a promoter.
Treatment of batch in the detection, calibration, and quantification of immunoassays in large-scale epidemiologic studies

Many laboratory assays measure biomarkers via a 2-stage process. Direct measurement yields relative measures that are subsequently transformed to the unit of interest by using a calibration experiment. The calibration experiment is performed within the main experiment and uses a validation set for w
AII Amacrine Cells Limit Scotopic Acuity in Central Macaque Retina: A Confocal Analysis of Calretinin Labeling

We have used calretinin antibodies to label selectively the mosaic of AII amacrine cells in the macaque retina. Confocal analysis of double-labeled material indicated that AII dendrites spiral down around descending rod bipolar axons before enveloping the synaptic terminals. Processes from a previously observed dopaminergic plexus in the inner nuclear layer were observed to contact the somata of calretinin-positive AII somata. Intracellular neurobiotin injection revealed that AII amacrine cells are tracer coupled to other AII amacrine cells and to some unidentified cone bipolar cells. An analysis of the retinal distribution of macaque AII amacrine cells, including an area in and around the fovea, showed a peak density of approximately 5,000 cells/mm(2) at an eccentricity of 1.5 mm. Staining of AII amacrine cells in central retina with antibodies to calretinin was confirmed by confocal microscopy. These results indicate that calretinin antibodies can be used to label the AII amacrine cell population selectively and that primate AII amacrine cells share many of the features of previously described mammalian AII amacrine cells. The peak AII cell density closely matched the peak sampling rate of scotopic visual acuity. Calculations suggest that, in central macaque retina, where midget ganglion cells are more numerous, AII amacrine cells form the limit of scotopic visual acuity (Wassle et al. [1995] J. Comp. Neurol. 361:537-551). As the ganglion cell density falls rapidly away from the fovea, there is a cross-over point at around 15 degrees eccentricity that matches the inflection point in a psychophysically derived plot of scotopic visual acuity versus eccentricity (Lennie and Fairchild [1994] Vision Res. 34:477-482). The correspondence between the anatomic and psychophysical data supports our interpretation that the anatomic sampling rate of AII amacrine cells limits central scotopic acuity.
Mapping LIDC, RadLex™, and Lung Nodule Image Features

Ideally, an image should be reported and interpreted in the same way (e.g., the same perceived likelihood of malignancy) or similarly by any two radiologists; however, as much research has demonstrated, this is not often the case. Various efforts have made an attempt at tackling the problem of reducing the variability in radiologists’ interpretations of images. The Lung Image Database Consortium (LIDC) has provided a database of lung nodule images and associated radiologist ratings in an effort to provide images to aid in the analysis of computer-aided tools. Likewise, the Radiological Society of North America has developed a radiological lexicon called RadLex. As such, the goal of this paper is to investigate the feasibility of associating LIDC characteristics and terminology with RadLex terminology. If matches between LIDC characteristics and RadLex terms are found, probabilistic models based on image features may be used as decision-based rules to predict if an image or lung nodule could be characterized or classified as an associated RadLex term. The results of this study were matches for 25 (74%) out of 34 LIDC terms in RadLex. This suggests that LIDC characteristics and associated rating terminology may be better conceptualized or reduced to produce even more matches with RadLex. Ultimately, the goal is to identify and establish a more standardized rating system and terminology to reduce the subjective variability between radiologist annotations. A standardized rating system can then be utilized by future researchers to develop automatic annotation models and tools for computer-aided decision systems.
Modification and Performance Evaluation of the Faster-Than-Real-Time Hybrid Simulator

The basic capability of the long term dynamics hybrid simulator was described in the RP908-1 final Report [1], [2]. As a part of the RP908-2 project, the capability of the simulator has been improved and expanded [3] The generator model was improved to a two axis model allowing the full representation of the subtransient and transient reactance values. The generator model now adequately represents the short term dynamics as well as the long term dynamics.
X-ray Diffraction by Liquid-Crystalline Polymers

Abstract Following a brief introduction to how acicular molecules form liquid-crystalline (LC) arrays in polymers, relevant elements of x-ray diffraction theory are discussed. It is shown that meaningful structural information can be obtained only when molecular arrays aligned by external forces are examined, a condition that is frequently easier to achieve in polymer than in monomer arrays. The published results of x-ray studies are reviewed critically and the interpretations of recorded intensity distributions are discussed in terms of model calculations and cylindrical distribution functions. Examples cited include side-group and main-chain LC homopolymers and main-chain copolymers.
Dealing with the unknown: metabolomics and metabolite atlases.

Metabolomics is the comprehensive profiling of the small molecule composition of a biological sample. Since metabolites are often the indirect products of gene expression, this approach is being used to provide new insights into a variety of biological systems (clinical, bioenergy, etc.). A grand challenge for metabolomics is the complexity of the data, which often include many experimental artifacts. This is compounded by the tremendous chemical diversity of metabolites. Identification of each uncharacterized metabolite is in many ways its own puzzle (compared with proteomics, which is based on predictable fragmentation patterns of polypeptides). Therefore, effective data reduction/prioritization strategies are critical for this rapidly developing field. Here we review liquid chromatography electrospray ionization mass spectrometry (LC/MS)-based metabolomics, methods for feature finding/prioritization, approaches for identifying unknown metabolites, and construction of method specific ‘Metabolite Atlases’.
Ethanol administration to cystic fibrosis knockout mice results in increased fatty acid ethyl ester production.

Abstract: Background: Fatty acid ethyl esters (FAEE) are nonoxidative ethanol metabolites shown to produce toxic effects in the liver and pancreas in vivo and in vitro. Because alcohol-induced chronic pancreatitis is associated with mutations in the gene responsible for cystic fibrosis (CFTR), we hypothesized that CFTR dysfunction leads to increased levels of these toxic nonoxidative ethanol metabolites following alcohol administration. Methods: Cystic fibrosis (CF) and wild-type (WT) mice were injected intraperitoneally with 1, 2, or 3 g/kg of 50% ethanol. Mice were sacrificed and the liver and pancreas removed for FAEE analysis. Results: The mean FAEE concentration (pmol/g) detected in the liver of cftr−/− mice following injection with 2 g/kg of ethanol was significantly greater than the amount detected in WT (p < 0.005). A similar trend in FAEE concentration was seen in the pancreas, but the difference was not statistically different. In both the liver and pancreas, analysis of individual FAEE species demonstrated a selective increase in ethyl oleate. Conclusion: These data show an association between CFTR dysfunction and qualitative and quantitative changes in FAEE in liver and pancreas upon ethanol exposure.
EFFECTS OF ULTRASONIC TREATMENT ON BINDING STRENGTH IN CURED HAM ROLLS

The purpose of the study was to determine the effects of ultrasonic treatment on muscle microstructure, breaking strength, cook yield, and protein extractability of ground cured ham rolls. A miniaturized system was designed which subjected ground ham to slow mixing and ultrasonic treatment. The samples were mixed for various times up to 2 hr, then stuffed into stoppered glass tubes for cooking in 80°C water bath. Controls were treated similarly, but without ultrasonic treatment. Results showed that ultrasound caused changes in muscle microstructure, increased breaking strength as measured in g/cm2 on an Instron Universal Testing Machine, decreased cooking loss and increased the extractability of salt-soluble protein. Ultrasound had no effect on the extractability of water-soluble protein.
Polymelanosomes of the Melanocyte and their Substructures

THE importance of studying visceral melanocytes has already been emphasized1–4 and the liver of Amphiuma tridactylum—a rich source of melanocytes—is a suitable material to use. The melanoprotein of the liver of Amphiuma is very similar to that of human liver melanoma5, and the melanin polymer (free from protein) closely resembles that of human substantia nigra pigment and synthetic catecholamine pigment formed by incubating the various amines with a mitochondrial preparation containing monoamine oxidase4. Structural and functional studies of the hepatic melanocytes of Amphiuma may therefore have a bearing on other pigmentary systems. We have reported (refs. 1 and 6 and unpublished work of Prasad) that the melanocytes of Amphiuma constitute about 20 per cent of the liver cell population (hepatocytes and melanocytes). Most of these melanocytes (70–80 per cent of total pigment cell population) are lightly pigmented and have an abundance of melanin-containing organelles which we named polymelanosomes6. The darkly pigmented cells contain closely packed granules lying freely in the cytoplasm, but no polymelanosomes. There is some morphological evidence that melanin-synthesis occurs in the polymelanosomes, and the light melanocytes which have an abundance of these organelles probably represent the younger form6. Polymelanosomes possess three mitochondrial enzymes, monoamine oxidase, cytochrome oxidase and succinic oxidase7.
Brain receptor autoradiography with [3H]-YM 09151-2: A ligand for labeling dopamine D-2 receptors

Using the technique of in vitro receptor autoradiography to slide-mounted tissue sections, we studied the suitability of [3H]-YM-09151-2 as a ligand for labeling D-2 receptors in adult F344 rat brains. Specific [3H]-YM-09151-2 binding accounted for 70-80% of the total bound ligand and reached equilibrium after a 60-90 minute incubation. Scatchard analysis revealed a Kd of 626 pM. The apparent Bmax was 23.2 fmol/tissue section. Autoradiographs demonstrated high grain densities in the striatum and olfactory tubercle. Diffuse specific binding was also observed in the cortex.
Multimodality imaging of triple receptor-negative tumors with mammography, ultrasound, and MRI.

OBJECTIVE. We retrospectively reviewed imaging findings for 44 patients with triple receptor–negative breast carcinomas on mammography, sonography, and MRI to determine the imaging characteristics of triple receptor–negative cancers that may improve diagnosis at the time of presentation.CONCLUSION. Despite their large size at presentation, triple receptor–negative cancers may be occult on mammography or sonography and frequently have benign or indeterminate features. MRI identified all triple receptor–negative cancers and showed features that had a high positive predictive value for malignancy.
The oxidation of carbon monoxide on Rh(100) under steady state conditions: An FT-IR study

The steady-state oxidation of CO on clean Rh(100) at low pressures has been investigated using in-situ infrared spectroscopy and mass spectrometry. The results show that at a fixed CO pressure, the temperature at which the CO2 formation rate maximizes decreases as a function of increasing O2 pressure. Vibrational data indicate that this maximum rate coincides with a CO coverage of less than 0.01 monolayers.
The amoral character of our attitudes about death: Some implications.

So much has been said recently about death and dying that one is tempted to begin with an apology. In spite of the proliferation of research (as well as the popular stylistic writing), certain dimensions of our attitudes about death and the dying person have been given insufficient attention. This essay deals with one such dimension. My thesis is that our current attitudes about death and those who are dying are amoral, that is, largely outside the realm of our moral sensibilities and ethical thinking. Further, I hope to show how the amoral status of death in this culture helps to create secondary, or derivative ethical dilemmas, especially perhaps for health professionals. Near the end I hope to relocate the discussion of death to a theological context?not because theology can or should provide answers but because the roots of the problem of death are grounded in the Judeo-Christian theological framework that is our cultural heritage.
Producer Services, Trade and the Social Division of Labour

GOE W. R. (1990) Producer services, trade and the social division of labour, Reg. Studies 24, 327–342. Several hypotheses have been advanced to explain the growth in employment and output of producer services industries in US metropolitan and regional economies. One hypothesis contends that this growth is attributable to the increasing externalization of service activities by corporate managerial offices to independent producer services firms. This has contributed to the growth of corporate complex agglomerations in urban regions. Manufacturing industries have traditionally been viewed as being the motivating force underlying this growth. A second hypothesis contends that the growth of producer services industries is attributable to their evolution into basic industries and the growth of export trade. This paper examines the validity of these hypotheses using data collected from a survey of business establishments in producer services industries located in the four metropolitan areas of the northeast regi...
Semi‐Empirical Technique for Computation of Glass Density

We present a semi-empirical technique for computation of glass density based on the enthalpy landscape approach. The technique incorporates thermal history and entropy effects into a scaling factor, which is determined using a computed enthalpy versus volume curve and a single experimental density value. We demonstrate the technique on a series of calcium aluminosilicate glasses.
MicroRNA-758 Regulates Cholesterol Efflux Through Posttranscriptional Repression of ATP-Binding Cassette Transporter A1

Objective— The ATP-binding cassette transporter A1 (ABCA1) is a major regulator of macrophage cholesterol efflux and protects cells from excess intracellular cholesterol accumulation; however, the mechanism involved in posttranscriptional regulation of ABCA1 is poorly understood. We previously showed that microRNA-33 (miR-33) is 1 regulator. Here, we investigated the potential contribution of other microRNAs (miRNAs) to posttranscriptional regulation of ABCA1 and macrophage cholesterol efflux. Methods and Results— We performed a bioinformatic analysis for identifying miRNA target prediction sites in ABCA1 gene and an unbiased genome-wide screen to identify miRNAs modulated by cholesterol excess in mouse peritoneal macrophages. Quantitative real-time reverse transcription–polymerase chain reaction confirmed that miR-758 is repressed in cholesterol-loaded macrophages. Under physiological conditions, high dietary fat excess in mice repressed miR-758 both in peritoneal macrophages and, to a lesser extent, in the liver. In mouse and human cells in vitro, miR-758 repressed the expression of ABCA1, and conversely, the inhibition of this miRNA by using anti-miR-758 increased ABCA1 expression. In mouse cells, miR-758 reduced cellular cholesterol efflux to apolipoprotein A1 (apoA1), and anti-miR-758 increased it. miR-758 directly targets the 3′-untranslated region of Abca1 as assessed by 3′-untranslated region luciferase reporter assays. Interestingly, miR-758 is highly expressed in the brain, where it also targets several genes involved in neurological functions, including Slc38a1, Ntm, Epha7 , and Mytl1 . Conclusion— We identified miR-758 as a novel miRNA that posttranscriptionally controls ABCA1 levels in different cells and regulates macrophage cellular cholesterol efflux to apoA1, opening new avenues to increase apoA1 and raise high-density lipoprotein levels.
Follistatin-Like 3 Across Gestation in Preeclampsia and Uncomplicated Pregnancies Among Lean and Obese Women

The purpose of this study was to examine circulating maternal follistatin-like 3 (FSTL-3) by gestational age and obesity in pregnancy and preeclampsia. FSTL-3 was quantified in maternal plasma collected in each trimester from prepregnancy body mass index-determined groups: 15 lean and 24 obese controls and 20 obese women who developed preeclampsia. Repeated measures mixed models and logistic regression were conducted (P ≤ .05). FSTL-3 was not related to maternal adiposity. FSTL-3 changed across pregnancy in lean controls and obese preeclampsia but not in obese controls. FSTL-3 was higher in preeclampsia in the second trimester compared to lean controls and in the third trimester compared to both control groups. Elevated FSTL-3 at mid-gestation was associated with an increased odds of preeclampsia (odds ratio 3.15; 95% confidence interval 1.19-8.36; P = .02). Elevated FSTL-3 concentrations were attributable to preeclampsia and were associated with increased likelihood of later developing preeclampsia, suggesting further study as a biomarker prior to clinically evident disease.
A comparison of individual-based and matrix projection models for simulating yellow perch population dynamics in Oneida Lake, New York, USA

Abstract Both individual-based models (IBMs) and matrix projection models are commonly used to simulate fish population dynamics. We questioned whether matrix models could be used to predict population responses of the prey in a highly coupled predator–prey system. The matrix approach was evaluated for predicting yellow perch population responses to changes in survival, and comparing the responses to those from a detailed IBM. The IBM explicitly modeled effects of walleye predation and competition with yellow perch, whereas the matrix models used averaged values, and in some cases density-dependent relationships, for survival, growth, and reproduction of yellow perch that implicitly included walleye effects. We used the output from a 200-year simulation of the IBM as data for estimating the elements of three alternative versions of a matrix projection model. We constructed an age-structured matrix model and two stage-within-age matrix models for yellow perch. The stage-within-age versions both represented the young-of-the-year (YOY) stages, but differed in the timestep used for updating their density-dependent relationships (annual or daily). The predictions of the matrix models were first compared with the IBM under baseline conditions to confirm that parameter estimation of the matrix models was reasonable. We then simulated reduced and increased egg or adult survival in each model, and compared the relative responses among the four models. Predicted yellow perch spawner abundance under baseline conditions was similar among the IBM and two matrix models that used annual density-dependence, but underestimated by the stage-within-age matrix model that used daily density-dependence. Averaged annual abundances, YOY and yearling survival rates, and sizes at age were generally similar between the IBM and matrix models under baseline conditions. Density-dependent YOY survival was critical for accurately predicting yellow perch responses to changed egg and adult survival rates. Predicted responses to changed survival rates from the stage-within-age matrix model with daily density-dependence differed most from the IBM, and consistently predicted changes in juvenile stage survival opposite to those predicted by the other models. The matrix models that used annual density-dependence predicted similar abundance responses as the IBM to changed egg and adult survival rates. If sufficient data are available, we recommend a population and multispecies modeling approach. If data are available only for the species of interest, then we favor the stage-within-age matrix model with annual density-dependence because the stage structure for YOY allows for flexibility and because it performed better than other matrix models when compared to the IBM.
The effects of temperature on bacterial production in a dimictic eutrophic lake

The incorporation of [3H](methyl)thymidine into DNA by the planktonic heterotropic bacteria of Little Crooked Lake (Noble Country, IN) was determined at different incubation temperatures. The highest rates of thymidine incorporation generally occurred at temperatures exceeding the in situ temperature of the sample. The optimal temperature for thymidine incorporation ranged from 1.0–3.4 times the in situ temperature. As the summer of 1983 progressed, the optimal temperatures for thymidine incorporation by epilimnetic samples and the in situ temperatures converged. This trend was reversed as fall overturn was approached.
Multi-Subject Behavior Functions Logically Based on Shine's Actualized and Pure Single-Subject Behavior Functions

For multi-subject experiments with all factors repeated (a single independent group of subjects), three multi-subject behavior functions are identified which are logically based on Shine's actualized and pure single-subject behavior functions. These three multi-subject behavior functions are discussed and methods for statistically analyzing them are indicated. The basic ideas are extended to multi-subject experiments with some factors nonrepeated (several independent groups of subjects).
Signalling cross-talk between hepatocyte nuclear factor 4α and growth-hormone-activated STAT5b

In the present study, we have characterized signalling cross-talk between STAT5b (signal transducer and activator of transcription 5b) and HNF4alpha (hepatocyte nuclear factor 4alpha), two major regulators of sex-dependent gene expression in the liver. In a HepG2 liver cell model, HNF4alpha strongly inhibited beta-casein and ntcp (Na+/taurocholate cotransporting polypeptide) promoter activity stimulated by GH (growth hormone)-activated STAT5b, but had no effect on interferon-gamma-stimulated STAT1 transcriptional activity. By contrast, STAT5b synergistically enhanced the transcriptional activity of HNF4alpha towards the ApoCIII (apolipoprotein CIII) promoter. The inhibitory effect of HNF4alpha on STAT5b transcription was associated with the inhibition of GH-stimulated STAT5b tyrosine phosphorylation and nuclear translocation. The short-chain fatty acid, butyrate, reversed STAT5b transcriptional inhibition by HNF4alpha, but did not reverse the inhibition of STAT5b tyrosine phosphorylation. HNF4alpha inhibition of STAT5b tyrosine phosphorylation was not reversed by pervanadate or by dominant-negative phosphotyrosine phosphatase 1B, suggesting that it does not result from an increase in STAT5b dephosphorylation. Rather, HNF4alpha blocked GH-stimulated tyrosine phosphorylation of JAK2 (Janus kinase 2), a STAT5b tyrosine kinase. Thus STAT5b and HNF4alpha exhibit bi-directional cross-talk that may augment HNF4alpha-dependent gene transcription while inhibiting STAT5b transcriptional activity via the inhibitory effects of HNF4alpha on JAK2 phosphorylation, which leads to inhibition of STAT5b signalling initiated by the GH receptor at the cell surface.
Differential inhibition of HIV-1 and SIV envelope-mediated cell fusion by C34 peptides derived from the C-terminal heptad repeat of gp41 from diverse strains of HIV-1, HIV-2, and SIV

The spectrum of inhibition of human (HIV) and simian (SIV) immunodeficiency virus envelope (Env)-mediated cell fusion by C34, a 34 residue peptide corresponding to the C-heptad repeat of gp41 (residues 628-661 of HIV-1 Env), has been examined using a panel of five envelope glycoproteins, three from HIV-1 (LAV, SF162 and 89.6) and two from SIV (mac239 and mac316), and six C34 peptides derived from three strains of HIV-1 (LAV, N CM, and O CM), two strains of HIV-2 (EHO and ALI), and one strain of SIV (African Green Monkey, AGM). A quantitative vaccinia-based reporter gene cell fusion assay was employed. The inhibition data from the panel of 30 C34/envelope glycoprotein combinations, which can be fit to a simple activity relationship with IC(50) values spanning a range of over 4 orders of magnitude from 4 nM to 70 microM, permits one to rationalize both the potency and broadness of the inhibitory properties of the C34 peptides in terms of computed interaction free energies between the C34 peptides and the N-helical trimeric coiled-coil of gp41 and the helical propensities of the free C34 peptides. Of particular interest is the finding that the C34 peptide derived from the EHO strain of HIV-2 is a broad spectrum, highly potent inhibitor of Env-mediated cell fusion with IC(50) values spanning a very narrow range from only 4 to 25 nM over the entire panel of HIV-1 and SIV envelope glycoproteins tested. This result suggests that C34 from HIV-2 EHO may present a potentially useful therapeutic agent against diverse and/or resistant strains of HIV-1.
Data smoothing algorithm

The paper describes the development of an algorithm for smoothing ship attitude angle data and the use of a spreadsheet for developing and evaluating the performance of the algorithm. The specific project involved the integration of global positioning system (GPS) (AN/WRN-6) to a ships attitude measurement system (SAMS) on board the USNS Observation Island. The SAMS its an inertial navigation system (INS) or more specific, a modified AN/WSN-5. The data output from the SAMS is used by the ship's radar tracking computer to predict a pointing angle and to drive the radar mount pointing angle to the desired object being tracked. Noise on the angle data will propagate through the track computation and will result in mount servo drive errors to compromise the radar's performance. The stabilization angle data output from the SAMS (level, crosslevel, and azimuth) is considerably better than the specification, but not as good as the existing source of data which was used in the development of the tracking computation. It describes the development of the data smoothing algorithm using what is known about the frequency and amplitude of the noise and ship's motion. The algorithm uses the current data point and previous data as required to predict a current smoothed data point in real time for the radar tracking computation. It also describes how a spreadsheet is used to first characterize the data signal and noise using the statistical and plotting tools available in a spreadsheet program. Secondly, it describes the use of the spreadsheet in development of a simulator which is used to characterize the performance of the data smoothing algorithm. The advantage of this is that it is not necessary to use a ship to exercise every possible condition. >
On the causal power generation limit for a vibratory energy harvester in broadband stochastic response

This article illustrates that certain relatively well-known results from feedback control theory can be used to determine the maximum-attainable power generation for a vibratory energy harvester excited by a stationary broadband stochastic disturbance. For such applications, control techniques based on impedance matching theory cannot be used to optimize power generation, because the dynamic controller they prescribe is always anticausal. However, an optimal causal controller does exist, and can be derived using H 2 /LQG theory. Levels of power generation with this controller are compared to those of the anticausal optimal performance, as well as to traditional 'tuning' techniques which match the anticausal impedance only at the resonant frequency. It is demonstrated that tuning techniques can be significantly sub-optimal in broadband applications, especially when electronic conversion is relatively efficient. In addition to being useful in the design of controllers for energy harvesting applications, these results may also be used to ascertain the insurpassable power generation limits associated with a given combination of transducer and electronic hardware.
Residual polyadenylation in poly(A) polymerase I (pcnB ) mutants of Escherichia coli does not result from the activity encoded by the f310 gene

As extracts of poly(A) polymerase I (PAP I) deficient strains of Escherichia coli appeared to contain considerable residual polyadenylating activity, efforts were undertaken to identify a second poly(A) polymerase. Recently, a gene (f310 ) encoding the putative second poly(A) polymerase was cloned and sequenced. Here we have tested the ability of the F310 protein to add poly(A) tails in vivo by measuring total poly(A) levels in both f310 mutants and strains that overproduce F310. In addition, we have visualized poly(A) tails and examined ColE1 plasmid copy number in various genetic backgrounds. We also carried out direct biochemical measurements of AMP incorporation, using cell extracts after amplification of F310. All the data obtained indicate that F310 is not a poly(A) polymerase. Although the presence of two potential ATP binding domains in the F310 protein may account for its apparent ATP binding activity, its true biochemical function remains to be identified. In addition, we show that the f310 gene is transcribed, almost exclusively, during stationary phase from a σs promoter.
Space-time gestures

A method for learning, tracking, and recognizing human gestures using a view-based approach to model articulated objects is presented. Objects are represented using sets of view models, rather than single templates. Stereotypical space-time patterns, i.e., gestures, are then matched to stored gesture patterns using dynamic time warping. Real-time performance is achieved by using special purpose correlation hardware and view prediction to prune as much of the search space as possible. Both view models and view predictions are learned from examples. Results showing tracking and recognition of human hand gestures at over 10 Hz are presented. >
An update on the pathophysiology of complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a neuropathic pain disorder with significant autonomic features. Few treatments have proven effective, in part, because of a historically poor understanding of the mechanisms underlying the disorder. CRPS research largely conducted during the past decade has substantially increased knowledge regarding its pathophysiologic mechanisms, indicating that they are multifactorial.Bothperipheralandcentralnervoussystemmechanisms are involved. These include peripheral and central sensitization, inflammation, altered sympathetic and catecholaminergic function, altered somatosensory representation in the brain, genetic factors, and psychophysiologic interactions. Relative contributions of the mechanisms underlying CRPS may differ across patients and even within a patient over time, particularly in the transition from “warm CRPS” (acute) to “cold CRPS” (chronic). Enhanced knowledge regarding the pathophysiology of CRPS increases the possibility of eventually achieving the goal of mechanismbased CRPS diagnosis and treatment.
The Reed—Sternberg Cell, An Activated T-cell? The Evidence Has Come Full Circle

The origin of the malignant Reed-Sternberg (RS) cell in the most common histologic types of Hodgkin's disease (HD) has been controversial. Early attempts to study RS-cells in vitro for T-cell characteristics were not fruitful. Recent studies with more sensitive immunohistochemical methods have revealed that RS-cells express T-lineage antigens in 25-60% of cases of all types of HD except nodular lymphocyte predominance which appears to be a B-cell disorder. All RS-cells express lymphocyte activation antigens. This insight should permit a more complete understanding of the histopathology, clinical features and ctiology of HD through an investigation of lymphokines, growth factors and viruses associated with activated T and B lymphocytes.
Pleistocene volcanic eruptions in New Zealand recorded in deep-sea sediments

Abstract Five layers of rhyolitic ash have been identified in deep-sea cores, taken within about 1000 km east of New Zealand. Paleomagnetic stratigraphy has been established in the cores and used for dating of the ash layers. The earliest sediment penetrated is about 3 m.y. old, and the ages of the ash layers are as follows: 0.86; 0.73; 0.67; 0.31, and 0.27 m.y. B.P. The ash layers have the same age range as the New Zealand ignimbrites, suggesting a significant ash fall phase, until now little known, associated with eruptions of ignimbrites.
Late positive potential to explicit sexual images associated with the number of sexual intercourse partners

Risky sexual behaviors typically occur when a person is sexually motivated by potent, sexual reward cues. Yet, individual differences in sensitivit yt o sexual cues have not been examined with respect to sexual risk behaviors. A greater responsiveness to sexual cues might provide greater motivation for 10 a person to act sexually; a lower responsiveness to sexual cues might lead a person to seek more intense, novel, possibly risky, sexual acts. In this study, event-related potentials were recorded in 64 men and women while they viewed a series of emotional, including explicit sexual, photographs. The motivational salience of the sexual cues was varied by including more and less explicit sexual images. Indeed, the more explicit sexual stimuli resulted in enhanced late positive potentials (LPP) relative to the less explicit sexual images. Participants with fewer sexual intercourse partners in the last year had reduced LPP amplitude to the less explicit sexual images than the more explicit sexual images, whereas participants with more partners responded 15 similarly to the more and less explicit sexual images. This pattern of results is consistent with a greater responsivity model. Those who engage in more sexual behaviors consistent with risk are also more responsive to less explicit sexual cues.
Evolving Therapeutic Strategies for Dystrophinopathies Potential for Conflict Between Cardiac and Skeletal Needs

The importance of cardiomyopathy to the clinical course of the dystrophinopathies varies according to the nature of the dystrophin defect. In Becker muscular dystrophy (BMD), cardiac involvement is often the most important determinant of clinical status and long-term outcome. For the Duchenne muscular dystrophy (DMD) patient, cardiac manifestations are often masked by inactivity and respiratory muscle compromise. However, the increasing use of ventilatory assist devices has allowed cardiac failure to emerge as a more prevalent feature of the disease.1 Furthermore, a wide range of therapeutic interventions to improve skeletal muscle strength are being explored,2 some of which may not have equivalent benefit for cardiac muscle. The article by Jefferies et al3 is therefore timely, reporting the potential cardiac benefits of early treatment of patients with DMD and BMD with afterload-reducing therapy. These authors present a retrospective review of the outcome of their patients with DMD or BMD who were managed according to a clinical treatment protocol that included initiation of ACE inhibitor (ACEI) therapy at the time of first recognition of ventricular dysfunction. β-Blocker (BB) therapy was added for patients who had no evidence of improvement in their ventricular function after 3 months. There are at least 3 important findings in their reported experience. First, there were no significant adverse clinical effects attributable to medical therapy. Although these agents have a remarkable safety profile overall, neuromuscular diseases in general are notorious for unanticipated pharmacological responses, and this result is therefore reassuring. Second, over the average follow-up duration of 3.3 years, there was a significant improvement in ventricular function (ejection fraction) and evidence of improved ventricular geometry (reduced sphericity). Third, the authors report an association between cardiac involvement and specific exon deletion, which is perhaps the least expected of these 3 results. Article p 2799 Despite the clear …
Therapeutic effects of glatiramer acetate and grafted CD115+ monocytes in a mouse model of Alzheimer’s disease

Weekly glatiramer acetate immunization of transgenic mice modelling Alzheimer's disease resulted in retained cognition (Morris water maze test), decreased amyloid-β plaque burden, and regulation of local inflammation through a mechanism involving enhanced recruitment of monocytes. Ablation of bone marrow-derived myeloid cells exacerbated plaque pathology, whereas weekly administration of glatiramer acetate enhanced cerebral recruitment of innate immune cells, which dampened the pathology. Here, we assessed the therapeutic potential of grafted CD115(+) monocytes, injected once monthly into the peripheral blood of transgenic APPSWE/PS1ΔE9 Alzheimer's disease mouse models, with and without weekly immunization of glatiramer acetate, as compared to glatiramer acetate alone. All immune-modulation treatment groups were compared with age-matched phosphate-buffered saline-injected control transgenic and untreated non-transgenic mouse groups. Two independent cohorts of mice were assessed for behavioural performance (6-8 mice/group); treatments started in 10-month-old symptomatic mice and spanned a total of 2 months. For all three treatments, our data suggest a substantial decrease in cognitive deficit as assessed by the Barnes maze test (P < 0.0001-0.001). Improved cognitive function was associated with synaptic preservation and reduction in cerebral amyloid-β protein levels and astrogliosis (P < 0.001 and P < 0.0001), with no apparent additive effects for the combined treatment. The peripherally grafted, green fluorescent protein-labelled and endogenous monocytes, homed to cerebral amyloid plaques and directly engulfed amyloid-β; their recruitment was further enhanced by glatiramer acetate. In glatiramer acetate-immunized mice and, moreover, in the combined treatment group, monocyte recruitment to the brain was coupled with greater elevation of the regulatory cytokine IL10 surrounding amyloid-β plaques. All treated transgenic mice had increased cerebral levels of MMP9 protein (P < 0.05), an enzyme capable of degrading amyloid-β, which was highly expressed by the infiltrating monocytes. In vitro studies using primary cultures of bone marrow monocyte-derived macrophages, demonstrated that glatiramer acetate enhanced the ability of macrophages to phagocytose preformed fibrillar amyloid-β1-42 (P < 0.0001). These glatiramer acetate-treated macrophages exhibited increased expression of the scavenger receptors CD36 and SCARA1 (encoded by MSR1), which can facilitate amyloid-β phagocytosis, and the amyloid-β-degrading enzyme MMP9 (P < 0.0001-0.001). Overall, our studies indicate that increased cerebral infiltration of monocytes, either by enrichment of their levels in the circulation or by weekly immunization with glatiramer acetate, resulted in substantial attenuation of disease progression in murine Alzheimer's models by mechanisms that involved enhanced cellular uptake and enzymatic degradation of toxic amyloid-β as well as regulation of brain inflammation.
Expression of Toll-Like Receptors (TLR) and Responsiveness to TLR Agonists by Polarized Mouse Uterine Epithelial Cells in Culture

The objective of the present study was to examine the expression of Toll-like receptors (TLRs) by mouse uterine epithelial cells and to determine if stimulation of the expressed TLR induces changes in cytokine and/or chemokine secretion. Using RT-PCR, the expression of TLRs 1–6 by mouse uterine epithelial cells was demonstrated, with TLRs 7–9 expressed only periodically. In the absence of pathogen-associated molecular patterns, polarized uterine epithelial cells constitutively secrete interleukin (IL) 1A, cysteine-cysteine ligand (CCL) 2, IL6, granulocyte-macrophage colony-stimulating factor 2 (CSF2), tumor necrosis factor A (TNFA), CSF3, and IL8 in vitro, with levels of cytokines/chemokines secreted into the apical compartment being significantly greater than those released into the basolateral compartment. When added to the apical surface for 48 h before analysis, the TLR2-agonist Pam 3 Cys-Ser-(Lys) 4 and TLR1/6-agonist peptidoglycan increased epithelial cell apical secretion of IL1A, CCL2, and IL6 and apical/basolateral bidirectional secretion of CSF2, TNFA, CSF3, and IL8 when compared to controls. The TLR3-agonist poly (I:C) significantly increased bidirectional secretion of CCL2, IL6, TNFA, and CSF2 and basolateral secretion of CSF3. Lastly, the TLR4-agonist lipopolysaccharide increased bidirectional secretion CCL2, CSF2, TNFA, CSF3, and IL8 and apical secretion of IL6. These results indicate that mRNAs for Tlr1 through Tlr6 are expressed by uterine epithelialcellsandthattreatmentwithspecificTLRagonistsalters the expression of key chemokines and proinflammatory cytokines that contribute to the defense of the uterus against potential pathogens. female reproductive tract, uterus, vagina
Major Depression During and After the Menopausal Transition: Study of Women’s Health Across the Nation (SWAN)

BackgroundIt is unclear whether risk for major depression during the menopausal transition or immediately thereafter is increased relative to pre-menopause. We aimed to examine whether the odds of experiencing major depression were greater when women were peri- or post-menopausal compared to when they were pre-menopausal, independent of a history of major depression at study entry and annual measures of vasomotor symptoms (VMS), serum levels of, or changes in, estradiol (E2), follicular stimulating hormone (FSH) or testosterone (T) and relevant confounders.MethodParticipants included the 221 African American and Caucasian women, aged 42–52 years, who were pre-menopausal at entry into the Pittsburgh site of a community-based study of menopause, the Study of Women's Health Across the Nation (SWAN). We conducted the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) to assess diagnoses of lifetime, annual and current major depression at baseline and at annual follow-ups. Psychosocial and health factors, and blood samples for assay of reproductive hormones, were obtained annually.ResultsWomen were two to four times more likely to experience a major depressive episode (MDE) when they were peri-menopausal or early post-menopausal. Repeated-measures logistic regression analyses showed that the effect of menopausal status was independent of history of major depression and annually measured upsetting life events, psychotropic medication use, VMS and serum levels of or changes in reproductive hormones. History of major depression was a strong predictor of major depression throughout the study.ConclusionsThe risk of major depression is greater for women during and immediately after the menopausal transition than when they are pre-menopausal.
MAPK signal transduction pathway mediates agrin effects on neurite elongation in cultured hippocampal neurons.

We have previously shown that agrin regulates the rates of axonal and dendritic elongation by modulating the expression of microtubule-associated proteins in cultured hippocampal neurons. However, the mechanisms by which agrin-induced signals are propagated to the nucleus where they can lead to the phosphorylation, and hence the activation, of transcription factors, are not known. In the present study, we identified downstream elements that play essential roles in the agrin-signaling pathway in developing central neurons. Our results indicate that agrin induces the combined activation of the extracellular signal-regulated kinases (ERK1/ERK2) and p38 in central neurons. In addition, they showed that PD98059 and SB202190, synthetic inhibitors of ERK1/ERK2 and p38 respectively, prevented the changes in the rate of neurite elongation induced by agrin in cultured hippocampal neurons. Collectively, these results suggest that agrin might modulate the expression of neuron-specific genes involved in neurite elongation by inducing CREB phosphorylation through the activation of the MAPK signal transduction pathway in cultured hippocampal neurons.
Optimization and stabilization of visibility in interferometric fiber-optic sensors using input-polarization control

The effects of input polarization on the output fringe visibility of two-beam interferometric fiber-optic sensors are investigated, and an analysis which predicts the existence of input states of polarization of eigenmodes of the interferometer for which optimum output visibility is obtained is presented. Experimental results obtained using both a bulk-optic and a fiber Mach-Zehnder interferometer are reported that verify this analysis. Active feedback stabilization of the output fringe visibility of an interferometric sensor using automatic input-polarization control is demonstrated. >
Accuracy of Self-reported Hearing Loss

The purpose of this study was to assess the accuracy, in older adults, of questions assessing hearing loss. Study participants (n=3,556), aged 48-92 years, were examined in a population-based study of age-related hearing loss in Beaver Dam, Wisconsin. Self-report data from the ten-question Hearing Handicap Inventory for the Elderly-screening Version (HHIE-S), and four additional questions were compared with hearing loss as measured by pure-tone air conduction audiometry. The single question, 'Do you feel you have a hearing loss?' was the most sensitive question (sensitivity=71 per cent); its overall and gender-specific prevalence estimates were within 3.2 per cent of prevalence measures derived audiometrically, although age-group specific estimates were not as accurate. Using an HHIE-S total score >8 resulted in low sensitivity (34 per cent) and inaccurate prevalence estimates. These results indicate that, for some applications, one simple question may be sufficient for prevalence surveys of hearing loss among older adults.