CiteULike: Author Martini

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial.

Nicolino Ruperto — 2008-07-22T00:47:27-00:00

Lancet (14 July 2008)

BACKGROUND: Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. METHODS: We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. FINDINGS: Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who continued abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups. Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, both in controls (p=0.50). INTERPRETATION: Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. FUNDING: Bristol-Myers Squibb.

Estrogen regulation of adipose tissue functions: involvement of estrogen receptor isoforms.

V Pallottini — 2008-07-17T23:25:53-00:00

Infectious disorders drug targets, Vol. 8, No. 1. (March 2008), pp. 52-60.

Adipose tissue has recently been described as one of the major endocrine gland that plays a role in energy homeostasis, lipid metabolism, immune response, and reproduction. An excess of white adipose tissue, caused by a complex interaction between genetic, hormonal, behavioral, and environmental factors, results in obesity: a heterogeneous disorder that predisposes humans to a variety of diseases. Among several hormones, estrogens promote, maintain, and control the typical distribution of body fat and adipose tissue metabolism through still unknown mechanisms. These steroids are known to regulate fat mass, adipose deposition and differentiation, and adipocyte metabolism. Moreover, estrogen deficiency results in increases in adipose tissue, preferentially in visceral fat, which would link obesity to the susceptibility of related disorders. In this review the role of estrogens in adipose tissue differentiation and in the protection against the onset of obesity will be discussed with particular attention being drawn to the underlying molecular mechanisms mediated by estrogen receptor isoforms ERalpha and ERbeta.

On sequential frame synchronization in AWGN channels

M Chiani — 2008-07-08T14:54:49-00:00

Communications, IEEE Transactions on, Vol. 54, No. 2. (2006), pp. 339-348.

We present a framework for the analysis of frame synchronization based on synchronization words (SWs), where the detection is based on the following sequential algorithm. The received samples are observed over a window of length equal to the SW; over this window, a metric (e.g., correlation) is computed; an SW is declared if the computed metric is greater than a proper threshold, otherwise the observation window is time-shifted one sample. We assume a Gaussian channel, antipodal signaling, equally distributed data symbols, and coherent detection, where soft values are provided to the frame synchronizer. We state the problem starting from the hypothesis testing theory, deriving the optimum metric [optimum likelihood ratio test (LRT)] according to the Neyman-Pearson lemma. When the data distribution is unknown, we design a simple and effective test based on the generalized LRT (GLRT). We also analyze the performance of the commonly used correlation metric, both with "hard" and "soft" values at the synchronizer input. We show that synchronization can be greatly improved by using the LRT and GLRT metrics instead of correlation and that, among correlation-based tests, sometimes hard correlation is better than soft correlation. The obtained closed-form expressions allow the derivation of the receiver operating characteristic (ROC) curves for the LRT and GLRT synchronizers, showing a remarkable gain with respect to synchronization based on correlation metric.

Influenza pandemics, immune cross-reactivity, and pandemic control strategies.

C Gioia — 2008-07-08T04:04:11-00:00

The Journal of infectious diseases, Vol. 198, No. 2. (15 July 2008), pp. 294-295.

Body composition changes in haemodialysis patients with secondary hyperparathyroidism after parathyroidectomy measured by conventional and vector bioimpedance analysis.

BS Peters — 2008-07-03T09:45:37-00:00

The British journal of nutrition, Vol. 95, No. 2. (February 2006), pp. 353-357.

Considering the negative effects of secondary hyperparathyroidism (SHPT) in patients with chronic renal failure (CRF), the objective of the present study was to evaluate body composition changes using conventional and vector bioimpedance analysis in patients before and after parathyroidectomy (PTX). Twelve adult patients, mean age 43.4 (sd 12.7) years, were evaluated prior to and 6 months after PTX. Diets were assessed with 3 d dietary records, and mean energy, protein, calcium and phosphorus intake were estimated from these inventories. Weight, height, BMI and bioelectrical impedance were measured; and biochemical markers of nutritional status (albumin and total protein) and bone metabolism (calcium, phosphorus and intact parathyroid hormone) were determined. No significant differences were observed in mean energy, protein and phosphorus after surgery. There was a significant increase in calcium intake after PTX (382.3 (sd 209.6) mg to 656.6 (sd 313.8) mg; P<0.05). Mean weight, BMI, conventional bioelectrical impedance measurements, total body fat, lean body mass and total body water were unaffected by surgery. However, the phase angle and reactance significantly increased after PTX (5.0 degrees (sd 1.4) to 5.6 degrees (sd 1.3); 44.1 (sd 15.6) Omega to 57.1 (sd 14.4) Omega, respectively). The high levels of intact parathyroid hormone before surgery had a negative effect on total body fat (r -0.69, P<0.05). After PTX, the mean albumin significantly increased (3.9 (sd 0.4) g/dl to 4.2 (sd 0.6) g/dl; P<0.05). PTX for SHPT is associated with certain changes in laboratory values, dietary intake and body composition. The latter is best seen with bioimpedance vector analysis.

Vitamin D and blood pressure connection: update on epidemiologic, clinical, and mechanistic evidence.

LA Martini — 2008-06-17T03:45:06-00:00

Nutrition reviews, Vol. 66, No. 5. (May 2008), pp. 291-297.

Hypertension is an important risk factor for cardiovascular and kidney disease. High blood pressure is a growing public health problem that is expected to affect 1.6 billion people worldwide by the year 2025. In light of emerging evidence of a widespread global problem of vitamin D deficiency, there has been increasing interest concerning the role of vitamin D in chronic disease. The recent publication of several studies, highlighted in this brief review, supports an association between vitamin D status and blood pressure. It remains to be determined what level of vitamin D status needs to be achieved in different subpopulations to assure the maximum benefit of vitamin D status on blood pressure.

Coherence for sharing proof-nets

Stefano Guerrini — 2008-06-10T12:21:02-00:00

Theor. Comput. Sci., Vol. 294, No. 3. (February 2003), pp. 379-409.

Juvenile idiopathic arthritis.

A Ravelli — 2008-06-06T05:21:47-00:00

Lancet, Vol. 369, No. 9563. (3 March 2007), pp. 767-778.

Juvenile idiopathic arthritis is a broad term that describes a clinically heterogeneous group of arthritides of unknown cause, which begin before 16 years of age. This term encompasses several disease categories, each of which has distinct methods of presentation, clinical signs, and symptoms, and, in some cases, genetic background. The cause of disease is still poorly understood but seems to be related to both genetic and environmental factors, which result in the heterogeneity of the illness. Although none of the available drugs has a curative potential, prognosis has greatly improved as a result of substantial progresses in disease management. The most important new development has been the introduction of drugs such as anticytokine agents, which constitute a valuable treatment option for patients who are resistant to conventional antirheumatic agents. Further insights into the disease pathogenesis and treatment will be provided by the continuous advances in understanding of the mechanisms connected to the immune response and inflammatory process, and by the development of new drugs that are able to inhibit selectively single molecules or pathways.

S1P modulator FTY720 limits matrix expansion in acute anti-thy1 mesangioproliferative glomerulonephritis.

S Martini — 2008-05-01T09:33:29-00:00

American journal of physiology. Renal physiology, Vol. 292, No. 6. (June 2007)

FTY720 is a novel immune modulator whose primary action is blood lymphocyte depletion through interaction with sphingosine-1-phosphate (S1P) receptors. The present study analyzes the effect of FTY720 on both the early mesangial cell injury and the subsequent matrix expansion phase of experimental mesangioproliferative glomerulonephritis. Disease was induced by injection of OX-7 anti-thy1 antibody into male Wistar rats. In both protocols, FTY720 administration (0.3 mg/kg body wt) resulted in a selective and very marked reduction in blood lymphocyte count. In the injury experiment, the S1P receptor modulator was given starting 5 days before and continued until 1 day after antibody injection. FTY720 did not significantly affect the degree of anti-thy1-induced mesangial cell lysis and glomerular-inducible nitric oxide production. In the matrix expansion experiment, FTY720 treatment was started 1 day after antibody injection and continued until day 7. In this protocol, the S1P modulator reduced proteinuria, histological matrix expansion, and glomerular protein expression of TGF-beta(1), fibronectin, and PAI-1. Glomerular collagen III staining intensity was decreased. FTY720 reduced markedly glomerular lymphocyte number per cross section and to a lesser degree macrophage infiltration. In conclusion, FTY720 significantly limits TGF-beta(1) overexpression and matrix protein expression following induction of acute anti-thy glomerulonephritis, involving reductions in blood and glomerular lymphocyte numbers. The results suggest that lymphocytes actively contribute to matrix expansion in experimental mesangioproliferative glomerulonephritis. Our study expands on findings on FTY720's beneficial effects on tubulointerstitial and functional disease progression previously reported in anti-thy1-induced chronic glomerulosclerosis.

Link stability in mobile wireless ad hoc networks

M Gerharz — 2005-08-24T09:14:49-00:00

Local Computer Networks, 2002. Proceedings. LCN 2002. 27th Annual IEEE Conference on (2002), pp. 30-39.

We develop adaptive metrics to identify stable links in a mobile wireless networking environment based on the analysis of link durations in several different mobility scenarios. Our metrics only rely on online statistical evaluation of observed link durations. Neither do they require information on signal strength, radio conditions, or spacing of the mobile devices, nor do they depend on the availability of additional hardware such as GPS receivers or a synchronisation of the devices. We demonstrate the ability of the metrics to select stable links with a high probability in a wide range of scenarios.

A computational interpretation of modal proofs

S Martini — 2008-04-04T14:03:31-00:00

(1995)

The usual (e.g. Prawitz's) treatment of natural deduction for modal logics involves a complicated rule for the introduction of the necessity, since the naive one does not allow normalization. We propose natural deduction systems for the positive fragments of the modal logics K, K4, KT, and S4, extending previous work by Masini on a two-dimensional generalization of Gentzen's sequents (2-sequents). The modal rules closely match the standard rules for an universal quantifier and different logics...

Some applications of cross-section measures in Minkowski spaces

Martini — 2007-03-11T13:27:46-00:00

Periodica Mathematica Hungarica, Vol. 53, No. 1-2. (September 2006), pp. 185-197.

The Wlds mutation delays robust loss of motor and sensory axons in a genetic model for myelin-related axonopathy.

M Samsam — 2008-04-01T13:58:56-00:00

J Neurosci, Vol. 23, No. 7. (1 April 2003), pp. 2833-2839.

Mice deficient in the peripheral myelin component P0 mimic severe forms of inherited peripheral neuropathies in humans, with defective myelin formation and consequent axonal loss. We cross-bred these mice with the spontaneous mutant C57BL/Wld(s) typically showing protection from Wallerian degeneration because of fusion of the ubiquitination factor E4B (Ube4b) and nicotinamide mononucleotide adenylyltransferase (Nmnat) genes. We found that in the double mutants, the robust myelin-related axonal loss is reduced at 6 weeks and 3 months of age. Moreover, retrograde labeling from plantar nerves revealed an increased survival of motor axons. These motor axons appeared functionally active because both the amplitude of compound muscle action potentials and muscle strength were less reduced in the double mutants. At 6 months of age, reduction of axonal loss was no longer detectable in the double mutants when compared with littermates carrying the P0 null mutation only, although the Wld(s) gene was not reduced in its expression at this age. We conclude that myelin-related axonal loss is a process having some features in common with Wallerian degeneration. Introducing the Wld(s) gene would be a promising approach to delaying detrimental axonal loss in myelin disorders.

Independent component analysis applied to the removal of motion artifacts from electrocardiographic signals

M Milanesi — 2008-03-14T21:33:57-00:00

Medical and Biological Engineering and Computing, Vol. 46, No. 3. (16 March 2008), pp. 251-261.

Abstract Electrocardiographic (ECG) signals are affected by several kinds of artifacts that may hide vital signs of interest. In this study we apply independent component analysis (ICA) to isolate motion artifacts. Standard or instantaneous ICA, which is currently the most addressed ICA model within the context of artifact removal, is compared to two other ICA techniques. The first technique is a frequency domain approach to convolutive mixture separation. The second is based on temporally constrained ICA, which enables the estimation of only one component close to a particular reference signal. Performance indexes evaluate ECG complex enhancement and relevant heart rate errors. Our results show that both convolutive and constrained ICA implementations perform better than standard ICA, thus opening up a new field of application for these two methods. Moreover, statistical analysis reveals that constrained ICA and convolutive ICA do not significantly differ concerning heart rate estimation, even though the latter overcomes the former in ECG morphology recovery.

A Population of Massive Globular Clusters in NGC 5128

P Martini — 2008-03-12T17:54:06-00:00

Astrophys. J., Vol. 610 (July 2004), pp. 233-246.

We present velocity dispersion measurements of 14 globular clusters in NGC 5128 (Centarus A) obtained with the MIKE echelle spectrograph on the 6.5 m Magellan Clay telescope. These clusters are among the most luminous globular clusters in NGC 5128 and have velocity dispersions comparable to the most massive clusters known in the Local Group, ranging from 10 to 30 km s<SUP>-1</SUP>. We describe in detail our cross-correlation measurements, as well as simulations to quantify the uncertainties. These 14 globular clusters are the brightest NGC 5128 globular clusters with surface photometry and structural parameters measured from the Hubble Space Telescope. We have used these measurements to derive masses and mass-to-light ratios for all of these clusters and establish that the fundamental plane relations for globular clusters extend to an order-of-magnitude higher mass than in the Local Group. The mean mass-to-light ratio for the NGC 5128 clusters is ~3+/-1, higher than measurements for all but the most massive Local Group clusters. These massive clusters begin to bridge the mass gap between the most massive star clusters and the lowest mass galaxies. We find that the properties of NGC 5128 globular clusters overlap quite well with the central properties of nucleated dwarf galaxies and ultracompact dwarf galaxies. As six of these clusters also show evidence for extratidal light, we hypothesize that at least some of these massive clusters are the nuclei of tidally stripped dwarfs.

The magnitude of early response to methotrexate therapy predicts long-term outcome of patients with juvenile idiopathic arthritis.

M Bartoli — 2008-02-26T07:55:36-00:00

Ann Rheum Dis, Vol. 67, No. 3. (March 2008), pp. 370-374.

OBJECTIVE: To investigate the relationship between the magnitude of clinical response in the first 6 months of methotrexate (MTX) therapy and long-term outcome in children with juvenile idiopathic arthritis (JIA). METHODS: The clinical charts of 125 JIA patients who were started with MTX and then followed for at least 5 years were reviewed. Based on the level of American College of Rheumatology (ACR) Pediatric response at 6 months, patients were divided in four mutually exclusive groups: (1) non-responders, (2) responders at 30%, (3) responders at 50%, and (4) responders at 70%. The long-term outcome in each response group was evaluated by calculating the percentage change in active and restricted joint counts from baseline to 1, 2 and 5 years and the frequency of inactive disease at 5 years. RESULTS: At 6 months, 42 patients were classified as non-responders, 24 as 30% responders, 26 as 50% responders, and 33 as 70% responders. Patients who had achieved a 70% response showed a significantly greater percentage improvement in active joint count between baseline to 5 years compared with non-responders and 30% responders, and a significantly greater percentage improvement in restricted joint count between baseline to 5 years compared with 30% responders. The 70% responders also had a greater frequency of inactive disease at 5 years compared with 30% responders, CONCLUSIONS: Our results show that the achievement of an ACR Pediatric 70 response at 6 months after start of MTX therapy predicts a more favorable long-term outcome of patients with JIA.

Content adaptive network aware joint optimization of wireless video transmission

Maria Martini — 2007-02-14T18:56:51-00:00

IEEE Communications Magazine, Vol. 45, No. 1. (January 2007), pp. 84-90.

A content adaptive, network aware approach for joint optimization of wireless video transmission is presented in this article. The joint system optimization approach has been developed in the framework of the IST PHOENIX project (www.ist-phoenix.org). After a description of the considered cross-layer approach and of the information to be exchanged among the system component blocks, the concept of "JSCC/D controllers" is introduced. Results obtained through the demonstrator realized as proof-of-concept for the described paradigm are then shown, confirming the validity of the described joint optimization approach

Steroid metabolism and effects in central and peripheral glial cells.

RC Melcangi — 2008-02-12T18:23:31-00:00

J Neurobiol, Vol. 40, No. 4. (15 September 1999), pp. 471-483.

Hormonal steroids participate in the control of a large number of functions of the central nervous system (CNS); recent data show that they may also intervene at the level of the peripheral nervous system (PNS). Both the CNS and the PNS metabolize endogenous as well as exogenous steroids; one of the major enzymatic system is represented by the 5alpha-reductase-3alpha-hydroxysteroid complex. This is a versatile system, since every steroid possessing the delta 4-3keto configuration (e.g., testosterone, progesterone, deoxycorticosterone) may be a substrate. High levels of 5alpha-reductase are found in the white matter of the CNS and in purified myelin. The observation that, in addition to neurons, glia may be a target for steroid action is an important recent finding. The effects of progesterone, testosterone, corticoids, and their respective 5alpha and 3alpha-5alpha derivatives on the expression of glial genes are presented and discussed. It has also been found that progesterone and/or its 5alpha-reduced metabolites increase the mRNA for the two major proteins of peripheral myelin, the glycoprotein Po and the peripheral myelin protein 22, in the sciatic nerve of normal and aged animals and in Schwann cells. The hypothesis has been put forward that glycoprotein Po might be under the control of progestagens acting mainly via the progesterone receptor, and that peripheral myelin protein 22 might be controlled via an interaction of steroids with the gamma-aminobutyric acid (GABA)ergic system. It is known that tetrahydroprogesterone, the 3alpha-5alpha-reduced metabolite of progesterone, interacts with the GABA(A) receptor. Our recent data show that several subunits of this receptor are present in sciatic nerve as well as in Schwann cells that reside in this nerve. These data open multiple possibilities for new therapeutic approaches to demyelinating diseases.

The 5alpha-reductase in the central nervous system: expression and modes of control.

RC Melcangi — 2008-02-11T19:10:50-00:00

J Steroid Biochem Mol Biol, Vol. 65, No. 1-6. (April 1998), pp. 295-299.

The present paper will summarize two important aspects of the interactions between steroids and the brain, which have recently been studied in the authors' laboratory. In particular the paper will consider data on: (1) the significance of the two isoforms of the 5alpha-R during brain ontogenesis and development, and (2) the cross-talk between glial and neuronal elements, particularly in relation to the metabolism of sex hormones. (1) The data obtained have shown that the 5alpha-R type 1 enzyme is constitutively expressed in the rat CNS at all stages of brain development. Moreover, the expression of the 5alpha-R type 1 is similar in males and in females, and does not appear to be controlled by androgens. The gene expression of the 5alpha-R type 2 is totally different. This isoform appears to be expressed in the rat brain almost exclusively in the late fetal/early post-natal life and is controlled by testosterone. (2) The present data show that two cell lines derived respectively from a rat glioma (C6 cell line) and from a human astrocytoma (1321N1 cell line) are able to convert testosterone and progesterone into their corresponding 5alpha-reduced metabolites dihydrotestosterone and dihydroprogesterone. The possibility that secretory products of normal and tumoral brain cells might be able to influence steroid metabolism occurring in the two glial cell lines previously mentioned has been considered.

Progesterone 5-alpha-reduction in neuronal and in different types of glial cell cultures: type 1 and 2 astrocytes and oligodendrocytes.

RC Melcangi — 2008-02-11T19:10:49-00:00

Brain Res, Vol. 639, No. 2. (14 March 1994), pp. 202-206.

Progesterone, like testosterone, can be converted in the brain into 5-alpha-reduced metabolites (5-alpha-pregnan-3,20-dione, DHP; 5-alpha-pregnan-3-alpha-ol-20-one, THP). Recently we have shown that testosterone is 5-alpha-reduced to DHT mainly in neurons, while glial cells possess this enzymatic activity only in limited amounts. On the other hand, a glial cell type (type 1 astrocytes) is almost exclusively responsible for the further metabolism of DHT into 3-alpha-diol. The aim of the present studies was that of evaluating the formation of the 5-alpha-reduced metabolites of progesterone in cultures of neurons, type 1 and 2 astrocytes and oligodendrocytes. The data here presented indicate that, similarly to what happens when testosterone is used as the substrate, the 5-alpha-reductase which metabolizes progesterone shows a significantly higher activity in neurons than in glial cells; however, also type-1 and type-2 astrocytes as well as oligodendrocytes possess some ability to 5-alpha-reduce progesterone. On the contrary, the 3-alpha-hydroxysteroid dehydrogenase (3-alpha-HSD), the enzyme which converts DHP into THP, appears to be mainly present in type-1 astrocytes; much lower levels of this enzyme are present in neurons and in type-2 astrocytes. At variance with the previous results obtained utilizing androgens as precursors, oligodendrocytes show a considerable 3-alpha-HSD activity, even if this is statistically lower than that present in type-1 astrocytes. The existence of isoforms of the enzymes involved in androgen and progesterone metabolism may explain these data.

Glial cells: a target for steroid hormones.

RC Melcangi — 2008-02-11T19:07:42-00:00

Prog Brain Res, Vol. 132 (2001), pp. 31-40.

Formation and effects of neuroactive steroids in the central and peripheral nervous system.

RC Melcangi — 2008-02-11T16:40:27-00:00

Int Rev Neurobiol, Vol. 46 (2001), pp. 145-176.

This chapter summarizes several observations that emphasize the importance of neuroactive steroids in the physiology of the central and peripheral nervous systems. A new, and probably important, concept is emerging: Neuroactive steroids not only modify neuronal physiology but also intervene in the control of glial cell functions. The data presented here underscore that (1) the mechanism of action of the various steroidal molecules may involve both classical (progesterone and androgens) and nonclassical steroid receptors [gamma-aminobutyric acid type A (GABAA) receptor], (2) in many instances, the actions of hormonal steroids are not due to their native molecular forms but to their 5 alpha- and 3 alpha,5 alpha-reduced metabolites, (3) several neuroactive steroids exert dramatic actions on the proteins proper of the peripheral myelin (e.g., glycoprotein Po and peripheral myelin protein 22), and (4) the effects of steroids and of their metabolites might have clinical significance in cases in which the rebuilding of the peripheral myelin is needed (e.g., aging, peripheral injury).

Cue-Elicited Reward-Seeking Requires Extracellular Signal-Regulated Kinase Activation in the Nucleus Accumbens

Michael Shiflett — 2008-02-06T17:43:10-00:00

J. Neurosci., Vol. 28, No. 6. (6 February 2008), pp. 1434-1443.

The motivation to seek out rewards can come under the control of stimuli associated with reward delivery. The ability of cues to motivate reward-seeking behavior depends on the nucleus accumbens (NAcc). The molecular mechanisms in the NAcc that underlie the ability of a cue to motivate reward-seeking are not well understood. We examined whether extracellular signal-regulated kinase (ERK), an important intracellular signaling pathway in learning and memory, has a role in these motivational processes. We first examined p42 ERK (ERK2) activation in the NAcc after rats were trained to associate an auditory stimulus with food delivery and found that, as a consequence of training, presentation of the auditory cue itself was sufficient to increase ERK2 activation in the NAcc. To examine whether inhibition of ERK in the NAcc prevents cue-induced reward-seeking, we infused an inhibitor of ERK, U0126, into the NAcc before assessing rats' instrumental responding in the presence versus absence of the conditioned cue. We found that, whereas vehicle-infused rats showed increased instrumental responding during cue presentation, rats infused with U0126 showed a profound impairment in cue-induced instrumental responding. In contrast, intra-NAcc U0126 infusion had no effect on rats' food-reinforced instrumental responding or their ability to execute conditioned approach behavior. Our results demonstrate learning-related changes in ERK signaling in the NAcc, and that disruption of ERK activation in this structure interferes with the incentive-motivational effects of conditioned stimuli. The molecular mechanisms described here may have implications for cue-elicited drug craving after repeated exposure to drugs of abuse. 10.1523/JNEUROSCI.2383-07.2008

Estrogen Receptors alpha and beta Mediate Distinct Pathways of Vascular Gene Expression, Including Genes Involved in Mitochondrial Electron Transport and Generation of Reactive Oxygen Species

Raegan O'Lone — 2008-02-03T01:32:07-00:00

Mol Endocrinol, Vol. 21, No. 6. (1 June 2007), pp. 1281-1296.

Estrogen plays an important role in the regulation of vascular tone and in the pathophysiology of cardiovascular disease. Physiological effects of estrogen are mediated through estrogen receptors alpha (ERalpha) and beta (ERbeta), which are both expressed in vascular smooth muscle and endothelial cells. However, the molecular pathways mediating estrogen effects in blood vessels are not well defined. We have performed gene expression profiling in the mouse aorta to identify comprehensive gene sets the expression of which is regulated by long-term (1 wk) estrogen treatment. The ER subtype dependence of the alterations in gene expression was characterized by parallel gene expression profiling experiments in ERalpha-deficient [ERalpha knockout (ERalphaKO)] and ERbeta-deficient (ERbetaKO) mice. Importantly, these data revealed that ERalpha- and ERbeta-dependent pathways regulate distinct and largely nonoverlapping sets of genes. Whereas ERalpha is essential for most of the estrogen-mediated increase in gene expression in wild-type aortas, ERbeta mediates the large majority (nearly 90%) of estrogen-mediated decreases in gene expression. Biological functions of the estrogen-regulated genes include extracellular matrix synthesis, in addition to electron transport in the mitochondrion and reactive oxygen species pathways. Of note, the estrogen/ERbeta pathway mediates down-regulation of mRNAs for nuclear-encoded subunits in each of the major complexes of the mitochondrial respiratory chain. Several estrogen-regulated genes also encode transcription factors. Computational analysis of promoters from coexpressed genes revealed overrepresentation of binding sites for such factors, lending support for an estrogen-regulatory transcriptional network in the vasculature. Overall, these findings provide a foundation for understanding the molecular basis for estrogen effects on vasculature gene expression. 10.1210/me.2006-0497

Ligand-induced down-regulation of the cannabinoid 1 receptor is mediated by the G-protein-coupled receptor-associated sorting protein GASP1

Lene Martini — 2008-02-01T05:31:54-00:00

FASEB J., Vol. 21, No. 3. (1 March 2007), pp. 802-811.

The cannabinoid 1 receptor (CB1R) is one of the most abundant seven transmembrane (7TM) spanning/G-protein-coupled receptors in the central nervous system and plays an important role in pain transmission, feeding, and the rewarding effects of cannabis. Tolerance to cannabinoids has been widely observed after long-term use, with concomitant receptor desensitization and/or down-regulation depending on the brain region studied. Several CB1R agonists promote receptor internalization after activation, but the postendocytic sorting of the receptor has not been studied in detail. Utilizing human embryonic kidney (HEK293) cells stably expressing the CB1R and primary cultured neurons expressing endogenous CB1R, we show that treatment with cannabinoid agonists results in CB1R degradation after endocytosis and that the G-protein-coupled receptor-associated sorting protein GASP1 plays a major role in the postendocytic sorting process. Thus, these results may identify a molecular mechanism underlying tolerance and receptor down-regulation after long-term use of cannabinoids.--Martini, L., Waldhoer, M., Pusch, M., Kharazia, V., Fong, J., Lee, J. H., Freissmuth, C., Whistler, J. L. Ligand-induced down-regulation of the cannabinoid 1 receptor is mediated by the G-protein-coupled receptor-associated sorting protein GASP1. 10.1096/fj.06-7132com

Simultaneous control of DNA and RNA processing efficiency using a nucleic acid calibration set.

B Bartolini — 2007-12-31T15:39:11-00:00

Biotechniques, Vol. 42, No. 4. (April 2007)

Tenascin-C expression during wallerian degeneration in C57BL/Wlds mice: possible implications for axonal regeneration.

M Fruttiger — 2007-12-12T17:04:01-00:00

J Neurocytol, Vol. 24, No. 1. (January 1995), pp. 1-14.

Schwann cells in the distal stumps of lesioned peripheral nerves strongly express the extracellular matrix glycoprotein tenascin-C. To gain insights into the relationship between Wallerian degeneration, lesion induced tenascin-C upregulation and regrowth of axons we have investigated C57BL/Wlds (C57BL/Ola) mice, a mutant in which Wallerian degeneration is considerably delayed. Since we found a distinct difference in the speed of Wallerian degeneration between muscle nerves and cutaneous nerves in 16-week-old C57BL/Wlds mice, as opposed to 6-week-old animals in which Wallerian degeneration is delayed in both, we chose the older animals for closer investigation. Five days post lesion tenascin-C was upregulated in the muscle branch (quadriceps) but not in the cutaneous branch (saphenous) of the femoral nerve in 16-week-old animals. In addition myelomonocytic cells displaying endogenous peroxidase activity invaded the muscle branch readily whereas they were absent from the cutaneous branch at this time. We could further show that it is only a subpopulation of axon-Schwann cell units (mainly muscle efferents) in the muscle branch which undergo Wallerian degeneration and upregulate tenascin-C at normal speed and that the remaining axon-Schwann cell units (mainly afferents) displayed delayed Wallerian degeneration and no tenascin-C expression. Regrowing axons could only be found in the tenascin-C-positive muscle branch where they always grew in association with axon-Schwann cell units undergoing Wallerian degeneration. These observations indicate a tight relationship between Wallerian degeneration, upregulation of tenascin-C expression and regrowth of axons, suggesting an involvement of tenascin-C in peripheral nerve regeneration.

A Flexible Dynamic Partitioning Algorithm for Optimistic Distributed Simulation

Patrick Peschlow — 2007-06-21T00:39:55-00:00

(2007), pp. 219-228.

Elements of basic category theory

A Martini — 2007-07-08T15:51:01-00:00

(1996)

Category theory provides an elegant and powerful means of expressing relationships across a wide area of mathematics. But further than this it has had a considerable impact on the conceptual basis both of mathematics and many parts of theoretical computer science. Important connections in computer science include the design of both functional and imperative programming languages, semantic models of programming languages, semantics of concurrency, specification and development of algorithms,...

Peripheral-type benzodiazepine receptor binding sites in platelets of patients with panic disorder associated to separation anxiety symptoms.

S Pini — 2007-11-12T03:22:34-00:00

Psychopharmacology (Berl), Vol. 181, No. 2. (September 2005), pp. 407-411.

RATIONALE: Although it is still a matter of debate whether panic disorder (PD) and separation anxiety (SA) are associated or causally linked disorders, some investigators have suggested that SA may be a specific subtype of panic-agoraphobic spectrum. Several psychiatric disorders, including PD, are associated with lower levels of peripheral-type benzodiazepine receptor (PBR). OBJECTIVES: The aim of the present study was to evaluate the kinetic binding parameters of the specific PBR ligand, PK 11195, in platelets from patients with PD in relation to the presence and severity of adulthood SA. METHODS: Using the specific radioligand, [(3)H] PK 11195, the kinetic binding parameters of PBR were determined on platelet membranes of 27 adult outpatients with a DSM-IV diagnosis of PD and 18 healthy controls. Patients were assessed with the SCID-I, the Panic Disorder Severity Scale, the Structured Clinical Interview for Separation Anxiety Symptoms and the Adult Separation Anxiety Checklist. RESULTS: PD patients had significantly lower PBR density than controls. However, the lower density was only evident in the subgroup of PD patients who also fulfilled the DSM-IV criteria for adult separation anxiety disorder. PBR density was negatively correlated with each of the two SA scales total scores. CONCLUSIONS: Patients with SA symptoms had significantly lower densities of PBRs. PBR expression might become a useful biological marker of these two associated conditions.

From the Cover: The origin of European cattle: Evidence from modern and ancient DNA

Albano Beja-Pereira — 2006-05-27T19:25:43-00:00

PNAS, Vol. 103, No. 21. (23 May 2006), pp. 8113-8118.

Cattle domestication from wild aurochsen was among the most important innovations during the Neolithic agricultural revolution. The available genetic and archaeological evidence points to at least two major sites of domestication in India and in the Near East, where zebu and the taurine breeds would have emerged independently. Under this hypothesis, all present-day European breeds would be descended from cattle domesticated in the Near East and subsequently spread during the diffusion of herding and farming lifestyles. We present here previously undescribed genetic evidence in contrast with this view, based on mtDNA sequences from five Italian aurochsen dated between 7,000 and 17,000 years B.P. and >1,000 modern cattle from 51 breeds. Our data are compatible with local domestication events in Europe and support at least some levels of introgression from the aurochs in Italy. The distribution of genetic variation in modern cattle suggest also that different south European breeds were affected by introductions from northern Africa. If so, the European cattle may represent a more variable and valuable genetic resource than previously realized, and previous simple hypotheses regarding the domestication process and the diffusion of selected breeds should be revised. 10.1073/pnas.0509210103

Enhancing cGMP in experimental progressive renal fibrosis: soluble guanylate cyclase stimulation vs. phosphodiesterase inhibition.

Y Wang — 2007-09-05T09:20:17-00:00

Am J Physiol Renal Physiol, Vol. 290, No. 1. (January 2006)

cGMP serves as the main second messenger of nitric oxide (NO). Antifibrotic effects of enhancing renal cGMP levels have recently been documented in experimental acute anti-Thy-1 glomerulonephritis. The present study compares the effects of the cGMP production-increasing soluble guanylate cyclase (sGC) stimulator BAY 41-2272 with those of the cGMP degradation-limiting phosphodiesterase inhibitor pentoxifylline (PTX) in a progressive model of renal fibrosis. At 1 wk after induction of anti-Thy-1-induced chronic glomerulosclerosis (cGS), rats were randomly assigned to groups as follows: cGS, cGS + BAY 41-2272 (10 mg x kg body wt(-1) x day(-1)), or cGS + PTX (50 mg x kg body wt(-1) x day(-1)). BAY 41-2272 and PTX reduced systolic blood pressure significantly. At 16 wk, tubulointerstitial expressions of sGC mRNA and NO-induced cGMP synthesis were increased in untreated cGS animals, whereas their glomerular activity was depressed compared with normal controls. Tubulointerstitial and glomerular cGMP production in response to NO were significantly enhanced in animals treated with BAY 41-2272, but not in those treated with PTX. BAY 41-2272 administration resulted in marked reductions of glomerular and tubulointerstitial histological matrix accumulation, expression of TGF-beta1 and fibronectin, macrophage infiltration, and cell proliferation as well as improved renal function. In contrast, only moderate and nonsignificant renoprotective changes were observed in the cGS + PTX group. In conclusion, increasing renal cGMP production through BAY 41-2272 significantly improved renal NO-cGMP signaling and limited progression in anti-Thy-1-induced chronic renal fibrosis, whereas inhibition of cGMP degradation by PTX was only moderately effective. The findings indicate that pharmacological enhancement of renal cGMP levels by sGC stimulation represents a novel and effective antifibrotic approach in progressive kidney disorders.

The geometry of Minkowski spaces -- a survey. Part I

Horst Martini — 2007-08-22T13:04:53-00:00

(21 Aug 2007)

We survey elementary results in Minkowski spaces (i.e. finite dimensional Banach spaces) that deserve to be collected together, and give simple proofs for some of them. We place special emphasis on planar results. Many of these results have often been rediscovered as lemmas to other results. In Part I we cover the following topics: The triangle inequality and consequences such as the monotonicity lemma, geometric characterizations of strict convexity, normality (Birkhoff orthogonality), conjugate diameters and Radon curves, equilateral triangles and the affine regular hexagon construction, equilateral sets, circles: intersection, circumscribed, characterizations, circumference and area, inscribed equilateral polygons.

Changes in regional cerebral blood flow caused by deep-brain stimulation of the subthalamic nucleus in Parkinson's disease.

S Sestini — 2007-08-03T15:47:15-00:00

J Nucl Med, Vol. 43, No. 6. (June 2002), pp. 725-732.

The aim of this study was to investigate the effect of deep-brain stimulation of the subthalamic nucleus (STN) on regional cerebral blood flow (rCBF) throughout the entire brain volume in patients with Parkinson's disease and to evaluate which of the brain areas showing an rCBF increase during STN stimulation related significantly to the improvement in motor function. METHODS: Ten consecutive Parkinson's disease patients (6 men, 4 women; mean age +/- SD, 59 +/- 8 y) with bilateral STN stimulators underwent 3 rCBF SPECT examinations at rest: the first preoperatively and the second and third postoperatively (follow-up, 4.8 +/- 1.4 mo) with STN stimulators on and off, respectively. The motor unified Parkinson's disease rating scale, the Hoehn and Yahr disability scale, and the Schwab and England activities-of-daily-living scale were used to evaluate the clinical state under each condition. Statistical parametric mapping was used to investigate rCBF during STN stimulation in comparison with rCBF preoperatively and with STN stimulators off. Also evaluated with statistical parametric mapping was the relationship between rCBF and individual motor scores used as covariates of interest. RESULTS: STN stimulation significantly changed rCBF in the right pre-supplementary motor area (pre-SMA), anterior cingulate cortex, and dorsolateral prefrontal cortex and in the medial Brodmann's area 8 (BA8) as defined in the atlas of Talairach and Tournoux (P < 0.05 corrected for multiple comparisons). The rCBF in these areas increased from the preoperative condition to the stimulators-on condition and decreased again after the stimulators were switched off. A significant correlation was detected between the improvement in motor scores and the rCBF increase only in the right pre-SMA and in the anterior cingulate motor area (P < 0.005, uncorrected). CONCLUSION: According to the topographic organization of the primate STN, our study shows that stimulation of the STN leads to rCBF increases in the motor (pre-SMA), associative, and limbic territories (anterior cingulate) in the frontal cortex. The significant correlation between motor improvement and rCBF increase in the pre-SMA and the anterior cingulate motor area reinforces the hypothesis that STN stimulation in parkinsonian patients can potentiate the cortical areas participating in higher-order aspects of motor control.

Category Theory and the Simply-Typed lambda-Calculus

Alfio Martini — 2007-07-08T15:51:45-00:00

This report deals with the question on how to provide a categorical model for the simply-typed -calculus. We first introduce cartesian closed categories and work in detail a number of results concerning this construction. Next, we present the basic concepts related with the typed -calculus, i.e., concrete syntax for -terms, occurrence of variables, context substitution and equivalence of -terms. Then we present the typing rules and an equational proof system together with reduction rules that...

A Molecular Basis of Analgesic Tolerance to Cannabinoids

Anke Tappe-Theodor — 2007-06-18T02:28:25-00:00

J. Neurosci., Vol. 27, No. 15. (11 April 2007), pp. 4165-4177.

Clinical usage of cannabinoids in chronic pain states is limited by their central side effects and the pharmacodynamic tolerance that sets in after repeated dosage. Analgesic tolerance to cannabinoids in vivo could be caused by agonist-induced downregulation and intracellular trafficking of cannabinoid receptors, but little is known about the molecular mechanisms involved. We show here that the type 1 cannabinoid receptor (CB1) interacts physically with G-protein-associated sorting protein 1 (GASP1), a protein that sorts receptors in lysosomal compartments destined for degradation. CB1-GASP1 interaction was observed to be required for agonist-induced downregulation of CB1 in spinal neurons ex vivo as well as in vivo. Importantly, uncoupling CB1 from GASP1 in mice in vivo abrogated tolerance toward cannabinoid-induced analgesia. These results suggest that GASP1 is a key regulator of the fate of CB1 after agonist exposure in the nervous system and critically determines analgesic tolerance to cannabinoids. 10.1523/JNEUROSCI.5648-06.2007

2-(Benzimidazol-2-yl)quinoxalines: a novel class of selective antagonists at human A(1) and A(3) adenosine receptors designed by 3D database searching.

E Novellino — 2007-05-17T16:11:56-00:00

J Med Chem, Vol. 48, No. 26. (29 December 2005), pp. 8253-8260.

The Cambridge Structural Database (CSD) was searched through two 3D queries based on substructures shared by well-known antagonists at the A(1) and A(3) adenosine receptors (ARs). Among the resulting 557 hits found in the CSD, we selected five compounds to purchase, synthesize, or translate synthetically into analogues better tailored to interact with the biological targets. Binding experiments using human ARs showed that four out of five tested compounds turned out to be antagonists at the A(1)AR or A(3)AR with K(i) values between 50 and 440 nM. Lead optimizations of 2-(benzimidazol-2-yl)quinoxalines (BIQs, 3) gave the best results in terms of potency and selectivity at the A(1) and A(3) ARs. Particularly, 2-(4-ethylthiobenzimidazol-2-yl)quinoxaline (3e) exhibited K(i) values at the A(1)AR, A(2A)AR, and A(3)AR of 0.5, 3440, and 955 nM, respectively, whereas 2-(4-methylbenzimidazol-2-yl)quinoxaline (3b) displayed at the same ARs K(i) values of 8000, 833, and 26 nM, respectively.

Intracellular Ca2+ buffers can dramatically affect Ca2+ conductances in hair cells.

M Martini — 2007-04-05T14:55:43-00:00

Hear Res, Vol. 195, No. 1-2. (September 2004), pp. 67-74.

The effects of endogenous and exogenous Ca(2+) buffers on Ca(2+) current kinetics have been investigated by patch clamp in hair cells mechanically isolated from frog semicircular canals. This preparation displays at least three different Ca(2+) channel types: transient currents flow through a drug-resistant channel ("R1"), while non-inactivating channels sustain a steady, plateau current comprised of a large L component and a small drug-resistant fraction ("R2"). In the perforated-patch condition a large and stable Ca(2+) current was recorded, with all three components. In whole-cell, a buffer-free pipette solution did not prevent a complete Ca(2+) response. The size of the transient and plateau current fractions were greatly reduced, but the ratio between the two fractions, as well as the activation, inactivation and deactivation kinetics, were substantially unmodified. Current amplitude partially recovered with 5 mM EGTA in the pipette solution. With 50 mM EGTA all the kinetic parameters were slowed down and the transient component, but not the plateau component, markedly increased in size. Response kinetics slowed down even more with 30 mM Cs-BAPTA and the Ca(2+) waveform was substantially modified. The transient component was very large and inactivated slowly; the remaining very small plateau fraction deactivated along a slow, single exponential time. Under this condition nifedipine (10 microM) produced a great reduction of the transient current, leaving plateau and deactivation phase unaltered. This suggests that only R2 channels were still active at the end of the test and that the minor remaining transient component flowed through slowly but completely inactivating R1 channels. These results confirm the presence of several channel types in semicircular canal receptors, at difference with cochlear hair cells, and highlight a dramatic alteration of L-type channel behavior when intracellular Ca(2+) buffers are sufficiently concentrated and fast to interfere with rapid and local changes in Ca(2+) levels.

Spectroscopy and Dynamics of Nanometer-Sized Noble Metal Particles

JH Hodak — 2007-03-20T22:42:02-00:00

J. Phys. Chem. B, Vol. 102, No. 36. (3 September 1998), pp. 6958-6967.

Abstract: Electron-phonon coupling in 11 ± 2 nm diameter Au particles and 10 ± 3 nm and 50 ± 10 nm Ag particles has been examined by ultrafast pump-probe spectroscopy. The observed relaxation times are strongly dependent on the pump laser power. At the lowest pump powers used, the time constants for relaxation are 0.8 ± 0.1 ps for the 11 nm Au particles, 1.1 ± 0.1 ps for the 10 nm Ag particles, and 1.0 ± 0.1 ps for the 50 nm Ag particles. The measured relaxation times are similar to those for bulk metals, which implies that there are no size-dependent effects in the dynamics for particles in this size region. The transient absorption/bleach recovery signals for the particles were modeled using the theory developed by Rosei et al. (Surf. Sci. 1973, 37, 689). These calculations yield the transient absorption spectrum as a function of the temperature of the electron distribution. The time dependence of the electronic temperature after pump laser excitation was calculated using the two-temperature model for electron-phonon coupling. The experimental signal versus time traces at selected wavelengths were then simulated by combining the two calculations. The results from the simulations are in semiquantitative agreement with the experimental results. In particular, the low-power relaxation times are correctly predicted by the model calculations. At very high pump laser power (>5 mJ/cm2) the transient bleach signal for Ag shows an unusual 10 ps growth. This growth is attributed to either a change in the dielectric constant of the surrounding medium due to heat transfer from the particles or thermally induced dissociation of adsorbed molecules.

Dynamics of intracellular calcium in hair cells isolated from the semicircular canal of the frog.

G Rispoli — 2007-03-04T16:04:25-00:00

Cell Calcium, Vol. 30, No. 2. (August 2001), pp. 131-140.

Changes in cytosolic free Ca(2+) concentration ([Ca(2+)]i) were monitored optically in hair cells mechanically isolated from frog semicircular canals using the membrane-impermeant form of the Ca(2+)-selective dye Oregon Green 488 BAPTA-1 (OG, 100 microM). Cells stimulated by depolarization under whole-cell voltage clamp conditions revealed Ca(2+) entry at selected sites (hotspots) located mostly in the lower (synaptic) half of the cell body. [Ca(2+)]i at individual hotspots rose with a time constant tau1 approximately 70 ms and decayed with a bi-exponential time-course (tau2 approximately 160, tau3 approximately 2500 ms) following a 160 ms depolarization to -20 mV. With repeated stimulation [Ca(2+)]i underwent independent amplitude changes at distinct hotspots, suggesting that the underlying Ca(2+) channel clusters can be regulated differentially by intracellular signalling pathways. Block by nifedipine indicated that the L-type Ca(2+)channels are distributed at different densities in distinct hotspots. No diffusion barrier other than the nuclear region was found in the cytosol, so that, during a prolonged depolarization (lasting up to 1s), Ca(2+) was able to reach the cell apical ciliated pole. The effective Ca(2+) diffusion constant, measured from the progression of Ca(2+) wavefronts in the cytosol, was approximately 57 microm(2)/s. Our results indicate that in these hair cells, buffered diffusion of Ca(2+) proceeds evenly from the source point to the cell interior and is dominated by the diffusion constant of the endogenous mobile buffers.

Aggregation and proteasome: The case of elongated polyglutamine aggregation in spinal and bulbar muscular atrophy.

Paola Rusmini — 2006-10-26T06:40:35-00:00

Neurobiol Aging (14 June 2006)

Aggregates, a hallmark of most neurodegenerative diseases, may have different properties, and possibly different roles in neurodegeneration. We analysed ubiquitin-proteasome pathway functions during cytoplasmic aggregation in polyglutamine (polyQ) diseases, using a unique model of motor neuron disease, the SpinoBulbar Muscular Atrophy. The disease, which is linked to a polyQ tract elongation in the androgen receptor (ARpolyQ), has the interesting feature that ARpolyQ aggregation is triggered by the AR ligand, testosterone. Using immortalized motor neurons expressing ARpolyQ, we found that a proteasome reporter, YFPu, accumulated in absence of aggregates; testosterone treatment, which induced ARpolyQ aggregation, allowed the normal clearance of YFPu, suggesting that aggregation contributed to proteasome de-saturation, an effect not related to AR nuclear translocation. Using AR antagonists to modulate the kinetic of ARpolyQ aggregation, we demonstrated that aggregation, by removing the neurotoxic protein from the soluble compartment, protected the proteasome from an excess of misfolded protein to be processed.

Short-term memory for scenes with affective content.

V Maljkovic — 2005-11-08T17:36:34-00:00

J Vis, Vol. 5, No. 3. (18 March 2005), pp. 215-229.

The emotional content of visual images can be parameterized along two dimensions: valence (pleasantness) and arousal (intensity of emotion). In this study we ask how these distinct emotional dimensions affect the short-term memory of human observers viewing a rapid stream of images and trying to remember their content. We show that valence and arousal modulate short-term memory as independent factors. Arousal influences dramatically the average speed of data accumulation in memory: higher arousal results in faster accumulation. Valence has a more interesting effect: while a picture is being viewed, information from positive and neutral scenes accumulates in memory at a constant rate, whereas information from negative scenes is encoded slowly at first, then increasingly faster. We provide evidence showing that neither differences in low-level image properties nor differences in the ability to apprehend the meaning of images at short exposures can account for the observed results, and propose that the effects are specific to the short-term memory mechanism. We interpret this pattern of results to mean that information accumulation in short-term memory is a controlled process, whose gain is modulated by valence and arousal acting as endogenous attentional cues.

A Cooperative Nearest Neighbours Topology Control Algorithm for Wireless Ad Hoc Networks

Michael Gerharz — 2005-02-18T21:20:16-00:00

Telecommunication Systems, Vol. 28, No. 3-4. (March 2005), pp. 317-331.

An extension of system F with subtyping

L Cardelli — 2006-06-28T13:14:04-00:00

(1991)

System F is a well-known typed l-calculus with polymorphic types, which provides a basis for polymorphic programming languages. We study an extension of F, called F <: (pronounced ef-sub) that combines parametric polymorphism with subtyping. The main focus of the paper is the equational theory of F <: , which is related to PER models and the notion of parametricity. We study some categorical properties of the theory when restricted to closed terms, including interesting categorical...

Minimizing multimodal functions of continuous variables with the “simulated annealing” algorithm

A Corana — 2006-05-17T21:20:23-00:00

ACM Trans. Math. Softw., Vol. 13, No. 3. (September 1987), pp. 262-280.

Why does Low-Luminosity AGN Fueling Remain an Unsolved Problem?

Paul Martini — 2006-04-11T05:05:40-00:00

(21 Apr 2004)

Despite many years of effort, observational studies have not found a strong correlation between the presence of any proposed fueling mechanism and low-luminosity AGN. After a discussion of the mass requirements for fueling, I summarize this observational work and provide a number of hypotheses for why the nature of AGN fueling has remained unresolved. In particular, I stress the potential importance of the increasing number of candidate fueling mechanisms with decreasing mass accretion rate, the relevant spatial scales for different fueling mechanisms, and the lifetime of an individual episode of nuclear accretion. The episodic AGN lifetime is a particularly relevant complication if it is comparable to or shorter than the time that the responsible fueling mechanisms are observationally detectable. I conclude with a number of relatively accessible areas for future investigation.

Low-degree minimal spanning trees in normed spaces

Horst Martini — 2006-03-18T07:56:54-00:00

(16 Mar 2006)

We give a complete proof that in any finite-dimensional normed linear space a finite set of points has a minimal spanning tree in which the maximum degree is bounded above by the strict Hadwiger number of the unit ball, i.e., the largest number of unit vectors such that the distance between any two is larger than 1.

Spectroscopic Confirmation of a Large AGN Population in Clusters of Galaxies

Paul Martini — 2006-02-24T10:24:25-00:00

(22 Feb 2006)

We have completed a spectroscopic survey of X-ray point sources in eight low-redshift clusters of galaxies (0.05<z<0.31) and have identified 40 cluster members with broad-band (0.3-8 keV) X-ray luminosities between L_X = 8x10^40 and 4x10^43 erg/s. There are between two and ten X-ray sources per cluster. We use visible-wavelength emission lines, X-ray spectral shapes, and multiwavelength flux ratios to determine that at least 35 of these galaxies are Active Galactic Nuclei (AGN). From our spectroscopic survey of other candidate cluster members we estimate that the AGN fraction f_A is ~5% for cluster galaxies more luminous than M_R = -20 mag hosting AGN with broad-band X-ray luminosities above L_X = 10^41 erg/s, or f_A(M_R<-20;L_X>10^41) ~ 5%. We stress that additional, lower-luminosity AGN are expected to be present in the M_R < -20 mag cluster members. Our data unambiguously demonstrate that cluster galaxies host AGN more frequently than previously expected. Only four of these galaxies have obvious visible-wavelength AGN signatures, even though their X-ray luminosities are too high for their X-ray emission to be due to populations of low-mass X-ray binaries or hot, gaseous halos. We attribute the significant difference in visible and X-ray AGN identification to dilution of low-luminosity AGN spectral signatures by host galaxy starlight and/or obscuration of accretion onto the central, supermassive black hole.

An overview of the different excipients useful for the direct compression of tablets

Mira Jivraj — 2006-01-30T12:19:20-00:00

Pharmaceutical Science & Technology Today, Vol. 3, No. 2. (1 February 2000), pp. 58-63.

The humble tablet dosage form still accounts for more than 80% of all dosage forms administered to man. This review will outline the various excipients that have been used as fillers in direct compression formulations, with particular emphasis on what is expected from such excipients in terms of their functionality. It is intended that this overview (which is by no means exhaustive) will serve as an ‘aide-memoire’ to the formulation scientist.

Disruption of the mouse L1 gene leads to malformations of the nervous system.

M Dahme — 2006-01-11T18:56:06-00:00

Nat Genet, Vol. 17, No. 3. (November 1997), pp. 346-349.

The adhesion molecule L1 is a member of the immunoglobulin superfamily. L1 is involved in various recognition processes in the CNS and PNS, and binding to L1 can activate signal transduction pathways. Mutations in the human L1 gene are associated with a variable phenotype, including mental retardation and anomalous development of the nervous system, referred to as 'CRASH' (corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia, and hydrocephalus). We generated an animal model of these conditions by gene targetting. Mutant mice were smaller than wild-type and were less sensitive to touch and pain, and their hind-legs appeared weak and uncoordinated. The size of the corticospinal tract was reduced and, depending on genetic background, the lateral ventricles were often enlarged. Non-myelinating Schwann cells formed processes not associated with axons and showed reduced association with axons. In vitro, neurite outgrowth on an L1 substrate and fasciculation were impaired. The mutant mouse described here will help to elucidate the functions of L1 in the nervous system and how these depend on genetic influences.