bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV‐1 neuropathogenesis: glial mechanisms revealed through substance abuse
Authors: Hauser Kurt F. , El‐Hage Nazira , Stiene‐Martin Anne , Maragos William F. , Nath Avindra , Persidsky Yuri , Volsky David J. , Knapp Pamela E.
Published: December 2006

Neuronal dysfunction and degeneration are ultimately responsible for the neurocognitive impairment and dementia manifest in neuroAIDS. Despite overt neuronal pathology, HIV‐1 does not directly infect neurons; rather, neuronal dysfunction or death is largely an indirect consequence of disrupted glial function and the cellular and viral toxins released by infected glia. A role for glia in HIV‐1 neuropathogenesis is revealed in experimental and clinical studies examining substance abuse–HIV‐1 interactions. Current evidence suggests that glia are direct targets of substance abuse and that glia contribute markedly to the accelerated neurodegeneration seen with substance abuse in HIV‐1 infected individuals. Moreover, maladaptive neuroplastic responses to chronic drug abuse might create a latent susceptibility to CNS disorders such as HIV‐1. In this review, we consider astroglial and microglial interactions and dysfunction in the pathogenesis of HIV‐1 infection and examine how drug actions in glia contribute to neuroAIDS.
Molecular cloning of prostaglandin EP3 receptors from canine sensory ganglia and their facilitatory action on bradykinin‐induced mobilization of intracellular calcium
Authors: Kozaki Yasuko , Kambe Fukushi , Hayashi Yoshitaka , Ohmori Sachiko , Seo Hisao , Kumazawa Takao , Mizumura Kazue
Published: December 2006

We previously demonstrated that the activation of prostaglandin E‐prostanoid‐3 (EP3) receptor sensitized the canine nociceptor response to bradykinin (BK). To elucidate the molecular mechanism for this sensitization, we cloned two cDNAs encoding EP3s with different C‐terminals, from canine dorsal root ganglia, and established the transformed cell lines stably expressing them. In both transformants, EP3 agonist did not increase intracellular cAMP levels, but it attenuated forskolin‐dependent cAMP accumulation in a pertussis toxin (PTX)‐sensitive manner and increased intracellular calcium levels in a PTX‐resistant manner, indicating that both EP3s can couple with Gi and Gq, but not with Gs proteins. As the nociceptor response to BK is mediated by BK B2 receptor, it was transfected into the transformants and the effects of EP3 agonist on BK‐dependent calcium mobilization were investigated. When BK was applied twice with a 6‐min interval, the second response was markedly attenuated. Pre‐treatment with EP3 agonist had no effect on the initial response, but restored the second response in a PTX‐sensitive manner. A protein kinase A inhibitor mimicked the effect of EP3 agonist. These results demonstrate that the activation of EP3 restores the response to BK by attenuating the desensitization of BK B2 receptor activity via Gi protein.
HIV‐1 gp120 as Well as Alcohol Affect Blood–Brain Barrier Permeability and Stress Fiber Formation: Involvement of Reactive Oxygen Species
Authors: Shiu Carlum , Barbier Elisabeth , Cello Francescopaolo Di , Choi Hee Jung , Stins Monique
Published: December 2006

Background: HIV‐1 infection commonly leads to serious HIV‐1–associated neurological disorders, such as HIV‐1–associated encephalopathy and dementia. In addition, alcohol is commonly used and/or abused among AIDS patients, but it is unclear whether alcohol affects the disease progression and if it affects it, how this occurs. We hypothesized that alcohol could affect the blood–brain barrier (BBB) integrity and thus could affect the onset and/or progression of HIV‐associated neurological disorders.

Methods: Human brain microvascular endothelial cells (HBMEC) in a BBB model system were pretreated with alcohol (17 and 68 mM) and subsequently coexposed with HIV‐1 gp120. Expression of chemokine receptors CCR3, CCR5, and CXCR4 was assessed by enzyme‐linked immunosorbent assay and real‐time polymerase chain reaction. Changes in the permeability of the HBMEC monolayer were assessed using paracellular markers [3H]inulin or propidium iodide. Actin rearrangements in HBMEC were visualized by fluorescence microscopy and viability assessed using Live/Dead™ stain.

Results: Both gp120 and alcohol increased the permeability of the BBB model by up to 141%, without affecting HBMEC viability. Cotreatment with alcohol and gp120 did not result in a significant synergistic effect. Gp120 permeability involved chemokine receptor CCR5. Alcohol did not affect chemokine receptor expression on brain endothelial cells. Both gp120 and alcohol reorganized the cytoskeleton and induced stress fiber formation. Inhibition of reactive oxygen species (ROS) formation through NADPH blocked the effects of both gp120 and alcohol on permeability and stress fiber formation.

Conclusion: These results indicate that both HIV‐1 gp120 and alcohol induce stress fibers, causing increased permeability of the human BBB endothelium. Alcohol (68 mM)‐mediated permeability increase was linked to ROS formation. The alcohol‐mediated physiological changes in the HBMEC monolayers may increase diffusion of plasma components and viral penetration across the BBB. This suggests that alcohol, especially at levels attained in heavy drinkers, can potentially contribute in a negative fashion to HIV‐1 neuropathogenesis.
Primary invasive melanoma and basal cell carcinoma (collision tumor) with blue nevus‐like cutaneous metastases
Authors: King R. , Lyons J. , Meyers A. L. , Googe P. B. , Page R. N. , Gupta V. K.
Published: December 2006

The simultaneous presence of two disparate neoplasms occurring in the same specimen has been well documented, albeit uncommonly. The juxtaposition of malignant melanoma and basal cell carcinoma (BCC) has been rarely reported in case reports, with most cases describing melanoma in situ and BCC. We present two cases of invasive melanoma (Clark level IV, no microscopic satellites present) intimately associated with BCC, and in areas distinction of the two lesions was difficult. Immunohistochemical studies delineated the two cell populations. In addition, one patient presented with multiple cutaneous metastases, all simulating blue nevi. The metastases occurred in the same anatomical region as the primary tumor, and histologically consisted of pigmented dendritic melanocytes and melanophages in the superficial and mid‐dermis and arranged in a blue nevus‐like lesion. Histologic clues suggesting the possibility of a metastatic melanoma included a sparse lymphocytic infiltrate, the presence of an epithelioid component and atypia of the dendritic melanocytes. However, without appropriate clinical history, the lesions could be overlooked as ordinary blue nevus. Collision tumors containing invasive melanoma and BCC are rare and this is the first report of a collision tumor with blue nevus‐like metastasis. Awareness of this phenomenon and pattern of metastasis, together with the clinical findings will aid in the correct classification of these lesions.
Extensive neurocristic hamartoma with skeletal muscle involvement
Authors: Denlinger Chadrick E. , Slingluff Craig L. , Mihm Martin C. , Patterson James W.
Published: December 2006

Neurocristic hamartomas (NCH) are rare pigmented skin lesions based in the deep subcutaneous tissues that may be either congenital or acquired. The clinical importance of these lesions is the potential for misdiagnosis and the development of malignant melanomas over a poorly described time course. Histological pleomorphism precludes meaningful random biopsies as a means of cancer surveillance. We present the case of an extensive NCH in a 67‐year‐old man, with a reported duration of greater than 50 years and no current clinical or histological indication of malignancy. Incisional biopsies of nodular areas showed bland‐appearing pigmented cells that extended into subcutaneous adipose tissue and skeletal muscle. The specimens contained numerous clusters of differing configurations and cell types. Positron emission tomography (PET) scanning was used as an adjunct to physical examination in follow up. A PET‐avid mass was detected but proved to be a banal nodular melanocytic proliferation within the NCH. In conclusion, NCH may be characterized by extensive deep tissue involvement in the absence of overt malignancy. The possible development of malignant melanoma in such lesions warrants close surveillance.
Modulation of Ca2+ entry and plasma membrane potential by human TRPM4b
Authors: Fliegert Ralf , Glassmeier Günter , Schmid Frederike , Cornils Kerstin , Genisyuerek Selda , Harneit Angelika , Schwarz Jürgen R. , Guse Andreas H.
Published: December 2006

TRPM4b is a Ca2+‐activated, voltage‐dependent monovalent cation channel that has been shown to act as a negative regulator of Ca2+ entry and to be involved in the generation of oscillations of Ca2+ influx in Jurkat T‐lymphocytes. Transient overexpression of TRPM4b as an enhanced green fluorescence fusion protein in human embryonic kidney (HEK) cells resulted in its localization in the plasma membrane, as demonstrated by confocal fluorescence microscopy. The functionality and plasma membrane localization of overexpressed TRPM4b was confirmed by induction of Ca2+‐dependent inward and outward currents in whole cell patch clamp recordings. HEK‐293 cells stably overexpressing TRPM4b showed higher ionomycin‐activated Ca2+ influx than wild‐type cells. In addition, analysis of the membrane potential using the potentiometric dye bis‐(1,3‐dibutylbarbituric acid)‐trimethine oxonol and by current clamp experiments in the perforated patch configuration revealed a faster initial depolarization after activation of Ca2+ entry with ionomycin. Furthermore, TRPM4b expression facilitated repolarization and thereby enhanced sustained Ca2+ influx. In conclusion, in cells with a small negative membrane potential, such as HEK‐293 cells, TRPM4b acts as a positive regulator of Ca2+ entry.
Beneficial Effect of Prolyl Oligopeptidase Inhibition on Spatial Memory in Young but Not in Old Scopolamine‐Treated Rats
Authors: Jalkanen Aaro J. , Puttonen Katja A. , Venäläinen Jarkko I. , Sinervä Veijo , Mannila Anne , Ruotsalainen Sirja , Jarho Elina M. , Wallén Erik A. A. , Männistö Pekka T.
Published: December 2006

Abstract:  The effects of a novel prolyl oligopeptidase (POP) inhibitor KYP‐2047 on spatial memory of young (3‐month‐old) and old (8‐ to 9‐month‐old) scopolamine‐treated rats (0.4 mg/kg intraperitoneally) was investigated in the Morris water maze. In addition, the concentrations of promnesic neuropeptide substrates of POP, substance P and neurotensin in various brain areas after acute and chronic POP inhibition were measured in young rats. In addition, inositol‐1,4,5‐trisphosphate (IP3) levels were assayed in rat cortex and hippocampus after effective 2.5‐day POP inhibition. KYP‐2047 (1 or 5 mg/kg 30 min. before daily testing) dose‐dependently improved the escape performance (i.e. latency to find the hidden platform and swimming path length) of the young but not the old rats in the water maze. POP inhibition had no consistent effect on substance P levels in cortex, hippocampus or hypothalamus, and only a modest increase in neurotensin concentration was observed in the hypothalamus after a single dose of KYP‐2047. Moreover, IP3 concentrations remained unaffected in cortex and hippocampus after POP inhibition. In conclusion, the behavioural data support the earlier findings of the promnesic action of POP inhibitors, but the mechanism of the memory‐enhancing action remains unclear.
Our Common European Model of Agriculture
Authors: Korkeaoja Juha
Published: December 2006

Our Common European Model of Agriculture

Future internal and external forces on European agriculture mean that the CAP may look very different after 2013. However large these changes, the CAP will need to retain its common principles based on the European Model of Agriculture (EMA). This became clear in an informal September meeting of EU agriculture ministers in Oulu, arranged by the Finnish Presidency. A strong CAP will be needed in the future but it will have to evolve to meet upcoming challenges. Work on the future CAP will need to start soon and the Oulu meeting may become known as the starting point for those discussions. The CAP will have to provide a reasonable environment for practicing agriculture for very different farmers in very diverse conditions, and facilitate the supply of a wide variety of goods and services to consumers and taxpayers as only truly multifunctional agriculture can. If the CAP can maintain these characteristics it has an important role to play in a future Europe. The meeting in Oulu was also an important milestone for a very special reason: for the first time, all ten New Member States took an active part in the EMA‐debate with full rights and responsibilities as part of the Union. Once again this underlines the central role of our common European Model of Agriculture.
The EU Budget and the CAP: An Agenda for the Review?
Authors: Ackrill Rob , Kay Adrian , Harvey David
Published: December 2006

Counterpoint ‐ Ackrill and Kay

Professor David Harvey's proposed agenda for CAP reform in EuroChoices 5(1) is, we believe, unrealistic. It pays insufficient attention to the politics of EU policy‐making and ignores the importance countries place on protecting their shares of EU spending. We recognise the incremental nature of CAP reform, but believe this can lead to significant cumulative effects. Our proposal builds on modulation to transfer more CAP spending from Pillar I to Pillar II. Farmers receiving the largest payments should have their payments cut through higher compulsory modulation rates. We also seek a reduction of EU spending on the CAP, with greater national contributions achieved through the established channel of co‐financing.

Reply to Ackrill and Kay ‐ David Harvey

Ackrill and Kay (A&K) say my suggestions for national subscription, co‐financing and discretion for CAP Pillar 1 spending and associated elimination of the troublesome UK rebate risk a stalemate, and that the further reform will necessarily be incremental, rather than radical. In reply, I argue that some radical reform will eventually be necessary, so that it makes sense to think about the required directions now. I also argue that my own suggestions are not so far from A&K's analysis as they seem to suppose. My suggestions seem little more likely to generate a stalemate than A&K's incremental change forecasts.
Roux‐en‐Y or ‘uncut’ Roux procedure? Relation of intestinal migrating motor complex recovery to the preservation of the network of interstitial cells of Cajal in pigs
Authors: Kiciak Adam , Woliñski Jarosław , Borycka Katarzyna , Zabielski Romuald , Bielecki Krzysztof
Published: December 2006

We designed a conscious pig model to investigate myoelectric activity and the number of interstitial cells of Cajal (ICC) in the proximal jejunum following the Roux‐en‐Y and ‘uncut’ Roux procedures in relation to clinical outcomes. Twelve male Polish White pigs (8 weeks old, 10–13 kg) underwent surgery under general anaesthesia first to implant bipolar electrodes and telemetry transmitters for continuous electromyography recordings and then, after 1 week recovery, to create Roux‐en‐Y (n= 6) and ‘uncut’ Roux loops (n= 6). Upper gut tissue specimens were studied for the expression of c‐kit staining procedure to quantitatively identify the presence of interstitial cells of Cajal. The intestinal migrating motor complex was restored within 10.5 and 37 h in ‘uncut’ Roux and Roux‐en‐Y pigs, respectively (P < 0.05). During 2 weeks, the ‘uncut’ Roux piglets increased their body weight by 18.0%, whereas the Roux‐en‐Y piglets increased their body weight by only 7.3% (P≤ 0.05). Two weeks after surgery, the number of ICC located in the region of Auerbach's plexus was higher and adhesions in the abdominal cavity lower in the ‘uncut’ Roux group. In conclusion, in the pig model, preservation of smooth muscle and ICC network continuity in the proximal jejunum may play an important role in early postsurgical recovery.
Spinal use‐dependent plasticity of synaptic transmission in humans after a single cycling session
Authors: Meunier Sabine , Kwon Jeongyi , Russmann Heike , Ravindran Shashi , Mazzocchio Riccardo , Cohen Leonardo
Published: December 2006

The spinal cord is able to express use‐dependent plasticity, as demonstrated in spinalized cats following treadmill training. In humans, spinal use‐dependent plasticity is inferred from modifications in the size of H reflex, which are often more prominent after skilled motor training. Plasticity can develop at synaptic connections between afferent fibres and/or descending tracts and motoneurones or interneurones interposed in the spinal pathways. Here we explore whether skilled training induces a change in synaptic efficacy at the synapse between Ia afferents and soleus (Sol) motoneurones. Synaptic efficacy can be modulated presynaptically through changes of the probability of transmitter release (homosynaptic depression, HD). The frequency‐related depression of the Sol H reflex, thought to reflect HD, was tested at rest, before and after one single skilled (14 subjects) or non‐skilled (9 subjects) cycling training session. Performance improved in both groups but to a larger extent with skilled training, while HD increased immediately after and the day following skilled training in the absence of changes with non‐skilled training. These results support the view that spinal cord function is able to encode a local motor memory.
An Introduction of a Novel Friction Drive: Metal Belt Drive With Magnets
Authors: Luo Shanming , Wu Yue , Yu Yidao , Zhu Shimin
Published: December 2006

A novel friction drive—a metal belt drive with magnets (MBDM)—is proposed in this paper, and its structure and principle are introduced. Based on theories of friction drive and electromagnetism, a mechanical model of the MBDM is presented and a Euler formula of this drive is deduced. Finally, several performance parameters of the MBDM are experimentally measured and compared to conventional belt drives. The results show that the MBDM transmits motion and power by using the coupling action between the magnetic attraction and initial tension. The transmission efficiency of the MBDM can reach 95-98%, while its elastic creep rate is <0.1% under normal running conditions.
A Secreted Serine-Threonine Kinase Determines Virulence in the Eukaryotic Pathogen
Toxoplasma gondii
Authors: Taylor S. , Barragan A. , Su C. , Fux B. , Fentress S. J. , Tang K. , Beatty W. L. , Hajj H. El , Jerome M. , Behnke M. S. , White M. , Wootton J. C. , Sibley L. D.
Published: December 2006

Toxoplasma gondii
strains differ dramatically in virulence despite being genetically very similar. Genetic mapping revealed two closely adjacent quantitative trait loci on parasite chromosome VIIa that control the extreme virulence of the type I lineage. Positional cloning identified the candidate virulence gene
ROP18
, a highly polymorphic serine-threonine kinase that was secreted into the host cell during parasite invasion. Transfection of the virulent
ROP18
allele into a nonpathogenic type III strain increased growth and enhanced mortality by 4 to 5 logs. These attributes of ROP18 required kinase activity, which revealed that secretion of effectors is a major component of parasite virulence.
Nannoplankton Extinction and Origination Across the Paleocene-Eocene Thermal Maximum
Authors: Gibbs Samantha J. , Bown Paul R. , Sessa Jocelyn A. , Bralower Timothy J. , Wilson Paul A.
Published: December 2006

The Paleocene-Eocene Thermal Maximum (PETM, ∼55 million years ago) was an interval of global warming and ocean acidification attributed to rapid release and oxidation of buried carbon. We show that the onset of the PETM coincided with a prominent increase in the origination and extinction of calcareous phytoplankton. Yet major perturbation of the surface-water saturation state across the PETM was not detrimental to the survival of most calcareous nannoplankton taxa and did not impart a calcification or ecological bias to the pattern of evolutionary turnover. Instead, the rate of environmental change appears to have driven turnover, preferentially affecting rare taxa living close to their viable limits.
Nitrogen Fixation at 92°C by a Hydrothermal Vent Archaeon
Authors: Mehta Mausmi P. , Baross John A.
Published: December 2006

A methanogenic archaeon isolated from deep-sea hydrothermal vent fluid was found to reduce N
2
to NH
3
at up to 92°C, which is 28°C higher than the current upper temperature limit of biological nitrogen fixation. The 16
S
ribosomal RNA gene of the hyperthermophilic nitrogen fixer, designated FS406-22, was 99% similar to that of non–nitrogen fixing
Methanocaldococcus jannaschii
DSM 2661. At its optimal growth temperature of 90°C, FS406-22 incorporated
15
N
2
and expressed
nifH
messenger RNA. This increase in the temperature limit of nitrogen fixation could reveal a broader range of conditions for life in the subseafloor biosphere and other nitrogen-limited ecosystems than previously estimated.
Organics Captured from Comet 81P/Wild 2 by the Stardust Spacecraft
Authors: Sandford Scott A. , Aléon Jérôme , Alexander Conel M. O'D. , Araki Tohru , Bajt Sas̆a , Baratta Giuseppe A. , Borg Janet , Bradley John P. , Brownlee Donald E. , Brucato John R. , Burchell Mark J. , Busemann Henner , Butterworth Anna , Clemett Simon J. , Cody George , Colangeli Luigi , Cooper George , D'Hendecourt Louis , Djouadi Zahia , Dworkin Jason P. , Ferrini Gianluca , Fleckenstein Holger , Flynn George J. , Franchi Ian A. , Fries Marc , Gilles Mary K. , Glavin Daniel P. , Gounelle Matthieu , Grossemy Faustine , Jacobsen Chris , Keller Lindsay P. , Kilcoyne A. L. David , Leitner Jan , Matrajt Graciela , Meibom Anders , Mennella Vito , Mostefaoui Smail , Nittler Larry R. , Palumbo Maria E. , Papanastassiou Dimitri A. , Robert François , Rotundi Alessandra , Snead Christopher J. , Spencer Maegan K. , Stadermann Frank J. , Steele Andrew , Stephan Thomas , Tsou Peter , Tyliszczak Tolek , Westphal Andrew J. , Wirick Sue , Wopenka Brigitte , Yabuta Hikaru , Zare Richard N. , Zolensky Michael E.
Published: December 2006

Organics found in comet 81P/Wild 2 samples show a heterogeneous and unequilibrated distribution in abundance and composition. Some organics are similar, but not identical, to those in interplanetary dust particles and carbonaceous meteorites. A class of aromatic-poor organic material is also present. The organics are rich in oxygen and nitrogen compared with meteoritic organics. Aromatic compounds are present, but the samples tend to be relatively poorer in aromatics than are meteorites and interplanetary dust particles. The presence of deuterium and nitrogen-15 excesses suggest that some organics have an interstellar/protostellar heritage. Although the variable extent of modification of these materials by impact capture is not yet fully constrained, a diverse suite of organic compounds is present and identifiable within the returned samples.
NASA Returns Rocks from a Comet
Authors: Burnett Don S.
Published: December 2006

Cometary particles returned by the Stardust Discovery Mission are primarily silicate materials of solar system origin. Some of the grains were formed at high temperatures close to the Sun, but then transported far out to the Kuiper belt region of the solar system before being incorporated in the comet.
Synthesis of D-Galactopyranosylphosphonic and (D-Galactopyranosylmethyl)phosphonic Acids as Intermediates of Inhibitors of Galactosyltransferases
Authors: Heissigerová Helena , Kočalka Petr , Hlaváčková Martina , Imberty Anne , Breton Christelle , Chazalet Valerie , Moravcová Jitka
Published: December 2006

Employing the Michaelis-Arbuzov reaction of 1-O-acetyl-2,3,4,6-tetra-O-benzyl-D-galactopyranose with triethyl phosphite and trimethylsilyl trifluoromethanesulfonate, α- and β-D-galactopyranosylphosphonic acids were prepared in 33 and 28% yields, respectively. (α-D-Galactopyranosylmethyl)phosphonic acid was synthesized by a five-step route from 2,3,4,6-tetra-O-benzyl-D-galactopyranose in 52% overall yield. When tested against bovine α-1,3- and β-1,4-galactosyltransferases, all three compounds showed, at best, very poor inhibitions. Both enzymes were inhibited more effectively by β-D-galactopyranosylphosphonic acid (IC50 = 17 mmol l-1 at 13.5 μmol l-1 of UDP-Gal for β4GalT).
MONTE CARLO SIMULATION OF BOSON LATTICES
Authors: APAJA VESA , SYLJUÅSEN OLAV F.
Published: December 2006

Boson lattices are theoretically well described by the Hubbard model. The basic model and its variants can be effectively simulated using Monte Carlo techniques. We describe two newly developed approaches, the Stochastic Series Expansion (SSE) with directed loop updates and continuous–time Diffusion Monte Carlo (CTDMC). SSE is a formulation of the finite temperature partition function as a stochastic sampling over product terms. Directed loops is a general framework to implement this stochastic sampling in a non–local fashion while maintaining detailed balance. CTDMC is well suited to finding exact ground–state properties, applicable to any lattice model not suffering from the sign problem; for a lattice model the evolution of the wave function can be performed in continuous time without any time discretization error. Both the directed loop algorithm and the CTDMC are important recent advances in development of computational methods. Here we present results for a Hubbard model for anti–ferromagnetic spin–1 bosons in one dimensions, and show evidence for a dimerized ground state in the lowest Mott lobe.
THERMAL ENTANGLEMENT IN SPIN SYSTEMS
Authors: CANOSA N. , ROSSIGNOLI R.
Published: December 2006

We examine the entanglement of thermal states of n spins interacting through an XYZ type Heisenberg coupling in the presence of a uniform magnetic field, by evaluating the negativities of bipartite partitions of the whole system and subsystems. The corresponding limit temperatures for entanglement are also examined. Results indicate that limit temperatures for global entanglement depend on the type of partition and are higher than those limiting pairwise entanglement, and that their behavior with anisotropy and applied magnetic field may differ significantly from that of the corresponding mean field critical temperature.
SPIN 1/2 FERMIONS IN THE UNITARY REGIME AT FINITE TEMPERATURE
Authors: BULGAC AURBL , DRUT JOAQUIN E. , MAGIERSKI PIOTR
Published: December 2006

We have performed a fully non-perturbative calculation of the thermal properties of a system of spin 1/2 fermions in 3D in the unitary regime. We have determined the critical temperature for the superfluid-normal phase transition. The thermodynamic behavior of this system presents a number of unexpected features, and we conclude that spin 1/2 fermions in the BCS-BEC crossover should be classified as a new type of superfluid.
RETRIEVING HEART RATE SEQUENCES
Authors: NILSSON MARKUS
Published: December 2006

In this paper, we present a method with a low complexity for analysing short and dynamic biomedical sequences. The method uses the Daubechies D4 wavelet in combination with similarity fitness schemes for retrieval. We also present a more traditional way of retrieving dynamical biomedical sequences based on stretching the sequences in time. The first mentioned method has been shown to outperform Fourier based methods in retrieving biomedical sequences of dynamic lengths, as well as the Haar wavelet.
LICENSE-PLATE RECOGNITION USING DWT AND NEURAL NETWORK
Authors: CHEN TIAN-DING
Published: December 2006

This paper presents a new approach for license-plate recognition using Discrete Wavelet Transform (DWT) and Plastic Perception Neural Network (PPNN). It accomplishes the preliminary license-plate localization by applying low-pass wavelet coefficients. Since the amount of data reduces to 1/4, this approach saves a lot of running time, simplifies computational complexity, and economizes memory usage. It adopts the LL and HH sub-bands, which come from a two-dimensional Haar DWT to implement the localization and segmentation for license plates. The proposed methodology provides high accuracy for locating a license plate from an image, and has a high tolerance for license plate displacement in the images. Back-Propagation Neural Network (BPNN) has the advantage of anti-noise and anti-distortion, but the problems of traditional BPNN are a longer learning period, iterations are not prone to convergence, and local minimum. The proposed methods combine the parallel distributive process concept with the BPNN structure modification to solve the above problems. This paper also utilizes PPNN to solve taking position, scale and rotation of the license-plate recognition.
GUARANTEED COST CONTROL OF NETWORKED CONTROL SYSTEMS WITH TIME-DELAYS AND PACKET LOSSES
Authors: LI SHANBIN , WANG YONGQIANG , XIA FENG , SUN YOUXIAN
Published: December 2006

In this paper, the random time-delays and packet losses issues of networked control systems (NCS) within the framework of guaranteed cost control for Markovian jump linear systems (MJLSs) are addressed. A new delay-dependent sufficient condition for the existence of guaranteed cost controller and an upper bound of the cost function are presented by a new stochastic Lyapunov–Krasovskii functional. The state feedback problem for such system is formulated as a convex optimization over a set of linear matrix inequalities (LMIs) which can be very efficiently solved by interior-point methods. As examples to verify the proposed method, two plants in the networked setup are considered. The simulation results demonstrate the effectiveness of the method.
GENETICS OF SOFT TISSUE TUMORS
Authors: Rijn Matt van de , Fletcher Jonathan A.
Published: December 2006

Sarcomas form a highly diverse group of rare tumors that are derived from connective tissue. More than 100 different malignant and benign soft tissue neoplasms can be recognized by histologic examination. Few diagnostic markers exist, and the cell of origin for many soft tissue tumors is unknown. The accurate diagnosis of many of these tumors therefore remains a challenge. The study of sarcomas has yielded many insights that can be applied to other neoplasms such as carcinoma. For example, the success of the treatment of gastrointestinal stromal tumor with Imatinib has led to an increased effort to find targeted therapies for other malignancies. Here we describe the known molecular changes in a number of sarcomas and focus on novel scientific approaches that can be expected to lead to improved diagnosis, prognostication, and therapy of sarcoma.
NEURODEGENERATIVE DISEASES: New Concepts of Pathogenesis and Their Therapeutic Implications
Authors: Skovronsky Daniel M. , Lee Virginia M.-Y. , Trojanowski John Q.
Published: December 2006

Neurodegenerative diseases as diverse as Alzheimer's, Parkinson's, and Creutzfeldt-Jakob disease share a common pathogenetic mechanism involving aggregation and deposition of misfolded proteins, which leads to progressive central nervous system disease. Although the type of aggregated protein and the regional and cellular distribution of deposition vary from disease to disease, these disorders may all be linked by similar pathways of protein aggregation with fibril formation and amyloid deposition. This perspective on pathogenesis suggests that a wide variety of neurodegenerative diseases can be grouped mechanistically as brain amyloidoses, an outlook that yields novel insights into potential therapeutic approaches that may be applicable across the broad spectrum of neurodegenerative disease.
Discovery and development of anticancer aptamers
Authors: Ireson Christopher R. , Kelland Lloyd R.
Published: December 2006

Aptamers, also termed as decoys or “chemical antibodies,” represent an emerging class of therapeutics. They are short DNA or RNA oligonucleotides or peptides that assume a specific and stable three-dimensional shape in vivo, thereby providing specific tight binding to protein targets. In some cases and as opposed to antisense oligonucleotides, effects can be mediated against extracellular targets, thereby preventing a need for intracellular transportation. The first aptamer approved for use in man is a RNA-based molecule (Macugen, pegaptanib) that is administered locally (intravitreally) to treat age-related macular degeneration by targeting vascular endothelial growth factor. The most advanced aptamer in the cancer setting is AS1411, formerly known as AGRO100, which is being administered systemically in clinical trials. AS1411 is a 26-mer unmodified guanosine-rich oligonucleotide, which induces growth inhibition in vitro, and has shown activity against human tumor xenografts in vivo. The mechanism underlying its antiproliferative effects in cancer cells seems to involve initial binding to cell surface nucleolin and internalization, leading to an inhibition of DNA replication. In contrast to other unmodified oligonucleotides, AS1411 is relatively stable in serum-containing medium, probably as a result of the formation of dimers and a quartet structure. In a dose escalation phase I study in patients with advanced solid tumors, doses up to 10 mg/kg/d (using a four or seven continuous infusion regime) have been studied. Promising signs of activity have been reported (multiple cases of stable disease and one near complete response in a patient with renal cancer) in the absence of any significant adverse effects. Further trials are ongoing in renal and non–small cell lung cancers. In preclinical studies, additional aptamers have been described against several cancer targets, such as tenascin-C, the transcription factor signal transducer and activator of transcription 3, and antiapoptotic and Ku proteins. [Mol Cancer Ther 2006;5(12):2957–62]
Growth inhibition and induction of apoptosis in acute myeloid leukemia cells by new indolinone derivatives targeting fibroblast growth factor, platelet-derived growth factor, and vascular endothelial growth factor receptors
Authors: Kulimova Emma , Oelmann Elisabeth , Bisping Guido , Kienast Joachim , Mesters Rolf M. , Schwäble Joachim , Hilberg Frank , Roth Gerald J. , Munzert Gerd , Stefanic Martin , Steffen Björn , Brandts Christian , Müller-Tidow Carsten , Kolkmeyer Astrid , Büchner Thomas , Serve Hubert , Berdel Wolfgang E.
Published: December 2006

In acute myeloid leukemia (AML), receptor tyrosine kinase ligands promote growth and survival and contribute to AML-associated marrow neoangiogenesis. We have tested simultaneous inhibition of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptor signaling by novel indolinone derivatives using 14 myeloid, including 11 human leukemic, cell lines. Compounds inhibited colony formation of all cell lines in a dose-dependent fashion. Inhibitory concentrations for 50% of the colony formation/survival (IC50) for BIBF1000 were <100 nmol/L for 3 of 11, ≤500 nmol/L for 6 of 11, and <1,000 nmol/L for 10 of 11 leukemic cell lines, with one cell line being resistant in the dose range <1,000 nmol/L. BIBF1120 was less effective with 4 of 11 leukemic cell lines being resistant within the dose range <1,000 nmol/L. Testing of myeloid 32D cells transfected with empty vector, wild-type Flt3, or Flt3 carrying an internal tandem duplication mutation revealed higher resistance for the internal tandem duplication mutant. These effects of the compounds were associated with inhibition of tyrosine phosphorylation and the mitogen-activated protein kinase pathway. Furthermore, both compounds induced apoptosis in the sensitive cell lines. In Mono-Mac1 cells, the compounds had a direct proapoptotic effect that was increasing the proapoptotic effect of 1-β-d-arabinofuranosylcytosine. The data provide a rationale for clinical evaluation of these tyrosine kinase inhibitors in AML. [Mol Cancer Ther 2006;5(12):3105–12]
Glucocorticoid receptor transcriptional isoforms and resistance in multiple myeloma cells
Authors: Sánchez-Vega Beatriz , Krett Nancy , Rosen Steven T. , Gandhi Varsha
Published: December 2006

Although glucocorticoids play an important role in the treatment of multiple myeloma, some patients do not respond or develop resistance. The glucocorticoid receptor (GR), a single gene, mediates the effects of glucocorticoids. Using a model system of a multiple myeloma cell line sensitive to glucocorticoids and its early and late resistant variants, we have analyzed mutations in the GR gene, detected the presence of different transcriptional isoforms, quantified their levels of expression, and identified the promoters that regulate their expression. Levels of GR transcripts were comparable with the expression of total GR protein. Development of resistance correlates with an overall reduction in GR mRNA levels. This decrease in GR levels is neither due to mutation of the gene nor due to methylation. GRα is the predominant isoform in the sensitive cell line decreasing in expression in the early resistant cells and virtually undetectable in late resistant cells. GR-P is expressed at equivalent levels in both sensitive and early resistant cells, whereas in the late resistant cells, GR-P is the predominant isoform. GR-A is only expressed in the early resistant cell line. GRβ is the least expressed isoform in all cell lines. Interestingly, the level of expression of exon 1-exon 2 RNA fragments remains similar in sensitive and resistant cell lines. Resistant cells became sensitive to glucocorticoids after GRα transfection. In conclusion, we show different patterns of expression of the GR isoforms and provide evidence that a decline in the expression of GRα may be associated with development of resistance. [Mol Cancer Ther 2006;5(12):3062–70]
Photodynamic therapy mediates the oxygen-independent activation of hypoxia-inducible factor 1α
Authors: Mitra Soumya , Cassar Scott E. , Niles David J. , Puskas John A. , Frelinger John G. , Foster Thomas H.
Published: December 2006

Photodynamic therapy (PDT) induces the expression of the hypoxia-inducible factor 1α (HIF-1α) subunit of the HIF-1 transcription factor and its target genes in vitro and in vivo. PDT also induces the expression of the enzyme cyclooxygenase-2 and its metabolite, prostaglandin E2 (PGE2). PGE2 and hypoxia act independently and synergistically to increase HIF-1α accumulation and nuclear translocation. To examine the expression of HIF-1 target genes in response to PDT-mediated oxidative stress and PGE2 under normoxic conditions, we established EMT6 cells transfected with a plasmid consisting of a hypoxia response element promoter and a downstream gene encoding for green fluorescent protein (GFP). To examine the temporal kinetics of HIF-1α nuclear translocation in response to PDT, we transfected a second line of EMT6 cells with a GFP-tagged HIF-1α fusion vector. Cell monolayers were incubated with 1 μg mL−1 Photofrin for 24 h and irradiated with fluences of 1, 2.5, and 5 J cm−2. Direct measurement of oxygen concentration during irradiation confirmed that cells remained well oxygenated. Cells were also exposed to 1 and 10 μmol/L PGE2 for 3 h. In normoxic conditions, Photofrin, PDT, and PGE2 treatment activated HIF-1α and induced its nuclear translocation. Maximal Photofrin-PDT–mediated HIF-1α activation was intermediate in magnitude between that induced by PGE2 and that by the hypoxia mimic cobalt chloride. This work establishes that PDT induces significant activation of the HIF-1α pathway in the absence of hypoxia and supports the interpretation that the induction of HIF-1 target genes by PDT may be mediated, at least in part, by the prostaglandin pathway. [Mol Cancer Ther 2006;5(12):3268–74]
Gallic acid causes inactivating phosphorylation of cdc25A/cdc25C-cdc2 via ATM-Chk2 activation, leading to cell cycle arrest, and induces apoptosis in human prostate carcinoma DU145 cells
Authors: Agarwal Chapla , Tyagi Alpna , Agarwal Rajesh
Published: December 2006

We recently reported that gallic acid is a major active agent responsible for grape seed extract activity in DU145 human prostate carcinoma cells. The present study was conducted to examine its efficacy and associated mechanism. Gallic acid treatment of DU145 cells resulted in a strong cell growth inhibition, cell cycle arrest, and apoptotic death in a dose- and time-dependent manner, together with a decrease in cyclin-dependent kinases and cyclins but strong induction in Cip1/p21. Additional mechanistic studies showed that gallic acid induces an early Tyr15 phosphorylation of cell division cycle 2 (cdc2). Further upstream, gallic acid also induced phosphorylation of both cdc25A and cdc25C via ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 (Chk2) activation as a DNA damage response evidenced by increased phospho-histone 2AX (H2A.X) that is phosphorylated by ATM in response to DNA damage. Time kinetics of ATM phosphorylation, together with those of H2A.X and Chk2, was in accordance with an inactivating phosphorylation of cdc25A and cdc25C phosphatases and cdc2 kinase, suggesting that gallic acid increases cdc25A/C-cdc2 phosphorylation and thereby inactivation via ATM-Chk2 pathway following DNA damage that induces cell cycle arrest. Caffeine, an ATM/ataxia telangiectasia-rad3-related inhibitor, reversed gallic acid–caused ATM and H2A.X phosphorylation and cell cycle arrest, supporting the role of ATM pathway in gallic acid–induced cell cycle arrest. Additionally, gallic acid caused caspase-9, caspase-3, and poly(ADP)ribose polymerase cleavage, but pan-caspase inhibitor did not reverse apoptosis, suggesting an additional caspase-independent apoptotic mechanism. Together, this is the first report identifying gallic acid efficacy and associated mechanisms in an advanced and androgen-independent human prostate carcinoma DU145 cells, suggesting future in vivo efficacy studies with this agent in preclinical prostate cancer models. [Mol Cancer Ther 2006;5(12):3294–302]
Spatial Variations in Eulemur fulvus rufus and Lepilemur mustelinus Densities in Madagascar
Authors: Lehman Shawn M.
Published: December 2006

I present data on variations in Eulemur fulvus rufus and Lepilemur mustelinus densities as well as tree characteristics (height, diameter and stem frequency) between edge and interior forest habitats in southeastern Madagascar. Line transect surveys were conducted from June 2003 to November 2005 in edge and interior forest habitats in the Vohibola III Classified Forest. Although E. f. rufus densities were significantly lower in edge habitats than in interior habitats, density estimates for L. mustelinus did not differ significantly between habitats. Trees in edge habitats were significantly shorter, had smaller diameters and had lower stem frequencies (for those 25 cm in diameter) than trees in interior habitats. Spatial characteristics of food abundance and quality may explain lemur density patterns in Vohibola III. Low E. f. rufus densities may reduce seed dispersal in edge habitats, which has important consequences for the long-term viability of forest ecosystems in Madagascar.
The Basic, Quantifiable Parameter of Dialysis Prescription Is Kt/V Urea; Treatment Time Is Determined by the Ultrafiltration Requirement; All Three Parameters Are of Equal Importance
Authors: Gotch Frank
Published: December 2006

There have only been two randomized controlled trials studying outcome as a function of dose in hemodialysis (HD). The first was the National Cooperative Dialysis Study which showed that adequate dialysis was achieved with spKt/V >1.00. The second study was HEMO which was originally designed to study spKt/V 1.2 compared to spKt/V 1.45. Unfortunately by the time HEMO was started, observational studies (OS) had convinced the nephrology community that the minimum adequate dose of spKt/V was 1.40, so the lower target was increased to 1.4 and the upper target to 1.7. The study showed no difference in outcome, although OS have now demonstrated that outcome improves up to spKt/v 2.00. Analysis of HEMO as treated showed that there is a fundamental flaw in dose-targeted OS in that the optimal dose always, but spuriously, increases as the studied dose increases due to dose-targeting bias. Similar flaws exist in the association of treatment time to outcome.
Regulation of Postangiogenic Neovessel Survival by β1 and β3 Integrins in Collagen and Fibrin Matrices
Authors: Carnevale Edvige , Fogel Eric , Aplin Alfred C. , Gelati Maurizio , Howson Karen M. , Zhu Wen-Hui , Nicosia Roberto F.
Published: December 2006

We used the aortic ring model of angiogenesis to investigate the role of β1 and β3 integrins in postangiogenic vascular survival in collagen and fibrin matrices. Confocal microscopy studies showed that both β1 and β3 integrins were expressed in endothelial cells and pericytes of sprouting neovessels. Antibody blocking experiments demonstrated that β1 integrins but not β3 integrins were required for angiogenic sprouting in collagen. Conversely, in fibrin, blockade of both integrins was needed to inhibit angiogenesis whereas treatment with either antibody alone was ineffective. Antibody-mediated blockade of β1 but not β3 integrins accelerated vascular regression in collagen. In contrast, both anti-β1 and -β3 integrin antibodies were required to promote neovessel breakdown in fibrin. These results demonstrate that angiogenic sprouting and postangiogenic neovessel survival in collagen are critically dependent on β1 integrins. They also indicate that these processes involve a redundant repertoire of β1 and β3 integrins when angiogenesis occurs in fibrin. Thus, pharmacologic targeting of integrin receptors aimed at blocking neovessel formation and survival must be tailored to the specific extracellular matrix environment in which angiogenesis takes place.
C8orf4/TC-1(Thyroid Cancer-1) Gene Expression in Thyroid Cancer and Goiter
Authors: de Melo Martins Poliana Cristina , Parise Junior Orlando , Pereira Hors Cora , Villela Miguel Roberto Elias , da Costa Andrade Valéria Cristina , Garicochea Bernardo
Published: December 2006

Background: The expression of the thyroid cancer-1(TC-1) gene seems to be related with malignant transformation in the thyroid tissue. Objective: We evaluated the potential use of TC-1 gene expression as a marker of malignancy in thyroid nodules. Methods: A total of 92 frozen thyroid samples were studied, including 46 samples from thyroid nodules (19 papillary carcinomas, 1 follicular carcinoma, 24 adenomatous goiters, and 2 follicular adenomas) and 46 samples from normal surrounding thyroid tissue. Total RNA was extracted and TC-1 expression was assessed by semiquantitative Multiplex PCR. Results were verified using real-time RT-PCR in some of the samples. Results: Overall mean TC-1 gene expression (normalized by the ABL gene) was 1.73 ± 1.67 (0.33–9.33). There was a significant difference (p < 0.001) between TC-1 gene expression in benign thyroid lesions (1.07 ± 0.10) and carcinomas (2.73 ± 0.51). Conclusion: Our results suggest that TC-1 gene expression may be useful in the differential diagnosis of goiters and thyroid papillary carcinomas.
In vitro Antibacterial Activity of Lucilia sericata Maggot Secretions
Authors: Daeschlein G. , Mumcuoglu K.Y. , Assadian O. , Hoffmeister B. , Kramer A.
Published: December 2006

Maggots of the green blowfly, Lucilia sericata, are used as an alternative to surgical intervention and long-term antiseptic therapy for the treatment of chronic wounds. The secretions of maggots are known to have antibacterial properties. To quantify the bactericidal effect of secretions from larvae of L. sericata, an in vitro test model based on the modified European quantitative suspension test (EN 1040) was developed, in which a co-culture of maggots and bacteria (Micrococcus luteus,Escherichia coli, methicillin-sensitive Staphylo-coccus aureus) in tryptic soy broth was tested. The numbers of bacterial colonies with and without maggot exposure were compared after 24, 48 and 72 h of exposure. The mean log10 reduction factor (RF) for bacterial elimination per maggot was >4 at all examined times for all tested bacteria. Thus, maggot secretion fulfilled the required definitions of an antiseptic. In addition, the maggots’ ability to ingest bacteria was also evaluated. Maggots contained viable bacteria after 48 h of contact with the respective organisms. These maggots also continued excreting bacteria. Therefore, maggots should be disposed of after use as they must be regarded as medical waste.