bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidation and haem loss kinetics of poly(ethylene glycol)-conjugated haemoglobin (MP4): dissociation between in vitro and in vivo oxidation rates
Authors: Vandegriff Kim D. , Malavalli Ashok , Minn Charles , Jiang Eva , Lohman Jeff , Young Mark A. , Samaja Michele , Winslow Robert M.
Published: October 2006

Haemoglobin-based oxygen carriers can undergo oxidation of ferrous haemoglobin into a non-functional ferric form with enhanced rates of haem loss. A recently developed human haemoglobin conjugated to maleimide-activated poly(ethylene glycol), termed MP4, has unique physicochemical properties (increased molecular radius, high oxygen affinity and low cooperativity) and lacks the typical hypertensive response observed with most cell-free haemoglobin solutions. The rate of in vitro MP4 autoxidation is higher compared with the rate for unmodified SFHb (stroma-free haemoglobin), both at room temperature (20–22 °C) and at 37 °C (P<0.001). This appears to be attributable to residual catalase activity in SFHb but not MP4. In contrast, MP4 and SFHb showed the same susceptibility to oxidation by reactive oxygen species generated by a xanthine–xanthine oxidase system. Once fully oxidized to methaemoglobin, the rate of in vitro haem loss was five times higher in MP4 compared with SFHb in the fast phase, which we assign to the β subunits, whereas the slow phase (i.e. haem loss from α chains) showed similar rates for the two haemoglobins. Formation of MP4 methaemoglobin in vivo following transfusion in rats and humans was slower than predicted by its first-order in vitro autoxidation rate, and there was no appreciable accumulation of MP4 methaemoglobin in plasma before disappearing from the circulation. These results show that MP4 oxidation and haem loss characteristics observed in vitro provide information regarding the effect of poly(ethylene glycol) conjugation on the stability of the haemoglobin molecule, but do not correspond to the oxidation behaviour of MP4 in vivo.
Ubiquitin-binding domains
Authors: Hurley James H. , Lee Sangho , Prag Gali
Published: October 2006

The covalent modification of proteins by ubiquitination is a major regulatory mechanism of protein degradation and quality control, endocytosis, vesicular trafficking, cell-cycle control, stress response, DNA repair, growth-factor signalling, transcription, gene silencing and other areas of biology. A class of specific ubiquitin-binding domains mediates most of the effects of protein ubiquitination. The known membership of this group has expanded rapidly and now includes at least sixteen domains: UBA, UIM, MIU, DUIM, CUE, GAT, NZF, A20 ZnF, UBP ZnF, UBZ, Ubc, UEV, UBM, GLUE, Jab1/MPN and PFU. The structures of many of the complexes with mono-ubiquitin have been determined, revealing interactions with multiple surfaces on ubiquitin. Inroads into understanding polyubiquitin specificity have been made for two UBA domains, whose structures have been characterized in complex with Lys48-linked di-ubiquitin. Several ubiquitin-binding domains, including the UIM, CUE and A20 ZnF (zinc finger) domains, promote auto-ubiquitination, which regulates the activity of proteins that contain them. At least one of these domains, the A20 ZnF, acts as a ubiquitin ligase by recruiting a ubiquitin–ubiquitin-conjugating enzyme thiolester adduct in a process that depends on the ubiquitin-binding activity of the A20 ZnF. The affinities of the mono-ubiquitin-binding interactions of these domains span a wide range, but are most commonly weak, with Kd>100 μM. The weak interactions between individual domains and mono-ubiquitin are leveraged into physiologically relevant high-affinity interactions via several mechanisms: ubiquitin polymerization, modification multiplicity, oligomerization of ubiquitinated proteins and binding domain proteins, tandem-binding domains, binding domains with multiple ubiquitin-binding sites and co-operativity between ubiquitin binding and binding through other domains to phospholipids and small G-proteins.
Association study of ACE2 (angiotensin I-converting enzyme 2) gene polymorphisms with coronary heart disease and myocardial infarction in a Chinese Han population
Authors: Yang Wei , Huang Wentao , Su Shaoyong , Li Biao , Zhao Weiyan , Chen Shufeng , Gu Dongfeng
Published: October 2006

Results are accumulating that ACE2 (angiotensin I-converting enzyme 2) might act as a protective protein for cardiovascular diseases; however, only a few studies in human populations have been carried out. This prompted us to perform a case-control study to investigate the relationship of ACE2 polymorphisms with CHD (coronary heart disease) and MI (myocardial infarction). Three single nucleotide polymorphisms in the ACE2 gene (1075A/G, 8790A/G and 16854G/C) were genotyped by PCR-RFLP (restriction-fragment-length polymorphism) in 811 patients with CHD (of which 508 were patients with MI) and 905 normal controls in a Chinese population. The polymorphisms were in linkage disequilibrium (r2=0.854–0.973). Analyses were conducted by gender, because the ACE2 gene is on the X chromosome. In females, an association was detected with MI for 1075A/G (P=0.026; odds ratio=1.98) and 16854G/C (P=0.028; odds ratio=1.97) in recessive models after adjusting for covariates. In male subjects, two haplotypes (AAG and GGC) were common in frequency. In male subjects not consuming alcohol, the haplotype GGC was associated with a 1.76-fold risk of CHD [95% CI (confidence interval), 1.15–2.69; P=0.007] and a 1.77-fold risk of MI (95% CI, 1.12–2.81; P=0.015) with environmental factors adjusted, when compared with the most common haplotype AAG. In conclusion, the results of the present study indicate that common genetic variants in the ACE2 gene might impact on MI in females, and may possibly interact with alcohol consumption to affect the risk of CHD and MI in Chinese males.
Influences of the breathing route on upper airway dynamics properties in normal awake subjects with constant mouth opening
Authors: Wang Wei , Verin Eric , Sériès Frédéric
Published: October 2006

MB (mouth breathing) promotes the occurrence of sleep-disordered breathing even in non-apnoeic subjects. Considering that MO (mouth opening) contributes to an increase in UA (upper airway) collapsibility independently of MB, the aim of the present study was to assess the influence of breathing route on UA dynamics in the presence of MO. Bilateral anterior magnetic phrenic nerve stimulation was performed 2 s after expiratory onset in 12 healthy male subjects during wakefulness (age, 50±5 years; body mass index, 27.8±2.4 kg/m2) during MB through a mouthpiece and during exclusive NB (nasal breathing) with the same mouthpiece in place. Twitch-induced V̇I (instantaneous flow), Pph and Pes (pharyngeal and oesophageal pressures respectively) were recorded and the corresponding resistances were measured. A polynomial regression model, V̇I=k1Pd+k2Pd2, was used to characterize flow–pressure relationship and to determine the Pd value at which UA collapses. There was no difference in UA dynamic properties between NB and MB when UA collapse occurred above the pharyngeal catheter. For twitches where UA collapse occurred lower in the UA, pharyngeal resistance decreased from NB to MB (2.0±0.3 and 1.5±0.2 cmH2O·l−1·s respectively; P=0.02; values are means±S.D.), whereas closing pressure increased (−25.7±10.1 and −18.0±3.0 cmH2O respectively; P=0.04). We conclude that (i) in the presence of MO the dynamic properties of the proximal UA free of phasic activity do not differ between NB and MB, and (ii) MB decreases the upstream resistance and increases collapsibility of the distal UA.
Osteopontin and carotid atherosclerosis in patients with essential hypertension
Authors: Kurata Mie , Okura Takafumi , Watanabe Sanae , Fukuoka Tomikazu , Higaki Jitsuo
Published: October 2006

OPN (osteopontin), a pro-inflammatory cytokine, has recently emerged as a key factor in both vascular remodelling and the development of atherosclerosis. However, the relationship between OPN and atherosclerosis in patients without symptomatic cardiovascular disease is not clear. Therefore we measured plasma OPN levels and evaluated the correlation between plasma OPN levels and atherosclerosis as target organ damage in patients with EHT (essential hypertension). Plasma OPN levels were measured in 76 patients with EHT using a solid-phase sandwich ELISA. IMT (intima-media thickness), and Vd and Vs (mean diastolic and systolic flow velocities respectively) were evaluated by carotid ultrasound. The Vd/Vs ratio, an index of peripheral arterial resistance, was also calculated. The patients were divided on the basis of median OPN levels into a high-OPN group and a low-OPN group. The mean IMT and aldosterone levels were higher (P=0.024 and 0.031 respectively) and Vd/Vs was lower (P=0.007) in the high-OPN group than in the low-OPN group. Plasma OPN levels were positively correlated with mean IMT (r=0.308, P=0.0068) and negatively with Vd/Vs (r=−0.293, P=0.010). Stepwise regression analysis revealed that OPN was an independent determinant of mean IMT (P=0.007) and Vd/Vs (P=0.009), and aldosterone was an independent determinant of OPN. These results suggest that OPN plays a role in the development of atherosclerosis and may be a potential clinical marker for the prediction of atherosclerosis in patients with EHT.
Detection of inflamed atherosclerotic lesions with diadenosine-5′,5‴-
P
1
,
P
4
-tetraphosphate (Ap
4
A) and positron-emission tomography
Authors: Elmaleh D. R. , Fischman A. J. , Tawakol A. , Zhu A. , Shoup T. M. , Hoffmann U. , Brownell A.-L. , Zamecnik P. C.
Published: October 2006

Diadenosine-5′,5‴-
P
1
,
P
4
-tetraphosphate (Ap
4
A) and its analog
P
2
,
P
3
-monochloromethylene diadenosine-5′,5‴-
P
1
,
P
4
-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with
P
2
,
P
3
-[
18
F]monofluoromethylene diadenosine-5′,5‴-
P
1
,
P
4
-tetraphosphate ([
18
F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [
18
F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [
18
F]AppCHFppA uptake (
r
= 0.87,
P
< 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [
18
F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [
18
F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [
18
F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation.
Weakly null sequences in 𝐿₁
Authors: Johnson William , Maurey Bernard , Schechtman Gideon
Published: October 2006

We construct a weakly null normalized sequence

{

f
i

}

i
=
1

∞

\{f_i\}_{i=1}^{\infty }

in

L
1

L_1

so that for each

ε
>
0

\varepsilon >0

, the Haar basis is

(
1
+
ε
)

(1+\varepsilon )

-equivalent to a block basis of every subsequence of

{

f
i

}

i
=
1

∞

\{f_i\}_{i=1}^{\infty }

. In particular, the sequence

{

f
i

}

i
=
1

∞

\{f_i\}_{i=1}^{\infty }

has no unconditionally basic subsequence. This answers a question raised by Bernard Maurey and H. P. Rosenthal in 1977. A similar example is given in an appropriate class of rearrangement invariant function spaces.
NMPP: a user-customized NimbleGen microarray data processing pipeline
Authors: Wang Xiangfeng , He Hang , Li Lei , Chen Runsheng , Deng Xing Wang , Li Songgang
Published: October 2006

Summary: NMPP package is a bundle of user-customized tools based on established algorithms and methods to process self-designed NimbleGen microarray data. It features a command-line-based integrative processing procedure that comprises five major functional components, namely the raw microarray data parsing and integrating module, the array spatial effect smoothing and visualization module, the probe-level multi-array normalization module, the gene expression intensity summarization module and the gene expression status inference module.

Availability:  

Contact:  Xiangfeng.Wang@Yale.edu

Supplementary information: The supplementary materials, figures, testing dataset, software instructions and a typical workflow of using NMPP package are accessible through the above homepage.
Interleukin-6 and vascular endothelial growth factor release by renal cell carcinoma cells impedes lymphocyte–dendritic cell cross-talk
Authors: Cabillic F , Bouet-Toussaint F , Toutirais O , Rioux-Leclercq N , Fergelot P , De La Pintière C Thomas , Genetet N , Patard J-J , Catros-Quemener V
Published: October 2006

Anti-tumour T cell response requires antigen presentation via efficient immunological synapse between antigen presenting cells, e.g. dendritic cells (DC), and specific T cells in an adapted Th1 cytokine context. Nine renal cell carcinoma (RCC) primary culture cells were used as sources of tumour antigens which were loaded on DC (DC-Tu) for autologous T cell activation assays. Cytotoxic activity of lymphocytes stimulated with DC-Tu was evaluated against autologous tumour cells. Assays were performed with 75 grays irradiated tumour cells (Tu irr) and with hydrogen peroxide ± heat shock (Tu H2O2 ± HS) treated cells. DC-Tu irr failed to enhance cytotoxic activity of autologous lymphocytes in seven of 13 assays. In all these defective assays, irradiated tumour cells displayed high interleukin (IL)-6 and vascular endothelial growth factor (VEGF) release. Conversely, when tumour cells released low IL-6 levels (n = 4), DC-Tu irr efficiently enhanced CTL activity. When assays were performed with the same RCC cells treated with H2O2 + HS, DC-Tu stimulation resulted in improved CTL activity. H2O2 + HS treatment induced post-apoptotic cell necrosis of tumour cells, totally abrogated their cytokine release [IL-6, VEGF, transforming growth factor (TGF)-β1] and induced HSP70 expression. Taken together, data show that reduction in IL-6 and VEGF release in the environment of the tumour concomitantly to tumour cell HSP expression favours induction of a stronger anti-tumour CTL response.
Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high‐risk nondiabetic patients
Authors: CESARI M. , PESSINA A. C. , ZANCHETTA M. , DE TONI R. , AVOGARO A. , PEDON L. , DORIGATTI F. , MAIOLINO G. , ROSSI G. P.
Published: October 2006

Objective.  To investigate the association of plasma adiponectin levels with coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance (IR) in nondiabetic Caucasian patients.

Design.  We measured plasma adiponectin levels, IR (HOMA index), and the CAD atherosclerotic burden (angiography‐based modified Duke Index score) in 400 nondiabetic patients undergoing coronary angiography. HT was diagnosed by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines or if patients were on antihypertensive treatment.

Results.  Coronary artery disease was found in 62% of the patients and ruled out in the rest (non‐CAD group). Plasma adiponectin levels were inversely related to the CAD score (β = −0.12, P = 0.029) and predicted the coronary atherosclerotic burden independent of other cardiovascular risk factors. However, they were similar in NT and HT and showed no correlation with blood pressure values. In non‐CAD, but not in CAD patients, they were lower in patients with than without IR (8.3 ± 1.2 vs. 11.3 ± 1.3, respectively; P = 0.007).

Conclusions.  In nondiabetic high‐risk Caucasian patients plasma adiponectin levels are inversely related to CAD severity and IR; however, they are not strongly related to blood pressure values.
Characterization of native and reconstituted exosome complexes from the hyperthermophilic archaeon Sulfolobus solfataricus
Authors: Walter Pamela , Klein Franziska , Lorentzen Esben , Ilchmann Anne , Klug Gabriele , Evguenieva‐Hackenberg Elena
Published: October 2006

The eukaryotic exosome is a protein complex with essential functions in processing and degradation of RNA. Exosome‐like complexes were recently found in Archaea. Here we characterize the exosome of Sulfolobus solfataricus. Two exosome fractions can be discriminated by density gradient centrifugation. We show that the Cdc48 protein is associated with the exosome from the 30S−50S fraction but not with the exosome of the 11.3S fraction. While only some complexes contain Cdc48, the archaeal DnaG‐like protein was found to be a core exosome subunit in addition to Rrp4, Rrp41, Rrp42 and Csl4. Assays with depleted extracts revealed that the exosome is responsible for major ribonucleolytic activity in S. solfataricus. Various complexes consisting of the Rrp41‐Rrp42 hexameric ring and Rrp4, Csl4 and DnaG were reconstituted. Dependent on their composition, different complexes showed variations in RNase activity indicating functional interdependence of the subunits. The catalytic activity of these complexes and of the native exosome can be ascribed to the Rrp41‐Rrp42 ring, which degrades RNA phosphorolytically. Rrp4 and Csl4 do not exhibit any hydrolytic RNase activity, either when assayed alone or in context of the complex, but influence the activity of the archaeal exosome.
Structure‐based mutagenesis of SigE verifies the importance of hydrophobic and electrostatic residues in type III chaperone function
Authors: Knodler Leigh A. , Bertero Michela , Yip Calvin , Strynadka Natalie C. J. , Steele‐Mortimer Olivia
Published: October 2006

Despite sharing little sequence identity, most type III chaperones display a similar homodimeric structure characterized by negative charges distributed broadly over their entire surface, interspersed with hydrophobic patches. Here we have used SigE from Salmonella as a model for class IA type III chaperones to investigate the role of these surface‐exposed residues in chaperone function. SigE is essential for the stability, secretion and translocation of its cognate effector, SopB (SigD). We analysed the effect of mutating nine conserved hydrophobic and electronegative surface‐exposed amino acids of SigE on SopB binding, stability, secretion and translocation. Six of these mutations affected some aspect of SigE function (Leu14, Asp20, Leu22, Leu23, Ile25 and Asp51) and three were without effect (Leu54, Glu92 and Glu99). Our results highlight that both hydrophobic and electronegative surfaces are required for the function of SigE and provide an important basis for the prediction of side‐chain requirements for other chaperone–effector pairs.
The Vibrio motor proteins, MotX and MotY, are associated with the basal body of Na+‐driven flagella and required for stator formation
Authors: Terashima Hiroyuki , Fukuoka Hajime , Yakushi Toshiharu , Kojima Seiji , Homma Michio
Published: October 2006

The four motor proteins PomA, PomB, MotX and MotY, which are believed to be stator proteins, are essential for motility by the Na+‐driven flagella of Vibrio alginolyticus. When we purified the flagellar basal bodies, MotX and MotY were detected in the basal body, which is the supramolecular complex comprised of the rotor and the bushing, but PomA and PomB were not. By antibody labelling, MotX and MotY were detected around the LP ring. These results indicate that MotX and MotY associate with the basal body. The basal body had a new ring structure beneath the LP ring, which was named the T ring. This structure was changed or lost in the basal body from a ΔmotX or ΔmotY strain. The T ring probably comprises MotX and MotY. In the absence of MotX or MotY, we demonstrated that PomA and PomB were not localized to a cell pole. From the above results, we suggest that MotX and MotY of the T ring are involved in the incorporation and/or stabilization of the PomA/PomB complex in the motor.
A new domain of conjugative relaxase TrwC responsible for efficient oriT‐specific recombination on minimal target sequences
Authors: César Carolina Elvira , Machón Cristina , De La Cruz Fernando , Llosa Matxalen
Published: October 2006

We show that relaxase TrwC promotes recombination between two directly repeated oriTs while related relaxases TraI of F and pKM101 do not. Efficient recombination required also relaxosome accessory protein TrwA even after deletion of TrwA binding sites at oriT, suggesting that the effect of TrwA is mediated by protein–protein interactions. TrwC relaxase domain was necessary but not sufficient to catalyse recombination efficiently. Full recombinase activity was obtained with the N‐terminal 600 residues of TrwC. The minimal target sequences required for recombination were different at each of the two involved oriTs: oriT1 could be reduced to the nic site and TrwC binding site, while oriT2 required an extended sequence including a set of iterons that are not required for conjugation. TrwC‐mediated integration of a transferred DNA into a resident oriT copy required a complete oriT in the recipient. We observed dramatic changes in the efficiency of recombination between tandem oriTs linked to the direction of plasmid replication and transcription through oriT1. We propose that recombination is triggered by the generation of a single‐stranded DNA at oriT1 that causes TrwC nicking. The resulting TrwC‐DNA complex reacts with oriT2, excising the intervening DNA. This intermediate can be resolved by host‐encoded replication functions.
Meningococcal biofilm formation: structure, development and phenotypes in a standardized continuous flow system
Authors: Lappann Martin , Haagensen Janus A. J. , Claus Heike , Vogel Ulrich , Molin Søren
Published: October 2006

We show that in a standardized in vitro flow system unencapsulated variants of genetically diverse lineages of Neisseria meningitidis formed biofilms, that could be maintained for more than 96 h. Biofilm cells were resistant to penicillin, but not to rifampin or ciprofloxacin. For some strains, microcolony formation within biofilms was observed. Microcolony formation in strain MC58 depended on a functional copy of the pilE gene encoding the pilus subunit pilin, and was associated with twitching of cells. Nevertheless, unpiliated pilE mutants formed biofilms showing that attachment and accumulation of cells did not depend on pilus expression. Mutation and complementation analysis revealed that the type IV pilus‐associated protein PilX, which was recently shown to mediate interbacterial aggregation, indirectly supported microcolony formation by contributing to pilus expression. A large number of PilX alleles was identified among genetically diverse meningococcal strains. PilX alleles differed in their propensity to support autoaggregation of cells in suspension, but not in their ability to support microcolony formation within biofilms in the continuous flow system.
Wolbachia‐induced unidirectional cytoplasmic incompatibility and the stability of infection polymorphism in parapatric host populations
Authors: FLOR M. , HAMMERSTEIN P. , TELSCHOW A.
Published: October 2006

Wolbachiaare intracellular, maternally inherited bacteria that are widespread among arthropods and commonly induce a reproductive incompatibility between infected male and uninfected female hosts known as unidirectional cytoplasmic incompatibility (CI). If infected and uninfected populations occur parapatrically, CI acts as a post‐zygotic isolation barrier. We investigate the stability of such infection polymorphisms in a mathematical model with two populations linked by migration. We determine critical migration rates below which infected and uninfected populations can coexist. Analytical solutions of the critical migration rate are presented for mainland‐island models. These serve as lower estimations for a more general model with two‐way migration. The critical migration rate is positive if eitherWolbachiacauses a fecundity reduction in infected female hosts or its transmission is incomplete, and is highest for intermediate levels of CI. We discuss our results with respect to local adaptations of theWolbachiahost, speciation, and pest control.
The origin of theChorthippus parallelushybrid zone: chromosomal evidence of multiple refugia for Iberian populations
Authors: BELLA J. L. , SERRANO L. , ORELLANA J. , MASON P. L.
Published: October 2006

A study of the variation in pattern and frequency of constitutive heterochromatin and nucleolar organizing regions of the X chromosomes of maleChorthippus parallelusgrasshoppers in 25 populations within the Iberian peninsula requires us to revise our interpretation of the biogeography and evolutionary history of this species. Hybridization between the subspeciesCp erythropusandCp parallelus, previously only known from populations in the Pyrenean cols, is shown to extend at least 400 km further into north‐west Spain. A novel X‐chromosome variant is described that appears to be close to fixation in 18 populations, mainly from the centre and south of Spain. Our findings indicate a possible independent origin for each of three distinct, nonderivative X variants present in Spain: the northernCp erythropusandCp parallelusvariants, and a central‐southernCp erythropusvariant. The first two are distinguished by interstitial and distal C bands, respectively, whereas the central‐southern form has neither. This central‐southern form is probably the current representative of the ancestral Iberian X variant. The pattern of variation supports the hypotheses of multiple refugia for Iberian populations and that more hybrid zones exist between these chromosomal variants.
Anomalies in Copyright Law
Authors: Mazumder Anirban
Published: October 2006

The word copyright is a misnomer. The law of copyright is based on the encouragement of motive. Plagiarism is not necessarily copyright infringement and copyright infringement is not necessarily plagiarism. Copyright law is concerned, in essence, with the negative right of preventing the copying of physical material. Copyright is not a monopoly, unlike patent and registered design. Thus, if it can be shown that two precisely similar works were in fact produced wholly independently of one another, there can be no infringement of copyright by one or the other. Substantial similarity leading to copyright infringement is a grey area in copyright law. As per copyright law principles, making a digital copy itself is copyright infringement, no matter what amount of work is accessible to users. If a compilation work satisfies the originality criteria, that is ‘creativity’, then it will be protected. There is no copyright in facts per se, but original expression of factual compilation can have copyright protection.
Intellectual Property Rights Jurisprudence in Tanzania: Turning an Eye to the Commercial Division of the High Court
Authors: Kihwelo Paul Faustin
Published: October 2006

This article seeks to address the practice and judicial development in Tanzania insofar as interpretation of matters relating to intellectual property (IP) are concerned. The article begins by examining the various forms of IP and proceeds to illucidate legal frameworks both globally, which includes matters relating to the World Intellectual Property Organization as well as the Agreement on Trade‐Related Aspects of Intellectual Property Rights (TRIPS) provisions, and the Tanzania legal framework. In addition, the article examines the genesis and framework of the commercial court in Tanzania and proceeds to make an in‐depth analysis of TRIPS enforcement provisions with emphasis on the practice of the commercial court. The author proceeds to examine a number of selected cases decided by the commercial court since its inception to date.
India's Product Patent Protection Regime: Less or More of “Pills for the Poor”?
Authors: Sampath Padmashree Gehl
Published: October 2006

The year 2005 marks the end of the transition period for many developing countries with competent pharmaceutical sectors that previously competed in supplying generic versions of patented drugs to least‐developed countries (LDCs), thereby inducing price competition and enhancing access to medicines. In a post‐2005 scenario, the critical issue is whether LDCs without adequate manufacturing capabilities can make use of compulsory licensing expeditiously to induce price competition and secure lower prices. This article uses empirical evidence collected during a firm‐level survey of the Indian pharmaceutical sector to generate evidence on emerging strategies of firms. It shows that the vigour of compulsory licensing as a price‐leveraging instrument post‐2005 is incumbent mainly on its economic feasibility. It shows that Indian firms view the market potential (in terms of market size and profits involved in such supply, especially if they have to make specific technological investments to produce the drug) of the mechanism much more severely than before, and may be less inclined to engage in such production if their commercial expectations are grossly unmet. The analysis assesses implications of emerging strategies of firms in the Indian pharmaceutical sector for access to medicines both domestically and internationally, and highlights the challenges involved.
Neurosteroid pregnenolone sulfate enhances glutamatergic synaptic transmission by facilitating presynaptic calcium currents at the calyx of Held of immature rats
Authors: Hige Toshihide , Fujiyoshi Yoshinori , Takahashi Tomoyuki
Published: October 2006

Pregnenolone sulfate (PREGS) is an endogenous neurosteroid widely released from neurons in the brain, and is thought to play a memory‐enhancing role. At excitatory synapses PREGS facilitates transmitter release, but the underlying mechanism is not known. We addressed this issue at the calyx of Held in rat brainstem slices, where direct whole‐cell recordings from giant nerve terminals are feasible. PREGS potentiated nerve‐evoked excitatory postsynaptic currents (EPSCs) without affecting the amplitude of miniature EPSCs, suggesting that its site of action is presynaptic. In whole‐cell recordings from calyceal nerve terminals, PREGS facilitated Ca2+ currents, by accelerating their activation kinetics and shifting the half‐activation voltage toward negative potentials. PREGS had no effect on presynaptic K+ currents, resting conductance or action potential waveforms. In simultaneous pre‐ and postsynaptic recordings, PREGS did not change the relationship between presynaptic Ca2+ influx and EPSCs, suggesting that exocytotic machinery downstream of Ca2+ influx is not involved in its effect. PREGS facilitated Ba2+ currents recorded from nerve terminals and also from HEK 293 cells expressed with recombinant N‐ or P/Q‐type Ca2+ channels, suggesting that PREGS‐induced facilitation of voltage‐gated Ca2+ channels (VGCCs) is neither Ca2+ dependent nor VGCC‐type specific. The PREGS‐induced VGCC facilitation was blocked by the PREGS scavenger (2‐hydroxypropyl)‐β‐cyclodextrin applied from outside, but not from inside, of nerve terminals. We conclude that PREGS facilitates VGCCs in presynaptic terminals by acting from outside, thereby enhancing transmitter release. We propose that PREGS may directly modulate VGCCs acting on their extracellular domain.
Key role of selective viral‐induced mortality in determining marine bacterial community composition
Authors: Bouvier T. , Del Giorgio P. A.
Published: October 2006

Viral infection is thought to play an important role in shaping bacterial community composition and diversity in aquatic ecosystems, but the strength of this interaction and the mechanisms underlying this regulation are still not well understood. The consensus is that viruses may impact the dominant bacterial strains, but there is little information as to how viruses may affect the less abundant taxa, which often comprise the bulk of the total bacterial diversity. The potential effect of viruses on the phylogenetic composition of marine bacterioplankton was assessed by incubating marine bacteria collected along a North Pacific coastal‐open ocean transect in seawater that was greatly depleted of ambient viruses. The ambient communities were dominated by typical marine groups, including alphaproteobacteria and the Bacteroidetes. Incubation of these communities in virus‐depleted ambient water yielded an unexpected and dramatic increase in the relative abundance of bacterial groups that are generally undetectable in the in situ assemblages, such as betaproteobacteria and Actinobacteria. Our results suggest that host susceptibility is not necessarily only proportional to its density but to other characteristics of the host, that rare marine bacterial groups may be more susceptible to viral‐induced mortality, and that these rare groups may actually be the winners of competition for resources. These observations are not inconsistent with the ‘phage kills the winner’ hypothesis but represent an extreme and yet undocumented case of this paradigm, where the potential winners apparently never actually develop beyond a very low abundance threshold in situ. We further suggest that this mode of regulation may influence not just the distribution of single strains but of entire phylogenetic groups.
Information Sharing and Oligopoly in Agricultural Markets: The Role of the Cooperative Bargaining Association
Authors: Hueth Brent , Marcoul Philippe
Published: October 2006

We study incentives for information sharing among agricultural intermediaries in imperfectly competitive markets for farm output. Information sharing always increases expected grower and total surplus, but may reduce expected intermediary profits. Even when expected profits increase with information sharing, intermediary firms face a prisoner's dilemma where it is privately rational to withhold information, given that other firms report truthfully. This equilibrium can be avoided if firms' information reports are verifiable, and if firms commit to an ex ante contract that enforces participation in information sharing. We show how agricultural bargaining legislation can implement such a contract with the bargained farm price representing a sufficient statistic of all information held by intermediary firms.
Urban Sprawl and Farmland Prices
Authors: Livanis Grigorios , Moss Charles B. , Breneman Vincent E. , Nehring Richard F.
Published: October 2006

A theoretical model of farmland valuation is developed to explicitly account for three effects of urban sprawl: conversion of farmland to urban uses, effect on agricultural returns, and speculative effect as represented by farmland conversion risk. This model is estimated using county‐level data in the continental United States. Evidence is found for all three effects of urban sprawl on farmland values. Counties more accessible to major urban centers have higher net agricultural returns. Subsidiary evidence supports that the latter effect may be attributed to survival of (or conversion to) high‐valued agriculture around urban centers.
Illegal Landings: An Aggregate Catch Self‐Reporting Mechanism
Authors: Hansen Lars Gårn , Jensen Frank , Brandt Urs Steiner , Vestergaard Niels
Published: October 2006

To solve the problem of illegal landings this article proposes a new tax mechanism based on the regulator's own aggregate catch estimates and ex ante self‐reports of planned catch by fishermen. We show that the mechanism avoids illegal landings while ensuring (nearly) optimal exploitation and generating (nearly) correct entry and exit incentives. Finally we simulate the mechanism for the Danish cod fishery in Kattegat to obtain a rough indicator of the size of the tax. It turns out that the average tax payment as a percentage of profit is surprisingly low.
Consumers' Willingness to Pay for the Color of Salmon: A Choice Experiment with Real Economic Incentives
Authors: Alfnes Frode , Guttormsen Atle G. , Steine Gro , Kolstad Kari
Published: October 2006

In most retail markets, sellers post the price and consumers choose which products to buy. We designed an experimental market with posted prices to investigate consumers' willingness to pay for the color of salmon. Salmon fillets varying in color and price were displayed in twenty choice scenarios. In each scenario, the participants chose which of two salmon fillets they wanted to buy. To induce real economic incentives, each participant drew one binding scenario; the participants then had to buy the salmon fillet they had chosen in their binding scenario. The choice data were analyzed with a mixed logit model.
A Composite Likelihood Cross‐validation Approach in Selecting Bandwidth for the Estimation of the Pair Correlation Function
Authors: GUAN YONGTAO
Published: October 2006

Abstract.  A useful tool while analysing spatial point patterns is the pair correlation function (e.g. Fractals, Random Shapes and Point Fields, Wiley, New York, 1994). In practice, this function is often estimated by some nonparametric procedure such as kernel smoothing, where the smoothing parameter (i.e. bandwidth) is often determined arbitrarily. In this article, a data‐driven method for the selection of the bandwidth is proposed. The efficacy of the proposed approach is studied through both simulations and an application to a forest data example.
Critical Issues in Participatory GIS: Deconstructions, Reconstructions, and New Research Directions
Authors: Elwood Sarah
Published: October 2006

In the mid‐1990s, several critical texts raised concerns about the social, political, and epistemological implications of GIS. Subsequent responses to these critiques have fundamentally altered the technological, political, and intellectual practices of GIScience. Participatory GIS, for instance, has intervened in multiple ways to try to ameliorate uneven access to GIS and digital spatial data and diversify the forms of spatial knowledge and spatial logic that may be incorporated in a GIS. While directly addressing core elements of the ‘GIS & Society’ critique, these reconstructions of a critical GIScience introduce their own ambiguities with respect to access, equity, digital representation of spatial knowledge, and epistemologies of new GIS research practices. In this paper, I examine some of the new and persistent ambiguities of participatory GIS that bear inclusion in future critical GIScience research.
WHY I BELIEVE IN AN EXTERNAL WORLD
Authors: LANGSAM HAROLD
Published: October 2006

Abstract: I claim in this article that if my experience is such that it seems to me that there is an external object before me, then I have reason to believe that there is an external object before me. The sceptic argues that since my having the experience is compatible both with there being and with there not being an external object before me, I have no reason to believe that the former possibility obtains and not the latter. I respond that the sceptic has ignored a relevant difference between the two possibilities: I can make sense of the former possibility but not of the latter. I examine two broad categories of sceptical possibilities (dreams and hallucinations), explain why I cannot make sense of them, and explain why my inability to make sense of them gives me reason to believe they do not obtain.
FANTASY, FICTION, AND FEELINGS
Authors: KREITMAN NORMAN
Published: October 2006

Abstract:The nature offantasyhas been little discussed, despite its importance in the arts. Its significance is brought out here in relation to the long‐standing debate on the alleged paradox of fiction—that we respond emotionally to characters and events known to be unreal. Examination of the paradox shows it to be ill founded once the nature of fantasy is appreciated. Moreover, a detailed consideration of fantasy shows that it can itself provide a plausible account of our emotional reactions to creative literature, an account that, after a review of some possible objections, is then contrasted with the leading contemporary theories.
Towards a European Code Napoléon/ABGB/BGB? Recent EC Activities for a European Contract Law
Authors: Röttinger Moritz
Published: October 2006

Abstract:  Contract law issues on European or international level have been studied for several decades in academic circles. Contract law issues and other questions affecting European private law have already been regulated in the past on EC level, especially in the framework of several consumer protection directives. The European Contract Law project initiated by the European Commission received new impetus with the Commission's Green Paper of 2004. Emphasis is laid on developing a ‘common frame of reference’ (CFR) which shall be ready by 2009. A so‐called ‘optional instrument’ and standard terms of contract are also looked at. The article explains the reasons behind these activities, describes the work currently under way, and points to a series of open questions of a legal or political nature.
European Political Development, Regulatory Governance, and the European Social Model: the Challenge of Substantive Legitimacy
Authors: Wincott Daniel
Published: October 2006

Abstract:  This article takes issue with aspects of the influential ‘regulatory’ perspective on European governance, especially as developed by Majone and Moravcsik. While many of their claims are compelling, these accounts become much less convincing when they move from empirical analysis to normative prescription—an argument developed in the article's first major section. The article charts the ambivalent treatment of connections between national democracies and at the EU level by regulatory theorists, considers their treatment of democracy, efficiency, welfare, social citizenship, understood here as features or legacies of majoritarian, or more accurately mass, democracy in Europe. The second section offers an alternative academic agenda for the analysis of Europe's multi‐level politics, which places it in historical perspective. It seeks to contribute to a growing body of EU scholarship that finds inspiration in the macro‐comparative approach of Rokkan, while also drawing links with studies in American political development. A rounded assessment of the prospects for democracy, legitimacy and political stability in Europe needs at least to integrate national and Europe level trends.
Still in Deficit: Rights, Regulation, and Democracy in the EU1
Authors: Bellamy Richard
Published: October 2006

Abstract:  Critics of the EU's democratic deficit standardly attribute the problem to either sociocultural reasons, principally the lack of a demos and public sphere, or institutional factors, notably the lack of electoral accountability because of the limited ability of the European Parliament to legislate and control the executive powers of the Commission and the Council of Ministers. Recently two groups of theorists have argued neither deficit need prove problematic. The first group adopts a rights‐based view of democracy and claims that a European consensus on rights, as represented by the Charter of Fundamental European Rights, can offer the basis of citizen allegiance to EU wide democracy, thereby overcoming the demos deficit. The second group adopts a public‐interest view of democracy and argues that so long as delegated authorities enact policies that are ‘for’ the people, then the absence of institutional forms that facilitate democracy ‘by’ the people are likewise unnecessary—indeed, in certain areas they may be positively harmful. This article argues that both views are normatively and empirically flawed. This is because there is no consensus on rights or the public interest apart from the majority view of a demos secured through parliamentary institutions. To the extent that these remain absent at the EU level, a democratic deficit continues to exist.
Difference as a Potential for European Constitution Making
Authors: Landfried Christine
Published: October 2006

Abstract:  This article examines the hypothesis that the impact of difference of ideas and interests on European constitution making can, under certain conditions, be a positive potential for legitimate and effective constitution making. The prerequisite conditions include actors that take differences seriously, structures of constitution making that are suitable for recognising differences, and processes of constitution making in which actors deal with differences in a democratic and communicative way. The analytical approach will be applied to the European Convention. Two case studies concerning the Convention's work will be examined: the process of decision‐making that led to the protocol on national parliaments and the decision‐making process concerning a permanent president of the European Council. Both case studies give evidence that the way in which members of the Convention were dealing with difference influenced the degree to which the positive potential of difference was activated for a legitimate and effective European constitutional treaty.
THE ANALYSIS OF SECOND MILLENNIUM GLASS FROM EGYPT AND MESOPOTAMIA, PART 1: NEW WDS ANALYSES*
Authors: SHORTLAND A. J. , EREMIN K.
Published: October 2006

A recent analytical study by SEM–WDS was carried out on 226 glasses from the Late Bronze Age, analysing each of the glasses for a total of at least 22 elements, the largest such analytical study conducted on these glasses. The aim of the analysis was first to identify which elements were brought in with each of the raw materials and, second, to accurately characterize those raw materials. Since different glassmaking sites in Egypt and the Near East would probably use at least some local raw materials and these raw materials will vary slightly from site to site, this has potential for provenancing the glass. Analysis showed new patterns in the compositions of glass from the various sites and led to new conclusions about the supply of raw materials and personnel for the glass workshops. This forms the basis for further work by LA–ICPMS to be presented in part 2 of this paper.
THE AMBER OF EL DORADO: CLASS IB ARCHAEOLOGICAL AMBERS ASSOCIATED WITH LAGUNA GUATAVITA*
Authors: ANDERSON K. B. , BRAY W.
Published: October 2006

Laguna Guatavita, a crater‐like lake located in central Colombia, was used by pre‐Columbian Muisca people for a variety of socio‐religious ceremonies, many of which involved casting offerings into the lake. Of these, the installation of a new ‘king’ became the basis of the El Dorado myth that was carried back to Europe by 16th century conquistadores. In the present study, beads collected from Laguna Guatavita during a late 19th/early 20th century attempt to recover valuables from the lake bed, have been subjected to geochemical analysis. Results establish that these artefacts have been fabricated from Class Ib amber. Class Ib ambers have not previously been reported in either the geological or archaeological records of Central or South America, and their existence in this context implies that the Muisca people had access to a unique local or regional source of amber, knowledge of which has subsequently been lost.