bluuebunny/crossref_metadata_2025 huggingface dataset:
Adapting International Law to the Development of the Third World
Authors: Flory Maurice
Published: July 2009

What is the connection between international law and economic development? The answer will very likely be different according to whether the question is asked in a developed country or in one of the 120 less-developed countries. Consequently the answer can only be found in international law itself.

Criticism has been levelled against the International Law Commission on the ground that its work only deals with the traditional topics which constitute the core of international law. Such criticism implies that the Commission has failed to perceive the need for developing international law adequately to encompass new areas.

Of course this assertion could be disputed. However, the General Secretary of the United Nations, in a Survey of International Law published in April, 1971, clearly points to a number of newly emerging areas of concern, including the law relating to economic development which comprises the following headings:

1. international legal rules and measures concerning regulation and coordination of the economic activities of states;

2. international trade;

3. economic and technical assistance.

In order to assess the full implication of this question, it should be appreciated that the activities of the U.N. and of a growing number of international economic institutions are now devoted increasingly to development. The numerous relevant publications issued especially, but not only, by Third World lawyers show how this matter is becoming of fundamental importance. Indeed, there can be little doubt that Foreign Office legal advisers would readily admit that much of their daily work involves questions of international economic law. Nevertheless, if one looks at the role allocated to this subject by what may loosely be called the established international law, one must recognise that this is, indeed, a very modest role.
Opting out of the common law: recent developments in the legal system of the Sudan
Authors: Mustafa Zaki
Published: July 2009

On October 1st, 1972, the Minister of Justice of the Democratic Republic of the Sudan constituted a committee consisting of 25 leading members of the Sudanese Legal Profession for the purpose of “re-examining fully the Sudan Civil Code, 1971, the Civil Procedure Code, 1972, the Civil Evidence Code, 1972, and the draft Penal and Commercial Codes”. The Committee was requested to recommend to the Minister whether all or any of the aforementioned codes should be abrogated, temporarily suspended (if already in force), kept as it is, or amended. The Committee was asked to submit its findings and recommendations as soon as possible and was authorised “to receive evidence from experts as well as from those directly connected with the application of the law”.
The use of oral data in legal anthropology: a Senegalese example
Authors: Snyder F. G.
Published: July 2009

Oral data are an integral part of the raw material used in anthropological research on social organization. They have also been heavily relied upon in the study of disappearing American Indian societies and, more recently, in the reconstruction of African history. By contrast, with some striking exceptions, they are in danger of being neglected in the anthropological study of law. Oral data have only recently been employed in Frenchsponsored studies in this field. In the English-speaking world, the dominant theme of dispute settlement and its apparent corollary, the case method, may leave little room for the systematic collection and the careful analysis of oral data.
La réforme du droit civil au Zaïre comment concilier tradition et développement?
Authors: Pauwels Johan M.
Published: July 2009

En République du Zaïre, la conscience de la nécessité de remettre en honneur les valeurs traditionnelles et de puiser aux richesses de la culture africaine, la volonté de “recourir à l’authenticité” comme on a coutume de dire, est actuellement très forte. Cela laisse supposer que la réforme du droit civil, récemment mise sur le chantier, sera marquée par la volonté de revaloriser la tradition.
Introduction
Authors: Twining W. L.
Published: July 2009

Since the day when, in my first year of teaching, I found myself trying to explain the feudal origins of trover to a puzzled class of Sudanese students, I have had occasional flickers of doubt whether the English law of torts has been one of Britain's most appropriate colonial legacies. One journey down the Lagos-Ibadan road should suffice to raise questions about the suitability of the common-law action for negligence as an instrument for compensating for or reducing road accidents in Nigeria; while the amount of damages awarded in some East African personal injuries actions, like the Mercedes Benz, contrasts sharply with the general living standards of the vast majority of the local population. Nevertheless the distinction between libel and slander, and between aggravated and punitive damages, and even some survivals from the Year Books have found their way into the law reports and treatises of some African jurisdictions. The elegant generalities of civilian doctrines of extra-contractual obligation seem, not surprisingly, to have made the transition to warmer climates more smoothly.
Circulars of the Sharī'a Courts in the Sudan (Manshūrāt el-Mahākim el-Sharī'a fi Sūdān) 1902–1979
Authors: Fluehr-Lobban Carolyn
Published: July 2009

An excellent documentation of the twentieth century history of the Sharī'a in Sudan is contained within the Judicial Circulars which have been issued from the office of the Grand Qadi from 1902–1979. During the colonial period and in the post-independence period the Circulars provided a unique means for modifying the adapting Sharī'a law in the Sudan, drawing on opinions of the Hanafī and Mālikī schools of juristic interpretation.

These Circulars and Memoranda are, in fact, basic to an understanding of the practice and application of the Sharī'a law in the Sudan. It is with these Circulars that I began my study of Sharī'a law and it is because of their importance that they were translated for my own work and in the hope that they may shortly be offered to students of the law of the Sudan who lack proficiency in the Arabic language.
The Origins of Forest Law and Policy in Ghana during the Colonial Period
Authors: Agbosu L. K.
Published: July 2009

John Whittow in a recent book observes that droughts, unlike an earthquake, a tsunami or an avalanche do not suddenly appear in a dramatic fashion hitting the newspaper headlines of an unsuspecting world. Drought, he says, is slow and insidious, a creeping death which gradually paralyses entire nations and changes the course of history.

That is how it seems Ghana was taken unawares by the recent prolonged droughts that have been affecting the country since the early part of 1982. Until then, people in Ghana had taken for granted constant water supplies, uninterrupted supply of electricity and other energy resources, principally from the Volta hydroelectric dam—the largest man-made lake in the world—feeling secure in the mistaken belief that drought comes only to the geographically arid or semi-arid parts of the world.
The Development and Reform of the Law in Kenya
Authors: Cotran Eugene
Published: July 2009

The purpose of this article is to trace the development of some aspects of the law of Kenya, commencing with the colonial period (Part I) and then considering the reforms in the post-independence era (Part II). Part III deals with the setting up of the Law Reform Commission in 1982 and considers some of the subjects which it might deal with.
OPPORTUNITY FOR NATURAL SELECTION AMONG THE INDIAN POPULATION: SECULAR TREND, COVARIATES AND IMPLICATIONS
Authors: GAUTAM RAJESH K.
Published: July 2009

Crow's index is widely used for indirect quantitative estimation of natural selection using birth and death rates. The present investigation is based on 179 studies among 144 different endogamous communities belonging to nineteen states and six geographical regions of India, categorized into six social groups. These studies appeared in 33 different years over six decades (1956 to 2007). The secular trend in Crow's index (It) and its mortality and fertility components (Im and If) shows a gradual decline in It and radical shift in the relative contributions of Im and If. Before 1990 the opportunity for natural selection was mainly determined by differential pre-reproductive mortality (Im), whereas after 1990 it has been determined by differential fertility (If). To find out the covariates of It, Im and If sixteen socio-demographic variables were considered, and nine were found to be significantly correlated with It: total dependency ratio, decadal growth rate 1991–2001, young age dependency ratio, crude death rate, total fertility rate, child mortality rate, under-5 mortality rate, old age dependency ratio and decadal growth rate 1981–1991. On the basis of multivariate stepwise regression analysis, female literacy emerged as one of the most important predictors of It. The declining trend of It, Im and If shows that the Indian population is passing through the demographic transition.
Pharmacological action of tick saliva upon haemostasis and the neutralization ability of sera from repeatedly infested hosts
Authors: RECK J. , BERGER M. , MARKS F. S. , ZINGALI R. B. , CANAL C. W. , FERREIRA C. A. S. , GUIMARÃES J. A. , TERMIGNONI C.
Published: July 2009

Ticks are blood-feeding arthropods widely distributed in the world and vectors of several diseases. As haematophagy demands evasion strategies and repeatedly infested hosts develop protective immune responses, we investigated the mechanisms of theRhipicephalus (Boophilus) microplussaliva anti-haemostatic activity and the possible relationship between the acquired natural anti-tick host resistance and anti-haemostatic action. For this purpose, we studied the effects ofR. microplussaliva on different pathways of haemostasis and tested whether repeated infested bovine sera (RIBS) are able to abolish salivary anti-haemostatic activities.R. microplussaliva (i) displays inhibitory activity upon collagen-induced platelet aggregation; (ii) inhibits the induction of endothelial pro-coagulant state; and (iii) reduces thrombogenesisin vivo. RIBS were shown to be able to partially block the delay of coagulation and the anti-thrombotic effect of saliva, and to totally abolish the modulation of endothelium activation. Conversely, RIBS has no effect on the inhibition of platelet aggregation. These results show, for the first time, the neutralization ability of sera from acquired resistance hosts against tick anti-haemostatics. Moreover, this is the first report of a haematophagous parasite able to modulate endothelial cell pro-coagulant state, and addresses the presence of anti-platelet and anti-thrombotic activity inR. microplussaliva.
The advantage of errorless learning for the acquisition of new concepts' labels in alcoholics
Authors: Pitel A. L. , Perruchet P. , Vabret F. , Desgranges B. , Eustache F. , Beaunieux H.
Published: July 2009

Background

Previous findings revealed that the acquisition of new semantic concepts' labels was impaired in uncomplicated alcoholic patients. The use of errorless learning may therefore allow them to improve learning performance. However, the flexibility of the new knowledge and the memory processes involved in errorless learning remain unclear.

Method

New concepts' labels acquisition was examined in 15 alcoholic patients and 15 control participants in an errorless learning condition compared with 19 alcoholic patients and 19 control subjects in a trial-and-error learning condition. The flexibility of the new information was evaluated using different photographs from those used in the learning sessions but representing the same concepts. All of the participants carried out an additional explicit memory task and an implicit memory task was also performed by subjects in the errorless learning condition.

Results

The alcoholic group in the errorless condition differed significantly from the alcoholic group in the trial-and-error condition but did not differ from the two control groups. There was no significant difference between results in the learning test and the flexibility task. Finally, in the alcoholic group, the naming score in the learning test was correlated with the explicit memory score but not with the implicit memory score.

Conclusions

Using errorless learning, alcoholics improved their abilities to learn new concepts' labels. Moreover, new knowledge acquired with errorless learning was flexible. The errorless learning advantage may rely on explicit rather than implicit memory processes in these alcohol-dependent patients presenting only mild to moderate deficits of explicit memory capacities.
Paternal and maternal ages at conception and risk of bipolar affective disorder in their offspring
Authors: Menezes P. R. , Lewis G. , Rasmussen F. , Zammit S. , Sipos A. , Harrison G. L. , Tynelius P. , Gunnell D.
Published: July 2009

Background

A consistent association between paternal age and their offspring's risk of schizophrenia has been observed, with no independent association with maternal age. The relationship of paternal and maternal ages with risk of bipolar affective disorders (BPAD) in the offspring is less clear. The present study aimed at testing the hypothesis that paternal age is associated with their offspring's risk of BPAD, whereas maternal age is not.

Method

This population-based cohort study was conducted with individuals born in Sweden during 1973–1980 and still resident there at age 16 years. Outcome was first hospital admission with a diagnosis of BPAD. Hazard ratios (HRs) were calculated using Cox's proportional hazard regression.

Results

After adjustment for all potential confounding variables except maternal age, the HR for risk of BPAD for each 10-year increase in paternal age was 1.28 [95% confidence interval (CI) 1.11–1.48], but this fell to 1.20 (95% CI 0.97–1.48) after adjusting for maternal age. A similar result was found for maternal age and risk of BPAD [HR 1.30 (95% CI 1.08–1.56) before adjustment for paternal age, HR 1.12 (95% CI 0.86–1.45) after adjustment]. The HR associated with having either parent aged 30 years or over was 1.26 (95% CI 1.01–1.57) and it was 1.45 (95% CI 1.16–1.81) if both parents were >30 years.

Conclusions

Unlike schizophrenia, the risk of BPAD seems to be associated with both paternal and maternal ages.
GEOFFREY POOLE AT 60: A TRIBUTE
Authors: Ertan Deniz
Published: July 2009

Friends, pupils and ex-colleagues of Geoffrey Poole (I write as all three) find it difficult to believe that this year witnesses his sixtieth birthday. In the past 40 years, he has consolidated his aesthetic position and career as a British composer of multifarious interests and distinctive personality. This article is a testament to his compositional integrity, staying power, humanity and humility. It is necessarily provisional, because each new work by Poole is a fresh beginning, expanding further outwards but also going deeper within, contributing to Western art music's capacity for regeneration and self-adaptation.
‘WHAT REALLY MAKES THE HEART SING’: DAVID JOHNSON IN INTERVIEW
Authors: Snedden Ian
Published: July 2009

Editorial Note: Just after the following interview had been edited for inclusion in the present issue of Tempo, we were saddened to learn of the sudden death of David Johnson at his home in Edinburgh on about 30 March, aged 66. He had been an occasional reviewer of Scottish musical events for Tempo. The projects mentioned in the interview were destined to remain unfulfilled, but his substantial legacy of compositions and scholarship had made a distinct and independent-minded contribution to the Scottish musical scene.
Algebra of programming in Agda: Dependent types for relational program derivation
Authors: MU SHIN-CHENG , KO HSIANG-SHANG , JANSSON PATRIK
Published: July 2009

Relational program derivation is the technique of stepwise refining a relational specification to a program by algebraic rules. The program thus obtained is correct by construction. Meanwhile, dependent type theory is rich enough to express various correctness properties to be verified by the type checker. We have developed a library, AoPA (Algebra of Programming in Agda), to encode relational derivations in the dependently typed programming language Agda. A program is coupled with an algebraic derivation whose correctness is guaranteed by the type system. Two non-trivial examples are presented: an optimisation problem and a derivation of quicksort in which well-founded recursion is used to model terminating hylomorphisms in a language with inductive types.
Subconvexity bounds for automorphicL-functions
Authors: Diaconu A. , Garrett P.
Published: July 2009

We break the convexity bound in thet-aspect forL-functions attached to cusp formsffor GL2(k) over arbitrary number fieldsk. The argument uses asymptotics with error term with a power saving, for second integral moments over spectral families of twistsL(s,f⊗χ) by Grossencharacters χ, from our previous paper on integral moments.
Morphological and compositional changes in the skeletons of new coral recruits reared in acidified seawater: Insights into the biomineralization response to ocean acidification
Authors: Cohen Anne L. , McCorkle Daniel C. , de Putron Samantha , Gaetani Glenn A. , Rose Kathryn A.
Published: July 2009

We reared primary polyps (new recruits) of the common Atlantic golf ball coral Favia fragum for 8 days at 25°C in seawater with aragonite saturation states ranging from ambient (Ω = 3.71) to strongly undersaturated (Ω = 0.22). Aragonite was accreted by all corals, even those reared in strongly undersaturated seawater. However, significant delays, in both the initiation of calcification and subsequent growth of the primary corallite, occurred in corals reared in treatment tanks relative to those grown at ambient conditions. In addition, we observed progressive changes in the size, shape, orientation, and composition of the aragonite crystals used to build the skeleton. With increasing acidification, densely packed bundles of fine aragonite needles gave way to a disordered aggregate of highly faceted rhombs. The Sr/Ca ratios of the crystals, measured by SIMS ion microprobe, increased by 13%, and Mg/Ca ratios decreased by 45%. By comparing these variations in elemental ratios with results from Rayleigh fractionation calculations, we show that the observed changes in crystal morphology and composition are consistent with a >80% decrease in the amount of aragonite precipitated by the corals from each “batch” of calcifying fluid. This suggests that the saturation state of fluid within the isolated calcifying compartment, while maintained by the coral at levels well above that of the external seawater, decreased systematically and significantly as the saturation state of the external seawater decreased. The inability of the corals in acidified treatments to achieve the levels of calcifying fluid supersaturation that drive rapid crystal growth could reflect a limit in the amount of energy available for the proton pumping required for calcification. If so, then the future impact of ocean acidification on tropical coral ecosystems may depend on the ability of individuals or species to overcome this limitation and achieve the levels of calcifying fluid supersaturation required to ensure rapid growth.
Differential Effect of Weight Loss on Adipocyte Size Subfractions in Patients With Type 2 Diabetes
Authors: Pasarica Magdalena , Tchoukalova Yourka D. , Heilbronn Leonie K. , Fang Xiaobing , Albu Jeanine B. , Kelley David E. , Smith Smith R. , Ravussin Eric ,   The Look AHEAD Adipose Research Group
Published: July 2009

The size of adipocytes influences their function suggesting a differential responsiveness to intervention. We hypothesized that weight loss in patients with type 2 diabetes mellitus (T2DM) predominantly decreases the size of large and very‐large adipocyte subfractions in parallel with beneficial changes in serum adipokines and improved insulin sensitivity. A total of 44 volunteers from the Look Action for Health in Diabetes trial, who lost weight after 1‐year of intense lifestyle intervention, were included. Insulin sensitivity (hyperinsulinemic–euglycemic clamp), size of subcutaneous abdominal adipocytes (osmium fixation), and selected serum adipokines were measured. A 13% weight loss was accompanied by 46% improvement in insulin sensitivity (increased glucose disposal rate from 5.9 ± 2.2 to 8.6 ± 2.7 mg/min/kg fat‐free mass, P < 0.05) in parallel with a 36% increase in plasma adiponectin concentration (6.1 ± 3.1 to 8.3 ± 3.9 µg/ml, P < 0.05], but no changes in the proinflammatory cytokines interleukin‐6 and tumor necrosis factor‐α. Change in adiponectin correlated with changes in glucose disposal rate (r = 0.34, P < 0.05). Mean adipocyte size decreased (0.84 ± 0.25 to 0.64 ± 0.23 µl, P < 0.05), mainly due to changes in the large adipocyte subfraction (size 0.75–0.44 µl, relative number 19–26%; P < 0.05). Our data suggest that change in the large adipocyte subfraction may contribute to the improvement in insulin sensitivity via an increase in serum adiponectin. Such a relationship, which does not imply cause and effect, could not be obtained by measuring only mean adipocyte size. These data provide support for the measures of adipocyte size distribution in concert with in vitro adipokine secretion and lipolysis in future studies.
Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications
Authors: Musselman Catherine A. , Mansfield Robyn E. , Garske Adam L. , Davrazou Foteini , Kwan Ann H. , Oliver Samuel S. , O'Leary Heather , Denu John M. , Mackay Joel P. , Kutateladze Tatiana G.
Published: July 2009

CHD4 (chromodomain helicase DNA-binding protein 4) ATPase is a major subunit of the repressive NuRD (nucleosome remodelling and deacetylase) complex, which is involved in transcriptional regulation and development. CHD4 contains two PHD (plant homeodomain) fingers of unknown function. Here we show that the second PHD finger (PHD2) of CHD4 recognizes the N-terminus of histone H3 and that this interaction is facilitated by acetylation or methylation of Lys9 (H3K9ac and H3K9me respectively) but is inhibited by methylation of Lys4 (H3K4me) or acetylation of Ala1 (H3A1ac). An 18 μM binding affinity toward unmodified H3 rises to 0.6 μM for H3K9ac and to 0.9 μM for H3K9me3, whereas it drops to 2.0 mM for H3K4me3, as measured by tryptophan fluorescence and NMR. A peptide library screen further shows that phosphorylation of Thr3, Thr6 or Ser10 abolishes this interaction. A model of the PHD2–H3 complex, generated using a combination of NMR, data-driven docking and mutagenesis data, reveals an elongated site on the PHD2 surface where the H3 peptide is bound. Together our findings suggest that the PHD2 finger plays a role in targeting of the CHD4/NuRD complex to chromatin.
Exploitation of plant and archaeal viruses in bionanotechnology
Authors: Evans David J.
Published: July 2009

CPMV (cowpea mosaic virus), a plant virus, is a naturally occurring sphere-like nanoparticle, and is used as a synthon and/or template in bionanoscience. The virions formed by CPMV can be regarded as programmable nanobuilding blocks with a diameter of ∼30 nm. A range of molecules have been attached to this viral nanoscaffold, yielding stable nanoparticles that display multiple copies of the desired molecule. It has been shown that, in addition to surface amine groups, surface carboxy groups are also addressable, and a procedure has been developed that enables introduction of reactive thiols at the virion surface that avoids virus aggregation. Furthermore, the virions can be functionalized to form electroactive nanoparticles. Methods for the construction of arrays and multilayers, using a layer-by-layer approach, have been established. As proof of concept, for example, CPMV particles have been immobilized on surfaces and arranged in defined layers. Engineered variants of CPMV can be used as templates for mineralization with, for example, silica to give monodisperse robust silica nanoparticles of ∼32 nm. SIRV2 (Sulfolobus islandicus rod-shaped virus 2), is a robust archaeal virus, resistant to high temperature and low pH. SIRV2 can act as a template for site-selective and spatially controlled chemical modification. Both the ends and the body of the virus, or the ends only, can be chemically addressed; SIRV2 can be regarded as a structurally unique nanobuilding block.
Electrodes modified with lipid membranes to study quinone oxidoreductases
Authors: Weiss Sophie A. , Jeuken Lars J.C.
Published: July 2009

Quinone oxidoreductases are a class of membrane enzymes that catalyse the oxidation or reduction of membrane-bound quinols/quinones. The conversion of quinone/quinol by these enzymes is difficult to study because of the hydrophobic nature of the enzymes and their substrates. We describe some biochemical properties of quinones and quinone oxidoreductases and then look in more detail at two model membranes that can be used to study quinone oxidoreductases in a native-like membrane environment with their native lipophilic quinone substrates. The results obtained with these model membranes are compared with classical enzyme assays that use water-soluble quinone analogues.
The fine details of evolution
Authors: Laskowski Roman A. , Thornton Janet M. , Sternberg Michael J.E.
Published: July 2009

Charles Darwin's theory of evolution was based on studies of biology at the species level. In the time since his death, studies at the molecular level have confirmed his ideas about the kinship of all life on Earth and have provided a wealth of detail about the evolutionary relationships between different species and a deeper understanding of the finer workings of natural selection. We now have a wealth of data, including the genome sequences of a wide range of organisms, an even larger number of protein sequences, a significant knowledge of the three-dimensional structures of proteins, DNA and other biological molecules, and a huge body of information about the operation of these molecules as systems in the molecular machinery of all living things. This issue of Biochemical Society Transactions contains papers from oral presentations given at a Biochemical Society Focused Meeting to commemorate the 200th Anniversary of Charles Darwin's birth, held on 26–27 January 2009 at the Wellcome Trust Conference Centre, Cambridge. The talks reported on some of the insights into evolution which have been obtained from the study of protein sequences, structures and systems.
Structural and functional restraints in the evolution of protein families and superfamilies
Authors: Gong Sungsam , Worth Catherine L. , Bickerton G. Richard J. , Lee Semin , Tanramluk Duangrudee , Blundell Tom L.
Published: July 2009

Divergent evolution of proteins reflects both selectively advantageous and neutral amino acid substitutions. In the present article, we examine restraints on sequence, which arise from selectively advantageous roles for structure and function and which lead to the conservation of local sequences and structures in families and superfamilies. We analyse structurally aligned members of protein families and superfamilies in order to investigate the importance of the local structural environment of amino acid residues in the acceptance of amino acid substitutions during protein evolution. We show that solvent accessibility is the most important determinant, followed by the existence of hydrogen bonds from the side-chain to main-chain functions and the nature of the element of secondary structure to which the amino acid contributes. Polar side chains whose hydrogen-bonding potential is satisfied tend to be more conserved than their unsatisfied or non-hydrogen-bonded counterparts, and buried and satisfied polar residues tend to be significantly more conserved than buried hydrophobic residues. Finally, we discuss the importance of functional restraints in the form of interactions of proteins with other macromolecules in assemblies or with substrates, ligands or allosteric regulators. We show that residues involved in such functional interactions are significantly more conserved and have differing amino acid substitution patterns.
Multi-substrate–activity space and quasi-species in enzyme evolution: Ohno's dilemma, promiscuity and functional orthogonality
Authors: Mannervik Bengt , Runarsdottir Arna , Kurtovic Sanela
Published: July 2009

A functional enzyme displays activity with at least one substrate and can be represented by a vector in substrate–activity space. Many enzymes, including GSTs (glutathione transferases), are promiscuous in the sense that they act on alternative substrates, and the corresponding vectors operate in multidimensional space. The direction of the vector is governed by the relative activities of the diverse substrates. Stochastic mutations of already existing enzymes generate populations of variants, and clusters of functionally similar mutants can serve as parents for subsequent generations of enzymes. The proper evolving unit is a functional quasi-species, which may not be identical with the ‘best’ variant in its generation. The manifestation of the quasi-species is dependent on the substrate matrix used to explore catalytic activities. Multivariate analysis is an approach to identifying quasi-species and to investigate evolutionary trajectories in the directed evolution of enzymes for novel functions.
Evolution of spectrin function in cytoskeletal and membrane networks
Authors: Baines Anthony J.
Published: July 2009

Spectrin is a cytoskeletal protein thought to have descended from an α-actinin-like ancestor. It emerged during evolution of animals to promote integration of cells into tissues by assembling signalling and cell adhesion complexes, by enhancing the mechanical stability of membranes and by promoting assembly of specialized membrane domains. Spectrin functions as an (αβ[H])2 tetramer that cross-links transmembrane proteins, membrane lipids and the actin cytoskeleton, either directly or via adaptor proteins such as ankyrin and 4.1. In the present paper, I review recent findings on the origins and adaptations in this system. (i) The genome of the choanoflagellate Monosiga brevicollis encodes α-, β- and βHeavy-spectrin, indicating that spectrins evolved in the immediate unicellular precursors of animals. (ii) Ankyrin and 4.1 are not encoded in that genome, indicating that spectrin gained function during subsequent animal evolution. (iii) Protein 4.1 gained a spectrin-binding activity in the evolution of vertebrates. (iv) Interaction of chicken or mammal β-spectrin with PtdInsP2 can be regulated by differential mRNA splicing, which can eliminate the PH (pleckstrin homology) domain in βI- or βII-spectrins; in the case of mammalian βII-spectrin, the alternative C-terminal region encodes a phosphorylation site that regulates interaction with α-spectrin. (v) In mammalian evolution, the single pre-existing α-spectrin gene was duplicated, and one of the resulting pair (αI) neo-functionalized for rapid make-and-break of tetramers. I hypothesize that the elasticity of mammalian non-nucleated erythrocytes depends on the dynamic rearrangement of spectrin dimers/tetramers under the shearing forces experienced in circulation.
Overcoming steroid unresponsiveness in airways disease
Authors: Adcock Ian M. , Chou Pai-Chien , Durham Andrew , Ford Paul
Published: July 2009

Most of the patients with asthma are found to be successfully treated with conventional therapy. However, there are a small proportion of asthmatic patients who fail to respond to corticosteroids even at high doses or with supplementary therapy. In addition, even high doses of corticosteroids have a minimal effect on the inexorable decline in lung function in COPD (chronic obstructive pulmonary disease) and only a small effect in reducing exacerbations. Corticosteroid-insensitivity therefore presents a profound management problem. Corticosteroids act through a cytosolic receptor [GR (glucocorticoid receptor)], which is activated and translocates to the nucleus. Once in the nucleus, it either binds to DNA and switches on the expression of anti-inflammatory genes or represses the activity of distinct signalling pathways such as NF-κB (nuclear factor κB), AP-1 (activator protein-1) or MAPKs (mitogen-activated protein kinases). This latter step requires the recruitment of co-repressor molecules. A failure to respond to corticosteroids may therefore result from lack of binding to GR, reduced GR expression, lack of co-repressor activity or enhanced activation of inflammatory pathways. These events can be modulated by oxidative stress or high levels of inflammatory cytokines, which may lead to a reduced clinical outcome. Understanding the molecular mechanisms of GR action, and inaction, may lead to the development of new anti-inflammatory drugs or reverse the relative corticosteroid-insensitivity that is characteristic of these diseases.
Array of hope: expression profiling identifies disease biomarkers and mechanism
Authors: Bhattacharya Soumyaroop , Mariani Thomas J.
Published: July 2009

High-throughput, genome-wide analytical technologies are now commonly used in all fields of medical research. The most commonly applied of these technologies, gene expression microarrays, have been shown to be both accurate and precise when properly implemented. For over a decade, microarrays have provided novel insight into many complex human diseases. Microarray-based discovery can be classified into three components, biomarker detection, disease (sub)classification and identification of causal mechanism, in order of accomplishment. Within the respiratory system, the application of microarrays has achieved significant success in all components, particularly with respect to lung cancer. Numerous studies over the last half-decade have applied this technology to the characterization of non-malignant respiratory diseases, animal models of respiratory disease and normal developmental processes. Studies of obstructive lung diseases by many groups, including our own, have yielded not only disease biomarkers, but also some novel putative pathogenic mechanisms. We have successfully used an integrative genomics approach, combining microarray analysis with human genetics, to identify susceptibility genes for COPD (chronic obstructive pulmonary disease). Interestingly, we find that the assessment of quantitative phenotypic variables enhances gene discovery. Our studies contribute to the identification of obstructive lung disease biomarkers, provide data associated with disease phenotypes and support the use of an integrated approach to move beyond marker identification to mechanism discovery.
IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response
Authors: Sureshbabu Angara , Okajima Hiroshi , Yamanaka Daisuke , Shastri Surya , Tonner Elizabeth , Rae Colin , Szymanowska Malgorzata , Shand John H. , Takahashi Shin-Ichiro , Beattie James , Allan Gordon J. , Flint David J.
Published: July 2009

Fibrosis involves activation of fibroblasts, increased production of collagen and fibronectin and transdifferentiation into contractile myofibroblasts. The process resembles aspects of wound-healing but remains unresolved and can be life-threatening when manifest in the kidneys, lungs and liver, in particular. The causes are largely unknown, but recent suggestions that repetitive micro-injury results in the eventual failure of epithelial cell repair due to replicative senescence are gaining favour. This is consistent with the onset of fibrotic diseases in middle age. Because epithelial injury often involves blood loss, inflammatory responses associated with the fibrotic response have been considered as therapeutic targets. However, this has proved largely unsuccessful and focus is now switching to earlier events in the process. These include EMT (epithelial–mesenchymal transition) and fibroblast activation in the absence of inflammation. TGFβ1 (transforming growth factor-β1) induces both EMT and fibroblast activation and is considered to be a major pro-fibrotic factor. Recently, IGFBP-5 [IGF (insulin-like growth factor)-binding protein-5] has also been shown to induce similar effects on TGFβ1, and is strongly implicated in the process of senescence. It also stimulates migration of peripheral blood mononuclear cells, implicating it in the inflammatory response. In this paper, we examine the evidence for a role of IGFBP-5 in fibrosis and highlight its structural relationship with other matrix proteins and growth factors also implicated in tissue remodelling.
53BP1: function and mechanisms of focal recruitment
Authors: FitzGerald Jennifer E. , Grenon Muriel , Lowndes Noel F.
Published: July 2009

53BP1 (p53-binding protein 1) is classified as a mediator/adaptor of the DNA-damage response, and is recruited to nuclear structures termed foci following genotoxic insult. In the present paper, we review the functions of 53BP1 in DNA-damage checkpoint activation and DNA repair, and the mechanisms of its recruitment and activation following DNA damage. We focus in particular on the role of covalent histone modifications in this process.
Development of a novel mass spectrometric technique for studying DNA damage
Authors: Merrigan Tony L. , Hunniford C. Adam , Timson David J. , Catney Martin , McCullough Robert W.
Published: July 2009

An experimental system, based upon UV and IR laser desorption, has been constructed to enable the production and characterization of neutral biomolecular targets. These targets are to be used for interaction experiments investigating radiation-induced damage to DNA. The viability of the laser-desorption techniques of MALDI (matrix-assisted laser-desorption ionization), SALDI (surface-assisted laser-desorption ionization) and DIOS (desorption/ionization on silicon), for production of these gas targets is discussed in the present paper. Fluorescent dye tagging and LIF (laser-induced fluorescence) imaging has been used to characterize the biomolecular plumes, revealing their spatial density profiles and temporal evolution.
An experimental study on the pressure dependence of viscosity in silicate melts
Authors: Del Gaudio Piero , Behrens Harald
Published: July 2009

The effect of pressure on melt viscosity was investigated for five compositions along the join An(CaAl2Si2O8)–Di(CaMgSi2O6) and four alkali silicates containing lithium, sodium, and potassium in constant ratio of ∼1:1:1, but alkali-silica ratios are varying. The experiments were performed in an internally heated gas pressure vessel at pressures from 50 to 400 MPa in the viscosity range from 108 to 1011.5 Pa⋅s using parallel plate viscometry. The polymerized An composition shows a negative pressure dependence of viscosity while the other, more depolymerized compositions of the join An–Di have neutral to positive pressure coefficients. The alkali silicates display neutral to slightly positive pressure coefficients for melt viscosity. These findings in the high viscosity range of 108–1011 Pa⋅s, where pressure appears to be more efficient than in low viscous melts at high temperature, are consistent with previous results on the viscosity of polymerized to depolymerized melts in the system NaAlSi3O8–CaMgSi2O6 by Behrens and Schulze [H. Behrens and F. Schulze, Am. Mineral. 88, 1351 (2003)]. Thus we confirm that the sign of the pressure coefficient for viscosity is mainly related to the degree of melt polymerization in silicate and aluminosilicate melts.
Influence of the parallel nonlinearity on zonal flows and heat transport in global gyrokinetic particle-in-cell simulations
Authors: Jolliet S. , McMillan B. F. , Vernay T. , Villard L. , Hatzky R. , Bottino A. , Angelino P.
Published: July 2009

In this paper, the influence of the parallel nonlinearity on zonal flows and heat transport in global particle-in-cell ion-temperature-gradient simulations is studied. Although this term is in theory orders of magnitude smaller than the others, several authors [L. Villard, P. Angelino, A. Bottino et al., Plasma Phys. Contr. Fusion 46, B51 (2004); L. Villard, S. J. Allfrey, A. Bottino et al., Nucl. Fusion 44, 172 (2004); J. C. Kniep, J. N. G. Leboeuf, and V. C. Decyck, Comput. Phys. Commun. 164, 98 (2004); J. Candy, R. E. Waltz, S. E. Parker et al., Phys. Plasmas 13, 074501 (2006)] found different results on its role. The study is performed using the global gyrokinetic particle-in-cell codes TORB (theta-pinch) [R. Hatzky, T. M. Tran, A. Könies et al., Phys. Plasmas 9, 898 (2002)] and ORB5 (tokamak geometry) [S. Jolliet, A. Bottino, P. Angelino et al., Comput. Phys. Commun. 177, 409 (2007)]. In particular, it is demonstrated that the parallel nonlinearity, while important for energy conservation, affects the zonal electric field only if the simulation is noise dominated. When a proper convergence is reached, the influence of parallel nonlinearity on the zonal electric field, if any, is shown to be small for both the cases of decaying and driven turbulence.
Displacement current analysis of carrier behavior in pentacene field effect transistor with poly(vinylidene fluoride and tetrafluoroethylene) gate insulator
Authors: Yoshita Shuhei , Tamura Ryousuke , Taguchi Dai , Weis Martin , Lim Eunju , Manaka Takaaki , Iwamoto Mitsumasa
Published: July 2009

The carrier injection mechanism was investigated using a field effect transistor (FET) system with a ferroelectric gate insulator: poly(vinylidene fluoride and tetrafluoroethylene). The carrier injection and the turnover voltage of the spontaneous polarization were measured by application of ramp gate voltage with various sweep rates. Three peaks appeared in the gate current-gate voltage characteristics (Ig-Vg) because of the turnover of the spontaneous polarization and the long-range carrier motion of injected carriers. We accounted for the peaks generated and analyzed the Ig-Vg characteristics. For FETs with Al electrodes, the increase in the sweep rate caused a larger turnover voltage. For FETs with Au electrodes, the turnover voltage was constant. Results show that the difference of the injection property well accounted for these results.
Colloidal interactions in thermal and athermal polymer solutions: The Derjaguin approximation, and exact results for mono- and polydisperse ideal chains
Authors: Forsman Jan , Woodward Clifford E.
Published: July 2009

Polymer density functional theory is used to test the accuracy of the Derjaguin approximation in describing the interaction between two spherical colloidal particles immersed in a polymer solution. The density functional equations are solved numerically in a cylindrical geometry and thus a rigorous comparison is afforded, within the density functional framework. The density functional theory provides an exact (albeit numerical) treatment for ideal polymers. We investigate both nonadsorbing and telechelic chains, as well as consider the behavior of widely polydisperse samples (living chains). We make comparisons with the commonly used penetrable sphere models for polymers and are able to identify strengths and weaknesses in the latter. We find that the Derjaguin approximation performs surprisingly well, even for particle sizes that are comparable to the radius of gyration of the polymers.
Intermediate vibronic coupling in sexithiophene single crystals. II. Three-particle contributions
Authors: Stradomska Anna , Petelenz Piotr
Published: July 2009

Validity of the approach recently proposed to describe intermediate-to-strong linear vibronic coupling in an infinite molecular crystal is tested by assessing the importance of the (previously neglected) three-particle excitations. The Hamiltonian, denoted in the Lang–Firsov representation and including the three-particle terms, is numerically diagonalized to yield the eigenstates and ultimately the absorption spectrum. In addition, the wave functions are analyzed to probe the size and nature of the phonon cloud surrounding the exciton. The results demonstrate a marginal role of three-particle excitations but highlight the importance of a sufficiently extended vibrational basis to adequately describe the high-energy levels.
Nonlinear alternating electric field dipolophoresis of spherical nanoparticles
Authors: Miloh Touvia
Published: July 2009

We consider the nonlinear electrokinetic problem of a freely suspended conducting (infinitely polarized) spherical micro- or nanosize particle surrounded by an unbounded electrolyte solution. The uncharged particle is exposed to an alternating (ac), nonuniform, and axisymmetric ambient electric field. As a result, the particle acquires a dipolophoretic (DIP) mobility of magnitude, which is quadratic in the amplitude of the applied electric field. The resulting phoretic velocity is driven by two independent nonlinear mechanisms. One is the common dielectrophoretic effect, whereby the nonuniform field exerts an electrostatic force on the image multipole singularity system within the particle. The other is the so-called “induced-charge electrophoresis” resulting from the action of the electric field on the excess charge around the particle induced in the diffused layer by the field itself. Both effects are quadratic in the amplitudes of the electric field and depend on the forcing frequency and on the dimensionless Debye screening length scale. It is demonstrated in the sequel that the two generally act in opposite directions which may result in mutual cancellation. Under the assumptions of a “weak” electric field and the neglect of surface conductance, we present a concise analysis of the resulting nonlinear streaming (dc) velocity (averaged over a period) for a spherical metalic particle that is exposed to a time-harmonic oscillating (ac) electric field. The analysis of this fundamental nonlinear DIP problem is provided for arbitrary forcing frequencies and for any Debye thickness. Numerical simulations are given for the case of a “two-mode” interaction consisting of a uniform-gradient electric field combined with a uniform field, where the two modes are either “in” or “out” of phase.
Collisional phase shifts between two colliding solitary waves in a three-dimensional magnetized dusty plasma
Authors: Liang Gui-zhen , Han Jiu-ning , Lin Mai-mai , Wei Ju-na , Duan Wen-shan
Published: July 2009

Interaction of dust acoustic solitary waves in two different directions in a three-dimensional dusty plasma is investigated. The phase shifts after collision of two solitary waves with arbitrary angle in a three-dimensional magnetized dusty plasma are studied. By using the extended Poincaré–Lighthill–Kuo perturbation method, two Korteweg–de Vries equations for nonlinear waves in both ξ and η directions are obtained. The effects of the collision angle θ, the ratio of dust temperature to ion temperature σ, the ratio of ion temperature to electron temperature β, the ratio of effective temperature to ion temperature s, and the ratio of the number densities of both ion and electron to the density of dust particles μ and ν on the phase shifts are discussed.