bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Relational Marketplaces’ and the Rise of Boutiques in London's Corporate Finance Industry
Authors: Hall Sarah
Published: July 2007

In this paper I examine the rise of corporate finance boutiques in London's financial district from the early 2000s onwards. These small firms, typically employing no more than 25 people, specialise in a single corporate finance client sector (such as telecommunications or the media). It is argued that the growth of these boutiques is best understood with reference to the changing circumstances faced by London's established investment banks. Boutiques grew both in number and in size whilst well-known investment banking brands suffered significant decreases in profit margins, and redundancies were made across the financial services sector more widely. Two related theoretical perspectives are deployed to understand the growth of corporate finance boutiques in London within a ‘relational marketplace’. First, the concept of a marketplace is developed by spatialising recent work in new economic sociology on markets. Second, a relational perspective is used to conceptualise the coconstitutive networks that exist between corporate finance boutiques and investment banks within this marketplace.
“The Rigours of an Arctic Experiment”: The Precarious Authority of Field Practices in the Canadian High Arctic, 1958–1970
Authors: Powell Richard C
Published: July 2007

The author examines the development of the notion of the field experiment in High Arctic environmental sciences during the period 1958–70. After a discussion of the philosophy and sociology of experiment, the author considers a set of field practices conducted under the auspices of the Canadian Government's Polar Continental Shelf Project. Drawing on archival and oral historical research, he argues that field scientists had to deal with a number of logistical, corporeal, and epistemic difficulties in the High Arctic. It is demonstrated that these obstacles hindered attempts to develop a scientific literature based upon experimental practices during fieldwork. In doing so, the author attempts to set new agendas for historical geographers of science around the analysis of the geographical sciences, whilst also contributing to discussions about the epistemic status of variegated field practices.
Symptomatic Acts, Experimental Embodiments: Theatres of Scientific Protest in Interwar Germany
Authors: Vasudevan Alexander
Published: July 2007

The author builds on recent geographical approaches to the investigation of scientific experimentation. While a number of studies have explored the various sites of scientific practice and the role of space in the constitution of experimental matters of fact, far less attention has been directed toward the cultural geographies of experimental science and the extrascientific zones in which modes of experimental practice were themselves developed and contested. Drawing on the reception of professional psychiatry in interwar Berlin (1919–1933), the author traces an alternative set of ‘experimental systems’ which seized on and countered the credibility of psychiatric expertise. The focus is on a series of modernist experiments in interwar Germany which actively reconfigured psychiatric science as a series of critical aesthetic interventions themselves tasked with performing ‘scientific experiments’. The paper is triangulated around three case studies, which chart the multiple traffickings between psychiatric experimentation and modernist art. The first revisits the traumatic reenactments of Berlin Dada in the broader context of mechanized war, rationalized work, and metropolitan life. The second explores the psychotechnical techniques that were crucial to the operations of Brechtian epic theatre, and the third case study explores the relationship between clinical therapy and modernist fiction as it came to characterize the work of Alfred Döblin during the 1920s. The paper concludes with further reflections on the significance of the ‘modern experimental turn’.
Using APSIM-soiltemp to simulate soil temperature in the podding zone of peanut
Authors: Chauhan Yash , Wright Graeme , Rachaputi Nageswara Rao , Krosch Stephen , Robertson Michael , Hargreaves John , Broome Alan
Published: July 2007

Measurement or accurate simulation of soil temperature is important for improved understanding and management of peanuts (Arachis hypogaea L.), due to their geocarpic habit. A module of the Agricultural Production Systems Simulator Model (APSIM), APSIM-soiltemp, which uses input of ambient temperature, rainfall and solar radiation in conjunction with other APSIM modules, was evaluated for its ability to simulate surface 5 cm soil temperature in 35 peanut on-farm trials conducted between 2001 and 2005 in the Burnett region (25°36′S to 26°41′S, 151°39′E to 151°53′E). Soil temperature simulated by the APSIM-soiltemp module, from 30 days after sowing until maturity, closely matched the measured values (R2 ≥ 0.80) in the first three seasons (2001–04). However, a slightly poorer relationship (R2 = 0.55) between the observed and the simulated temperatures was observed in 2004–05, when the crop was severely water stressed. Nevertheless, over all the four seasons, which were characterised by a range of ambient temperature, leaf area index, radiation and soil water, each of which was found to have significant effects on soil temperature, a close 1 : 1 relationship (R2 = 0.85) between measured and simulated soil temperatures was observed. Therefore, the pod zone soil temperature simulated by the module can be generally relied on in place of measured input of soil temperature in APSIM applications, such as quantifying climatic risk of aflatoxin accumulation.
Rapid decay of dolichos [Lablab purpureus (L.) Sweet] residue leads to loss of nitrogen benefit to succeeding maize (Zea mays L.)
Authors: Cheruiyot E. K. , Mwonga S. M. , Mumera L. M. , Macharia J. K. , Tabu I. M. , Ngugi J. G.
Published: July 2007

The traditional natural fallows are no longer practicable in sub-Saharan Africa and technologies to replace them are being popularised through management of short fallow systems. Dolichos [Lablab purpureus (L.) Sweet] is among the legumes used to improve such fallows and its residues are incorporated to improve yield of succeeding cereal. Two field studies were conducted to determine dolichos residue mineralisation schedule and response of maize to timing of the residue incorporation, to establish if the current residue incorporation practice maximises nutrient benefit to succeeding cereal. Dolichos residue was applied at 2 t/ha in litterbags, buried in the field at 15-cm depth and retrieved after 1, 2, 4, 8 and 16 weeks, and the remaining debris analysed for loss of weight, N, P and K. A parallel split-plot experiment was set up to determine response of maize to time of residue incorporation, with or without fertiliser nitrogen supplementation. The main plot treatments were nitrogen fertiliser applied at 0, 30 and 60 kg/ha at sixth fully opened leaf in maize. The subplot treatments were residue management regimes, which included four residue incorporation times of 2, 4, 6, and 8 weeks before sowing maize, residue removal off the field, residue mulched on surface and traditional weedy fallow. Results show rapid loss of N, with 50% being released within the first 2–4 weeks after burying. Residue incorporated at 2 and 4 weeks before sowing improved maize yield, while residue removal off-field reduced yield comparably with the traditional weedy fallow. However, there were no statistical differences among the timing of the dolichos residue incorporation. These results reflect poor synchrony of mineralised N and uptake by succeeding maize as currently practiced and suggest residue incorporation closer to sowing maize to benefit the cereal.
Coinoculation of chickpea with Rhizobium isolates from roots and nodules and phytohormone-producing Enterobacter strains
Authors: Mirza Babur Saeed , Mirza M. Sajjad , Bano Asghari , Malik Kauser A.
Published: July 2007

The aim of the present study was to isolate plant-beneficial bacteria (both Rhizobium and plant growth promoting rhizobacteria) from roots and nodules of chickpea (Cicer arietinum L.) and to study the effect of coinoculations on growth of two cultivars of chickpea. Four Rhizobium strains were obtained from roots and four from the nodules of field-grown chickpea cv. Parbat and identified on the basis of morphological characteristics, and biochemical and infectivity tests on the host seedlings. Only one type of nitrogen and carbon source utilisation pattern and DNA banding pattern of random amplified polymorphic DNA was observed in all isolates (Rn1, Rn2, Rn3, Rn4) from nodules, while two types of such patterns were detected among the isolates from roots. The isolate Rr1 from roots also exhibited a pattern identical to those of the isolates from nodules, whereas the remaining three isolates (Rr2, Rr3 and Rr4) from roots showed a different pattern. Two strains of plant growth-promoting rhizobacteria belonging to genus Enterobacter were also isolated from chickpea roots. All the Rhizobium strains and Enterobacter strains produced the plant growth hormones indole acetic acid and gibberellic acid in the growth medium. Effects of the bacterial isolates as single- or double-strain inocula were studied on two chickpea cultivars (NIFA 88 and Parbat) grown in sterilised soil. In cultivar NIFA 88, coinoculation of Rhizobium strain Rn1 with Enterobacter strain B resulted in maximum increase in plant biomass and nodulation, as compared with the control treatment (non-inoculated as well as inoculated with Rhizobium strain Rn1 only), whereas the combination of Rhizobium Rn1 with Enterobacter A was more efficient in growth promotion of chickpea cv. Parbat. In non-sterilised soil, the same combinations of the Rhizobium strain Rn1 with Enterobacter strains A and B were found to be the most effective inoculants for cvv. Parbat and NIFA 88, respectively. However, some negative effects on plant growth were also noted in cv. Parbat coinoculated with Rhizobium strain Rr2 and Enterobacter strain B.
A molecular mechanism directly linking E-cadherin adhesion to initiation of epithelial cell surface polarity
Authors: Nejsum Lene N. , Nelson W. James
Published: July 2007

Mechanisms involved in maintaining plasma membrane domains in fully polarized epithelial cells are known, but when and how directed protein sorting and trafficking occur to initiate cell surface polarity are not. We tested whether establishment of the basolateral membrane domain and E-cadherin–mediated epithelial cell–cell adhesion are mechanistically linked. We show that the basolateral membrane aquaporin (AQP)-3, but not the equivalent apical membrane AQP5, is delivered in post-Golgi structures directly to forming cell–cell contacts where it co-accumulates precisely with E-cadherin. Functional disruption of individual components of a putative lateral targeting patch (e.g., microtubules, the exocyst, and soluble N-ethylmaleimide–sensitive factor attachment protein receptors) did not inhibit cell–cell adhesion or colocalization of the other components with E-cadherin, but each blocked AQP3 delivery to forming cell–cell contacts. Thus, components of the lateral targeting patch localize independently of each other to cell–cell contacts but collectively function as a holocomplex to specify basolateral vesicle delivery to nascent cell–cell contacts and immediately initiate cell surface polarity.
The multifunctional protein p54nrb/PSF recruits the exonuclease XRN2 to facilitate pre-mRNA 3′ processing and transcription termination
Authors: Kaneko Syuzo , Rozenblatt-Rosen Orit , Meyerson Matthew , Manley James L.
Published: July 2007

Termination of RNA polymerase II transcription frequently requires a poly(A) signal and cleavage/polyadenylation factors. Recent work has shown that degradation of the downstream cleaved RNA by the exonuclease XRN2 promotes termination, but how XRN2 functions with 3′-processing factors to elicit termination remains unclear. Here we show that XRN2 physically associates with 3′-processing factors and accumulates at the 3′ end of a transcribed gene. In vitro 3′-processing assays show that XRN2 is necessary to degrade the downstream RNA, but is not required for 3′ cleavage. Significantly, degradation of the 3′-cleaved RNA was stimulated when coupled to cleavage. Unexpectedly, while investigating how XRN2 is recruited to the 3′-processing machinery, we found that XRN2 associates with p54nrb/NonO(p54)–protein-associated splicing factor (PSF), multifunctional proteins involved in several nuclear processes. Strikingly, p54 is also required for degradation of the 3′-cleaved RNA in vitro. p54 is present along the length of genes, and small interfering RNA (siRNA)-mediated knockdown leads to defects in XRN2 recruitment and termination. Together, our data indicate that p54nrb/PSF functions in recruitment of XRN2 to facilitate pre-mRNA 3′ processing and transcription termination.
Increased association of telomerase with short telomeres in yeast
Authors: Bianchi Alessandro , Shore David
Published: July 2007

Telomere function is mediated by the assembly of a protein complex on an array of telomeric DNA (TG) repeats synthesized by the telomerase enzyme. Telomerase action at chromosome ends is finely tuned by the telomeric complex so that a constant average number of repeats is maintained. This is achieved through a negative feedback process that is sensitive to TG tract length, but whose underlying mechanism is unknown. We show that short telomeres, which are preferential substrates for telomerase, display increased association with the enzyme in the S phase of the cell cycle, when telomerase acts. In addition, we provide support for a molecular mechanism by which this key step of telomerase recruitment is regulated by TG tract length.
Dependence of timing of mitotic events on the rate of protein synthesis and DNA replication in sea urchin early cleavages
Authors: Yamada K.
Published: July 2007

Abstract. To understand what processes affect the cell‐cycle timing of mitotic events in early cleavage cycles of sea urchin embryos, a study was made on the effects of (a) reducing protein synthesis with emetine and (b) DNA replication with aphidi‐colin, on the timing of nuclear envelope breakdown, anaphase onset and cytokinesis. When protein synthesis was slightly inhibited by administration of emetine, the delay in the mitotic events increased, with an increase in the delay in accumulation of proteins up to the levels to which cells must synthesize the proteins to execute the cleavage. This indicated that protein synthesis affects the timing of mitotic events. The delay in cleavage cycles caused by a slight inhibition of DNA replication with aphidicolin was in proportion to the concentration of aphidicolin administered, suggesting that DNA replication also affects the timing of mitotic events. Furthermore, it was confirmed that accumulation of the proteins to the levels required for execution of the first cleavage precedes completion of DNA replication as a requirement for execution of the first cleavage. These results imply the existence of process(es) affected by protein synthesis that are included in a feedback control system which prevents the initiation of mitosis until after the completion of DNA replication; it is the characteristic of a cell‐cycle control system that has been predicted theoretically.
Effects of thiols on topoisomerase‐IIα activity and cell cycle progression
Authors: Grdina D. J. , Murley J. S. , Roberts J. C.
Published: July 2007

Abstract. Thiol containing compounds exhibiting antioxidant properties are currently being evaluated for use in cytoprotection and chemoprevention. Many of these have also been found to be effective in inhibiting cell cycle progression and cellular proliferation., N‐Acetyl‐L‐cysteine (L‐NAC), along with its nonmetabolically active stereoisomer N‐acetyl‐D‐cysteine (D‐NAC), together with captopril and dithiothreitol (DTT) were investigated to assess their effects on cell cycle progression as determined by flow cytometry. Topoisomerase‐IIa (topo‐IIα) activity, an enzyme involved in DNA synthesis, was also monitored as a function of drug dose using a kinetoplast DNA (kDNA) decatenation assay. Chinese hamster ovary (CHO) AA8 cells were exposed to each thiol at concentrations ranging from 4 μM to 4 mM for a period of 3 h. Following the removal of the thiols, cell cultures were followed for an additional 5 h to assess changes in cell cycle progression. L‐NAC, which also serves as a precursor for glutathione (GSH) synthesis, effectively inhibited topo‐IIa activity by at least 50% at all concentrations tested. Associated with this reduction in enzyme activity was a sixfold increase in the relative number of cells accumulating in G2 phase. D‐NAC, which is unable to participate in GSH synthesis, was only half as effective as L‐NAC at each concentration tested in inhibiting topo‐IIa activity as well as perturbing cell progression through G2. In comparison, captopril, an inhibitor of angiotensin converting enzyme (ACE), had little effect on the progression of cells into G2 phase. In contrast to the repressive effects of L‐NAC and D‐NAC, it enhanced topo‐IIa activity over control values by ≅20%. DTT, a well characterized thiol known to be capable of reducing disulphides in proteins, was observed to be relatively ineffective in either perturbing cell cycle progression or affecting topo‐IIa activity. This suggests an involvement of a mechanism(s) in addition to thiol mediated affects on reduction/oxidation processes. The inhibitory effects of L‐NAC and D‐NAC on topo‐IIa activity, in contrast to the other two thiols, may be due in part to the presence of amine groups which could allow for their participation in polyamine related processes. The difference in the magnitude of the effect exhibited by L‐NAC, as compared to D‐NAC, on the repression topo‐IIa activity also suggests a role for GSH in this process. Inhibition of cellular progression and proliferation by thiols can therefore be mediated by diverse mechanisms which include both cycle‐phase specific (i.e. L‐NAC and D‐NAC) and non cell cycle specific (i.e. captopril) processes.
Differential expression of adhesion molecules and chemokines between nasal and small intestinal mucosae: implications for T‐ and sIgA+ B‐lymphocyte recruitment
Authors: Bourges Dorothée , Chevaleyre Claire , Wang CaiHong , Berri Mustapha , Zhang XiaoMei , Nicaise Laetitia , Meurens François , Salmon Henri
Published: July 2007

Nasal and small intestinal mucosae are the first sites of contact with infectious agents and the sites of T‐cell‐mediated and secreted immunoglobulin A (IgA)‐mediated defences against pathogens. We investigated the factors controlling the infiltration of CD3+ T lymphocytes and surface IgA+ (sIgA+) B lymphocytes into swine epithelium and lamina propria (LP) within and between these two mucosal effector sites. Vascular addressins, vascular cell adhesion molecule 1 and mucosal addressin cell adhesion molecule‐1 were reciprocally expressed in both mucosae. Strong expression of α4β1 relative to α4β7 was characteristic of CD3+ T cells in nasal mucosa LP and epithelium and of sIgA+ cells in nasal mucosa epithelium. The same profile was observed on corresponding blood cells. Conversely, higher levels of integrins β7 and α4β7 than α4β1 were characteristic of CD3+ T cells and sIgA+ cells in the small intestine. However, about 40% of the LP‐activated sIgA+ cells displayed sIgAhigh, integrin α4 and integrin α4 expression. Whereas CCL19, CXCL12, CCL21 and CCL28 messenger RNAs were similarly expressed in both mucosae, CCL25 messenger RNA was only expressed in the small intestine. Thus, the nasal and small intestine mucosae represent separate compartments for infiltration by CD3+ T cells and sIgA+ effector cells, with the exception of a population of small intestine activated sIgA+ cells, which may gain access to both mucosae.
Pathological Survivin Expression Links Viral Infections with Pathogenesis of Erosive Rheumatoid Arthritis
Authors: Bokarewa M. , Tarkowski A. , Magnusson M.
Published: July 2007

Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage and bone destruction. Insufficient apoptosis in the inflamed RA synovium along with accumulation of highly differentiated B‐ and T‐lymphocytes as well as invasive growth of macrophages and fibroblasts is among the major mechanisms supporting joint destruction. We have recently shown that circulating survivin, an apoptotis inhibitor tightly bound to tumorigenesis, is an independent predictor of development and progression of joint destruction in RA. In this review we discuss the possible connectivity between viral infection, leading to interferon (IFN)‐alpha production, survivin expression, and subsequent joint inflammation. The role of IFN‐α and the involvement of IFN transcription factors and phosphoinositide‐3‐kinase signalling as essential modulators of arthritogenic process are discussed in the context of survivin.
Progress in Serodiagnosis of Mycobacterium tuberculosis Infection
Authors: Abebe F. , Holm‐Hansen C. , Wiker H. G. , Bjune G.
Published: July 2007

One‐third of the world population is estimated to have Mycobacterium tuberculosis infection. Accurate and timely identification of infected individuals is critical for treatment and control. The current diagnostic methods lack the desired sensitivity and specificity, require sophisticated equipment and skilled workforce or take weeks to yield results. Diagnosis of extrapulmonary TB, TB‐HIV co‐infection, childhood TB and sputum smear‐negative pulmonary TB pose serious challenges. Interest in developing serodiagnostic methods is increasing because detection of antibody is rapid, simple and relatively inexpensive, and does not require a living cell for detection. Three types of tests, namely screening tests to overcome diagnostic delay, specific tests for diagnosis of extrapulmonary TB and other bacteriologically negative cases, and tests for vaccine‐induced immunity need critical consideration. Several factors must be considered to develop serodiagnostic methods for TB. Antigen recognition by infected individuals is highly heterogeneous due to stage of disease, differences in HLA types, strain of the bacilli, health of the patient and bacillary load. With advances in molecular biological techniques, a number of novel antigens have been identified. Some of these antigens have proven valuable in detecting specific antibodies in some of the most challenging TB patients. The best example is a fusion protein containing several M. tuberculosis proteins (e.g. CFP‐10, MTB8, MTB48, MTB81 and the 38‐kDa protein) which showed encouraging results in detecting antibodies in sera of patients, including TB‐HIV co‐infection. This review presents progress made in the serodiagnosis of TB during the last decade.
Allosteric Changes in the TCR/CD3 Structure Upon Interaction With Extra‐ or Intra‐cellular Ligands
Authors: Rubin B. , Knibiehler M. , Gairin J. E.
Published: July 2007

T lymphocytes are activated by the interaction between the T‐cell antigen receptor (TCR) and peptides presented by major histocompatibility complex (MHC) molecules. The avidity of this TCR–pMHC interaction is very low. Therefore, several hypotheses have been put forward to explain how T cells become specifically activated despite this handicap: conformational change model, aggregation model, kinetic segregation model, sequential interaction model and permissive geometry model. In the present paper, we conducted experiments to distinguish between the TCR‐aggregation model and the TCR‐conformational change model. The results obtained using a TCR capture ELISA with Brij 98‐solubilized TCR molecules from normal or activated T cells showed that the ligand–TCR interaction causes structural changes in the CD3ε cytoplasmic tail as well as in the extracellular TCRβ FG loop region. Size‐fractionation experiments with Brij 98‐solubilized TCR/CD3/co‐receptor complexes from naïve or activated CD4+ or CD8+ T cells demonstrated that such complexes are found as either dimers or tetramers. No monomers or multimers were detected. We propose that: (1) ligand–TCR interaction results in conformational changes in the CD3ε cytoplasmic tail leading to T‐cell activation; (2) CD3ε cytoplasmic tail interaction with intracellular proteins may dissociate pMHC and co‐receptors (CD4 or CD8) from TCR/CD3 complexes, thus leading to the arrest of T‐cell activation; and (3) T‐cell activation appears to occur among dimers or tetramers of TCR/CD3/co‐receptor complexes interacting with self and non‐self (foreign) peptide‐MHC complexes.
Deceptive simplicity: Systemic oxygen delivery and pulse oximetry
Authors: Collins Clare L , Andersen Chad C
Published: July 2007

Abstract:  Pulse oximetry is often perceived to be a measure of the adequacy of oxygen delivery. It is, however, only a measure of oxygen bound to haemoglobin. Systemic oxygen delivery is principally determined by cardiac output, haemoglobin concentration and haemoglobin saturation. Changes to both cardiac output and haemoglobin concentration will significantly alter oxygen delivery without changing oxygen saturation. This article will describe the components of systemic oxygen delivery and the physiologic limitation of pulse oximetry and caution against over‐interpretation of oximetry in the care of newborns.
Macrogol 3350 plus electrolytes for chronic constipation in children: A single‐centre, open‐label study
Authors: Hardikar Winita , Cranswick Noel , Heine Ralf G
Published: July 2007

Aim:  A Macrogol 3350‐based, iso‐osmotic laxative has become available for the treatment of chronic constipation in adults. This open‐label, non‐randomised study aimed to evaluate the safety and efficacy of this preparation in the treatment of chronic constipation in children.

Methods:  Seventy‐eight children, aged 2–11 years, with chronic constipation for greater than 3 months were enrolled. All children received Macrogol 3350 plus electrolytes for 12 weeks. The primary efficacy variable was the number of spontaneous defaecations per week. Secondary efficacy variables were faecal form, abdominal pain, rectal bleeding, pain on defaecation, straining, soiling, amount of stool, stool withholding and assessments of efficacy by the investigators and parents. Safety and compliance were also assessed.

Results:  The mean number of spontaneous defaecations per week increased from 1.4 ± 0.55 (SD) at baseline to 6.8 ± 3.45 after 14 days, and 7.1 ± 3.45 at 12 weeks (P < 0.001). Similar improvements were found in the secondary efficacy variables. There was a significant reduction in reported abdominal pain from 53 (69%) children at baseline to 3 (4%) at the final visit (P < 0.0001). Similarly, 61 (79%) children had pain on defaecation at baseline, compared with 7 (9%) at the final visit (P < 0.0001). Treatment was well tolerated. Of 318 adverse events, 262 (82%) were considered mild, and 241 (76%) were deemed unrelated to treatment. Only 3 (4%) children were withdrawn because of poor compliance.

Conclusions:  Macrogol 3350 plus electrolytes is a safe and effective treatment for constipation in children aged 2–11 years.
Non‐compliance in pyridoxine‐dependent seizures and a way out
Authors: Kumar Praveen , Gupta Vijay K , Mishra Devendra
Published: July 2007

Abstract:  Pyridoxine dependency is a rare autosomal‐recessive disorder causing intractable seizures in neonates and infants. Life‐long therapy with pyridoxine is required for prevention of seizure recurrence and for an optimum intellectual outcome. With the availability of newer biochemical confirmatory tests, the conventional pyridoxine‐withdrawal test is being used less frequently for diagnosis. This report describes an infant whose parents were non‐compliant with pyridoxine therapy and proposes that pyridoxine‐withdrawal test may be useful in demonstrating to parents the need for life‐long pyridoxine therapy, thereby reducing non‐compliance.
Efficacy and Safety of Oral Lacosamide as Adjunctive Therapy in Adults with Partial‐Onset Seizures
Authors: Ben‐Menachem Elinor , Biton Victor , Jatuzis Dalius , Abou‐Khalil Bassel , Doty Pamela , Rudd G. David
Published: July 2007

Summary:  Purpose: To evaluate the efficacy and safety of lacosamide when added to 1 or 2 antiepileptic drugs (AEDs) in adults with uncontrolled partial‐onset seizures, and assess plasma concentrations of concomitant AEDs to determine any potential for drug interactions.

Methods: During this multicenter, double‐blind, placebo‐controlled trial, patients were randomized to placebo or lacosamide 200, 400, or 600 mg/day after an 8‐week baseline period. Lacosamide was titrated in weekly increments of 100 mg/day over 6 weeks and maintained for 12 weeks. Results were analyzed on an intention‐to‐treat basis.

Results: Four hundred eighteen patients were randomized and received trial medication; 312 completed the trial. The median percent reduction in seizure frequency per 28 days was 10%, 26%, 39%, and 40% in the placebo, lacosamide 200, 400, and 600 mg/day treatment groups, respectively. The median percent reduction in seizure frequency over placebo was significant for lacosamide 400 mg/day (p = 0.0023) and 600 mg/day (p = 0.0084). The 50% responder rates were 22%, 33%, 41%, and 38% for placebo, lacosamide 200, 400, and 600 mg/day, respectively. The 50% responder rate over placebo was significant for lacosamide 400 mg/day (p = 0.0038) and 600 mg/day (p = 0.0141). Adverse events that appeared dose‐related included dizziness, nausea, fatigue, ataxia, vision abnormal, diplopia, and nystagmus. Lacosamide did not affect mean plasma concentrations of concomitantly administered AEDs.

Conclusions: In this trial, adjunctive lacosamide significantly reduced seizure frequency in patients with uncontrolled partial‐onset seizures. Along with favorable pharmacokinetic and tolerability profiles, these results support further development of lacosamide as an AED.
MODEL OF THE RECEPTION OF HEDGEHOG MORPHOGEN CONCENTRATION GRADIENT: COMPARISON WITH AN EXTENDED RANGE OF EXPERIMENTAL DATA
Authors: GUNBIN KONSTANTIN V. , OMELYANCHUK LEONID V. , KOGAI VLADISLAV V. , FADEEV STANISLAV I. , KOLCHANOV NIKOLAY A.
Published: July 2007

The model for reception of the concentration gradient of the Hedgehog morphogen has been developed. The mechanism of co-operation of the proteins Patched, Smoothened, and Hedgehog is theoretically analyzed in terms of different versions of interactions within this group of proteins. The parametric stability of the modeled system is considered.
MOLECULAR NETWORKS IN MICROARRAY ANALYSIS
Authors: SIVACHENKO ANDREY Y. , YURYEV ANTON , DARASELIA NIKOLAI , MAZO ILYA
Published: July 2007

Microarray-based characterization of tissues, cellular and disease states, and environmental condition and treatment responses provides genome-wide snapshots containing large amounts of invaluable information. However, the lack of inherent structure within the data and strong noise make extracting and interpreting this information and formulating and prioritizing domain relevant hypotheses difficult tasks. Integration with different types of biological data is required to place the expression measurements into a biologically meaningful context. A few approaches in microarray data interpretation are discussed with the emphasis on the use of molecular network information. Statistical procedures are demonstrated that superimpose expression data onto the transcription regulation network mined from scientific literature and aim at selecting transcription regulators with significant patterns of expression changes downstream. Tests are suggested that take into account network topology and signs of transcription regulation effects. The approaches are illustrated using two different expression datasets, the performance is compared, and biological relevance of the predictions is discussed.
MATHEMATICAL MODEL FOR SUPPRESSION OF SUBGENOMIC HEPATITIS C VIRUS RNA REPLICATION IN CELL CULTURE
Authors: MISHCHENKO ELENA L. , BEZMATERNYKH KIRILL D. , LIKHOSHVAI VITALY A. , RATUSHNY ALEXANDER V. , KHLEBODAROVA TAMARA M. , YU. SOURNINA NATALIA , IVANISENKO VLADIMIR A. , KOLCHANOV NIKOLAI A.
Published: July 2007

A mathematical model for suppression of the hepatitis C virus RNA replicon replication in Huh-7 cell culture in the presence of potential drugs was built. There was a good agreement between the experimental and theoretical kinetic data for the decrease in the level of viral RNA in the cell in the presence of the competitive HCV NS3 protease inhibitor. Using the model, we verified the estimates for the efficiency of the effect of potential drugs on replication of viral RNA and viral protein processing. It was demonstrated that the tested drugs are most efficient at the replication step of viral RNA. The efficiency of the combined action of real and putative inhibitors target on the host and viral proteins was also studied. It was found that the action of the inhibitor at low concentrations on the host factors considerably enhances the suppressive effect on viral RNA replication in the presence of even the low affine NS3 protease inhibitors. The developed mathematical model may serve as a tool for the evaluation of the efficiency of potential drugs on the HCV genome.
ON COOPERATIVE QUASI-EQUILIBRIUM MODELS OF TRANSCRIPTIONAL REGULATION
Authors: MJOLSNESS ERIC
Published: July 2007

Mechanistic models for transcriptional regulation are derived using the methods of equilibrium statistical mechanics, to model equilibrating processes that occur at a fast time scale. These processes regulate slower changes in the synthesis and expression of transcription factors that feed back and cooperatively regulate transcription, forming a gene regulation network (GRN). We rederive and extend two previous quasi-equilibrium models of transcriptional regulation, and demonstrate circumstances under which they can be approximated at each transcription complex by feed-forward artificial neural network (ANN) models. A single-level mechanistic model can be approximated by a successfully applied phenomenological model of GRNs which is based on single-layer analog-valued ANNs. A two-level hierarchical mechanistic model, with separate activation states for modules and for the whole transcription complex, can be approximated by a two-layer feed-forward ANN in several related ways. The sufficient conditions demonstrated for the ANN approximations correspond biologically to large numbers of binding sites each of which have a small effect. A further extension to the single-level and two-level models allows one-dimensional chains of overlapping and/or energetically interacting binding sites within a module. Partition functions for these models can be constructed from stylized diagrams that indicate energetic and logical interactions between binary-valued state variables. All parameters in the mechanistic models, including the two approximations, can in principle be related to experimentally measurable free energy differences, among other observables.
Tertiary-Quaternary intra-plate magmatism in Europe and its relationship to mantle dynamics
Authors: Wilson Marjorie , Downes Hilary
Published: July 2007

Anorogenic intra-plate magmatism was widespread in Europe from early Tertiary to Recent times, extending west to east from Spain to Bulgaria, and south to north from Sicily to central Germany. Magmatism is spatially and temporally associated with Alpine-Pyrenean collisional tectonics, the development of an extensive lithospheric rift system in the northern foreland of the Alps, and, locally, with uplift of Variscan basement massifs (Massif Central, Rhenish Massif, Bohemian Massif). The volcanic regions vary in volume from large central volcanoes (e.g. Cantal, Massif Central;Vogelsberg, central Germany), to small isolated plugs (e.g. Urach and Hegau provinces in southern Germany). Within the Mediterranean region, the Dinarides, the Pannonian Basin and Bulgaria, anorogenic volcanism locally post-dates an earlier phase of subduction-related magmatism. The major and trace element and Sr-Nd-Pb isotope characteristics of the most primitive mafic magmatic rocks (MgO > 6 wt%) provide important constraints on the nature of the mantle source and the conditions of partial melting. These are predominantly sodic (melilitites, nephelinites, basanites and alkali olivine basalts); however, locally, potassic magma types (olivine leucitites, leucite nephelinites) also occur. In several localities (e.g. Sicily; Vogelsberg and the Rhine Graben, Germany; Calatrava, central Spain) olivine and quartz tholeiites form a significant component of the magmatism. The sodic magmas were derived by variable degrees of partial melting (c. 0.5-5%) within a transitional zone between garnet-peridotite and spinel-peridotite mantle facies, close to the base of the lithosphere; the potassic magma types are interpreted as partial melts of enriched domains within the lithospheric mantle. Mantle partial melting was induced by adiabatic decompression of the asthenosphere, locally in small-scale, plume-like, diapirs, which appear to upwell from c. 400 km depth
Contrasting modes of ophiolite emplacement in the Eastern Mediterranean region
Authors: Robertson Alastair H. F.
Published: July 2007

The Eastern Mediterranean region is characterized by one of the largest concentrations of ophiolites anywhere in the world. Many of these ophiolites are fragmentary or highly deformed, such that their initial mode of tectonic emplacement cannot easily be inferred from the local field relations. The emplacement of many of these ophiolites can usefully be compared with the intact Oman ophiolite, one of the largest and best-studied ophiolites in the world. The Oman ophiolite is commonly believed to have been created in Late Cretaceous time (c. 95 Ma) above an oceanward-dipping, intra-oceanic subduction zone. This was followed by collision of the subduction zone with the downflexed Arabian passive margin, facilitating the emplacement of the ophiolite onto the continental margin. A less likely alternative is that the Oman ophiolite formed at a mid-ocean ridge that then collapsed, initiating the emplacement of the ophiolite. An Oman-type model is applicable to many of the Mid-Jurassic and the Late Cretaceous ophiolites of the Eastern Mediterranean region that were thrust over former passive continental margins. These ophiolites are again mainly of suprasubduction-zone type. Such ophiolites include many of the Jurassic ophiolites of Greece, Albania and former Yugoslavia, and also the Late Cretaceous ophiolites of Turkey and northern Syria. These ophiolites were emplaced from both more northerly and southerly Neotethyan ocean basins. In contrast, the opposing (northerly) margins of these oceanic basins experienced a history of subduction-accretion, marginal arc volcanism and back-arc basin formation ('Cordilleran-type' ophiolites). Ophiolites that were emplaced associated with active margin settings range from large accreted thrust sheets to small slices within accretionary prisms and back-arc basins. Examples include the Late Cretaceous ophiolites that are related both to the northern margin of the southern Neotethys and to the northern margin of the northern Neotethys in Turkey. Not all ophiolites were emplaced in response to large-scale horizontal tectonic transport (e.g. Jurassic Guevgueli ophiolite, northern Greece), and several ophiolites experienced dominantly strike-slip or transpression (e.g. the Late Cretaceous Antalya ophiolites, SW Turkey). In general, the mode of ophiolite emplacement, especially the direction of emplacement relative to the orientation of the adjacent continental margin was influenced by the regional palaeogeographical setting.
Physical differences in the deep lithosphere of Northern and Central Europe
Authors: Gregersen Soren , Voss Peter , Shomali Z. Hossein , Grad Marek , Roberts Roland G. ,   TOR Working Group
Published: July 2007

A number of large-scale integrated studies, including the TOR and POLONAISE'97 projects, with an emphasis on seismic methods, have been used to elucidate the southwestern boundary (suture zone) between the East European Craton and the Phanerozoic terranes of Western Europe. Results indicate that a thick slab of mantle lithosphere below the craton thins southwestwards beneath the Trans-European Suture Zone and is not seen south of the Variscan front. The thinning is not gradual, but is interrupted by at least two abrupt deep boundaries, the most significant of which corresponds to the surface position of the Tornquist Zone, a major fault. The present geometry of the lithosphere is the result of modification of the margin of the Neoproterozoic continent Baltica by Phanerozoic processes, including the development of the Tornquist Zone and the stretching of the lithosphere in a broad central block SW of this zone. Seismic results and their interpretations from the TOR tomographic project are presented and compared with results from the POLONAISE'97 controlled source project to the SE. Both investigations have shown high-angle, non-symmetrical features extending deep into the mantle.
The evolution of the southern margin of Eastern Europe (Eastern European and Scythian platforms) from the Latest Precambrian- Early Palaeozoic to the Early Cretaceous
Authors: Saintot Aline , Stephenson Randell A. , Stovba Sergiy , Brunet Marie-Françoise , Yegorova Tamara , Starostenko Vitaly
Published: July 2007

The southern part of the Eastern European continental landmass consists mainly of a thick platform of Vendian and younger sediments overlying Precambrian basement, referred to as the East European and Scythian platforms (EEP and SP). Some specific geological features, such as the Late Devonian Pripyat-Dniepr-Donets rift basin, the Karpinsky Swell, the Permo(?)-Triassic troughs of the SP, and the deformed belt running from Dobrogea to Crimea and the Greater Caucasus, in which rocks as old as Palaeozoic crop out, form a record of the geodynamic processes affecting this part of the European lithosphere. Hard constraints on the Palaeozoic history of the SP are very sparse. The conventional view has been that the SP is a Late Palaeozoic orogenic belt. However, it is shown that the few available data are also consistent with an alternative interpretation in which it is the thinned margin of the Precambrian continent, reworked by Late Palaeozoic-Early Mesozoic rifting events. The geodynamic setting of the margin is classically reported as one of active convergence throughout the Late Palaeozoic and Early Mesozoic, with subduction of the Palaeotethys Ocean beneath Europe. Actually, there are no direct observations constraining the polarity of Palaeotethys subduction in this area although indirect evidence is not inconsistent with the conventional model. In such a case, the sedimentary-tectonic record of the SP suggests that convergence during the Permo-Triassic(?) and certainly during the Early and Mid-Jurassic was oblique. An Eo-Cimmerian (Late Triassic-Early Jurassic) event is widespread and implies a tectonic compressional regime with systematic inversion of most sedimentary basins. There is also a widespread unconformity at the end of the Mid-Jurassic and in the Late Jurassic. These can be interpreted as indicators of compressional tectonics; however, nowhere is there evidence of intense shortening or other orogenic processes. A revised tectonic model is proposed for the area but, given the degree of uncertainty characterizing the geology of this area, it is best considered as a basis for further discussion.
Marital Interaction in Depression: A Comparison of Structural Analysis of Social Behavior and the Kategoriensystem für Partnerschaftliche Interaktion
Authors: Backenstrass Matthias , Fiedler Peter , Kronmüller Klaus-Thomas , Reck Corinna , Hahlweg Kurt , Mundt Christoph
Published: July 2007

Background: A number of studies have shown that marital interaction plays an important role regarding etiology, maintenance, and course of depression. The Kategoriensystem für Partnerschaftliche Interaktion (KPI; ‘Coding System for Marital/Family Interaction’) and the Structural Analysis of Social Behavior (SASB) are both widely used to describe and quantify the interactional behavior of patients and their relatives. To evaluate the validity of extrapolating research findings from one system to another, especially in the field of depressive disorders, the two coding systems were compared in an empirical analysis. Sampling and Methods: Videotaped marital problem-solving interaction tasks of 29 married couples with a depressed spouse were coded by means of both systems by separate teams of observers. Results: Between-system comparisons revealed that convergent validity on the level of SASB clusters and KPI verbal categories were moderate and differentiated between the behavior of patients and that of spouses. The KPI nonverbal positive and negative categories were not simply correlated with the SASB affiliation dimension. Conclusion: The results underline the importance of undertaking validation studies with different samples.
LBA–ESECAFLOR Artificially Induced Drought in Caxiuanã Reserve, Eastern Amazonia: Soil Properties and Litter Spider Fauna
Authors: Ruivo Maria de Lourdes Pinheiro , Barreiros José Augusto Pereira , Bonaldo Alexandre Bragio , da Silva Rosecélia Moreira , Sá Leonardo Deane Abreu , Lopes Elessandra Laura Nogueira
Published: July 2007

A review is presented of soil properties and litter fauna of an experimental site in the Caxiuanã forest, eastern Amazonia, as a contribution to the Large-Scale Biosphere–Atmosphere Experiment in Amazonia (LBA). This study’s main scientific goal is to compare some biogeochemical soil properties of an undisturbed forest ecosystem with those of an experimental (1 ha) plot in which rainfall was artificially excluded to simulate drought [the Efeitos da Seca da Floresta (ESECAFLOR) experiment]. A second scientific objective is to investigate the space variability of soil profile characteristics in the experimental sites, particularly organic carbon concentration, moisture, and texture. It is expected that such soil property variability influences greatly the distribution of several biological species such as spiders. To investigate such effects in the litter spider community, we applied percentual complementarity and Simpson diversity index to available data. Our results suggest that a faunal transition was under way in the treatment plot, shifting from a rich and even community to a less diverse one.
Cellular immune therapy for chronic lymphocytic leukemia
Authors: Kater Arnon P. , van Oers Marinus H. J. , Kipps Thomas J.
Published: July 2007

Although chemotherapy can induce complete responses in patients with chronic lymphocytic leukemia (CLL), it is not considered curative. Treated patients generally develop recurrent disease requiring additional therapy, which can cause worsening immune dysfunction, myelosuppression, and selection for chemotherapy-resistant leukemia-cell subclones. Cellular immune therapy promises to mitigate these complications and potentially provide for curative treatment. Most experience with this is in the use of allogeneic hematopoietic stem-cell transplantation (allo-HSCT), in which graft-versus-leukemia (GVL) effects can be observed and shown responsible for long-term disease-free survival. However, use of allo-HSCT for CLL is limited because of the lack of suitable donors and the treatment-related morbidity/mortality for elderly patients, who constitute the majority at risk for developing this disease. The GVL effect, however, suggests there are specific CLL-associated antigens that could be targeted in autologous cellular immune therapy. Effective strategies for this will have to overcome the disease-related acquired immune deficiency and the capacity of the leukemia-cell to induce T-cell tolerance, thereby compromising the activity of even conventional vaccines in patients with this disease. We will discuss the different strategies being developed to overcome these limitations that might provide for effective cellular immune therapy of CLL.