bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilepsy: A Review of Selected Clinical Syndromes and Advances in Basic Science
Authors: Stafstrom Carl E
Published: January 2006

Epilepsy is a common neurologic disorder that manifests in diverse ways. There are numerous seizure types and numerous mechanisms by which the brain generates seizures. The two hallmarks of seizure generation are hyperexcitability of neurons and hypersynchrony of neural circuits. A large variety of mechanisms alters the balance between excitation and inhibition to predispose a local or widespread region of the brain to hyperexcitability and hypersynchrony. This review discusses five clinical syndromes that have seizures as a prominent manifestation. These five syndromes differ markedly in their etiologies and clinical features, and were selected for discussion because the seizures are generated at a different ‘level’ of neural dysfunction in each case: (1) mutation of a specific family of ion (potassium) channels in benign familial neonatal convulsions; (2) deficiency of the protein that transports glucose into the CNS in Glut-1 deficiency; (3) aberrantly formed local neural circuits in focal cortical dysplasia; (4) synaptic reorganization of limbic circuitry in temporal lobe epilepsy; and (5) abnormal thalamocortical circuit function in childhood absence epilepsy. Despite this diversity of clinical phenotype and mechanism, these syndromes are informative as to how pathophysiological processes converge to produce brain hyperexcitability and seizures.
An equilibrium calculation of the thermal transport coefficients between two planes of arbitrary separation in a condensed phase
Authors: Petravic Janka , Harrowell Peter
Published: January 2006

We present a method for the direct calculation at equilibrium of the shear viscosity and thermal conductivity over distances as short as one molecular diameter. The method is directly applicable to the calculation of viscosity and thermal conductivity in inhomogeneities such as the interface between coexisting phases. The method makes use of a novel extension of our recently developed boundary fluctuation theory.
Nonequilibrium superoperator GW equations
Authors: Harbola Upendra , Mukamel Shaul
Published: January 2006

Hedin’s equations [Phys. Rev. 139, 796 (1965)] for the one-particle equilibrium Green’s function of a many-electron system are generalized to nonequilibrium open systems using two fields that separately control the evolution of the bra and the ket of the density matrix. A closed hierarchy is derived for the Green’s function, the self-energy, the screened potential, the polarization, and the vertex function, all expressed as Keldysh matrices in Liouville space.
Calculation of the vibronic structure of the X̃Π2 photoelectron spectra of XCN,X=F, Cl, and Br
Authors: Mishra Sabyashachi , Vallet Valérie , Poluyanov Leonid V. , Domcke Wolfgang
Published: January 2006

The vibronic structure of the photoelectron spectra of the X̃Π2 state of XCN+ (X=F, Cl, and Br) has been calculated, assuming that the X̃Π2 state can be considered as an isolated electronic state. The Renner-Teller coupling of the two components of the Π2 state via the degenerate bending mode as well as spin-orbit coupling effects are taken into account. The two stretching modes are treated within the so-called linear vibronic-coupling model. The vibronic and spin-orbit parameters have been determined by accurate ab initio electronic-structure calculations. While spin-orbit effects are small in FCN+, the large spin-orbit splitting of the X̃Π2 state of the BrCN+ leads to a complete quenching of the Renner-Teller effect. The X̃Π2 state of the ClCN+ is shown to be of particular interest: here the resonance condition for linear-relativistic Renner-Teller coupling is approximately fulfilled. This coupling mechanism leads to a significant intensity transfer to vibronic levels with odd quanta of the bending mode. The calculated spectrum indicates that this novel relativistic vibronic-coupling effect should be observable in high-resolution (electron energy resolution of the order of a few meV) photoelectron spectra of ClCN.
Effects of anharmonicity on nonadiabatic electron transfer: A model
Authors: Yeganeh Sina , Ratner Mark A.
Published: January 2006

The effect of anharmonicity in the intramolecular modes of a model system for exothermic intramolecular nonadiabatic electron transfer is probed by examining the dependence of the transition probability on the exoergicity. The Franck-Condon factor for the Morse potential is written in terms of the Gauss hypergeometric function both for a ground initial state and for the general case, and comparisons are made between the first-order perturbation theory results for transition probability for harmonic and Morse oscillators. These results are verified with quantum dynamical simulations using wave-packet propagations on a numerical grid. The transition-probability expression incorporating a high-frequency quantum mode and low-frequency medium mode is compared for Morse and harmonic oscillators in different temperature ranges and with various coarse-graining treatments of the delta function from the Fermi golden rule expression. We find that significant deviations from the harmonic approximation are expected for even moderately anharmonic quantum modes at large values of exoergicity. The addition of a second quantum mode of opposite displacement negates the anharmonic effect at small energy change, but in the inverted regime a significantly flatter dependence on exoergicity is predicted for anharmonic modes.
Extended coherent exciton states in quantum dot arrays
Authors: Al-Ahmadi Ameenah N. , Ulloa Sergio E.
Published: January 2006

Resonant energy transfer is a mechanism for excitation exchange in quantum dot arrays. We explore this process by calculating the coupling strength, and by studying the detailed dynamics of extended coherent exciton states created in an array of quantum dots. Estimates of the Förster coupling VF are obtained from a microscopic description of the exciton levels in the quantum dot. We present results for different materials (CdS, CdSe, GaAs, and InP) as function of dot features. VF shows a nonmonotonic variation with a maximum value that depends on the specific dot sizes, material parameters, and dot separation. Analysis of coupled quantum dots using the time evolution of the density matrix when the Förster channel is open shows that a coherent coupling appears in different regimes. Realistic parameters, used throughout the study of the dynamics, suggest the practical realization of these phenomena in actual systems.
COCO-CL: hierarchical clustering of homology relations based on evolutionary correlations
Authors: Jothi Raja , Zotenko Elena , Tasneem Asba , Przytycka Teresa M.
Published: January 2006

Motivation: Determining orthology relations among genes across multiple genomes is an important problem in the post-genomic era. Identifying orthologous genes can not only help predict functional annotations for newly sequenced or poorly characterized genomes, but can also help predict new protein–protein interactions. Unfortunately, determining orthology relation through computational methods is not straightforward due to the presence of paralogs. Traditional approaches have relied on pairwise sequence comparisons to construct graphs, which were then partitioned into putative clusters of orthologous groups. These methods do not attempt to preserve the non-transitivity and hierarchic nature of the orthology relation.

Results: We propose a new method, COCO-CL, for hierarchical clustering of homology relations and identification of orthologous groups of genes. Unlike previous approaches, which are based on pairwise sequence comparisons, our method explores the correlation of evolutionary histories of individual genes in a more global context. COCO-CL can be used as a semi-independent method to delineate the orthology/paralogy relation for a refined set of homologous proteins obtained using a less-conservative clustering approach, or as a refiner that removes putative out-paralogs from clusters computed using a more inclusive approach. We analyze our clustering results manually, with support from literature and functional annotations. Since our orthology determination procedure does not employ a species tree to infer duplication events, it can be used in situations when the species tree is unknown or uncertain.

Contact:  jothi@mail.nih.gov, przytyck@mail.nih.gov

Supplementary information:  Supplementary materials are available at Bioinformatics online.
Dynamics of pneumococcal colonization in healthy Dutch children
Authors: Bogaert D. , Sluijter M. , Toom N. Lemmens-den , Mitchell T. J. , Goessens W. H. F. , Clarke S. C. , de Groot R. , Hermans P. W. M.
Published: January 2006

A recent study of pneumococcal colonization in 3198 healthy children of 1–19 years of age in The Netherlands showed pneumococcal colonization in 19 % of the children, with a peak incidence of 55 % at the age of 2 years; an age-related serotype distribution was also found. In the present study, the genetic background and resistance profiles of 578 pneumococcal isolates from the latter study were characterized by means of chromosomal genotyping and susceptibility testing. In contrast to the age-related serotype distribution observed previously, the genetic background of the strains was not age related. Few strains were found showing close homology (>95 %) with the international clones Spain9V-3 (ten isolates showed homology), England14-9 (four isolates), Tennessee23F-4 (two isolates), CSR14-10 (one isolate) and Sweden15A-25 (one isolate). In total, 19 % of strains showed resistance to one or more antibiotics. Resistance to cotrimoxazole, tetracycline, erythromycin and penicillin was found in 12·9, 5·6, 5·0 and 2·7 % of isolates, respectively. Multidrug resistance was found in 1·9 % of strains. In conclusion, pneumococcal colonization isolates from healthy Dutch children represent a heterogeneous, mostly antibiotic susceptible, genetic population.
Inhibition of competence development in Streptococcus pneumoniae by increased basal-level expression of the ComDE two-component regulatory system
Authors: Guiral Sébastien , Hénard Vincent , Granadel Chantal , Martin Bernard , Claverys Jean-Pierre
Published: January 2006

Natural competence for genetic transformation in Streptococcus pneumoniae is controlled by the ComCDE signal-transduction pathway. Together, ComD, a membrane histidine kinase, and ComE, its cognate response regulator, constitute a typical two-component regulatory system involved in sensing the comC-encoded competence-stimulating peptide (CSP). The comCDE operon is strongly upregulated when CSP reaches a critical threshold, probably to coordinate competence induction throughout the population. During a study of the early regulation of the comCDE operon, a mutation which resulted in increased β-galactosidase production from a comC : : lacZ fusion was isolated. This mutation, which was characterized as a G→T change in the transcription terminator of the tRNAArg located immediately upstream of comCDE, is suggested to destabilize the terminator and to allow transcriptional readthrough of comCDE. Here, it is shown that, quite unexpectedly, the mutation confers reduced transformability. A series of experiments undertaken with the aim of understanding this surprising phenotype is described. Evidence is presented that increased basal-level expression of comDE impedes both spontaneous and CSP-induced competence in S. pneumoniae. There is a discussion of how an increased concentration of ComD and/or ComE could affect competence development.
Differential expression of key pneumococcal virulence genes in vivo
Authors: LeMessurier Kim S. , Ogunniyi Abiodun David , Paton James C.
Published: January 2006

Few studies have examined in vivo virulence gene expression in Streptococcus pneumoniae. In this study, expression of key pneumococcal virulence genes cbpA, pspA, ply, psaA, cps2A, piaA, nanA and spxB in the nasopharynx, lungs and bloodstream of mice was investigated, following intranasal challenge with the serotype 2 strain D39. Bacterial RNA was extracted, linearly amplified and assayed by real-time RT-PCR. At 72 h, cbpA mRNA was present at higher levels in the nasopharynx and lungs than in the blood. At this time-point, the mRNAs for PspA and PiaA were most abundant in the nasopharynx, whereas no significant difference in gene expression between niches was observed for ply, psaA and cps2A. Both nanA and spxB mRNAs were present in higher amounts in the nasopharynx than in the lungs or blood. These findings illustrate the dynamic nature of pneumococcal virulence gene expression in vivo.
Disabling conditions and registration for child abuse and neglect: a population‐based study
Authors: Reading Richard
Published: January 2006

.
 
Spencer N.,
Devereux E.,
Wallace A.,
Sundrum R.,
Shenoy M.,
Bacchus C. &
Logan S.
(
2005
)

,
116
,
609
–
613
.

Objective  To study the relationship between disabling conditions and registration for child abuse and neglect in a 19‐year whole‐population birth cohort.

Setting  West Sussex area of the United Kingdom.

Study design  Retrospective whole‐population cohort.

Main outcomes  Child‐protection registration, physical abuse, sexual abuse, emotional abuse and neglect.

Population and participants  Infants born in West Sussex (119 729) between January 1983 and December 2001 with complete data including birthweight, gestational age, maternal age and postal code.

Results  Cerebral palsy, speech and language disorder, learning difficulties, conduct disorders and non‐conduct psychological disorders were all significantly associated with child‐protection registration before adjustment, and all but cerebral palsy retained significance after adjustment for birthweight, gestational age and socioeconomic status. Autism and sensory disabilities (vision and hearing) were not associated with an increased risk of child‐protection registration. Conduct disorders and moderate/severe learning difficulty were associated with registration in each of the four categories after adjustment for socioeconomic status, birthweight and gestational age. Children with speech and language disorders and mild learning difficulties were at increased risk of physical abuse, emotional abuse and neglect. Non‐conduct psychological disorders were associated with all categories except neglect, and cerebral palsy was associated with all categories except physical abuse and neglect.

Conclusions  Children with disabling conditions seem to be at increased risk of registration for child abuse and neglect, although the pattern of registration varies with the specific disabling condition. The strong association with registration noted for conditions such as conduct disorder and learning difficulties is likely to arise, in part, because these conditions share a common aetiological pathway with child abuse and neglect.
Surveying biotransformations with à la carte genetic traps: translating dehydrochlorination of lindane (gamma‐hexachlorocyclohexane) into lacZ‐based phenotypes
Authors: Mohn William W. , Garmendia Junkal , Galvao Teca C. , De Lorenzo Víctor
Published: January 2006

The ability of the product of a desired reaction to activate a bacterial transcriptional regulator was exploited to develop genetic traps that render the catalytic activity born by a DNA clone into a selectable/scorable phenotype. We established this strategy with a system to expose the activity of dehydrochlorinases acting upon gamma‐hexachlorocyclohexane (γ‐HCH or lindane). To this end, the effector‐binding protein, XylR, was evolved by gene shuffling plus mutagenic polymerase chain reaction to be optimally responsive to the major product of γ‐HCH dehydrochlorination, 1,2,4‐trichlorobenzene (TCB). We then derived Escherichia coli strains that constitutively expressed the modified XylR variant (named XylR5) and had lacZ under control of the Pu promoter, which is activated by XylR. A robotic β‐galactosidase assay indicated that when the resulting strain was transformed with a linA+ clone (expressing a γ‐HCH dehydrochlorinase from Sphingomonas paucimobilis UT26), it had levels of β‐galactosidase that were dependent on the γ‐HCH concentration. This à la carte host thus translated the conversion of γ‐HCH to TCB into upregulation of lacZ. An alternate host additionally expressing LacY grew efficiently on lactose only when LacZ was upregulated in a fashion dependent on TCB or other effectors of XylR5. These results demonstrated the power of deriving a host for the genetic scrutiny, rather than enzymatic screening, of clones expressing a given catabolic enzyme.
No evidence of population structure across three isolated subpopulations of Russula brevipes in an oak/pine woodland
Authors: Bergemann Sarah E. , Douhan Greg W. , Garbelotto Matteo , Miller Steven L.
Published: January 2006

Russula brevipes is common ectomycorrhizal (EM) fungus that is associated with several hosts across temperate forest ecosystems. A previous study has demonstrated that substructuring across large geographic distances (1500 km) occurs in the western USA.

To examine genetic structure over a more localized scale, basidiocarps of Russula brevipes from three subpopulations, separated by distances of 230–1090 m, were collected over two consecutive years in an oak/pine woodland. Microsatellite loci were used to test for population differentiation both among subpopulations and by year.

No significant population differentiation was detected between subpopulations (θST = 0.01) or between years (θST = 0.01). Most loci were consistent with a Hardy–Weinburg equilibrium and 82% of the genets between seasons from similar sampling localities constituted new genotypes.

These results indicate that R. brevipes constitutes a randomly mating population with no genetic differentiation between locations or across successive fruiting seasons.
Access to Health Care Services for the Disabled Elderly
Authors: Taylor Donald H. , Hoenig Helen
Published: January 2006

Objective. To determine whether difficulty walking and the strategies persons use to compensate for this deficit influenced downstream Medicare expenditures.

Data Source. Secondary data analysis of Medicare claims data (1999–2000) for age‐eligible Medicare beneficiaries (N=4,997) responding to the community portion of the 1999 National Long Term Care Survey (NLTCS).

Study Design. Longitudinal cohort study. Walking difficulty and compensatory strategy were measured at the 1999 NLTCS, and used to predict health care use as measured in Medicare claims data from the survey date through year‐end 2000.

Data Extraction. Respondents to the 1999 community NLTCS with complete information on key explanatory variables (walking difficulty and compensatory strategy) were linked with Medicare claims to define outcome variables (health care use and cost).

Principal Findings. Persons who reported it was very difficult to walk had more downstream home health visits (1.1/month, p<.001), but fewer outpatient physician visits (−0.16/month, p<.001) after controlling for overall disease burden. Those using a compensatory strategy for walking also had increased home health visits/month (0.55 for equipment, 1.0 for personal assistance, p<.001 for both) but did not have significantly reduced outpatient visits. Persons reporting difficulty walking had increased downstream Medicare costs ranging from $163 to $222/month (p<.001) depending upon how difficult walking was. Less than half of the persons who used equipment to adapt to walking difficulty had their difficulty fully compensated by the use of equipment. Persons using equipment that fully compensated their difficulty used around $300/month less in Medicare‐financed costs compared with those with residual difficulty.

Conclusions. Difficulty walking and use of compensatory strategies are correlated with the use of Medicare‐financed services. The potential impact on the Medicare program is large, given how common such limitations are among the elderly.
Adverse outcome of pregnancy following air travel: A myth or a concern?
Authors: CHIBBER Rachana , AL‐SIBAI M. Hisham , QAHTANI Noura
Published: January 2006

Objective:  To assess whether air travel elevates the risk of adverse pregnancy outcomes in essentially healthy women with single non‐anomalous fetuses at a gestational age greater than 20 weeks.

Methods:  A retrospective analysis of air travel during the current pregnancy and pregnancy outcome was undertaken in 992 women admitted for delivery over a 12‐month period. The study group of 546 (55%) women, of whom 57% were primigravidae, travelled at least once during pregnancy, and were compared with a control group of 447 women (45%), of whom 54% were primigravidae, who did not travel by air.

Results:  The primigravidae in the study group showed an increased risk of preterm birth, and this risk was statistically significant between the gestations of 34 and 37 weeks (adjusted odds ratio 1.5, 95% confidence intervals 1.2, 1.8); this risk remained elevated after adjustment for covariates. These women's pregnancies were appreciably shorter than those of primigravidae who did not fly (36.1 ± 0.8 vs. 39.2 ± 2.1 weeks) and their babies had lower birthweights (2684 ± 481 vs. 3481 ± 703 g). and were more likely to be admitted to the neonatal intensive care unit. This group of air travellers is unusual for the uncommonly long and frequent duration of air travel, which is not routinely undertaken in most parts of the world. There were no thromboembolic events complicating any pregnancies.

Conclusions:  Primigravid women who travel by air appear to be at higher risk for preterm birth. Multicentre large studies are required to confirm or repute these findings.
Biocompatible properties of surgical mesh using an animal model
Authors: KRAUSE Hannah G. , GALLOWAY Stuart J. , KHOO Soo K. , LOURIE Richard , GOH Judith T. W.
Published: January 2006

Aim:  To study the biocompatibility of surgical meshes for use in pelvic reconstructive surgery using an animal model.

Methods:  Eight different types of mesh: Atrium, Dexon, Gynemesh, IVS tape, Prolene, SPARC tape, TVT tape and Vypro II, were implanted into the abdominal walls of rats for 3 months’ duration. Explanted meshes were assessed, using light microscopy, for parameters of rejection and incorporation.

Results:  Type 1 (Atrium, Gynemesh, Prolene, SPARC and TVT) and type 3 (Vypro II, Dexon and IVS) meshes demonstrated different biocompatible properties. Inflammatory cellular response and fibrosis at the interface of mesh and host tissue was most marked with Vypro II and IVS. All type 1 meshes displayed similar cellular responses despite markedly different mesh architecture.

Conclusions:  The inflammatory response and fibrous reaction in the non‐absorbable type 3 meshes tested (IVS and Vypro II) was more marked than the type 1 meshes. The increased inflammatory and fibrotic response may be because of the multifilamentous polypropylene components of these meshes. Material and filament composition of mesh is the main factor in determining cellular response.
The Association of Sexual Experience with Attitudes, Beliefs, and Risk Behaviors of Inner‐City Adolescents
Authors: Silver Ellen Johnson , Bauman Laurie J.
Published: January 2006

We compared knowledge, attitudes, and demographic characteristics of 630 sexually experienced and 422 inexperienced inner‐city adolescents aged 14–17 years. Sexual experience was associated with indicators of risk previously reported in the literature: male gender, older age, single‐family home, smoking, drinking, and poorer academic performance. We found lower HIV knowledge in sexually inexperienced youth, which suggested an area of vulnerability compared with sexually active teens. However, most inexperienced adolescents intended to remain virgins for the next 6 months, most had peer groups they also perceived to be virgins, and they were more positive and confident about remaining abstinent. Differences between the groups suggest there may be benefits to developing intervention programs targeted to their different strengths and weaknesses.
Game On: Diminishing Risks for Depressive Symptoms in Early Adolescence Through Positive Involvement in Team Sports
Authors: Boone Erin M. , Leadbeater Bonnie J.
Published: January 2006

While research shows that low levels of social acceptance and elevated body dissatisfaction increase risks for depressive symptoms among both girls and boys, little is known about protective factors that can mediate these risks. We test the hypothesis that positive team sports involvement mediates the effects of these risks on depression in a cross‐sectional study involving a diverse group of 449 Canadian students (49.7% girls) recruited from grades 8 to 10. Findings showed that positive team sports involvement partially mediated risks for depressive symptoms for both boys and girls. Implications for community‐ and school‐based sports programs are discussed.
E‐mail Communication and the Policy Process in the State Legislature
Authors: Richardson Lilliard E. , Cooper Christopher A.
Published: January 2006

E‐mail has changed the policy process in state legislatures because political actors now have a new way to present their message to state legislators. What little research has been conducted on this topic examines e‐mail communication generally and does not compare results by policy actor. Using an original survey of state legislators in eight states, we test for systematic effects of variables on general e‐mail views and for effects specific to particular policy actors. We find that legislators have a nuanced approach to e‐mail usage in the policy process with their assessment of its impact differing significantly for constituents, intermediary groups, and policy insiders. Only gender consistently shapes legislators’ beliefs about e‐mail with all groups, but institutional features, legislator characteristics, and legislator beliefs shape views on e‐mail with different target groups. Clearly, legislators are attuned to the audience communicating via e‐mail, and they value e‐mail with each group differently.
Challenges and future of renal replacement therapy
Authors: DE FRANCISCO Angel L. M. , PIÑERA Celestino
Published: January 2006

Renal community increasingly recognizes the challenges of very high mortality, morbidity and low quality of life among dialysis patients. Current hemodialysis (HD) schedule provides less than 10% of the clearance power of the natural kidneys and therefore current standard HD treatment is still a long way from providing adequate renal replacement. In the future it would be expected to improve dialysis control with the development of new technology: membranes, dialysate buffer, electrolyte concentration, system interface, arteriovenous access monitoring. Online technology must be adapted to routine HD for new prescription monitoring such as creatinine online sensing technology, sodium‐specific electrode or hydrogen ion concentration. Online convective therapies offer the opportunity for a more biological renal replacement therapy increasing convective transport in order to “reproduce” glomerular function and improving small and middle molecular clearance in an economically feasible and safe way. The paradigm of thrice‐weekly dialysis is faced with diminishing returns, with the possible exception of long dialysis sessions. More frequent (daily) dialysis represents a very promising tool for improving dialysis outcomes and quality of life. Future technologies for renal replacement include bioartificial kidneys based in continuous hemofiltration and bioartificial tubules. Although Phase I/II clinical trial on 10 patients with acute renal failure has been reported the procedure requires further evaluation. Organogenesis, therapeutic cloning, or cloning and organogenesis combined might in the future produce a functional and histocompatible kidney. The continuous increase in incidence and prevalence of renal‐replacement therapy is a world‐wide phenomenon, although the rates in Europe are still much lower than in the U.S. The increase in rates applies especially to older patients, patients with diabetes mellitus and renal vascular disease and the consequences of this important comorbidity are very important in terms of mortality.
Online hemodiafiltration: 4 years of clinical experience
Authors: MUÑOZ Rosa , GALLARDO Isabel , VALLADARES Evandro , SARACHO Ramón , MARTÍNEZ Isabel , OCHARAN Julen , MONTENEGRO Jesús
Published: January 2006

Online hemodiafiltration (online HDF) is a new hemodialysis technique combining convection and diffusion and thus also enabling the purification of large molecules. As yet, only a small number of clinical experiences have been published about the effectiveness and safety of online HDF. We present a prospective and observational study conducted on 31 patients treated with online HDF in our center in the last 4 years. The purpose of the study is to compare the evolution of the following aspects before and after starting online HDF: dose of dialysis, purification of medium‐sized/large molecules, inflammation, nutrition, Ca‐P metabolism, anemia, and intradialytic complications. Online HDF increased Kt/V to 31.0% (p>0.001) and reduced postdialysis β2‐M to 66.4% (p>0.001). The rest of the parameters analyzed did not vary significantly. During online HDF, episodes of symptomatic hypotension fell by 45% in relation to conventional hemodialysis, and no relevant complication occurred. Online HDF is very useful in patients in whom we need to increase replacement therapy, such as patients with a large body surface, those in whom we suspect a residual syndrome or those who have been receiving dialysis for a long time and for whom we wish to prevent amyloidosis. Online HDF is safe and better tolerated than conventional hemodialysis.
Melatonin protects against pressure ulcer‐induced oxidative injury of the skin and remote organs in rats
Authors: Şener Göksel , Sert Gülten , Özer Şehirli A. , Arbak Serap , Gedik Nursal , Ayanoğlu‐Dülger Gül
Published: January 2006

Abstract:  Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs; the damage is believed to be due to ischemia/reperfusion (I/R) injury. In this study, we examined the role of oxidative damage in PU and the beneficial effect of treatment with the antioxidant melatonin. PU were induced by applying magnets over steel plates that were implanted under the skin of rats; this compressed the skin and caused ischemia. Within a 12‐hr period, rats were subjected to five cycles of I/R (2 and 0.5 hr respectively), followed by an additional 12 hr of ischemia (to simulate the period at sleep at night). This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, melatonin (5 mg per rat) was either applied locally as an ointment on skin, or administered i.p. (10 mg/kg). At the end of the experimental period, blood and tissue (skin, liver, kidney, lung, stomach, and ileum) samples were taken for determination of biochemical parameters and for histological evaluation. Local treatment with melatonin inhibited the increase in malondialdehyde levels; an index of lipid peroxidation, myeloperoxidase activity; an indicator of tissue neutrophil infiltration, and the decrease in glutathione; a key antioxidant, in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and collagen levels in animals with PU were prevented by melatonin treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU rats. Tissue injury was decreased especially in the locally treated group. Findings of the present study suggest that local and/or systemic melatonin treatment may prove beneficial in the treatment of PU.
Melatonin inhibits both ERα activation and breast cancer cell proliferation induced by a metalloestrogen, cadmium
Authors: Martínez‐Campa C. , Alonso‐González C. , Mediavilla M. D. , Cos S. , González A. , Ramos S. , Sánchez‐Barceló E. J.
Published: January 2006

Abstract:  Cadmium (Cd) is a heavy metal affecting human health both through environmental and occupational exposure. There is evidence that Cd accumulates in several organs and is carcinogenic to humans. In vivo, Cd mimics the effect of estrogens in the uterus and mammary gland. In estrogen‐responsive breast cancer cell lines, Cd stimulates proliferation and can also activate the estrogen receptor independent of estradiol. The ability of this metalloestrogen to increase gene expression in MCF7 cells is blocked by anti‐estrogens suggesting that the activity of these compounds is mediated by ERα. The aims of this work were to test whether melatonin inhibits Cd‐induced proliferation in MCF7 cells, and also to study whether melatonin specifically inhibits Cd‐induced ERα transactivation. We show that melatonin prevents the Cd‐induced growth of synchronized MCF7 breast cancer cells. In transient transfection experiments, we prove that both ERα‐ and ERβ‐mediated transcription are stimulated by Cd. Melatonin is a specific inhibitor of Cd‐induced ERα‐mediated transcription in both estrogen response elements (ERE)‐ and AP1‐containing promoters, whereas ERβ‐mediated transcription is not inhibited by the pineal indole. Moreover, the mutant ERα‐(K302G, K303G), unable to bind calmodulin, is activated by Cd but becomes insensitive to melatonin treatment. These results proved that melatonin inhibits MCF7 cell growth induced by Cd and abolishes the stimulatory effect of the heavy metal in cells expressing ERα at both ERE‐luc and AP1‐luc sites. We can infer from these experiments that melatonin regulates Cd‐induced transcription in both ERE‐ and AP1 pathways. These results also reinforce the hypothesis of the anti‐estrogenic properties of melatonin as a valuable tool in breast cancer therapies.
Low Levels of Pyrazinamide and Ethambutol in Children with Tuberculosis and Impact of Age, Nutritional Status, and Human Immunodeficiency Virus Infection
Authors: Graham S. M. , Bell D. J. , Nyirongo S. , Hartkoorn R. , Ward S. A. , Molyneux E. M.
Published: January 2006

Recent pharmacokinetic studies that included children found that serum drug levels were low compared to those of adults for whom the same dosages were used. This study aimed to characterize the pharmacokinetics of pyrazinamide and ethambutol in Malawian children and to examine the impact of age, nutritional status, and human immunodeficiency virus (HIV) infection. We conducted a pharmacokinetic study of children treated for tuberculosis with thrice-weekly pyrazinamide (
n
= 27; mean age, 5.7 years) and of a separate group of children treated with thrice-weekly ethambutol (
n
= 18; mean age, 5.5 years) as portions of tablets according to national guidelines. Malnutrition and HIV infection were common in both groups. Blood samples were taken just prior to oral administration of the first dose, and subsequent samples were taken at intervals of 2, 3, 4, 7, 24, and 48 h after drug administration. Serum drug levels were low in all children for both drugs; in almost all cases, the maximum concentration of the drug in serum (
C
max
) failed to reach the MIC for
Mycobacterium tuberculosis
. The
C
max
of pyrazinamide was significantly lower in younger children (<5 years) than in older children. The
C
max
of pyrazinamide was also lower for HIV-infected children and children with severe malnutrition, but these differences did not reach statistical significance. No differences were found for ethambutol in relation to age, HIV infection, or malnutrition, but the
C
max
was <2 mg/liter in all cases. Studies of pharmacokinetic parameters and clinical outcomes obtained by using higher dosages of drugs for treatment of childhood tuberculosis are needed, and recommended dosages may need to be increased.
Novel Yeast Cell-Based Assay To Screen for Inhibitors of Human Cytomegalovirus Protease in a High-Throughput Format
Authors: Cottier Valérie , Barberis Alcide , Lüthi Urs
Published: January 2006

The protease encoded by the human cytomegalovirus (HCMV) is an attractive target for antiviral drug development because of its essential function in viral replication. We describe here a cellular assay in the yeast
Saccharomyces cerevisiae
for the identification of small molecule inhibitors of HCMV protease by conditional growth in selective medium. In this system, the protease cleavage sequence is inserted into the
N
-(5′-phosphoribosyl)anthranilate isomerase (Trp1p), a yeast protein essential for cell proliferation in the absence of tryptophan. Coexpression of HCMV protease with the engineered Trp1p substrate in yeast cells results in site-specific cleavage and functional inactivation of the Trp1p enzyme, thereby leading to an arrest of cell proliferation. This growth arrest can be suppressed by the addition of validated HCMV protease inhibitors. The growth selection system presented here provides the basis for a high-throughput screen to identify HCMV protease inhibitors that are active in eukaryotic cells.
Discordances between Interpretation Algorithms for Genotypic Resistance to Protease and Reverse Transcriptase Inhibitors of Human Immunodeficiency Virus Are Subtype Dependent
Authors: Snoeck Joke , Kantor Rami , Shafer Robert W. , Van Laethem Kristel , Deforche Koen , Carvalho Ana Patricia , Wynhoven Brian , Soares Marcelo A. , Cane Patricia , Clarke John , Pillay Candice , Sirivichayakul Sunee , Ariyoshi Koya , Holguin Africa , Rudich Hagit , Rodrigues Rosangela , Bouzas Maria Belen , Brun-Vézinet Françoise , Reid Caroline , Cahn Pedro , Brigido Luis Fernando , Grossman Zehava , Soriano Vincent , Sugiura Wataru , Phanuphak Praphan , Morris Lynn , Weber Jonathan , Pillay Deenan , Tanuri Amilcar , Harrigan Richard P. , Camacho Ricardo , Schapiro Jonathan M. , Katzenstein David , Vandamme Anne-Mieke
Published: January 2006

The major limitation of drug resistance genotyping for human immunodeficiency virus remains the interpretation of the results. We evaluated the concordance in predicting therapy response between four different interpretation algorithms (Rega 6.3, HIVDB-08/04, ANRS [07/04], and VGI 8.0). Sequences were gathered through a worldwide effort to establish a database of non-B subtype sequences, and demographic and clinical information about the patients was gathered. The most concordant results were found for nonnucleoside reverse transcriptase (RT) inhibitors (93%), followed by protease inhibitors (84%) and nucleoside RT inhibitor (NRTIs) (76%). For therapy-naive patients, for nelfinavir, especially for subtypes C and G, the discordances were driven mainly by the protease (PRO) mutational pattern 82I/V + 63P + 36I/V for subtype C and 82I + 63P + 36I + 20I for subtype G. Subtype F displayed more discordances for ritonavir in untreated patients due to the combined presence of PRO 20R and 10I/V. In therapy-experienced patients, subtype G displayed a lot of discordances for saquinavir and indinavir due to mutational patterns involving PRO 90 M and 82I. Subtype F had more discordance for nelfinavir attributable to the presence of PRO 88S and 82A + 54V. For the NRTIs lamivudine and emtricitabine, CRF01_AE had more discordances than subtype B due to the presence of RT mutational patterns 65R + 115 M and 118I + 215Y, respectively. Overall, the different algorithms agreed well on the level of resistance scored, but some of the discordances could be attributed to specific (subtype-dependent) combinations of mutations. It is not yet known whether therapy response is subtype dependent, but the advice given to clinicians based on a genotypic interpretation algorithm differs according to the subtype.
New TEM-Derived Extended-Spectrum β-Lactamase and Its Genomic Context in Plasmids from
Salmonella enterica
Serovar Derby Isolates from Uruguay
Authors: Vignoli Rafael , Cordeiro Nicolas F. , García Virginia , Mota María Inés , Betancor Laura , Power Pablo , Chabalgoity José A. , Schelotto Felipe , Gutkind Gabriel , Ayala Juan A.
Published: January 2006

A small (8.2-kb) ColE1 plasmid encoding TEM-144 (a new β-lactamase with a ceftazidimase profile) was sequenced by a gene-walking strategy. The
bla
TEM
allele was carried on a Tn
2
element, disrupting a Rom protein gene. TEM-144 differs from TEM-1 by two mutations (R164C and E240K) and from the ceftazidime-hydrolyzing TEM-91 by one mutation (T182M).
In Vitro Activity of DX-619, a Novel Des-Fluoro(6) Quinolone, against a Panel of
Streptococcus pneumoniae
Mutants with Characterized Resistance Mechanisms
Authors: Wickman Paul A. , Moland Ellen Smith , Black Jennifer A. , Thomson Kenneth S.
Published: January 2006

The in vitro activities of DX-619 and four other quinolones were compared against
Streptococcus pneumoniae
mutants that contained a variety of alterations within the quinolone resistance-determining regions. DX-619 was the most potent quinolone and was least affected by the mutations.
Tobacco sales in pharmacies: time to quit
Authors: Hudmon K Suchanek , Fenlon C M , Corelli R L , Prokhorov A V , Schroeder S A
Published: January 2006

Objective:To assess the pharmacy profession’s perceptions of tobacco sales in US pharmacies and explore whether a policy prohibiting sales of tobacco in pharmacies would alter adult consumer shopping behaviour.

Subjects and design:In California, surveys were administered to 1168 licensed pharmacists and 1518 pharmacy students, and telephone interviews were conducted with 988 adult consumers.

Results:Most (58.1%) licensed pharmacists were strongly against sales of tobacco in pharmacies, 23.6% were against it, 16.7% were neutral, 1.2% were in favour of it, and 0.4% were strongly in favour of it. Pharmacists who were current tobacco users were more likely to be in favour of tobacco sales in pharmacies than were pharmacists who were current non-users (p < 0.005). Similar statistics were observed for pharmacy students. Most consumers (72.3%) disagreed with the statement, “I am in favour of tobacco products being sold in drugstores”; 82.6% stated that if the drugstore where they most commonly shopped were to stop selling tobacco products, they would shop there just as often, 14.2% would shop there more often, and 3.2% would shop there less often.

Conclusion:Little professional or public support exists for tobacco sales in pharmacies.
ON THE BEHAVIOR OF PHYSICAL PARAMETERS OF AQUEOUS SOLUTIONS AFFECTED BY THE INERTON FIELD OF TESLAR® TECHNOLOGY
Authors: KRASNOHOLOVETS VOLODYMYR , SKLIARENKO SERGIY , STROKACH OLEXANDER
Published: January 2006

We present studies of the behavior of the permittivity of such liquid systems as pure distilled water, alcohol and 50%-aqueous solutions of alcohol as affected by the inerton field generated by a special signal generator contained within a wrist-watch or bracelet made by so-called Teslar® technology. It has been found that the changes are in fact significant. The method employed has allowed us to fix the value of frequency of the field generated by the Teslar® chip. The frequency has been determined to be approximately 8 Hz. The phenomenological consideration and submicroscopic foundations of a significant increase of the permittivity are studied, taking into account an additional interaction, namely, the mass interaction between polar water molecules, which is caused by the inerton field of the Teslar® chip. This is one more proof of Krasnoholovets' concept regarding the existence of a substructure of the matter waves of moving/vibrating entities, i.e. the inerton field, which has been predicted in a series of his previous works.
EFFECTIVE MAGNETIC ANISOTROPY AND COERCIVITY IN Fe NANOPARTICLES PREPARED BY INERT GAS CONDENSATION
Authors: RAFIQ SHAH LUBNA , ALI BAKHTYAR , HASANAIN S. K. , MUMTAZ A. , BAKER C. , ISMAT SHAH S.
Published: January 2006

We present magnetic measurements on iron ( Fe ) nanoparticles in the size range 10–30 nm produced by the Inert Gas Condensation process (IGC). Structural characterization studies show the presence of a core/shell structure, where the core is bcc Fe while the surface layer is Fe -oxide. Analysis of the magnetic measurements shows that the nanoparticles display very large uniaxial anisotropy, K eff ≈3 - 4 × 106 erg/cc. The observed room temperature coercivities lie in the range ≈600 – 973 Oe , much larger than those expected from the Stoner–Wohlfarth model using the bulk iron anisotropy. It can be inferred from the coercivity variation with the particle size that there is a general trend of the coercivity increasing with size, culminating finally in a decrease for high sizes (30 nm) possibly due to the onset of non-coherent magnetization reversal processes.
TOWARDS A RESOURCE-BASED VIEW OF CORPORATE INCUBATORS
Authors: GASSMANN OLIVER , BECKER BARBARA
Published: January 2006

Corporate incubators for technology development are a recent phenomenon whose functioning and implications are not yet well understood. The resource-based view can offer an explanatory model on how corporate incubators function as specialised corporate units that hatch new businesses. While tangible resources, such as the financial, physical and even explicit knowledge flow, are all visible, and therefore easy to measure, intangible resources such as tacit knowledge and branding flow are harder to detect and localise. Managing the resource flow requires the initial allocation of resources to the corporate incubator during its set-up as well as a continuous resource flow to the technology venture and, during the harvest phase, also from it. Two levels of analysis need to be distinguished: (1) the resource flow between the corporate incubator and the technology venture and (2) the resource flow interface between the corporate incubator and the technology venture. Our empirical findings are based on two phases: First, in-depth case studies of 22 companies through 47 semi-structured interviews that were conducted with managers of large technology-intensive corporations' corporate incubators in Europe and the U.S., and second, an analysis of the European Commission's benchmarking survey of 77 incubators.
Floating Nanodot Gate Memory Devices Based on Biomineralized Inorganic Nanodot Array as a Storage Node
Authors: Miura Atsushi , Hikono Takio , Matsumura Takashi , Yano Hiroshi , Hatayama Tomoaki , Uraoka Yukiharu , Fuyuki Takashi , Yoshii Shigeo , Yamashita Ichiro
Published: January 2006

The memory effect in floating nanodot gate field-effect-transistor (FET) was investigated by fabricating biomineralized inorganic nanodot embedded metal–oxide–semiconductor (MOS) devices. Artificially biomineralized cobalt (Co) oxide cores accommodated in ferritins were utilized as a charge storage node of floating gate memory. Two dimensional array of Co oxide core accommodated ferritin were, after selective protein elimination, buried into the stacked dielectric layers of MOS capacitors and MOSFETs. Fabricated MOS capacitors and MOSFETs presented a clear hysteresis in capacitance–voltage (C–V) characteristics and drain current–gate voltage (I
D–V
G) characteristics, respectively. The observed hysteresis in C–V and I
D–V
G are attributed to the electron and hole confinement within the embedded ferritin cores. These results clearly support the biologically synthesized cores work as charge storage nodes. This work proved the feasibility of the biological path for fabrication of electronic device components.
1 V and Stable Dynamic Operation of Laser Diode Using Active Multi-Mode Interferometer
Authors: Shimizu Syogo , Razali Mohd Dannial Bin , Kasahara Kenichi , Ohya Masaki , Naniwae Koichi , Sudo Shinya , Sasaki Tatsuya , Hamamoto Kiichi
Published: January 2006

A low operation voltage of only 1 V at 10 mW was achieved for 1.5 µm wavelength active multi-mode-interferometer laser diodes (MMI-LDs) due to a significant reduction in resistance of 60% compared with that of conventional LDs. We also investigated the dynamic characteristics of the MMI-LDs. Although there was concern that current modulation might cause changes in refractive index, thus, deteriorating self-imaging properties, stable 1 Gbps operation without jitter and improved roll-off frequency due to the low resistance were confirmed experimentally.