bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the FIB to characterize nanoparticle materials
Authors: PERREY C. R. , CARTER C. B. , MICHAEL J. R. , KOTULA P. G. , STACH E. A. , RADMILOVIC V. R.
Published: May 2004

In the 1–100‐nm size regime, the properties of materials can differ significantly from those of their bulk counterparts. The present study applies the focused ion beam (FIB) tool to the characterization of nanoscale structures for scanning and transmission electron microscopy. The strength of this method is its ability to manufacture samples that cannot be produced using traditional means. The films of nanoparticles examined here are examples of such systems; the films are found to be not fully dense, composed of chemically heterogeneous areas and mechanically different from the substrate. Distinct advantages of the application of the FIB for characterization of nanoscale structures are highlighted for several nanoparticle structures. This successful application of FIB techniques provides a pathway to integrate the study of nanoscale production techniques and their resulting structure–property relationships.
Anxiety After Miscarriage: A Review of the Empirical Literature and Implications for Clinical Practice
Authors: Brier Norman
Published: May 2004

Abstract:  Background: Most practitioners now view a miscarriage as a significant psychosocial stressor that results in a high level of dysphoria and grief. Anxiety, although also commonly present, is less frequently considered and less frequently addressed. A review of the empirical literature was conducted to determine if anxiety after a miscarriage is elevated, and if risk is increased for particular types of anxiety syndromes. An attempt was also made to identify the types of interventions that have been found to be helpful in alleviating anxiety. Methods: An electronic search of the Medline and Psych Info databases were conducted using the keywords “miscarriage,”“perinatal loss,”“pregnancy loss,”“anxiety,”“trauma,” and “stress.” The searches were not intentionally circumscribed by date. Further searches were then carried out using references. Studies were subsequently included only if most women in a study sample experienced the pregnancy loss before 20 weeks’ gestation. Results: The literature was relatively limited. With respect to level of anxiety after a miscarriage, 4 studies were located that employed a matched comparison group design, and 3 that employed a follow‐up design. Three studies that used a matched comparison design were located with respect to an increased risk for particular anxiety syndromes. A significant percentage of women experience elevated levels of anxiety after a miscarriage up until about 6 months post‐miscarriage, and they are at increased risk for obsessive‐compulsive and posttraumatic stress disorder. Conclusions: Practitioners, as part of routine care after a miscarriage, should screen for signs of anxiety as well as depression. When signs of anxiety are present, opportunities for catharsis, understanding, and legitimation are likely to be helpful, as is reassurance that the stress is likely to appreciably lessen over the next 6 months.
Photosynthetic characteristics of dwarf and fringe Rhizophora mangle L. in a Belizean mangrove
Authors: CHEESEMAN J. M. , LOVELOCK C. E.
Published: May 2004

Twin Cays (Belize) is a highly oligotrophic mangrove archipelago dominated by Rhizophora mangle L. Ocean‐fringing trees are 3–7 m tall with a leaf area index (LAI) of 2.3, whereas in the interior, dwarf zone, trees are 1.5 m or less, and the LAI is 0.7. P‐fertilization of dwarf trees dramatically increases growth. As a partial explanation of these characteristics, it was hypothesized that differences in stature and growth rates would reflect differences in leaf photosynthetic capacity, as determined by the photochemical and biochemical characteristics at the chloroplast level. Gas exchange and chlorophyll fluorescence were used to compare photosynthesis of dwarf, fringe and fertilized trees. Regardless of zonation or treatment, net CO2 exchange (A) and photosynthetic electron transport were light saturated at less than 500 µmol photons m−2 s−1, and low‐light quantum efficiencies were typical for healthy C3 plants. On the other hand, light‐saturated A was linearly related to stomatal conductance (gs), with seasonal, zonal and treatment differences in photosynthesis corresponding linearly to differences in the mean gs. Overall, photosynthetic capacity appeared to be co‐regulated with stomatal conductance, minimizing the variability of Ci at ambient CO2 (and hence, Ci/Ca). Based on the results of in vitro assays, regulation of photosynthesis in R. mangle appeared to be accomplished, at least in part, by regulation of Rubisco activity.
Developmental process of sun and shade leaves in Chenopodium album L.
Authors: YANO S. , TERASHIMA I.
Published: May 2004

The authors’ previous study of Chenopodium album L. revealed that the light signal for anatomical differentiation of sun and shade leaves is sensed by mature leaves, not by developing leaves. They suggested that the two‐cell‐layered palisade tissue of the sun leaves would be formed without a change in the total palisade tissue cell number. To verify that suggestion, a detailed study was made of the developmental processes of the sun and shade leaves of C. album with respect to the division of palisade tissue cells (PCs) and the data was expressed against developmental time (leaf plastochron index, LPI). The total number of PCs per leaf did not differ between the sun and shade leaves throughout leaf development (from LPI −1 to 10). In both sun and shade leaves, anticlinal cell division of PCs occurred most frequently from LPI −1 to 2. In sun leaves, periclinal division of PCs occurred synchronously with anticlinal division. The constancy of the total number of PCs indicates that periclinal divisions occur at the expense of anticlinal divisions. These results support the above suggestion that two‐cell‐layered palisade tissue is formed by a change of cell division direction without a change in the total number of PCs. PCs would be able to recognize the polarity or axis that is perpendicular to the leaf plane and thereby change the direction of their cell divisions in response to the light signal from mature leaves.
Petrographic and trace element analysis of uranium‐rich tufa calcite, middle Miocene Barstow Formation, California, USA
Authors: Cole Jennifer M. , Rasbury E. Troy , Montañez Isabel P. , Pedone Vicki A. , Lanzirotti Antonio , Hanson Gilbert N.
Published: May 2004

An integrated petrographic and spectroscopic (X‐ray diffraction, phosphor imaging and synchrotron X‐ray absorption spectroscopy) study of tufas from the Miocene Barstow Formation, California, relates sample morphology, mineralogy and geochemical composition. The tufas, composed mainly of calcite that formed at the interface between an ancient alkaline lake and ground or spring waters, have textures similar to those of microbially mediated terrestrial stromatolites and travertines. The tufas have elevated concentrations of a number of trace elements including Mn, Fe, Sr and U. Synchrotron X‐ray fluorescence analyses show that U concentrations can exceed 500 p.p.m. X‐ray absorption spectroscopy indicates that the U in these samples is incorporated as U(IV). It is suggested here that alkaline lake waters had a high U/Ca ratio and tufa calcite formed where groundwater or (possibly epithermal) springs brought in Ca and trace elements such as Sr. The rapid, and possibly microbially mediated, precipitation of calcite allowed for incorporation of high concentrations of trace metals as either structural substitutes or extremely fine‐scale inclusions.
The cyclic hierarchy of the ‘Purbeckian’ Sierra del Pozo Section, Lower Cretaceous (Berriasian), southern Spain
Authors: Anderson Edwin J.
Published: May 2004

The lowermost Cretaceous (Berriasian) Sierra del Pozo Formation is divisible into metre‐scale cycles that are bundled in a four‐tiered hierarchy of cycles and cyclic sequences. At the smallest scale, sixth‐order cycles, thought to be the product of precessionally forced sea‐level fluctuations (c. 20 ka), average less than a metre in thickness, shallow upward and are bounded by surfaces where deeper facies abruptly overlie shallower facies. Bundles of sixth‐order cycles, called fifth‐order sequences, are recognized by two types of asymmetric patterns in facies distribution. First, more pronounced facies changes occur at sixth‐order cycle boundaries lower in a sequence, whereas smaller facies changes occur at cycle boundaries higher in a sequence. Secondly, subtidal marine limestones (i.e. biomicrites and biosparites) are the dominant facies lower in a cyclic sequence, whereas more restricted or shallower water facies (i.e. mud‐cracked microbial laminites, dolomites, shale and clay) are more predominant higher in a cyclic sequence. The bundling of sixth‐order cycles is explained as a product of periodic change (100 ka) in the eccentricity of the earth's orbit. The degree of orbital eccentricity modulates the magnitude of precessional sea‐level fluctuations, which in turn determine the relative facies contrasts at sixth‐order cycle boundaries. Larger scale fourth‐ and third‐order sequences are defined by similar patterns in facies contrast at successive sequence boundaries and by a change in predominant facies type from bottom to top. These patterns are explained as the product of 400 ka and 2 Ma periodic variations in the eccentricity of the earth's orbit. In summary, the strength of the precessional signal varies in consort with periodic changes in orbital eccentricity at three time scales producing a stacked hierarchy of cycles and sequences of cycles. Change in obliquity of the earth's axis may modulate the effects of the precessional signal and thereby modify patterns of preserved cyclic structure. This interpretation of cyclicity in the Sierra del Pozo section is markedly different from that of Jiménez de Cisneros & Vera (1993), who attributed all rock cycles to a single process (obliquity) even though the cycles they described varied in thickness from less than 1 m to more than 4 m. The cycles they described are shown here to be either precessional cycles or composite sets of precessional cycles (100 ka sequences). In this new hierarchical interpretation, ninety‐six 100 ka and twenty‐four 400 ka sequences are recognized, extending the time of deposition of the Sierra del Pozo section to more than 9·6 Ma.
Large earthquakes kill coral reefs at the north‐west Gulf of Aqaba
Authors: Shaked Y. , Agnon A. , Lazar B. , Marco S. , Avner U. , Stein M.
Published: May 2004

Down‐faulting at the north‐west margins of the Gulf of Aqaba is inferred to have triggered a catastrophic sedimentary event at 2.3 ka that killed the Elat fringing coral reef. Whereas segments of the Holocene reef were perfectly fossilized and preserved beneath a veneer of siliciclastic sediments, other segments were abraded, settled by nomads, and later re‐submerged under 4 m of water. Repeated damage triggered by down‐throwing earthquakes degenerate the fringing reefs of the north‐west end of the gulf. Conversely, on the north‐eastern and southern parts of the gulf, where earthquakes uplift the margins, modern reefs are thriving, attached to uplifted fossil reef terraces. Therefore, coastal subsidence moderates the development of fringing coral reefs during the late Holocene sea‐level stand still.
Scaling laws between seismo‐electric/magnetic fields and earthquake magnitude
Authors: Takeuchi A. , Nagahama H.
Published: May 2004

The mechanisms generating the charges/potentials and abnormal electromagnetic radiation that accompany earthquakes have been discussed based on observational, theoretical and laboratory studies, in particular over the last few decades. We previously conducted stick‐slip tests using precut granite cores with a contact electrode on the sample side, and proposed that surface charges released from charge trapping centres on sheared asperities are a possible source of the above‐mentioned charges or potentials. Here we discuss seismo‐electric and magnetic fields formed by the surface charges, and derive their scaling laws with the earthquake magnitude at a distance. According to our model, detectability of these fields at a point on the ground surface depends strongly on wet/dry condition at a fault zone (sheared asperities).
The Effectiveness of Intervention Studies to Decrease Alcohol Use in College Undergraduate Students: An Integrative Analysis
Authors: Hunter Fager Judith , Mazurek Melnyk Bernadette
Published: May 2004

Aims: This analysis was performed to critique intervention studies targeted at decreasing alcohol use in college students for the purpose of (1) synthesizing the various types of interventions and outcomes used, (2) evaluating the effectiveness of the interventions, and (3) identifying the strengths and limitations of prior studies to make recommendations for evidence‐based clinical practice and future research.

Methods: An exhaustive literature search was performed for experimental studies conducted in the past 10 years.

Findings: Analysis using 15 identified studies indicated the following strengths: (1) use of random assignment in many of the studies, (2) use of theoretical frameworks to guide the interventions, (3) replication of previous studies, and (4) inclusion of outcome measures of alcohol use, quantity, and frequency. Limitations included: (1) small convenience samples; (2) use of multiple tools to elicit outcomes, making it difficult to compare results across studies; (3) lack of long‐term follow‐up to assess sustainability of the interventions; (4) use of only self‐report outcome measures, which rely on subject's recall memory; (5) lack of manipulation checks to assure that subjects actually processed the interventions; and (6) a paucity of stress and coping interventions.

Conclusions and Implications for Practice: Extensive research to address the problem of college alcohol use indicates that while education is an integral part of the approach for this problem, it is ineffective when used alone as an intervention strategy. However, some empirical support exists for the use of brief motivational interventions to reduce alcohol use and harm. A personalized approach addressing expectancies and normative use employing a motivational interviewing style may produce desired outcomes.

In addition, theory‐based manualized approaches using stress and coping intervention strategies need to be developed and tested. In the design of future studies, careful attention also should be given to methodological issues such as sampling, measurement issues, and inclusion of more long‐term follow‐up measures.
Effectiveness of Ciprofloxacin, Levofloxacin, or Moxifloxacin for Treatment of Experimental
Staphylococcus aureus
Keratitis
Authors: Dajcs Joseph J. , Thibodeaux Brett A. , Marquart Mary E. , Girgis Dalia O. , Traidej Mullika , O'Callaghan Richard J.
Published: May 2004

The purpose of this study was to quantitatively compare, in a rabbit keratitis model, the levels of effectiveness of moxifloxacin, levofloxacin, and ciprofloxacin for the treatment of
Staphylococcus aureus
isolates of diverse antibiotic susceptibilities. Rabbit eyes were intrastromally injected with approximately 100 CFU of methicillin-sensitive or methicillin-resistant
S. aureus
(MSSA or MRSA, respectively) organisms that were either sensitive or resistant to ofloxacin. One drop of moxifloxacin (0.5%), levofloxacin (0.5%), or ciprofloxacin (0.3%) was topically applied hourly from 4 to 9 (early) or 10 to 15 (late) h postinfection. At 1 h after cessation of therapy, the corneas were harvested, and the number of CFU per cornea was determined. For the ofloxacin-sensitive strains, early treatment of MSSA or MRSA with moxifloxacin, levofloxacin, or ciprofloxacin produced approximately a 5-log decrease in CFU per cornea relative to that in untreated eyes (
P
≤ 0.0001). For late therapy of ofloxacin-sensitive strains, moxifloxacin, levofloxacin, and ciprofloxacin produced approximately 5-, 4-, and 2- to 3-log reductions in CFU per cornea, respectively (
P
≤ 0.0001). Early treatment of the ofloxacin-resistant strains with either moxifloxacin or levofloxacin produced a ≥4-log or ≥3-log decrease, respectively, in the MSSA or MRSA strains (
P
≤ 0.0001), whereas ciprofloxacin treatment produced a 1-log decrease in CFU per cornea relative to that in untreated eyes (
P
= 0.1540). For late treatment of ofloxacin-resistant strains, levofloxacin and ciprofloxacin failed to significantly reduce the number of CFU per cornea (
P
≥ 0.3627), whereas moxifloxacin produced a significant reduction in CFU per cornea of approximately 1 log (
P
≤ 0.0194). Therefore, for three of the four treatments tested, moxifloxacin demonstrated greater effectiveness than either levofloxacin or ciprofloxacin.
Candidate Topical Microbicides Bind Herpes Simplex Virus Glycoprotein B and Prevent Viral Entry and Cell-to-Cell Spread
Authors: Cheshenko Natalia , Keller Marla J. , MasCasullo Veronica , Jarvis Gary A. , Cheng Hui , John Minnie , Li Jin-Hua , Hogarty Kathleen , Anderson Robert A. , Waller Donald P. , Zaneveld Lourens J. D. , Profy Albert T. , Klotman Mary E. , Herold Betsy C.
Published: May 2004

Topical microbicides designed to prevent acquisition of sexually transmitted infections are urgently needed. Nonoxynol-9, the only commercially available spermicide, damages epithelium and may enhance human immunodeficiency virus transmission. The observation that herpes simplex virus (HSV) and human immunodeficiency virus bind heparan sulfate provided the rationale for the development of sulfated or sulfonated polymers as topical agents. Although several of the polymers have advanced to clinical trials, the spectrum and mechanism of anti-HSV activity and the effects on soluble mediators of inflammation have not been evaluated. The present studies address these gaps. The results indicate that PRO 2000, polystyrene sulfonate, cellulose sulfate, and polymethylenehydroquinone sulfonate inhibit HSV infection 10,000-fold and are active against clinical isolates, including an acyclovir-resistant variant. The compounds formed stable complexes with glycoprotein B and inhibit viral binding, entry, and cell-to-cell spread. The effects may be long lasting due to the high affinity and stability of the sulfated compound-virus complex, as evidenced by surface plasmon resonance studies. The candidate microbicides retained their antiviral activities in the presence of cervical secretions and over a broad pH range. There was little reduction in cell viability following repeated exposure of human endocervical cells to these compounds, although a reduction in secretory leukocyte protease inhibitor levels was observed. These studies support further development and rigorous evaluation of these candidate microbicides.
Tn
2009
, a Tn
916
-Like Element Containing
mef
(E) in
Streptococcus pneumoniae
Authors: Del Grosso Maria , Scotto d'Abusco Anna , Iannelli Francesco , Pozzi Gianni , Pantosti Annalisa
Published: May 2004

The association between the macrolide efflux gene
mef
(E) and the
tet
(M) gene was studied in two clinical strains of
Streptococcus pneumoniae
that belonged to serotypes 19F and 6A, respectively, and that were resistant to both tetracycline and erythromycin. The
mef
(E)-carrying element mega (macrolide efflux genetic assembly; 5,511 bp) was found to be inserted into a Tn
916
-like genetic element present in the chromosomes of the two pneumococcal strains. In both strains, mega was integrated at the same site, an open reading frame identical to
orf6
of Tn
916
. The new composite element, Tn
2009
, was about 23.5 kb and, with the exception of the
tet
(M)-coding sequence, appeared to be identical in both strains. By sequencing of the junction fragments of Tn
2009
at the site of insertion into the chromosome, it was possible to show that (i) the insertion site was identical in the two clinical strains and (ii) the integration of Tn
2009
caused a 9.5 kb-deletion in the pneumococcal chromosome. It was not possible to detect the conjugal transfer of Tn
2009
to a recipient pneumococcal strain; however, transfer of the whole element by transformation was shown to occur. It is possible to hypothesize that Tn
2009
relies on transformation for its spread among clinical strains of
S. pneumoniae
.
Effects of Growth Phase and Extracellular Slime on Photodynamic Inactivation of Gram-Positive Pathogenic Bacteria
Authors: Gad Faten , Zahra Touqir , Hasan Tayyaba , Hamblin Michael R.
Published: May 2004

The emergence of antibiotic resistance among pathogenic bacteria has led to efforts to find alternative antimicrobial therapeutics to which bacteria will not be easily able to develop resistance. One of these may be the combination of nontoxic dyes (photosensitizers [PS]) and visible light, known as photodynamic therapy, and we have reported its use to treat localized infections in animal models. While it is known that gram-positive species are generally susceptible to photodynamic inactivation (PDI), the factors that govern variation in degrees of killing are unknown. We used isogenic pairs of wild-type and transposon mutants deficient in capsular polysaccharide and slime production generated from
Staphylococcus epidermidis
and
Staphylococcus aureus
to examine the effects of extracellular slime on susceptibility to PDI mediated by two cationic PS (a polylysine-chlorin

e6

conjugate, pL-c

e6

, and methylene blue [MB]) and an anionic molecule, free c

e6

, and subsequent exposure to 665-nm light at 0 to 40 J/cm
2
. Free c

e6

gave more killing of mutant strains than wild type, despite the latter taking up more PS. Log-phase cultures were killed more than stationary-phase cultures, and this correlated with increased uptake. The cationic pL-c

e6

and MB gave similar uptakes and killing despite a 50-fold difference in incubation concentration. Differences in susceptibility between strains and between growth phases observed with free c

e6

largely disappeared with the cationic compounds despite significant differences in uptake. These data suggest that slime production and stationary phase can be obstacles against PDI for gram-positive bacteria but that these obstacles can be overcome by using cationic PS.
Posaconazole Therapy of Disseminated Phaeohyphomycosis in a Murine Model
Authors: Graybill John R. , Najvar Laura K. , Johnson Elizabeth , Bocanegra Rosie , Loebenberg David
Published: May 2004

Immunocompetent (nu/+) and athymic (nu/nu) BALB/c mice were infected intravenously withWangiella dermatitidisand treated with posaconazole. Posaconazole reduced the counts in tissues and prolonged survival. Of particular interest, posaconazole reduced the counts of this neurotropic pathogen in the brain.
IMP-1 and a Novel Metallo-β-Lactamase, VIM-6, in Fluorescent Pseudomonads Isolated in Singapore
Authors: Koh Tse Hsien , Wang Grace Chee Yeng , Sng Li-Hwei
Published: May 2004

Four carbapenem-resistant
Pseudomonas
spp. were isolated from patients in Singapore. One
Pseudomonas putida
isolate contained a
bla
IMP-1
identical to that first described in Japan. The sequence of a variant
bla
IMP-1
in
Pseudomonas fluorescens
contained four silent mutations compared with the original sequence. The remaining
P. putida
isolates contained
bla
VIM-6
, a novel VIM gene variant.
Closed posteromedial dislocation of the tibiotalar joint without fracture in a basketball player
Authors: Uyar M , Tan A , Işler M , Cetinus E
Published: May 2004

Acute ankle injury is one of the most common problems in sports medicine. Although most are ankle sprains, dislocations are occasionally seen. The case is presented of a closed posteromedial ankle dislocation without fracture which occurred during a basketball match. The literature is also reviewed.
Quantitative sports and functional classification (QSFC) for disabled people with spasticity
Authors: Khalili M A
Published: May 2004

Although sports classification for cerebral palsy has been in use for several years, it is complicated both for training and for scoring. People with cerebral palsy are difficult to fit into classification systems that are appropriate for other disability groups. The aim of this report is to describe the development of a framework for a simple quantitative classification of cerebral palsy. It was designed to be easily understood by all who are investigating, treating, training, coaching, and working with spastic disabled people. The scoring system is accurate and quick, so long as the definitions of items listed are adhered to.
Local corticosteroid injection in iliotibial band friction syndrome in runners: a randomised controlled trial
Authors: Gunter P , Schwellnus M P
Published: May 2004

Objective:To establish whether a local injection of methylprednisolone acetate (40 mg) is effective in decreasing pain during running in runners with recent onset (less than two weeks) iliotibial band friction syndrome (ITBFS).

Methods:Eighteen runners with at least grade 2 ITBFS underwent baseline investigations including a treadmill running test during which pain was recorded on a visual analogue scale every minute. The runners were then randomly assigned to either the experimental (EXP; nine) or a placebo control (CON; nine) group. The EXP group was infiltrated in the area where the iliotibial band crosses the lateral femoral condyle with 40 mg methylprednisolone acetate mixed with a short acting local anaesthetic, and the CON group with short acting local anaesthetic only. The same laboratory based running test was repeated after seven and 14 days. The main measure of outcome was total pain during running (calculated as the area under the pain versus time graph for each running test).

Results:There was a tendency (p  =  0.07) for a greater decrease in total pain (mean (SEM)) during the treadmill running in the EXP group than the CON group tests from day 0 (EXP  =  222 (71), CON  =  197 (31)) to day 7 (EXP  =  140 (87), CON  =  178 (76)), but there was a significant decrease in total pain during running (p  =  0.01) from day 7 (EXP  =  140 (87), CON  =  178 (76)) to day 14 (EXP  =  103 (89), CON  =  157 (109)) in the EXP group compared with the CON group.

Conclusion:Local corticosteroid infiltration effectively decreases pain during running in the first two weeks of treatment in patients with recent onset ITBFS.
Recurrent macroscopic haematuria due to bladder blood vessels after exercise induced haematuria
Authors: Lüthje P , Nurmi I
Published: May 2004

The case is reported of exercise induced asymptomatic macroscopic haematuria, which became recurrent haematuria no longer induced by exercise. The cause, diagnosis, and management are discussed. An overview of the potential causes of sport related haematuria is presented.
THE SUNYAEV–ZEL'DOVICH EFFECT BY MULTIPLE SCATTERING: NUMERICAL SOLUTION OF THE TRANSFER EQUATIONS
Authors: SENGUPTA SUJAN
Published: May 2004

The radiative transfer equations for multiple inverse Compton scattering of the Cosmic Microwave Background Radiation (CMBR) by the hot intra-cluster electrons are solved numerically. The spherical isothermal and inhomogeneous β model has been considered for the electron distribution. The anisotropy of the CMBR caused by scattering, known as thermal Sunyaev–Zel'dovich effect, along the radial axis of the medium is compared with the analytical solution of Kompaneets equation. The X-ray data of several clusters of galaxies at low redshifts provide an estimation of the central electron density n0 to be of the order 10-3. It is found that for this value of n0 the effect of multiple scattering is negligible. The numerically calculated anisotropy along the radial axis matches well with the analytical solution that describes single scattering. The result incorporating multiple scattering is fitted with the recent observation of Sunyaev–Zel'dovich effect in the cluster Abell 2163. It is shown that if n0 is greater by an order of magnitude, which could be possible for cluster of galaxies at comparatively higher redshift, multiple scattering would play a significant role at the Wien region of the anisotropy spectrum. A fitting formula for the correction to the Sunyaev–Zel'dovich effect due to multiple scattering is provided.
TOWARDS THE STANDARD MODEL SPECTRUM FROM ELLIPTIC CALABI–YAU MANIFOLDS
Authors: ANDREAS BJÖRN , CURIO GOTTFRIED , KLEMM ALBRECHT
Published: May 2004

We show that it is possible to construct supersymmetric three-generation models with the Standard Model gauge group in the framework of non-simply-connected elliptically fibered Calabi–Yau threefolds, without section but with a bi-section. The fibrations on a cover Calabi–Yau threefold, where the model has six generations of SU(5) and the bundle is given via the spectral cover description, use a different description of the elliptic fiber which leads to more than one global section. We present two examples of a possible cover Calabi–Yau threefold with a free involution: one is a fiber product of rational elliptic surfaces dP9; another example is an elliptic fibration over a Hirzebruch surface. We compute the necessary amount of chiral matter by "turning on" a further parameter which is related to singularities of the fibration and the branching of the spectral cover.
Transcription Factors in Islet Development and Physiology: Role of PDX‐1 in Beta‐Cell Function
Authors: MELLOUL DANIELLE
Published: May 2004

Abstract: Differentiation of early foregut endoderm into pancreatic endocrine and exocrine cells depends on a cascade of gene activation events controlled by various transcription factors. The first molecular marker identified that specifies the early pancreatic epithelium is the homeodomain‐containing transcription factor PDX‐1. Its absence in mice and humans during development leads to agenesis of the pancreas. Later, it becomes restricted primarily to β cells where it regulates the expression of β cell‐specific genes, and, most importantly, mediates the glucose effect on insulin gene transcription. Although exposure of β cells to high glucose concentrations for relatively short periods stimulates insulin gene expression, chronic exposure has adverse effects on many β‐cell functions, including insulin gene transcription. These events appear to correlate with pdx‐1 gene expression and its ability to bind the insulin gene. We consider that loss of PDX‐1 function or altered pdx‐1 gene expression due to mutations or functional impairment of transcription factors controlling its expression can lead to diabetes.
Molecular Signaling of Somatostatin Receptors
Authors: LAHLOU HICHAM , GUILLERMET JULIE , HORTALA MARYLIS , VERNEJOUL FABIENNE , PYRONNET STÉPHANE , BOUSQUET CORINNE , SUSINI CHRISTIANE
Published: May 2004

Abstract: Somatostatin is a neuropeptide family that is produced by neuroendocrine, inflammatory, and immune cells in response to different stimuli. Somatostatin acts as an endogenous inhibitory regulator of various cellular functions including secretions, motility, and proliferation. Its action is mediated by a family of G‐protein‐coupled receptors (called sst1‐sst5) that are widely distributed in the brain and periphery. The five receptors bind the natural peptides with high affinity, but only sst2, sst5, and sst3 bind the short synthetic analogs used to treat acromegaly and neuroendocrine tumors. This review covers the current knowledge in somatostatin receptor biology and signaling.
Cadherin Switch in Tumor Progression
Authors: HAZAN RACHEL B. , QIAO RUI , KEREN RINAT , BADANO INES , SUYAMA KIMITA
Published: May 2004

Abstract: The loss of E‐cadherin expression or function in epithelial carcinomas has long been thought as a primary reason for disruption of tight epithelial cell‐cell contacts and release of invasive tumor cells from the primary tumor. Indeed, E‐cadherin serves as a widely acting suppressor of invasion and growth of epithelial cancers, and its functional elimination represents a key step in the acquisition of the invasive phenotype for many tumors. Recent evidence indicates, however, that in addition to the loss of the “invasion‐suppressor” E‐cadherin, another adhesion molecule, N‐cadherin, becomes upregulated in invasive tumor cell lines. N‐cadherin was shown to be present in the most invasive and dedifferentiated breast cancer cell lines, and its exogenous expression in tumor cells induces a scattered morphology and heightened motility, invasion, and metastasis. N‐cadherin cooperates with the FGF receptor, resulting in signals that lead to the up‐modulation of MMP‐9 and, hence, cellular invasion. In addition to a signaling function in metastasis, N‐cadherin probably also supports the systemic dissemination of tumor cells by enabling circulating tumor cells to associate with the stroma and the endothelium at distant sites. Here, we summarize the various aspects of the E‐ to N‐cadherin switching in epithelial carcinomas and its potential impact on metastatic progression.
Lipid Rafts and Apical Membrane Traffic
Authors: FÜLLEKRUG JOACHIM , SIMONS KAI
Published: May 2004

Abstract: Lipid rafts are dynamic assemblies floating freely in the surrounding membranes of living cells. This membrane heterogeneity provides a useful concept for understanding processes as diverse as cell polarity, signal transduction, and membrane sorting. Individual rafts are small entities containing thousands of lipids but only a few proteins. Regulation of raft association and size is an elementary feature of interactions at the molecular level. By clustering small rafts into a bigger platform, proteins are brought together for modification. Oligomerization might transform a monomeric weakly raft‐associated protein into an assembly with higher raft affinity. Lectins are multivalent glycoprotein‐binding proteins and are likely to be key players in mediating the clustering of rafts in vivo. Glycosylation‐dependent surface delivery in a polarized fashion is a feature conserved across evolution, and we expect lectins to be at the heart of the molecular machinery responsible for lipid raft delivery to the cell surface. Currently, we are evaluating candidate proteins by affinity chromatography, proteomics, and RNA interference.
Principles of Exocytosis and Membrane Fusion
Authors: JAHN REINHARD
Published: May 2004

Abstract: Exocytosis is a ubiquitous process occurring in every eukaryotic cell including processes as diverse as membrane expansion during growth and the highly regulated release of neurotransmitter from neurons. Work during the past decade has established that exocytotic membrane fusion is mediated by members of conserved protein families including Rab proteins and SNAREs. SNAREs are probably catalyzing membrane fusion, and major progress has been made in unraveling their molecular mechanism. In contrast, less is known about regulatory mechanisms. Here, a brief overview is given about the current state of knowledge, focusing on SNAREs involved in neuronal exocytosis.
PET in the Diagnosis of Neuroendocrine Tumors
Authors: SUNDIN ANDERS , ERIKSSON BARBRO , BERGSTRÖM MATS , LÅNGSTRÖM BENGT , ÖBERG KJELL , ÖRLEFORS HÅKAN
Published: May 2004

Abstract: For general oncological imaging, positron emission tomography (PET) using [18F]fluoro‐deoxy‐glucose (FDG) has evolved as a powerful functional imaging modality. Unfortunately, FDG‐PET has not been as advantageous for imaging gastropancreatic neuroendocrine tumors, and only tumors with high proliferative activity and low differentiation have shown an increased FDG uptake. Therefore, the 11C‐labeled amine precursors L‐dihydroxyphenylalanine and 5‐hydroxy‐L‐tryptophan (5‐HTP) were developed for PET imaging of these tumors. Because of the higher tumor uptake of the latter tracer in a study of patients with endocrine pancreatic tumors, 11C‐5‐HTP was chosen for further evaluation. In comparative studies of patients with carcinoids and endocrine pancreatic tumors, 5‐HTP‐PET proved better than CT and somatostatin receptor scintigraphy for tumor visualization, and many small, previously overlooked lesions were diagnosed by 11C‐5‐HTP‐PET. The strong correlation found during medical treatment between the changes in the transport rate constant at repeated PET and those of U‐HIAA indicates the possible use of 11C‐5‐HTP‐PET also for therapy monitoring. By premedication of patients with Carbidopa orally before PET examination, in order to block the aromatic amino acid decarboxylase enzyme, the decarboxylation rate of 11C‐5‐HTP was decreased, leading to a higher tumor uptake and a considerably lower urinary radioactivity concentration.
Generalized Networks: The Theory of Preprocessing and an Empirical Analysis
Authors: Kennington Jeffery L. , Lewis Karen R.
Published: May 2004

The idea of preprocessing a linear program with the goal of eliminating constraints or columns is well established. The default setting for CPLEX is to apply preprocessing prior to application of any of its four solvers. In this investigation, a set of preprocessing procedures is developed for the special case of a generalized network flow problem. Some procedures involve adding or replacing arcs to eliminate a node. These procedures all produce an optimal basic feasible solution and optimal dual solution to the original problem. In an empirical analysis, our generalized network preprocessor ran approximately seven times faster than the CPLEX 6.5.3 preprocessor, resulting in an overall solution time reduction of over 20%.
Role of Fomepizole in the Management of Ethylene Glycol Toxicity
Authors: Druteika Deon P. , Zed Peter J. , Ensom Mary H. H.
Published: May 2004

Objective. To systematically review English‐language articles on fomepizole administration in patients with ethylene glycol poisoning.

Data Sources. MEDLINE, EMBASE, Current Contents, and PubMed. Search terms were fomepizole, 4‐methylpyrazole, and ethylene glycol. The search was supplemented with a bibliographic review of all relevant articles.

Study Selection. All published reports of fomepizole administration in patients with ethylene glycol poisoning were reviewed, irrespective of study design. We identified one clinical trial and subsequent pharmacokinetic study, one case series, and 13 case reports.

Results. Fomepizole has been investigated in 70 patients in open, unblinded studies. Most patients received an intravenous loading dose, with subsequent variable maintenance doses every 12 hours until plasma ethylene glycol levels became undetectable. Additional hemodialysis treatment generally was administered when patients had renal insufficiency or ethylene glycol levels above 50 mg/dl. Many patients had detectable ethanol levels either because of coadministration or as a result of adjunctive treatment at a referring center. Poorer patient outcomes, such as death and renal insufficiency, were associated with later clinical presentation time after ingestion. At therapeutic fomepizole levels (> 8.6 mg/ml), the half‐life of ethylene glycol was prolonged to over 19 hours. Fomepizole appeared to be well tolerated by most patients.

Conclusion. Fomepizole is an effective alcohol dehydrogenase inhibitor that decreases production of ethylene glycol metabolites. Reduced mortality and morbidity are undetermined because of the small number of patients evaluated to date. Data on comparative efficacy of fomepizole versus ethanol and data on administration of fomepizole in children are limited.
Gastrointestinal Bleeds Associated with Rofecoxib
Authors: Foral Pamela A. , Wilson Amy F. , Nystrom Kelly K.
Published: May 2004

Data suggest that cyclooxygenase (COX)‐2 inhibitors are safer for the gastrointestinal tract than traditional nonsteroidal antiinflammatory drugs (NSAIDs). Rofecoxib, a COX‐2‐specific NSAID, does not inhibit the COX‐1 enzyme, thereby decreasing the potential for gastrointestinal‐related adverse effects. Patients who are at an increased risk for NSAID‐related gastrointestinal bleeding are therefore appropriate candidates for COX‐2 inhibitors. Although the agents provide benefits for many patients, gastrointestinal‐related side effects may occur, and caution should be practiced when prescribing COX‐2 inhibitors. We report two patients who were admitted to the hospital with diagnoses of gastrointestinal bleeds while they were taking rofecoxib.
Effect of Antibiotics on Polymorphonuclear Neutrophil Apoptosis
Authors: Healy Daniel P. , Silverman Paul A. , Neely Alice N. , Holder Ian Alan , Babcock George F.
Published: May 2004

Study Objective. To evaluate the effects of various antibiotics—direct and indirect as a result of bacterial killing—on polymorphonuclear neutrophil (PMN) apoptosis.

Design. In vitro analysis.

Setting. Research laboratory.

Intervention. Whole blood collected from healthy human subjects was incubated with and without Klebsiella pneumoniae (1.0 × 105 colony‐forming units [cfu]/ml) plus ceftazidime 50 μg/ml, gentamicin, ciprofloxacin, trovafloxacin, tetracycline, doxycycline, erythromycin, azithromycin (each 5 μg/ml), or lipopolysaccharide 10 μg/ml. After staining with fluorescein‐conjugated annexin V, red blood cells were lysed, and the remaining white blood cells were assessed by flow cytometry with gating on PMNs.

Measurements and Main Results. In the absence of K. pneumoniae infection, antibiotic exposure directly decreased PMN apoptosis by 17.8% (range −25.0% to −13.9%, p=0.008) compared with untreated cells. In the presence of K. pneumoniae, all antibiotic treatments, even those with poor in vitro activity for the bacterial isolate, decreased PMN apoptosis by 26.2% (range ×38.0% to −17.8%, p>0.001) compared with untreated control cells and by 36.6% compared with untreated (no antibiotic) K. pneumoniae‐stimulated cells (range −46.2% to −28.0%, p>0.001).

Conclusions. All tested antibiotics in clinically relevant concentrations resulted in modest yet consistent decreases in PMN apoptosis. The magnitude of this change increased slightly in the presence of K. pneumoniae infection. In vivo studies are needed to determine whether antibiotic‐associated prolongation of PMN survival improves host response to infection.
Pharmacotherapy of Xerostomia in Primary Sjögren's Syndrome
Authors: Wall Geoffrey C. , Magarity Michelle L. , Jundt Jeffrey W.
Published: May 2004

We reviewed the current literature concerning the treatment of dry mouth in patients with primary Sjögren's syndrome (SJS). Computerized MEDLINE search engines were used with the terms Sjögren, xerostomia, dry mouth, and treatment. References from key articles were searched, and all pertinent articles were procured and reviewed. Primary SJS is an uncommon but serious disorder. Dry mouth caused by SJS can lead to dental erosion, dysphagia, oral infections, and discomfort. Preventing these complications is of paramount importance. Pharmacotherapy is limited to topical saliva substitutes, which are considered first, followed by muscarinic stimulators such as pilocarpine or cevimeline, if required. Immunosuppressive therapy is being investigated. Patients should have regular oral and dental examinations to detect complications. Satisfaction with the efficacy and tolerability of treatment should be monitored frequently. The clinician may have to use a trial‐and‐error approach to determine a successful regimen.
Atypical Neuroleptic Malignant Syndrome Associated with Olanzapine
Authors: Reeves Roy R. , Torres Raphael A. , Liberto Vincent , Hart Roy H.
Published: May 2004

Neuroleptic malignant syndrome (NMS) is a potentially life‐threatening adverse effect of antipsychotic agents. It generally is characterized by fever, altered mental status, rigidity, and autonomic dysfunction. A 53‐year‐old man developed NMS without rigidity while taking olanzapine. Such atypical cases may support either a spectrum concept of NMS or the theory that NMS secondary to atypical antipsychotics differs from that caused by conventional neuroleptics. More flexible diagnostic criteria than currently mandated by the the Diagnostic and Statistical Manual of Mental Disorders, Fourth Revision, may be warranted.
In Vitro Performance Characteristics of Valved Holding Chamber and Spacer Devices with a Fluticasone Metered‐Dose Inhaler
Authors: Asmus Michael J. , Liang Judy , Coowanitwong Intira , Hochhaus Günther
Published: May 2004

Study Objective. To compare the in vitro aerosol deposition characteristics of several commercially available valved holding chamber (VHC) and spacer devices used with a fluticasone metered‐dose inhaler (MDI).

Design. In vitro aerosol deposition study.

Setting. University‐affiliated research center.

Devices. Seven VHC devices: BreatheRite, E‐Z Spacer, EasiVent, AeroChamber, InspirEase, OptiChamber, and Space Chamber. Six spacer devices: OptiHaler, Aerosol Cloud Enhancer (ACE), Gentle‐Haler, MediSpacer, Ellipse, and a 6‐inch tube (1‐inch inside diameter).

Intervention. The respirable dose (aerosol particles 1–5 μm) of fluticasone was determined by sampling 10 220‐μg actuations from five runs with each spacer or VHC plus MDI combination, by using a well‐established in vitro cascade impactor method.

Measurements and Main Results. Fluticasone aerosol was washed from the impactor with methanol and quantified by means of high‐performance liquid chromatography. Differences among outcomes were determined with analysis‐of‐variance testing. Among spacers, Ellipse had the highest respirable dose (104 μg, p<0.01). Respirable doses for the 6‐inch tube (74.3 μg), Gentle‐Haler (81.7 μg), and MediSpacer (82.6 μg) were no different from that of the MDI (p>0.05), whereas respirable doses of OptiHaler (44.6 μg) and ACE (47.2 μg) were less than those of all other spacers (p<0.001). Among VHC devices, respirable doses from EasiVent (35.6 μg), AeroChamber (47.0 μg), InspirEase (52.7 μg), OptiChamber (53.1 μg), and Space Chamber (58.3 μg) were not different (p>0.05), whereas BreatheRite (13.1 μg) and E‐Z Spacer (27.3 μg) respirable doses were less than those of the other VHC devices (p<0.05).

Conclusion. Spacers and VHC devices available in the United States do not demonstrate equivalent in vitro performance with the fluticasone MDI. The difference between highest and lowest respirable doses in each device category would likely lead to clinically relevant differences in the quantity of fluticasone delivered to a patient.