bluuebunny/crossref_metadata_2025 huggingface dataset:
UV-modulated one-dimensional photonic-crystal resonator for visible lights
Authors: Yang S. Y. , Yang P. H. , Liao C. D. , Chieh J. J. , Chen Y. P. , Horng H. E. , Hong Chin-Yih , Yang H. C.
Published: December 2006

The one-dimensional photonic-crystal (A∕SiO2)6∕ZnO∕(SiO2∕A)6 resonators at visible lights are fabricated and characterized, where A may be ZnO or indium tin oxide. Owing to the absorption of ultraviolet (UV) light by the ZnO layers, the refractive index of ZnO layers is changed temporally. This fact led to a temporary shifting of the forbidden band and the resonant mode of the resonator under UV irradiation. Besides, via adjusting the thickness of the ZnO defect layer, the resonant wavelength is manipulated. These experimental data show good consistence with simulated results.
Magnetization reversal, asymmetry, and role of uncompensated spins in perpendicular exchange coupled systems
Authors: Camarero J. , Miguel J. , Goedkoop J. B. , Vogel J. , Romanens F. , Pizzini S. , Garcia F. , Sort J. , Dieny B. , Brookes N. B.
Published: December 2006

Soft x-ray resonant magnetic scattering has been used to investigate the element-selective microscopic magnetization reversal behavior of room temperature perpendicular exchange coupled ferromagnetic∕antiferromagnetic (F∕AF) systems and to study the role of the interfacial coupling strength on it. Different nucleation processes and domain size distributions along the decreasing and increasing branches of the reversal have been found. The size of the magnetic domains during reversal depends on both the F anisotropy and F∕AF coupling strength, decreasing when one of them increases. Evidence of the exchange bias (coercivity enhancement) being induced by pinned (unpinned) uncompensated AF interfacial spins is also shown.
Pair distribution function study and mechanical behavior of as-cast and structurally relaxed Zr-based bulk metallic glasses
Authors: Fan Cang , Liaw P. K. , Wilson T. W. , Choo H. , Gao Y. F. , Liu C. T. , Proffen Th. , Richardson J. W.
Published: December 2006

Contrary to reported results on structural relaxation inducing brittleness in amorphous alloys, the authors found that structural relaxation actually caused an increase in the strength of Zr55Cu35Al10 bulk metallic glass (BMG) without changing the plasticity. Three dimensional models were rebuilt for the as-cast and structurally relaxed BMGs by reverse Monte Carlo (RMC) simulations based on the pair distribution function (PDF) measured by neutron scattering. Only a small portion of the atom pairs was found to change to more dense packing. The concept of free volume was defined based on the PDF and RMC studies, and the mechanism of mechanical behavior was discussed.
First principles calculations on martensitic transformation and phase instability of Ni–Mn–Ga high temperature shape memory alloys
Authors: Chen Jie , Li Yan , Shang Jiaxiang , Xu Huibin
Published: December 2006

Martensitic transformation and phase instability of Ni8+xMn4Ga4−x high-temperature shape memory alloys have been investigated by first principles calculations using the pseudopotentials plane wave method. The tetragonality (the ratio between the lattice parameter c and a) increases with the increasing of Ni content. The total energy difference between parent and martensite phases plays an important role on the martensitic transformation. The formation energy calculations indicate the instability of Ni–Mn–Ga alloy with extra high Ni content. The densities of states of the alloys are discussed.
Investigation of whispering gallery mode dependence on cavity geometry of quasiperiodic photonic crystal microcavity lasers
Authors: Lee Po-Tsung , Lu Tsan-Wen , Tsai Feng-Mao , Lu Tien-Chang
Published: December 2006

Dodecagonal (12-fold) quasiperiodic photonic crystal (DQPC) microcavity lasers sustaining whispering gallery mode (WGM) are fabricated. Lasing characteristics of DQPC D2 microcavity lasers are obtained and compared with triangular lattice D2 photonic crystal (PC) lasers, and ultralow threshold is obtained. The strong WGM mode dependence on 12 nearest airholes of DQPC D2 microcavity and its fabrication tolerance is investigated and discussed by randomly varying the lattice of two separate regions. This mode dependence also indicates that one can enhance a WGM in different PC microcavities by modifying the cavity boundary to be circular.
Ultrafast carrier thermalization in InN
Authors: Wen Yu-Chieh , Chen Cheng-Ying , Shen Chang-Hong , Gwo Shangjr , Sun Chi-Kuang
Published: December 2006

Carrier thermalization dynamics in heavily doped n-type InN was investigated at room temperature with a femtosecond transient transmission measurement. The dependence of hot carrier cooling time on the total electron density indicates that the plasma screening of electron-LO phonon interactions is responsible for the reduction in energy-loss rate. Under low excitation, the carriers with different excess energies can be found to cool down with a fixed thermalization time of 1.4ps. Intensity dependent study suggests that this relatively slow carrier cooling time could be attributed to the screening effect by high-background-doping plasma rather than the hot phonon effect.
Magnetic and superconducting properties of single crystals of Sr2HoRu1−xCuxO6 grown from high temperature solutions
Authors: Rao S. M. , Wang K. J. , Yen N. Y. , Chen Y. Y. , Tsai C. B. , Neeleshwar S. , Wu M. K. , Srivastava J. K. , Ling M. C. , Liu H. L. , Ling D. C.
Published: December 2006

Single crystals of Sr2HoRu1−xCuxO6 (with x=0–0.2), measuring 2–3mm across have been grown from PbO–PbF2 based solutions in the temperature range of 1250–1150°C. The crystals exhibit octahedral morphology and belong to the monoclinic space group P21∕n. While Sr2HoRuO6 is found to be antiferromagnetic with weak ferromagnetism below 30K, the solid solutions containing Cu exhibit a diamagnetic transition at 31K which increases in magnitude and temperature with increasing Cu. Through a correlation of magnetic and calorimetric properties, these crystals are concluded to be spin-glass superconductors.
Roles of oxygen and water vapor in the oxidation of halogen terminated Ge(111) surfaces
Authors: Sun Shiyu , Sun Yun , Liu Zhi , Lee Dong-Ick , Pianetta Piero
Published: December 2006

The initial stage of the oxidation of Cl and Br terminated Ge(111) surfaces is studied using photoelectron spectroscopy. The authors perform controlled experiments to differentiate the effects of different factors in oxidation, and find that water vapor and oxygen play different roles. Water vapor effectively replaces the halogen termination layers with the hydroxyl group, but does not oxidize the surfaces further. In contrast, little oxidation is observed for Cl and Br terminated surfaces with dry oxygen alone. However, with the help of water vapor, oxygen oxidizes the surface by breaking the Ge–Ge back bonds instead of changing the termination layer.
Generalization of the fire line rotation model to curved fire lines
Authors: Oliveras Imma , Piñol Josep , Viegas Domingos X.
Published: December 2006

The concept of fire line rotation was applied to curved fire line elements like those of a point ignition fire in a slope or in a wind field. Convective effects induced by the fire modify the shape of the flame around its perimeter and affect the propagation of the fire front. From the analysis of laboratory experiments under wind or slope conditions, the existence of a rotation movement of the fire line elements is demonstrated. It is also shown that the semi-empirical law developed for straight lines is applicable with some adjustments to curved fire lines.
Simulation of prescribed burning strategies in south-west Tasmania, Australia: effects on unplanned fires, fire regimes, and ecological management values
Authors: King Karen J. , Cary Geoffrey J. , Bradstock Ross A. , Chapman Joanne , Pyrke Adrian , Marsden-Smedley Jonathon B.
Published: December 2006

Computer simulation modelling provides a useful approach for determining the trade-offs between the extent of prescribed burning and the long-term impacts of unplanned fires on management values. In the present study, FIRESCAPE-SWTAS, a process-based fire regime and vegetation dynamics model, was used in the World Heritage Area of south-west Tasmania, Australia, to investigate the implications of different prescribed burning treatments on identified management objectives. Treatments included annual prescribed burning of different proportions of the most flammable vegetation community, buttongrass moorlands. Additionally, a proposed strategic burning treatment for this landscape was simulated for comparison with these treatments. Simulations identified the nature of the relationships between the prescribed burn treatment level and the fire size distributions, the mean incidence, and the mean annual areas burnt by unplanned fires, with all three parameters declining with increases in treatment level. The study also indicated that strategically located treatment units were able to enhance the reduction in the fire risk to vegetation species susceptible to fire (fire-intolerant species).
Investigation of the wind speed threshold above which discarded cigarettes are likely to be moved by the wind
Authors: Xanthopoulos Gavriil , Ghosn Dany , Kazakis George
Published: December 2006

Cigarette butts thrown from passing cars often become fire ignition sources. However, this is only possible if a butt ends up on dead and dry fuels on the roadside. The current paper presents two experiments, carried out in a wind tunnel, designed to investigate the wind speed thresholds above which a butt thrown on the road is unlikely to stay on the road surface but will roll with the wind. The work was done for three road surfaces: asphalt, cement, and compacted soil. The experiments demonstrated that a lower wind speed is necessary for cigarette butts to start rolling from a still condition than the wind speed needed for whole cigarettes. Three wind speed thresholds, 0.88 m s–1 for asphalt, 1.63 m s–1 for cement, and 2.33 m s–1 for compacted soil, represent a conservative lower limit below which movement of still butts is highly unlikely. Three logistic regression equations were developed for calculating the probability that a cigarette butt thrown on the road surface under wind will continue to roll. They show that for wind speeds of less than 4.5 m s–1, a cigarette butt thrown on a dirt road is much less likely to be carried by the wind than if it was thrown on an asphalt or cement surface. The wind speed values refer to a height of 5 cm. The present paper provides a discussion of how this value relates to commonly used meteorological wind previsions. It also includes an example of how the findings can be used for fire prevention purposes.
Influence of topography and forest structure on patterns of mixed severity fire in ponderosa pine forests of the South Dakota Black Hills, USA
Authors: Lentile Leigh B. , Smith Frederick W. , Shepperd Wayne D.
Published: December 2006

We examined the influence of topography and stand structure on fire effects within the perimeter of the ~34 000 ha Jasper fire of 2000 in ponderosa pine (Pinus ponderosa Laws.) forests of the South Dakota Black Hills, USA. We used a remotely sensed and field-verified map of post-fire burn severity (accuracy 69%, kappa statistic 0.54), the Digital Elevation Model, and vegetation databases maintained by the Black Hills National Forest to empirically test relationships at 500 randomly located points in each of three severity classes. Burn severity was defined as the relative degree of post-fire change based on fire effects on soil, forest floor, and vegetation. This fire burned rapidly, yet created a patchy mosaic of effects (25, 48, and 27% low, moderate, and high severity). Stands burned by low and moderate severity fire had fewer trees (stand density index <470 with fewer than 230 trees >13 cm diameter at breast height ha–1) and were found on less steep sites (slope < 18%). Denser stands (stand density index >470) with larger trees (average stand diameter >24 cm) or many small trees were more likely to burn with high severity effects. Our results suggest that managers should consider topography and stand structure together when making strategic decisions about which stands to thin or otherwise manage to reduce the severity with which forests will burn in wildfires.
Fire regimes and soil erosion in north Australian hilly savannas
Authors: Russell-Smith Jeremy , Yates Cameron , Lynch Brian
Published: December 2006

Soil erosion is recognised as a major landscape management issue in northern Australia, given highly erodible soils, and high rainfall erosivity associated with low soil surface cover and intense storm events at the commencement of the wet season. Although recent continental-scale erosion modelling addresses such conditions, it does not take account of contemporary fire regimes dominated by annual, late dry season wildfires, especially in extensive higher slope (≥5%) regions of monsoonal Australia. The present paper reports a simple erosion pin assessment at two sites, contrasting soil loss and movement on unburnt and late dry season-burnt hillslopes over one wet season. Although very significant erosion was observed on both unburnt and burnt treatments, overall there was roughly three times the net soil loss and two times more soil movement on late dry season-burnt plots. The landscape scale of late dry season fire regimes, and implications for increased impacts of soil erosion on soil organic matter, nutrients, and ecosystem health are discussed. Collectively, assembled data suggest that more attention needs to be given to understanding and managing the impacts of contemporary fire regimes on hillslope soil erosion processes in the seasonal Australian tropics.
Accurate estimation of mean fire interval for managing fire
Authors: Kou Xiaojun , Baker William L.
Published: December 2006

Accurate fire-history data are needed if local management of fire or costly national plans for restoring and managing fire and forest structure are to succeed. Fire-history researchers often use fire scars and the composite fire interval method to reconstruct parameters of past fire regimes, such as the population mean fire interval, but the composite method has serious limitations. We modified an alternative non-composite fire interval method, the individual-tree fire-interval method, to derive a more accurate new method, the all-tree fire-interval method. A stochastic fire-scar generating model to assess the accuracy of the new method and its predecessors was then used. Three factors (scarring ratio, population mean fire interval, and tree age) that affect accuracy were varied in the model runs. More complexity (trees with varied scarring ratio between the first scar and successive scars) also was modelled to test the robustness of the method. The all-tree fire-interval method was shown to greatly improve accuracy and provide unbiased estimates of the population mean fire interval. The method also produced encouraging results when scarring was more complex. The new all-tree fire-interval method will require further research on the rates at which trees are scarred by fire, but this would be generally beneficial to understanding fire history.
Response of boreal plant communities to variations in previous fire-free interval
Authors: Johnstone Jill F.
Published: December 2006

The present study used overlapping burn scars from natural wildfires to examine the effects of changes in the fire-free interval on early successional plant communities in boreal forests of central Yukon Territory, Canada. Data on plant community composition and residual organic material were collected in the first decade of post-fire regeneration in two study areas with recent fire overlap. Sites with a shorter fire-free interval had reduced loads of deadwood and shallower organic layers after the most recent fire. Multivariate analysis of species cover indicated that sites in and out of the burn overlap zones also supported distinct plant communities. Differences in the plant communities were associated with a greater abundance of woody deciduous species, such as Populus tremuloides, Salix spp., and Shepherdia canadensis, at sites that had recently re-burned. Sites that burned after a longer interval had higher moss cover and greater abundance of Picea mariana, Calamagrostis canadensis, and Ribes glandulosum in one study area, and Epilobium angustifolium in the second area. Ordinations of species cover indicated that plant community patterns were most strongly associated with gradients related to fire history and topography. In general, shorter fire-free intervals reduced pools of residual plant material and favored dominance of resprouting, woody deciduous species.
Atmospheric nitrogen deposition promotes carbon loss from peat bogs
Authors: Bragazza Luca , Freeman Chris , Jones Timothy , Rydin Håkan , Limpens Juul , Fenner Nathalie , Ellis Tim , Gerdol Renato , Hájek Michal , Hájek Tomáš , Iacumin Paola , Kutnar Lado , Tahvanainen Teemu , Toberman Hannah
Published: December 2006

Peat bogs have historically represented exceptional carbon (C) sinks because of their extremely low decomposition rates and consequent accumulation of plant remnants as peat. Among the factors favoring that peat accumulation, a major role is played by the chemical quality of plant litter itself, which is poor in nutrients and characterized by polyphenols with a strong inhibitory effect on microbial breakdown. Because bogs receive their nutrient supply solely from atmospheric deposition, the global increase of atmospheric nitrogen (N) inputs as a consequence of human activities could potentially alter the litter chemistry with important, but still unknown, effects on their C balance. Here we present data showing the decomposition rates of recently formed litter peat samples collected in nine European countries under a natural gradient of atmospheric N deposition from ≈0.2 to 2 g·m
−2
·yr
−1
. We found that enhanced decomposition rates for material accumulated under higher atmospheric N supplies resulted in higher carbon dioxide (CO
2
) emissions and dissolved organic carbon release. The increased N availability favored microbial decomposition (

i

) by removing N constraints on microbial metabolism and (

ii

) through a chemical amelioration of litter peat quality with a positive feedback on microbial enzymatic activity. Although some uncertainty remains about whether decay-resistant
Sphagnum
will continue to dominate litter peat, our data indicate that, even without such changes, increased N deposition poses a serious risk to our valuable peatland C sinks.
Zfp423
controls proliferation and differentiation of neural precursors in cerebellar vermis formation
Authors: Alcaraz Wendy A. , Gold David A. , Raponi Eric , Gent Peter M. , Concepcion Dorothy , Hamilton Bruce A.
Published: December 2006

Neural stem cells and progenitors in the developing brain must choose between proliferation with renewal and differentiation. Defects in navigating this choice can result in malformations or cancers, but the genetic mechanisms that shape this choice are not fully understood. We show by positional cloning that the 30-zinc finger transcription factor Zfp423 (OAZ) is required for patterning the development of neuronal and glial precursors in the developing brain, particularly in midline structures. Mutation of
Zfp423
results in loss of the corpus callosum, reduction of hippocampus, and a malformation of the cerebellum reminiscent of human Dandy–Walker patients. Within the cerebellum,
Zfp423
is expressed in both ventricular and external germinal zones. Loss of
Zfp423
results in diminished proliferation by granule cell precursors in the external germinal layer, especially near the midline, and abnormal differentiation and migration of ventricular zone-derived neurons and Bergmann glia.
Vaccination and Infection as Causative Factors in Japanese Patients With Rasmussen Syndrome: Molecular Mimicry and HLA Class I
Authors: Takahashi Yukitoshi , Matsuda Kazumi , Kubota Yuko , Shimomura Jiro , Yamasaki Etsuko , Kudo Tatsuya , Fukushima Katsuyuki , Osaka Hitoshi , Akasaka Noriyuki , Imamura Atsushi , Yamada Shinji , Kondo Naomi , Fujiwara Tateki
Published: December 2006

Rasmussen syndrome is an intractable epilepsy with a putative causal relation with cellular and humoral autoimmunity. Almost half of the patients have some preceding causative factors, with infections found in 38.2%, vaccinations in 5.9% and head trauma in 8.9% of Japanese patients. In a patient with seizure onset after influenza A infections, cross‐reaction of the patient′s lymphocytes with GluRε2 and influenza vaccine components was demonstrated by lymphocyte stimulation test. Database analyses revealed that influenza A virus hemagglutinin and GluRε2 molecules contain peptides with the patient′s HLA class I binding motif (HLA ࢤ A*0201). The relative risks of HLA class I genotypes for Rasmussen syndrome are 6.1 (A*2402), 6.4 (A*0201), 6.3 (A*2601) and 11.4 (B*4601). The relative risks of HLA class I‐A and B haplotypes are infinity (A*2601+B*5401), 21.1 (A*2402+B*1501), 13.3 (A*2402+B*4801) and 5.1 (A*2402+B*5201). Some alleles and haplotypes of HLA class I may be the risk factors in Japanese patients. Cross‐reactivity of cytotoxic T lymphocytes may contribute to the processes leading from infection to the involvement of CNS.
HIV‐1 Tat Triggers TGF‐β Production and NK Cell Apoptosis that is Prevented by Pertussis Toxin B
Authors: Poggi Alessandro , Zocchi Maria Raffaella
Published: December 2006

Herein, we show that PTX‐B and its non‐toxic mutant PT9K/129G inhibit transcription and secretion of TGF‐β elicited by HIV‐1 Tat in NK cells. Moreover, Tat strongly activates the cJun component of the multimolecular complex AP‐1, while TGF‐β triggers cFos and cJun. Treatment of NK cells In turn,with PTX‐B or PT9K/129G inhibits Tat and TGF‐β‐induced activation of AP‐1. TGF‐β enhances starvation‐induced NK cell apoptosis, reduces the transcription of the antiapoptotic protein Bcl‐2 and inhibits Akt phosphorylation induced by oligomerization of the triggering NK cell receptor NKG2D. All these TGF‐β‐mediated effects are prevented by PTX‐B or PT9K/129G, through a PI‐3K‐dependent mechanism. Finally, PTX‐B and PT9K/129G upregulate Bcl‐xL, the isoform of Bcl‐x that protects cells from starvation‐induced apoptosis. Of note, in NK cells from patients with HIV‐1 infection, mRNA expression of Bcl‐2 and Bcl‐xL was consistently lower than that of healthy donors; interestingly, TGF‐β and Tat were detected in the sera of these patients. These data suggest that Tat‐induced TGF‐β production and the consequent NK cell failure, possibly occurring during early HIV‐1 infection, may be regulated by PTX‐B and PT9K/129G.
Serum Reactivity Against Bacterial Pyruvate Dehydrogenase: Increasing the Specificity of Anti‐Mitochondrial Antibodies for the Diagnosis of Primary Biliary Cirrhosis
Authors: Miyakawa Hiroshi , Tanaka Atsushi , Selmi Carlo , Hosoya Naomi , Mataki Norikazu , Kikuchi Kentaro , Kato Takashi , Arai Junya , Goto Toshihiro , Gershwin M. Eric
Published: December 2006

Antimitochondrial antibodies (AMA) are the serum hallmark of primary biliary cirrhosis (PBC). However, AMA‐positivity can be found in non‐PBC sera when lower dilutions are used, thus raising issues about the specificity and sensitivity of the test. AMA reacts primarily with the lipoylated domains of pyruvate dehydrogenase‐E2 (PDC‐E2) which is highly conserved across species, including bacteria. We studied 77 serum samples, including 24 from patients with anti‐PDC‐E2‐positive PBC and 53 controls (16 with autoimmune hepatitis (AIH), 10 with primary sclerosing cholangitis (PSC), and 27 healthy individuals) for their reactivities at serial dilutions (1:10, 1:20 and 1:40) against Escherichia coli DH5 alpha lysate overexpressing human PDC‐E2 using immunoblotting (IB). A murine anti‐human PDC‐E2 monoclonal antibody (mAB) was used as control. We further studied positive sera using adsorption with a synthetic E. coli peptide sharing similarity with human PDC‐E2. Finally, we verified whether a unique buffer for E. coli preparation could reduce non‐specific serum reactivity. Results demonstrated that 100% of anti‐PDC‐E2‐positive PBC and up to 38% of control sera at 1:10 dilution recognized E. coli PDC‐E2 at IB while dilution tests indicated that the overall potency of PBC reactivity was 100‐fold higher compared to controls. In fact, a subgroup (20‐38%) of non‐PBC sera were positive at low titers but lost the reactivity when absorbed with the synthetic E. coli peptide. Finally, our unique buffer reduced the reactivity of non‐PBC sera as measured by ELISA. In conclusion, we demonstrated that weak cross‐reactivity with E. coli PDC‐E2 occurs in non‐PBC sera at lower dilutions and that such reactivity is not due to AMA‐positivity. The use of a specific buffer might avoid the risk of false positive AMA determinations when E. coli‐expressed recombinant antigens are used.
Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes
Authors: Aoki Christopher A. , Dawson Kevin , Kenny Thomas P. , Gershwin M. Eric , Bowlus Christopher L.
Published: December 2006

Primary sclerosing cholangitis (PSC) is a chronic disease of the bile ducts characterized by an inflammatory infiltrate and obliterative fibrosis. The precise role of the immune system in the pathogenesis of PSC remains unknown. We used RNA microarray analysis to identify immune‐related genes and pathways that are differentially expressed in PSC. Messenger RNA (mRNA) from peripheral blood mononuclear cells (PBMC) was isolated from both patients with PSC and age and sex matched healthy controls. Samples from 5 PSC patients and 5 controls were analyzed by microarray and based upon rigorous statistical analysis of the data, relevant genes were chosen for confirmation by RT‐PCR in 10 PSC patients and 10 controls. Using unsupervised hierarchical clustering, gene expression in PSC was statistically different from our control population. Interestingly, genes within the IL‐2 receptor beta, IL‐6 and MAP Kinase pathways were found to be differently expressed in patients with PSC compared to controls. Further, individual genes, TNF‐α induced protein 6 (TNFaip6) and membrane‐spanning 4‐domains, subfamily A (ms4a) were found to be upregulated in PSC while similar to Mothers against decapentaplegic homolog 5 (SMAD 5) was downregulated. In conclusion, several immune‐related pathways and genes were differentially expressed in PSC compared to control patients, giving further evidence that this disease is systemic and immune‐mediated.
Influenza Vaccination of Patients With Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA)
Authors: Stojanovich Ljudmila
Published: December 2006

The role of influenza vaccination in patients suffering from autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), has long been a subject of discussion. The risk of exacerbation of the main disease following vaccination is of particular concern, and needs to be carefully evaluated against the risk of disease flares as a result of infections. Our study included 69 SLE patients and 54 RA patients, all in stable condition. We split the groups into two subgroups each: patients in SLE1 (23 patients) and RA1 (23 patients) received the flu vaccine (“Vaxigrip”, Aventis Pasteur) in November 2003. Patients in SLE2 (46 patients) and RA2 (31 patients) were not vaccinated. Throughout the following year, we studied parameters of disease activity and the occurrence of viral respiratory and bacterial infections in our patients. The vaccine was well tolerated in all cases. Vaccinated patients had significantly fewer occurrences of infections. Every viral and bacterial infection resulted in the worsening of the main disease. We believe that influenza vaccine is indicated for SLE and RA patients in stable condition. However, this decision must be made on a patient‐by‐patient basis. We plan to continue our study with the goal of formulating a better protocole for the clinical practice.
The Possible Role of Transplacentally‐Acquired Antibodies to Infectious Agents, With Molecular Mimicry to Nervous System Sialic Acid Epitopes, as Causes of Neuromental Disorders: Prevention and Vaccine Implications
Authors: Nahmias André J. , Nahmias Susanne Beckman , Danielsson Dan
Published: December 2006

Proof of causality of most neuromental disorders (NMD′s) is largely unavailable. Lessons from four‐decade investigations of the epidemiology, immunology, pathogenesis, prevention and therapy of perinatal infectious agents, which invade directly the nervous system, have led us to propose a new indirect effect hypothesis: maternal transplacentally‐acquired antibodies, to agents with epitope molecular mimicry with the developing nervous system, can cross the fetus/infant′s blood–nervous system barriers to cause NMD′s, clinically manifest years later.

Further rationale is provided by relevant evolutionary/developmental (EVO–DEVO) considerations—applicable also to some vaccines. The hypothesis is being tested in: (a) older pregnancy studies with available maternal and newborn sera, and follow‐up of the progeny for NMD′s; and (b) NMD registry individuals linked to their stored newborn blood spots. Preliminary results support a possible role for schizophrenia of high‐tittered antibodies to some agents (toxoplasma, influenza and herpes simplex type 2 virus).

A model that includes likely genetic and postnatal influences is schematized and a list of putative agents and factors, based on varying rationales, is tabulated. In case pilot studies are confirmed, the identified agent(s) and antibodies would need to be tested in new prospectively enrolled pregnant women, so as to establish further risk factors leading to possible preventive modalities.
Saving Death: Apoptosis for Intervention in Transplantation and Autoimmunity
Authors: Li Alice , Ojogho Okechukwu , Escher Alan
Published: December 2006

Long considered immunologically “bland,” apoptotic cells are now recognized as important modulators of immune responses. The role of apoptosis in immunological homeostasis has been inferred from several findings, for example, induction of tolerance after injection of apoptotic cells and the capacity of APCs like macrophages and DCs to induce and maintain tolerance after phagocytosis of dead cells. Processing of apoptotic cells by DCs is of particular interest, because DCs are the only known APCs capable of activating naïve T lymphocytes to become effector or regulatory cells. In that regard, recent evidence suggests that phagocytosis of apoptotic cells by DCs can induce Tregs, a finding that has significant implications for the treatment of a variety of immune‐mediated inflammatory disorders. Here, we review the relationship between apoptotic cells, DCs, and Tregs, and its impact on prevention of transplant rejection and treatment of autoimmune diseases.
Is there a Common Genetic Basis for Autoimmune Diseases?
Authors: Anaya Juan-Manuel , Gómez LuisMiguel , Castiblanco John
Published: December 2006

Autoimmune diseases (ADs) represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. The commonality between them however, is the damage to tissues and organs that arises from the response to self‐antigens. The presence of shared pathophysiological mechanisms within ADs has stimulated searches for common genetic roots to these diseases. Two approaches have been undertaken to sustain the “common genetic origin” theory of ADs. Firstly, a clinical genetic analysis showed that autoimmunity aggregates within families of probands diagnosed with primary Sjögren′s (pSS) syndrome or type 1 diabetes mellitus (T1D). A literature review supported the establishment of a familiar cluster of ADs depending upon the proband′s disease phenotype. Secondly, in a same and well‐defined population, a large genetic association study indicated that a number of polymorphic genes (i.e. HLA-DRB1, TNF and PTPN22) influence the susceptibility for acquiring different ADs. Likewise, association and linkage studies in different populations have revealed that several susceptibility loci overlap in ADs, and clinical studies have shown that frequent clustering of several ADs occurs. Thus, the genetic factors for ADs consist of two types: those which are common to many ADs (acting in epistatic pleitropy) and those that are specific to a given disorder. Their identification and functional characterization will allow us to predict their effect as well as to indicate potential new therapeutic interventions. Both autoimmunity family history and the co‐occurrence of ADs in affected probands should be considered when performing genetic association and linkage studies.
Oral Tolerance: Therapeutic Implications for Autoimmune Diseases
Authors: Faria Ana M. C. , Weiner Howard L.
Published: December 2006

Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL‐4/IL‐10) and Th3 (TGF‐β) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL‐4, IL‐10, anti‐IL‐12, TGF‐β, cholera toxin B subunit (CTB), Flt‐3 ligand, anti‐CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE), uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD) mouse, plus non‐autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag‐specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy and early therapy.
Immune‐Neuroendocrine Interactions and Autoimmune Diseases
Authors: Jara Luis J. , Navarro Carmen , Medina Gabriela , Vera-Lastra Olga , Blanco Francisco
Published: December 2006

The relationship between immune‐neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune‐neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.

Autoimmune rheumatic diseases (ARD) are characterized by aberrant production of pro‐inflammatory cytokines, which are a potent activator of the HPA axis. In consequence, high levels of pro‐inflammatory hormones such as estrogens and prolactin, and low levels of glucocorticoids, an anti‐inflammatory hormone, have been described in the active phase of ARD. In addition, high levels of pro‐inflammatory hormones and cytokines have also been frequently detected in organ involvement of patients with ARD, suggesting an abnormal local neuroendocrine immune interaction. There is evidence that hormonal changes may appear before the symptomatic phase of the disease. Therefore, it is possible that a pro‐inflammatory hormone favors the rupture of tolerance, which is a key feature of autoimmune diseases. The interactions between the immune‐neuroendocrine system have a major impact on our understanding of the pathogenic mechanisms, diagnosis and therapy of ARD.
The Conservative Physiology of the Immune System. A Non‐Metaphoric Approach to Immunological Activity
Authors: Vaz Nelson M. , Ramos Gustavo C. , Pordeus Vitor , Carvalho Claudia R.
Published: December 2006

Historically, immunology emerged as a biomedical science, concerned with host defense and production of anti‐infectious vaccines. In the late 50s, selective theories were proposed and from then on, immunology has been based in a close association with the neo‐Darwinian principles, such as random generation of variants (lymphocyte clones), selection by extrinsic factors (antigens)—and, more generally, on genetic determinism and functionalism. This association has had major consequences: (1) immunological jargon is full of “cognitive” metaphors, founded in the idea of “foreignness”; (2) the immune system is described with a random clonal origin, coupled to selection by random encounters; and (3) physiological events are virtually absent from immunological descriptions. In the present manuscript, we apply systemic notions to bring forth an explanation including systemic mechanisms able to generate immunological phenomena. We replace “randomness plus selection” and the notion of foreignness by a history of structural changes which are determined by the coherences of the system internal architecture at any given moment. The importance of this systemic way of seeing is that it explicitly attends to the organization that defines the immune system, within which it is possible to describe the conservative physiology of the immune system. Understanding immune physiology in a systemic way of seeing also suggests mechanisms underlying the origin of immunopathogeny and therefore suggests new insights to therapeutic approaches. However, if seriously acknowledged, this systemic/historic approach to immunology goes along with a global conceptual change which modifies virtually everything in the domain of biology, as suggested by Maturana.
Type III Mixed Cryoglobulinemia and Antiphospholipid Syndrome in a Patient With Partial DiGeorge Syndrome
Authors: Chang Alice D. , Tachdjian Raffi , Gallagher Kerry , McCurdy Deborah K. , Lassman Charles , Stiehm E. Richard , Yadin Ora
Published: December 2006

We studied a 14 year‐old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated β2‐glycoprotein I IgM antibodies. Infectious work‐up revealed only positive anti‐streptolysin O (ASO) and anti‐DNAse B titers. Autoimmune studies showed strongly positive anti‐platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.
Increased Fas and Bcl‐2 Expression on Peripheral Blood T and B Lymphocytes from Juvenile‐Onset Systemic Lupus Erythematosus, but not from Juvenile Rheumatoid Arthritis and Juvenile Dermatomyositis
Authors: Liphaus Bernadete L. , Kiss Maria H. B. , Carrasco Solange , Goldenstein-Schainberg Claudia
Published: December 2006

Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl‐2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl‐2 protein on peripheral blood T and B lymphocytes from patients with juvenile‐onset systemic lupus erythematosus (JSLE), juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDM). Thirty‐eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC) were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl‐2 molecules. Expressions were measured by three‐color flow cytometry. Statistical analysis was performed using Kruskal–Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl‐2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl‐2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl‐2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl‐2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation.
Subpopulations Within Juvenile Psoriatic Arthritis: A Review of the Literature
Authors: Stoll Matthew L. , Nigrovic Peter A.
Published: December 2006

The presentation of juvenile psoriatic arthritis (JPsA) has long been recognized to be clinically heterogeneous. As the definition of JPsA expanded to accommodate atypical manifestations of psoriasis in young children, studies began to reflect an increasingly clear biphasic distribution of age of onset, with peaks in the first few years of life and again in early adolescence. These two subpopulations differ in gender ratio, pattern of joint involvement, laboratory findings and potentially response to therapy. Intriguingly, a similar distribution of age of onset has been observed in juvenile rheumatoid arthritis (JRA), and correlates with patterns of HLA association. While a secure classification of subpopulations within JPsA awaits improved pathophysiologic understanding, future research must consider the possibility that different disease mechanisms may be operative in distinct subsets of patients with this disorder.
In Vivo Analysis of Chromosome Condensation inSaccharomyces cerevisiae
Authors: Vas Amit C.J. , Andrews Catherine A. , Kirkland Matesky Kathryn , Clarke Duncan J.
Published: December 2006

Although chromosome condensation in the yeast Saccharomyces cerevisiae has been widely studied, visualization of this process in vivo has not been achieved. Using Lac operator sequences integrated at two loci on the right arm of chromosome IV and a Lac repressor-GFP fusion protein, we were able to visualize linear condensation of this chromosome arm during G2/M phase. As previously determined in fixed cells, condensation in yeast required the condensin complex. Not seen after fixation of cells, we found that topoisomerase II is required for linear condensation. Further analysis of perturbed mitoses unexpectedly revealed that condensation is a transient state that occurs before anaphase in budding yeast. Blocking anaphase progression by activation of the spindle assembly checkpoint caused a loss of condensation that was dependent on Mad2, followed by a delayed loss of cohesion between sister chromatids. Release of cells from spindle checkpoint arrest resulted in recondensation before anaphase onset. The loss of condensation in preanaphase-arrested cells was abrogated by overproduction of the aurora B kinase, Ipl1, whereas in ipl1-321 mutant cells condensation was prematurely lost in anaphase/telophase. In vivo analysis of chromosome condensation has therefore revealed unsuspected relationships between higher order chromatin structure and cell cycle control.
Negative Regulation of Yeast Eps15-like Arp2/3 Complex Activator, Pan1p, by the Hip1R-related Protein, Sla2p, during Endocytosis
Authors: Toshima Jiro , Toshima Junko Y. , Duncan Mara C. , Cope M. Jamie T.V. , Sun Yidi , Martin Adam C. , Anderson Scott , Yates John R. , Mizuno Kensaku , Drubin David G.
Published: December 2006

Control of actin assembly nucleated by the Arp2/3 complex plays a crucial role during budding yeast endocytosis. The yeast Eps15-related Arp2/3 complex activator, Pan1p, is essential for endocytic internalization and proper actin organization. Pan1p activity is negatively regulated by Prk1 kinase phosphorylation after endocytic internalization. Phosphorylated Pan1p is probably then dephosphorylated in the cytosol. Pan1p is recruited to endocytic sites ∼25 s before initiation of actin polymerization, suggesting that its Arp2/3 complex activation activity is kept inactive during early stages of endocytosis by a yet-to-be-identified mechanism. However, how Pan1p is maintained in an inactive state is not clear. Using tandem affinity purification–tagged Pan1p, we identified End3p as a stoichiometric component of the Pan1p complex, and Sla2p, a yeast Hip1R-related protein, as a novel binding partner of Pan1p. Interestingly, Sla2p specifically inhibited Pan1p Arp2/3 complex activation activity in vitro. The coiled-coil region of Sla2p was important for Pan1p inhibition, and a pan1 partial loss-of-function mutant suppressed the temperature sensitivity, endocytic phenotypes, and actin phenotypes observed in sla2ΔCC mutant cells that lack the coiled-coil region. Overall, our results establish that Sla2p's regulation of Pan1p plays an important role in controlling Pan1p-stimulated actin polymerization during endocytosis.
Bayesian-based selection of metabolic objective functions
Authors: Knorr Andrea L. , Jain Rishi , Srivastava Ranjan
Published: December 2006

Motivation: A critical component of in silico analysis of underdetermined metabolic systems is the identification of the appropriate objective function. A common assumption is that the objective of the cell is to maximize growth. This objective function has been shown to be consistent in a few limited experimental cases, but may not be universally appropriate. Here a method is presented to quantitatively determine the most probable objective function.

Results: The genome-scale metabolism of Escherichia coli growing on succinate was used as a case-study for analysis. Five different objective functions, including maximization of growth rate, were chosen based on biological plausibility. A combination of flux balance analysis and linear programming was used to simulate cellular metabolism, which was then compared to independent experimental data using a Bayesian objective function discrimination technique. After comparing rates of oxygen uptake and acetate production, minimization of the production rate of redox potential was determined to be the most probable objective function. Given the appropriate reaction network and experimental data, the discrimination technique can be applied to any bacterium to test a variety of different possible objective functions.

Contact:  srivasta@engr.uconn.edu

Supplementary information: Additional files, code and a program for carrying out model discrimination are available at .