bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional consequences of exchanging domains between LacI and PurR are mediated by the intervening linker sequence
Authors: Tungtur Sudheer , Egan Susan M. , Swint‐Kruse Liskin
Published: April 2007

Homologue function can be differentiated by changing residues that affect binding sites or long‐range interactions. LacI and PurR are two proteins that represent the LacI/GalR family (>500 members) of bacterial transcription regulators. All members have distinct DNA‐binding and regulatory domains linked by ∼18 amino acids. Each homologue has specificity for different DNA and regulatory effector ligands; LacI and PurR also exhibit differences in allosteric communication between DNA and effector binding sites. A comparative study of LacI and PurR suggested that alterations in the interface between the regulatory domain and linker are important for differentiating their functions. Four residues (equivalent to LacI positions 48, 55, 58, and 61) appear particularly important for creating a unique interface and were predicted to be necessary for allosteric regulation. However, nearby residues in the linker interact with DNA ligand. Thus, differences observed in interactions between linker and regulatory domain may be the cause of altered function or an effect of the two proteins binding different DNA ligands. To separate these possibilities, we created a chimeric protein with the LacI DNA‐binding domain/linker and the PurR regulatory domain (LLhP). If the interface requires homologue‐specific interactions in order to propagate the signal from effector binding, then LLhP repression should not be allosterically regulated by effector binding. Experiments show that LLhP is capable of repression from lacO1 and, contrary to expectation, allosteric response is intact. Further, restoring the potential for PurR‐like interactions via substitutions in the LLhP linker tends to diminish repression. These effects are especially pronounced for residues 58 and 61. Clearly, binding affinity of LLhP for the lacO1 DNA site is sensitive to long‐range changes in the linker. This result also raises the possibility that mutations at positions 58 and 61 co‐evolved with changes in the DNA‐binding site. In addition, repression measured in the absence and presence of effector ligand shows that allosteric response increases for several LLhP variants with substitutions at positions 48 and 55. Thus, while side chain variation at these sites does not generally dictate the presence or absence of allostery, the nature of the amino acid can modulate the response to effector. Proteins 2007. © 2007 Wiley‐Liss, Inc.
SVM‐Cabins: Prediction of solvent accessibility using accumulation cutoff set and support vector machine
Authors: Wang Jung‐Ying , Lee Hahn‐Ming , Ahmad Shandar
Published: April 2007

A number of methods for predicting levels of solvent accessibility or accessible surface area (ASA) of amino acid residues in proteins have been developed. These methods either predict regularly spaced states of relative solvent accessibility or an analogue real value indicating relative solvent accessibility. While discrete states of exposure can be easily obtained by post prediction assignment of thresholds to the predicted or computed real values of ASA, the reverse, that is, obtaining a real value from quantized states of predicted ASA, is not straightforward as a two‐state prediction in such cases would give a large real valued errors. However, prediction of ASA into larger number of ASA states and then finding a corresponding scheme for real value prediction may be helpful in integrating the two approaches of ASA prediction. We report a novel method of obtaining numerical real values of solvent accessibility, using accumulation cutoff set and support vector machine. This so‐called SVM‐Cabins method first predicts discrete states of ASA of amino acid residues from their evolutionary profile and then maps the predicted states onto a real valued linear space by simple algebraic methods. Resulting performance of such a rigorous approach using 13‐state ASA prediction is at least comparable with the best methods of ASA prediction reported so far. The mean absolute error in this method reaches the best performance of 15.1% on the tested data set of 502 proteins with a coefficient of correlation equal to 0.66. Since, the method starts with the prediction of discrete states of ASA and leads to real value predictions, performance of prediction in binary states and real values are simultaneously optimized. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Evaluation of pool‐riffle naturalization structures on habitat complexity and the fish community in an urban Illinois stream
Authors: Schwartz John S. , Herricks Edwin E.
Published: April 2007

Urbanization and its associated stressors such as flow alteration, channel modification and poor water quality is a leading cause of ecological degradation to rivers and streams. Driven by public concern to address this issue, there has been a dramatic increase in urban restoration projects since 1990 using in‐stream structures. Attempts at restoring the ecological condition of urban streams using structures have produced varied results, but projects do not often meet planned ecological goals. A major challenge to improving the ecological health of urban streams is to better understand how to incorporate ecological assessments into a ‘restoration’ design framework with reasonable expectations for ecological recovery. A naturalization design framework was used in a project on a 0.62‐km reach of the North Branch of the Chicago River in Northbrook, Illinois. Initial surveys of channel morphology, habitat and biota identified poor pool‐riffle bed structure and fish biodiversity, which became the basis for research and development of a pool‐riffle structure specifically designed for constrained, low‐gradient channels. Habitat and fish surveys were conducted pre‐ and post‐construction. The project improved mesohabitat structure, and fish abundance, and biomass and diversity were greater for 2 years following construction (2002–2003) compared to 3 years prior to construction (1999–2001). However, the improved fish metrics were in the low range when compared to rural streams in the same ecoregion, and the fish community consisted primarily of tolerant, slow‐water species. Absent were intolerant and riffle dwelling species, such as insectivorous cyprinids and darters. Assessment of pre‐ and post‐project ecological condition and the use of species information provided a basis for ecologically informed design and expanded our understanding of the limitations to restoring urban streams. Copyright © 2007 John Wiley & Sons, Ltd.
Structure and growth of oxides on polycrystalline nickel surfaces
Authors: Payne Brad P. , Grosvenor Andrew. P. , Biesinger Mark C. , Kobe Brad A. , McIntyre N. Stewart
Published: April 2007

The oxidation of polycrystalline nickel (Ni) metal surfaces after exposure to oxygen gas (O2) at 25 and 300 °C and pressures near 130 Pa, was studied using X‐ray photoelectron spectroscopy (XPS). Oxide structures involving both divalent (Ni2+) and trivalent (Ni3+) species could be distinguished using Ni 2p spectra, while surface adsorbed O2 and atomic oxygen (O) species could be differentiated from bulk oxide (O2−) using O 1s spectra. Oxide thicknesses and distributions were determined using QUASES™, and the average oxide thickness was verified using the Strohmeier formula. The reaction kinetics for oxide films grown at 300 °C followed a parabolic mechanism, with an oxide thickness of greater than 4 nm having formed after 60 min. Exposure at 25 °C followed a direct logarithmic mechanism with an oxide growth rate about four to five times slower than at 300 °C. Reaction of a Ni (100) single crystal under comparable conditions showed much slower reaction rates compared to polycrystalline specimens. The higher reaction rate of the polycrystalline materials is attributed to grain boundary transport of Ni cations. Oxide thickness was measured on a microscopic scale for polycrystalline Ni exposed to large doses of O2 at 25 and 300 °C. The thickness of oxide was not strongly localized on this scale. However, the QUASES™ analysis suggests that there is localized growth on a nanometric scale—the result of island formation. Copyright © 2007 John Wiley & Sons, Ltd.
Assessing self‐authorship
Authors: Pizzolato Jane Elizabeth
Published: April 2007

Institutional and programmatic effectiveness in promoting self‐authorship requires an understanding of how to assess self‐authorship.
The journey of self‐authorship: Next steps to the destination
Authors: Meszaros Peggy S.
Published: April 2007

This chapter reiterates the need for attention to the journey of self‐authorship and suggests next steps for institutions and educators.
Position paper of the European Federation of IASP Chapters (EFIC) on the subject of pain management
Authors: Niv David , Devor Marshall
Published: April 2007

Among the complaints that bring patients to see their physician, pain in its various manifestations is the most frequent. In spite of this, pain is often not adequately addressed or managed. The aim of this position paper is to present the viewpoint and recommendations of EFIC on the subject of pain management. Our overall objective is to encourage adoption by architects of healthcare systems in Europe and worldwide of a set of specific recommendations. Every patient is entitled to the implementation of these recommendations in a professional, accessible and timely manner.
Serotonergic response to stress: A protective factor against abnormal dopaminergic reactivity in schizophrenia?
Authors: Brunelin Jerome , D'amato Thierry , Os Jim van , Dalery Jean , Suaud-Chagny Marie-Françoise , Saoud Mohamed
Published: April 2007

In a double-blind-crossover-study, 10 patients with schizophrenia, 10 of their unaffected siblings and 9 healthy controls randomly received metabolic stressor and placebo. A significant HVA plasma elevation in response to stress was found in siblings whose response was intermediate to that of patients and controls. Only siblings additionally displayed an exaggerated 5HIAA response.
Role of the COMT gene Val158Met polymorphism in mental disorders: A review
Authors: Hosák Ladislav
Published: April 2007

The Val158Met polymorphism of the COMT gene is functional, easily detectable, and significantly related to metabolism of catecholamines, which underlie pathogenesis of a significant number of mental disorders. Evidence for the role of this polymorphism in schizophrenia, substance dependence, bipolar disorder, obsessive-compulsive disorder, anorexia nervosa and attention deficit hyperactivity disorder is summed up in this review article. The results make it unlikely that the COMT gene plays an important role in these mental disorders, although a minor effect can not be excluded. Future studies on the COMT gene in mentally ill subjects should be stratified by clinical subtypes of the disorder, gender and ethnicity. Studies of endophenotypes instead of the complex disorder seem to be another promising research strategy. Gene-gene and gene-environment interactions should also be considered. The COMT gene is probably not “a gene for” any mental disorder, but the Val158Met polymorphism appears to have pleiotropic effects on human behavior.
Annual precipitation in the yellowstone National Park region since AD 1173
Authors: Gray Stephen T. , Graumlich Lisa J. , Betancourt Julio L.
Published: April 2007

Cores and cross sections from 133 limber pine (Pinus flexilis James) and Douglas fir (Pseudotsuga menziesii (Mirbel) Franco) at four sites were used to estimate annual (July to June) precipitation in the Yellowstone National Park region for the period from AD 1173 to 1998. Examination of the long-term record shows that the early 20th century was markedly wet compared to the previous 700 yr. Extreme wet and dry years within the instrumental period fall within the range of past variability, and the magnitude of the worst-case droughts of the 20th century (AD 1930s and 1950s) was likely equaled or exceeded on numerous occasions before AD 1900. Spectral analysis showed significant decadal to multidecadal precipitation variability. At times this lower frequency variability produces strong regime-like behavior in regional precipitation, with the potential for rapid, high-amplitude switching between predominately wet and predominately dry conditions. Over multiple time scales, strong Yellowstone region precipitation anomalies were almost always associated with spatially extensive events spanning various combinations of the central and southern U.S. Rockies, the northern U.S.–Southern Canadian Rockies and the Pacific Northwest.
Effects of Astaxanthin Supplementation on Lipid Peroxidation
Authors: Karppi  , Rissanen  , Nyyssönen  , Kaikkonen  , Olsson  , Voutilainen  , Salonen
Published: April 2007

Astaxanthin, the main carotenoid pigment in aquatic animals, has greater antioxidant activity in vitro (protecting against lipid peroxidation) and a more polar configuration than other carotenoids. We investigated the effect of three-month astaxanthin supplementation on lipid peroxidation in healthy non-smoking Finnish men, aged 19–33 years by using a randomized double-blind study design. Also absorption of astaxanthin from capsules into bloodstream and its safety were evaluated. The intervention group received two 4-mg astaxanthin (Astaxin®) capsules daily, and the control group two identical-looking placebo capsules. Astaxanthin supplementation elevated plasma astaxanthin levels to 0.032 μmol/L (p < 0.001 for the change compared with the placebo group). We observed that levels of plasma 12- and 15-hydroxy fatty acids were reduced statistically significantly in the astaxanthin group (p = 0.048 and p = 0.047 respectively) during supplementation, but not in the placebo group and the change of 15-hydroxy fatty acid was almost significantly greater (p = 0.056) in the astaxanthin group, as compared with the placebo group. The present study suggests that intestinal absorption of astaxanthin delivered as capsules is adequate, and well tolerated. Supplementation with astaxanthin may decrease in vivo oxidation of fatty acids in healthy men.
Restoration of Thiamine Status with White or Whole Wheat Bread in a Thiamine-Depleted Rat Model
Authors: Batifoulier  , Verny  , Besson  , Chanliaud  , Rémésy  , Demigné
Published: April 2007

Long-term thiamine deficiency has been largely documented, whilst little is known about effects of short-term depletion/repletion periods on thiamine vitamers status. Rats were submitted to short-term depletion (8 days) followed by different durations of repletion (3 or 14 days) with thiamine from bread (whole wheat bread or white bread, whole B and white B respectively) or corresponding controls. Short-term depletion drastically decreased plasma thiamine (–97%) and its urinary excretion (–77%). TDP (thiamine diphosphate) was strongly affected in liver (–67%) but less affected in cerebellum (–38%) or kidneys (–45%). Short-term repletion (3 days) with whole B diet or its control restored TDP at initial values in cerebellum and kidneys. A longer repletion (14 days) was required to restore liver TDP. Comparison of the diet groups indicates that thiamine status in tissues of rat fed whole B or white B diet was comparable to that of rats fed purified thiamine. Plasma thiamine concentration could not be restored at initial values in the bread groups or respective controls. In conclusion, thiamine in whole wheat bread appears effective in preventing marginal deficiencies and plasma thiamine is a less reliable indicator of thiamine status than tissue TDP levels.
Pflege und Technik – Annäherung an ein spannungsreiches Verhältnis Zum gegenwärtigen Stand der internationalen Diskussion – 1. Teil
Authors: Hülsken-Giesler Manfred
Published: April 2007

Professionelle Pflege sieht sich im Zuge grundlegender gesellschaftlicher Veränderungen und darauf reagierender stetiger Reformprozesse im Bereich der Gesundheitsversorgung vor große Herausforderungen gestellt. Die Etablierung einer wissenschaftlichen Disziplin der Pflege gilt hier als eine Antwort auf diese Entwicklung. Zu den dringenden Aufgaben der Pflegewissenschaft wird eine Auseinandersetzung mit Fragen des Verhältnisses von Pflege und Technik in einer zunehmend technisierten Umgebung der Gesundheitsversorgung angemahnt. Ein intensiver pflegewissenschaftlicher Diskurs um diese Problematik steht im deutschsprachigen Raum bis heute aus. Um einen Anstoß zu einer solchen Debatte zu liefern, wird mit diesem Beitrag der internationale Diskussionsstand zum Verhältnis von Pflege und Technik zusammengetragen und kritisch diskutiert. Der vorliegende erste Teil fokussiert dabei zunächst auf traditionellen, essentialistischen Positionen. Der zweite Teil bildet den aktuellen internationalen Diskurs mit Blick auf ein dialektisches Verhältnis von Pflege und Technik ab.
Belastungen und Bewältigungsstrategien von Frauen mit Brustkrebs in der Phase der chirurgischen Primärtherapie – die Sicht der Pflegenden
Authors: Holtgräwe Martina , Pinkert Christiane , Remmers Hartmut
Published: April 2007

Die hier dargestellten Ergebnisse stellen einen Ausschnitt eines größeren von der Deutschen Krebshilfe e.V. finanzierten Forschungsprojektes dar, das zum Ziel hat, die Belastungen, Copingstrategien und Bedürfnisse von Frauen mit Brustkrebs während der chirurgischen Primärtherapie zu untersuchen. Brustkrebs führt für die betroffenen Frauen und ihre Familien zu zahlreichen Belastungen. Dabei setzen Frauen verschiedene Strategien ein, um die Krankheit zu bewältigen. Fremd- und Selbsteinschätzungen von Belastungen und Bewältigungsstrategien führen gelegentlich zu unterschiedlichen Ergebnissen, indem Experten zum Beispiel die Angst oder Depression ihrer Patientinnen überschätzen, oder Copingstrategien aufdecken, die für die Betroffenen nicht sichtbar sind. Es wurden qualitative Interviews mit zwölf Krankenschwestern aus drei norddeutschen Krankenhäusern durchgeführt. Die inhaltsanalytische Auswertung der Interviews erfolgte in Anlehnung an Mayring. Vor allem Ungewissheit und Angst sind für die betroffenen Frauen kennzeichnend. Die wahrgenommenen Bewältigungsstrategien lassen sich fünf Kategorien zuordnen: die Krankheit verleugnen, sich verschließen, sich mitteilen, die Krankheit verstehen, die Krankheit annehmen. Vor allem Verhaltensweisen wie Rückzug und Verleugnung stellen große Herausforderungen an das Kommunikationsverhalten Pflegender dar. Die Ergebnisse der Studie geben erste Hinweise auf einen möglichen Bedarf an geeigneten Pflegeinterventionen und Weiterbildungs- und Qualifikationsmaßnahmen für Pflegefachkräfte in der Betreuung von Brustkrebspatientinnen. Es ist zu erwarten, dass wissenschaftlich gestützte Pflegekonzepte und spezialisierte Pflegekräfte den besonderen Bedürfnissen der betroffenen Frauen entgegenkommen.
Similar microearthquakes observed in western Nagano, Japan, and implications for rupture mechanics
Authors: Cheng Xin , Niu Fenglin , Silver Paul G. , Horiuchi Shigeki , Takai Kaori , Iio Yoshihisa , Ito Hisao
Published: April 2007

We have applied a waveform cross correlation technique to study the similarity and the repeatability of more than 21,000 microearthquakes (0 < M < 4.5) in the aftershock zone of the 1984 western Nagano earthquake in central Japan. We find that the seismicity in this particular intraplate fault essentially consists of no repeating earthquakes that occurred on the same patch of the fault in a quasiperiodic manner in the study period between 1995 and 2001. On the other hand, we identify a total of 278 doublets and 62 multiplets (807 events) that occurred consecutively within seconds to days. On the basis of the relative arrival times of the P and S waves, we have obtained precise relative locations of these consecutive events with an error between several meters to a few tens of meters. There is a clear lower bound on the distances measured between these consecutive events and the lower bound appears to be proportional to the size of the first events. This feature is consistent with what Rubin and Gillard [2000] have observed near the San Juan Bautista section of the San Andreas Fault. Shear stress increases at the edge of an earthquake rupture, and the rupture edge becomes the most likely place where the second events are initiated. The observed minimum distance thus reflects the rupture size of the first events. The minimum distance corresponds to the rupture size calculated from a circular fault model with a stress drop of 10 MPa. We found that using different time windows results in a slight difference in the delay time estimates and the subsequent projection locations, which may reflect the finite size nature of earthquake ruptures.
Cell surface chondroitin sulfate glycosaminoglycan in melanoma: role in the activation of pro-MMP-2 (pro-gelatinase A)
Authors: Iida Joji , Wilhelmson Krista L. , Ng Janet , Lee Peter , Morrison Charlotte , Tam Eric , Overall Christopher M. , McCarthy James B.
Published: April 2007

We previously reported that CS (chondroitin sulfate) GAG (glycosaminoglycan), expressed on MCSP (melanoma-specific CS proteoglycan), is important for regulating MT3-MMP [membrane-type 3 MMP (matrix metalloproteinase)]-mediated human melanoma invasion and gelatinolytic activity in vitro. In the present study, we sought to determine if CS can directly enhance MT3-MMP-mediated activation of pro-MMP-2. Co-immunoprecipitation studies suggest that MCSP forms a complex with MT3-MMP and MMP-2 on melanoma cell surface. When melanoma cells were treated with βDX (p-nitro-β-D-xylopyranoside) to inhibit coupling of CS on the core protein, both active form and proform of MMP-2 were no longer co-immunoprecipitated with either MCSP or MT3-MMP, suggesting a model in which CS directly binds to MMP-2 and presents the gelatinase to MT3-MMP to be activated. By using recombinant proteins, we determined that MT3-MMP directly activates pro-MMP-2 and that this activation requires the interaction of the C-terminal domain of pro-MMP-2 with MT3-MMP. Activation of pro-MMP-2 by suboptimal concentrations of MT3-MMP is also significantly enhanced in the presence of excess C4S (chondroitin 4-sulfate), whereas C6S (chondroitin 6-sulfate) or low-molecular-mass hyaluronan was ineffective. Affinity chromatography studies using CS isolated from aggrecan indicate that the catalytic domain of MT3-MMP and the C-terminal domain of MMP-2 directly bind to the GAG. Thus the direct binding of pro-MMP-2 with CS through the C-domain would present the catalytic domain of pro-MMP-2 to MT3-MMP, which facilitates the generation of the active form of MMP-2. These results suggest that C4S, which is expressed on tumour cell surface, can function to bind to pro-MMP-2 and facilitate its activation by MT3-MMP-expressing tumour cells to enhance invasion and metastasis.
Cross-talk between IRAK-4 and the NADPH oxidase
Authors: Pacquelet Sandrine , Johnson Jennifer L. , Ellis Beverly A. , Brzezinska Agnieszka A. , Lane William S. , Munafo Daniela B. , Catz Sergio D.
Published: April 2007

Exposure of neutrophils to LPS (lipopolysaccharide) triggers their oxidative response. However, the relationship between the signalling downstream of TLR4 (Toll-like receptor 4) after LPS stimulation and the activation of the oxidase remains elusive. Phosphorylation of the cytosolic factor p47phox is essential for activation of the NADPH oxidase. In the present study, we examined the hypothesis that IRAK-4 (interleukin-1 receptor-associated kinase-4), the main regulatory kinase downstream of TLR4 activation, regulates the NADPH oxidase through phosphorylation of p47phox. We show that p47phox is a substrate for IRAK-4. Unlike PKC (protein kinase C), IRAK-4 phosphorylates p47phox not only at serine residues, but also at threonine residues. Target residues were identified by tandem MS, revealing a novel threonine-rich regulatory domain. We also show that p47phox is phosphorylated in granulocytes in response to LPS stimulation. LPS-dependent phosphorylation of p47phox was enhanced by the inhibition of p38 MAPK (mitogen-activated protein kinase), confirming that the kinase operates upstream of p38 MAPK. IRAK-4-phosphorylated p47phox activated the NADPH oxidase in a cell-free system, and IRAK-4 overexpression increased NADPH oxidase activity in response to LPS. We have shown that endogenous IRAK-4 interacts with p47phox and they co-localize at the plasma membrane after LPS stimulation, using immunoprecipitation assays and immunofluorescence microscopy respectively. IRAK-4 was activated in neutrophils in response to LPS stimulation. We found that Thr133, Ser288 and Thr356, targets for IRAK-4 phosphorylation in vitro, are also phosphorylated in endogenous p47phox after LPS stimulation. We conclude that IRAK-4 phosphorylates p47phox and regulates NADPH oxidase activation after LPS stimulation.
Structural study on ligand specificity of human vitamin B12 transporters
Authors: Wuerges Jochen , Geremia Silvano , Randaccio Lucio
Published: April 2007

Studies comparing the binding of genuine cobalamin (vitamin B12) to that of its natural or synthetic analogues have long established increasing ligand specificity in the order haptocorrin, transcobalamin and intrinsic factor, the high-affinity binding proteins involved in cobalamin transport in mammals. In the present study, ligand specificity was investigated from a structural point of view, for which comparative models of intrinsic factor and haptocorrin are produced based on the crystal structure of the homologous transcobalamin and validated by results of published binding assays. Many interactions between cobalamin and its binding site in the interface of the two domains are conserved among the transporters. A structural comparison suggests that the determinant of specificity regarding cobalamin ligands with modified nucleotide moiety resides in the β-hairpin motif β3-turn-β4 of the smaller C-terminal domain. In haptocorrin, it provides hydrophobic contacts to the benzimidazole moiety through the apolar regions of Arg357, Trp359 and Tyr362. Together, these large side chains may compensate for the missing nucleotide upon cobinamide binding. Intrinsic factor possesses only the tryptophan residue and transcobalamin only the tyrosine residue, consistent with their low affinity for cobinamide. Relative affinity constants for other analogues are rationalized similarly by analysis of steric and electrostatic interactions with the three transporters. The structures also indicate that the C-terminal domain is the first site of cobalamin-binding since part of the β-hairpin motif is trapped between the nucleotide moiety and the N-terminal domain in the final holo-proteins.
Induced JunD in intestinal epithelial cells represses CDK4 transcription through its proximal promoter region following polyamine depletion
Authors: Xiao Lan , Rao Jaladanki N. , Zou Tongtong , Liu Lan , Marasa Bernard S. , Chen Jie , Turner Douglas J. , Passaniti Antonino , Wang Jian-Ying
Published: April 2007

Maintenance of intestinal epithelial integrity requires cellular polyamines that regulate expression of various genes involved in cell proliferation, growth arrest and apoptosis. In prior studies, depletion of cellular polyamines has been shown to stabilize JunD, a member of the AP-1 (activator protein-1) family of transcription factors, leading to inhibition of intestinal epithelial cell proliferation, but the exact downstream targets of induced JunD remain elusive. CDK4 (cyclin-dependent kinase 4) is essential for the G1- to S-phase transition during the cell cycle and its expression is primarily controlled at the transcriptional level. In the present study, we show that induced JunD in IECs (intestinal epithelial cells) is a transcriptional repressor of the CDK4 gene following polyamine depletion. Increased JunD in polyamine-deficient cells was associated with a significant inhibition of CDK4 transcription, as indicated by repression of CDK4-promoter activity and decreased levels of CDK4 mRNA and protein, all of which were prevented by using specific antisense JunD oligomers. Ectopic expression of the wild-type junD also repressed CDK4-promoter activity and decreased levels of CDK4 mRNA and protein without any effect on CDK2 expression. Gel shift and chromatin immunoprecipitation assays revealed that JunD bound to the proximal region of the CDK4-promoter in vitro as well as in vivo, while experiments using different CDK4-promoter mutants showed that transcriptional repression of CDK4 by JunD was mediated through an AP-1 binding site within this proximal sequence of the CDK4-promoter. These results indicate that induced JunD in IECs represses CDK4 transcription through its proximal promoter region following polyamine depletion.
Characterization of the transactivation domain in the peroxisome-proliferator-activated receptor γ co-activator (PGC-1)
Authors: Sadana Prabodh , Park Edwards A.
Published: April 2007

The PGC-1s (peroxisome-proliferator-activated receptor γ co-activators) are a family of transcriptional regulators that induce the expression of various metabolic genes. PGC-1 proteins stimulate genes involved in mitochondrial biogenesis, fatty acid oxidation and hepatic gluconeogenesis. Previous studies have demonstrated that the PGC-1α and β isoforms interact with nuclear receptors through the conserved LXXLL (leucine-X-X-leucine-leucine) motifs. In the present study, we have investigated the mechanisms by which these PGC-1 isoforms stimulate gene expression. We have determined that the N-terminus of PGC-1 is responsible for transcriptional activation. Two conserved peptide motifs were identified in the N-terminus of PGC-1α and β isoforms. These domains were named AD1 and AD2 (activation domain 1 and 2). Deletion of both of these motifs decreased the induction of various PGC-1-regulated genes including the PEPCK (phosphoenolpyruvate carboxykinase) and CPT-I (carnitine palmitoyltransferase-I) genes. It was determined that amino acids containing a negative charge in AD1 and the leucine residues in AD2 were important for the transcriptional induction of the PEPCK and CPT-I genes. Disruption of the AD motifs did not diminish the ability of the PGC-1α protein to associate with the PEPCK or CPT-I genes. In addition, deletion of the AD domains did not eliminate the ability of PGC-1α to interact with the thyroid hormone receptor. The data indicate that the AD1 and AD2 motifs mediate the induction of many PGC-1- responsive genes, but they do not contribute to the recruitment of PGC-1 to target genes.
Functional characterization of human bitter taste receptors
Authors: Sainz Eduardo , Cavenagh Margaret M. , Gutierrez Joanne , Battey James F. , Northup John K. , Sullivan Susan L.
Published: April 2007

The T2Rs belong to a multi-gene family of G-protein-coupled receptors responsible for the detection of ingested bitter-tasting compounds. The T2Rs are conserved among mammals with the human and mouse gene families consisting of about 25 members. In the present study we address the signalling properties of human and mouse T2Rs using an in vitro reconstitution system in which both the ligands and G-proteins being assayed can be manipulated independently and quantitatively assessed. We confirm that the mT2R5, hT2R43 and hT2R47 receptors respond selectively to micromolar concentrations of cycloheximide, aristolochic acid and denatonium respectively. We also demonstrate that hT2R14 is a receptor for aristolochic acid and report the first characterization of the ligand specificities of hT2R7, which is a broadly tuned receptor responding to strychnine, quinacrine, chloroquine and papaverine. Using these defined ligand–receptor interactions, we assayed the ability of the ligand-activated T2Rs to catalyse GTP binding on divergent members of the Gα family including three members of the Gαi subfamily (transducin, Gαi1 and Gαo) as well as Gαs and Gαq. The T2Rs coupled with each of the three Gαi members tested. However, none of the T2Rs coupled to either Gαs or Gαq, suggesting the T2Rs signal primarily through Gαi-mediated signal transduction pathways. Furthermore, we observed different G-protein selectivities among the T2Rs with respect to both Gαi subunits and Gβγ dimers, suggesting that bitter taste is transduced by multiple G-proteins that may differ among the T2Rs.
The β-cell specific transcription factor Nkx6.1 inhibits glucagon gene transcription by interfering with Pax6
Authors: Gauthier Benoit R. , Gosmain Yvan , Mamin Aline , Philippe Jacques
Published: April 2007

The transcription factor Nkx6.1 is required for the establishment of functional insulin-producing β-cells in the endocrine pancreas. Overexpression of Nkx6.1 has been shown to inhibit glucagon gene expression while favouring insulin gene activation. Down-regulation resulted in the opposite effect, suggesting that absence of Nkx6.1 favours glucagon gene expression. To understand the mechanism by which Nkx6.1 suppresses glucagon gene expression, we studied its effect on the glucagon gene promoter activity in non-islet cells using transient transfections and gel-shift analyses. In glucagonoma cells transfected with an Nkx6.1-encoding vector, the glucagon promoter activity was reduced by 65%. In BHK21 cells, Nkx6.1 inhibited by 93% Pax6-mediated activation of the glucagon promoter, whereas Cdx2/3 and Maf stimulations were unaltered. Although Nkx6.1 could interact with both the G1 and G3 element, only the former displayed specificity for Nkx6.1. Mutagenesis of the three potential AT-rich motifs within the G1 revealed that only the Pax6-binding site preferentially interacted with Nkx6.1. Chromatin immunoprecipitation confirmed interaction of Nkx6.1 with the glucagon promoter and revealed a direct competition for binding between Pax6 and Nkx6.1. A weak physical interaction between Pax6 and Nkx6.1 was detected in vitro and in vivo suggesting that Nkx6.1 predominantly inhibits glucagon gene transcription through G1-binding competition. We suggest that cell-specific expression of the glucagon gene may only proceed when Nkx6.1, in combination with Pdx1 and Pax4, are silenced in early α-cell precursors.
Structure and magnetic properties of EuMnxGa3−x
Authors: Guo Yongquan , Grin Yuin , Schnelle Walter , Li Wei
Published: April 2007

The crystal structure and magnetic properties of EuMnxGa3−x intermetallics have been investigated using powder x-ray diffraction and magnetic measurement. EuMnxGa3−x crystallizes in an orthorhombic structure with a space group of Cmcm, and Z=4. The lattice parameters are a=4.294(1)–4.287(1)Å, b=18.50(3)–18.57(3)Å, and c=4.384(6)–4.372(9)Å. In each unit cell, there are four nonequivalent 4c crystal positions for 4Eu, 4GaI, 4(GaII,Mn), and 4GaIII. EuMnxGa3−x (x<0.27) intermetallic compounds are antiferromagnetic at low temperature. A magnetic transition from the paramagnetic to the ferromagnetic occurs in EuMn0.3Ga2.7 at room temperature when applying a low field of 40Oe. Moreover, this ferromagnetic order is very weak and sensitive to the applied field. With increasing the applied field, the ferromagnetic order tends to vanish. This phenomenon might be interpreted as the Mn spin state change induced by charge balance at low field.
Mean field theory for the intermolecular and intramolecular conformational transitions of a single flexible polyelectrolyte chain
Authors: Shew Chwen-Yang , Yoshikawa Kenichi
Published: April 2007

The diMarzio theory has been extended to elucidate the intermolecular and intramolecular phase segregations of a single flexible chain polyelectrolyte in dilute salt-free solutions. At the long chain limit, this theory yields the formalism obtained from the more sophisticated Edward Hamiltonian for polyelectrolyte problems. The calculated phase diagram exhibits the features of a first-order phase transition, with continuous and discontinuous transitions separated by a critical point. Under the discontinuous transition, the polyelectrolyte chain exhibits coexistent expanded and collapsed conformational states, same as intermolecular phase segregation. For a limiting long chain, the mean chain size at critical point is roughly 90% of the size of an ideal chain. Such a result implies that partial contraction within a chain molecule is required to collapse a flexible polyelectrolyte chain. Moreover, the theory predicts that for a longer chain, intramolecular segregated conformations differ significantly from intermolecular segregated conformations, but the difference becomes small for shorter chains. Besides, the charge needed to induce intramolecular segregation is smaller than that of intermolecular segregation for a given chain length. These findings are consistent with previous literature results.
Changes in mechanical properties of Zr-based bulk metallic glass under linear heating and cooling
Authors: Tamura S. , Fukuhara M. , Inoue A.
Published: April 2007

In order to observe the temperature dependence of the mechanical properties in a bulk metallic glass (BMG), sound velocity and attenuation in Zr-based BMG for longitudinal and transverse waves under linear heating and cooling with a peak temperature of 673K were measured by an ultrasonic pulse echo technique. The elastic property, Poisson’s ratio, and internal frictions were calculated from the sound velocities and attenuations. In the temperature range of 547–619K, steep changes in the mechanical properties were observed. During the first heating cycle, the material’s density and Young’s modulus increased; however, during subsequent heat treatments, the density and Young’s modulus decreased somewhat. This suggests that an initial reduction in free volume during the first temperature cycle was followed by increases in free volume during subsequent temperature cycling. The behavior of reduction and increase in the free volume under heat treatment in the vicinity of calorimetric glass transition temperature was discussed on the basis of the viscoelastic model with partial nanocluster formation.
Robust optimization in electromagnetic scattering problems
Authors: Bertsimas Dimitris , Nohadani Omid , Teo Kwong Meng
Published: April 2007

In engineering design, the physical properties of a system can often only be described by numerical simulation. Optimization of such systems is usually accomplished heuristically without taking into account that there are implementation errors that lead to very suboptimal, and often, infeasible solutions. We present a robust optimization method for electromagnetic scattering problems with large degrees of freedom and report on results when this technique is applied to optimization of aperiodic dielectric structures. The spatial configuration of 50 dielectric scattering cylinders is optimized to match a desired target function such that the optimal arrangement is robust against placement and prototype errors. Our optimization method inherently improves the robustness of the optimized solution with respect to relevant errors and is suitable for real-world design of materials with unconventional electromagnetic functionalities, as relevant to nanophotonics.
Temperature-dependent magnetic resonance force microscopy studies of a thin Permalloy film
Authors: Nazaretski E. , Thompson J. D. , Movshovich R. , Zalalutdinov M. , Baldwin J. W. , Houston B. , Mewes T. , Pelekhov D. V. , Wigen P. , Hammel P. C.
Published: April 2007

We used magnetic resonance force microscopy (MRFM) to study a 50nm thick continuous Permalloy film. We mechanically measured the ferromagnetic resonance signal in the temperature range between 10 and 70K in the presence of a static magnetic field applied normal to the surface of the film. The measurements show a decrease of the ferromagnetic resonance field with increasing temperature. We attribute this behavior to the temperature-dependent changes of the saturation magnetization. Our experiments demonstrate the potential of MRFM to perform quantitative ferromagnetic resonance measurements as a function of temperature.
Shape stability and violent collapse of microbubbles in acoustic traveling waves
Authors: Calvisi Michael L. , Lindau Olgert , Blake John R. , Szeri Andrew J.
Published: April 2007

Acoustically driven bubbles can develop shape instabilities and, if forced sufficiently strongly, distort greatly and break up. Perturbation theory provides some insight as to how these nonspherical shape modes grow initially but loses validity for large deformations. To validate the perturbation theory, we use a numerical model based on the boundary integral method capable of simulating nonspherical, axisymmetric bubbles subject to acoustic driving. The results show that the perturbation theory compares well with numerical simulations in predicting bubble breakup and stability. Thereafter, we compare the peak temperatures and pressures of spherical to nonspherical bubble collapses by forcing them with standing waves and traveling waves, respectively. This comparison is made in parameter ranges of relevance to both single bubble sonoluminescence and multibubble sonoluminescence and sonochemistry. At moderate forcing, spherical and nonspherical collapses achieve similar peak temperatures and pressures but, as the forcing is increased, spherical collapses become much more intense. The reduced temperature of nonspherical collapses at high forcing is due to residual kinetic energy of a liquid jet that pierces the bubble near the time of minimum volume. This is clarified by a calculation of the (gas) thermal equivalent of this liquid kinetic energy.
Determination of the coefficients of Langevin models for inhomogeneous turbulent flows by three-dimensional particle tracking velocimetry and direct numerical simulation
Authors: Walpot R. J. E. , van der Geld C. W. M. , Kuerten J. G. M.
Published: April 2007

A promising and, in terms of computer power, low-cost way of describing flow properties such as turbulent diffusion is by Langevin models. The development of such models requires knowledge of Lagrangian statistics of turbulent flows. Our aim is to determine Lagrangian statistics of inhomogeneous flows, as most turbulent flows found in practical applications are inhomogeneous. The present paper describes how a Lagrangian measurement technique, three-dimensional particle tracking velocimetry, has been developed and applied to the most common example of inhomogeneous flows: turbulent pipe flow. A new direct numerical simulation (DNS) code has been developed and experimental results have been compared with results of this DNS code. The results concern Eulerian and Lagrangian velocity statistics at two Reynolds numbers. Based on these, coefficients of the Langevin model have been determined and physical consequences for Langevin modeling and turbulent dispersion have been explained.
Epitaxial properties of ZnO thin films on SrTiO3 substrates grown by laser molecular beam epitaxy
Authors: Wei X. H. , Li Y. R. , Zhu J. , Huang W. , Zhang Y. , Luo W. B. , Ji H.
Published: April 2007

Epitaxial ZnO thin films with different orientations have been grown by laser molecular beam epitaxy on (001)-, (011)-, and (111)-orientated SrTiO3 single-crystal substrates. The growth behavior was in situ monitored by reflection high-energy electron diffraction, and the epitaxial orientation relations were reconfirmed by ex situ x-ray diffraction measurements. In the case of ZnO on SrTiO3(001), four orthogonal domains coexisted in the ZnO epilayer, i.e., ZnO(110)‖SrTiO3(001) and ZnO[−111]‖SrTiO3⟨100⟩. For (011)- and (111)-orientated substrates, single-domain epitaxy with c axial orientation was observed, in which the in-plane relationship was ZnO[110]‖SrTiO3[110] irrespective of the substrate orientations. Additionally, the crystalline quality of ZnO on SrTiO3(111) was better than that of ZnO on SrTiO3(011) because of the same symmetry between the (111) substrates and (001) films. The obtained results can be attributed to the difference of the in-plane crystallographic symmetry. Furthermore, those alignments can be explained by the interface stress between the substrates and the films.
Effects of oxygen and illumination on the photovoltaic properties of organic solar cells based on phtalocyanine:fullerene bulk heterojunction
Authors: Rusu M. , Strotmann J. , Vogel M. , Lux-Steiner M. Ch. , Fostiropoulos K.
Published: April 2007

The authors report factors that limit the photovoltaic parameters of organic solar cells based on phtalocyanine:fullerene bulk heterojunction. They show that the device photovoltaic properties and their stability are strongly influenced by O2 impurities. Oxygen affects mostly the photoelectrical properties of the fullerene and the state of the interface between phtalocyanine and fullerene domains. The illumination of the devices, especially in the wavelength range <570nm, induces photodiffusion of the oxygen into fullerene material and promotes formation of O2-fullerene dipoles and additional recombination levels due to C–O reactions that accelerate the device degradation.
Magnetoelectric effect in epitaxial Pb(Zr0.52Ti0.48)O3∕La0.7Sr0.3MnO3 composite thin film
Authors: Ma Y. G. , Cheng W. N. , Ning M. , Ong C. K.
Published: April 2007

The magnetoelectric effect (ME) in the epitaxial Pb(Zr0.52Ti0.48)O3∕La0.7Sr0.3MnO3 (PZT/LSMO) composite thin film deposited on LaAlO3 substrate was reported. This effect is generally negligible in the strictly condensed composite films, where the thick substrates would inhibit any free deformations of the ferroic films (as usually called as “substrate clamping”). In this work, the authors found that the substrate influence could be effectively declined by the formation of columnar-grain structures in the magnetostrictive LSMO layer. Quick release of the clamping strength along the film normal direction allowed for free deformation of the upper part of the LSMO columns and thus the piezoelectric PZT layer as well. The maximum ME voltage coefficients αE of 3.0 and 4.2mVcm−1Oe−1, respectively, for the “transverse” and “parallel” measurement modes were obtained.
High quality factor microcavity lasers realized by circular photonic crystal with isotropic photonic band gap effect
Authors: Lee Po-Tsung , Lu Tsan-Wen , Fan Jyun-Hao , Tsai Feng-Mao
Published: April 2007

The photonic band gap (PBG) effect and its isotropy of sunflower-type circular photonic crystal (CPC) are obtained and investigated from the transmission spectra performed by finite-difference time-domain (FDTD) method. The PBG directional width variation is found to be only 6.7%. A well-confined whispering gallery mode (WGM) with azimuthal number of 6 is obtained by FDTD simulation from the CPC microcavity formed by seven missing air holes (C2). Ascribed to the deep and isotropic PBG confinement, the WGM lasing with very-low threshold (∼0.13mW) and very-high-quality (Q) factor (>10000) is obtained from well-fabricated CPC C2 microcavity lasers.