bluuebunny/crossref_metadata_2025 huggingface dataset:
Ryanodine receptor binding to FKBP12 is modulated by channel activation state
Authors: Jones Jonathan-Lee , Reynolds Deborah F. , Lai F. Anthony , Blayney Lynda M.
Published: September 2005

Ryanodine receptor (RyR) Ca2+ release channels undergo a conformational change between the open and closed states. Its protein modulator, FK506 binding protein 12 (FKBP12), stabilises the channel gating between the four subunits that surround a central Ca2+-conducting pore. To understand the interdependence of RyR and FKBP12 binding, physiological and pharmacological agents were used to modulate the RyR open/closed state. ELISA sandwich binding assays showed that FKBP12 binding was dependent on the free Ca2+ and was lower at 1-10 μM free Ca2+ compared with 1 mM EGTA and 1 mM Ca2+, and this effect was enhanced by the inclusion of 1 mM ATP. Ruthenium red increased the binding of FKBP12. [3H]Ryanodine binding confirmed that 1 mM EGTA, 1 mM Ca2+ and 1 μM ruthenium red closed the channel, whereas 1 μM free Ca2+, 1 μM free Ca2+ + 1 mM ATP, or 10 mM caffeine opened it. These binding conditions were used in surface plasmon resonance studies to measure equilibrium binding kinetics. The affinity constant KA was significantly greater for the closed than the open channel, a change mediated by a decreased dissociation rate constant, kd. The results show that surface plasmon resonance is a powerful technique that can measure differences in RyR1 equilibrium binding kinetics with FKBP12.
TGF-β-induced apoptosis in endothelial cells mediated by M6P/IGFII-R and mini-plasminogen
Authors: Leksa Vladimír , Godar Samuel , Schiller Herbert B. , Fuertbauer Elke , Muhammad Arshad , Slezakova Katarina , Horejsi Vaclav , Steinlein Peter , Weidle Ulrich H. , Binder Bernd R. , Stockinger Hannes
Published: September 2005

Transforming growth factor-β (TGF-β), a key modulator of endothelial cell apoptosis, must be activated from the latent form (LTGF-β) to induce biological responses. In the present study, we report activation of TGF-β by functional and physical co-operation of the mannose-6-phosphate/insulin-like-growth-factor-II receptor (CD222) and the urokinase-type plasminogen activator receptor (CD87). We show that endothelial cells express CD222 and CD87 in a membrane complex and demonstrate that the association of these two receptors is essential for the release of active TGF-β in the transduced mouse fibroblast used as model cells. By contrast, smooth-muscle cells, which express CD222 and CD87 at similar density to endothelial cells but not in complexed form, do not activate TGF-β. We also have found that mini-plasminogen is a high-affinity ligand for CD222 and is essential for the activation of TGF-β by the CD87-CD222 complex to induce apoptosis in endothelial cells. This specific mechanism of TGF-β-mediated apoptosis in endothelial cells is thus a potential novel target to be considered for treatment of pathological vascular disorders (e.g. tumor angiogenesis).
Spherical Nanostructured LiNi1/3Co1/3Mn1/3O2 Powders Prepared via an Ultrasonic Spray Pyrolysis Process
Authors: Wu Hung-Chun , Guo Zheng-Zhao , Yang Mo-Hua , Lu Chung-Hsin , Wu Tai-Yuan , Taniguchi Izumi
Published: September 2005

Nanostructured LiNi1/3Co1/3Mn1/3O2 powders were successfully synthesized via an ultrasonic spray pyrolysis process. The prepared powders were composed of nanosized crystallites and formed a spherical shape. Well-crystallized structure was obtained after calcination at 800 °C. The prepared LiNi1/3Co1/3Mn1/3O2 powders exhibited a high discharge capacity of 184 mAh/g within the voltage range of 2.5–4.5 V. The capacity retention was 78% after 100 cycles test at 1C charging and 3C discharging rate at 55 °C.
Synthesis and Structure of a Base-stabilized Silyl(silylene)tantalum Complex
Authors: Koshikawa Hidenori , Okazaki Masaaki , Matsumoto Shun-ichi , Ueno Keiji , Tobita Hiromi , Ogino Hiroshi
Published: September 2005

Thermal reaction of Cp2Ta(η2-C3H6) with HSiMe2SiMe2OMe in toluene at 60 °C gave Cp2Ta{SiMe2···O(Me)···SiMe2} (7%) and Cp2TaH(SiMe2SiMe2OMe)2 (8%). The former methoxy-stabilized silyl(silylene) complex was characterized by X-ray diffraction study.
Immobilization of Methylene Blue between Electrodepsoited Manganese Oxide Multilayers
Authors: Nakayama Masaharu , Komatsu Hiroyuki , Ozuka Shotaro , Araki Yuto , Ogura Kotaro
Published: September 2005

Cationic methylene blue (MB) ions were intercalated into the galleries of a layered manganese oxide film that was deposited anodically on an indium–tin oxide electrode. The MB+ ions once incorporated are not ion-exchanged with small cations and can communicate with the electrode surface through manganese oxide sheets.
Evidence of Photocarrier Generation via the Singlet and Triplet States in a Poly(N-vinylcarbazole) Film
Authors: Ikoma Tadaaki , Ito Fuyuki , Ogiwara Toshinari , Akiyama Kimio , Tero-Kubota Shozo
Published: September 2005

A significant wavelength dependence of the excitation light was observed in the magnetic field effects (MFE) on the photocarrier generation of a benzene-1,2,4,5-tetracarbonitrile-doped poly(N-vinylcarbazole) film. The excitation of the carbazole induces positive MFEs, indicating an enhancement of the photoconductivity originating from the charge separation through the triplet exciton. In contrast, a singlet spin state governs the photocarrier generation in the case of the charge transfer band excitation, because negative MFEs are induced.
Stereoselective Construction of 1,3-Diol Derivatives via Nucleophilic Reaction to β-Methoxyacylsilanes
Authors: Honda Mitsunori , Mikami Yoshimi , Sanjyo Takeshi , Segi Masahito , Nakajima Tadashi
Published: September 2005

The stereoselectivity of 1,3-asymmetric induction in the nucleophilic addition to β-methoxyacylsilanes having no substituent at the α-position is largely dependent on the kind of nucleophiles. In a similar reaction employed α-substituted β-methoxyacylsilanes, three diastereoisomers of 1,3-diol derivatives having the three contiguous stereogenic centers among four possible diastereomeric products are yielded with high stereoselectivity. The protiodesilylation of the resulting α-silylalcohols proceeds with complete retention of the configuration.
RNA-directed construction of structurally complex and active ligase ribozymes through recombination
Authors: HAYDEN ERIC J. , RILEY CRAIG A. , BURTON AARON S. , LEHMAN NILES
Published: September 2005

RNA-directed recombination can be used to catalyze a disproportionation reaction among small RNA substrates to create new combinations of sequences. But the accommodation of secondary and tertiary structural constraints in the substrates by recombinase ribozymes has not been explored. Here, we show that the Azoarcus group I intron can recombine oligoribonucleotides to construct class I ligase ribozymes, which are catalytically active upon synthesis. The substrate oligonucleotides, ranging in size from 58 to 104 nucleotides (nt), along with the 152-nt ligase ribozymes they reconstitute, can contain significant amounts of secondary structure. However, substrate recognition by the Azoarcus ribozyme depends on the existence of a single accessible CAU triplet for effective recombination. A biphasic temperature reaction profile was designed such that the sequential recombination/ligation events could take place in a thermocycler without human intervention. A temperature-dependent pH shift of the reaction buffer contributes to the success of the net reaction. When the substrate for the ligase ribozyme is introduced into the reaction mixture, as much as 11% can be observed being converted to product by the recombined ligase in the same reaction vessel. Recombination followed by ligation can also occur under isothermal conditions at 37°C. Tertiary structure formation of the ligase upon construction can provide some protection from cleavage by the Azoarcus ribozyme when compared to the constituent substrates. These data suggest that RNA-directed recombination can, in fact, articulate complex ribozymes, and that there are logical rules that can guide the optimal placement of the CAU recognition sequence.
Competition of PTB with TIA proteins for binding to a U-rich cis-element determines tissue-specific splicing of the myosin phosphatase targeting subunit 1
Authors: SHUKLA SUPRIYA , DEL GATTO-KONCZAK FABIENNE , BREATHNACH RICHARD , FISHER STEVEN A.
Published: September 2005

A considerable amount of smooth muscle phenotypic diversity is generated by tissue-specific and developmentally regulated splicing of alternative exons. The control mechanisms are unknown. We are using a myosin phosphatase targeting subunit-1 (MYPT1) alternative exon as a model to investigate this question. In the present study, we show that the RNA binding proteins TIA and PTB function as antagonistic enhancers and suppressors of splicing of the alternative exon, respectively. Each functions through a single U-rich element, containing two UCUU motifs, just downstream of the alternative exon 5′ splice site. Tissue-specific down-regulation of TIA protein in the perinatal period allows PTB to bind to the U-rich element and suppress splicing of the alternative exon as the visceral smooth muscle acquires the fast-phasic smooth muscle contractile phenotype. This provides a novel role for PTB in the tissue-specific regulation of splicing of alternative exons during the generation of smooth muscle phenotypic diversity.
Topiramate in Opiate Withdrawal-Comparison with Clonidine and with Carbamazepine/Mianserin
Authors: Zullino Daniele Fabio , Krenz Sonia , Zimmermann Grégoire , Miozzari Amos , Rajeswaran Rajini , Kolly Stéphane , Khazaal Yasser
Published: September 2005

There are some rationales for developing anticonvulsants for the treatment of substance abuse. The blockade of the AMPA/kainate subtype of glutamate receptor by topiramate may be of particular interest, as preclinical studies of withdrawal from opioids suggest that whilst AMPA-receptor antagonists may not be able to prevent tolerance or dependence from developing, they may ameliorate both physical and emotional consequences of withdrawal.

Methods.

Ten consecutively admitted patients treated with topiramate were compared in a retrospective naturalistic drug utilization observation study with 10 consecutively admitted patients treated with clonidine and with 10 consecutively admitted patients treated with a carbamazepine/ mianserin combination.

Results.

In 9 cases of the clonidine group and in 7 carbamazepine/mianserin treated patients the dose had been reduced, whereas this occurred in only 2 topiramate treated patients (p < 0.01). Patients in the topiramate group received less p.r.n. myorelaxant medication than the two other groups, and there was a significant difference between the three groups with regard to p.r.n. analgesics (p < 0.05), topiramate and clonidine treated patients receiving fewer analgesics than the carbamazepine/mianserin group.

Conclusions.

Compared to clonidine and carbamazepine/mianserin, a detoxification scheme using high initial and then decreasing doses of topiramate appeared to be appropriate for most patients and as associated with less analgesic and myorelaxant comedication, indicating a more promising efficacy at the used doses.
Obsessions and Compulsions Are Associated With Different Cognitive and Mood Factors
Authors: Bhar Sunil S. , Kyrios Michael
Published: September 2005

This study examined whether nonclinical obsessions and nonclinical compulsions relate differently to cognitive and mood factors such as responsibility, perfectionism, trait anxiety and depressed mood. Two hundred and three nonclinical undergraduate psychology students (70.4% females, 29.6% males, mean age = 18.7,SD= 1.1) completed questionnaires. After controlling for the relationship between obsessions and compulsions, obsessions were found to relate significantly more strongly to depressed mood, trait anxiety, socially prescribed perfectionism and responsibility than compulsions. Conversely, compulsions were found to relate more strongly to self-oriented perfectionism than obsessions. These results were interpreted as providing support for the notion that obsessive-compulsive disorder (OCD) is maintained by a conflicted mental representation of the self and the world. Obsessions were interpreted as reflecting an overdeveloped vigilance for threat, responsibility and need for social approval. Compulsions were interpreted as emanating from the belief that the self is self-sufficient and resourceful, and that the world is ordered and systematic. Implications for the treatment of OCD were discussed.
The Relationship Between Mental Health, Cultural Identity and Cultural Values in Non-English Speaking Background (NESB) Australian Adolescents
Authors: Sawrikar Pooja , Hunt Caroline J.
Published: September 2005

In Australia, acculturating adolescents from a non-English speaking background (NESB) face two important challenges: developing a cultural identity and establishing a set of cultural values. These challenges are achieved by balancing a native and Australian orientation. It was expected that NESB adolescents who did not achieve these tasks would experience poor mental health. This study focused on adolescents because a significant relationship between cultural identity, cultural values and mental health in this group will highlight a need for sensitivity to such cultural and developmental issues. Two hundred and sixty-three NESB adolescents completed questionnaires that assessed cultural identity (Australian and native), cultural values (individualism and collectivism), state mental health (depression, anxiety and stress) and trait mental health (positive affectivity [PA] and negative affectivity [NA]). Results indicated that high Australian pride and high native pride are associated with lower depression, anxiety, stress and NA, and higher PA. Results also indicated that adolescents high on individualism and collectivism reported lower depression and stress, and higher PA. Furthermore, adolescents with a separated cultural identity (high native pride and low Australian pride) reported the highest levels of depression, but adolescents with separated cultural values (high collectivism and low individualism) reported the lowest levels of depression and anxiety. We concluded that cultural identity and cultural values are differentially related to mental health, and such relationships, albeit moderate, emerge during adolescence.
Parental Perceptions of Overprotection: Specific to Anxious Children or Shared Between Siblings?
Authors: Hudson Jennifer L. , Rapee Ronald M.
Published: September 2005

Parents of children with anxiety disorders (n = 45) and parents of nonclinical children (n = 33) were interviewed regarding the rearing of two children in their family. The purpose of the study was to determine whether overprotective parenting, according to parent report, occurs specifically in the context of relationships with the anxiety-disordered child or whether parents also perceive themselves to be overprotective of the anxious child's sibling. Self-reports of overprotection by parents of anxious children were also compared to self-reports of overprotection by parents of nonclinical children. Mothers in the clinical group were more likely to report that they were more protective of the anxious child than they were to report being either more protective of the sibling or equally protective of both children. Both mothers and fathers in the clinical group were no more likely than nonclinical parents to perceive themselves as being more protective overall than other parents.
The Influence of Competitive Intensity and Market Dynamism on Knowledge Management Capabilities of Multinational Corporation Subsidiaries
Authors: Cui Anna Shaojie , Griffith David A. , Cavusgil S. Tamer
Published: September 2005

The authors use the environment–strategy–performance theoretical framework to examine the direct influence of the environmental market conditions of competitive intensity and market dynamism on knowledge management capabilities of multinational corporation (MNC) subsidiaries and resultant subsidiary performance. The results of a survey of the managers of Croatian subsidiaries of foreign MNCs indicate that though both competitive intensity and market dynamism individually influence knowledge management capabilities, when examined jointly, market dynamism is a more influential environmental market condition than competitive intensity. The authors also find a significant, positive relationship between a subsidiary's knowledge management capabilities and its performance. The findings indicate the importance of understanding local market conditions and developing proper strategic configurations for MNC subsidiaries.
Genotyping of the 19-bp insertion/deletion polymorphism in the 5′ flank of β-hydroxylase gene by dissociation analysis of allele-specific PCR products
Authors: Rasmussen Henrik Berg , Werge Thomas
Published: September 2005

The 19-bp insertion/deletion polymorphism in the 5′ flank of the dopamine β-hydroxylase (
Serum proteins profile as an indicator of malignancy: multivariate logistic regression and ROC analyses
Authors: Rasouli Mehdi , Okhovatian Ali , Enderami Atena
Published: September 2005

The electrophoretic pattern of serum proteins of 85 patients carrying different types of neoplasia and 85 matched healthy adults were comparatively studied by agarose gel electrophoresis, to find out if there is a specific protein pattern common to different types of cancer. Each protein fraction was analyzed quantitatively by densitometry. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were performed using SPSS software. When total protein and albumin were measured by colorimetric methods, cancer patients, compared to controls, had a decreased concentration of total protein (66.0±11.5g/L vs. 76.4±6.8g/L, p≤0.0001) and of albumin (39.0±8.1g/L vs. 46.0±4.3g/L, p≤0.0001). The electrophoretic data of serum proteins showed that the ratio of albumin to globulin (0.92±0.30 vs. 1.21±0.16, p≤0.0001), percent of the fractions albumin (46.7±8.5% vs. 54.4±3.5%, p≤0.0001) and β-globulin (11.6±4.4% vs. 13.0±1.9%, p≤0.001) were decreased and α
Alterations of glycosaminoglycan metabolism in the development of diabetic complications in relation to metabolic control
Authors: Komosińska-Vassev Katarzyna , Olczyk Krystyna , Koźma Ewa M. , Olczyk Paweł , Wisowski Grzegorz , Winsz-Szczotka Katarzyna
Published: September 2005

Disturbed metabolism of glycosaminoglycans (GAGs) has been proposed to play an important role in the pathogenesis of late diabetic complications. The effect of diabetic complications and metabolic control on both total serum GAGs content and the serum activity of lysosomal glycosidases (N-acetyl-β-D-glucosaminidase, α-L-fucosidase, β-D-galactosidase, and α-D-mannosidase) contributing to GAGs degradation, was investigated in 48 patients with type 2 diabetes mellitus. The activity of β-D-glucosidase and acid phosphatase, the lysosomal enzymes unrelated to GAGs metabolism, was determined for comparison. The elevated serum total GAG concentration in diabetic patients was strongly and positively influenced by poor metabolic compensation of diabetes and the presence of vascular complications. A similar tendency has been shown in regard to the activity of enzymes involved in GAG degradation, especially N-acetyl-β-D-glucosaminidase, α-L-fucosidase and β-D-galactosidase. Furthermore, the total serum GAG concentrations, as well as the activity of lysosomal enzymes involved in the extracellular matrix degradation, closely followed metabolic compensation, regardless of diabetic vascular complications. Thus, we suggest that increased values of the investigated parameters may indicate the degree of endothelial cell dysfunction and may be useful to predict the development of diabetic vascular pathology.
Diagnostic and analytical performance of a screening panel for allergy
Authors: Herzum Ileana , Blümer Nicole , Kersten Werner , Renz Harald
Published: September 2005

Worldwide, allergic diseases are increasing in prevalence and incidence. Early assessment of the immunoglobulin E (IgE) sensitisation status has a major impact on clinical outcome and selection of therapeutic options. Recently, a number of new IgE-detecting test systems have entered the market, including screening tests allowing identification of a wide spectrum of sensitising allergens. We evaluated the analytical and diagnostic performance of the newly developed Allergy Screen test panel for atopy (Mediwiss Analytic, Moers, Germany). The evaluation was performed for four major respiratory and four major nutritional allergens in 142 patients with clinical suspicion of respiratory and/or food allergies. For all allergens, the test showed acceptable concordance to the skin-prick test and the in vitro IgE CAP system (Pharmacia, Freiburg, Germany). The analytical performance was acceptable, with CVs between 2 and 8% in the positive range and good dilution linearity (R=0.9735). Imprecision in the low IgE concentration range dramatically improved by lowering the cut-off value to 0.2IU/mL IgE. In conclusion, the Allergy Screen panel yields reliable results in the detection of allergic sensitisation to common allergens.
Fluorescence Anisotropy Imaging Reveals Localization of meso‐Tetrahydroxyphenyl Chlorin in the Nuclear Envelope
Authors: Foster Thomas H. , Pearson Benjamin D. , Mitra Soumya , Bigelow Chad E.
Published: September 2005

We have measured the intrinsic fluorescence anisotropies of six photosensitizers in homogeneous solution, and we have imaged the anisotropies of these sensitizers in tumor cell monolayers using polarization‐sensitive laser‐scanning confocal microscopy. The intrinsic anisotropies are unremarkable and are within the approximate range of 0.2–0.27. In cells, however, very interesting behavior is exhibited by meso‐tetrahydroxyphenyl chlorin (mTHPC). Polarization‐sensitive images of mTHPC's fluorescence show a pronounced banding of alternating high and low anisotropy consistent with an ordering of the sensitizer in the nuclear envelope, indicating that this structure is a target of photodynamic damage with this sensitizer. None of the other sensitizers exhibits localization to the nuclear envelope. The frequency distributions of the intracellular anisotropies of the sensitizers exhibit variable peaks and widths. An unusual case is that of Photofrin, with a peak in its anisotropy frequency distribution of –0.12. The change from a positive intrinsic anisotropy in homogeneous solution to a negative value in cells suggests an environmentally induced change in the relative orientations of the absorption and emission dipole moments.
Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells
Authors: Veveris-Lowe T L , Lawrence M G , Collard R L , Bui L , Herington A C , Nicol D L , Clements J A
Published: September 2005

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.
Lovastatin suppresses invasiveness of anaplastic thyroid cancer cells by inhibiting Rho geranylgeranylation and RhoA/ROCK signaling
Authors: Zhong W-B , Liang Y-C , Wang C-Y , Chang T-C , Lee W-S
Published: September 2005

Lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, inhibits the conversion of mevalonate from HMG-CoA. Previously, we have reported that lovastatin treatment induced the occurrence of apoptosis and differentiation in ARO anaplastic thyroid cancer cells. Here, we demonstrated that lovastatin inhibited the ARO cell invasiveness and delineated the underlying molecular mechanism. Lovastatin significantly suppressed the EGF-induced cell adhesion, actin filament reorganization and transmigration. Lovastatin also reduced EGF-induced increases in the levels of phosphorylated p125FAK and paxillin. These inhibitory effects mediated by lovastatin can be prevented by pretreatment of the cells with mevalonate or geranylgeraniol (GGOH), but not farnesol (FOH). Accordingly, the consuming and depletion of geranylgeranyl pyrophosphate and consequent suppression of the protein geranylgeranylation, which is essential for activation of Rho GTPases, might account for the lovastatin-induced inhibition of cell motility and invasion. Western blot analysis showed that lovastatin inhibited membrane translocation of Rho (e.g. RhoA and Rac1) through decreasing post-translational geranylgeranyl modification of Rho. In addition, treatment of the cells with specific inhibitors against Rho (Clostridium botulinum C3 transferase) or ROCK (Y-27632) abolished the GGOH-mediated prevention of, and restored the lovastatin-induced decrease of cell invasion. Taken together, our results suggested that lovastatin suppressed EGF-induced ARO cell invasiveness through the reduction of Rho geranylgeranylation, which in turn suppressed the membrane translocation, and subsequent suppression of Rho/ROCK and FAK/paxillin signaling.
The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers
Authors: Rau K-M , Kang H-Y , Cha T-L , Miller S A , Hung M-C
Published: September 2005

Breast and prostate cancer are the most well-characterized cancers of the type that have their development and growth controlled by the endocrine system. These cancers are the leading causes of cancer death in women and men, respectively, in the United States. Being hormone-dependent tumors, antihormone therapies usually are effective in prevention and treatment. However, the emergence of resistance is common, especially for locally advanced tumors and metastatic tumors, in which case resistance is predictable. The phenotypes of these resistant tumors include receptorpositive, ligand-dependent; receptor-positive, ligand-independent; and receptor-negative, ligand-independent. The underlying mechanisms of these phenotypes are complicated, involving not only sex hormones and sex hormone receptors, but also several growth factors and growth factor receptors, with different signaling pathways existing alone or together, and with each pathway possibly linking to one another. In this review, we will discuss the potential mechanisms of antihormonetherapy resistance in breast and prostate cancers, especially focusing on the similarities and differences of these two cancers. We will also discuss novel agents that have been applied in clinical practice or with clinical potential in the future.
The Intragroup Conflict Scale: Development and Psychometric Properties
Authors: Cox Kathleen B.
Published: September 2005

Managers in health care organizations spend an average of 20% of their time dealing with conflict. Hence, a well-developed measure of intragroup conflict is needed to assess work environments. The Intragroup Conflict Scale was developed to measure views of conflict, perceptions of behavior, and perceptions of affective states, that occur in the core process of conflict. The scale was pilot tested with a sample of 184 staff nurses and was later used in a study of antecedents and effects of intragroup conflict in the nursing unit (n = 141). Data from the two studies were merged (n = 325). Using PCA with varimax rotation in the analysis of merged data, three factors that explained 69.2% of variance were extracted. Factor 1 reflects opposition processes and negative emotion; factor 2 reflects trust and freedom of expression; and factor 3 reflects views of conflict. Factor loadings ranged from .60 to .88 on factor 1, from .62 to .79 on factor 2, and from .69 to .80 on factor 3. Coefficient alpha for the three factors were .89 for factor 1, .88 for factor 2, and .79 for factor 3. Correlations with existing scales provided support for construct validity. The scale has evidence for its reliability and validity, and may have the potential to contribute to the understanding of intragroup conflict in organizations. The new Intragroup Conflict Scale demonstrates sufficient construct validity to warrant its continued evaluation.
Concept Advancement: Extending Science Through Concept-Driven Research
Authors: Penrod Janice , Hupcey Judith E.
Published: September 2005

As methods for concept analysis have evolved, scholars have confounded the initial exploration of a concept with techniques for developing the conceptual unit, extending nursing theory, and establishing nursing knowledge. We argue that nursing is at a critical juncture in the methodological development of concept-driven research. In order to maximize the potential contribution of this type of research, approaches to concept analysis must be held separate and distinct from approaches to concept advancement. We advocate the use of principle-based concept analysis to determine appropriate techniques for advancing a concept. Concept advancement refers to strategic concept-driven inquiries that incrementally build the specification of conceptual meaning to a more precisely defined unit of meaning that has greater utility for research application. Examples of a project that employed strategic techniques for concept advancement are used to illustrate the flow of serial small projects.
Bio‐mimetic scaling of mechanical behavior of thin films, coatings, and surfaces by Laser Interference Metallurgy
Authors: Daniel C. , John Balk T. , Wübben T. , Mücklich F.
Published: September 2005

Biological solutions to enhance strength and stability often use hierarchical composite structures. The effect is not based on large chemical variations, but instead is realized by structural composites with long‐range order. Laser Interference Metallurgy is a newly developed technique that utilizes this biological approach to optimize the mechanical properties of surfaces and thin films. The possibility of scaling mechanical properties is quantitatively analyzed and compared with the biological approach.
Zintl Phases as Thermoelectric Materials: Tuned Transport Properties of the Compounds CaxYb1–xZn2Sb2
Authors: Gascoin F. , Ottensmann S. , Stark D. , Haïle S. M. , Snyder G. J.
Published: September 2005

Zintl phases are ideal candidates for efficient thermoelectric materials, because they are typically small‐bandgap semiconductors with complex structures. Furthermore, such phases allow fine adjustment of dopant concentration without disrupting electronic mobility, which is essential for optimizing thermoelectric material efficiency. The tunability of Zintl phases is demonstrated with the series CaxYb1–xZn2Sb2 (0 ≤ x ≤ 1). Measurements of the electrical conductivity, Hall mobility, Seebeck coefficient, and thermal conductivity (in the 300–800 K temperature range) show the compounds to behave as heavily doped semiconductors, with transport properties that can be systematically regulated by varying x. Within this series, x = 0 is the most metallic (lowest electrical resistivity, lowest Seebeck coefficient, and highest carrier concentration), and x = 1 is the most semiconducting (highest electrical resistivity, highest Seebeck coefficient, and lowest carrier concentration), while the mobility is largely independent of x. In addition, the structural disorder generated by the incorporation of multiple cations lowers the overall thermal conductivity significantly at intermediate compositions, increasing the thermoelectric figure of merit, zT. Thus, both zT and the thermoelectric compatibility factor (like zT, a composite function of the transport properties) can be finely tuned to allow optimization of efficiency in a thermoelectric device.
Resorcin[4]arene Cavitand‐Based Molecular Switches
Authors: Azov V. A. , Beeby A. , Cacciarini M. , Cheetham A. G. , Diederich F. , Frei M. , Gimzewski J. K. , Gramlich V. , Hecht B. , Jaun B. , Latychevskaia T. , Lieb A. , Lill Y. , Marotti F. , Schlegel A. , Schlittler R. R. , Skinner P. J. , Seiler P. , Yamakoshi Y.
Published: September 2005

Resorcin[4]arene cavitands with four quinoxaline bridges are a family of macrocycles that adopt, at elevated temperature, a contracted, vase‐type conformation, capable of guest inclusion, whereas at low temperature they switch to an expanded, kite‐type conformation with a large flat surface. The present investigations lay the foundation for the use of such dynamic cavitands as miniaturized mechanical grippers for supramolecular construction at the single‐molecule level. New vase–kite switching modes, stimulated by pH changes or stoichiometric metal‐ion complexation, have been discovered and monitored by 1H NMR and optical absorption spectroscopy. The solid‐state geometries of the two states have been revealed by X‐ray crystallography, and the kinetics and thermodynamics of the switching processes in solution as well as their solvent dependency has been investigated in great detail. Monolayers of the cavitand in the vase form have been studied by scanning tunneling microscopy at molecular resolution; conformational switching is also observed in Langmuir monolayers at the air/water interface. Synthetic protocols have been developed for preparation of partially and asymmetrically bridged resorcin[4]arene cavitands, which are also shown to undergo conformational switching. These synthetic advances pave the way to new, dynamic molecular receptors for steroids, tetrathiofulvalene‐bridged grippers with the potential to undergo electrochemically induced conformational switching, and systems with greatly extended, rigid cavity walls functionalized at the termini by dipyrrometheneboron difluoride dyes. The latter cavitands are shown by fluorescence resonance energy transfer to undergo geometrically precisely defined motions between a contracted (≈ 7 Å linear extension) and a strongly expanded (≈ 7 nm linear extension) state.
Macroporous Silicon Microcavities for Macromolecule Detection
Authors: Ouyang H. , Christophersen M. , Viard R. , Miller B. L. , Fauchet P. M.
Published: September 2005

Macroporous silicon microcavities for detection of large biological molecules have been fabricated from highly doped n‐type silicon. Well‐defined controllable pore sizes up to 120 nm have been obtained by systematically optimizing the etching parameters. The dependence of the sensor sensitivity on pore size is discussed. Excellent infiltration inside these macroporous silicon microcavities is demonstrated using 60 nm diameter latex spheres and rabbit IgG (150 kDa; 1Da = 1 g mol–1). The sensing performance of the device is tested using a biotin/streptavidin couple, and protein concentration down to 1–2 μM (equivalent to 0.3 ng mm–2) could be detected. Simulations show that the sensitivity of the technique is currently approximately 1–2 % of a protein monolayer.
Efficient Infrared Electroluminescent Devices Using Solution‐Processed Colloidal Quantum Dots
Authors: Konstantatos G. , Huang C. , Levina L. , Lu Z. , Sargent E. H.
Published: September 2005

We report efficient electroluminescence in the near‐infrared from PbS–MEH‐PPV (poly(2‐methoxy‐5‐(2′‐ethylhexyloxy)‐1,4‐phenylenevinylene)) large‐area, solution‐cast nanocomposite devices. We employ multivariate optimization of the structural and materials components that govern the radiative, energy‐transfer, and bipolar‐injection efficiencies into the devices. As a result, we report an external electroluminescence quantum efficiency of 0.27 %, which corresponds to an internal electroluminescence quantum efficiency of 1.9 %. The very best devices exhibit internal‐radiative‐efficiency‐limited performance and not transport‐ or capture‐limited performance, indicating that further gains in efficiency may be achieved if the internal radiative efficiency of the nanocrystal–polymer composite can be further increased without compromising transfer and device bipolar‐injection efficiency.
Software system for three‐dimensional volumetric reconstruction of histological sections: A case study for the snake chondrocranium
Authors: Hofstadler‐Deiques Clarice , Walter Marcelo , Mierlo Fábio , Ruduit Rodrigo
Published: September 2005

Volumetric digital computer‐assisted reconstruction of histological sections is an attractive possibility for developmental studies. Commercial solutions are very expensive for many educational institutions. Therefore, we developed a software system for three‐dimensional reconstruction of anatomical virtual models. The input data for the system are the digitized images from the histological samples of the chondrocranium of two crotalines, Bothrops jararaca and Crotalus durissus terrificus, and one colubrid, Philodryas olfersii, using a stereomicroscope connected to a digital camera. These images are then manually registered and segmented. We use computer graphics visualization algorithms such as marching cubes and ray casting to generate three‐dimensional visualizations of the volumes. The results show that the digital reconstruction is as good as the manual reconstruction with the advantages of speed of reconstruction, accuracy, and flexibility to handle and study the volume. Compared with commercial options, our system has approximately the same features, and it is available free for the scientific community. © 2005 Wiley‐Liss, Inc.
Global expression profiling of Bacillus subtilis cells during industrial‐close fed‐batch fermentations with different nitrogen sources
Authors: Jürgen Britta , Tobisch Steffen , Wümpelmann Mogens , Gördes Dirk , Koch Andreas , Thurow Kerstin , Albrecht Dirk , Hecker Michael , Schweder Thomas
Published: September 2005

A detailed gene expression analysis of industrial‐close Bacillus subtilis fed‐batch fermentation processes with casamino acids as the only nitrogen source and with a reduced casamino acid concentration but supplemented by ammonia was carried out. Although glutamine and arginine are supposed to be the preferred nitrogen sources of B. subtilis, we demonstrate that a combined feeding of ammonia and casamino acids supports cell growth under fed‐batch fermentation conditions. The transcriptome and proteome analyses revealed that the additional feeding of ammonia in combination with a reduced amino acid concentration results in a significantly lower expression level of the glnAR or tnrA genes, coding for proteins, which are mainly involved in the nitrogen metabolism of B. subtilis. However, the mRNA levels of the genes of the ilvBHC‐leuABD and hom‐thrCB operons were significantly increased, indicating a valine, leucine, isoleucine, and threonine limitation under these fermentation conditions. In contrast, during the fermentation with casamino acids as the only nitrogen source, several genes, which play a crucial role in nitrogen metabolism of B. subtilis (e.g., glnAR, nasCDE, nrgAB, and ureABC), were up‐regulated, indicating a nitrogen limitation under these conditions. Furthermore, increased expression of genes, which are involved in motility and chemotaxis (e.g., hag, fliT) and in acetoin metabolism (e.g., acoABCL), was determined during the fermentation with the mixed nitrogen source of casamino acids and ammonia, indicating a carbon limitation under these fermentation conditions. Under high cell density and slow growth rate conditions a weak up‐regulation of autolysis genes could be observed as well as the induction of a number of genes involved in motility, chemotaxis and general stress response. Results of this study allowed the selection of marker genes, which could be used for the monitoring of B. subtilis fermentation processes. The data suggest for example acoA as a marker gene for glucose limitation or glnA as an indicator for nitrogen limitation. © 2005 Wiley Periodicals, Inc.
Production of 2‐phenylethanol and 2‐phenylethylacetate from L‐phenylalanine by coupling whole‐cell biocatalysis with organophilic pervaporation
Authors: Etschmann Maria M.W. , Sell Dieter , Schrader Jens
Published: September 2005

An integrated bioprocess for the production of the natural rose‐like aroma compounds, 2‐phenylethanol (2‐PE) and 2‐phenylethylacetate (2‐PEAc), from L‐phenylalanine (L‐phe) with yeasts was investigated. The hydrophobicity of the products leads to product inhibition, which can be compensated by in situ product removal (ISPR). An organophilic pervaporation unit, equipped with a polyoctylmethylsiloxane (POMS) membrane, was coupled via a bypass to a bioreactor and proved to be a suitable technique for the in situ removal of high‐boiling products from culture broth. With batch cultures of the thermotolerant yeast Kluyveromyces marxianus CBS 600 in a standard medium at 35°C, the use of pervaporation resulted in a double 2‐PE concentration (2.2 g/L) and 1.3 g/L 2‐PEAc, which only accumulated transiently in low concentrations during cultivation without ISPR. Using a previously optimized medium, the variation of the temperature from 30°C to 40°C caused an increase in the total conversion yield from 63% to 79%, corresponding to total product concentrations of 5.23 and 5.85 g/L, respectively. In the 40°C batch experiment, the volumetric productivity (2‐PE + 2‐PEAc) during the exponential phase was 5.2 mmol/L h. While for 2‐PE, there is still potential for further optimization, the more hydrophobic 2‐PEAc was nearly completely removed from the aqueous culture broth (enrichment factor >400), resulting in highly aroma‐enriched permeates. Due to the temperature‐correlated performance of the pervaporation, the bioconversion was still efficient even at 45°C (conversion yield: 69%). Surprisingly, at 45°C, the molar ratio of the two products inverted and 2‐PEAc turned out to be the main product (4.0 g/L), which opens easy control of the reaction's selectivity by external means. Retrofitting the process with interim heating and cooling equipment to use different temperature levels for cultivation and pervaporation resulted in a decreased yield and product concentration caused by multiple stress factors. The medium composition affected the pervaporation efficiency with molasses acting detrimental. © 2005 Wiley Periodicals, Inc.
The prediction error in CLS and PLS: the importance of feature selection prior to multivariate calibration
Authors: Nadler Boaz , Coifman Ronald R.
Published: September 2005

Classical least squares (CLS) and partial least squares (PLS) are two common multivariate regression algorithms in chemometrics. This paper presents an asymptotically exact mathematical analysis of the mean squared error of prediction of CLS and PLS under the linear mixture model commonly assumed in spectroscopy. For CLS regression with a very large calibration set the root mean squared error is approximately equal to the noise per wavelength divided by the length of the net analyte signal vector. It is shown, however, that for a finite training set withnsamples inpdimensions there are additional error terms that depend on σ2p2/n2, where σ is the noise level per co‐ordinate. Therefore in the ‘largep—smalln’ regime, common in spectroscopy, these terms can be quite large and even dominate the overall prediction error. It is demonstrated both theoretically and by simulations that dimensional reduction of the input data via their compact representation with a few features, selected for example by adaptive wavelet compression, can substantially decrease these effects and recover the asymptotic error. This analysis provides a theoretical justification for the need to perform feature selection (dimensional reduction) of the input data prior to application of multivariate regression algorithms. Copyright © 2005 John Wiley & Sons, Ltd.
The role of loop ZA and Pro371 in the function of yeast Gcn5p bromodomain revealed through molecular dynamics and experiment
Authors: Pizzitutti Francesco , Giansanti Andrea , Ballario Paola , Ornaghi Prisca , Torreri Paola , Ciccotti Giovanni , Filetici Patrizia
Published: September 2005

Biological experiments were combined with molecular dynamics simulations to understand the importance of amino acidic residues present in the bromodomain of the yeast histone acetyltransferase Gcn5p. It was found that residue Pro371 plays an important role in the molecular recognition of the acetylated histone H4 tail by Gcn5p bromodomain. Crystallographic analysis of the complex showed that this residue does not directly interact with the histone substrate. It has been demonstrated that a double mutation Pro371Thr and Met372Ala in the Gcn5p bromodomain impairs chromatin remodeling activity. It is demonstrated here that, in this double mutant and in the fully deleted bromodomain strain, there is lower growth under amino acid deprivation conditions. By in vitro surface plasmon resonance (Biacore) experiments it is shown that the binding affinity of the double mutation to acetyl lysine 16 histone H4 peptide decreases. Molecular dynamics simulations were used to explain this loss in acetyl lysine–Gcn5p bromodomain affinity, in the double mutant. By comparing nanosecond molecular dynamics trajectories of the native as well as the single and doubly mutated bromodomain, it is concluded that the presence of Pro371 is important to the functionality of the Gcn5p bromodomain. In the simulation a point mutation involving this highly conserved residue induced an increase in the flexibility of the ZA loop, which in turn modulated the exposure of the binding pocket to the acetyl lysine. The combined double mutations (Pro371Thr‐Met372Ala) not only markedly perturb the motion of the ZA loop but also destabilize the entire structure of the bromodomain. Copyright © 2005 John Wiley & Sons, Ltd.