A panel method free-wake code for aeroelastic rotor predictions

A panel method free-wake model to analyse the rotor flapping is presented. The aerodynamic model consists of a panel method, which takes into account the three-dimensional rotor geometry, and a free-wake model, to determine the wake shape. The main features of the model are the wake division into a near-wake sheet and a far wake represented by a single tip vortex, and the modification of the panel method formulation to take into account this particular wake description. The blades are considered rigid with a flap degree of freedom. The problem solution is approached using a relaxation method, which enforces periodic boundary conditions. Finally, several code validations against helicopter and wind turbine experimental data are performed, showing good agreement

Hysteresis in transverse galloping: the role of the inflection points

Transverse galloping is here considered as a one-degree-of-freedom oscillator subjected to aerodynamic forces, which are described by using the quasi-steady hypothesis. The hysteresis of transverse galloping is also analyzed. Approximate solutions of the model are obtained by assuming that the aerodynamic and damping forces are much smaller than the inertial and stiffness ones. The analysis of the approximate solution, which is obtained by means of the method of Krylov–Bogoliubov, reveals the existing link between the hysteresis phenomenon and the number of inflection points at the aerodynamic force coefficient curve, Cy(α)Cy(α); CyCy and αα being, respectively, the force coefficient normal to the incident flow and the angle of attack. The influence of the position of these inflection points on the range of flow velocities in which hysteresis takes place is also analyzed.

Genetic instability of cancer cells is proportional to their degree of aneuploidy

Genetic and phenotypic instability are hallmarks of cancer cells, but their cause is not clear. The leading hypothesis suggests that a poorly defined gene mutation generates genetic instability and that some of many subsequent mutations then cause cancer. Here we investigate the hypothesis that genetic instability of cancer cells is caused by aneuploidy, an abnormal balance of chromosomes. Because symmetrical segregation of chromosomes depends on exactly two copies of mitosis genes, aneuploidy involving chromosomes with mitosis genes will destabilize the karyotype. The hypothesis predicts that the degree of genetic instability should be proportional to the degree of aneuploidy. Thus it should be difficult, if not impossible, to maintain the particular karyotype of a highly aneuploid cancer cell on clonal propagation. This prediction was confirmed with clonal cultures of chemically transformed, aneuploid Chinese hamster embryo cells. It was found that the higher the ploidy factor of a clone, the more unstable was its karyotype. The ploidy factor is the quotient of the modal chromosome number divided by the normal number of the species. Transformed Chinese hamster embryo cells with a ploidy factor of 1.7 were estimated to change their karyotype at a rate of about 3% per generation, compared with 1.8% for cells with a ploidy factor of 0.95. Because the background noise of karyotyping is relatively high, the cells with low ploidy factor may be more stable than our method suggests. The karyotype instability of human colon cancer cell lines, recently analyzed by Lengnauer et al. [Lengnauer, C., Kinzler, K. W. & Vogelstein, B. (1997) Nature (London) 386, 623–627], also corresponds exactly to their degree of aneuploidy. We conclude that aneuploidy is sufficient to explain genetic instability and the resulting karyotypic and phenotypic heterogeneity of cancer cells, independent of gene mutation. Because aneuploidy has also been proposed to cause cancer, our hypothesis offers a common, unique mechanism of altering and simultaneously destabilizing normal cellular phenotypes.

The degree of nonlinearity and anisotropy of blood vessel elasticity

Blood vessel elasticity is important to physiology and clinical problems involving surgery, angioplasty, tissue remodeling, and tissue engineering. Nonlinearity in blood vessel elasticity in vivo is important to the formation of solitons in arterial pulse waves. It is well known that the stress–strain relationship of the blood vessel is nonlinear in general, but a controversy exists on how nonlinear it is in the physiological range. Another controversy is whether the vessel wall is biaxially isotropic. New data on canine aorta were obtained from a biaxial testing machine over a large range of finite strains referred to the zero-stress state. A new pseudo strain energy function is used to examine these questions critically. The stress–strain relationship derived from this function represents the sum of a linear stress–strain relationship and a definitely nonlinear relationship. This relationship fits the experimental data very well. With this strain energy function, we can define a parameter called the degree of nonlinearity, which represents the fraction of the nonlinear strain energy in the total strain energy per unit volume. We found that for the canine aorta, the degree of nonlinearity varies from 5% to 30%, depending on the magnitude of the strains in the physiological range. In the case of canine pulmonary artery in the arch region, Debes and Fung [Debes, J. C. & Fung, Y. C.(1995) Am. J. Physiol. 269, H433–H442] have shown that the linear regime of the stress–strain relationship extends from the zero-stress state to the homeostatic state and beyond. Both vessels, however, are anisotropic in both the linear and nonlinear regimes.

Functional activation in motor cortex reflects the direction and the degree of handedness

Handedness is the clearest example of behavioral lateralization in humans. It is not known whether the obvious asymmetry manifested by hand preference is associated with similar asymmetry in brain activation during movement. We examined the functional activation in cortical motor areas during movement of the dominant and nondominant hand in groups of right-handed and left-handed subjects and found that use of the dominant hand was associated with a greater volume of activation in the contralateral motor cortex. Furthermore, there was a separate relation between the degree of handedness and the extent of functional lateralization in the motor cortex. The patterns of functional activation associated with the direction and degree of handedness suggest that these aspects are independent and are coded separately in the brain.

PDB-REPRDB: a database of representative protein chains from the Protein Data Bank (PDB)

PDB-REPRDB is a database of representative protein chains from the Protein Data Bank (PDB). The previous version of PDB-REPRDB provided 48 representative sets, whose similarity criteria were predetermined, on the WWW. The current version is designed so that the user may obtain a quick selection of representative chains from PDB. The selection of representative chains can be dynamically configured according to the user’s requirement. The WWW interface provides a large degree of freedom in setting parameters, such as cut-off scores of sequence and structural similarity. One can obtain a representative list and classification data of protein chains from the system. The current database includes 20 457 protein chains from PDB entries (August 6, 2000). The system for PDB-REPRDB is available at the Parallel Protein Information Analysis system (PAPIA) WWW server (http://www.rwcp.or.jp/papia/).

4-Hydroxylation of estrogens as marker of human mammary tumors.

Estrogen is a known risk factor in human breast cancer. In rodent models, estradiol has been shown to induce tumors in those tissues in which this hormone is predominantly converted to the catechol metabolite 4-hydroxyestradiol by a specific 4-hydroxylase enzyme, whereas tumors fail to develop in organs in which 2-hydroxylation predominates. We have now found that microsomes prepared from human mammary adenocarcinoma and fibroadenoma predominantly catalyze the metabolic 4-hydroxylation of estradiol (ratios of 4-hydroxyestradiol/2-hydroxyestradiol formation in adenocarcinoma and fibroadenoma, 3.8 and 3.7, respectively). In contrast, microsomes from normal tissue obtained either from breast cancer patients or from reduction mammoplasty operations expressed comparable estradiol 2- and 4-hydroxylase activities (corresponding ratios, 1.3 and 0.7, respectively). An elevated ratio of 4-/2-hydroxyestradiol formation in neoplastic mammary tissue may therefore provide a useful marker of benign or malignant breast tumors and may indicate a mechanistic role of 4-hydroxyestradiol in tumor development.

Improved biodistribution, tumor targeting, and reduced immunogenicity in mice with a gamma 4 variant of Campath-1H.

Radiolabeled antibodies have shown promise for the treatment of lymphoma and for solid tumor targeting. Campath-1H is a humanized monoclonal antibody that reacts with the CD52 antigen present on human lymphoid and myeloid cells. Campath-1H is a gamma1 (G1) isotype that induces lymphopenia via an Fc-mediated mechanism(s). Isotype switches were engineered, and the resulting antibodies were expressed in NS0 mouse myeloma cells and biosynthetically radiolabeled with [35S]methionine. The forms included G1, G4, and a G4 variant that contained alanine substitutions at (EU numbering) Leu-235, Gly-237, and Glu-318. All isotypes bound antigen equivalently as assessed by target cell binding in vitro. The G4 variant had a greatly reduced capacity to interact with Fc receptor by virtue of reduced binding to THP-1 human myeloid cells and by a 1000-fold increase in EC50 to intermediate antibody-dependent cellular cytotoxicity. The pharmacokinetics of the isotypes were compared in CD-1 (nu/nu) mice bearing an experimental antigen-expressing tumor. The plasma half-life and tumor uptake were increased for the G4 variant. The G4 variant showed significantly less spleen, liver, and bone uptake but similar uptake in the lung, kidney, and stomach and lower tissue-to-blood ratios. Immunogenicity was assessed after repeated monthly administrations of unlabeled antibody in BALB/c mice. A 50% reduction in the incidence of anti-globulin response was observed for the G4 variant. These properties suggest that antibodies with reduced Fc receptor interaction merit additional study as potential targeting vehicles relative to other isotypes for radioimmunotherapy or situations where diminished normal tissue binding contributes to efficacy.

4-Hydroxylation of estradiol by human uterine myometrium and myoma microsomes: implications for the mechanism of uterine tumorigenesis.

Estradiol is converted to catechol estrogens via 2- and 4-hydroxylation by cytochrome P450 enzymes. 4-Hydroxyestradiol elicits biological activities distinct from estradiol, most notably an oxidant stress response induced by free radicals generated by metabolic redox cycling reactions. In this study, we have examined 2- and 4-hydroxylation of estradiol by microsomes of human uterine myometrium and of associated myomata. In all eight cases studied, estradiol 4-hydroxylation by myoma has been substantially elevated relative to surrounding myometrial tissue (minimum, 2-fold; mean, 5-fold). Estradiol 2-hydroxylation in myomata occurs at much lower rates than 4-hydroxylation (ratio of 4-hydroxyestradiol/2-hydroxyestradiol, 7.9 +/- 1.4) and does not significantly differ from rates in surrounding myometrial tissue. Rates of myometrial 2-hydroxylation of estradiol were also not significantly different from values in patients without myomata. We have used various inhibitors to establish that 4-hydroxylation is catalyzed by a completely different cytochrome P450 than 2-hydroxylation. In myoma, alpha-naphthoflavone and a set of ethynyl polycyclic hydrocarbon inhibitors (5 microM) each inhibited 4-hydroxylation more efficiently (up to 90%) than 2-hydroxylation (up to 40%), indicating > 10-fold differences in Ki (<0.5 microM vs. > 5 microM). These activities were clearly distinguished from the selective 2-hydroxylation of estradiol in placenta by aromatase reported previously (low Km, inhibition by Fadrozole hydrochloride or ICI D1033). 4-Hydroxylation was also selectively inhibited relative to 2-hydroxylation by antibodies raised against cytochrome P450 IB1 (rat) (53 vs. 17%). These data indicate that specific 4-hydroxylation of estradiol in human uterine tissues is catalyzed by a form(s) of cytochrome P450 related to P450 IB1, which contribute(s) little to 2-hydroxylation. This enzyme(s) is therefore a marker for uterine myomata and may play a role in the etiology of the tumor.

Volunteer Engagement: Does Engagement Predict the Degree of Satisfaction among New Volunteers and the Commitment of Those who have been Active Longer?

This study examines the concept of engagement in samples of volunteers from different non-profit organisations. Study 1 analyzes the psychometric properties of the abbreviated version of the Utrecht Work Engagement Scale (UWES) (Schaufeli, Bakker, & Salanova, 2006a). Two factorial structures are examined: one-dimensional and three-dimensional structures. Based on the Three-Stage Model of Volunteers’ Duration of Service (Chacón, Vecina, & Dávila, 2007), Study 2 investigates the relationship between engagement, volunteer satisfaction, and intention to remain in a sample of new volunteers and the relationship between engagement, organisational commitment, and intention to remain in a sample of veteran volunteers. Moderated mediation analysis is provided using duration of service as a moderator in order to set a splitting point between new and veteran volunteers. The results of the confirmatory factor analysis suggest that the three-factor model fits better to the data. Regarding the structural models, the first one shows that engagement is crucial to volunteer satisfaction during the first stage, while volunteer satisfaction is the key variable in explaining intention to continue. The second structural model shows that engagement reinforces the participant’s commitment to the organisation, while organizational commitment predicts intention to continue. Both models demonstrate a notable decline when samples are changed.

Construction of Structures I in Moodle: a new teaching methodology in the Degree of Building Engineer

The subject of Construction of Structures I studies, from a constructive point of view and taking into account current legislation, reinforced concrete structures used in buildings, through the acquisition of knowledge and construction criteria required in the profession of a Technical Architect. The contents acquired in this course are essential for further professional development of technicians and are closely related to many of the subjects taught in the same or other courses of the Degree in Technical Architecture at the University of Alicante. The aim of this paper is to present, analyze and discuss the development of a new methodology proposed in the mentioned subject, as it supposed an important change in the traditional way of teaching Construction and Structures I. In order to incorporate new teaching tools in 2013-2014, the course has been implemented by using a Moodle software tool to promote blended learning with online exercises. Our Moodle community allows collaborative work within an open-source platform where teachers and students share a new and personalized learning environment. Students are easily used to the interface and the platform, value the constant connection with teachers or other fellows and completely agree with the possibility of making questions or share documents 24 hours a day. The proposed methodology consists of lectures and practical classes. In the lectures, the basics of each topic are discussed; class attendance, daily study and conducting scheduled exercises are indispensable. Practical classes allow to consolidate the knowledge gained in theory classes by solving professional exercises and actual construction problems related to structures, that shall be compulsorily delivered online. So, after the correction of the teacher and the subsequent feedback of students, practical exercises ensure lifelong learning of the student, who can download any kind of material at any time (constructive details, practical exercises and even corrected exams). Regarding the general evaluation system, goals achievement is assessed on an ongoing basis (65% of the final mark) along the course through written and graphic evidences in person and online, as well as a individual development of a workbook. In all cases, the acquisition of skills, the ability to synthesize, the capacity of logical and critical thinking are assessed. The other 35 % of the mark is evaluated by a complementary graphic exam. Participation in the computing platform is essential and the student is required to do and present, at least 90% of the practices proposed. Those who do not comply with the practices in each specific date could not be assessed continuously and may only choose the final exam. In conclusion, the subject of Construction of Structures I is essential in the development of the regulated profession of Technical Architect as they are considered, among other professional profiles, as specialists in construction of building structures. The use of a new communication platform and online teaching allows the acquisition of knowledge and constructive approaches in a continuous way, with a more direct and personal monitoring by the teacher that has been highly appreciated by almost 100% of the students. Ultimately, it is important to say that the use of Moodle in this subject is a very interesting tool, which was really well welcome by students in one of the densest and important subjects of the Degree of Technical Architecture.

Large scale optimization of a sour water stripping plant using surrogate models

In this work, we propose a new methodology for the large scale optimization and process integration of complex chemical processes that have been simulated using modular chemical process simulators. Units with significant numerical noise or large CPU times are substituted by surrogate models based on Kriging interpolation. Using a degree of freedom analysis, some of those units can be aggregated into a single unit to reduce the complexity of the resulting model. As a result, we solve a hybrid simulation-optimization model formed by units in the original flowsheet, Kriging models, and explicit equations. We present a case study of the optimization of a sour water stripping plant in which we simultaneously consider economics, heat integration and environmental impact using the ReCiPe indicator, which incorporates the recent advances made in Life Cycle Assessment (LCA). The optimization strategy guarantees the convergence to a local optimum inside the tolerance of the numerical noise.

No. 4 Petition of the Committee [sic] of the Town of Cambridge, 1799 January

Two folio-sized leaves containing a handwritten copy of a petition to the Massachusetts House of Representatives from the Committee of the Town of Cambridge (comprised by James Winthrop, William Winthrop, and Ebenezer Stedman). The petition includes eight points related to the tax exemptions of Harvard real estate and the personal property of College administrators and faculty, and requests further tax legislation to remove any ambiguity that prevents the College and associated individuals "from paying a just & equitable proportion of Town and Parish Charges."