Macroporous uniform azide- and alkyne-functional polymer microspheres with tuneable surface area: synthesis, in-depth characterization and click-modification

A series of uniform, macroporous poly(styrene-co-divinylbenzene) microspheres with diameters ranging from 6.6 ± 0.6 to 8.6 ± 0.2 μm was prepared in a multistep procedure involving precipitation polymerization synthesis of polystyrene seed particles, swelling of seed particles with plasticiser and porogen, and polymerization of styrene–divinylbenzene (S–DVB) inside the seed particles. Particles prepared with varying DVB feed ratios had comparable diameters (as evidenced by scanning electron microscopy) with specific surface areas increasing with DVB content from 11 to 467 m2 g−1 (measured by nitrogen adsorption). Residual double bonds were converted into azide functionality (through HBr addition and bromo-azide substitution) or alkyne functionality (Br2 addition followed by double elimination) which allowed for CuAAC-click chemistry conjugation with reagents carrying the respective complimentary alkyne or azide functional groups including the fluorescent dye derivatives 7-nitro-4-(prop-2-ynylamino)benzofuran (NBD-alkyne) and Rhodamine B hexylazide synthesised for this purpose.Efficiency of chemical transformations was determined using a combination of CHN and IC elemental analyses, solid state NMR spectroscopy, FT-IR spectroscopy, Raman spectroscopy, and confocal scanning fluorescence microscopy. Although the respective second steps in each modification route (substitution and elimination) suffered from lower yields ( 35%), porous particles with azide loadings of up to 0.71 mmol g−1 and alkyne loadings of up to 0.78 mmol g−1 were prepared. Confocal laser scanning microscopy on Rhodamine B-labelled microspheres indicated functionalization throughout the particles featuring a core–shell structure with higher functionalization in the outer layer of particles. Results are expected to contribute to the development of advanced, well-defined, macroporous particles with high, chemically accessible surface areas

A combinatorial smoothness criterion for spherical varieties

We suggest a combinatorial criterion for the smoothness of an arbitrary spherical variety using the classification of multiplicity-free spaces, generalizing an earlier result of Camus for spherical varieties of type $A$.Comment: 14 pages, 2 table

Tissue-Specific Expression of Human Lipoprotein Lipase: EFFECT OF THE 3′-UNTRANSLATED REGION ON TRANSLATION

Lipoprotein lipase (LPL) is a central enzyme in lipoprotein metabolism and is expressed predominantly in adipose tissue and muscle. In these tissues, the regulation of LPL is complex and often opposite in response to the same physiologic stimulus. In addition, much regulation of LPL occurs post-transcriptionally. The human LPL cDNA is characterized by a long 3′-untranslated region, which has two polyadenylation signals. In this report, human adipose tissue expressed two LPL mRNA species (3.2 and 3.6 kb) due to an apparent random choice of sites for mRNA polyadenylation, whereas human skeletal and heart muscle expressed predominantly the longer 3.6-kb mRNA form. To determine whether there was any functional significance to this tissue-specific mRNA expression, poly(A)-enriched RNA from adipose tissue and muscle were translated in vitro, and the poly(A)-enriched RNA from muscle was more efficiently translated into LPL protein. The increased translatability of the 3.6-kb form was also demonstrated by cloning the full-length 3.2- and 3.6-kb LPL cDNA forms, followed by in vitro translation of in vitro prepared transcripts. To confirm that this increased efficiency of translation occurred in vivo, Chinese hamster ovary cells were transfected with the 3.2- and 3.6-kb LPL cDNAs. Cells transfected with the 3.6-kb construct demonstrated increased LPL activity and synthesis, despite no increase in levels of LPL mRNA. Thus, human muscle expresses the 3.6-kb form of LPL due to a non-random choice of polyadenylation signals, and this form is more efficiently translated than the 3.2-kb form

On Computing Groebner Basis in the Rings of Differential Operators

Insa and Pauer presented a basic theory of Groebner basis for differential operators with coefficients in a commutative ring in 1998, and a criterion was proposed to determine if a set of differential operators is a Groebner basis. In this paper, we will give a new criterion such that Insa and Pauer's criterion could be concluded as a special case and one could compute the Groebner basis more efficiently by this new criterion

Diseño e implementación de un programa de intervención clínica para adultos con distrés desde un modelo biopsicosocia

En las últimas décadas el término estrés ha adquirido un protagonismo cada vez mayor en los ámbitos científicos y académicos y también, formando parte del vocabulario cotidiano. Actualmente el ser humano nace, crece y se desarrolla en sociedades que le han brindado cierto grado de confort en relación con épocas pasadas. No obstante, sigue rodeado de numerosas situaciones (reales o imaginarias) que provocan la activación de mecanismos que intentan ajustarlo a las diversas demandas que diariamente se le presentan. En algunas ocasiones, y mediante un gran esfuerzo tanto a nivel biológico como psicológico y social, los seres humanos logran adaptarse a estos requerimientos e incluso salir fortalecidos de ellos. Sin embargo, en otros momentos, este esfuerzo es tan intenso y/o tan prolongado que sobreviene un fracaso adaptativo. Entre estos dos polos se ubican los conceptos de estrés y distrés, constituyéndose en innegables objetos de estudio de la Psicología debido a la impronta que ambos tienen sobre los procesos de salud y enfermedad, y, principalmente, porque esta disciplina cuenta con las herramientas para modificar o modular gran parte de las variables que, de modo directo o indirecto, generan las respuestas de estrés

Lunar Exploration Orbiter (LEO): Providing a Globally Covered, Highly Resolved, Integrated Geological, Geochemical and Gephysical Data Base of the Moon

The German initiative for the Lunar Exploration Orbiter (LEO) originated from the national conference “Exploration of our Solar System”, held in Dresden in November 2006. Major result of this conference was that the Moon is of high interest for the scientific community for various reasons, it is affordable to perform an orbiting mission to Moon and it insures technological and scientific progress necessary to assist further exploration activities of our Solar System. Based on scientific proposals elaborated by 50 German scientists in January 2007, a preliminary payload of 12 instruments was defined. Further analysis were initated by DLR in the frame of two industry contracts, to perform a phase-zero mission definition. The Moon, our next neighbour in the Solar System is the first choice to learn, how to work and live without the chance of immediate support from earth and to get prepared for further and farther exploration missions. We have to improve our scientific knowledge base with respect to the Moon applying modern and state of the art research tools and methods. LEO is planed to be launched in 2012 and shall orbit the Moon for about four years in a low altitude orbit

Interference with work in fibromyalgia - effect of treatment with pregabalin and relation to pain response

BACKGROUND: Clinical trials in chronic pain often collect information about interference with work as answers to component questions of commonly used questionnaires but these data are not normally analysed separately. METHODS: We performed a meta-analysis of individual patient data from four large trials of pregabalin for fibromyalgia lasting 8-14 weeks. We analysed data on interference with work, inferred from answers to component questions of Fibromyalgia Impact Questionnaire (FIQ), Short Form 36 Health Survey, Sheehan Disability Scale, and Multidimensional Assessment of Fatigue, including "How many days in the past week did you miss work, including housework, because of fibromyalgia?" from FIQ. Analyses were performed according to randomised treatment group (pregabalin 150-600 mg daily or placebo), pain improvement (0-10 numerical pain rating scale scores at trial beginning vs. end), and end of trial pain state (100 mm visual analogue pain scale [VAS]). RESULTS: Comparing treatment group average outcomes revealed modest improvement over the duration of the trials, more so with active treatment than with placebo. For the 'work missed' question from FIQ the change for patients on placebo was from 2.2 (standard deviation [SD] 2.3) days of work lost per week at trial beginning to 1.9 (SD 2.1) days lost at trial end (p < 0.01). For patients on 600 mg pregabalin the change was from 2.1 (SD 2.2) days to 1.6 (SD 2.0) days (p < 0.001). However, the change in days of work lost was substantial in patients with a good pain response: from 2.0 (SD 2.2) days to 0.97 (SD 1.6) days (p < 0.0001) for those experiencing >/= 50% pain improvement and from 1.9 (SD 2.2) days to 0.73 (SD 1.4) days (p < 0.0001) for those achieving a low level of pain at trial end (<30 mm on the VAS). Patients achieving both >/= 50% pain improvement and a pain score <30 mm on the VAS had the largest improvement, from 2.0 (SD 2.2) days to 0.60 (SD 1.3) days (p < 0.0001). Analysing answers to the other questions yielded qualitatively similar results. CONCLUSIONS: Effective pain treatment goes along with benefit regarding work. A reduction in time off work >1 day per week can be achieved in patients with good pain responses

A Seven-Marker Signature and Clinical Outcome in Malignant Melanoma: A Large-Scale Tissue-Microarray Study with Two Independent Patient Cohorts

Current staging methods such as tumor thickness, ulceration and invasion of the sentinel node are known to be prognostic parameters in patients with malignant melanoma (MM). However, predictive molecular marker profiles for risk stratification and therapy optimization are not yet available for routine clinical assessment.; Using tissue microarrays, we retrospectively analyzed samples from 364 patients with primary MM. We investigated a panel of 70 immunohistochemical (IHC) antibodies for cell cycle, apoptosis, DNA mismatch repair, differentiation, proliferation, cell adhesion, signaling and metabolism. A marker selection procedure based on univariate Cox regression and multiple testing correction was employed to correlate the IHC expression data with the clinical follow-up (overall and recurrence-free survival). The model was thoroughly evaluated with two different cross validation experiments, a permutation test and a multivariate Cox regression analysis. In addition, the predictive power of the identified marker signature was validated on a second independent external test cohort (n?=?225). A signature of seven biomarkers (Bax, Bcl-X, PTEN, COX-2, loss of ?-Catenin, loss of MTAP, and presence of CD20 positive B-lymphocytes) was found to be an independent negative predictor for overall and recurrence-free survival in patients with MM. The seven-marker signature could also predict a high risk of disease recurrence in patients with localized primary MM stage pT1-2 (tumor thickness ?2.00 mm). In particular, three of these markers (MTAP, COX-2, Bcl-X) were shown to offer direct therapeutic implications.; The seven-marker signature might serve as a prognostic tool enabling physicians to selectively triage, at the time of diagnosis, the subset of high recurrence risk stage I-II patients for adjuvant therapy. Selective treatment of those patients that are more likely to develop distant metastatic disease could potentially lower the burden of untreatable metastatic melanoma and revolutionize the therapeutic management of MM

Role of Fibronectin in the Adhesion of Acinetobacter baumannii to Host Cells

Adhesion to host cells is an initial and important step in Acinetobacter baumannii pathogenesis. However, there is relatively little information on the mechanisms by which A. baumannii binds to and interacts with host cells. Adherence to extracellular matrix proteins, such as fibronectin, affords pathogens with a mechanism to invade epithelial cells. Here, we found that A. baumannii adheres more avidly to immobilized fibronectin than to control protein. Free fibronectin used as a competitor resulted in dose-dependent decreased binding of A. baumannii to fibronectin. Three outer membrane preparations (OMPs) were identified as fibronectin binding proteins (FBPs): OMPA, TonB-dependent copper receptor, and 34 kDa OMP. Moreover, we demonstrated that fibronectin inhibition and neutralization by specific antibody prevented significantly the adhesion of A. baumannii to human lung epithelial cells (A549 cells). Similarly, A. baumannii OMPA neutralization by specific antibody decreased significantly the adhesion of A. baumannii to A549 cells. These data indicate that FBPs are key adhesins that mediate binding of A. baumannii to human lung epithelial cells through interaction with fibronectin on the surface of these host cells