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In this paper we introduce the one-sided weighted spaces ${\mathcal L}^{-}_w (\beta)$, $-1 < \beta < 1$. The purpose of this definition is to obtain an extension of the Weyl fractional integral operator $I_{\alpha}^+$ from $L^p_w$ into a suitable weighted space. Under certain condition on the weight $w$, we have that ${\mathcal L}^{-}_w (0)$ coincides with the dual of the Hardy space $H_{-}^1(w)$. We prove for $0

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Highlights • Plasma ALP could be used as a discriminating marker in presence of bone lesions in solid tumor or MM. • Multiple Myeloma, ALP values were mainly in the range of normality than those observed in patients with solid cancers and bone lesions. • Lower or normal values, should suggest further investigations such as urinary and serum electrophoresis., Introduction Bone involvement in Multiple Myeloma results from increased osteoclast formation and activity that occurs in proximity to myeloma cells. The role of Alkaline Phosphatse (ALP) in this process and the diagnostic significance of plasma levels in patients with MM are unclear. Aim To compare plasma ALP levels in patients with MM and solid cancers and metastatic lesions to the bone. Results In this observational retrospective study we enrolled 901 patients were enrolled: 440 patients (49%) with Multiple Myeloma, 461 (51%) with solid cancers. All 901 patients had bone lesions. Among patients with Multiple Myeloma, ALP values were mainly in the range of normality than those observed in patients with solid cancers and bone lesions. This difference is independent of stage, number and type of bone lesions. Conclusion This study suggests that plasma ALP has a different clinical significance in MM than in other neoplasms and could be used as a discriminating marker in presence of bone lesions. In particular, lower or normal values, should suggest further investigations such as urinary and serum electrophoresis, associated with bone marrow aspirate in case of the presence of a monoclonal component, in order to confirm or exclude a MM diagnosis.

Introduction A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with curative intent, the local relapse risk is still relatively high, thus increasing the risk of dedifferentiation and metastatic spread. This study aims to better define the role of postoperative radiotherapy (RT) in meningeal SFTs. Patients and methods A retrospective study was performed across seven sarcoma centers. Clinical information was retrieved from all adult patients with meningeal primary localized SFT treated between 1990 and 2018 with surgery alone (S) compared to those that also received postoperative RT (S + RT). Differences in treatment characteristics between subgroups were tested using independent samplest-test for continuous variables and chi-square tests for proportions. Local control (LC) and overall survival (OS) rates were calculated as time from start of treatment until progression or death from any cause. LC and OS in groups receiving S or S + RT were compared using Kaplan-Meier survival curves. Results Among a total of 48 patients, 7 (15%) underwent S and 41 (85%) underwent S + RT. Median FU was 65 months. LC was significantly associated with treatment. LC after S at 60 months was 60% versus 90% after S + RT (p = 0.052). Furthermore, R1 resection status was significantly associated with worse LC (HR 4.08,p = 0.038). OS was predominantly associated with the mitotic count (HR 3.10,p = 0.011). Conclusion This retrospective study, investigating postoperative RT in primary localized meningeal SFT patients, suggests that combining RT to surgery in the management of this patient population may reduce the risk for local failures.

Daratumumab (DARA) is a human IgG-K monoclonal antibody (MoAb) targeting CD38 that is approved alone or in combination with bortezomib and dexamethasone or lenalidomide and dexamethasone for relapsed or refractory MM (RRMM) in patients previously exposed or double refractory to proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs). However, there are limited data on its clinical activity and tolerability in real-world patients. Therefore, in the present study, we aim to determine the efficacy and toxicity profile of daratumumab in a real-life setting. In this study, we report the experience of the multiple myeloma GIMEMA Lazio Group in 62 relapsed/refractory MM patients treated with daratumumab as monotherapy who had previously received at least two treatment lines including a PI and an IMiDs or had been double refractory. Patients received DARA 16 mg/kg intravenously weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks until disease progression or unacceptable toxicity. The overall response rate to daratumumab was 46%. Median progression-free survival (PFS) and overall survival reached 2.7 and 22.4 months, respectively. DARA was generally well tolerated; however, 2 patients interrupted their therapy due to adverse events. Present real-life experience confirms that DARA monotherapy is an effective strategy for heavily pre-treated and refractory patients with multiple myeloma, with a favorable safety profile.

Este estudo transversal de base escolar teve como objetivo caracterizar as aulas de Educação Física nos anos iniciais do ensino fundamental das escolas públicas e privadas da cidade de Pelotas, RS. Foram analisadas a duração e a intensidade dos esforços físicos, contexto e ação do professor durante as aulas. Compuseram a amostra 19 escolas da zona urbana e rural da cidade, totalizando 93 turmas e 404 alunos. Para as observações de 275 aulas de Educação Física foi utilizado o instrumento System for Observing Fitness Instruction Time (SOFIT). O nível de atividade física dos estudantes durante as aulas foi mensurado pelo acelerômetro Actigraph wGT3X+. A duração média de tempo das aulas de Educação Física observada pelo SOFIT foi de 29,9 minutos (DP 8,1). Destes, 14,2 minutos (47,8%) foram despendidos em atividades sedentárias, 7,8 minutos (26,2%) em atividades leves, 2,8 minutos (9,3%) em atividades moderadas e 4,9 minutos (16,7%) em atividades físicas vigorosas de acordo com a acelerometria. O contexto de aula mais frequente foi o de jogos estruturados (36,0%). Já a ação do professor gerenciando (45,6%) foi a mais observada. Ficou evidenciada a necessidade de um maior aproveitamento do tempo das aulas para o desenvolvimento de atividades físicas moderadas a vigorosas. Contudo, a Educação Física do 1º ao 5º ano se mostrou mais bem estruturada e planejada com relação à ação do professor e aos conteúdos desenvolvidos, especialmente quando comparado com estudos realizados no ensino médio e anos finais do ensino fundamental.

The development of radioisotopes of inorganic elements (as 68Ga(III) and 188Re(I)) has gained much interest in recent years for diagnostic and therapeutic application in nuclear medicine1. Small peptides are employed for complexing the radiometal in a biologically stable environment. They have some advantages: easy of synthesis and modification, tumorpenetrating ability and good biocompatibility2. Aim of the present work has been the interaction between Ga3+ ion with a bishistidine oligopeptide, PHIS (Fig.1) in aqueous solutions, by the following methods: Potentiometry, Spectrofluorimetry, FT−IR and 1HNMR Spectroscopy as also by Circular Dichroism. All the measurements have been investigated at 25 °C in 0.1 M NaClO4 media. Information on coordination sites are obtained with model molecule such as histidine (His). By processing the experimental data, it has been possible to obtain the complexation constants. Spectroscopy data are in agreement with the potentiometric measurement. 1H-NMR measurements conducted in H2O as solvent at different metal/ligand ratio indicate that imidazolic rings are involved in coordination with metal ions investigated .

Conformational constrained β-hairpin peptides are useful tool to modulate protein-protein interactions. A triazole bridge in hydrogen-bonded positions between two antiparallel strands induces a conformational stabilization of the β-hairpin peptide. The entity of the stability of the β-hairpin peptide depends on the length of the bridge.

Summary Salminus brasiliensis, a characin regionally named ‘dourado’ (meaning goldfish), is the biggest characid fish, this species is cited in a list of fishes that are vulnerable. The goal of the present work was to try to identify, through AFLP technique to convert them into single locus markers (SCARs), in order to improve the sex identification in S. brasiliensis. Between possible sex-specific AFLP markers in this study, one male-specific were isolated (Les1) and converted into a SCAR marker. Les1 marker was confirmed sex-specific in all samples tested. A sex-specific DNA marker applicable to fish would be very useful for elucidating sex determination mechanism in fish.

Organometallic tricarbonyl complexes of Rhenium(I) and Technetium(I), fac−[M(H2O)3(CO)3]+ (M = Re, Tc), especially the aqueous complexes, have recently assumed an important role for diagnostic and therapeutic applications. In this regard, fac−[Re(H2O)3(CO)3]+ cation is readily conjugated to biomolecules which contain coordinating N, P, O, S atoms [1], where one or more water molecules can be replaced by ligands to obtain very stable d6 low−spin complexes [2]. Recently study has showed interaction between fac − [Re(H2O)3(CO)3]+ and histidine/imidazole molecule. Aim of this work is the study of the interaction among fac − [Re(H2O)3(CO)3]+ and some aminoacids that have been investigated using different instrumental techniques. Potentiometric titrations conducted with glass electrode in the pH range 2−10 estabilish that a complexation effect is observed. Information on complexes formation can be obtained also by spectrophotometric UV−VIS and fluorimetric measurements in solutions with different metal/ligand ratio.

Magnetic fields in the sun's outer atmosphere -- the corona -- control both solar-wind acceleration and the dynamics of solar eruptions. We present the first clear observational evidence of coronal magnetic nulls in off-limb linearly polarized observations of pseudostreamers, taken by the Coronal Multichannel Polarimeter (CoMP) telescope. These nulls represent regions where magnetic reconnection is likely to act as a catalyst for solar activity. CoMP linear-polarization observations also provide an independent, coronal proxy for magnetic expansion into the solar wind, a quantity often used to parameterize and predict the solar wind speed at Earth. We introduce a new method for explicitly calculating expansion factors from CoMP coronal linear-polarization observations, which does not require photospheric extrapolations. We conclude that linearly-polarized light is a powerful new diagnostic of critical coronal magnetic topologies and the expanding magnetic flux tubes that channel the solar wind.

The corrosion behavior of bare and chromate–phosphate treated aluminum alloys 8006 and 8079, employed for the production of heat exchangers, was investigated in aqueous aerated 3.5% NaCl solution using electrochemical impedance spectroscopy (EIS). Experimental results indicate that bare 8079 alloy is less sensitive to corrosion in NaCl containing environments than bare 8006 alloy. This behavior was attributed to the lower content of metallic segregates in the 8079 alloy. For the bare samples, the chromate–phosphate treatment improves the corrosion resistance of both alloys; nevertheless their behavior is still dominated by alloy composition. The application of a polymeric coating, ranging from 5 to 7 μm, provided improved protection for the foils investigated during this study. The reliability of these coatings is however dominated by the application procedure and curing.

This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ⩾75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ⩾3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ⩾3 AEs included infections (8–20%), and constitutional (10–14%) and cardiovascular events (4–12%); peripheral neuropathy was limited (4–6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients.

Improvement of grazing-tolerance in lucerne (Medicago sativa L.) is an objective of interest worldwide for the acknowledged potential of this species in pastures. A breeding programme applied standard methods of the selection for this trait, which implies continuous stocking and intensive grazing, to germplasm preliminarily selected for reportedly positive morphological attributes (large and deep crowns; non-erect growth habit). In this study six experimental cultivars, originating from this programme, and three check varieties were evaluated. Grazing tolerance was assessed under continuous sheep stocking for 2 years. Herbage yield in 3 years and seed yield (in the second year) were also evaluated in distinct and contiguous sub-experiments. One experimental cultivar had a prostrate habit, two were semi-prostrate, and three were semi-erect. Under grazing, five of them showed final persistence similar to, or better than, that of the tolerant check variety adopted in the standard test. In particular, the prostrate experimental cultivar (termed Camporegio) had remarkable persistence, although associated with low vigour, associated with the introgression of M. sativa ssp. falcata into its parentage. A semi-erect cultivar (termed Verbena) possessed a good balance between grazing tolerance, potential dry-matter yield and seed yield.

A recent approach to restoration of degraded mountain landscapes (e.g. ski slopes) recommend to sow seed mixtures including ‘site-specific’ species, i.e. native germplasm adapted to the prevailing conditions and ecologically compatible with the area of intervention. To better exploit the potential of these species and enhance their spread in revegetation projects, deeper knowledge is needed, however, on the existing variation in their germplasm, particularly for economically useful traits such as seed yield. Snow clover is one of the recommended ‘site-specific’ legumes. This study evaluated 12 populations of snow clover, collected in three valleys of the Rhaetian Alps, Italy, to assess their variation and highlight any promising material. The evaluation encompassed a mountain and a lowland site, to verify the behaviour of the germplasm also in one environment markedly different from that of origin. Differences among valleys were observed for flower colour, growth habit and type, flowering time and susceptibility to mildew, although the overall pattern of phenotypic diversity was similar among valleys. Some effect of the evaluation site on the expression of morphological and seed production traits, and on the overall diversity, was also evident. Furthermore, the lowland site experienced very high plant mortality towards the end of the first growing season. Individual populations proved a valuable source of variation for seed production. Some populations, in particular, were worth of attention for a possible selection of high-seed-yielding snow clover cultivars. An assessment of the mating system suggested a lack of self-tripping or an almost absolute self-incompatibility in snow clover.

Summary Background Epidermolysis bullosa (EB) is caused by mutations in genes that encode proteins belonging to the epidermal–dermal junction assembly. Due to the extreme clinical/genetic heterogeneity of the disease, the current methods available for diagnosing EB involve immunohistochemistry of biopsy samples and transmission electron microscopy followed by single-candidate gene Sanger sequencing (SS), which are labour-intensive and expensive clinical pathways. Objectives According to the recently published recommendations for the diagnosis and treatment of EB, the assessment of the mutational landscape is now a fundamental step for developing a comprehensive diagnostic path. We aimed to develop a customized, cost-effective amplicon panel for the complete and accurate sequencing of all the pathogenic genes already identified in EB, and to minimize the processing time required for the execution of the test and to refine the analysis pipeline to achieve cost-effective results from the perspective of a routine laboratory set-up. Next-generation sequencing (NGS) via the parallel ultra-deep sequencing of many genes represents a proper method for reducing the processing time and costs of EB diagnostics. Materials and methods We developed an EB disease-comprehensive AmpliSeq panel to accomplish the NGS on an Ion Torrent Personal Genome Machine platform. The panel was performed on 10 patients with known genetic diagnoses and was then employed in eight family trios with unknown molecular footprints. Results The panel was successful in finding the causative mutations in all 10 patients with known mutations, fully confirming the SS data and providing proof of concept of the sensitivity, specificity and accuracy of this procedure. In addition to being consistent with the clinical diagnosis, it was also effective in the trios, identifying all of the variants, including ones that the SS missed or de novo mutations. Conclusions The NGS and AmpliSeq were shown to be an effective approach for the diagnosis of EB, resulting in a cost- and time-effective 72-h procedure.

S Rossi, A Orrico, C Santamaria, V Romano, L De Rosa, F Simonelli, G De RosaMultidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic, Second University ofNaples, Naples, ItalyPurpose: Evaluating the clinical results of trans-epithelial collagen cross-linking (CXL) and standard CXL in patients with progressive keratoconus.Methods: This prospective study comprised 20 eyes of 20 patients with progressive keratoconus. Ten eyes were treated by standard CXL and ten by trans-epithelial cross-linking (TE-CXL, epithelium on) with 1year of follow-up. All patients underwent complete ophthalmologic testing that included pre- and postoperative uncorrected visual acuity, corrected visual acuity, spherical error, spherical equivalent, corneal astigmatism, simulated maximum, minimum, and average keratometry, coma and spherical aberration, optical pachymetry, and endothelial cell density. Intra- and postoperative complications were recorded. The solution used for standard CXL comprised riboflavin 0.1% and dextran 20.0% (Ricrolin), while the solution for TE-CXL (Ricrolin, TE) comprised riboflavin 0.1%, dextran 15.0%, trometamol (Tris), and ethylenediaminetetraacetic acid. Ultraviolet-A treatment was performed with UV-X System at 3mW/cm2.Results: In both the standard CXL group (ten patients, ten eyes; mean age, 30.4±7.3years) and the TE-CXL group (ten patients, ten eyes; mean age, 28±3.8years), uncorrected visual acuity and corrected visual acuity improved significantly after treatment. Furthermore, a significant improvement in topographic outcomes, spherical error, and spherical equivalent was observed in both groups at month 12 posttreatment. No significant variations were recorded in other parameters. No complications were noted.Conclusion: A 1-year follow-up showed stability of clinical and refractive outcomes after standard CXL and TE-CXL.Keywords: corneal disease, corneal thickness, keratoconus, refractive outcomes, surgical technique

Riesz transforms associated to Hermite functions were introduced by S. Thangavelu, who proved that they are bounded operators on L^p(R^d ), 1 < p < ∞ . In this paper we give a different proof that allows us to show that the Lp-norms of these operators are bounded by a constant not depending on the dimension d. Moreover, we define Riesz transforms of higher order and free dimensional estimates of the L^p-bounds of these operators are obtained. In order to prove the mentioned results we give an extension of the Littlewood-Paley theory that we believe of independent interest. Fil: Harboure, Eleonor Ofelia. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Departamento de Matemáticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática Alberto Calderón; Argentina Fil: Rosa, L. de. Universidad de Buenos Aires; Argentina Fil: Segovia Fernandez, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática Alberto Calderón; Argentina Fil: Torrea Hernández, José Luis. Universidad Autónoma de Madrid; España

Several polyimide resins were tested as possible scratch resistant coatings for aluminosilicate glass centrifuge tubes. Tubes with siloxane pretreatments provided the best adhesion between the polyimide and glass surface. Resins synthesized with an alkoxysilane group incorporated into the polyimide chain also showed improved adhesion, but the results were not as significant as when the pretreatment was used. Elastic recovery and effective Young's modulus of the polyimide coatings were calculated from nano-scratching. The results indicate that polyimides with a lower modulus, and higher elastic recovery, protected the glass surface best, exhibiting compression of the coating layer. An example was poly-4-4′-oxydiphenylene pyromellitimide (PMDA-ODA), whereas the coatings with a high effective Young's modulus and low elastic recovery ruptured. An example of a failed coating was poly-4,4′-carbonyldiphenylene 3,3′,4,4′-biphenylenetetracarboximide (BPDA-DABP) which had low amount of elastic recovery, high effect...

The aim of the study was to analyze the real cost of single or tandem high-dose chemotherapy (HDC) and peripheral blood progenitor cell autologous transplant (PBPCT) in patients with breast cancer. We analyzed the costs of 40 PBPCT performed in 20 patients. Tandem transplant was planned for each patient. Resources used and direct costs were identified for each patient. The study was carried out using the hospital perspective and monetary values were reported in 1999 Euro. The mean cost of whole procedure for single transplant was 20816.63 Euro, while the mean cost of tandem transplant was 38770.83 Euro. The cost distribution in the two groups was similar: the most expensive phase of procedure was the supportive phase post transplant (about 60% of total cost), with the categories of cost most represented being professional fees (about 28%) and pharmacy (about 35%). Awaiting more convincing trials of the clinical advantage of HDC in breast cancer, our analytical evaluation of transplant costs for different therapeutic options, single or tandem, permits identification of the most expensive categories in order to intervene for cost savings. Bone Marrow Transplantation (2001) 27, 1031–1035.

In this article we give sufficient conditions on a pair of weight (w, v) for some one-sided operators to be bounded from Lp (vp) to Lp (wp). The operators we deal with include the one-sided fractional maximal operator and the one-sided singular integrals. For the first operator, necessary and sufficient conditions are known (see [8, 6]). These conditions usually amount to checking the boundedness of the operator on functions that are powers of the weights and are hard to check. Our conditions are of Ap type and are therefore easy to verify. Similar results for two-sided operators were obtained by C. Perez in [9] and [10].

A critical step in protecting aluminum alloys from corrosion is surface pretreatment. According to ASTM D-1730, many combinations of acid, alkaline, or solvent cleanings may be used and re...

Using velocity and magnetogram data extracted from the full-disk field of view of MDI during the 1999 Dynamics Program, we have studied the dynamics of small-scale magnetic elements (3–7 Mm in size) over time periods as long as six days while they are readily visible on the solar disk. By exploiting concurrent time series of magnetograms and Doppler images, we have compared the motion of magnetic flux elements with the supergranular velocity field inferred from the correlation tracking of mesogranular motions. Using this new method (which combines the results from correlation tracking of mesogranules with detailed analysis of simultaneous magnetograms), it is now possible to correlate the motions of the velocity field and magnetic flux for long periods of time and at high temporal resolution. This technique can be utilized to examine the long-term evolution of supergranulation and associated magnetic fields, for it can be applied to data that span far longer time durations than has been possible previously. As tests of its efficacy, we are able to use this method to verify many results of earlier investigations. We confirm that magnetic elements travel at approximately 350 m s −1 throughout the duration of their lifetime as they are transported by supergranular outflows. We also find that the positions of the magnetic flux elements coincide with the supergranular network boundaries and adjust as the supergranular network itself evolves over the six days of this data set. Thus we conclude that this new method permits us to study the extended evolution of the supergranular flow field and its advection of magnetic elements. Since small-scale magnetic elements are strongly advected by turbulent convection, their dynamics can give important insight into the properties of the subsurface convection.

The corrosion and passivation behaviour of molybdenum thin films obtained by Physical Vapor Deposition (PVD) was investigated in aerated chloride and sulfate solutions at different pH values. Open circuit potential (ocp) measurements, polarisation experiments and electrochemical impedance spectroscopy (EIS) were employed. The experimental results suggest that the metal surface is covered by a passive film; however, corrosion still occurs. For the samples assessed during the current research, the acidic electrolytes tended to be less corrosive; however, a limited passive region was associated with the most basic sulfate or chloride solution. The effect of the pH was found to be more pronounced than the effect of the ion (chloride or sulfate).

In the past few years there has been increased interest in molybdenum thin films, which are commonly prepared by magnetron sputtering. There is a variety of novel applications of molybdenum such as, for example, components for soft X-ray optics based on Mo/Si multi-layers, the back contact in thin film solar cells, NO gas detection, and microelectronics. Molybdenum is, also, widely used as an alloying addition in stainless steels to facilitate the formation of the passive film and to improve resistance to pitting at-tack. Its corrosion behaviour is complex and many aspects still need to be clarified. During this study, the corrosion behaviour of the PVD-Mo thin film immersed in aerated sulfate and chloride solutions at 85 degreesC was investigated with both polarization and electrochemical impedance spectroscopy (EIS) measurements. It is apparent that the Mo thin film exhibits increased susceptibility to corrosion in more alkaline environments.

At the mountain area close to the city of Madrid, common beans were one of the main food crops present in everyday diet until 1960. This paper describes the morphological diversity, for forty-six phenological and morphological traits, found in forty-three traditional varieties of common beans collected in this area and seven commercial varieties used as reference. That comparison suggests that common bean breeding programs have led to later varieties with a higher production of straight pods. Quantitative traits showed also similar values when compared to the Iberian common bean collection, except for the phenological and seed size characters. The phenological differences could suggest an ecological adaptation of the studied landraces to the regional environmental conditions. The different seed size averages of both collections might correspond to the scarce presence of smaller seed-type common beans in Madrid collection. All the accessions collected in the Sierra Norte of Madrid belong to any of the groups included in the Spanish core collection. Madrilenian collection is also composed by indeterminate growth habit varieties, while the presence of bush accessions is relatively uncommon. Most of the Madrilenian landraces have a remarkable fitness for green-pod consumption (42 %) and their seeds are mainly white (30 %), ovate-shape (49 %) and medium-large (40 %). The study of seed storage protein allowed to classify the landraces according to their domesticated gene pools. Most of them (72 %), with T and C phaseolin type, seem to belong to Andean germplasm, while the remaining (28 %), with S and B phaseolin type, to Mesoamerican one. The remarkable morphological diversity of common beans found in this small area is a symptom of a broad genetic base despite genetic erosion, what indicates a widespread crop in the past. Therefore, it is advisable to design agro-environmental policies to promote the production and commercialization of common bean landraces in Sierra Norte of Madrid. © 2013 Springer Science+Business Media Dordrecht.

164 CRISPR/Cas9-mediated gene repair in the COL7A1 gene S Hainzl, T Kocher, EM Murauer, F Larcher, M Steiner, JW Bauer, J Reichelt and U Koller 1 EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology, University Hospital of the Paracelsus Medical University, Salzburg, Austria, 2 Department of Dermatology, Paracelsus Medical University, Salzburg, Austria, 3 Epithelial Biomedicine Division, CIEMAT, Madrid, Spain and 4 3rd Medical Department, Paracelsus Medical University Salzburg, Austria, Laboratory for Immunological and Molecular Cancer Research, Salzburg, Austria The CRISPR/Cas9 system turned out to be a powerful tool for genome editing and is therefore a promising option for the specific repair of gene mutations causing the blistering skin disease epidermolysis bullosa (EB). We have exploited the CRISPR/Cas9-mediated homologydirected repair (HDR) approach for the correction of a homozygous mutation in COL7A1 exon 80, leading to a complete loss of type VII collagen within the basement membrane zone of the skin. We have predicted a guide RNA (gRNA) specific for intron 80 of COL7A1, which was then cloned either into a wild-type Cas9 dual vector system, inducing double strand breaks, or a D10A Cas9 dual vector system, causing single strand breaks within the target intron. Homology COL7A1 arms for HDR were cloned into a donor vector, including a selection cassette. Transfected patient keratinocytes were selected either via antibiotic selection or fluorescent-activated cell sorting (FACS). RT-PCR on genomic DNA of treated cells and subsequent restriction enzyme digest analysis of the resulting PCR products showed the genetic correction of the COL7A1 mutation. The mutation-specific enzymatic digest revealed the presence of 26% reverted alleles. Additionally, type VII collagen restoration was confirmed via Western blot analysis and immunofluorescence staining. Our data indicate that genome editing using the CRISPR/Cas9 system can be an elegant tool for the repair of genes involved in the severe skin disease epidermolysis bullosa. 165 Combining antisense molecules with splicing modulation for KRT14 repair in epidermolysis bullosa B Liemberger, C Arzt, S Hainzl, J Pinon Hofbauer, V Wally, EM Murauer, JW Bauer, J Reichelt and U Koller 1 EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology, University Hospital of the Paracelsus Medical University, Salzburg, Austria and 2 Department of Dermatology, Paracelsus Medical University Salzburg, Austria, Salzburg, Austria Epidermolysis bullosa (EB) is an inherited skin disease characterized by severe blistering of the skin and mucous membranes after minor mechanical trauma. In EB simplex (EBS) dominant mutations within KRT14 encoding keratin 14 lead to loss of integrity of the intermediate filament network within basal keratinocytes. In order to correct a dominant mutation in an EBS patient cell line, we exploited the RNA trans-splicing technology which utilizes the cell’s endogenous splicing machinery to facilitate a trans-splicing reaction between two RNAs, generating a new chimeric product at the pre-mRNA level. The designed RNA transsplicing molecule (RTM), containing a binding domain, splicing elements, and the wild-type KRT14 region to be introduced, has already been shown to be able to partially revert the EBS phenotype at the cellular level. In order to increase the repair efficiency mediated by RNA trans-splicing, antisense RNAs (asRNAs) specific for splice sites or splicing enhancer sequences within the KRT14 target pre-mRNA region were randomly generated with the aim of blocking these cis-splicing elements thereby increasing the trans-splicing rate. We analysed the functionality of 76 individual asRNAs by exploiting our fluorescence-based screening system, in which reconstitution of a GFP signal acts as a readout for accurate trans-splicing between a generated KRT14 minigene (KRT14-MG) and the RTM. Triple transfection experiments in HEK293 cells of the KRT14-MG, the RTM, and the most functional asRNA revealed an increase in trans-splicing efficiency of up to 7 fold as monitored by flow cytometry. Our data suggest that the inclusion of asRNAs can increase the trans-splicing efficiency to levels needed to overcome the EBS phenotype.

Este estudo objetivou identificar as verbas por tipo e modalidade de bolsas de ensino e pesquisa concedidas pelo CNPq entre 2005 e 2014 nas grandes áreas de conhecimento, especialmente a de Ciências da Saúde com foco na subárea da Educação Física. As buscas ocorreram no mês de março de 2015 e realizadas no painel de investimentos do CNPq (http://www.cnpq.br/painel-de-investimentos) para informações sobre bolsas e no site da CAPES para identificar os cursos de pós-graduação. Foram investidos R$813.435.000,00 nas diferentes modalidades de bolsa, principalmente produtividade em pesquisa (30,0%). A área de Ciências da Saúde foi a quinta em termos de recebimento de verbas (11,0%). Entre as subáreas das Ciências da Saúde, a Medicina foi a que mais recebeu bolsas de ensino e pesquisa (38%) e a Educação Física ficou em sétimo lugar (4,0%). As subáreas que mais cresceram em investimentos no período analisado foram a Fisioterapia/Terapia Ocupacional (775%) e a Educação Física (738%), sendo esta última a sétima das subáreas em recebimento de bolsas de produtividade. Entretanto, foi a quarta em termos de crescimento de investimentos. Do total de bolsas de ensino e pesquisa, 64,3% foram destinadas a pesquisadores da região Sudeste, 15,4% na região Sul e 14,6% no Nordeste. Em contrapartida, apenas 4,1% para a região Centro-oeste e 1,6% a pesquisadores da região Norte.

Lucerne (Medicago sativa L.) is rated as moderately susceptible to soil salinity, a major stress whose incidence is increasing in drought-prone regions because of irrigation with saline water. Three-year dry-matter yield (DMY) of 14 populations (cultivars or landraces) of different origin was assessed across ten agricultural environments of Algeria, Italy, Morocco and Tunisia whose electrical conductivity (ECe) in the 0–30 cm soil layer ranged between 0.2 and 6.0 dS m− 1. The adaptive responses of the populations were modeled by factorial regression as a function of ECe and one or two additional significant covariates. Ameristand 801S (a benchmark variety for salt tolerance) and the Moroccan landrace Erfoud 1 displayed positive genotype × environment (GE) interaction in environments with high soil salinity. Nine populations and one additional Algerian landrace (Tamantit) underwent a seed germination test under saline conditions, to verify the ability of this test to predict the field-based adaptive responses to soil salinity of the populations. The salt concentration required to inhibit germination of 50 % of viable seeds (IC(50)) ranged from 1.13 % NaCl of Prosementi to 2.61 % NaCl of Ameristand 801S. IC(50) values of the populations displayed moderately high correlation (r = 0.70; P < 0.03) with the genotype slope as a function of ECe in the factorial regression (β ECe). Salt-tolerant genetic resources could be found in north African landraces which evolved in less favourable oasis environments, such as Tamantit and Erfoud 1.

La presente aportación pretende analizar las rebeliones nativistas que tuvieron lugar en Brasil entre los siglos XVII y XIX y que alcanzaron su máxima expresión, en términos numéricos, en el siglo XVIII, consolidando el movimiento hacia la independencia proclamada el 7 de septiembre de 1822.

Mondi doppiati approfondisce gli aspetti principali della traduzione audiovisiva dal portoghese (europeo e brasiliano) all’italiano attraverso l’analisi di vari generi di prodotti audiovisivi brasiliani e portoghesi. Il volume è pensato come supporto agli studenti, ai traduttori e ai traduttologi interessati alle più diffuse pratiche di trasposizione linguistica in ambito audiovisivo, come la sottotitolazione e il doppiaggio. Pertanto, a partire dallo stato dell’arte della traduzione audiovisiva, professionale e di ricerca, l'autore intende offrire spunti di riflessione su una serie di pratiche e modalità sviluppate nell’ambito traduttivo per il parlato filmico portoghese e brasiliano, analizzando i riflessi del processo di ristandardizzazione del portoghese brasiliano (PB) e del portoghese europeo (PE); l’adeguatezza socio-pragmalinguistica della traduzione audiovisiva e le modalità di transposizione audiovisiva dello humor.

Of 17 patients with mild to moderate essential hypertension, 8 showed echocardiographic evidence of left ventricular hypertrophy. Cardiac and renal function evaluated by glomerular filtration rate (GFR) were studied in all patients before and after 20 weeks of quinapril treatment. Systolic pressure decreased from 174.7 +/- 16.7 to 131.7 +/- 7.7 mmHg (p.0001) and diastolic pressure decreased from 101.8 +/- 9.8 to 80 +/- 4.3 mmHg (p.0001). Left ventricular mass index decreased in the eight patients with left ventricular hypertrophy (p.01). Basal values of GFR were lower than normal in 41% of all patients; GFR increased significantly after 20 weeks of treatment (from 96.5 +/- 32.3 to 108.6 +/- 31.12 ml/min, p.01); it decreased in only one patient. Patients reported few adverse effects to quinapril, and no important clinical laboratory abnormality was observed. Quinapril not only lowered arterial pressure, but it had a distinct effect on regression of left ventricular hypertrophy and favorable effects on renal function.