Long-term outcomes and prognostic factors of skull-base chondrosarcoma patients treated with pencil-beam scanning proton therapy at the Paul Scherrer Institute

BACKGROUND Skull-base chondrosarcoma (ChSa) is a rare disease, and the prognostication of this disease entity is ill defined. METHODS We assessed the long-term local control (LC) results, overall survival (OS), and prognostic factors of skull-base ChSa patients treated with pencil beam scanning proton therapy (PBS PT). Seventy-seven (male, 35; 46%) patients with histologically confirmed ChSa were treated at the Paul Scherrer Institute. Median age was 38.9 years (range, 10.2-70.0y). Median delivered dose was 70.0 GyRBE (range, 64.0-76.0 GyRBE). LC, OS, and toxicity-free survival (TFS) rates were calculated using the Kaplan Meier method. RESULTS After a mean follow-up of 69.2 months (range, 4.6-190.8 mo), 6 local (7.8%) failures were observed, 2 of which were late failures. Five (6.5%) patients died. The actuarial 8-year LC and OS were 89.7% and 93.5%, respectively. Tumor volume > 25 cm(3) (P = .02), brainstem/optic apparatus compression at the time of PT (P = .04) and age >30 years (P = .08) were associated with lower rates of LC. High-grade (≥3) radiation-induced toxicity was observed in 6 (7.8%) patients. The 8-year high-grade TFS was 90.8%. A higher rate of high-grade toxicity was observed for older patients (P = .073), those with larger tumor volume (P = .069), and those treated with 5 weekly fractions (P = .069). CONCLUSIONS This is the largest PT series reporting the outcome of patients with low-grade ChSa of the skull base treated with PBS only. Our data indicate that protons are both safe and effective. Tumor volume, brainstem/optic apparatus compression, and age were prognosticators of local failures.

Tailoring the Scrum Development Process to Address Agile Product Line Engineering

Software Product Line Engineering (SPLE) is becoming widely used due to the improvement it means when developing software products of the same family. However, SPLE demands long-term investment on a product-line platform that might not be profitable due to rapid changing business settings. Since Agile Software Development (ASD) approaches are being successfully applied in volatile markets, several companies have suggested the idea of integrating SPLE and ASD when a family product has to be developed. Agile Product Line Engineering (APLE) advocates the integration of SPLE and ASD to address their lacks when they are individually applied to software development. A previous literature re-view of experiences and practices on APLE revealed important challenges about how to fully put APLE into practice. Our contribution address several of these challenges by tailoring the agile method Scrum by means of three concepts that we have defined: plastic partial components, working PL-architectures, and reactive reuse.

Dynamic & Cyclic behaviour of ballast in the long term as determined in Cedex's track box

The 6 cylinder servo-hydraulic loading system of CEDEX's track box (250 kN, 50 Hz) has been recently implemented with a new piezoelectric loading system (±20 kN, 300 Hz) allowing the incorporation of low amplitude high frequency dynamic load time histories to the high amplitude low frequency quasi-static load time histories used so far in the CEDEX's track box to assess the inelastic long term behavior of ballast under mixed traffic in conventional and high- speed lines. This presentation will discuss the results obtained in the first long-duration test performed at CEDEX's track box using simultaneously both loading systems, to simulate the pass-by of 6000 freight vehicles (1M of 225 kN axle loads) travelling at a speed of 120 km/h over a line with vertical irregularities corresponding to a medium quality lin3e level. The superstructure of the track tested at full scale consisted of E 60 rails, stiff rail pads (mayor que 450 kN/mm), B90.2 sleepers with USP 0.10 N/mm and a 0.35 m thick ballast layer of ADIF first class. A shear wave velocity of 250 m/s can be assumed for the different layers of the track sub-base. The ballast long-term settlements will be compared with those obtained in a previous long-duration quasi- static test performed in the same track, for the RIVAS [EU co-funded] project, in which no dynamic loads where considered. Also, the results provided by a high diameter cyclic triaxial cell with ballast tested in full size will be commented. Finally, the progress made at CEDEX's Geotechnical Laboratory to reproduce numerically the long term behavior of ballast will be discussed.

The activation domain of the enhancer binding protein p45NF-E2 interacts with TAFII130 and mediates long-range activation of the α- and β-globin gene loci in an erythroid cell line

We have used the interaction between the erythroid-specific enhancer in hypersensitivity site 2 of the human β-globin locus control region and the globin gene promoters as a paradigm to examine the mechanisms governing promoter/enhancer interactions in this locus. We have demonstrated that enhancer-dependent activation of the globin promoters is dependent on the presence of both a TATA box in the proximal promoter and the binding site for the erythroid-specific heteromeric transcription factor NF-E2 in the enhancer. Mutational analysis of the transcriptionally active component of NF-E2, p45NF-E2, localizes the critical region for this function to a proline-rich transcriptional activation domain in the NH2-terminal 80 amino acids of the protein. In contrast to the wild-type protein, expression of p45 NF-E2 lacking this activation domain in an NF-E2 null cell line fails to support enhancer-dependent transcription in transient assays. More significantly, the mutated protein also fails to reactivate expression of the endogenous β- or α-globin loci in this cell line. Protein-protein interaction studies reveal that this domain of p45 NF-E2 binds specifically to a component of the transcription initiation complex, TATA binding protein associated factor TAFII130. These findings suggest one potential mechanism for direct recruitment of distal regulatory regions of the globin loci to the individual promoters.

Effect of fibre base and reflectors profile on the efficiency of ultra- long laser cavities

We study the effect of fibre base and grating profile on the efficiency of ultra-long Raman lasers. We show that for the studied parameters, FBG profile does not affect the performance when operating away from the zero-dispersion wavelength.

Effect of fibre base and reflectors profile on the efficiency of ultra- long laser cavities

We study the effect of fibre base and grating profile on the efficiency of ultra-long Raman lasers. We show that for the studied parameters, FBG profile does not affect the performance when operating away from the zero-dispersion wavelength.

Effects of microstructure on long and short crack growth in nickel base superalloys

The use of engineering materials in critical applications necessitates the accurate prediction of component lifetime for inspection and renewal purposes. In fatigue limited situations, it is necessary to be able to predict the growth rates of cracks from initiation at a defect through to final fracture. To this end, fatigue crack growth data are presented for different microstructures of typical nickel base superalloys used in gas turbine engines. Crack growth behaviour throughout the life history of the crack, i.e. from the short crack through to the long crack propagation regime, is described for each microstructural condition and discussed in terms of current theories of fatigue crack propagation.

Sistemas de cálculo, análise e operação virtual: interferências de campos elétricos e magnéticos produzidas por estações radio base de acesso múltiplo por divisão de código em banda larga - WCDMA

In this work it was developed mathematical resolutions taking as parameter maximum intensity values for the interference analysis of electric and magnetic fields and was given two virtual computer system that supports families of CDMA and WCDMA technologies. The first family were developed computational resources to solve electric and magnetic field calculations and power densities in Radio Base stations , with the use of CDMA technology in the 800 MHz band , taking into account the permissible values referenced by the Commission International Protection on non-Ionizing Radiation . The first family is divided into two segments of calculation carried out in virtual operation. In the first segment to compute the interference field radiated by the base station with input information such as radio channel power; Gain antenna; Radio channel number; Operating frequency; Losses in the cable; Attenuation of direction; Minimum Distance; Reflections. Said computing system allows to quickly and without the need of implementing instruments for measurements, meet the following calculated values: Effective Radiated Power; Sector Power Density; Electric field in the sector; Magnetic field in the sector; Magnetic flux density; point of maximum permissible exposure of electric field and power density. The results are shown in charts for clarity of view of power density in the industry, as well as the coverage area definition. The computer module also includes folders specifications antennas, cables and towers used in cellular telephony, the following manufacturers: RFS World, Andrew, Karthein and BRASILSAT. Many are presented "links" network access "Internet" to supplement the cable specifications, antennas, etc. . In the second segment of the first family work with more variables , seeking to perform calculations quickly and safely assisting in obtaining results of radio signal loss produced by ERB . This module displays screens representing propagation systems denominated "A" and "B". By propagating "A" are obtained radio signal attenuation calculations in areas of urban models , dense urban , suburban , and rural open . In reflection calculations are present the reflection coefficients , the standing wave ratio , return loss , the reflected power ratio , as well as the loss of the signal by mismatch impedance. With the spread " B" seek radio signal losses in the survey line and not targeted , the effective area , the power density , the received power , the coverage radius , the conversion levels and the gain conversion systems radiant . The second family of virtual computing system consists of 7 modules of which 5 are geared towards the design of WCDMA and 2 technology for calculation of telephone traffic serving CDMA and WCDMA . It includes a portfolio of radiant systems used on the site. In the virtual operation of the module 1 is compute-: distance frequency reuse, channel capacity with noise and without noise, Doppler frequency, modulation rate and channel efficiency; Module 2 includes computes the cell area, thermal noise, noise power (dB), noise figure, signal to noise ratio, bit of power (dBm); with the module 3 reaches the calculation: breakpoint, processing gain (dB) loss in the space of BTS, noise power (w), chip period and frequency reuse factor. Module 4 scales effective radiated power, sectorization gain, voice activity and load effect. The module 5 performs the calculation processing gain (Hz / bps) bit time, bit energy (Ws). Module 6 deals with the telephone traffic and scales 1: traffic volume, occupancy intensity, average time of occupancy, traffic intensity, calls completed, congestion. Module 7 deals with two telephone traffic and allows calculating call completion and not completed in HMM. Tests were performed on the mobile network performance field for the calculation of data relating to: CINP , CPI , RSRP , RSRQ , EARFCN , Drop Call , Block Call , Pilot , Data Bler , RSCP , Short Call, Long Call and Data Call ; ECIO - Short Call and Long Call , Data Call Troughput . As survey were conducted surveys of electric and magnetic field in an ERB , trying to observe the degree of exposure to non-ionizing radiation they are exposed to the general public and occupational element. The results were compared to permissible values for health endorsed by the ICNIRP and the CENELEC .

Species and size selectivity in a Portuguese multispecies artisanal long-line fishery

The species and size selectivity of long-lines using small hooks were studied off the south coast of Portugal using ''Mustad'' brand round bent, flatted sea hooks (Quality 2316 DT) numbers 15, 13, and 11 baited with razor shell clam (Ei-isis siliqua). Hook numbers 13 and 11 are 49 and 109% larger respectively than number 15 hooks in terms of overall size (maximum width x maximum length). A total of 39 900 hooks were fished in 45 sets and 35 species of fish and cephalopods were caught. As a group, 13 species of sea breams (Sparidae) dominated the catch by numbers (58%) and weight (73%). Six species of sea breams, along with the greater weever fish (Trachinus draco) accounted for 81% of the total catch by weight, with the common or white sea bream (Diplodus sargus) bring the most important (29%). Catch size distributions by hook size were, in general, highly overlapped for all species and hook size had little apparent effect on minimum size at capture. All hooks caught a wide range of sizes per species, but the catch rate (number of fish per 100 hooks) was significantly lower for the largest hook. Except for the black sea bream (Spondyliosoma cantharus), capture of illegally sized or immature fish was minimal. Small increases in average size with hook size were evident for four species: Diplodus sargus, D. vulgaris, Lithognathus mormyrus and Serranus cabrilla. No differences in size selectivity were detected for Boops boops, D. annularis, Spondyliosoma cantharus and Trachinus draco. A skew-normal model adequately described differences in size selectivity in five of six species. (C) 1996 International Council for the Exploration of the Sea

Catch composition, catch rates and size selectivity of three long-line methods in the Algarve (southern Portugal)

Three long-line methods have been studied in the Algarve: 1) small-hook long-line for inshore (less than 30 m) ‘white’ sea breams (Sparidae); 2) small-hook long-line for deeper water (40-60 m) ‘red’ sea breams; and 3) deep water (500-700 m) semi-pelagic long-line for hake Merluccius merluccius (Linnaeus, 1758). Selectivity studies were carried out with three hook sizes in the first two cases: Mustad round-bent Quality 2369 hooks, numbers 15, 13, and 11, baited with a standardsized razor-shell Ensis siliqua (Linnaeus, 1758). Four hook sizes (numbers 10, 9, 7, and 5) of Stell round-bent, eyed hooks were used in the semi-pelagic long-line selectivity study, baited with a half of a standard-sized sardine. Some factors affecting catch composition and catch rates of the small hook long-lines were also evaluated: bait, gangion length, setting time, fishing ground, and depth. Species diversity was relatively high, with 40, 36 and 27 species, respectively, in the three studies. However, the catches were dominated by a limited number of species. Catch rates (number of fish per 100 hooks) were variable (< 5 %; > 20 %), with a general decrease in catch rate with increasing hook size in all the studies. In general, the catch size distributions for the different hook sizes for each species were highly overlapping, with little or no evidence of differences in size selectivity. Hooks caught a wide size-range for each species, with few or no illegal-sized fish, in most cases. Some implications of these results for the management of multi-species, multi-gear fisheries are discussed.

TECTONIC CONTROLS ON FLUVIAL LANDSCAPE DEVELOPMENT IN CENTRAL-EASTERN PORTUGAL: INSIGHTS FROM LONG PROFILE TRIBUTARY STREAM ANALYSES

This study examines the long profiles of tributaries of the Tejo (Tagus) and Zêzere rivers in central eastern Portugal (West Iberia) in order to provide new insights into the patterns, timing and controls on drainage development during the Pleistocene to Holocene incision stage. The long profiles were extracted from lower order tributary streams associated with the trunk drainage of the Tejo River and one main tributary, the Zêzere River (Fig. 1). These streams flow through a landscape strongly influenced by variations in bedrock lithology (mainly granites and metasediments), fault structures delimiting crustal blocks with distinct uplift rates, and a base-level lowering history (tectonic uplift / eustatic). The long profiles of the tributaries of the Tejo and Zêzere rivers record a series of transient and permanent knickpoints. The permanent knickpoints have direct correlation with the bedrock strength, corresponding to the outcropping of very hard quartzites or to the transition from softer (slates/metagreywaques) to harder (granite) basement. The analyzed streams/rivers record also an older transient knickpoint/knickzone separating: a) an upstream relict graded profile, with lower steepness and higher concavity, that reflects a long period of quasi-equilibrium conditions reached after the beginning of the incision stage; and b) a downstream reach displaying a rejuvenated long profile, with steeper gradient and lower concavity, particularly for the final segment, which is often convex (Fig. 2). The rejuvenated reaches testify the upstream propagation of several incision waves that are the response of each stream to continuous or increasing crustal uplift and dominant periods of base-level lowering by the trunk drainages, coeval of low sea level conditions. The long profiles and their morphological configurations enabled spatial and relative temporal patterns of incision to be quantified for each individual tributary stream. The incision values of streams flowing in uplifted blocks of the Portuguese Central Range (PCR) (ca.380-280 m) indicate differential uplift and are higher than the incision values of streams flowing on the adjacent South Portugal planation surface – the Meseta (ca. 200 m). The normalized steepness index, calculated using the method of Wobus et al. (2006), proved to be sensitive to active tectonics, as lower ksn values were found in relict graded profiles of streams located in less uplifted blocks, (e.g. Sertã stream in the PCR), or in those flowing through tectonic depressions. Fig. 1 – Geological map of the study area. 1 – fluvial terraces (Pleistocene); 2 – sedimentary cover (Paleogene and Neogene); 3 – slates and metasandstones (Devonian); 4 – slates and quartzites (Silurian); 5 – quartzites (Ordovician); 6 – slates and metagreywackes (Precambrian to Cambrian); 7 – slates, metagreywackes and limestones (Precambrian); 8 – granites and ortogneisses; 9 – diorites and gabros; 10 - fault. SFf – Sobreira Formosa fault; Sf – Sertã fault; Pf – Ponsul fault; Gf – Grade fault. The differential uplift indicated by the distribution of the ksn values and by the fluvial incision was likely accumulated on a few major faults, as the Sobreira Formosa fault (SFf), thus corroborating the tectonic activity of these faults. Due to the fact that the relict graded profiles can be correlated with other geomorphic references documented in the study area, namely the T1 terrace of the Tagus River (with an age of ca. 1 Myr), the following incision rates can be estimated: a) for the studied streams located in uplifted blocks of the PCR, 0.38 m/kyr to 0.28 m/kyr; b) for the streams flowing on the South Portugal planation surface, 0.20 m/kyr. The differential uplift inferred between crustal blocks in the study area corroborates the neotectonic activity of the bordering faults, which has been proposed in previous studies based upon less robust data. Fig. 2 – Longitudinal profile of the Nisa stream a tributary of the Tejo River. Note the equilibrium relict profile upstream the older transient knickpoint (hatched line) and the downstream rejuvenated profile (continuous line). Legend: tKP – transient knickpoint; rKp – resistant knickpoint; Mt – schist and phyllite; Gr – granite; Hf – hornfels; Og – orthogneisse. In the inset Distance – Slope plots, fill circles correspond to the relict graded profile, crosses correspond to the rejuvenated profile located downstream the older transient knickpoint (tKP).