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The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo. Strikingly, progressively decreasing epithelial cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, we find that persistent EPCAM expression marks epithelial clones that resist EMT induction and propagate competitively. In contrast, loss of EPCAM defines clones arrested in a mesenchymal state, with concomitant suppression of tumorigenicity and metastatic potential. This dichotomy results from distinct clonal trajectories impacting global epigenetic programs that are determined by the interplay between human ZEB1 and its target GRHL2. Collectively, our results indicate that susceptibility to irreversible EMT restrains clonal propagation, whereas resistance to mesenchymal reprogramming sustains disease spread in multiple models of human metastatic breast cancer, including patient-derived cells in vivo.

Contains fulltext : 226874.pdf (Publisher’s version ) (Open Access) Continuïteit van zorg in de forensische keten heeft al geruime tijd de aandacht. Ondanks vele initiatieven blijven er toch knelpunten bestaan. Voor cliënten is gebrek aan continuïteit niet alleen vervelend, maar kan ook tot vertraging in het zorgtraject of nieuwe delicten leiden. In dit artikel beschrijven we de ervaringen van cliënten met aspecten van (dis)continuïteit in forensische zorg die uit ons onderzoek naar continuïteit van zorg, vanuit het perspectief van professionals en cliënten, naar voren kwamen. Ook geven we door hen aangedragen oplossingsrichtingen. 5 p.

BACKGROUND: Leave is an essential part of treatment within the framework of the tbs measure (court ordered psychiatric treatment for offenders with a mental disorder). Traditionally, these leaves lead to concerns about safety. AIM: To study how often tbs-patients do not return from leave (on time) and how often they commit a crime during an unauthorized absence (UA). In addition, we investigate whether patient or offence characteristics can predict an UA. METHOD: All UA’s between 2009-2020 were examined. We also analysed the patient characteristics of 11,525 permit applications between 2010 and 2018 from the registration system of the Advisory Board for Permitting Leave TBS (AVT). RESULTS: 2.5% of the applications for leave between 2009 and 2020 involved an UA and 0.15% involved an UA with a recidivism. Patients with a cluster B personality disorder, substance use disorder, mood disorder, attention disorder, arson or a serious violent crime as an index offence had a significantly higher chance of having an UA. However, these associations were very weak. The risk factor violation of conditions (from the Dutch risk assessment tool, the HKT (Historical, Clinical, Future)) was also a significant but very weak predictor of UA. CONCLUSION: UA is a rare event. Despite the fact that some patient and offence characteristics were associated with an UA, this relationship is weak and predicting an UA is difficult.

The probationer–probation officer working alliance plays an important role in the outcome of probation supervision. This study explored the development of the working alliance between probationers and probation officers in the Netherlands, from the perspective of both probationers and probation officers. More specifically, we explored the significance of different aspects of the working alliance at the start of probation supervision and after a three-month period, as well as the role played by critical incidents during the supervisory process and their subsequent effect on the working alliance. Overall, the study showed that clarity over goals and restrictions was initially the most salient issue for both parties, and that after a three-month period the working alliance evolved into a trusting relationship. Several incidents were identified, probationers identified more positive moments and less negative moments than their PO counterparts. If these types of incidents are managed accordingly by the probation officer, then they can ultimately serve to strengthen the relationship.

As a growing number of nanotherapeutics enters the market, improved analytical techniques for measuring the drug release are required. Biorelevant release tests have become a standard in the prediction of in vivo pharmacokinetics but also in quality control of novel dosage forms. In the present study, two methods for testing the drug release from nanocarriers, namely the filtration technique and the dispersion releaser technology, have been investigated. Initially, the in vitro release rates were determined using two different biorelevant media. Additionally, the effect of each method on a simulated in vivo pharmacokinetic profile was studied using advanced PBPK modelling. The two methods resulted in slightly different release profiles. Applying the filtration method, an early plateau of 91.0 ± 5.3% was reached at the first sampling time point. In comparison, the release rate steadily increased to a maximum of 100.9 ± 4.1% when the dispersion releaser technology was used. Sensitivity analysis revealed how these differences translated into the PBPK-based simulation. A change in the total dissolution rate of 10% resulted in cmax values of +1.6% and −11.0%, respectively, when using input data obtained with the dispersion releaser. Data obtained by filtration translated into cmax values of ±1.8%.

In their invasive ranges Argentine ant populations often form one geographically vast supercolony genetically and chemically uniform within which there is no intraspecific aggression. Here we present regional patterns of intraspecific aggression cuticular hydrocarbons (CHCs) and population genetics of 18 nesting sites across Corsica and the French mainland. Aggression tests confirm the presence of a third European supercolony the Corsican supercolony which exhibits moderate to high levels of aggression depending on nesting sites with the Main supercolony and invariably high levels of aggression with the Catalonian supercolony. The chemical analyses corroborated the behavioural data with workers of the Corsican supercolony showing moderate differences in CHCs compared to workers of the European Main supercolony and strong differences compared to workers of the Catalonian supercolony. Interestingly there were also clear genetic differences between workers of the Catalonian supercolony and the two other supercolonies at both nuclear and mitochondrial markers but only very weak genetic differentiation between nesting sites of the Corsican and Main supercolonies (FST = 0.06). A detailed comparison of the genetic composition of supercolonies also revealed that if one of the last two supercolonies derived from the other it is the Main supercolony that derived from the Corsican supercolony rather than the reverse. Overall these findings highlight the importance of conducting more qualitative and quantitative analyses of the level of aggression between supercolonies which has to be correlated with genetic and chemical data. © 2012 Blackwell Publishing Ltd.

Industrial production of nanosized drug delivery devices is still an obstacle to the commercialization of nanomedicines. This study encompasses the development of nanoparticles for peroral application in photodynamic therapy, optimization according to the selected product specifications, and the translation into a continuous flow process. Polymeric nanoparticles were prepared by nanoprecipitation of EudragitA (R) RS 100 in presence and in absence of glycofurol. The photosensitizer temoporfin has been encapsulated into these carrier devices. Process parameters were optimized by means of a Design of Experiments approach and nanoparticles with optimal characteristics were manufactured by using microreactor technology. The efficacy was determined by means of cell culture models in A-253 cells. Physicochemical properties of nanoparticles achieved by nanoprecipitation from ethanolic solutions were superior to those obtained from a method based upon glycofurol. Nanoencapsulation of temoporfin into the matrix significantly reduced toxicity of this compound, while the efficacy was maintained. The release profiles assured a sustained release at the site of action. Finally, the transfer to continuous flow technology was achieved. By adjusting all process parameters, a potent formulation for application in the GI tract was obtained. The essential steps of process development and scale-up were part of this formulation development.

Coastal primary rainforests have suffered damage in Côte d'Ivoire as a result of a lack of protection and urban pressures. Consequently, the highly endemic and critically endangered Wimmer's shrew, Crocidura wimmeri, known only from its type locality, Adiopodoumé, near Abidjan, was considered to have been extinct since 1976. Shrew species assignment is often problematic because of strong phenotypic similarities among many species. The phylogenetic position of C. wimmeri within the African Crocidura species should thus be clarified. In light of its recent rediscovery in the nearby small Banco National Park (34 km2), we investigated the genetic identity of seven specimens of C. wimmeri, based on 1020 bp of the mitochondrial DNA cytochrome b gene compared to other species sampled in the same region and published sequences from GenBank. Crocidura wimmeri formed a well-defined clade, the closest-related species being Crocidura sp., with a distance of 9.3%, a yet unknown species from Taï and Ziama forests. These results thus confirmed the validity of this species. This genetic characterization not only contributes to our knowledge of the evolution of West African shrews, but also may help in the discovery of additional populations of this critically endangered species.

In dit artikel wordt de HCR-20 V3 voor het inschatten van het risico van gewelddadig gedrag geïntroduceerd. De HCR-20 V3 is de revisie van de HCR- 20 en is ontwikkeld op basis van jarenlang en wereldwijd onderzoek en klinische expertise. De belangrijkste doelstelling van deze revisie is om de waarde en bruikbaarheid van het instrument voor de dagelijkse praktijk verder te vergroten. Een adequate inschatting van het risico van geweld- dadig gedrag biedt concrete richtlijnen voor risicomanagement en behandeling, waarmee gewelddadige recidive kan worden voorkomen.

The driving engine of the Free Electron Laser in Hamburg (FLASH) is an L-band superconducting accelerator. It is designed to operate in burst mode with 800 microsecond pulse duration at a repetition rate of 10 Hz. The maximum accelerated beam current during the macropulse is 9 mA. Our analysis shows that the FLASH technology has great potential since it is possible to construct a FLASH like free electron laser operating at the wavelength of 13.5 and 6.8 nanometer with an average power up to 2.6 kW. Such a source meets the physical requirements for the light source for the next generation lithography., Comment: 18 pages, 9 figures

We have developed a high-resolution cavity-beam position monitor (BPM) to be used at the focal point of the ATF2, which is a test beam line that is now being built to demonstrate stable orbit control at $\ensuremath{\sim}\mathrm{\text{nanometer}}$ resolution. The design of the cavity structure was optimized for the Accelerator Test Facility (ATF) beam in various ways. For example, the cavity has a rectangular shape in order to isolate two dipole modes in orthogonal directions, and a relatively thin gap that is less sensitive to trajectory inclination. A two stage homodyne mixer with highly sensitive electronics and phase-sensitive detection was also developed. Two BPM blocks, each containing two cavity BPMs, were installed in the existing ATF beam line using a rigid support frame. After testing the basic characteristics, we measured the resolution using three BPMs. The system demonstrated 8.7 nm position resolution over a dynamic range of $5\text{ }\text{ }\ensuremath{\mu}\mathrm{m}$.

For achieving the high luminosity required at the International Linear Collider (ILC), it is critical to focus the beams to nanometer size with the ILC Beam Delivery System (BDS), and to maintain the beam collision with a nanometer-scale stability. To establish the technologies associated with this ultra-high precision beam handling, it has been proposed to implement an ILC-like final focus optics in an extension of the existing extraction beamline of ATF at KEK. The ATF is considered to be the best platform for this exercise, since it provides an adequate ultra-low emittance electron beam in a manner dedicated to the development of ILC. The two major goals for this facility, called ATF2, are : (A) Achievement of a 37 nm beam size, and (B) control of beam position down to 2 nm level. The scientific justification for the ATF2 project and its technical design have been described in Volume 1 of the ATF2 Proposal [1]. We present here Volume 2 of the ATF2 Proposal, in which we present specifics of the construction plans and the group organization to execute the research programs at ATF2. The sections in this report have been authored by relevant ATF2 subgroups within the International ATF Collaboration. The time line of the project is described in Section 2. Section 3 discuss the structure of the international collaboration. Sections 4 and 5 discuss budget considerations, which are presented as well as the design and construction tasks to be shared by the internationalcollaboration at ATF2. Concluding remarks have been contributed by Dr. Ewan Paterson, Chair of the International Collaboration Board of the ATF collaboration. The two major goals for this facility, called ATF2, are : (A) Achievement of a 37 nm beam size, and (B) control of beam position down to 2 nm level. The scientific justification for the ATF2 project and its technical design have been described in Volume 1 of the ATF2 Proposal. We present here Volume 2 of the ATF2 Proposal, in which we present specifics of the construction plans and the group organization to execute the research programs at ATF2.

The two major goals for this facility, called ATF2, are : (A) Achievement of a 37 nm beam size, and (B) control of beam position down to 2 nm level. The scientific justification for the ATF2 project and its technical design have been described in Volume 1 of the ATF2 Proposal. We present here Volume 2 of the ATF2 Proposal, in which we present specifics of the construction plans and the group organization to execute the research programs at ATF2.

DESY (2006).

ATF2 Group; The two major goals for this facility, called ATF2, are : (A) Achievement of a 37 nm beam size, and (B) control of beam position down to 2 nm level. The scientific justification for the ATF2 project and its technical design have been described in Volume 1 of the ATF2 Proposal. We present here Volume 2 of the ATF2 Proposal, in which we present specifics of the construction plans and the group organization to execute the research programs at ATF2.

4 pp. (2006)., International Linear Collider (ILC) interaction region beam sizes and component position stability requirements will be as small as a few nanometers. It is important to the ILC design effort to demonstrate that these tolerances can be achieved – ideally using beam-based stability measure- ments. It has been estimated that RF cavity beam position monitors (BPMs) could provide position measurement res- olutions of less than one nanometer and could form the ba- sis of the desired beam-based stability measurement. We have developed a high resolution RF cavity BPM system. A triplet of these BPMs has been installed in the extrac- tion line of the KEK Accelerator Test Facility (ATF) for testing with its ultra-low emittance beam. The three BPMs are rigidly mounted inside an alignment frame on variable- length struts which allow movement in position and angle. We have developed novel methods for extracting the posi- tion and tilt information from the BPM signals including a calibration algorithm which is immune to beam jitter. To date, we have been able to demonstrate a resolution of ap- proximately 20 nm over a dynamic range of +/- 20 microns. We report on the progress of these ongoing tests.

ATF2 Group; The two major goals for this facility, called ATF2, are : (A) Achievement of a 37 nm beam size, and (B) control of beam position down to 2 nm level. The scientific justification for the ATF2 project and its technical design have been described in Volume 1 of the ATF2 Proposal. We present here Volume 2 of the ATF2 Proposal, in which we present specifics of the construction plans and the group organization to execute the research programs at ATF2.

ATF2 Group; The two major goals for this facility, called ATF2, are : (A) Achievement of a 37 nm beam size, and (B) control of beam position down to 2 nm level. The scientific justification for the ATF2 project and its technical design have been described in Volume 1 of the ATF2 Proposal. We present here Volume 2 of the ATF2 Proposal, in which we present specifics of the construction plans and the group organization to execute the research programs at ATF2.

Some ants have an extraordinary unicolonial social organization, whereby individuals mix freely among physically separated nests. Recently, it was shown that the European population of Linepithema humile consisted of two enormous unicolonial supercolonies. Workers of the same supercolony are never aggressive to each other. In contrast, aggressiveness is invariably high between workers from different supercolonies. Here we investigated whether gene flow occurs between two supercolonies. We identified a contact zone in which we sampled 46 nests. For each nest, aggression tests were conducted against workers from reference nests from both supercolonies. Workers were always very aggressive towards workers of one of the supercolonies but not to workers of the other. Thus, all nests could be clearly assigned to one of the two supercolonies. For 22 of the 46 nests, we genotyped 15-16 workers at five microsatellite loci. A four-level hierarchical analysis of variance revealed very strong genetic differentiation between the two supercolonies (F(SUPERCOLONY-TOTAL) = 0.541) and low differentiation between sectors (i.e. group of nests connected together with trails) within supercolonies (F(SECTOR-SUPERCOLONY) = 0.064). The very high differentiation between the two supercolonies indicates a lack of ongoing gene flow, a conclusion further bolstered by the finding that the two supercolonies share no common alleles at two of the five microsatellite loci. A Bayesian clustering method also revealed the occurrence of two distinct clusters. These clusters exactly match the grouping obtained by aggression tests. None of the 332 genotyped individuals were admixed despite the fact that some nests of the two supercolonies were separated by less than 30 m. These results demonstrate that the two supercolonies have completely separate gene pools.

ATF2 Group Accelerator Physics

ATF2 Group Accelerator Physics

We report on the smallest vertical emittance achieved in single-bunch-mode operation of the ATF. The emittances were measured with a laser-wire beam-profile monitor installed in the damping ring. The bunch length and the momentum spread of the beam were also recorded under the same conditions. The smallest vertical rms emittance measured is 4 pm in the limit of zero current. It increases by a factor of 1.5 for a bunch intensity of 10^10 electrons. There are no discrepancies between the measured data and the calculations of intra-beam scattering.

Die vorliegende Studie beschreibt geschlechts- und medienspezifische Effekte bei der Bestimmung von Pflanzen. Das Ziel bestand darin, explorativ zu untersuchen, welche Auswirkungen die Arbeit mit einer Online-Lernumgebung im Gegensatz zu bisherigen Bestimmungsbüchern auf die Prozesse in gemischt-geschlechtlichen Dyaden hat. Hierzu wurden vorrangig die Anzahlen medien- und pflanzenbezogener Aktionen der Probanden untersucht. Generell zeigt die Studie, dass keine schwerwiegenden geschlechtsspezifischen Effekte zu erwarten sind. Allerdings muss bei der Implementierung der Lernumgebung darauf geachtet werden, dass keine Rollendifferenzierung derart entsteht, dass innerhalb der Lerndyaden ein Proband den Computer bedient und der andere die Pflanze untersucht. Die Einstellung der Probanden gegenüber der neuen Lernumgebung war positiv, so dass von Seiten der Studenten keine Akzeptanzprobleme bezüglich der Implementierung in die Kurse zu erwarten sind.

Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than $1%$ of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than $2.8\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}8}\mathrm{rad}\mathrm{m}$ at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.