Separate and Legally Unequal – How The Demonization of Immigrants Affects United States Policy

Samverkan blir allt vanligare som organisatorisk lösning på situationer där ansvarsområden är vaga eller skär över organisationsgränser. Inom området vård och omsorg om äldre korsar ansvaret gränser både avseende huvudmän och yrkesgrupper och satsningar på samverkan är därför frekvent förekommande. Särskilda satsningar på samverkan inom just rehabiliteringsområdet har också främjats av statliga stimulansmedel riktade mot vården och omsorgen om äldre. Föreliggande studie belyser hur kärntruppen, en grupp bestående av representanter för olika yrkesgrupper och huvudmän med ansvar för olika uppdrag i rehabiliteringen av äldre i Kinda kommit att samverka i syfte att skapa bättre samordning och samsyn kring brukaren. Materialet som studien bygger på består av fem års kontinuerliga mötesanteckningar, personliga intervjuer, en fokusgruppsintervju, ett års kontinuerligt nedskrivna mötesdagböcker samt övrig dokumentation om verksamheten. Studien visar hur samverkan kan utvecklas och samsyn frammanas i viktiga frågor genom att rätt personer involveras, personligt engagemang skapas och tid ges till diskussion om frågor som lyfts upp och bearbetas efter hand. Sett ur ett meningsskapandeperspektiv framträder betydelsen av gemensamma aktiviteter vid olika mötesarenor för den samsyn som åstadkoms. Brukaren, eller ”Kalle”, blir det objekt som företrädare för samtliga inblandade organisationer och yrkesgrupper kan samlas kring. Genom mötet dem emellan framträder kärntruppen som en organisation som fungerar som en länk mellan olika världar likväl som en brobyggare för att inkludera även andra i ett alternativt synsätt på brukaren.Rapporten tillgänglig för beställning via FoU-centrum, www.linkoping.se.</p

Functionalised graphene sheets as effective high dielectric constant fillers

A new functionalised graphene sheet (FGS) filled poly(dimethyl)siloxane insulator nanocomposite has been developed with high dielectric constant, making it well suited for applications in flexible electronics. The dielectric permittivity increased tenfold at 10 Hz and 2 wt.% FGS, while preserving low dielectric losses and good mechanical properties. The presence of functional groups on the graphene sheet surface improved the compatibility nanofiller/polymer at the interface, reducing the polarisation process. This study demonstrates that functionalised graphene sheets are ideal nanofillers for the development of new polymer composites with high dielectric constant values

Methylation inhibition for coping with epigenetic-based heterogeneity of CHO cell subclones and improving recombinant MAB production

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Is DNA Damage Response Ready for Action Anywhere?

Organisms are continuously exposed to DNA damaging agents, consequently, cells have developed an intricate system known as the DNA damage response (DDR) in order to detect and repair DNA lesions. This response has to be rapid and accurate in order to keep genome integrity. It has been observed that the condensation state of chromatin hinders a proper DDR. However, the condensation state of chromatin is not the only barrier to DDR. In this review, we have collected data regarding the presence of DDR factors on micronuclear DNA lesions that indicate that micronuclei are almost incapable of generating an effective DDR because of defects in their nuclear envelope. Finally, considering the recent observations about the reincorporation of micronuclei to the main bulk of chromosomes, we suggest that, under certain circumstances, micronuclei carrying DNA damage might be a source of chromosome instability

Molecular characterization of autophagic and apoptotic signaling induced by sorafenib in liver cancer cells

Sorafenib is the unique accepted molecular targeted drug for the treatment of patients in advanced stage of hepatocellular carcinoma. The current study evaluated cell signaling regulation of endoplasmic reticulum (ER) stress, c-Jun-N-terminal kinase (JNK), Akt, and 5′AMP-activated protein kinase (AMPK) leading to autophagy and apoptosis induced by sorafenib. Sorafenib induced early (3–12 hr) ER stress characterized by an increase of Ser51P-eIF2α/eIF2α, C/EBP homologous protein (CHOP), IRE1α, and sXBP1, but a decrease of activating transcription factor 6 expression, overall temporally associated with the increase of Thr183,Tyr185P-JNK1/2/JNK1/2, Thr172P-AMPKα, Ser413P-Foxo3a, Thr308P-AKt/AKt and Thr32P-Foxo3a/Foxo3a ratios, and reduction of Ser2481P-mammalian target of rapamycin (mTOR)/mTOR and protein translation. This pattern was related to a transient increase of tBid, Bim EL, Beclin-1, Bcl-xL, Bcl-2, autophagy markers, and reduction of myeloid cell leukemia-1 (Mcl-1) expression. The progressive increase of CHOP expression, and reduction of Thr308P-AKt/AKt and Ser473P-AKt/AKt ratios were associated with the reduction of autophagic flux and an additional upregulation of Bim EL expression and caspase-3 activity (24 hr). Small interfering-RNA (si-RNA) assays showed that Bim, but not Bak and Bax, was involved in the induction of caspase-3 in sorafenib-treated HepG2 cells. Sorafenib increased autophagic and apoptotic markers in tumor-derived xenograft model. In conclusion, the early sorafenib-induced ER stress and regulation of JNK and AMPK-dependent signaling were related to the induction of survival autophagic process. The sustained drug treatment induced a progressive increase of ER stress and PERK-CHOP-dependent rise of Bim EL, which was associated with the shift from autophagy to apoptosis. The kinetic of Bim EL expression profile might also be related to the tight balance between AKt- and AMPK-related signaling leading to Foxo3a-dependent BIM EL upregulation.Ministerio de Economía y Competitividad BFU2016‐75352‐PInstituto de Salud Carlos III PI15/00034, PI13/ 00021, PI16/00090, PI14/01349Ministerio de Educación FPU16/05127, FPU12/01433, FPU13/01237Junta de Andalucía CTS-6264, PI-00025-2013, PI-0127-2013, PI-0198-201

A Hybrid Coral Reefs Optimization – Variable Neighborhood Search Approach for the Unequal Area Facility Layout Problem

The Unequal Area Facility Layout Problem (UA-FLP) is a relevant optimization problem related to industrial design, that deals with obtaining the most effective allocation of facilities, that make up the rectangular manufacturing plant layout. The UA-FLP is known to be a hard optimization problem, where meta-heuristic approaches are a good option to obtain competitive solutions. Many of these computational approaches, however, usually fall into local optima, and suffer from lack of diversity in their population, mainly due to the huge search spaces and hard fitness landscapes produced by the traditional representation of UA-FLP. To solve these issues, in this paper we propose a novel hybrid meta-heuristic approach, which combines a Coral Reefs Optimization algorithm (CRO) with a Variable Neighborhood Search (VNS) and a new representation for the problem, called Relaxed Flexible Bay Structure (RFBS), which simplifies the encoding and makes its fitness landscape more affordable. Thus, the use of VNS allows more intensive exploitation of the searching space with an affordable computational cost, as well as the RFBS allows better management of the free space into the plant layout. This combined strategy has been tested over a set of UA-FLP instances of different sizes, which have been previously tackled in the literature with alternative meta-heuristics. The tests results show very good performance in all cases

Corticotropinoma as a Component of Carney Complex.

Known germline gene abnormalities cause one-fifth of the pituitary adenomas in children and adolescents, but, in contrast with other pituitary tumor types, the genetic causes of corticotropinomas are largely unknown. In this study, we report a case of Cushing disease (CD) due to a loss-of-function mutation in PRKAR1A, providing evidence for association of this gene with a corticotropinoma. A 15-year-old male presenting with hypercortisolemia was diagnosed with CD. Remission was achieved after surgical resection of a corticotropin (ACTH)-producing pituitary microadenoma, but recurrence 3 years later prompted reoperation and radiotherapy. Five years after the original diagnosis, the patient developed ACTH-independent Cushing syndrome, and a diagnosis of primary pigmented nodular adrenocortical disease was confirmed. A PRKAR1A mutation (c.671delG, p.G225Afs*16) was detected in a germline DNA sample from the patient, which displayed loss of heterozygosity in the corticotropinoma. No other germline or somatic mutations of interest were found. As corticotropinomas are not a known component of Carney complex (CNC), we performed loss of heterozygosity and messenger RNA stability studies in the patient's tissues, and analyzed the effect of Prkar1a silencing on AtT-20/D16v-F2 mouse corticotropinoma cells. No PRKAR1A defects were found among 97 other pediatric CD patients studied. Our clinical case and experimental data support a role for PRKAR1A in the pathogenesis of a corticotroph cell tumor. This is a molecularly confirmed report of a corticotropinoma presenting in association with CNC. We conclude that germline PRKAR1A mutations are a novel, albeit apparently infrequent, cause of CD

A novel multi-objective Interactive Coral Reefs Optimization algorithm for the Unequal Area Facility Layout Problem

The Unequal Area Facility Layout Problem (UA-FLP) has been widely analyzed in the literature using several heuristics and meta-heuristics to optimize some qualitative criteria, taking into account different restrictions and constraints. Nevertheless, the subjective opinion of the designer (Decision Maker, DM) has never been considered along with the quantitative criteria and restrictions. This work proposes a novel approach for the UA-FLP based on an Interactive Coral Reefs Optimization (ICRO) algorithm, which combines the simultaneous consideration of both quantitative and qualitative (DM opinion) features. The algorithm implementation is explained in detail, including the way of jointly considering quantitative and qualitative aspects in the fitness function of the problem. The experimental part of the paper illustrates the effect of including qualitative aspects in UA-FLP problems, considering three different hard UA-FLP instances. Empirical results show that the proposed approach is able to incorporate the DM preferences in the obtained layouts, without affecting much to the quantitative part of the solutions

Description of \u3cem\u3eLeucaena\u3c/em\u3e On-Offer Browse at Different \u3cem\u3eLeucaena\u3c/em\u3e Density

Leucaena (Lecuaena lecucephala (Lam.) de Wit) is a tree legume widely used to establish silvopastoral systems along with different tropical grasses. The relation of Leucaena density to browse available at the start of each grazing period in a rotational grazing management is important information when designing a silvopastoral pasture (Anguiano et al., 2013). Then the objective of the study was to determine Leucaena on-offer browse at different Leucaena density