The park and the city profile

För att locka nya invånare och turister strävar många städer efter att ge staden en positiv och tydlig profil. I arbetet har jag undersökt vilken roll stadens parker kan spela för stadens identitet genom att intervjua invånare i Uppsala och företrädare för trädgårdar och parker i staden. Parken är betydelsefull för stadens identitet genom att den spelar en roll som stadsbyggnadselement och ger karaktär åt staden. Parken har även betydelse för individens upplevelse av staden beroende på hennes föreställningar om parken. Detta kan bero på parkens tillgänglighet och attraktivitet och även på hur stor kunskap om platsen man har. Hur man på kommunen förmedlar och informerar om parkerna har därför betydelse för vilken betydelse de spelar för invånarna

Kvalitativa effekter av internetbaserad rehabilitering för hörapparatanvändare

Rehabilitering av personer med hörselnedsättning kan utformas på olika sätt. En nyare metod är internetbaserad hörselrehabilitering som bygger på deltagarnas egen aktivitet. Syftet med studien var att undersöka deltagarnas upplevelser av en internetbaserad rehabilitering som genomförts under år 2011. Studien utfördes som en kvalitativ intervjustudie. Tjugo personer som använt hörapparat i flera år intervjuades per telefon. Intervjuerna spelades in och samtalen transkriberades ortografiskt. Det insamlade materialet analyserades med innehållsanalys enligt en modell av Graneheim och Lundman (2004). Av studien framkom att deltagarnas upplevelser av kursen varit blandade. En bok som utgjort en del av kursmaterialet var mycket uppskattad. Deltagarna var intresserade av att få ny kunskap, samtidigt som de uppskattade att få bekräftelse på befintliga kunskaper. Via ett diskussionsforum kunde deltagarna utbyta erfarenheter och läsa om varandras erfarenheter. Datortekniska problem var en begränsning för några deltagare. Internetformen var generellt uppskattad eftersom den underlättar deltagande på valfria tider och platser. Studien visar att internetbaserad rehabilitering är ett värdefullt komplement till de rehabiliteringsformer som används traditionellt. Genom att övningsuppgifter genomförs aktiveras ibland också anhöriga, vilket ger förbättrat utfall kring kommunikationsstrategier. Det är dock viktigt att tydliga instruktioner kring datoranvändandet och bra datorsupport underlättar deltagarnas aktivitet

Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation

Maintenance of genome integrity is critical to guarantee transfer of an intact genome from parent to off-spring during cell division. DNA polymerases (Pols) provide roles in both replication of the genome and the repair of a wide range of lesions. Amongst replicative DNA Pols, translesion DNA Pols play a particular role: replication to bypass DNA damage. All cells express a range of translesion Pols, but little work has examined their function in parasites, including whether the enzymes might contribute to host-parasite interactions. Here, we describe a dual function of one putative translesion Pol in African trypanosomes, which we now name TbPolIE. Previously, we demonstrated that TbPolIE is associated with telomeric sequences and here we show that RNAi-mediated depletion of TbPolIE transcripts results in slowed growth, altered DNA content, changes in cell morphology, and increased sensitivity to DNA damaging agents. We also show that TbPolIE displays pronounced localization at the nuclear periphery, and that its depletion leads to chromosome segregation defects and increased levels of endogenous DNA damage. Finally, we demonstrate that TbPolIE depletion leads to deregulation of telomeric variant surface glycoprotein genes, linking the function of this putative translesion DNA polymerase to host immune evasion by antigenic variation

Blue justice : A survey for eliciting perceptions of environmental justice among coastal planners' and small-scale fishers in Northern-Norway

Ocean-based economic development arising from an increasing interest in the 'blue economy' is placing ecosystems and small-scale fisheries under pressure. The dominant policy response for dealing with multiple uses is the allocation of coastal space through coastal zone planning (CZP). Recent studies have shown that the rush to develop the blue economy and regulate coastal activity can result in social injustices and the exclusion of less powerful and unrecognized groups (e.g., small-scale fishers, women, Indigenous peoples and youth). To achieve a primary goal of the 2030 sustainable development agenda to "leave no one behind", it is important to understand the implications of coastal planning and development for these groups. Here, we present a social survey protocol for examining perceptions of justice related to small-scale fisheries (SSF) in the context of the blue economy in coastal areas. Specifically, we designed the survey instrument and sampling protocol to assess whether decisions about the use of the coastal zone over the last five years have i) followed principles of good governance, ii) recognized fishers' knowledge, culture and rights and iii) been attentive to impacts of changed coastal zone use on fisheries. The survey will engage coastal planners (N = app. 120) and fishers (N = app. 4300) in all the coastal municipalities (N = 81) in Northern-Norway. The sampling protocol is designed to ensure representation of different sectors of society, including those defined by gender, age, ethnicity and occupation (e.g., small-scale fishers, large-scale fishers, coastal planners).Peer reviewe

X-ray scattering from warm dense iron

We have carried out X-ray scattering experiments on iron foil samples that have been compressed and heated using laser-driven shocks created with the VULCAN laser system at the Rutherford-Appleton Laboratory. This is the highest Z element studied in such experiments so far and the first time scattering from warm dense iron has been reported. Because of the importance of iron in telluric planets, the work is relevant to studies of warm dense matter in planetary interiors. We report scattering results as well as shock breakout results that, in conjunction with hydrodynamic simulations, suggest the target has been compressed to a molten state at several 100 GPa pressure. Initial comparison with modelling suggests more work is needed to understand the structure factor of warm dense iron

Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours

Background: Berzosertib (formerly M6620, VX-970) is a highly potent and selective, first-in-class inhibitor of ataxia telangiectasia and Rad3-related protein kinase (ATR). We assessed multiple ascending doses of berzosertib + gemcitabine ± cisplatin in patients with resistant/refractory advanced solid tumours. Methods: We evaluated the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of intravenous berzosertib + gemcitabine ± cisplatin using a standard 3 + 3 dose-escalation design. The starting doses were berzosertib 18 mg/m2, gemcitabine 875 mg/m2 and cisplatin 60 mg/m2. Results: Fifty-two patients received berzosertib + gemcitabine and eight received berzosertib + gemcitabine + cisplatin. Four patients receiving berzosertib + gemcitabine had a total of seven dose-limiting toxicities (DLTs) and three receiving berzosertib + gemcitabine + cisplatin had a total of three DLTs. Berzosertib 210 mg/m2 (days 2 and 9) + gemcitabine 1000 mg/m2 (days 1 and 8) Q3W was established as the recommended Phase 2 dose (RP2D); no RP2D was determined for berzosertib + gemcitabine + cisplatin. Neither gemcitabine nor cisplatin affected berzosertib PK. Most patients in both arms achieved a best response of either partial response or stable disease. Conclusions: Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs. Clinical trial identifier: NCT02157792

Epigenome-wide association study of alcohol consumption in N = 8161 individuals and relevance to alcohol use disorder pathophysiology:identification of the cystine/glutamate transporter SLC7A11 as a top target

Alcohol misuse is common in many societies worldwide and is associated with extensive morbidity and mortality, often leading to alcohol use disorders (AUD) and alcohol-related end-organ damage. The underlying mechanisms contributing to the development of AUD are largely unknown; however, growing evidence suggests that alcohol consumption is strongly associated with alterations in DNA methylation. Identification of alcohol-associated methylomic variation might provide novel insights into pathophysiology and novel treatment targets for AUD. Here we performed the largest single-cohort epigenome-wide association study (EWAS) of alcohol consumption to date (N = 8161) and cross-validated findings in AUD populations with relevant endophenotypes, as well as alcohol-related animal models. Results showed 2504 CpGs significantly associated with alcohol consumption (Bonferroni p value < 6.8 × 10(−8)) with the five leading probes located in SLC7A11 (p = 7.75 × 10(−108)), JDP2 (p = 1.44 × 10(−56)), GAS5 (p = 2.71 × 10(−47)), TRA2B (p = 3.54 × 10(−42)), and SLC43A1 (p = 1.18 × 10(−40)). Genes annotated to associated CpG sites are implicated in liver and brain function, the cellular response to alcohol and alcohol-associated diseases, including hypertension and Alzheimer’s disease. Two-sample Mendelian randomization confirmed the causal relationship of consumption on AUD risk (inverse variance weighted (IVW) p = 5.37 × 10(−09)). A methylation-based predictor of alcohol consumption was able to discriminate AUD cases in two independent cohorts (p = 6.32 × 10(−38) and p = 5.41 × 10(−14)). The top EWAS probe cg06690548, located in the cystine/glutamate transporter SLC7A11, was replicated in an independent cohort of AUD and control participants (N = 615) and showed strong hypomethylation in AUD (p < 10(−17)). Decreased CpG methylation at this probe was consistently associated with clinical measures including increased heavy drinking days (p < 10(−4)), increased liver function enzymes (GGT (p = 1.03 × 10(−21)), ALT (p = 1.29 × 10(−6)), and AST (p = 1.97 × 10(−8))) in individuals with AUD. Postmortem brain analyses documented increased SLC7A11 expression in the frontal cortex of individuals with AUD and animal models showed marked increased expression in liver, suggesting a mechanism by which alcohol leads to hypomethylation-induced overexpression of SLC7A11. Taken together, our EWAS discovery sample and subsequent validation of the top probe in AUD suggest a strong role of abnormal glutamate signaling mediated by methylomic variation in SLC7A11. Our data are intriguing given the prominent role of glutamate signaling in brain and liver and might provide an important target for therapeutic intervention

Self-powered wireless carbohydrate/oxygen sensitive biodevice based on radio signal transmission

peer-reviewedHere for the first time, we detail self-contained (wireless and self-powered) biodevices with wireless signal transmission. Specifically, we demonstrate the operation of self-sustained carbohydrate and oxygen sensitive biodevices, consisting of a wireless electronic unit, radio transmitter and separate sensing bioelectrodes, supplied with electrical energy from a combined multi-enzyme fuel cell generating sufficient current at required voltage to power the electronics. A carbohydrate/oxygen enzymatic fuel cell was assembled by comparing the performance of a range of different bioelectrodes followed by selection of the most suitable, stable combination. Carbohydrates (viz. lactose for the demonstration) and oxygen were also chosen as bioanalytes, being important biomarkers, to demonstrate the operation of the self-contained biosensing device, employing enzyme-modified bioelectrodes to enable the actual sensing. A wireless electronic unit, consisting of a micropotentiostat, an energy harvesting module (voltage amplifier together with a capacitor), and a radio microchip, were designed to enable the biofuel cell to be used as a power supply for managing the sensing devices and for wireless data transmission. The electronic system used required current and voltages greater than 44 mu A and 0.57 V, respectively to operate; which the biofuel cell was capable of providing, when placed in a carbohydrate and oxygen containing buffer. In addition, a USB based receiver and computer software were employed for proof-of concept tests of the developed biodevices. Operation of bench-top prototypes was demonstrated in buffers containing different concentrations of the analytes, showcasing that the variation in response of both carbohydrate and oxygen biosensors could be monitored wirelessly in real-time as analyte concentrations in buffers were changed, using only an enzymatic fuel cell as a power supply.PUBLISHEDpeer-reviewe