Syfte: Syftet för studien var att undersöka om isometric mid-thigh pull (IMTP) tillsammans med (CMJ) kan anses som lämpliga testmetoder för att mäta prestation i hoppförmåga inom parkour/freerunning (PK/FR). Vi undersökte detta genom att mäta traceurers maximala styrka och explosiva styrka i de nedre extremiteterna, för att sedan jämföra resultaten med fysiskt aktiva idrottsstudenter på högskolenivå. Vi undersökte även om IMTP och CMJ korrelerar med varandra. Urval: 23 personer, 11 traceurer och 12 fysiskt aktiva idrottare rekryterades för denna studie. Metod: vi mätte maximal styrka: Peak force (PF) IMTP (N) på kraftplatta och maximal vertikal hopphöjd: CMJ (cm) på IR-matta. Statistisk analys: Shapiro Wilks användes för normalfördelningar, en oberoende tvåvägs Mann-Whitney U t-test användes för att undersöka skillnader mellan grupperna. Två Spearmans- och ett Pearsons korrelationskoefficienttest användes för att undersöka samband mellan IMTP och CMJ. Resultat: PK gruppen var normalfördelad i alla variabler IMTP (N) och CMJ (cm) men kontroll (KTRL) gruppen var ej normalfördelad i CMJ (cm) och gav utslag för IMTP (N). PK gruppen uppnådde ett IMTP (N) medianvärde på: 2269,9 ± 661.72N och CMJ medianvärde på 36.2 ± 7.48 cm. KTRL gruppen uppnådde ett IMTP (N) medianvärde på: 1626.9 ± 501.95N och ett CMJ medianvärde på: 31.8 ± 5.91cm. Ingen statistiskt signifikant skillnad hittades mellan grupperna, men traceurerna visar en trend för ett högre IMTP (N) värde. Ett statistiskt signifikant samband fanns mellan IMTP och CMJ för hela populationen. R-värde = 0.404. R² värde avrundades till 23%. P-värde = 0.031. Inget statistiskt signifikant samband fanns för PK eller KTRL grupperna individuellt. Slutsats: Traceurerna och de fysiskt aktiva högskolestudenterna visade snarlika resultat i maximal styrka och explosiv styrka i denna studie. Resultaten klassificerades som lågpresterande i förhållande till referensvärden från tidigare studier på traditionella idrotter för IMTP och på traceurer i CMJ. Den maximala styrkan från IMTP tycks förklara 23% av hoppförmågan i CMJ vilket kan vara en indikation av betydelse för traceurers prestation. Framtida forskare uppmuntras använda IMTP och CMJ på större populationer för att kartlägga traceurers force-velocity kurvor och/eller inrätta skadepreventiva program för PK/FR. Begrepp: Traceur (FRE) = tracer (ENG), spårare (SWE). Traceur = manlig Parkour utövare. Traceuse = kvinnlig Parkourutövare. PK/FR = Parkour/Freerunning. PK = Studiens Parkour grupp. KTRL = Studiens kontrollgrupp. Countermovement jump (CMJ), (N) = Newton. 1RM = en 100% maximal ansträngd repetition. / Purpose: The aim of the study was to investigate if IMTP together with CMJ can be considered as suitable methods to measure performance in jumping ability in PK/FR. We investigated this by measuring maximal strength and explosive strength of the lower extremities of traceurs and comparing the results with physically active college student athletes. We investigated also if IMTP and CMJ correlate with each other. Recruitment: 23 people, 11 traceurs and 12 psychical active collegial sport athletes were recruited for this study. Method: We measured maximal strength: PF IMTP (N) on force plate and maximal vertical jump height: CMJ (cm) on IR mat. Statistical analysis: Shapiro Wilks was used for normal distribution; an independent two-way Mann-Whitney U t-test was used to examine differences between groups. Linear regression tests with two Spearman's and one Pearson's correlation coefficient tests were used to examine relationships between IMTP and CMJ. R² values were calculated. Results: The PK group was normally distributed in IMTP (N) and CMJ (cm). The KTRL group was not normally distributed in CMJ (cm) and flagged an indication for IMTP (N). The PK group achieved a IMTP (N) median of 2269.9N SD ± 661.72N. And CMJ median of 36.2cm SD ± 7.48cm. The KTRL group achieved a IMTP (N) median of 1626.9N SD ± 501.95N. And a CMJ median of 31.8cm SD ± 5.91cm. No statistically significant differences were found between the groups. But the traceurs showed a trend for a higher IMTP (N) value. A statistically significant relationship was found between IMTP and CMJ for the entire population. R value = 0.404. R² value was rounded to 23%. P-value = 0.031. No statistically significant relationships were found for the PK- or the KTRL groups individually. Conclusion: The traceurs and the physically active college students were similar in maximal- and explosive strength in this study. The results were classified as low performance in comparison to previous studies of traditional sports on IMTP and on traceurs on CMJ. The maximal strength from the IMTP appears to account for 23% of the jumping ability in CMJ which may be an indication of importance for traceurs performance. Future researchers are encouraged to use IMTP and CMJ on larger populations to map force-velocity curves and/or establish injury prevention programs for PK/FR. Concepts: Traceur (FRE) = tracer (ENG), tracker (SWE). Traceur = male Parkour practitioner. Traceuse = female Parkour practitioner. PK/FR = Parkour/Freerunning. PK = The study's Parkour group. KTRL = Study control group. Countermovement jump (CMJ), Isometric mid-thigh pull (IMTP). 1 RM = a 100% maximum effort repetition. / <p>Ämneslärarprogrammet, Specialidrott</p>

Des résultats obtenus antérieurement au laboratoire ont démontré l'induction des facteurs de transcription C/EBPs par l'IL-1? ainsi que leur implication dans la régulation de la transcription de gènes de réponse inflammatoire telle que l'haptoglobine au niveau de la cellule épithéliale intestinale. En outre, il a déjà été démontré que la phosphoiylation des C/EBPs peut moduler leur activité et des études au laboratoire ont démontré l'interaction in vitro entre l'isoforme C/EBP? et la kinase DNA-PK. Par l'utilisation de l'inhibiteur non spécifique de la famille PI(3)K, la wortmannine, il a été observé que la DNA-PK phosphoryle C/EBP?. La DNA-PK est une kinase qui répare les bris d'ADN double brin en participant au processus de jonction des extrémités non-homologues. Ainsi, nous avons étudié la modulation de la réponse inflammatoire intestinale par la DNA-PK, en s'attardant plus particulièrement à deux familles de facteurs de transcription, soit NF-?B et les C/EBPs. Par l'utilisation d'un inhibiteur sélectif de la DNA-PK, le IC60211, la phosphorylation in vitro de la région N-terminale de C/EBP? par la DNA-PK a d'abord été confirmé. Puisque la DNA-PK est activée par les bris d'ADN double brin, la doxorubicine, un agent génotoxique, a été utilisé pour la suite du projet. Nous avons montré que la doxorubicine engendre une hausse de la capacité de liaison à l'ADN de NF-?B induite par l'IL-1? et que les complexes formés comprenaient surtout la sousunité p65. Ceci s'accompagne d'une hausse des niveaux nucléaires de p65 ainsi que d'une baisse d'expression de l'inhibiteur cytoplasmique de NF-?B, I?B?. Par contre, par l'utilisation de l'inhibiteur sélectif de la DNA-PK, le NU7026, nos résultats suggèrent que ces effets sont DNA-PK indépendants. En effet, un rétablissement de la capacité de liaison à l'ADN de NF-?B n'est pas observé lors d'une préincubation avec cet inhibiteur avant de traiter à la doxorubicine puis à l'IL-1?. En ce qui concerne les C/EBPs, nos résultats démontrent que la doxorubicine diminue l'activité transcriptionnelle de l'isoforme C/EBP? sur le promoteur du gène haptoglobine. Alors qu'un traitement à l'IL-1? induit une augmentation de la liaison des C/EBPs à HaptoA, nos résultats montrent qu'un pré-traitement à la doxorubicine empêche cette induction. De plus, les niveaux protéiques de C/EBP? et C/EBP? induits par l'IL-1? sont abaissés par la doxorubicine. Également, les niveaux d'ARNm de C/EBP? induits par l'IL-1 p et de deux de ses gènes cibles inflammatoires, l'haptoglobine et lipocalin2, sont diminués par un prétraitement à la doxorubicine. Par l'utilisation du NU7026, nous démontrons un rétablissement partiel de la capacité de liaison à l'ADN de C/EB13? et de C/EBP? qui était réduite par un traitement à la doxorubicine, à des niveaux comparables à la condition sans traitement et à la condition IL-1?, respectivement. Cependant, cet inhibiteur permet le rétablissement des niveaux de protéine et d'ARNm de C/EBP? (induits par l'IL-1?) qui étaient réprimés par un prétraitement à la doxorubicine mais non des niveaux protéiques de C/EBP?. Nos résultats suggèrent que la DNA-PK régule, au moins partiellement, la transcription de l'isoforme C/EBP? ainsi que son activité transcriptionnelle sur le promoteur de l'haptoglobine. Par contre, nos résultats suggèrent aussi que la DNA-PK module la capacité de liaison à l'ADN de C/EBP? et que l'effondrement des niveaux protéiques de C/EBP? par la doxorubicine est DNA-PK indépendant. [Symboles non conformes]

Antiretroviral drugs have revolutionized HIV care and enabled better management of the infection thus allowing patients survive for many years. One proposed approach to increase access to such drugs in sub-Saharan Africa is to use of a reduced-dose alternative of the drug efavirenz, with 400 mg rather than regular 600 mg dose. This effectively would provide medication for 50 percent more persons with the same amount of active ingredient. However, antiretroviral drugs require high patient adherence to achieve intended therapeutic effect, and it is unclear if a reduced-dose therapy would have sufficient efficacy, and if it would lead to an increased risk of viral resistance. The time profile of drug plasma concentration and corresponding long-term viral load was estimated using integrated population PK/PD simulations, with model parameters based on selected research studies. The results suggest a reduced dose 400 mg, rather than 600 mg regular dose, efavirenz in HIV therapy would place strict demands on patients to maintain very high adherence levels, at least 80-90 percent, to maintain sufficient drug concentration in blood plasma, and to minimize risk of viral failure. However, it is relatively rare for HIV therapy programs in sub-Saharan Africa to consistently achieve such high adherence levels. In addition, if patients are co-administered rifampin, a drug widely used in TB care, this increases hepatic metabolism and plasma clearance rate, resulting in further reduced average drug plasma concentration. These findings suggest a reduced dose efavirenz treatment alternative may be most (only) relevant for patient categories expected to maintain high adherence; and in particular among persons who have been confirmed to have CYP2B6 genotype consistent with inherently lower drug metabolism. At usual adherence levels it is estimated a reduced dose alternative may increase the share of patients at risk of viral failure by 5 to 15 percent vs. regular dose of 600 mg.

Erythrocyte pyruvate kinase (R-PK) is a key glycolytic enzyme catalyzing the transphosphorylation of phosphoenolpyruvate (PEP) and ADP to pyruvate and ATP respectively3,4. The substrate PEP and product pyruvate of this reaction are involved in a number of energetic and biosynthetic pathways; hence a tight regulation of R-PK activity is crucial not only for glycolysis, but also for the entire cellular metabolism. Deficiency of R-PK is one of the most common enzymatic defects of RBC, and may be caused by mutations of the PK-LR (pyruvate kinase liver red blood cell) gene31, 32. Clinically, R-PK deficiency manifests itself as a chronic life-long hemolysis ranging from very mild or fully compensated anemia to life-threatening neonatal anemia and pronounced jaundice. Current treatment options are limited to continuous blood transfusions and splenectomy. Thus, there is an urgent need for medications to counter R-PK deficiency without resorting to these complicated procedures. Our aim is to identify novel allosteric modifiers of R-PK using a combination of computational studies and enzyme activity assays. Such compounds could be of medical interest. Human R-PK was expressed in DH-5α cells and was purified by the procedure reported by Wang et al57. However, this method gave a very low yield of R-PIS (5mg/L). In an attempt to increase the yield, we expressed R-PK in Rosetta strain cells. Further, addition of His-tag to the protein's N-terminus simplified purification to a one step Ni-NTA (Nickel- nitrilotriacetic acid) column resulting in a 6-fold increase in the yield. Computational methods were applied to identify small molecules that bind to the allosteric activator fructose 1,6-bisphosphate (FBP) binding site of R-PK to identify compounds that could interact with the protein. The software UNITY, as present in the molecular modeling software Sybyl was used to perform 3D searches against the National Cancer Institute (NCI) chemical database. From these searches we obtained 29 hits that were subjected to further computational analysis. The small molecules were docked into the FBP binding site of R-PK with different docking methods includingFlexX, GOLD and energy minimization. The energy scoring function of HINT was then applied to analyze the interactions between the docked molecules and R-PK. Compounds with highest HINT score were requested fiom NCI and were subjected to further kinetic analysis to identify possible allosteric effectors of R-PK.In the kinetic analysis, we employed a lactate dehydrogenase (LDH) coupled spectrophotometric assay to determine the activity of R-PK in the presence of these compounds. The steady state kinetics of R-PK gave a typical S-shaped curve that fitted a signloidal function indicative of allosterism. All the kinetic parameters of our enzyme were in excellent agreement with native R-PK activity as previously reported5, 57. R-PK activity in the presence of the analyzed compounds revealed both activators and inhibitors of R-PK. X-ray crystallographic analysis of R-PK in the presence of FBP and the identified small molecule effectors are currently in progress. These experiments were initiated to reveal the binding site of the compounds in R-PK, allowing for further optimization of the starting phannacophores and syntheses of new molecular entities for enhanced allosteric activity.In conclusion, we have developed a simple and efficient method for the expression and purification of R-PK. Using computational screening and HINT analysis we have also identified several compounds that interact with R-PK and kinetic analysis revealed both activators and inhibitors of the protein. Crystals of R-PK in the presence of effectors have been obtained and identification of the binding site on R-PK is under investigation. R-PK effectors discovered in this study could prove to be lead compounds for developing medications for the treatment of anemia and other disorders arising from R-PK malfunction.

This thesis presents a study of Pakistani documentary, with a focus on the ways in which it represents Pakistan’s national identity and history. The study examines three sources of documentary production – state media, commercial television channels, and independent filmmakers – as three distinct voices of Pakistani documentary. The study argues that the discourses of these institutions are governed by their respective ideological, political, and economic priorities. These factors result in two competing approaches to Pakistan’s national history and identity: right-wing and left-wing. The Islamic ideology of the state governs the discourse of state-sponsored documentaries. The commercial television documentaries take an anti-establishment position, however, they remain faithful to Islamic ideology of the state to a large extend. The independent filmmakers, on the other hand, offer a liberal perspective of history and a secular identity of Pakistan. Hence, they offer a critical view of the state’s Islamic ideology as a governing principle of historiography and identity formation. The notion of representation entails the issues of authenticity, credibility, and truth-value, associated with the various methods adopted by the filmmakers. Hence, attention is paid to the styles and modes of documentary, with a reflection on the documentarian’s individual approaches to realism. The documentaries have been placed within historical and political contexts considering Pakistan as a postcolonial state, which also functions as a critical framework of this study.

Increasingly, school-based partnerships have been tied to education reform and the entrance of new private capital into the PK-12 sector. As a result, what may have been an at-will school-business partnership in the 1980s may today resemble an embedded multi-partner arrangement around professional development, teacher evaluation, or turnaround support. From curriculum to practice, and from human resources to operations, the notion of a simple YMCA after school partnership is being replaced by a new wave of collaborations focused on school improvement, integration, and scalability. The purpose of this investigation is to consider the historical context of public-private PK-12 partnerships and elucidate how recent policies emphasizing—sometimes mandating—collaboration between schools and outside agencies can lead to benefits and challenges for PK-12 leaders at the site level. A major challenge to school leaders is that they are relatively unfamiliar with managing partnerships in general, which leaves them even more unprepared to deal with new arrangements that are complex and reform-driven (Bennett & Thompson, 2011). This investigation introduces a new conceptual framework for understanding the environment in which school partnerships exist today. By coupling sources from a multitude of cross-disciplinary fields, such as urban studies, business, nonprofit management, and organizational theory, an effort is made to explain the emergence of this new system from both a historical and theoretical perspective. Further we introduce a proposed PK-12 Blended Capital Typology and methodology for analyzing how decision-making and accountability is shared between partners in these arrangements. Through a single sample case, our goal is to emerge with themes that will support additional research using this framework.

Depot intramuscularly administered testosterone cypionate (TC) is indicated for treatment of hypogonadism in males. However, illegal use of TC and other anabolic steroids in athletic competition has been occurring for over 50 years. A randomized three-arm clinical trial was conducted to investigate side effects of long-term abuse of testosterone cypionate. The objective of the thesis is to apply modeling approach to characterize pharmacokinetics of long-term TC injections as well as identify its side effects on healthy male volunteers. A linear one-compartment model with first-order absorption best described the concentration-time profile of testosterone obtained from 31 healthy males. The population clearance estimates for total and free testosterone were 2.42*103 and 6.03*105 L/day, respectively. Weight and albumin were identified as significant covariates for total testosterone. Given the known inhibitory effect of testosterone on HPG axis, an indirect effect model was applied to describe the suppression of luteinizing hormone and spermatogenesis. The estimated potency of total testosterone with respect to LH suppression was 9.38ng/ml. Model simulation showed that suppression of luteinizing hormone and spermatogenesis after TC injection was more severe and of greater duration in the highest dose level. A polynomial change point mixed effects model was successfully built to describe the change in weight and lipid profiles after weekly injection of testosterone cypionate. Model simulation showed that both 250mg and 500mg would incur an average increase of body weight of 3.5kg at 8 weeks after dosing. A polynomial change point model also identifies that there is a tendency for lipid decrease after TC administration. However, no difference was found in the lipid change between three dose groups, which precludes any definite conclusion on the effect of long-term TC administration on lipid profiles.

Platelet-derived growth factor (PDGF) is a potent stimulator of cell growth, survival and motility. PDGF exerts its function by binding to specific tyrosine kinase receptors, initiating receptor auotphosphorylation and initiation of specific signaling pathways that regulates the cellular response. It is critical that these signals can be modulated and terminated, since over-activation of signaling pathways are often found in diseases, such as cancer. Protein tyrosine phosphatases (PTPs) counteract the tyrosine kinases by dephosphorylating proteins, thereby playing a crucial role in the control of signaling events. The aim of this thesis has been to study the regulation of PDGF receptor signaling by the T-cell protein tyrosine phosphatase (TC-PTP). In the first two studies, we demonstrated that loss of TC-PTP specifically redirected the PDGF β-receptor towards a rapid Rab4a-dependent recycling after ligand-induced internalization. Furthermore, we found that the sorting of activated PDGF β-receptor into the recycling pathway was dependent on sequential PKCα and Rab4a activation. Since the PDGF α-receptor did not recycle in the absence of TC-PTP, this study displays the first evidence of differences in trafficking of the PDGF receptor family members. PDGF β-receptor recycling was also induced by activating PKCα through the LPA receptor. The LPA-induced PDGF β-receptor recycling correlated with increased receptor phosphorylation and cell migration at low concentrations of PDGF-BB. The data suggests that PKCα activation could serve as a point of cross-talk between receptor families, regulating the duration and magnitude of PDGF β-receptor signaling. In the last study, we searched for novel substrates for TC-PTP downstream of the PDGF β-receptor, and identified the pyruvate kinase M2, PK-M2, as a possible substrate. PK-M2 is expressed in cells that proliferate rapidly, including tumor cells. Our data suggests that TC-PTP can interact with the glycolytic complex, affecting the activity of PK-M2 and hence, altering the glucose metabolism for proliferating tumor cells.

This essay examines how humor is used in the making of stereotypes in the Kronlöf sister’s video SÅ JÄVLA PK! In addition I give my analysis of how power and resistance is shown in the video. Through Michel Foucault’s conception power and resistance together with Judith Butler’s theories about performativity I’d like to show how the characters you can see in the video, in addition to the humor, also put themselves in a public context. I discuss my material in relation to a number of similar and current events that concern sexism and racism in Sweden. I clarify in my essay how Bianca and Tiffany Kronlöf through their verbal expression use a man-dominated scene – humor/comedy – to spread their message on how to prevent racism and sexism. My conclusion is that the Kronlöf sisters through their video create performativity through the retelling of an event that has already taken place, as well as resist against the power that was taken away from Bianca Kronlöf. They regain their power through a performative action.

<p>Mångkultur har idag blivit ett begrepp för att tillskriva det svenska samhället ett visst tillstånd. I den här studien så utreds artiklar, bloggforum och SOU rapporter för att belysa hur svårt det är att föra ett kritiskt samtal kring det mångkulturella samhället. Ethno-Chic är en studie inom begreppet politisk korrekthet och dess diskursiva sammanhang i migrationsdebatten. Analysen leder till resonemanget att det politiskt korrekta har blivit en konsekvens av det antirasistiska, detta i sin tur har lett till att texter ständigt står under analys för vad som kan uppfattas som främlingsfientligt.</p> / <p>Ethno-Chic is a study of the discoursive appearance of the term political correctness in the Swedish debate on migration.</p>