Comparison of the TaqMan and LightCycler systems in pharmacogenetic testing: evaluation of the CYP2C9*2/*3 polymorphisms.

Background: Pharmacogenetic testing for drugmetabolizing enzymes is not yet widely used in clinical practice. Methods: In an attempt to facilitate the application of this procedure, we have compared two real-time PCRbased methods, the TaqMan_ and the LightCycler_ for the pharmacogenetic evaluation of CYP2C9*2/*3 polymorphisms. Results and Conclusion: Both procedures are suitable for pharmacogenetic studies. The TaqMan procedure was less expensive in terms of cost per sample, but the TaqMan apparatus is more expensive than the LightCycler apparatus

On packing and covering polyhedra in infinite dimensions

We consider the natural generalizations of packing and covering polyhedra in infinite dimensions, and study issues related to duality and integrality of extreme points for these sets. Using appropriate finite truncations we give conditions under which complementary slackness holds for primal/dual pairs of the infinite linear programming problems associated with infinite packing and covering polyhedra. We also give conditions under which the extreme points are integral. We illustrate an application of our results on an infinite-horizon lot-sizing problem. Keywords: Covering polyhedron; Packing polyhedron; Infinite linear program; Complementary slackness; Integral extreme poin

Depot differences in adipokine secretion from human omental and abdominal subcutaneous adipose tissues: potential role of adiporedoxin

Adiporedoxin (Adrx) is an adipose tissue specific protein discovered by the Pilch lab. It is a member of the peroxiredoxin family localized in the endoplasmic reticulum (ER). Previous studies showed that Adrx is involved in ER redox regulation and disulfide bond formation and secretion of adipokines. Further, Adrx mRNA expression and protein levels in human abdominal adipose tissue of young, healthy subjects, ranging in levels of obesity, correlated positively with adiponectin mRNA and protein, and negatively with adipose tissue inflammation (as indicated by phospho-Jun kinase). Since previous studies have shown depot differences in adipokine release, we wanted to determine the differences on adipose tissues depot in Adrx expression. However, there are no data on depot differences in Adrx expression and its association with changes in adipokine release in human adipose tissue. It is well known that omental adipose tissue is more inflamed, and reports on depot differences in adipokine release, especially adiponectin are inconsistent however leptin and IL-6 have being consistent. Adipokine release measured from adipose tissues reflects a more physiologic state and the characteristics of the subjects compared to cultured cells. Adiponectin is an insulin sensitizing protein, exclusively produced by mature adipocytes and highly secreted by adipose tissue. The native adiponectin exists as low molecular weight, middle-molecular weight and high molecular weight (HMW).The potency of adiponectin is linked to the HMW isoform. There are no previous reports on secretion of HMW adiponectin from human omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues. In this study the goal is to determine the depot differences in Adrx expression and adipokine release in human Abdsc and Om adipose tissue in obese and morbidly obese subjects, mostly females and to determine the relationship between Adrx protein expression and adipokine release in Abdsc versus Om and circulating levels of adipokines, primarily total and HMW adiponectin. To clarify whether Adrx expression is implicated in the release and secretion of circulating adipokines. Adrx protein levels (assessed by Western blot) were ~1.4 fold higher in Abdsc than Om (p<0.05; paired t-test values). As expected, secretion per gram of tissue in 3hr incubation of total adiponectin (~ 25%) and leptin (~50%) was higher, and IL-6 secretion was lower (~30%) in Abdsc compared to Om. In western blot, total adiponectin is higher in Abdsc compared to Om. However, HMW adiponectin and % HMW are higher in Om. Adrx protein levels were positively correlated with total adiponectin and HMW release in Abdsc and only with HMW in Om. Adrx levels were negatively correlated with % HMW in Abdsc but not in Om. Adrx protein levels in Abdsc showed a negative trend with total adiponectin circulating levels (ng/ml measured by ELISA) and a positive trend in Om. However, total adiponectin by Western Blot showed a positive trend with Adrx levels in both Abdsc and Om. HMW adiponectin levels tended to be slightly positive with Adrx levels in Abdsc and Om. However, the percent of HMW adiponectin levels are not correlated with Adrx levels in either tissues. Since in Adrx KO mice found that presented lower total adiponectin in circulation, it was hypothesized that Adrx were positively correlated with circulating adiponectin, and wanted to study the correlation with serum adipokines. However, none of the correlations with Adrx and adipokines in serum were statistically significant. These data suggest that depot differences in Adrx expression may influence depot differences in adipokine secretion. The mechanism of higher HMW adiponectin secretion in Om with low Adrx levels needs further study

From Kiruna to Giron

This independent project addresses the decolonization of the Kiirunavaara Mine’s landscape post-closure, focusing on landscape remediation, reclamation, and rehabilitation guided by Sami perspectives to promote the return of the ecosystem services, focusing on reindeer herding. Indigenous communities have the right to self-determination and deserve the restoration of their lands. This project serves as an example of decolonization and sets a precedent for land rehabilitation as other mines across Sweden close. The project identifies a research gap due to limited literature on the decolonization of mines and the return of land to indigenous peoples. It specifically explores how the decolonization of the Laevas and Gabna Sami Villages' winter pastures, encroached by the Kiirunavaara mine, could be achieved. To address these objectives, the research includes a comprehensive literature review on the historical and physical context of the area, theories on decolonization and sense of place, and the Sami concept of meahcci to start understanding their perspective on the landscape. Site analysis through visits and mapping exercises, along with art analysis of Duodji, roughly translated to Sami art, further inform the project. The outcome is a conceptual proposal integrating remediation, reclamation, and rehabilitation practices, presented through three consecutive scenarios spaced 15 years apart, representing the transition from Kiruna to Giron. Key findings highlight the importance of participation and community involvement in the decolonization process, which spans decades. The project reflects an understanding of landscape decolonization through traditional Sami knowledge, learned from Sami sources, and Sami art analysis, extended to the landscape design. However, it acknowledges limitations, particularly the absence of direct Sami participation, which is a significant gap in the research and design process. In conclusion, this thesis proposes a design solution for the remediation of the Kiirunavaara mine and calls for broader recognition and respect for the Sami's cultural and environmental rights. By reimagining Kiruna as Giron, the project aims to heal the land and restore the cultural heritage of the Sami people, offering a path toward reconciliation and a new sense of place

Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics.

We demonstrate the first integrated microfluidic tmRNA purification and nucleic acid sequence-based amplification (NASBA) device incorporating real-time detection. The real-time amplification and detection step produces pathogen-specific response in < 3 min from the chip-purified RNA from 100 lysed bacteria. On-chip RNA purification uses a new silica bead immobilization method. On-chip amplification uses custom-designed high-selectivity primers and real-time detection uses molecular beacon fluorescent probe technology; both are integrated on-chip with NASBA. Present in all bacteria, tmRNA (10Sa RNA) includes organism-specific identification sequences, exhibits unusually high stability relative to mRNA, and has high copy number per organism; the latter two factors improve the limit of detection, accelerate time-to-positive response, and suit this approach ideally to the detection of small numbers of bacteria. Device efficacy was demonstrated by integrated on-chip purification, amplification, and real-time detection of 100 E. coli bacteria in 100 microL of crude lysate in under 30 min for the entire process