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Enzymatic action of human glandular kallikrein 2 (hK2) substrate specificity and regulation by Zn2+ and extracellular protease inhibitors

Human glandular kallikrein 2 (hK2) is a serine protease expressed by the prostate gland with 80% identity in primary structure to prostate-specific antigen (PSA). Recently, hK2 was shown to activate the zymogen form of PSA (proPSA) in vitro and is likely to be the physiological activator of PSA in the prostate, hK2 is also able to activate urokinase and effectively cleave fibronectin. We studied t

Status Quo Bias and Hidden Condorcet Cycles in Binary Referendums

In most real-life binary referendums, there are several alternatives that potentially can challenge the status quo alternative. Depending on which alternative that is selected, the voters are also differently likely to caste their vote on it. The fact that there are several potential challenger alternatives also means that there may exist Condorcet cycles that only can be identified by taking into

Aminopeptidase activities as prospective urinary biomarkers for bladder cancer

Purpose: Proteases have been implicated in cancer progression and invasiveness. We have investigated the activities, as opposed to simple protein levels, of selected aminopeptidases in urine specimens to serve as potential novel biomarkers for urothelial cancer. Experimental design: The unique urinary proteomes of males and females were profiled to establish the presence of a gender-independent se

TMPRSS2-ERG Status in circulating tumor cells as a predictive biomarker of sensitivity in castration-resistant prostate cancer patients treated with abiraterone acetate

Background: Abiraterone acetate (AA) is an androgen biosynthesis inhibitor shown to prolong life in patients with castration-resistant prostate cancer (CRPC) already treated with chemotherapy. AA treatment results in dramatic declines in prostate-specific antigen (PSA) in some patients and no declines in others, suggesting the presence of molecular determinants of sensitivity in tumors. Objective:

Enzymatic activation of a doxorubicin-peptide prodrug by prostate- specific antigen

New approaches to target cytotoxic therapy specifically to metastatic prostate cancer sites are urgently needed. As such an approach, an inactive prodrug was synthesized by coupling the primary amine of doxorubicin to the COOH-terminal carboxyl of a seven-amino acid peptide carrier (i.e., Mu-His- Ser-Ser-Lys-Leu-Gln-Leu). The seven-amino acid peptide was documented to be hydrolyzable specifically

Ti thin films deposited by high-power impulse magnetron sputtering in an industrial system: Process parameters for a low surface roughness

The influence of the choice of process parameters in an industrial high-power impulse magnetron sputtering (HiPIMS) system on the surface roughness and crystallinity of Ti coatings is presented in this work. A current density of 1 A/cm2 was kept constant by varying the pulse frequency to control the average power. The films were characterised by scanning electron microscopy, atomic force microscop

A "giant furrow" or a "way to economic prosperity"? A conflict in the meaning of environmental sustainability - the case of Rail Baltica mega-project

This thesis examines the conflict situation that has emerged around the environmental discourse in the planning process of a railway mega-project in Estonia. A discourse analysis is carried out on policy documents, publications, and interviews following Laclau and Mouffe’s discourse theory and methodological guidelines, to examine the ways that the concept of sustainability conflicts between stake

The impact of planetary urbanization on the citizen’s everyday life

The Chinese government has been working on the Belt and Road Initiative (BRI) for the past 20 years to further its goal of expanding global hegemony. It attempts to increase its economic and political influence in the BRI destinations through several projects and six main corridors. These initiatives, in my opinion, have a significant impact on transforming the urban landscape. Considering that mo

Surface Guided Helical Tomotherapy for Total Marrow Irradiation

Leukemi kallas ibland blodcancer för att det drabbar de vita blodkropparna. I själva verket uppstår cancersjukdomen i de blodbildande organen, främst benmärgen och mjälten. Cellgiftsbehandling är den främsta behandlingstekniken men för patienter med hög risk för sjukdomsåterfall kan stamcellstransplantation vara aktuellt som del i behandlingen som ges i kombination med strålbehandling. StrålbehandBackground: Total marrow irradiation (TMI) with helical tomotherapy treatment (HT-TMI) can be used as conditioning regimen for leukemia patients prior to stem cell transplantation by radiating the skeletal tissue. To ensure adequate dose coverage a margin is applied to the clinical target volume (CTV), i.e. planning target volume (PTV) margin. By applying as small margin as possible the dose to or

Polymer gel dosimetry - Using MRI-readout, simplified relatively non-toxic mixing procedure tested on FLASH

Background: One of the polymer gel dosimeters available today is the N-isopropylamide (NIPAM) polymer gel dosimeter which has a less toxic monomer compared to other polymer gels and the advantage of being able to be manufactured under normal oxygen levels. Polymer gel dosimeters in general are advantageous independent dosimeters to use for verification of new radiation treatment techniques due to

The Memorial Sloan Kettering Cancer Center Recommendations for Prostate Cancer Screening

The Memorial Sloan Kettering Cancer Center (MSKCC) recommendations on prostate cancer screening were developed in response to three limitations of previous screening guidelines: insufficient evidence base, failure to link screening with treatment, and lack of risk stratification. The objective of the recommendations is to provide a schema for prostate cancer screening that maximizes the benefits,

Pesticide exposure and cortical brain activation among farmworkers in Costa Rica

Background: Previous epidemiological studies have reported associations of pesticide exposure with poor cognitive function and behavioral problems. However, these findings have relied primarily on neuropsychological assessments. Questions remain about the neurobiological effects of pesticide exposure, specifically where in the brain pesticides exert their effects and whether compensatory mechanism

Pharmacokinetics of terlipressin after single i.v. doses to healthy volunteers.

The pharmacokinetics of triglycyl-lysine-vasopressin (TGLVP) were studied in healthy male volunteers after single i.v. injections of 5, 10 and 20 micrograms/kg b. wt. The half-life of distribution and elimination was 8 and 50 min, respectively. The volume of distribution was 0.7 l/kg b.wt. and the plasma clearance 9 ml/kg b.wt./min. These values are different from those for arginine-vasopressin an

An empirical evaluation of guidelines on prostate-specific antigen velocity in prostate cancer detection

Background The National Comprehensive Cancer Network and American Urological Association guidelines on early detection of prostate cancer recommend biopsy on the basis of high prostate-specific antigen (PSA) velocity, even in the absence of other indications such as an elevated PSA or a positive digital rectal exam (DRE). Methods To evaluate the current guideline, we compared the area under the cu

An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality

Genome-wide association studies have identified multiple single-nucleotide polymorphsims (SNPs) associated with prostate cancer (PCa). Although these SNPs have been clearly associated with disease risk, their relationship with clinical outcomes is less clear. Our aim was to assess the frequency of known PCa susceptibility alleles within a single institution ascertainment and to correlate risk alle

“Dizziness of Freedom” : Anxiety Disorders and Metaphorical Meaning-making

Would metaphors used in the context of psychotherapy by people who experience various forms of anxiety disorders differ from those used by people who experience stress? We investigated this question with the help of the Motivation & Sedimentation Model (MSM), a theory of meaning-making developed within the synthetic new discipline of cognitive semiotics. The analysis of a sample of ten transcr

Specific and efficient peptide substrates for assaying the proteolytic activity of prostate-specific antigen

Prostate-specific antigen (PSA) is a serine protease secreted by hath normal prostate glandular celts and prostate cancer cells. The major proteolytic substrates for PSA are the gel-forming proteins in semen, semenogelin (Sg) I and II. On the basis of the PSA cleavage map for Sg I and II, a series of small peptides (ie., ≤ 7 amino acids) was synthesized and coupled at the COOH terminus to 7-amino-

Evaluating the PCPT risk calculator in ten international biopsy cohorts : Results from the Prostate Biopsy Collaborative Group

Objectives: To evaluate the discrimination, calibration, and net benefit performance of the Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) across five European randomized study of screening for prostate cancer (ERSPC), 1 United Kingdom, 1 Austrian, and 3 US biopsy cohorts. Methods: PCPTRC risks were calculated for 25,733 biopsies using prostate-specific antigen (PSA), digital rectal exa

Prognostic accuracy of head computed tomography for prediction of functional outcome after out-of-hospital cardiac arrest : Rationale and design of the prospective TTM2-CT-substudy

Background: Head computed tomography (CT) is a guideline recommended method to predict functional outcome after cardiac arrest (CA), but standardized criteria for evaluation are lacking. To date, no prospective trial has systematically validated methods for diagnosing hypoxic-ischaemic encephalopathy (HIE) on CT after CA. We present a protocol for validation of pre-specified radiological criteria

A qualitative case study examining individuals’ perceptions of mode choice and the possibility to reduce car mileage for everyday leisure trips

In the transition to more sustainable travel behaviour, there is a need to reduce car mileage for all sorts of trips including everyday leisure trips for social and recreational purposes. In this case study, qualitative interviews were conducted to improve and deepen the understanding of transport mode choice for such trips. The analyses of factors affecting mode choice for everyday leisure purpos