Examining effectiveness of an immigrant labor market integration intervention. The role of acculturation, discrimination, self-efficacy, outcome expectances, action and coping planning.

The designing of effective intervention tools to improve immigrants’ labor market integration remains an important topic in contemporary Western societies. This study examines whether and how a new intervention tool, Working Life Certificate (WLC), helps unemployed immigrants to find employment and strengthen their belief of their vocational skills. The study is based on quantitative longitudinal survey data from 174 unemployed immigrants of various origins who participated in the pilot phase of WLC examinations in 2009. Surveys were administered in three waves: before the test, right after it, and three months later. Although it is often argued that the unemployment among immigrants is due either to their lack of skills and cultural differences or to discrimination in recruitment, scholars within social psychology of behavior change argue that the best way of helping people to achieve their goals (e.g. finding employment) is to build up their sense of self-efficacy, alter their outcome expectances in a more positive direction or to help them to construct more detailed action and coping plans. This study aims to shed light on the role of these concepts in immigrants’ labor market integration. The results support the theories of behavior change moderately. Having positive expectances regarding the outcomes of various job search behaviors was found to predict employment in the future. Together with action and coping planning it also predicted increase in job search behavior. The intervention, WLC, was able to affect participants’ self-efficacy, but contrary to expectations, self-efficacy was found not to be related to either job search behavior or future labor market status. Also, perceived discrimination did not explain problems in finding employment, but hints of subtle or structural discrimination were found. Adoption of Finnish work culture together with strong family culture was found to predict future employment. Hence, in this thesis I argue that awarding people diplomas should be preferred in immigrant integration training as it strengthens people’s sense of self-efficacy. Instead of teaching new information, more attention should be directed at changing people’s outcome expectances in a more positive direction and helping them to construct detailed plans on how to achieve their goals.

Mode of action of antitumour antibiotics-III: Modulation of permeability of nuclear membrane in the presence of the antibiotics

The binding characteristics of the antibiotics to nuclei and their effect on the permeability of nuclear membrane with respect to histones and ribonucleic acids have been investigated. The binding constant for chromomycin A3 was found to be 1.4 × 104M?1 and number of binding sites was equal to 3.48 ± 1.08 × 1012 molecules/nuclei. The antibiotic chromomycin A3 enhanced the uptake of lysine-rich histone, actinomycin D decreased the uptake and ethidium bromide had no effect. Chromomycin A3 also enhanced the release of acid insoluble fraction containing RNA from the nuclei, actinomycin D and ethidium bromide inhibited the release of acid insoluble fraction containing RNA. The relevance of this finding to the role of nuclear envelope in understanding the mechanism of action of the antibiotic has been discussed.

Chemistry in Confined Spaces: High-Energy Conformer of a Piperidine Derivative is Favored Within a Water-Soluble Capsuleplex

Propyloxy-substituted piperidine in solution adopts a conformation in which its alkoxy group is equatorially positioned Surprisingly, two conformers of it that do not interconvert in the NMR time scale at room temperature have been found within an octa-acid capsule The serendipitous finding of the axial conformer of propyloxy-substituted piperidine within a supramolecular capsule highlights the value of confined spaces in physical organic chemistry.

Protein Kinase C and Anaplastic Lymphoma Kinase Targeted Compounds

The protein kinases (PKs) belong to the largest single family of enzymes, phosphotransferases, which catalyze the phosphorylation of other enzymes and proteins and function primarily in signal transduction. Consequently, PKs regulate cell mechanisms such as growth, differentiation, and proliferation. Dysfunction of these cellular mechanisms may lead to cancer, a major predicament in health care. Even though there is a range of clinically available cancer-fighting drugs, increasing number of cancer cases and setbacks such as drug resistance, constantly keep cancer research active. At the commencement of this study an isophthalic acid derivative had been suggested to bind to the regulatory domain of protein kinase C (PKC). In order to investigate the biological effects and structure-activity relationships (SARs) of this new chemical entity, a library of compounds was synthesized. The best compounds induced apoptosis in human leukemia HL-60 cells and were not cytotoxic in Swiss 3T3 fibroblasts. In addition, the best apoptosis inducers were neither cytotoxic nor mutagenic. Furthermore, results from binding affinity assays of PKC isoforms revealed the pharmacophores of these isophthalic acid derivatives. The best inhibition constants of the tested compounds were measured to 210 nM for PKCα and to 530 nM for PKCδ. Among natural compounds targeting the regulatory domain of PKC, the target of bistramide A has been a matter of debate. It was initially found to activate PKCδ; however, actin was recently reported as the main target. In order to clarify and to further study the biological effects of bistramide A, the total syntheses of the natural compound and two isomers were performed. Biological assays of the compounds revealed accumulation of 4n polyploid cells as the primary mode of action and the compounds showed similar overall antiproliferative activities. However, each compound showed a distinct distribution of antimitotic effect presumably via actin binding, proapoptotic effect presumably via PKCδ, and pro-differentiation effect as evidenced by CD11b expression. Furthermore, it was shown that the antimitotic and proapoptotic effects of bistramide A were not secondary effects of actin binding but independent effects. The third aim in this study was to synthesize a library of a new class of urea-based type II inhibitors targeted at the kinase domain of anaplastic lymphoma kinase (ALK). The best compounds in this library showed IC50 values as low as 390 nM for ALK while the initial low cellular activities were successfully increased even by more than 70 times for NPM-ALK- positive BaF3 cells. More importantly, selective antiproliferative activity on ALK-positive cell lines was achieved; while the best compound affected the BaF3 and SU-DHL-1 cells with IC50 values of 0.5 and 0.8 μM, respectively, they were less toxic to the NPM-ALK-negative human leukemic cells U937 (IC50 = 3.2 μM) and BaF3 parental cells (IC50 = 5.4 μM). Furthermore, SAR studies of the synthesized compounds revealed functional groups and positions of the scaffold, which enhanced the enzymatic and cellular activities.

Computer modelling studies on the mechanism of action of ribonuclease T1

The mechanism of action of ribonuclease (RNase) T1 is still a matter of considerable debate as the results of x-ray, 2-D nmr and site-directed mutagenesis studies disagree regarding the role of the catalytically important residues. Hence computer modelling studies were carried out by energy minimisation of the complexes of RNase T1 and some of its mutants (His40Ala, His40Lys, and Glu58Ala) with the substrate guanyl cytosine (GpC), and of native RNase T1 with the reaction intermediate guanosine 2',3'-cyclic phosphate (G greater than p). The puckering of the guanosine ribose moiety in the minimum energy conformer of the RNase T1-GpC (substrate) complex was found to be O4'-endo and not C3'-endo as in the RNase T1-3'-guanylic acid (inhibitor/product) complex. A possible scheme for the mechanism of action of RNase T1 has been proposed on the basis of the arrangement of the catalytically important amino acid residues His40, Glu58, Arg77, and His92 around the guanosine ribose and the phosphate moiety in the RNase T1-GpC and RNase T1-G greater than p complexes. In this scheme, Glu58 serves as the general base group and His92 as the general acid group in the transphosphorylation step. His40 may be essential for stabilising the negatively charged phosphate moiety in the enzyme-transition state complex.

Oxidation Of Spiroalcohols With 2,3-Dichloro-5,6-Dicyano-1,4-Benzoquinone (Ddq) .4. Structure Of A Novel Dioxepin Derivative

DDQ oxidation of the spiroalcohol 7a gives exclusively a compound to which the 13a-methyl-13aH-7a, 15-methano-15H-dinaphtho[2,1-b:2',1'-e][1,4]-dioxepin structure 8a has been assigned on the basis of two-dimensional homonuclear (H-1-H-1) and heteronuclear (H-1-C-13; FUCOUP) correlation spectroscopy experiments. Similar oxidation of spiroalcohols 7b-h gives the dioxepin derivatives 8b-h.