Expression in Escherichia coli of a cloned DNA sequence encoding the pre-S2 region of hepatitis B virus

A DNA sequence encoding the entire pre-S2 region (amino acids 120-174; serotype ayw) of human hepatitis B virus envelope protein has been inserted into the lacZ gene of the plasmid pSKS105 yielding a recombinant, pWS3. Lac+ colonies of the Escherichia coli M182 (lacIOPZYA), isolated after transformation with pWS3, produced a pre-S2 peptide-ß-galactosidase fusion protein. This fusion protein, which comprised as much as 3% of the total bacterial protein, was purified to >90% homogeneity by affinity chromatography on p-aminophenyl-ß-D-thiogalactoside-Sepharose. It is immunoprecipitable with rabbit antibodies to a synthetic peptide corresponding to amino acids 120-145 of the pre-S2 region of serotype adw [pre-S(120-145)] or with antibodies to hepatitis B virus. pre-S(120-145) completely blocked the binding of either antibody to the pre-S2 peptide-ß-galactosidase fusion protein. These results indicate that there are antigenic determinants on the fusion protein that are closely related to, if not identical to, determinants on synthetic pre-S(120-145) and on pre-S2 sequences of native hepatitis B virus particles. Thus, bacteria transformed with pWS3 can provide an abundant source of pre-S2-ß-galactosidase fusion protein, which may prove useful either as a diagnostic reagent possessing marker enzyme activity suitable for ELISA tests or as an immunogen with potential to contribute to active prophylaxis of hepatitis B

Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma

Patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) are treated with salvage regimens and may be considered for high-dose chemotherapy and autologous stem cell transplantation if disease is chemosensitive. Bendamustine is active in indolent B cell lymphomas and chronic lymphocytic leukemia but has not been extensively studied in aggressive lymphomas. This trial examines the combination of bendamustine and rituximab in patients with relapsed and refractory DLBCL. Patients received bendamustine at 90 mg/m2 (n = 2) or 120 mg/m2 (n = 57) on days 1 and 2 and rituximab at 375 mg/m2 on day 1 every 28 days for up to 6 cycles. The study evaluated objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and treatment safety. Fifty-nine patients were treated, and 48 were evaluable for response. Median age was 74; 89 % had stage III or IV disease, and 63 % had high revised International Prognostic Index scores; the median number of prior therapies was 1. Based on analysis using the intent-to-treat population, the ORR was 45.8 % (complete response, 15.3 %; partial response, 30.5 %). The median DOR was 17.3 months, and the median PFS was 3.6 months. Grade 3 or 4 hematological toxicities included neutropenia (36 %), leukopenia (29 %), thrombocytopenia (22 %), and anemia (12 %). The combination of bendamustine and rituximab showed modest activity in patients with relapsed and refractory DLBCL and has an acceptable toxicity profile

Financial Stress Interacts With CLOCK Gene to Affect Migraine.

Previous studies suggested that both maladaptive stress response and circadian dysregulation might have a role in the background of migraine. However, effects of circadian genes on migraine have not been tested yet. In the present study, we investigated the main effect of rs10462028 of the circadian locomotor output cycles kaput (CLOCK) gene and its interaction with different stress factors on migraine. In our cross-sectional study 2,157 subjects recruited from Manchester and Budapest completed the ID-Migraine questionnaire to detect migraine type headaches (migraineID). Additional stress factors were assessed by a shortened version of the Childhood Trauma Questionnaire, the List of Threatening Experiences questionnaire, and a validated questionnaire to identify financial difficulties. Rs10462028 showed no main genetic effect on migraineID. However, chronic stress indexed by financial difficulties showed a significant interaction effect with rs10462028 (p = 0.006 in recessive model) on migraineID. This result remained significant after correction for lifetime bipolar and unipolar depression and was replicated in both subsamples, although only a trend effect was reached after Bonferroni-correction, which is the strictest correction not considering interdependences. Childhood adversity (CHA) and Recent negative life events (RLE) showed no significant gene × stress interaction with rs10462028. In addition, in silico analysis demonstrated that the genetic region tagged by rs10462028 alters the binding of several miRNAs. Our exploratory study suggests that variations in the CLOCK gene, with moderating effect on gene function through miRNA binding, in interaction with financial difficulties might influence the risk of migraine-type headaches. Thus, financial hardship as a chronic stress factor may affect migraine through altering circadian rhythms

Comparative assessment of subsipopulations of tumor-associated macrophages in breast cancer depending on the response to chemotherapy

The key cells of the immune system that determine the relationship between tumor cells and the microenvironment, beginning with early stages of tumor growth, including regulation of neoangiogenesis and the terminal stage of malignant process, are tumor-associated macrophages (TAM). In the present study, identification of TAM markers in breast tumors in patients with neoadjuvant chemotherapy and a comparative assessment of the differences in the macrophages subpopulation in tumors with different response to chemotherapy were carried out. The data we obtained indicate the functional differences between TAM subpopulations that have various phenotypes, that are confirmed at the level of associative links with the effectiveness of chemotherapy

Modelling innovation support systems for regional development - analysis of cluster structures in innovation in Portugal

The present article offers a concise theoretical conceptualization and operational analysis of the contribution of innovation to regional development. The latter concepts are closely related to geographical proximity, knowledge diffusion and filters and clustering. Institutional innovation profiles and regional patterns of innovation are two mutually linked, novel conceptual elements in this article. Next to a theoretical framing, the article employs the regional innovation systems concept as a vehicle to analyse institutional innovation profiles. Our case study addresses three Portuguese regions and their institutions, included in a web-based inventory of innovation agencies which offered the foundation for an extensive database. This data-set was analysed by means of a recently developed principal coordinates analysis followed by a Logistic Biplot approach (leading to a Voronoi mapping) to design a systemic typology of innovation structures where each institution is individually represented. There appears to be a significant difference in the regional innovation patterns resulting from the diverse institutional innovation profiles concerned. These profiles appear to be region specific. Our conclusion highlights the main advantages in the use of the method used for policy-makers and business companies.info:eu-repo/semantics/publishedVersio

Knowledge and innovation: The strings between global and local dimensions of sustainable growth

The modern growth literature pays much attention to innovation and knowledge as drivers of endogenous developments in a competitive open economic system. This paper reviews concisely the literature in this field and addresses in particular micro- and macro-economic interactions at local or regional levels, based on clustering and networking principles, in which sustainability conditions also play a core role. The paper then develops a so-called knowledge circuit model comprising the relevant stakeholders, which aims to offer a novel framework for applied policy research at the meso-economic level

Firm-size distribution and price-cost margins in Dutch manufacturing

Industrial economists surmise a relation between the size distribution of firms and performance. Usually, attention is focused on the high end of the size distribution. The widely used 4-firm seller concentration, C4, ignores what happens at the low end of the size distribution. An investigation is presented of the extent to which the level and the growth of small business presence influence price-cost margins in Dutch manufacturing. A large data set of 66 industries for a 13-year period is used. This allows the investigation of both small business influences within a framework in which that of many other market structure variables is also studied. Evidence is shown that price-cost margins are influenced by large firm dominance, growth in small business presence, capital intensity, business cycle, international trade, and buyer concentration

The entrepreneurial ladder, gender, and regional development

Gender differences at five levels of entrepreneurial engagement are explained using country effects while controlling for individual-level variables. We distinguish between individuals who have never considered starting up a business, those who are thinking about it, and nascent, young, and established entrepreneurs. We use a large international dataset that includes respondents from 32 European countries, three Asian countries, and the United States. Findings show that cross-country gender differences are largest in the first and final transitions of the entrepreneurial process. In par

Macrocheles species (Acari: Macrochelidae) associated with human corpses in Europe

The biology of macrochelid mites might offer new venues for the interpretation of the environmental conditions surrounding human death and decomposition. Three human corpses, one from Sweden and two from Spain, have been analysed for the occurrence of Macrochelidae species. Macrocheles muscaedomesticae females were associated with a corpse that was found in a popular beach area of southeast Spain. Their arrival coincides with the occurrence of one of their major carrier species, the filth fly Fannia scalaris, the activity of which peaks during mid-summer. M. glaber specimens were collected from a corpse in a shallow grave in a forest in Sweden at the end of summer, concurrent with the arrival of beetles attracted by odours from the corpse. M. perglaber adults were sampled from a corpse found indoors in the rural surroundings of Granada city, Spain. The phoretic behaviour of this species is similar to that of M. glaber, but being more specific to Scarabaeidae and Geotrupidae dung beetles, most of which favour human faeces. M. muscaedomesticae is known from urban and rural areas and poultry farms; M. glaber from outdoors, particularly the countryside; while M. perglaber from outdoor, rural, and remote, potentially mountainous locations. M. muscaedomesticae and M. perglaber are reported for the first time from the Iberian Peninsula. This is the first record of M. perglaber from human remains