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Background Anthracyclines are effective chemotherapeutic agents commonly used in breast cancer (BC) treatment. Cardiotoxicity is a serious adverse effect of anthracyclines, but knowledge of long-term cardiac effects is limited. To our knowledge, no prior study has investigated both cardiorespiratory fitness assessed by peak oxygen consumption (V̇O2 peak) and left ventricular (LV) function in long-term follow up of BC survivors (BCS) treated with anthracyclines. Purpose To assess long-term adverse effects of Epirubicin on cardiorespiratory fitness and LV function in BCS. Methods The CAUSE-trial is an ongoing study comparing exercise effects in BCS of stage I-III BC recruited from the Cancer Registry of Norway and controls with no cancer diagnosis. We present preliminary results from the baseline assessments in this trial. BCS (n=93) treated with Epirubicin between 2008 and 2013 were compared to age-matched controls (n=11). V̇O2 peak was assessed by incremental treadmill cardiopulmonary exercise test and LV function by echocardiography. Results At baseline, BCS were 58±7 years old and had received a cumulative dose of 339±85 mg/m2 Epirubicin 11±1 years before examination. There was no difference in V̇O2 peak between BSC and controls. LV ejection fraction was lower in BCS compared to controls assessed by 2D (57±3% vs. 59±2%, p=0.01) and 3D echocardiography (57±3% vs. 61±4%, p=0.006). LV global longitudinal strain was also lower (in absolute value) in BCS compared to controls (−20.6±1.3% vs. −22.0±1.3%, p=0.002). There was no difference in global work index and efficiency between BCS and controls. Conclusion Our findings indicate no difference in cardiorespiratory fitness between BCS and controls a decade after Epirubicin treatment. Systolic LV function was slightly lower in BCS compared to controls. Importantly, systolic LV function in BCS was within normal range, and the difference is probably not of clinical importance. There was no difference in myocardial work between BCS and controls. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Cancer Registry of Norway

A survey was undertaken regarding the extent to which optical radiation is used in cosmetic treatments and the compliance with national regulations. Questionnaires were sent to 65 clinics, and 23 of these were later inspected. Only one of 41 class 4 lasers had been reported to the authorities according to the regulations prior to the survey. Among sources other than lasers, intense pulsed light (IPL) sources were the most frequent. Although qualified health personnel should be in charge of the treatment, it was observed that 30% of the clinics did not fulfil this requirement. Deviations with respect to personnel training, availability of written procedures, protective equipment and warning signs were frequently observed. The results give rise to concern about the safety of patients and employees.

The understanding of self–assembly and bonding mechanisms of organic molecules on semiconductor surfaces represents a central research aspect in the investigation of novel organic/inorganic interfaces and their technological applicability. Here, we investigated the adsorption and bond formation of cyclopentene and 1,4-cyclohexadiene on a GaAs(001)- c(4 × 4) surface in order to clarify the influence of the number of intra-molecular C=C double bonds on the respective adsorption sites. For a determination of the adsorption configuration, the interfaces were characterized electronically and optically by synchrotron based X-ray photoelectron spectroscopy (SXPS), low energy electron diffraction (LEED) and reflectance anisotropy spectroscopy (RAS). The results reveal significantly different adsorption configurations for the two molecules. While cyclopentene bonds with a single covalent bond to the surface, 1,4-cyclohexadiene adsorbs onto the surface by the formation of multiple covalent bonds, e.g. bridge bonds. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

This thesis covers a wide field of applications, with an emphasis on applications of reflectance spectroscopy for diagnostic purposes. Reflectance spectroscopy in the visible part of the spectrum has been proved to be a valuable tool in a variety of applications including e. g. port-wine stain diagnostics, diagnostics of liver pathology, neonatal jaundice and age determination of bruises for forensic applications.

Androgen deprivation therapy (ADT) improves life expectancy in prostate cancer (PCa) patients, but is associated with adverse effects on muscle mass. Here, we investigated the effects of strength training during ADT on muscle fiber cross-sectional area (CSA) and regulators of muscle mass. PCa patients on ADT were randomized to 16 weeks of strength training (STG) (n = 12) or a control group (CG; n = 11). Muscle biopsies were obtained from m. vastus lateralis and analyzed by immunohistochemistry and western blot. Muscle fiber CSA increased with strength training (898 μm(2) , P = 0.04), with the only significant increase observed in type II fibers (1076 μm(2) , P = 0.03). There was a trend toward a difference in mean change between groups myonuclei number (0.33 nuclei/fiber, P = 0.06), with the only significant increase observed in type I fibers, which decreased the myonuclear domain size of type I fibers (P = 0.05). Satellite cell numbers and the content of androgen receptor and myostatin remained unchanged. Sixteen weeks of strength training during ADT increased type II fiber CSA and reduced myonuclear domain in type I fibers in PCa patients. The increased number of satellite cells normally seen following strength training was not observed.

Underwater friction stud welding (FRSW) without a shroud around the stud requires controlling welding parameters to achieve optimal joint strength. A hydraulic FRSW unit has been designed and fabricated to perform FRSW without a shroud via a remotely operated underwater vehicle (ROV). An experimental study has been initiated to investigate the optimal FRSW parameter combinations and corresponding values leading to optimal ultimate tensile load capacity (UTLC) values in the welded joint. The engineering robust design (ERD) approach has been deployed to run the experiment. Each weld has been made with a S355 M12 stud on S355 structural steel plate. This paper discusses the experimental approach, results and conclusions reached in the parameter evaluation, estimation, and experimentation.

This study investigated the expression of ion transporters involved in intestinal fluid absorption and presents evidence for developmental changes in abundance and tissue distribution of these transporters during smoltification and seawater (SW) acclimation of Atlantic salmon Salmo salar. Emphasis was placed on Na(+) , K(+) -ATPase (NKA) and Na(+) , K(+) , Cl(-) co-transporter (NKCC) isoforms, at both transcriptional and protein levels, together with transcription of chloride channel genes. The nka α1c was the dominant isoform at the transcript level in both proximal and distal intestines; also, it was the most abundant isoform expressed in the basolateral membrane of enterocytes in the proximal intestine. This isoform was also abundantly expressed in the distal intestine in the lower part of the mucosal folds. The protein expression of intestinal Nkaα1c increased during smoltification. Immunostaining was localized to the basal membrane of the enterocytes in freshwater (FW) fish, and re-distributed to a lateral position after SW entry. Two other Nka isoforms, α1a and α1b, were expressed in the intestine but were not regulated to the same extent during smoltification and subsequent SW transfer. Their localization in the intestinal wall indicates a house-keeping function in excitatory tissues. The absorptive form of the NKCC-like isoform (sub-apically located NKCC2 and/or Na(+) , Cl(-) co-transporter) increased during smoltification and further after SW transfer. The cellular distribution changed from a diffuse expression in the sub-apical regions during smoltification to clustering of the transporters closer to the apical membrane after entry to SW. Furthermore, transcript abundance indicates that the mechanisms necessary for exit of chloride ions across the basolateral membrane and into the lateral intercellular space are present in the form of one or more of three different chloride channels: cystic fibrosis transmembrane conductance regulator I and II and chloride channel 3.

The duration of hypo-osmoregulatory capacity in downstream migrating Atlantic salmon Salmo salar L smolts previously stocked as startfed young-of-the year (YOY) parr was tested in the River Dalåa from mid-May to late-June 1999. Hypo-osmoregulatory capacity, measured as plasma osmolality and chloride, was assessed after seawater (SW) challenge tests (168 h, salinity = 35). All S. salar exhibited sufficient hypo-osmoregulatory capacity at the initiation of downstream migration in mid-May. Migrating S. salar smolts caught in mid-May and retained in fresh water displayed no signs of de-smoltification as they maintained hypo-osmoregulatory capacity through June. This indicates a physiological smolt window that lasts a minimum of 6 weeks (330 degree days; D°) for hatchery-produced S. salar smolts stocked as YOY parr. Based on the observed river migration speeds, it can be assumed that the S. salar smolts entered SW 2-4 weeks after initiation of migration in the upper parts of the River Dalåa. Hence, based on smolt migration and SW tolerance, it is suggested that stocking of YOY parr is a viable enhancement strategy in the River Dalåa.

Crack formation is a serious defect that may reduce the lifetime of unfinished wood in service. An accelerated weathering test was carried out to study crack formation of solid wood board specimens of aspen (Populus tremula L.) and Norway spruce (Picea abies (L.) Karst.). The influence of the boards' distance from the pith was also studied. The aspen specimens developed a higher number of cracks than the spruce specimens. However, these cracks were shorter and less injurious than those propagating in spruce wood. It is concluded that a solid wood siding of aspen will show at least as good a performance as spruce regarding crack injuries. For both aspen and spruce, boards taken from near the pith had a lower proportion of long cracks than boards taken further out. This supports the rule that boards with a high proportion of annual rings perpendicular to the surface (the boards near to the pith) have a higher resistance to crack formation than boards with a high proportion of horizontal annual rings.

In order to investigate how changes in gill Na(+) , K(+) -ATPase (NKA) α1a and α1b subunits, Na(+) , K(+) , 2Cl(-) co-transporter (NKCC1) and the apical cystic fibrosis trans-membrane conductance regulator-I (CFTR-I) transcripts in wild strain of Atlantic salmon, Salmo salar, smolts are affected by temperature during spring, hatchery-reared parr (mean ± s.e. fork length = 14·1 ± 0·5; mean ± s.e. body mass = 28·5 ± 4·5 g) originating from broodstock from the Vosso river (western Norway) were acclimated to three temperature regimes (4·1, 8·1 and 12·9° C) in May and reared under gradually increasing salinity between May and June. Changes in plasma Na(+) , haematocrit (Hct) and PCO2 were monitored in order to assess and compare key physiological changes with the transcriptional changes in key ion transporters. The temperatures reflect the natural temperature range in the River Vosso during late spring. Overall, higher gill NKA α1b mRNA levels, gill NKCC1a levels and CFTR-I levels were observed in the 4·1° C group compared to the 11·9° C group. This coincided with a 2-3 week period with decreased Hct and PCO2 and may indicate a critical window when smolts suffer from reduced physical performance during migration. Further research is needed to confirm the potential interaction between ecological and physiological conditions on mortality of hatchery-reared smolts from River Vosso during their natural migration.

Specific growth hormone (GH)-binding protein (Ghbp) was purified from Atlantic salmon Salmo salar and rainbow trout Oncorhynchus mykiss plasma with immunoprecipitation and characterized in cross-linking studies using autoradiography and western blots. The size of the Ghbp was estimated to be c. 53 kDa. A radioimmunoassay was established to measure Ghbp in salmonids, using antibodies specific against the extracellular segment of the S. salar growth hormone receptor 1 (grh1; GenBank AY462105). Plasma Ghbp levels were measured in S. salar smolts in fresh water and after transfer to seawater (SW; experiments 1 and 2), and in post-smolts kept at different salinities (0, 12, 22 and 34) for 3 months (experiment 3). A transient increase in plasma Ghbp, which lasted for 1 month or less, was noted in smolts after transfer to SW. Concomitantly, plasma GH and gill Na(+) -K(+) -ATPase activity increased during smoltification (in experiment 2). No difference in plasma Ghbp was evident between post-smolts kept at different salinities, although the fish kept at salinity 34 had higher plasma GH than the group kept at salinity 22 and higher hepatic ghr1 expression than post-smolts kept at salinity 12. This suggests that plasma Ghbp regulation may respond to salinity changes in the short term. The lack of correlation between Ghbp, plasma GH and hepatic ghr1 expression in the long-term post-smolt experiment indicates that Ghbp levels may be regulated independently of other components of the endocrine GH system in salmonids.

This study investigated the development of hypo-osmoregulatory capacity and timing of downstream migration in wild Atlantic salmon Salmo salar smolts from the River Stjørdalselva and stocked young-of-the-year (YOY), derived S. salar smolts from the tributary River Dalåa. Both wild and stocked S. salar smolts developed seawater (SW) tolerance in early May, persisting through June, measured as their ability to regulate plasma osmolality and chloride following 24 h SW (salinity = 35) exposure. Although the majority of downstream migration among the stocked S. salar smolts occurred later than observed in their wild counterparts, the development of SW tolerance occurred concurrently. The wild S. salar from Stjørdalselva and stocked YOY smolts from the River Dalåa started to migrate on the same cumulative day-degrees (D°). The study revealed no downstream migration before development of SW tolerance. This emphasizes the importance of incorporating physiological status when studying environmental triggers for downstream migration of S. salar smolts. Overall, these findings suggest that the onset of smolt migration in stocked S. salar smolts was within the smolt window from an osmoregulatory point of view.

Salmon parr-smolt transformation (smoltification) is a mid-life transitional stage between life in freshwater and seawater that entails a wide range of neural, endocrine and physiological modifications. In salmon, the neuroendocrine corticotropin-releasing factor (CRF) system regulates pituitary adrenocorticotrophic hormone and thyrotrophin release. Four experimental groups of Atlantic salmon, Salmo salar, were used to investigated CRF neurogenesis and its regulation during smoltification. We compared: (i) developmental stages (parr and early-smolt) in anadromous controls; (ii) a developmentally arrested model: anadromous reared under continuous light (LL) with anadromous controls; (iii) a natural hypoendocrine/incomplete smolt development salmon model (landlocked) with anadromous controls; and (iv) landlocked treated with thyroxine to anadromous control smolt levels. CRF neurogenesis between groups was studied with bromodeoxyuradine (BrdU) incorporation followed by double-labelling CRF and BrdU immunhistochemistry. The rate of CRF neurogenesis in the preoptic area (POA) increased from parr to early-smolts in anadromous salmon. By contrast, neurogenesis was inhibited in the LL group and reduced in the landlocked salmon. The administration of thyroxine in landlocked salmon to match anadromous levels increased the rate of CRF neurogenesis to anadromous levels. In conclusion, newly-formed CRF cells in the POA during smoltification are associated with increased retinal innervation to the POA and endocrine responsiveness to increased photoperiod. Both genetic and environmental factors influence the degree of salmon brain development. Thyroid hormones increase CRF neurogenesis during this critical period of development in salmon. We hypothesise that a positive-feedback of thyroid hormones on CRF neurogenesis may be an important event in reaching the developmental climax during critical periods.

Immunization of mice with irradiated Brugia larvae or parasite extracts has been shown to induce partial resistance to microfilaremia and enhance clearance of infective larvae. We recently reported the cloning of a 548 amino acid 62-kDa Brugia malayi Ag identified on the basis of reactivity with antisera to a subset of protective microfilarial Ag. Our study describes the protective efficacy against microfilaremia in mice, immunogenicity, and parasite stage-specificity of this candidate vaccine molecule. Immunization of Swiss or BALB/c mice with 1 to 3 micrograms of a 92-kDa trpE fusion protein encoding amino acids 1-479 reduced the intensity of microfilaremia by 40 to 60% compared to control animals given buffer or bacterial trpE (p less than 0.01 to 0.001). Mice immunized with the 92-kDa fusion protein developed delayed-type hypersensitivity reactivity to B. malayi as assessed by enhanced footpad swelling 24 and 48 h after intradermal injection of adult worm extract and in vitro lymph node mononuclear cell proliferation (3H-thymidine uptake) in response to the fusion protein (mean +/- SD stimulation index 4.7 +/- 0.8 vs 2.0 +/- 1.4 for trpE, p less than 0.05). Proliferative responses of lymph node cells coincubated with three other fusion proteins corresponding to the filarial protein truncated from its carboxyl-terminus suggest that dominant T cell epitopes of the 62-kDa Ag are encompassed by amino acids 437-479. Rabbit antibody to the 92-kDa trpE fusion protein immunoprecipitated a 62-kDa polypeptide from [35S] methionine biosynthetically labeled B. malayi microfilariae, adult female, and adult male worms. These data indicate that a recombinant Ag expressed in several developmental stages of B. malayi is capable of inducing partial resistance against microfilariae and Ag-specific T cell responses in mice.

The aims of this study were to improve the algorithms for calculating a transcutaneous bilirubin index (TcB), to follow the bilirubin concentrations during phototherapy and to evaluate possible changes in skin optical parameters such as pigmentation and erythema during phototherapy.Reflectance measurements were performed on 51 jaundiced newborns, of which 10 were subjected to phototherapy. The measurements were collected with a diode array spectrophotometer with an integrating sphere accessory, and a TcB was calculated from the measured spectra using algorithms based on diffusion theory. The newborns' birthweights wereor = 2000 g and their gestational age wasor = 35.5 wk. They had no substantial illnesses, and no newborns were submitted to the study until their second day. Heel prick blood samples were analysed for total serum bilirubin (Sbr) by the diazo reaction method. Phototherapy equipment was either an overhead lamp or lightbed.Measurements from the forehead gave the best correlation between TcB and Sbr (r = 0.81, p0.05). However, during phototherapy no significant correlation between TcB and Sbr was observed. A correlation (r = 0.45, p0.05) was found between phototherapy and melanin index obtained from the patients' back.Reflectance spectroscopy is useful in assessing bilirubin concentrations before phototherapy, and can also reveal changes in skin parameters such as pigmentation occurring as a result of phototherapy.

RNA performs a remarkable range of functions in all cells. In addition to its central role in information transfer from DNA to protein, it is essential for functions as diverse as RNA processing, chromosome end-maintenance and dosage compensation. The versatility of RNA derives from its unique ability to use direct readout via base-pairing for sequence specific targeting (or templating) in combination with its capacity to form elaborate three dimensional structures. Such structures can perform catalysis or serve as protein recognition surfaces. In this short review, we attempt to give a flavor for the diversity of functional RNAs in the cell and highlight, using selected examples, two quite distinct activities, catalysis and sequence specific targeting. Within each section, we discuss how the lessons we have learned from these systems may apply to other, less well understood, RNAs.

Cancer of the pancreas is highly fatal and, despite extensive scrutiny, only cigarette smoking stands out as a likely causal agent in epidemiological studies. To explore to what extent different lifestyle factors are associated with the risk of pancreatic cancer, data from a large health screening survey in a county in Norway were analyzed.Our study included 31,000 men and 32,374 women initially free from any diagnosed cancer, and during 12 years of follow-up, 166 incident cases of pancreatic cancer were diagnosed at the Cancer Registry.Compared with never smokers, we found a two-fold increased risk among current smokers, and a dose-response association with number of cigarettes (p for trend = 0.02 for both men and women) and with number of pack-years (p for trend = 0.02 for men and 0.01 for women). The risk among former smokers quitting more than 5 years before study entry was close to the risk of never smokers. Compared with persons who reported never or infrequently to be physically worn out after a day's work, the relative risk (RR) among those who nearly always became worn out was 2.9 (95% confidence interval (CI) = 1.4-5.8) for men and 3.8 (95% CI = 1.6-9.2) for women. Divorced or separated men had a risk of 3.1 (95% CI = 1.3-7.2) compared with married men. We observed a higher risk among women in occupations of high socioeconomic status (RR = 2.5; 95% CI = 1.2-5.2), and among men occupied in farming, agriculture or forestry (RR = 2.1; 95% CI = 1.1-4.0), compared with persons in occupations of low socioeconomic status.Our results confirm the findings of previous studies that indicate a causal role of cigarette smoking in pancreatic cancer. Moreover, we found that the risk of former smokers may approach the risk of never smokers within a few years subsequent to quitting.

Few risk factors for prostate cancer are known, but both endocrine changes and dietary factors have been implicated in the etiology of the disease. Anthropometry may therefore provide a tool in the search for carcinogenic mechanisms connected to these suggested causal components.We have studied the association between body size and prostate cancer risk in a prospective study of 22,248 Norwegian men. During 12 years of follow-up, 642 men developed cancer of the prostate. A possible association between anthropometry (height, weight, body mass index (BMI), and lean body mass (LBM)) and prostate cancer risk was assessed using Cox regression analysis.Overall, we observed no significant trend for any of the variables studied, although an excess risk of prostate cancer with increasing height was suggested by an age-adjusted relative risk of 1.2 (95% CI = 0.9-1.6) for the tallest compared to the shortest quintile of men. None of the other three variables (weight, BMI, and LBM) displayed any consistent relation with the risk of prostate cancer.We conclude that these results do not indicate a strong association between anthropometric factors and risk of prostate cancer.

The paper presents the Norwegian population's attitude to euthanasia and to legal abortion in 1982, 1990 and 1995, and compares the responses given in 1995 with the attitudes of a representative sample of 1,260 Norwegian physicians. The acceptance of legal abortion in the population seems to have remained constant, while the population's attitude towards euthanasia has become more liberal. Social criteria and a potential handicapped baby were less accepted as causes for abortion in 1995 than in 1990. The physicians are more liberal towards abortion and more sceptical towards euthanasia. The physicians are more reluctant, however, to accept a potential handicapped offspring as a reason for abortion.

Bone marrow cells (BMC) are involved in the pathogenesis of human cytomegalovirus++ (HCMV) infections, and the hematopoietic cells are probable sites of HCMV latency in healthy donors. In vitro studies have indicated both a direct inhibitory effect of HCMV on proliferation and differentiation of myeloid bone marrow progenitors and an impairment of bone marrow stroma cell function by HCMV. The purpose of the present study was to establish whether the suppressing effect could be limited to subsets of immature CD34+ BMC and to investigate the role of immature cell populations as possible sites of HCMV latency. CD34+ cells from healthy HCMV-seropositive and -seronegative donors were sorted according to the expression of HLA-DR (CD34+ HLA-DR+ and CD34+ HLA-DR- cells). The progenitor growth of hematopoietic progenitor cells from seronegative donors was examined by colony and single-cell assays after in vitro infection with HCMV. To determine the susceptibility of the CD34+ cells to HCMV infection in vitro and in vivo, cells of both subsets from seronegative and seropositive donors were analyzed for the presence of HCMV DNA by polymerase chain reaction. HCMV infection in vitro inhibited the interleukin-1alpha (IL-1alpha)-, IL-3-, granulocyte colony-stimulating factor-, granulocyte-macrophage colony-stimulating factor-, and stem cell factor-induced proliferation in single-cell assays of CD34+ HLA-DR-cells by 34%. In contrast, the colony growth of the CD34+ HLA-DR+ subset was suppressed in cells from only 3 of the 8 donors. However, in vitro HCMV infection of the CD34+ HLA-DR+ progenitor cells inhibited the proliferation of all donors tested when hematopoietic growth factors were used individually to promote progenitor growth. In addition, the formation of burst-forming units-erythroid and colony-forming units-granulocyte, erythrocyte, monocyte, megakaryocyte was reduced 40% to 60% by HCMV in vitro. In contrast, the growth of high proliferative potential colony-forming cells was not inhibited after in vitro HCMV infection. Furthermore, HCMV DNA was detected in both CD34+ HLA-DR- and CD34+ HLA-DR+ progenitors from in vitro-infected HCMV-seronegative donors and cells from HCMV- seropositive donors. Taken together, the early progenitors defined as CD34+ HLA-DR- and CD34+ HLA-DR+ are directly suppressed in their proliferation by HCMV in vitro, and hematopoietic stem cells are also sites of HCMV latency in healthy HCMV-seropositive donors.

Most nuclear pre-mRNAs in nematodes are processed by both cis- and trans-splicing. In trans-splicing, the 5' terminal exon, the spliced leader sequence (SL), is derived from a trans-splicing specific Sm snRNP, the SL RNP. Because U snRNPs are required cofactors for trans-splicing, and because this processing reaction proceeds via a two-step reaction pathway identical to that of cis-splicing, it has long been assumed that trans-splicing is catalyzed in a complex analogous to the cis-spliceosome. However, similarities or differences between cis- and trans-spliceosomes have not been established. In particular, the role of U5 snRNP in trans-splicing has been unclear. Here, we have used affinity selection to analyze the U snRNA constituents of nematode cis- and trans-spliceosomes. We find that U5 snRNP is an integral component of the trans-spliceosome and, using site-specific crosslinking, we show that U5 snRNP establishes specific Interactions with the SL RNA exon. We also identify two novel Sm snRNPs that are enriched in both cis- and trans-spliceosomes. Finally, we provide evidence that a SL RNP-containing multi-snRNP (SL, U4, U5, and U6 RNPs) may be a functional precursor in trans-spliceosome assembly.

Some pre-mRNAs in nematodes are processed by trans-splicing. In this reaction, a 22-nt 5' terminal exon (the spliced leader, SL) and its associated 2,2,7-trimethylguanosine cap are acquired from a specialized Sm snRNP, the SL RNP. Although it has been evident for many years that not all nematode mRNAs contain the SL sequence, the prevalence of trans-spliced mRNAs has, with the exception of Caenorhabditis elegans, not been determined. To address this question in an organism amenable to biochemical analysis, we have prepared a message-dependent protein synthesis system from developing embryos of the parasitic nematode, Ascaris lumbricoides. Using this system, we have used both hybrid-arrest and hybrid-selection approaches to show that the vast majority (80-90%) of A. lumbricoides mRNAs contain the SL sequence and therefore are processed by trans-splicing. Furthermore, to examine the effect of SL addition on translation, we have measured levels of protein synthesis in extracts programmed with a variety of synthetic mRNAs. We find that the SL sequence itself and its associated hypermethylated cap functionally collaborate to enhance translational efficiency, presumably at the level of initiation of protein synthesis. These results indicate that trans-splicing plays a larger role in nematode gene expression than previously suspected.

Varicella zoster virus (VZV) establishes latency in sensory ganglia following primary infection (chickenpox) and may reactivate decades later to produce zoster (shingles). The presence of VZV DNA in latently infected ganglia has been demonstrated by Southern blot hybridization as well as by polymerase chain reaction of DNA extracted from latently infected ganglia. Conflicting results have been obtained by in situ hybridization studies to determine the cell type in the ganglia harboring the latent VZV. To address this controversy we have utilized a more sensitive method than the previous studies. We have applied the technique of polymerase chain reaction to sections of ganglia from latently infected individuals and combined this with in situ hybridization to detect the amplified product. Primers specific for VZV were used to amplify VZV DNA in latently infected human trigeminal ganglia and demonstrated the presence of VZV DNA in neurons only. Sections from human kidney and ganglia from neonates as well as monkey ganglia served as controls and did not show amplification of VZV sequences. Amplification using primers for human genes, alpha tubulin and the oncogene Bcl-2, demonstrated the presence of these sequences in nearly all cells in the human tissues while only weak signals were seen in the monkey tissue. This is the first report where in situ amplification has been utilized to detect latent VZV in human ganglia.

We have used block-substitution mutagenesis and in vitro transcription assays to identify cis-acting DNA sequence elements important for initiation and 3'-end formation of a U1 small nuclear RNA (snRNA) in the parasitic nematode Ascaris lumbricoides. Efficient initiation of synthesis by RNA polymerase II requires a compact element centered approximately 50 base pairs upstream of the transcriptional start site. Surprisingly, 3'-end formation of U1 snRNAs synthesized in vitro is solely dependent upon elements within the U1 coding sequence. In all other systems studied thus far, 3'-end formation of U snRNAs requires signals present in the 3'-flanking region. We also show that sequence elements that direct 3'-end formation of the A. lumbricoides trans-spliced leader RNA function when RNA synthesis is initiated from the U1 promoter. These results indicate that 3'-end formation of U snRNAs in nematodes is mechanistically distinct from the analogous process in higher eukaryotes.

Trans-splicing is defined as the process whereby exons derived from two separately transcribed RNAs are joined together. In one type of trans-splicing, nuclear pre-mRNAs acquire their 5' terminal exon (the spliced leader) from a small spliced leader RNA (SL RNA) via an RNA processing reaction that is directly analagous to the removal of intervening sequences (cis-splicing). Such leader-addition by trans-splicing has been extensively studied in trypanosomatid protozoans and in nematodes. This review summarizes recent advances in research on trans-splicing in these two systems. Progress in elucidating functionally significant sequence elements within SL RNAs and progress in understanding the mechanism and biological role of trans-splicing is discussed.

Creation of the mature 5' terminus of human 18 S rRNA in vitro occurs via a two-step processing reaction. In the first step, an endonucleolytic activity found in HeLa cell nucleolar extract cleaves an rRNA precursor spanning the external transcribed spacer-18 S boundary at a position 3 bases upstream from the mature 18 S terminus leaving 2',3'-cyclic phosphate, 5' hydroxyl termini. In the second step, a nucleolytic activity(s) found in HeLa cell cytoplasmic extract removes the 3 extra bases and creates the authentic 5'-phosphorylated terminus of 18 S rRNA. Here we have examined the sequence requirements for the trimming reaction. The trimming activity(s), in addition to requiring a 5' hydroxyl terminus, prefers the naturally occurring adenosine as the 5'-terminal base. By a combination of deletion, site-directed mutagenesis, and chemical modification interference approaches we have also identified a region of 18 S rRNA spanning bases +6 to +25 (with respect to the mature 5' end) which comprises a critical recognition sequence for the trimming activity(s).

In nematodes, a fraction of mRNAs acquires a common 22-nucleotide 5'-terminal spliced leader sequence via a trans-splicing reaction. The same premessenger RNAs which receive the spliced leader are also processed by conventional cis-splicing. Whole cell extracts prepared from synchronous embryos of the parasitic nematode Ascaris lumbricoides catalyze both cis- and trans-splicing. We have used this cell-free system and oligodeoxynucleotide directed RNase H digestion to assess the U small nuclear RNA requirements for nematode cis- and trans-splicing. These experiments indicated that both cis- and trans-splicing require intact U2 and U4/U6 small nuclear ribonucleoproteins (snRNPs). However, whereas cis-splicing displays the expected requirement for an intact U1 snRNP, trans-splicing is unaffected when approximately 90% of U1 snRNP is degraded. These results suggest that 5' splice site identification differs in nematode cis- and trans-splicing.

The translational efficiency of cMyc mRNAs was assessed in a variety of cell lines: HeLa cells and Epstein-Barr virus-transformed lymphocytes, both of which contain only the germ line cMyc allele; Daudi, a Burkitt cell line containing a translocated cMyc gene with no apparent alteration; and P3HR-1, a Burkitt line in which the 5' end of the translocated cMyc gene has been altered by the chromosomal translocation. Translational efficiency was inferred by measuring the number of ribosomes associated with the cMyc mRNA, using a procedure by which individual polysomal fractions were analyzed by blot hybridization. Since polysome size is a function of the length of the translated sequence as well as the rate of initiation of protein synthesis, we also determined the number of ribosomes associated with a control mRNA (alpha tubulin) which codes for a protein of similar size to cMyc. We found that the cMyc mRNA was associated with a number of ribosomes comparable to that associated with alpha tubulin mRNA in all the cell lines tested.

SummaryA lower Tertiary lateritic paleosol resting on a plateau basalt was penetrated by drilling at DSDP Site 336 on the NE flank of the Iceland—Faeroe Ridge. The sea floor at the site is about 800 m below sea level and about 400 m below the generally smooth, flat and largely sediment-free top of the ridge. The paleosol is approximately 30 m thick and can be divided into four subunits, in ascending order, basaltic rubble, red clay with altered basaltic clasts, interlayered red and pale-orange clay, and red clay. The paleosol is overlain by about 300 m of marine mudstone of medial Eocene to medial late Oligocene age that was deposited in progressively deeper water through time. About 170 m of Pliocene and Pleistocene glacio-marine sediments unconformably overlie the Paleogene deposits.In the lowest subunit of the paleosol, feldspar, pyroxene, magnetite and chlorite decrease in abundance abruptly upward and are replaced by montmorillonite and small amounts of hematite and goethite. At the contact between the second and third subunits of the paleosol, kaolinite becomes an important constituent and increases greatly in abundance upward. In the uppermost red clay subunit, kaolinite has completely replaced montmorillonite and the amount of hematite and goethite increases markedly. Within the paleosol subunits, the relative amounts of silicon, ferrous iron, magnesium, calcium, sodium, and potassium decrease upward, whereas the amounts of aluminum, ferric iron, and titanium increase upward. The red and pale-orange clay subunit contains layers characterized by veinlet-like structures alternating with more massive layers. The veinlet network is thought to have developed by segregation of ferric iron and alumina as a result of chemical weathering of basalt and possibly thin overlying airfall tuffs.The paleosol indicates a humid, warm climate and demonstrates that the Iceland-Faeroe Ridge was above sea level during the early Tertiary. The ridge formed the main part of the Thulean land bridge that permitted free migration of land mammals between North America-Greenland and Europe prior to late Eocene time. It developed during the early Tertiary break-up and rifting apart of North America-Greenland and Europe. Formerly situated over an active mantle plume or hot spot, the ridge subsequently subsided in late Eocene and Oligocene time, eventually permittingfree interchange of marine waters between the Norwegian-Greenland Sea and the North Atlantic Ocean. Basalts of the Iceland-Faeroe Ridge are simijar in age and character to other basalts of the North Atlantic early Tertiary igneous province on the Rockall and Voring Plateaus, northern Ireland, Scotland, the Faeroe Islands, East and West Greenland, and Baffin Island. Bauxite, lignite, and laterite associated with some of these basalt sequences, as well as vertebrate, plant, and microfossil remains, suggest a relatively uniform, warm, humid climate in the early Tertiary throughout the North Atlantic area and into the region of the Arctic Ocean.

The principle of activated swelling has made available polymer particles in the range of 1–100 μm, highly uniform in size, and with great variations in morphology and chemical composition. A short description of the method is given. On the basis of monosized porous macroreticular particles, monosized magnetic polymer particles (MMP) are prepared which are uniform in size as well as in content of magnetic oxides. These particles have found applications in a number of selective cell separation procedures. Special types of MMP have been developed for isolation of organelles and viruses. The use of MMP as contrast agent in magnetic resonance imaging is shortly described.

The translational efficiency of cMyc mRNAs was assessed in a variety of cell lines: HeLa cells and Epstein-Barr virus-transformed lymphocytes, both of which contain only the germ line cMyc allele; Daudi, a Burkitt cell line containing a translocated cMyc gene with no apparent alteration; and P3HR-1, a Burkitt line in which the 5' end of the translocated cMyc gene has been altered by the chromosomal translocation. Translational efficiency was inferred by measuring the number of ribosomes associated with the cMyc mRNA, using a procedure by which individual polysomal fractions were analyzed by blot hybridization. Since polysome size is a function of the length of the translated sequence as well as the rate of initiation of protein synthesis, we also determined the number of ribosomes associated with a control mRNA (alpha tubulin) which codes for a protein of similar size to cMyc. We found that the cMyc mRNA was associated with a number of ribosomes comparable to that associated with alpha tubulin mRNA in all the cell lines tested.

The quantum corrections to the law of corresponding states are studied by calculating the critical pressure, temperature, and density to first order in Planck's constanth on an exactly soluble model. The ratio of the critical parameters to the corresponding classical values are found to be (pc/pc0)1/2=ρc/ρc0 = Tc/Tc0 = 1−0.67Λ, withΛ=hρc1/3(mkTc)−1/2. The critical ratio is independent ofh to first order. The results are compared with critical data for noble gases and hydrogen isotopes.

A lattice gas on an M×∞ square lattice with nearest‐neighbor exclusion is studied in a ``grand pressure ensemble.'' It is shown how to calculate the distribution of the zeros of the grand partition function. Explicit results for M

The Norwegian offshore oil industry is rapidly expanding. The health services for this industry have also developed quickly. An EDB-based medical registration system for the Norwegian continental shelf (MICS) has been planned in support of health services, health authorities and researchers. This information system will consist of an injury/disease register and a register of the population on the Norwegian continental shelf. The injury/disease register will comprise inter alia reported cases of occupational injury, occupational disease, notifiable infectious disease and summary data about rate of utilisation of ambulance transport and health services offshore. The system will be administered by the Norwegian Directorate of Health in cooperation with the Norwegian Oil Directorate. MICS will provide new possibilities for epidemiological studies of health and disease among the employees in the oil industry.

Several new occurrences of dish structure are documented herein: (1) Precambrian hornfels in the central Transantarctic Mountains, Antarctica; (2) Precambrian deltaic siltites of the Belt Supergroup in northern Idaho; (3) Oligocene turbidite sandstone recovered in a DSDP core from a small ridge located southeast of Jan Mayen Ridge in the Norwegian-Greenland Sea; (4) Oligocene fluvial deposits in the Caliente Range, California; and (5) Pliocene lacustrine deposits in the Ridge Basin, California.