Rapid disintegration and weakening of ice shelves in North Greenland.

The glaciers of North Greenland are hosting enough ice to raise sea level by 2.1 m, and have long considered to be stable. This part of Greenland is buttressed by the last remaining ice shelves of the ice sheet. Here, we show that since 1978, ice shelves in North Greenland have lost more than 35% of their total volume, three of them collapsing completely. For the floating ice shelves that remain we observe a widespread increase in ice shelf mass losses, that are dominated by enhanced basal melting rates. Between 2000 and 2020, there was a widespread increase in basal melt rates that closely follows a rise in the ocean temperature. These glaciers are showing a direct dynamical response to ice shelf changes with retreating grounding lines and increased ice discharge. These results suggest that, under future projections of ocean thermal forcing, basal melting rates will continue to rise or remain at high level, which may have dramatic consequences for the stability of Greenlandic glaciers.

Polarization-maintaining higher-order mode fiber module with anomalous dispersion at 1 µm.

This Letter demonstrates a polarization-maintaining higher-order mode fiber module that has anomalous dispersion at 1 µm. The group velocity dispersion of the module is measured, showing a split of the two polarization axes. The excellent polarization-maintaining properties of the relevant fiber modes for the higher-order mode fiber are likewise demonstrated employing a new simple method for the measurement of the beat length of higher-order modes at a single wavelength. The higher-order fiber module is intended for group velocity dispersion compensation.

Clinical outcome in children with acute renal failure treated with peritoneal dialysis after surgery for congenital heart disease.

The present single-center cohort study was based on a clinical intensive care unit database containing data on 1128 consecutive children undergoing their first operation for congenital heart disease between 1993 and 2002 at Aarhus University Hospital, Skejby, Denmark. A total of 130 (11.5%) children developed postoperative acute renal failure (ARF) managed with peritoneal dialysis (PD). Logistic regression analysis was used to examine risk factors for complications related to PD and to compare mortality between ARF and non-ARF patients controlling for potential confounding factors. A total of 43 complications related to PD were registered in 27 (20.8%) patients. Major complications were seen in eight (6.2%) patients, and only two (1.5%) patients were switched to hemodialysis after peritonitis and hemicolectomy due to bowel perforation. The main risk factors for complications to PD were duration of PD, high RACHS-1 score (Risk Adjusted Classification for Congenital Heart Surgery), and hyperkalemia at initiation of PD. Overall, in-hospital mortality was 6.8% (76/1128). Mortality of ARF patients was 20.0% compared to 5.0% among non-ARF patients (adjusted odds ratio=1.91, 95% confidence interval=1.10-3.36). After stratification, ARF was strongly associated with increased mortality in the subgroups of patients with the lowest overall risk of dying (age> or =1 year, body weight> or =5 kg, RACHS-1 score <3, and no preoperative cyanosis). For patients at high risk of dying (age <1 year, body weight <5 kg, RACHS-1 score> or =3, cardiopulmonary bypass time> or =60 min, and preoperative cyanosis), the association between ARF and mortality was substantially weaker. In conclusion, postoperative ARF was associated with increased mortality in children operated for congenital heart disease. Major complications to PD were few, and our data strongly support that PD is a simple, safe, feasible, and robust dialysis modality for the management of ARF in children.

Strong association between cervical and breast cancer screening behaviour among Danish women; A register-based cohort study.

High coverage is essential for the effectiveness of national screening programmes. Identifying non-screeners across different screening programmes may help inform strategies to improve uptake. This study aims to analyse the association between previous cervical cancer screening (CCS) coverage and participation in breast cancer screening (BCS). This historical register-based cohort study included 91,787 Danish women aged 50-64 years who were invited to participate in the first organised round of BCS in the Central Denmark Region (CDR) in 2008-09. CCS coverage was defined as having a smear registered in the 5 1/2 years preceding the BCS, and BCS participants were divided into participants and non-participants and further categorised as active non-participants (ANP) if they cancelled and passive non-participants (PNP) if they abstained from the appointment. Of all 91,787 women included in the study, 62,391 (68%) were covered both by CCS and participated in BCS. Women not covered by CCS were more likely to be non-participants in BCS than women covered by CCS (PRRadjusted = 2.80, 95% CI: 2.68-2.93). Both PNP (PRRadjusted = 3.99, 95% CI: 3.80-4.19) and ANP (PRRadjusted = 2.50, 95% CI: 2.34-2.68) were more likely not to be covered by the CCS. In conclusion, non-coverage by CCS was strongly associated with nonparticipation in BCS. Specific groups of women only participated in one screening programme. To increase uptake, future interventions may specifically target these groups.

Cloning and integration of DNA fragments in human cells via the inverted terminal repeats of the adeno-associated virus 2 genome.

In current systems for molecular cloning of eukaryotic genes, bacterial cells are routinely utilized as intermediate hosts. We investigated the possibility of using a viral system for cloning DNA fragments independent of bacterial cell usage. In this report, we provide an alternative approach for molecular cloning of DNA fragments in eukaryotic cells by utilizing the inverted terminal repeats (ITRs) of the genome of a nonpathogenic human parvovirus, the adeno-associated virus 2 (AAV). We constructed a series of chimeric linear duplex DNA molecules, ranging in length from 1.8 to 7.2 kb, containing the cruciform structures of AAV-ITRs at both ends. These 'no-end' (NE) DNA structures, when transfected into adenovirus-infected human cells in the presence of AAV replication proteins (Rep), underwent DNA replication. Furthermore, in the presence of AAV capsid proteins (Cap), all replicated DNA molecules of less than 5.0 kb were packaged into mature, biologically active AAV progeny virions. When a chimeric NE DNA (NE-neo) containing a gene (neo) encoding resistance to neomycin was transfected into human cells, neoR clones could be readily isolated in the presence of G418 (Geneticin). Southern-blot analysis of genomic DNA of several independently isolated neoR clones suggested stable integration of the NE-neo DNA into the host chromosomal DNA. AAV-ITRs, therefore, offer an alternative system for molecular cloning, as well as packaging of DNA fragments in mammalian cells independent of bacterial cell usage.

H(2)O(2)-induced egr-1, fra-1, and c-jun gene expression is mediated by tyrosine kinase in aortic smooth muscle cells.

Hydrogen peroxide (H(2)O(2)) has recently been shown to have a dual effect on cell growth by stimulating proliferation and triggering apoptosis. Apoptosis induced by H(2)O(2) is a direct consequence of oxidant injury, while the proliferative response to H(2)O(2) is thought to be a protective mechanism against oxidant injury. Signaling of the H(2)O(2)-induced proliferative effect has been proposed to occur via the activation of mitogen-activated protein kinase (MAPK) and increase in expression of transcription factors. In the present study, H(2)O(2)-induced mitogenic signaling in aortic smooth muscle cells (ASMC) was investigated with a specific focus on the roles of tyrosine kinase and tyrosine phosphatase in the regulation of the H(2)O(2)-stimulated egr-1, fra-1, and c-jun transcription. The results show that H(2)O(2)-induced increases in egr-1, fra-1, and c-jun mRNA levels, as measured by Northern blot analysis, are time and dose dependent with the peak of the response within 2 h. Tyrosine kinase inhibitors (genistein, amino-genistein, and tyrphostin 51) significantly attenuated H(2)O(2)-induced expression of these genes and a tyrosine phosphatase inhibitor (perox-vanadate) stimulated their expression. H(2)O(2) stimulated tyrosine kinase activities and caused protein tyrosine phosphorylation, which was blocked by tyrphostin 51. H(2)O(2) also caused tyrosine phosphorylation of platelet derived growth factor (PDGF) receptor. These data show that H(2)O(2) increases egr-1, fra-1, and c-jun mRNA levels in vascular smooth muscle cells, and the increase in expression of these genes is mediated by activation of tyrosine kinase. Our data also provide evidence that the H(2)O(2)-induced mitogenic response is, in part, mediated through the receptor tyrosine kinase, PDGF receptor.

Oligonucleotide purification in milligram quantities.

An inexpensive and simple procedure for the purification of synthetic oligonucleotides is described. Hands-on time is only 30 to 40 minutes and multiple samples can be prepared simultaneously. One- to two-milligram quantities can easily be handled by a single column with no further purification required for the DNA to be used in a wide variety of molecular biological uses.

Virucidal activity of hypericin against enveloped and non-enveloped DNA and RNA viruses.

Hypericin is a polycyclic anthrone first isolated from the plant St. Johnswort and was shown to have dramatic anti-retroviral activity against Friend leukemia virus and radiation leukemia virus in mice. Hypericin displayed marginal activity (IC50 = 6 micrograms/ml) against Moloney murine leukemia virus (Mo-MuLV) in vitro. Hypericin did not display selective antiviral activity against herpes simplex virus, influenza A, adenovirus, or poliovirus. The 50% cytotoxic concentration was approximately 25 micrograms/ml. When virus was incubated with hypericin before infecting cells, the drug was virucidal to all enveloped viruses tested (herpes simplex, influenza virus A, and Mo-MuLV) at concentrations of 1.56 micrograms/ml to 25 micrograms/ml. Hypericin was not virucidal to the non-enveloped viruses tested (adenovirus and poliovirus). These data indicate that the mechanism of viral inactivation for hypericin is dependent upon the presence of a viral lipid envelope. In vivo, hypericin (50 mg/ml) was effective against FLV or HSV-1 if incubated with the virus for 1 h at 37 degrees C before infecting mice, but was not effective if pre-incubated with virus for 1 h at 4 degrees C or if administered concurrently with virus.

Inhibition of duck hepatitis B virus replication by hypericin.

Hypericin was found to be active against a member of the hepatitis B virus family, duck hepatitis B virus (DHBV). After a single 1 h incubation with hypericin, cells stably-transfected with a clone of DHBV stopped producing infectious virus for several days, though virus-like particles continued to be released into the culture medium. Characterization of these virions revealed a buoyant density characteristic of infectious virus preparations and lower than that of virus cores, suggesting that the particles were enveloped. Western blot analysis suggested, however, that the viral preS protein in surface antigen particles and, by inference, in virions, was present in covalently cross-linked aggregates. Evidence of a similar level of aggregation of the core subunit of virion nucleocapsids was not found, nor was there evidence of a similar high level of aggregation of cell-associated core and preS proteins. Hypericin was only slightly virucidal against DHBV and culture medium from treated cultures did not block initiation of infection when added to DHBV susceptible cultures prior to a challenge with infectious DHBV. Thus, the primary antiviral activity of hypericin against DHBV replication appears to be exerted at a late step in viral morphogenesis.

The recA gene of Chlamydia trachomatis: cloning, sequence, and characterization in Escherichia coli.

The recA gene of Chlamydia trachomatis was isolated by complementation of an Escherichia coli recA mutant. The cloned gene restored resistance to methyl methanesulfonate in E. coli recA mutants. The DNA sequence of the chlamydial gene was determined and the deduced protein sequence compared with other RecA proteins. In E. coli recA deletion mutants, the cloned gene conferred moderate recombinational activity as assayed by Hfr matings. The chlamydial recA gene was efficient in repairing alkylated DNA but less so in repairing of UV damage when compared with the E. coli homologue. As detected by an SOS gene fusion, a small but measurable amount of LexA co-cleavage was indicated.

Ultraviolet-radiation and skin cancer. Effect of an ozone layer depletion.

The effect of changes in the ozone layer on the incidence of skin cancer was explored using data for Norway. Attempts were made to arrive at a relationship between the "environmental effective UV-dose" and the skin cancer incidence. Norway is well suited for this purpose because of the large variation in the annual UV-dose from north to south. Furthermore we have a well developed cancer registry and a homogeneous population with regard to skin type. Four different regions of the country, each with a broadness of 1 degree in latitude (approximately 111 km), were selected (located around 69.5, 63.5, 60 and 58.5 degrees N). The annual effective UV-doses for these regions were calculated, assuming normal ozone conditions throughout the year and the action spectrum proposed by CIE, which extends up to 400 nm. The incidence rate (in the period 1970-1980) of malignant melanoma and non-melanoma skin cancer (mainly basal cell carcinoma) increased with the annual environmental UV-doses. For both these types of cancer a quadratic dose-effect relationship seems to be valid to a first approximation. The present data indicate that the incidence of skin cancer would increase by approximately 2% for each percent ozone reduction.

Biological UV-doses and the effect of an ozone layer depletion.

Effective UV-doses were calculated based on the integrated product of the biological action spectrum (the one proposed by IEC, which extends to 400 nm, was adopted) and the spectral irradiance. The calculations include absorption and scattering of UV-radiation in the atmosphere, both for normal ozone conditions as well as for a depleted ozone layer. For Scandinavian latitudes the effective annual UV-dose increases by approximately 4% per degrees of latitude towards the Equator. An ozone depletion of one percent increases the annual UV-dose by approximately 1% at 60 degrees N (increases slightly at lower latitudes). A large depletion of 50% over Scandinavia (60 degrees N) would give these countries an effective UV-dose similar to that obtained, with normal ozone conditions, at a latitude of 40 degrees N (California or the Mediterranean countries). The Antarctic ozone hole increases the annual UV-dose by 20 to 25% which is a similar increase as that attained by moving 5 to 6 degrees of latitude nearer the Equator. The annual UV-dose at higher latitudes is mainly determined by the summer values of ozone. Both the ozone values and the effective UV-doses vary from one year to another (within +/- 4%). No positive or negative trend is observed for Scandinavia from 1978 to 1988.

16-Deethylindanomycin (A83094A), a novel pyrrole-ether antibiotic produced by a strain of Streptomyces setonii. Taxonomy, fermentation, isolation and characterization.

16-Deethylindanomycin (A83094A) is a novel pyrrole-ether antibiotic produced by a strain of Streptomyces setonii. The antibiotic, which is structurally similar to indanomycin (X-14547A), is active in vitro against Gram-positive bacteria as well as coccidia.

New azasteroidal antifungal antibiotics from Geotrichum flavo-brunneum. II. Isolation and characterization.

A novel group of antibiotics, comprising microbiologically-active structurally-related factors A25822A, B, D, H, L, M and N, produced by culturing Geotrichum flavo-brunneum NRRL 3862 under submerged aerobic fermentation conditions was isolated by extraction. The individual factors were separated and purified by chromatography and crystallization. The major factor, A25822B, a 15-aza-24-methylene-D-homocholestadiene is a white crystalline compound, C25H45NO. The antibiotics are highly active against fungi and marginally active against bacteria.

Structure of the new spiroketal-macrolide A82548A.

A new member of the spiroketal-containing macrolide class of fermentation-derived natural products was isolated from mycelial extracts of Streptomyces diastatochromogenes. The principal component, A82548A, was shown to possess a 22-membered macrolide ring system onto which was incorporated both a spiroketal and a hemiketal moiety. Relative stereochemistry was established by single crystal X-ray diffraction studies. Absolute stereochemistry was determined via hydrolysis of the amino sugar glycosidically linked to the aglycone, which was identified as L-kedarosamine. The overall three-dimensional structure is closely related to that of the macrolides cytovaricin, rutamycin, and ossamycin.

Hypothesis: pathogenesis of postmenopausal hot flush.

The pathogenesis of postmenopausal hot flush is still poorly understood. A hypothesis is presented where the perimenopausal decline in circulating estrogen levels may increase central norepinephrine and LH-RH secretion and produce a downward setting of the central thermostat resulting in a hot flush.