Influence of serine O-glycosylation or O-phosphorylation close to the vJun nuclear localisation sequence on nuclear import

Nuclear import triggered by the nuclear-localisation sequence (NLS) of the viral Jun (vJun) protein is mediated by phosphorylation of a serine close to the NLS. Since phosphorylation and glycosylation of serine residues are often in a reciprocal "yin-yang" relationship, we investigated whether glycosylation of this serine with O-linked N-acetylglucosamine (O-GlcNAc) would also regulate nuclear import via the vJun NLS. Peptides containing the vJun NLS with an adjacent O-phosphorylated, O-GlcNAc-functionalised or unmodified serine, and equipped with an N-terminal biotin or a 7-nitrobenz-2-oxa-1,3-diazolyl (NBD) fluorescent label, were synthesised on the solid phase by means of an Fmoc/Boc strategy and a Pd0-sensitive HYCRON linker. Fluorescence-polarisation measurements on the NBD-labelled peptides indicated that modification with phosphate or O-GlcNAc leads to a decrease in affinity to the import-mediating adapter protein, importin alpha, of about one order of magnitude compared to the unmodified NLS. Microinjection of biotinylated NLS peptide conjugated with fluorescently labelled avidin into NIH/3T3 and MDCK cells, revealed that avidin-unmodified-NLS peptide was rapidly imported into the nucleus. However, either phosphate or O-GlcNAc next to the NLS caused almost complete exclusion of the protein conjugate from nuclear import. These findings indicate that nuclear import by the vJun NLS might not be regulated by a "yin-yang" modification of an adjacent serine with phosphate or O-GlcNAc. Rather, negative regulation of binding between the polybasic NLS and importin by a negatively charged or a bulky, uncharged residue appears likely.     

Implementation of a new strain split to model unilateral contact within the phase field method

A new orthogonal split of strain tensor into compressive and tensile parts is implemented within the phase field model to mimic unilateral contact condition with which any existing cracks and any crack propagation have to comply. The resulting phase field model offers several advantages as compared to other available schemes. First, it involves rigorous orthogonality between traction and compression parts. Second, it yields remarkably simple, new analytical expressions of the projectors which provide computational saving during the crack propagation simulation. Finally, it can be applied to arbitrary initial elastic anisotropic media, which is not the case of other available strain tensor split operators. A detailed comparison of the fracture responses predicted by the present model and other approaches is provided. It is shown that the present orthogonal decomposition is able to accurately predict experimental results and removes spurious effects found in other schemes for specific loads like compression.     

Comparison EUROMET.EM-K8 of DC voltage ratio: results

A regional key comparison of dc voltage ratio has been carried out in Europe. The method to evaluate the comparison reference value, the resulting degrees of equivalence for the voltage ratios 1000 V/10 V and 100 V/10 V and the link to the corresponding worldwide key comparison CCEM-K8 are reported.     

Synthesis and Structure–Activity Correlation of a Brunsvicamide‐Inspired Cyclopeptide Collection

Cyanobacterial cyclopeptides : A series of analogues of the cyanobacterial cyclopeptide brunsvicamide A was prepared by effective solid‐support‐based total synthesis. Variations in stereochemistry revealed the importance of the D ‐lysine and the L ‐isoleucine residues for the substrate‐competitive inhibitory activity of brunsvicamide A against carboxypeptidase A.

     

Examination of a role for idiotypy in the disease remission of a long-term survivor of adult T cell leukemia treated with anti-Tac antibody

The alpha chain of the interleukin 2 receptor (IL2R alpha; Tac) was targeted in clinical trials with adult T cell leukemia using murine anti-Tac antibody. Of 19 patients, a single individual achieved a durable complete remission. The mechanism of this action by murine anti-Tac has not been defined. We examined the hypothesis that the maintenance of the long-term response after treatment might be related to induction of a network of anti-idiotypic antibodies, as proposed in other tumor settings. In contrast to anti-Tac non-responders, the patient was found to have produced a human anti-mouse antibody (HAMA) response, and specifically an anti-idiotypic (Ab2) response, that was readily detectable by standard assays 4 years after treatment. Using phage display antibody libraries, this response was shown to be monoclonal, consisting of a single IgG1,kappa antibody of moderate affinity. No evidence was found for anti-anti-idiotypic (Ab3) antibodies with reactivity for sTac, which might alternatively have maintained an autogenic human anti-Tac antibody response. An area of limited homology was noted between the Ab2 antibody and the IL2R in the domain of IL2 binding, but no binding of Ab2 to IL2 could be shown that might have reduced endogenous ligand (IL2) concentrations. Similarly, no anti-anti-idiotypic (T3) T cell response was detected. Thus, we are unable to confirm features of idiotypy that could suggest a role in maintaining an anti-tumor response by anti-Tac antibody therapy.     

Termination Proofs for String Rewriting Systems via Inverse Match-Bounds

Annotating a letter by a number, one can record information about its history during a rewrite derivation. In each rewrite step, numbers in the reduct are updated depending on the redex numbering. A string rewriting system is called match-bounded if there is a global upper bound to these numbers. Match-boundedness is known to be a strong sufficient criterion for both termination and preservation of regular languages. We show that the string rewriting systems whose inverse (left and right hand sides exchanged) is match-bounded, also have exceptional properties, but slightly different ones. Inverse match-bounded systems need not terminate; they effectively preserve context-free languages; their sets of normalizable strings and their sets of immortal strings are effectively regular. These languages can be used to decide the normalization, the uniform normalization, the termination and the uniform termination problem for inverse match-bounded systems. We also prove that the termination problem is decidable in linear time, and that a certain strong reachability problem is decidable, thereby solving two open problems of McNaughton’s. Like match-bounds, inverse match-bounds entail linear derivational complexity on the set of terminating strings.     

Indications, adverse effects and complications of lithium therapy

The application of lithium preparations in the therapy and prophylaxis of recidivations of affective psychoses has essentially gathered in point in psychiatry during the last years. Apart from the discussion of the indication, the contraindication and efficacy especially concomitant appearances, side effects and dangers as well as their influencibility are demonstrated, the knowledge of which is of importance also for the physician not dealing with psychiatry.     

Untersuchung nichtlinearer Schwingungseigenschaften zur zerstörungsfreien Zustandsprüfung am Beispiel von Stahlbetonbalken

The Investigation of Nonlinear Dynamic Behaviour for Non‐Destructive Damage Assessment of Reinforced Concrete Beams The detection of damages in civil engineering structures and bridges in particular is mainly done by visual examination. However, defects as for instance partial rupture of a prestressing cable or fatigue cracks in reinforcement can not be visually observed. It is well known that damage changes dynamic structural parameters like eigenfrequencies, eigenmodes and damping. However, the sensitivity to small damages is sometimes low. Therefore, as an alternative the occurrence and evaluation of non‐linear dynamic behaviour is considered. The basic idea is that non‐linear dynamic effects increase with growing cracks under forced excitation. The implementation of this idea in the regular inspection program of bridges presupposes exact knowledge of the eigenfrequencies of the undamaged structure that are also supposed to be force dependent. This paper presents the results of an experimental approach with three reinforced concrete beams of different damage states investigating the non‐linear behaviour due to the excitation force.     

Relationships among body condition score,milk constituents,and postpartum luteal function in Norwegian dairy cows

Relationships among body condition score (BCS), milk constituents, and resumption of postpartum luteal function were studied in 162 lactations of first- and second-parity Norwegian dairy cows. Milk components included acetone, lactose, fat, protein, urea, and ratios of fat to protein and fat to lactose. Milk progesterone concentrations were used to determine intervals from calving to first luteal response (> 5 ng/ml). Intervals to first luteal response were divided into categories of early (< or = 24 d) or late (> 24 d) responses. Higher BCS were observed during wk 4 and 5 postpartum among both first- and second-parity cows with early compared with delayed luteal responses. Second-parity cows with early onset of luteal function also had higher BCS from wk 6 through 12, whereas first-parity cows with early onset of luteal function had higher BCS from wk 13 through 15. Higher acetone levels from wk 2 through 4 postpartum were associated with late luteal response in second-parity cows. Greater milk lactose content during wk 1, 2, 3, 6, 7, and 8 postpartum and higher fat fractions during wk 4 postpartum were related to early luteal response in second-parity cows. Relationships between milk constituents and onset of luteal function were less evident and occurred later postpartum among first-parity cows than among second-parity cows. Measures of weekly milk composites obtained during the early postpartum period and BCS were closely associated with postpartum resumption of luteal function. Acetone and lactose values in milk from the first 4 wk postpartum predicted postpartum luteal function in second-parity cows at a sensitivity of 0.84 and specificity of 0.86.