Detection of hemophilia carriers during pregnancy

The accuracy of hemophilia A carrier detection during pregnancy has been determined using combined measurement of VIII:CAg and VIIIR:Ag. These immunoassays detect determinants that are sufficiently stable in plasma that the assays could be done on frozen samples that had been obtained when women were seen for antenatal diagnosis studies (carrier women) or for routine prenatal care (controls). A linear discriminant was calculated that best separated the data for 32 normal women and 25 obligate carriers of the hemophilia gene. Twenty-three of 25 carriers (92%) and all 32 control women were correctly identified in this analysis. The overall classification accuracy (55/57, 96%) is comparable to that obtained by VIII:C and VIIIR:Ag measurements using freshly drawn blood samples in nonpregnant individuals. This study demonstrates that hemophilia A carriers can be detected during pregnancy with sufficient accuracy that the information may be used for genetic counseling.     

The ALS6 and ALS7 genes of Candida albicans

ALS genes of Candida albicans encode a family of cell-surface glycoproteins that are composed of an N-terminal domain, a central domain of a tandemly repeated motif, and a relatively variable C-terminal domain. Although several ALS genes have been characterized, more ALS-like sequences are present in the C. albicans genome. Two short DNA sequences with similarity to the 5' domains of known ALS genes were detected among data from the C. albicans genome sequencing project. Probes developed from unique regions of these sequences were used to screen a genomic library from which two full-length genes, designated ALS6 and ALS7, were cloned. ALS6 and ALS7 encode features similar to other genes in the ALS family and map to chromosome 3, a chromosome previously not known to encode ALS sequences. ALS6 and ALS7 are present in all C. albicans strains examined. Additional analysis suggested that some C. albicans strains have another ALS gene with a 5' domain similar to that of ALS6. Characterization of ALS7 revealed a novel tandemly repeated sequence within the C-terminal domain. Unlike other ALS family tandem repeats, the newly characterized ALS7 repeat does not appear to define additional genes in the ALS family. However, our data and information from the C. albicans genome sequencing project suggest that there are additional ALS genes remaining to be characterized.     

A New High-Temperature Oscillating Cup Viscometer

A new oscillating cup viscometer for temperatures up to 2,300°C has been constructed. A vacuum furnace with a graphite heater is used for heating the sample. The temperatures of the furnace and sample are measured by both a thermocouple and a pyrometer. The temperature is controlled with a stability better than 1 K. The oscillation of the cup is measured with a reflected laser beam using a position sensitive detector. The measured values of angle and time are then fitted to an analytical oscillation function. From the parameters of this function, the viscosity values are calculated using the Roscoe formalism. Measurements were carried out on pure metals at temperatures up to 1,700°C because of limitations of the thermocouple. The obtained viscosity values showed good agreement with literature data.     

A β‐Hairpin‐Binding Protein for Three Different Disease‐Related Amyloidogenic Proteins

Amyloidogenic proteins share a propensity to convert to the β‐structure‐rich amyloid state that is associated with the progression of several protein‐misfolding disorders. Here we show that a single engineered β‐hairpin‐binding protein, the β‐wrapin AS10, binds monomers of three different amyloidogenic proteins, that is, amyloid‐β peptide, α‐synuclein, and islet amyloid polypeptide, with sub‐micromolar affinity. AS10 binding inhibits the aggregation and toxicity of all three proteins. The results demonstrate common conformational preferences and related binding sites in a subset of the amyloidogenic proteins. These commonalities enable the generation of multispecific monomer‐binding agents.     

Innovative Lösungsansätze für das Fügen von AMCs

Innovative solutions for joining AMCs The application of aluminium matrix composite materials (AMC) in structural components requires appropriate joining technologies. One important aspect is the preservation of the properties of the composite during the joining process. The thermal load of the base material is particularly critical as a result of the process‐related heat input. In order to keep it low, adapted joining technologies and low‐melting fillers are essential. The combination of an ultrasound process and an induction heating offers various advantages. On the one hand, the ultrasound introduction achieves a destruction of the surface oxides and therefore a wetting of the joining surfaces without the use of flux. On the other hand, local inductive heating allows to realise very short joining times so that the heat input into the base materials to be joined can be reduced to a minimum. The application form of the fillers plays an important role for the achievable compound strengths. Selected test results will show the advantages and disadvantages of different variants.     

Physical Properties of Sn<Subscript>96.5</Subscript>Ag<Subscript>3.5</Subscript>-Based Solders with Additions of Bi,Ge, and In

The melting temperature, electrical resistivity, surface tension, and density of the (Sn_0.965Ag_0.035)_95.17Bi_4.83, (Sn_0.965Ag_0.035)_95.17Bi_4.73Ge_0.1, and (Sn_0.965Ag_0.035)₉₄-Bi₂In₄ alloys have been studied in comparison with the Sn₆₀Pb₄₀ and Sn_96.5Ag_3.5 binary alloys (all wt.%). The electrical conductivity of the solid alloys based on Sn_96.5Ag_3.5 is comparable to that of the Sn₆₀Pb₄₀ alloy. The wetting behavior on Cu and Ni surfaces has been investigated in a wide temperature interval. It is established that the addition of Bi to Sn_96.5Ag_3.5 decreases the surface tension and improves the wetting properties of the alloy. The addition of a small quantity of Ge to the Sn-Ag-Bi alloy did not improve the wetting behavior on either Cu or Ni surfaces. The wetting ability of the (Sn_0.965Ag_0.035)₉₄Bi₂In₄ alloy was slightly worse as compared with (Sn_0.965Ag_0.035)_95.17Bi_4.83.     

From Membrane to Skin: Aqueous Permeation Control Through Light‐Responsive Amphiphilic Polymer Co‐Networks

The functionalization of amphiphilic polymer co‐networks with light‐responsive spiropyran and spirooxazine derivatives leads to a new type of light‐responsive materials. The material consisting of hydrophilic nanochannels shows desirable properties such as light‐responsive permeability changes of aqueous caffeine solutions, an exceptional repeatability of the photochromism, and tunable basic permeability rates. The versatility of the system is demonstrated by using different functionalization routes such as copolymerization of light‐responsive monomers or crosslinker as well as postmodification of the preformed amphiphilic network. Moreover, light‐responsive spirobenzopyran and novel spirooxazine derivatives are synthesized, which changes the properties of the light‐responsive membranes after inclusion into the amphiphilic co‐networks. Finally, the permeability of the delivery membrane can be tailored to match the properties of porcine skin, an in vitro model of human neonatal skin. One possible application might be the use of the light‐responsive membranes as key‐unit of a transdermal caffeine‐delivery system for preterm neonates.     

LIQUID-LIQUID EXTRACTION STUDIES OF METAL IONS WITH DITHIACROWN COMPOUNDS

The extraction properties of dibenzo-1, 10-dithia-[18]crown-6 compounds have been investigated. Especially thiophilic metals are effectively extracted. The extraction of Ag(I), Pd(II) and Au(III) is much greater than that of Hg(II) or Cu(I). Alkali and alkaline earth metals are not extracted. The experimental results show the coordination of metal ions with sulfur is decisive for the extraction. The variation of the subetituents at the macrocyclic ring from CH₃- t o CH₂Cl-groups influences the extraction power considerably. In contrast, the substitution on the benzo groups shows a less strong effect. The influence of diluents and counter anions on extraction are comparable with results in known crown ether systems. Synergistic extraction is observed for silver and mixtures of dithiacrown compounds and HDEHP, n-caprylic acid or TBP.     

Design, synthesis, and biological activities of potent and selective somatostatin analogues incorporating novel peptoid residues

We report the synthesis, bioactivity, and structure-activity relationship studies of compounds related to the Merck cyclic hexapeptide c[Pro6-Phe7-d-Trp8-Lys9-Thr10-Phe11], L-363,301 (the numbering in the sequence refers to the position of the residues in native somatostatin). The Pro residue in this compound is replaced with arylalkyl peptoid residues. We present a novel approach utilizing beta-methyl chiral substitutions to constrain the peptoid side-chain conformation. Our studies led to molecules which show potent binding and increased selectivity to the hsst2 receptor (weaker binding to the hsst3 and hsst5 receptors compared to L-363, 301). In vivo, these peptoid analogues selectively inhibit the release of growth hormone but have no effect on the inhibition of insulin. The biological assays which include binding to five recombinant human somatostatin receptors carried out in two independent laboratories and in vivo inhibition of growth hormone and insulin provide insight into the relationship between structure and biological activity of somatostatin analogues. Our results have important implications for the study of other peptide hormones and neurotransmitters.     

Preoperative application of glucocorticosteroids efficaciously reduces the primary immunological response in kidney transplantation

Early acute rejection episodes have a considerable influence on long-term prognosis of renal transplants. Therefore the aim of primary immunosuppressive therapy must be effective suppression of the immunological response following antigen recognition. Owing to their pharmacological properties, intravenously given glucocorticosteroids are suitable for the alteration of the primary immunological response. However, even after intravenous administration, glucocorticosteroids have a latency of hours prior to reaching maximum activity. In a prospective clinical study, 111 patients undergoing renal transplantation were preoperatively treated with 500 mg methylprednisolone for immunosuppressive induction. A historical group of 40 patients who had received the same dose as intraoperative bolus, was used for comparison. Postoperative immunosuppression did not substantially differ between the two groups. The incidence of acute rejections within 30 d after transplantation was a clinical parameter of the study. The mitogenic cytokine induction was measured in blood samples which were collected intraoperatively and on days 1, 2, and 5 after transplantation. Cytokine release served as an in vitro parameter for the immunological responsiveness of the transplant recipient. In the group under study, the incidence of acute rejections was 21% (23/111) and, in contrast, 43% (17/30) in the historical group (p < 0.05). 89% of the patients in the group being studied showed normal renal function after 1 yr, compared to 78% in the reference group (n.s.). Following preoperative (mean 5.09 h) administration of glucocorticosteroids, mitogenic cytokine induction (IL-1 beta, IL-2, sIL-2R and IFN-gamma) was almost completely blocked at the time of transplantation. A prospective, randomized study has just been started to evaluate the effect of preoperative administered glucocorticosteroids on the incidence of acute rejections and long-term allograft survival.