Temperature Dependence of Photoluminescence Intensity and Spin Contrast in Nitrogen-Vacancy Centers.

We report on measurements of the photoluminescence properties of single nitrogen-vacancy centers in diamond at temperatures between 4 K and 300 K. We observe a strong reduction of the PL intensity and spin contrast between ca. 10 K and 100 K that recovers to high levels below and above. Further, we find a rich dependence on magnetic bias field and crystal strain. We develop a comprehensive model based on spin mixing and orbital hopping in the electronic excited state that quantitatively explains the observations. Beyond a more complete understanding of the excited-state dynamics, our work provides a novel approach for probing electron-phonon interactions and a predictive tool for optimizing experimental conditions for quantum applications.

A flexion osteotomy for correction of a distal tibial recurvatum deformity: a retrospective case series.

AIMS: There is little information about how to manage patients with a recurvatum deformity of the distal tibia and osteoarthritis (OA) of the ankle. The aim of this study was to evaluate the functional and radiological outcome of addressing this deformity using a flexion osteotomy and to assess the progression of OA after this procedure. PATIENTS AND METHODS: A total of 39 patients (12 women, 27 men; mean age 47 years (28 to 72)) with a distal tibial recurvatum deformity were treated with a flexion osteotomy, between 2010 and 2015. Nine patients (23%) subsequently required conversion to either a total ankle arthroplasty (seven) or an arthrodesis (two) after a mean of 21 months (9 to 36). A total of 30 patients (77%), with a mean follow-up of 30 months (24 to 76), remained for further evaluation. Functional outcome, sagittal ankle joint OA using a modified Kellgren and Lawrence Score, tibial lateral surface (TLS) angle, and talar offset ratio (TOR) were evaluated on pre- and postoperative weight-bearing radiographs. RESULTS: Postoperatively, the mean score for pain, using a visual analogue scale, decreased significantly from 4.3 to 2.5 points and the mean American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score improved significantly from 59 to 75 points (both p < 0.001). The mean TLS angle increased significantly by 6.6°; the mean TOR decreased significantly by 0.24 (p < 0.001). Radiological evaluation showed an improvement or no progression of sagittal ankle joint OA in 32 ankles (82%), while seven ankles (18%) showed further progression. CONCLUSION: A flexion osteotomy effectively improved the congruency of the ankle joint. In 30 patients (77%), the joint could be saved, whereas in nine patients (23%), the treatment delayed a joint-sacrificing procedure. Cite this article: Bone Joint J 2019;101-B:682-690.

Signalling properties of an HIV-encoded angiogenic peptide mimicking vascular endothelial growth factor activity.

HIV-1 expresses a multifunctional protein called TAT (trans-acting transcriptional activator), the function of which in vivo is tightly correlated with the incidence of Kaposi's sarcoma in AIDS patients. TAT is angiogenic and apparently binds to receptors specific for vascular endothelial growth factor (VEGF). Amino acids 46-60 of HIV-TAT, known as the basic peptide, have been shown to be responsible for its functional interaction with VEGF receptors. To characterize further the binding properties of this peptide, its coding sequence was fused to the reading frame of bacterial thioredoxin, allowing the production of large amounts of chimaeric polypeptides in bacteria in a biologically active form. Binding of chimaeric proteins to VEGF receptors was studied in vitro in endothelial cell cultures expressing either of the two receptors. Chimaeric thioredoxin proteins carrying the basic domain of TAT bound to both VEGF receptors with affinities similar to those of HIV-TAT or VEGF. Interestingly, these polypeptides competed only partially with VEGF for receptor binding, implying different binding sites for the TAT peptide and VEGF. This suggests that TAT binds VEGF receptors at new sites that might be useful targets for pharmacological intervention during pathological angiogenesis. The thioredoxin/basic-peptide chimaeras are functional agonists that mediate VEGF receptor signalling: (1) they stimulate the growth of endothelial cells; (2) together with basic fibroblast growth factor they cause tube formation of endothelial cells in collagen gels; (3) they induce blood vessel formation on the chicken chorioallantoic membrane; and (4) they activate VEGF receptor kinase and mitogen-activated protein kinase activity.

Production of functionalized single-chain Fv antibody fragments binding to the ED-B domain of the B-isoform of fibronectin in Pichia pastoris.

The Pichia pastoris expression system was used to produce functionalized single-chain antibody fragments (scFv) directed against the ED-B domain of the B-fibronectin (B-Fn) isoform which was found to be present only in newly formed blood vessels during tumor angiogenesis. Therefore, scFv antibody fragments recognizing the ED-B domain are potential markers for angiogenesis. We constructed four functionalized scFv antibody fragments for direct labeling with radioactive molecules or toxins or for attachment to liposomes serving as carriers for cytotoxic or antiangiogenic compounds. The C-termini of the scFv antibody fragments contain 1-3 cysteine residues that are separated by a hydrophilic linker (GGSSGGSSGS) from the binding domain and are accessible for site-specific functionalization with thiol-reactive reagents. Plasmid expression, culture conditions, and purification were optimized in 1-L cultures. The scFv antibody fragments were purified by anion exchange chromatography. The yields were 5-20 mg/L culture medium. The large-scale production of one scFv antibody fragment in a 3.7-L fermenter gave a yield of 60 mg. The reactivity of the cyteines was demonstrated by labeling with the thiol-reactive fluorescent dye ABD-F. The four scFv antibody fragments bound specifically to ED-B-modified Sepharose and binding was further confirmed by immunofluorescence on cell cultures using ED-B-positive human Caco-2 tumor cells. Furthermore, we could demonstrate specific binding of scFv-modified liposomes to ED-B-positive tumor cells. Our results indicate that the P. pastoris expression system is useful for the large-scale production of cysteine-functionalized alpha-ED-B scFv antibody fragments.

Vascular endothelial growth factor (VEGF) and its receptors in tumor-bearing dogs.

The molecular biology of the angiogenic growth factor, vascular endothelial growth factor (VEGF), has been studied in the dog. All major isoforms of VEGF are present in the dog. The amino acid sequences are identical between human and dog in the loop regions that are responsible for receptor binding. Accordingly, the VEGF receptors of dogs and humans are very similar and permit functional exchange of the growth factor. Here we show that canine VEGF activates human endothelial cells to the same extent as human VEGF. Similarly, the two proteins display identical cell binding properties. The VEGF receptor 1 (Flt-1) shows the same alternative splicing in humans and dogs and is overexpressed in the majority of tumors in both species. VEGF occurs also in canine tumors in similar relative quantities as in human malignancies. Based on the literature and our study we suggest that the molecular biology and the function of the VEGF signaling system are virtually identical in humans and canines and in healthy as well as in disease conditions.

Antisense strategies for glycosylation engineering of Chinese hamster ovary (CHO) cells.

Novel glycoproteins, inaccessible by other techniques, can be obtained by metabolic engineering of the oligosaccharide biosynthesis pathway. Furthermore, alteration of cell-surface oligosaccharides can change the properties of receptors involved in cell-cell adhesion. Sialyl Lewis X (sLex) is a cell-surface oligosaccharide determinant which is specifically expressed on granulocytes and monocytes and which interacts with selectins to influence leukocyte trafficking, thrombosis, inflammation, and cancer. Antisense technology targeting fucosyltransferase VI (Fuc-TVI), an enzyme necessary for the synthesis of the sLex in engineered Chinese hamster ovary (CHO) cells, has reduced Fuc-TVI activity, sLex synthesis, and adhesion to endothelial cells. Antisense methodology to reduce targeted activity in oligosaccharide biosynthesis or other pathways is an important addition to CHO cell metabolic engineering capabilities.

Use of potentially abusive psychotropic substances in psychiatric inpatients.

A series of 417 consecutively admitted psychiatric inpatients were studied with regard to their use of potentially abusive psychotropic substances in the last 3 months preceding admission. In all patients face-to-face interviews were performed; in 354 of them urine specimens could also be tested. Alcohol and benzodiazepines belonged to the most frequently used substances followed by cannabis, opiates and cocaine. Barbiturates, hallucinogens and amphetamine derivatives were only exceptionally reported. The most important finding of the study is that every fifth patient regularly used "hard" drugs (opiates and/or cocaine), every fourth patient illegal drugs and every third patient alcohol. Substances were found in 54% of all urine specimens; methadone, opiates and cocaine were hardly found alone. For the latter substances excellent agreement was found between interview reports and urine exams. Excluding patients diagnosed as substance-use disorders, there were no statistically significant differences between schizophrenic, affective, neurotic/stress/somatoform and other disorders with regard to the use of "hard" drugs and illegal drugs. Regular substance use correlated with much worse psychosocial adjustment. Substance use has to be explored and considered in every individual psychiatric inpatient.

Reliable computer-assisted classification of the EEG: EEG variants in index cases and their first degree relatives.

A method which optimizes on global properties of sample recordings is proposed for the definition of and the discrimination between electroencephalogram (EEG) classes. The sample was drawn from students at the University of Heidelberg from 1974 to 1978 and consists of 15 healthy index cases clinically ascertained as belonging to the low voltage EEG group. In addition, the three clinically defined groups: diffuse beta (18 index cases), borderline alpha (12 index cases) and monomorphous alpha (18 index cases) have been included in the study, as well as the first degree relatives of the index cases, thus providing a clinical classification into four groups. The proposed method provides an automatic and reliable classification algorithm using discriminant and cluster analysis. The relation between such an automatized classification and clinical classification schemes is investigated. In particular, the inheritance of the low voltage EEG, the question on sex differences and the question of a simple Mendelian mechanism had been examined. The method of random splittings had been applied for discriminant and cluster analysis. Our findings can be summarized as follows: (1) except for the monomorphous alpha EEG group, the clinical classification shows rather marginal separation (discriminating performance 60% to 75%), while a new and more reliable grouping scheme improves the discriminating performance up to 87% to 91%. The latter scheme leads to the concept of personal channel pattern (PCP) and was compared to the clinical classification scheme by means of contingency tables; (2) only a weak correlation between the clinically and PCP-based groups could be found (Cramér Index: 0.27). Accordingly, we continued to investigate the extent to which the proposed EEG classification scheme can nevertheless explain the genetic mechanisms apparently involved in the low voltage EEG. We thus considered the role of sex differences manifest in our proposed new grouping scheme; (3) males occurred more frequently in the new group 3 and females more frequently in the new group 1. In this regard, a much better correlation of the new groups between mothers and children than between fathers and children was observed; and (4) with help of our new PCP scheme, we have been able to reproduce a simple two gene Mendelian scheme to explain inheritance of the clinical low voltage EEG group. In this PCP-based scheme, the low voltage property does not occur when dominance of a certain gene (called gene A) is absent.

Cellular site of synthesis and dynamics of cell surface re-expression of polysialic acid of the neural cell adhesion molecule.

Homopolymers of alpha-2,8-ketosidically linked sialic acid (polysialic acid) represent a posttranslational modification which, in mammals, appears to be unique for the neural cell adhesion molecule and the alpha subunit of sodium channels in brain. Under steady-state conditions, polysialic acid is detectable in the plasma membrane of different cell types but not in the cytoplasm. We have studied the site of synthesis and the cell surface re-expression of polysialic acid in a clonal subline of small cell lung carcinoma using the monoclonal antibody 735 and bacteriophage endosialidase, both specific reagents for polysialic acid. After enzymic removal, cell surface polysialic acid re-expression reached control levels only after 5 days. When Golgi to plasma membrane transport of endosialidase-treated cells was blocked by culture at 20 degrees C or in the presence of monensin at 37 degrees C, de-novo-synthesized polysialic acid became detectable in the Golgi apparatus. Our data show that synthesis of polysialic acid of the neural cell adhesion molecule with a degree of polymerization of at least nine occurs intracellular in the Golgi apparatus of a human small cell lung carcinoma cell line.

Efficacy of moclobemide in different patient groups. Results of new subscales of the Hamilton Depression Rating Scale.

Data from 38 double-blind and two single-blind studies with moclobemide vs. placebo and/or standard antidepressants (10 drugs) were available for an intent-to-treat meta-analysis (n = 2,371). In all, 236 subjects received placebo and 1,107 moclobemide. As a measure of efficacy, a > or = 50% decrease from the baseline on the Hamilton Rating Scale for Depression (HAM-D) and its new subscales was taken. Furthermore, the Global Assessment of Efficacy (GAE) was analyzed. New subscales of the HAM-D consist of a retarded depression and an agitation/anxiety scale. The two factors were obtained from factor analyses of 12 x 8 random subsamples resulting in a stable solution. The subjects were subclassified by severity (low, medium, high) prior to treatment. The response to placebo was consistently lower in high scorers. In contrast to that, high scorers on active drugs (moclobemide, imipramine, and clomipramine) showed a tendency to higher response rates. Response rates were, in general, higher on the subscale retarded depression than on agitation/anxiety for both placebo and active drugs. Response rates to moclobemide were highest in unipolar endogenous depressives (66%) followed by bipolars (57%), neurotic depressives (52%), and reactive depressives (43%).

Recurrent brief depression: a new subtype of affective disorder.

This paper presents the diagnostic criteria for a new subtype of affective disorder, recurrent brief depression (RBD). Data from a prospective longitudinal cohort of young adults from the general population of Zurich, Switzerland, showed that a substantial proportion met all of the criteria for major depression in current diagnostic systems except duration. The validity of the subtype of RBD was examined according to clinical manifestations, severity, longitudinal course, and family history. RBD was found to be similar to major depressive disorder (MDD) on most of the indicators of validity including symptomatology, association with somatic and psychiatric disorders, age at onset, family history, longitudinal course and levels of impairment, except duration of depressive episodes. This suggests that RBD constitutes a valid subtype of affective disorder. The major implications of these findings are that both recurrence and duration should be considered in developing diagnostic thresholds for depression and in assessing the severity of affective disorders.

[Premorbid personality of schizophrenic patients]. / Zur prämorbiden Persönlichkeit Schizophrener.

This review summarizes different studies on schizophrenics regarding their premorbid personality. Schizophrenics do not average other social classes (father's profession) than endogenous or reactive depressives do, nor do they differ from the general population in that respect. On the other hand, schizophrenics show an inferior schooling achievement, as compared to depressives, and partially for that reason belong to lower social classes prior to the onset of their illness. Detailed studies of the respective social network show that schizophrenics develop in a less emancipated manner than controls, that they stick more to their families of origin, and that they engage in fewer interpersonal relationships. The latter not only are quantitatively inferior to those of healthy people, but also in quality; their relationships are often distant and alienated. In a prospective epidemiological study, 28 schizophrenics were assessed with a multi-dimensional personality test, the FPI, on average 2 years prior to the onset of their illness. The selfrating results show that schizophrenics are introverted premorbidly, as compared to control groups; it is assumed that this personality trait will be understood as "schizoid" in non-selfrating. Surprisingly, schizophrenics premorbidly have a normal neuroticism score, i.e. they are not more irritable, more aggressive, more depressive or emotionally unstable than controls.

[Signs of the zodiac and personality]. / Tierkreiszeichen und Persönlichkeit

3074 young men resident in the canton of Zurich, representing 50% of the 19 year old male population, form the fully representative sample of our large scale investigation. We investigated whether personality traits measured by means of the differentiated "Freiburger personality inventory" (FPI) could in any way be correlated to the signs of the zodiac under which the young men were born. The statistical analysis did not reveal any correlation between signs of the zodiac and personality. The claim made by astrologers that people can be characterized according to their sign of the zodiac (sagitarius, taurus, cancer, scorpion) must be refuted. Of course the astrologically founded description of human personality does not base itself on the position of the sun only, however the latter does form a very essential part of the astrological evaluation of people. This, at any rate has been shown to be without any scientific basis. The fact that astrological evaluation of human personality is so popular nowadays can be explained by the fact that even modern people are inclined towards magical thinking.

[Methodological problems in studying psychotropic drugs with special reference of the AMP system]. / Methodische Probleme bei Psychopharmakastudien, unter besonderer Berücksichtigung des AMP-Systems

There are several methodical problems that have to be coped with when testing psychotropic drugs in psychiatric clinics. In this paper some relevant problems have been discussed which are encountered during that part of a clinical trial, starting with the assessment of the initial psychopathological state of the patients and ending with the statistical analysis. Especially the AMP-System was considered. Particularly the following points have been dealt with: comparison of different methods for the assessment of psychotropic effects, special problems of rating scales, studies on the AMP-system concerning psychopathological and methodical aspects, conversion and processing of AMP-data, general considerations on the statistical analysis of drug trials.