Experimental capabilities for liquid jet samples at sub-MHz rates at the FXE Instrument at European XFEL.

The Femtosecond X-ray Experiments (FXE) instrument at the European X-ray Free-Electron Laser (EuXFEL) provides an optimized platform for investigations of ultrafast physical, chemical and biological processes. It operates in the energy range 4.7-20 keV accommodating flexible and versatile environments for a wide range of samples using diverse ultrafast X-ray spectroscopic, scattering and diffraction techniques. FXE is particularly suitable for experiments taking advantage of the sub-MHz repetition rates provided by the EuXFEL. In this paper a dedicated setup for studies on ultrafast biological and chemical dynamics in solution phase at sub-MHz rates at FXE is presented. Particular emphasis on the different liquid jet sample delivery options and their performance is given. Our portfolio of high-speed jets compatible with sub-MHz experiments includes cylindrical jets, gas dynamic virtual nozzles and flat jets. The capability to perform multi-color X-ray emission spectroscopy (XES) experiments is illustrated by a set of measurements using the dispersive X-ray spectrometer in von Hamos geometry. Static XES data collected using a multi-crystal scanning Johann-type spectrometer are also presented. A few examples of experimental results on ultrafast time-resolved X-ray emission spectroscopy and wide-angle X-ray scattering at sub-MHz pulse repetition rates are given.

Mechanism and dynamics of fatty acid photodecarboxylase.

Fatty acid photodecarboxylase (FAP) is a photoenzyme with potential green chemistry applications. By combining static, time-resolved, and cryotrapping spectroscopy and crystallography as well as computation, we characterized Chlorella variabilis FAP reaction intermediates on time scales from subpicoseconds to milliseconds. High-resolution crystal structures from synchrotron and free electron laser x-ray sources highlighted an unusual bent shape of the oxidized flavin chromophore. We demonstrate that decarboxylation occurs directly upon reduction of the excited flavin by the fatty acid substrate. Along with flavin reoxidation by the alkyl radical intermediate, a major fraction of the cleaved carbon dioxide unexpectedly transformed in 100 nanoseconds, most likely into bicarbonate. This reaction is orders of magnitude faster than in solution. Two strictly conserved residues, R451 and C432, are essential for substrate stabilization and functional charge transfer.

[Routine outcome monitoring (ROM) early in treatment and disorder specific. Observational study into generic and specific questionnaires to measure the early change in depression treatment]. / ROM vroeg in de behandeling en specifiek; observationeel onderzoek naar generieke en specifieke vragenlijsten bij meten van vroege verandering bij depressiebehandeling.

BACKGROUND: Mental health care institutions use routine outcome monitoring (ROM) to determine whether a patient responds well to treatment. However, it has been still unanswered whether disorder specific or generic measurement instruments can best be used for this purpose. In addition, little is known about when a first indication can be given for the outcome of the treatment.
AIM: To provide insight into the sensitivity to change of two questionnaires: a generic and a specific one, which were both used for clients with a depressive disorder. An additional objective is to provide insight into when a first indication can be given for the outcome of the treatment.
METHOD: An observational cohort study with data from 518 patients with a depressive disorder. The Outcome Questionnaire (OQ-45.2) and the Inventory of Depressive Symptomatology (IDS-SR) were used to measure the course of treatment.
RESULTS: The depression specific IDS-SR appeared to be more sensitive to change than the generic OQ-45.2, especially at the beginning of treatment. With a measurement frequency of once every four weeks, the best time to get a first indication on the outcome of the treatment was between week 4 and week 8.
CONCLUSION: For clients and practitioners whose treatment focus is reducing depressive symptoms, a disorder specific questionnaire is preferable to monitor this. The measurement between 4 and 8 weeks is important for, if necessary, adjusting the treatment, and to improve the treatment outcome.

[Patients without DSM-IV-disorders and/or subclinical symptoms in generalistic and specialised mental health care]. / Patiënten zonder DSM-IV-diagnose en/of met subklinische klachten in de generalistische en specialistische ggz.

BACKGROUND: Our study was motivated mainly by the results from nemesis-2 which showed that four out of ten patients in ambulantory mental health care had not had any mental disorder in the previous 12 months. A dsm-iv classification of the symptoms of patients is required for receiving insured mental health care.
AIM: To find out whether patients who attended a mental health generalistic or specialised clinic had a dsm-classified mental disorder and to assess the severity of these patients' symptoms. We have given specific attention to the characteristics of patients with subclinical symptoms who turned up at the mental health care clinics.
METHOD: dsm-iv disorders of patients in mental health care were studied by means of the mini 5.0.0 (n = 3072). The oq-45 was used to determine the severity of symptoms in both generalistic (n = 2255) and specialised mental health care (n = 5009). Logistical regression was used to determine the differences between the characteristics of patients who had clinical scores and those of patients who had subclinical scores. For this purpose we also used anonymised data from the personal health records.
RESULTS: During the intake procedure at specialised mental health care clinics only 14.3 % of patients failed to meet the diagnostic criteria of a dsm-iv disorder. Also, 56.5 % of patients seen by a mental health generalist and 70,9 % of patients seen by a mental health specialist had high or very high symptomatic distress, according the oq-45. The proportion of patients with a dsm-iv disorder varied from 52.9 % for patients with subclinical oq-45 scores to 94.8 % for patients with very high oq-45 scores. Predictors of patients with subclinical oq-45 scores were similar in generalistic and specialised mental health care.
CONCLUSION: Only a small number of patients in specialised care did not have an axis 1 dsm-iv diagnosis. Most patients in generalistic and specialised mental health care reported severe symptomatic distress. Symptoms mentioned by patients with subclinical oq-scores at the start of treatment were mainly stress-related.

Molecular characterization of cat factor XII gene and identification of a mutation causing factor XII deficiency in a domestic shorthair cat colony.

Coagulation factor XII (FXII) may be important in cardiovascular and inflammatory diseases. We have identified and characterized a naturally occurring mutation in the feline FXII gene that results in a mutant protein and enzymatic loss of activity. Feline intron/exon gene structure and sequence were acquired by comparing DNA sequences obtained from a fragmented Felis catus genomic sequence and the National Center for Biotechnology Information's Cross Species Megablast of multiple species' FXII gene sequences. Fourteen exons ranging in size from 57 to 222 base pairs were confirmed spanning 8 Kb on chromosome A1. The 1828-base pair feline FXII messenger RNA (mRNA) sequence contains an open reading frame that encodes a protein of 609 amino acids with high homology to human FXII protein. Total RNA and mRNA purified from liver tissue of 4 wild-type/normal and 8 FXII-deficient cats confirmed the predicted mRNA sequence and identified one important single-nucleotide polymorphism (SNP). A single base deletion in exon 11 of the FXII coding gene in our colony of cats results in deficient FXII activity. Translation of the mRNA transcript shows a frame shift at L441 (C441fsX119) resulting in a nonsense mutation and a premature stop codon with a predicted 560-amino acid protein. The mutant FXII protein is truncated in the 3' proteolytic light chain region of the C-terminus, explaining its loss of enzymatic activity. This study is the first molecular characterization of the feline FXII gene and the first identification of an FXII mutation in the domestic cat, providing insights into the origin and nature of feline FXII deficiency.

A phase II prospective open-label escalating dose trial of recombinant interleukin-11 in mild von Willebrand disease.

von Willebrand factor (VWF) is a multimeric glycoprotein that mediates platelet adhesion and is decreased in von Willebrand disease (VWD). 1-8 deamino-d-arginine vasopressin (DDAVP), the most common treatment for VWD, is limited by tachyphylaxis and inconvenience, and in 20% of the patients, unresponsiveness. Recombinant human interleukin-11 (rhIL-11), a gp-130 signalling cytokine with haematopoietic and anti-inflammatory activity, increases VWF antigen and its activity in heterozygous VWF(+/-) mice and dogs. To determine the biological efficacy and safety of rhIL-11 in non-bleeding human subjects with mild VWD, we conducted a phase II prospective open-label trial of rhIL-11 at 10, 25 and 50 mug kg(-1) subcutaneously (s.c.), given daily for 7 days in nine subjects with mild VWD. VWF and factor VIII (FVIII) levels increased gradually and progressively after s.c. rhIL-11, which was sustained through 7 days of dosing to 1.5- to 3-fold over baseline. Following intravenous DDAVP, 0.3 mug kg(-1), on day 7 there was a further boost in VWF and FVIII levels, suggesting that the mechanism of rhIL-11 differs from that of DDAVP. Platelet VWF mRNA expression measured by quantitative PCR increased from two- to eightfold over baseline, suggesting that the mechanism of rhIL-11 effect may be upregulation of VWF mRNA. VWF and FVIII levels returned to baseline by day 14. rhIL-11 was well tolerated with less than grade-1 hypertension, hypokalaemia and fluid retention. Recombinant IL-11 increases VWF levels in humans with mild VWD, justifying future clinical trials to determine its potential in preventing or reducing bleeding in this patient population.

[Correction osteotomy and stabilization with the interlocking nail]. / Die Korrekturosteotomie und Stabilisierung mit dem Verriegelungsnagel.

Compression and angle plates fitted after corrective osteotomies for congenital or post-traumatic bony malalignment entail the disadvantage that a longer period of non-weight-bearing is needed before consolidation. This is in contrast to the advantages of medullary nailing with interlocking nails in dynamic and static applications, which allow early weight-bearing. The interlocking nail can be used after osteotomies to correct derotation and axial malalignment, but also after lengthening and shortening osteotomies, which we perform both as open procedures and as closed procedures with the aid of the Küntscher saw.

Effects of ozone, acid mist and soil characteristics on clonal Norway spruce (Picea abies (L.) Karst.)--an introduction to the joint 14 month tree exposure experiment in closed chambers.

This paper introduces a series of publications referring to a single 14-month laboratory study testing the hypothesis that the recent decline of Norway spruce (Picea abies (L.) Karst.) at higher elevations of the Bavarian Forest and comparable forests in medium-range mountains and in the calcareous Alps is caused by an interaction of elevated ozone concentrations, acid mist and site-specific soil (nutritional) characteristics. The effect of climatic extremes, a further important factor, was not included as an experimental variable but was considered by testing of the frost resistance of the experimental plants. Results of these individual studies are presented and discussed in the following 14 papers. Plants from six pre-selected clones of 3-year-old Norway spruce (Picea abies (L.) Karst.) were planted in April 1985 in an acidic soil from the Bavarian Forest, or a calcareous soil from the Bavarian Alps. After a transition period, plants were transferred, in July 1986, into four large environmental chambers and exposed for 14 months to an artificial climate and air pollutant regime based on long-term monitoring in the Inner Bavarian Forest. The climatic exposure protocol followed realistic seasonal and diurnal cycles (summer maximum temperature, 26 degrees C; total mean temperature, 9.8 degrees C; winter minimum, -14 degrees C; mean relative humidity, 70%; maximum irradiance, 500 W m(-2); daylength summer maximum, 17 h; winter minimum, 8 h). Plants were fumigated with ozone, generated from pure oxygen (control: annual mean of 50 microg m(-3); pollution treatment: annual mean of 100 microg m(-3) with 68 episodes of 130-360 microg m(-3) lasting 4-24 h), and background concentrations of SO(2) (22 microg m(-3)) and NO(2) (20 microg m(-3)); windspeed was set at a constant 0.6 m s(-1). Plants were additionally exposed to prolonged episodes of misting at pH 5.6 (control) and pH 3.0 (treatment). Simulation of the target climatic and fumigation conditions was highly reliable and reproducible (temperature +/-0.5 degrees C; rh+/-10%; ozone+/-10 microg m(-3);SO(2) and NO(2)+/-15 microg m(-3)).

Clone and soil effects on the growth of young Norway spruce during 14 months exposure to ozone plus acid mist.

Five clones of 3-year old Norway spruce (Picea abies [L.] Karst), planted in a soil from the Bavarian Forest (pH 4.4) or a soil from the Calcareous Bavarian Alps (pH 6.9), were exposed for two successive vegetation periods, in closed environmental chambers, to a pollution treatment consisting of acidic mist (pH 3.0) plus ozone levels of 100 microg m(-3) with episodes of 130-360 microg m(-3); control trees were exposed to mist of pH 5.6 and ozone levels of 50 microg m(-3). Climatic and pollution protocols followed the diurnal and seasonal pattern characteristic for the Inner Bavarian Forest in Southern Germany, an area affected by the new-type forest decline. Biometric parameters were strongly related to clone and soil. Pollution treatment had a limited effect on only a few growth parameters. The stem diameter growth increment of two clones was reduced by pollution treatment in both soils, a third clone was affected in the acidic soil only. Two other clones were not affected at all. Stem volume increment of three clones, calculated as D(2)H, was reduced by pollution treatment in the neutral soil, a fourth clone was affected in the acidic soil only. Bud break was either delayed (two clones) or accelerated (two other clones) by treatment. Depending on soil and clone, needle yellowing was observed in previous years' needles in both treatment and control trees exposed to increased light intensities. The 'spotted' yellowing was not identical to symptoms found in forest decline areas and was most likely a consequence of nutrient deficiencies during the vegetation period preceding the experiment. The results of this experiment are discussed with regard to field observations and forest productivity. The complex pattern of growth responses resulting from interactions between air pollution, soil and genetic factors is considered to reflect different susceptibilities of trees to air pollutants.

Influence of soil substrate and ozone plus acid mist on the pigment content and composition of needles from young Norway spruce trees.

The influence of an ozone + acid mist treatment on photosynthetic pigments has been examined with the needles of the (Picea abies) clones 11, 14, 16, and 133 by spectrophotometric analysis of the total pigment extract and of single components upon HPLC separation (Part A), and in terms of a detailed pigment analysis of the 1987 and 1986 needles of clone 14 by TLC (Part B). Clone 14 had been already analysed prior to the onset of the experiment. At the end of the 14-month experiment, which incorporated frost events during a simulated winter period, neither symptoms corresponding to those of spruce Type I or IV decline, nor those of ozone damage could be observed. However, the 1986 needles of the trees on soil 1, which exhibit an adequate nutrient content, showed zonal chlorosis independently of the ozone + acid mist treatment. Analysis of variance of chlorophyll contents and needle ages showed a clear reduction to nearly 50% in the 1986 needles of clone 11, soil 1, and clone 16, soil 2. In contrast, clones 14 and 16 (soil 1) formed significantly more chlorophylls during the shorter exposure time in the 1987 flush. The detailed analysis of the individual pigment components of clone 14 needles provided no evidence for a destructive influence of the treatment on the chlorophylls, xanthophylls and beta-carotene in the two needle generations which had developed during the experiment, in spite of the distinct K deficiency of the 1986 needles of the trees on soil 2 and the common chlorosis of the needles of the trees on soil 1. The observed increase in violaxanthin content upon O(3)-treatment observed in clone 14 can be considered as an expression of the protective function of the xanthophylls against photooxidative processes. In conclusion, the observed differences in the chlorophyll and carotenoid contents are better correlated with the individual clone and soil character than with the ozone + acid mist treatment. Comparing the results of the pigment analyses of the needles the differences in the pigment concentrations reflect the N and K contents (Pfirrmann et al., 1990), which differ significantly between the clones. Thus it is not possible to pool the pigment data of all clones without considering the different nutrient levels.

Biochemical response of Norway spruce (Picea abies (L.) Karst.) towards 14-month exposure to ozone and acid mist: part I--Effects on polyphenol and monoterpene metabolism.

Three-year-old clonal Picea abies (L.) Karst. plants, grown either on a sandy (No. 1) or on a calcareous (No. 2) soil, were treated with ozone (100 microg m(-3) and peaks of up to 360 microg m(-3)) and acid mist (pH 3.0) over two vegetation periods. Needles of the current (1987) and previous (1986) year were analysed at the end of the experiment for biosynthetic enzymes and in vivo activity of the phenylpropanoid pathway, for products of polyphenol metabolism (clones 11 and 14), and for mono- and sesquiterpenes (clones 14 and 16). 1. Polyphenol metabolism. The activity of cinnamyl alcohol dehydrogenase, an enzyme of the lignin pathway, was increased by the treatment by up to 83% in the needles of both age classes. Chalcone synthase was measured in mature tree material for the first time. This enzyme, as well as phenylalanine ammonia-lyase activities and the content of catechin, astringin, isorhapontin, picein and p-hydroxyacetophenone, exhibited no significant treatment-dependent differences. However, soil and age-class dependent differences occurred. Pulse-labelling experiments with l[U-(14)C]phenylalanine and [2-(14)C]acetate were carried out at four different stages of shoot development and showed label incorporation into (+)-catechin and proanthocyanidins. There was no effect of the ozone and acid mist treatment. 2. Monoterpenes. The content of needle terpenes was generally diminished by the ozone and acid mist treatment. Other factors tested, such as clone, needle age and soil, exerted a highly significant influence on the content of most of the needle monoterpenes.

[Nerve graft of collateral branches of fingers. Report of a series of 16 reviewed cases]. / Greffes nerveuses des collatéraux digitaux. A propos d'une série de 16 cas revus.

Sixteen digital nerve grafts (14 patients) were reviewed with an average follow-up of 43 months. Average age was 27 years (7-53 yrs). Eleven grafts were performed on the thumb or the index finger. The nerve lesion was always proximal to the proximal interphalangeal joint, and associated with a tendinous lesion in one case out of two. One graft was done in emergency, 6 for failure of sutures and 7 for neglected wounds. Delay before grafting was on average of 4 months (0-16 months). The n. cutaneus antebrachii medialis was used in 11 patients. An hypoesthetic area of an average of 78 cm2 was noted, at the inferomedial part of the forearm, but only one patient complained with discomfort. At follow-up 3 patients, all under 20, had discriminative sensibility, 4 had protective sensibility and 5 only some sensibility to touch. Half of our patients complained with little discomfort, but 9 of 14 suffered with cold among which two suffered daily.