The SASE1 X-ray beam transport system.

SASE1 is the first beamline of the European XFEL that became operational in 2017. It consists of the SASE1 undulator system, the beam transport system, and the two scientific experiment stations: Single Particles, Clusters, and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX), and Femtosecond X-ray Experiments (FXE). The beam transport system comprises mirrors to offset and guide the beam to the instruments and a set of X-ray optical components to align, manipulate and diagnose the beam. The SASE1 beam transport system is described here in its initial configuration, and results and experiences from the first year of user operation are reported.

Giant prolapsed submucous leiomyoma: a surgical challenge for gynecologists.

We present a case of a 45-year-old woman who presented with irregular vaginal bleeding and menorrhagia for two months, with an episode of massive bleeding initiating 24 hours before with hemodynamic shock. Vaginal inspection showed a soft, rounded, friable mass in vaginal introitus. After hospitalization, blood transfusion and hydration, she was submitted to vaginal myomectomy with the withdrawal of a 12-cm white, solid, huge, pedunculated, leiomyoma; however, hysterectomy was performed due to persistent uterine bleeding. The postoperation period had no complications. Macroscopy showed a retraction of the myoma pedicle. Gynecologists should prioritize clamping of a pedicle before surgery, reducing its size if the tumor is large.

Time-resolved investigation of nanometer scale deformations induced by a high flux x-ray beam.

We present results of a time-resolved pump-probe experiment where a Si sample was exposed to an intense 15 keV beam and its surface monitored by measuring the wavefront deformation of a reflected optical laser probe beam. By reconstructing and back propagating the wavefront, the deformed surface can be retrieved for each time step. The dynamics of the heat bump, build-up and relaxation, is followed with a spatial resolution in the nanometer range. The results are interpreted taking into account results of finite element method simulations. Due to its robustness and simplicity this method should find further developments at new x-ray light sources (FEL) or be used to gain understanding on thermo-dynamical behavior of highly excited materials.

Optimization of minimum set of protein-DNA interactions: a quasi exact solution with minimum over-fitting.

MOTIVATION: A major limitation in modeling protein interactions is the difficulty of assessing the over-fitting of the training set. Recently, an experimentally based approach that integrates crystallographic information of C2H2 zinc finger-DNA complexes with binding data from 11 mutants, 7 from EGR finger I, was used to define an improved interaction code (no optimization). Here, we present a novel mixed integer programming (MIP)-based method that transforms this type of data into an optimized code, demonstrating both the advantages of the mathematical formulation to minimize over- and under-fitting and the robustness of the underlying physical parameters mapped by the code. RESULTS: Based on the structural models of feasible interaction networks for 35 mutants of EGR-DNA complexes, the MIP method minimizes the cumulative binding energy over all complexes for a general set of fundamental protein-DNA interactions. To guard against over-fitting, we use the scalability of the method to probe against the elimination of related interactions. From an initial set of 12 parameters (six hydrogen bonds, five desolvation penalties and a water factor), we proceed to eliminate five of them with only a marginal reduction of the correlation coefficient to 0.9983. Further reduction of parameters negatively impacts the performance of the code (under-fitting). Besides accurately predicting the change in binding affinity of validation sets, the code identifies possible context-dependent effects in the definition of the interaction networks. Yet, the approach of constraining predictions to within a pre-selected set of interactions limits the impact of these potential errors to related low-affinity complexes. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effects of beta-endorphin on endothelial/monocytic endothelin-1 and nitric oxide release mediated by mu1-opioid receptors: a potential link between stress and endothelial dysfunction?

Observations have been made linking the presence of psychosocial factors associated with elevated beta-endorphin concentrations with atherosclerosis. In this study, the authors assume an important role of the stress hormone beta-endorphin in several mechanisms that contribute to a dysbalance of human endothelial and monocytic endothelin (ET)-1 and nitric oxide (NO) release, mediated by mu1-opioid receptors. ET-1 and NO release were quantified via enzyme-linked immunosorbent assay (ELISA) or fluorometrically. mu1-Opioid receptors were identified by polymerase chain reaction (PCR) after stimulation with beta-endorphin. beta-Endorphin significantly increased endothelial and monocytic ET-1 release. The effect was mediated by mu1-opioid receptors and abolished by naloxonazine, a selective mu1-opioid receptor antagonist. In contrast, NO release was decreased under the influence of beta-endorphin. mu1-Opioid receptors on human monocytes and endothelial cells mediated a beta-endorphin-induced stimulation of ET-1 release, whereas NO release was decreased. Thus, the authors hypothesize a role of beta-Endorphin in the pathogenesis of stress-induced endothelial dysfunction through peripherally circulating beta-endorphin, which may offset the balance of vasoactive mediators, leading to an unopposed vasoconstriction. The data may also provide a new concept of mu1-opioid receptor antagonists, preventing beta-endorphin-induced disorders of vascular biology.

Female sex hormones decrease constitutive endothelin-1 release via endothelial sigma-1/cocaine receptors: an action independent of the steroid hormone receptors.

Cardiovascular disease is rare in premenopausal women compared to men. The authors investigate sex hormone-induced endothelin-1 (ET-1) release and the involvement of classic sex hormone receptors as well as the ability of sigma-1/cocaine receptors to respond to sex hormones. ET-1 release was measured in the supernatant of endothelial cells after treatment with beta-estradiol, progesterone, testosterone, or combined with their antagonists, and with the sigma-1 receptor ligand ditolylguanidine (DTG), or haloperidol, a sigma-1 receptor antagonist. Binding assays were performed using 2.5 x 10(-8) M [3H]DTG. Female sex hormones decreased ET-1 release whereas testosterone increased it, sex hormone antagonists only slightly attenuated or had no effect on the respective hormone's effect. DTG totally blocked the female sex hormone-induced inhibition on ET-1 release, whereas testosterone-induced stimulation was not affected. However, haloperidol blocked both. [3H]DTG binding was displaced by beta -estradiol but not by testosterone. DTG-binding sites account for 513 +/- 114 per cell, KD 8.79 nM. These data suggest that besides classic steroid hormone receptors, sigma-1/cocaine receptors mediate the effects of female sex hormones on ET-1 release, an up to now unknown signalling pathway. Results also suggest that female and male sex hormones may bind to different sites on sigma-1 receptors, exerting opposite pharmacological effects.

Adenovirus-associated pneumonia and hepatitis in four llamas.

This report focuses on the diagnostic laboratory and necropsy findings in 4 llamas with adenovirus-associated hepatitis or pneumonia. In the 2 young llamas, clinical illness was characterized by chronic respiratory tract disease. In the 2 adult llamas, clinical illness was characterized by neurologic signs and a history of respiratory tract disease. Histologic examination, electron microscopy, virus isolation, and fluorescent antibody results indicated that adenovirus infection was associated with disease in all 4 llamas.

Investigation of an epizootic of bovine viral diarrhea virus infection in calves.

Eight of 19 calves born to bovine viral diarrhea virus (BVDV)-negative and -immunocompetent dams were determined to be infected with a noncytopathic strain of BVDV. Six of the 8 calves had diarrhea and 2 had no clinical signs of disease. In 3 euthanatized calves, lesions consistent with mucosal disease were found throughout the gastrointestinal tract, and the virus was isolated from the spleen, lymph nodes, and small intestine. In 5 calves, BVDV was isolated from mononuclear cells in blood samples obtained 21 days apart, indicating persistent infection. The virus was not isolated from sera obtained from 2 calves, with chronic nonclinical infections, that had neutralizing antibody titers > or = 1:512 against bovine viral diarrhea-Singer virus and titers > or = 1:256 against the persistent BVDV. Twenty-one days after vaccination with a vaccine that contained inactivated noncytopathic and cytopathic biotypes of BVDV, 4 of 5 persistently infected calves had neutralizing antibody titers < or = 1:4 against the bovine viral diarrhea-Singer virus and their persistent virus. Prior to vaccination, 2 of 11 virus-negative calves had neutralizing antibody titers < or = 1:128 against the bovine viral diarrhea-Singer virus, and after vaccination, only 1 virus-negative calf had a titer < or = 1:512. At 149 days after revaccination and prior to weaning, 4 virus-negative calves had neutralizing antibody titers < or = 1:512 (range, 1:16 to 1:384). Under the specific conditions in this herd, we were not able to detect a beneficial effect of vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)

Hexachlorophene toxicosis in a litter of Doberman pinschers.

A litter of 5-week-old Doberman Pinschers with pustular dermatitis was treated dermally with a hexachlorophene-containing emulsion. Shortly after a second treatment, all of the puppies developed neurologic signs consisting of muscle tremors, ataxia, and apparent muscle weakness. The clinical history and signs, histologic lesions within the central nervous system, and measurement of hexachlorophene in liver and kidney tissue confirmed a diagnosis of hexachlorophene toxicosis.

Extraskeletal osteosarcoma in two dogs.

Extraskeletal osteosarcoma (ESOS) of the spleen and jejunum was diagnosed in 2 dogs. As an extremely uncommon type of tumor that has proven difficult to treat, ESOS is associated with high rate of local recurrence and metastatic disease. Extraskeletal osteosarcoma principally affects older dogs, has no apparent breed predilection, and may develop more frequently in males. The cause of ESOS is unknown, but may involve malignant metaplasia of pluripotential mesenchymal cells into osteoblasts. Macroscopically, ESOS usually is observed as a hard mass and may appear similar to calcified hematoma or myositis ossificans. The classic radiographic appearance of ESOS is a soft tissue mass with focal mineralization and without adjacent bone involvement.

Equine degenerative myeloencephalopathy: a vitamin E deficiency that may be familial.

Two horse farms, on which there was a high incidence of proven and suspected equine degenerative myeloencephalopathy (EDM), were studied. Symmetric ataxia and paresis, along with laryngeal adductor, cervicofacial, local cervical, and cutaneous trunci hyporeflexia, characterized the syndrome. Serum vitamin E concentration reflected a deficient state in affected and unaffected horses on both farms when compared with selected reference groups and with published values. A high incidence of the disease was evident in offspring of two particular sires on one farm. Vitamin E supplementation resulted in correction of the deficient state in most horses and was associated with a drastic reduction in the incidence of EDM on one farm from 40% to less than 10% the year following vitamin E supplementation. In addition, during the last year, the severity of signs in the few cases was dramatically reduced. This information substantiates the hypothesis that EDM is a vitamin E-responsive disorder of Equidae with a possible familial predisposition.

Methods of euthanasia in poultry and food-producing animals.

This article summarizes the methods of euthanasia in poultry and food-producing animals and details some of the advantages and disadvantages of specific methods. Specific recommendations are made for each type of animal, with alternative methods for special circumstances. Reasons are given for recommending methods that are not "first-choice methods" of the AVMA Panel on Euthanasia. Detailed descriptions are included for selected methods of euthanasia.

Lymphocytic-plasmacytic enteritis in a cat.

A cat with severe weight loss and small bowel diarrhea was diagnosed as having lymphocytic-plasmacytic enteritis. Treatment with medium chain triglycerides and glucocorticoids was palliative. This disease appears similar to that reported in Basenji dogs. In retrospect, dietary therapy should also have been attempted since cats with a similar infiltration of the colon responded well to such therapy.

Interactions of cold stress and Pasteurella haemolytica in the pathogenesis of pneumonic pasteurellosis in calves: method of induction and hematologic and pathologic changes.

Six healthy neonatal calves were chilled with cold water and had focal tracheitis induced by spraying 5% acetic acid into the tracheal lumen. Subsequently, 20 ml of sterile saline solution was injected intratracheally. The effects of these interventions on total and differential white cell counts, plasma cortisol, histamine, and bradykinin, hematocrit, total plasma solids, and indices of the erythrocyte size and hemoglobin content were determined over the subsequent 12 hours. Cold stress increased plasma cortisol levels for less than 1 hour, but did not alter any other variable. This group of calves served as a control group for a second series of neonatal calves which were given 2 X 10(9) organisms of Pasteurella haemolytica intratracheally immediately following an identical period of chilling and acetic acid exposure. Calves given P haemolytica became neutropenic. There were increased numbers of circulating band neutrophils by 12 hours after exposure, and serum cortisol values were maintained at the same or greater than cold stress concentrations for all measurement periods subsequent to exposure. Infected calves had acute fibrinous pneumonia from which P haemolytica was isolated. Contrary to previous reports, these data may indicate a role for the neutrophil in the pathogenesis of early lesions of pasteurellosis. Although the association of circulating corticosteroids with stress and subsequent infection is clear, our data provide no evidence to indicate that circulating histamine or bradykinin are involved in the pathogenesis of the acute lesions of Pasteurella pneumonia.