bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Homozygous Single Base Pair Deletion in the Gene Coding for the Human Platelet Glycoprotein Ibα Causing Bernard-Soulier Syndrome
Authors: Simsek S , Admiraal L G , Modderman P W , van der Schoot C E , von dem Borne A E G Kr 
Published: September 2018

SummaryBernard-Soulier Syndrome (BSS) is a hereditary bleeding disorder which is caused by the absence or the dysfunction of the platelet glycoprotein Ib/IX/V (GP Ib/IX/V) complex, the major receptor for von Willebrand factor (vWf). BSS is characterized by the presence of giant platelets that show a reduced binding of vWf. Although BSS is a well-characterized disease, and many cases have been described in the literature, the molecular genetic basis of this disorder has been studied in only a few patients.We have studied the genetic basis of the defect in a BSS patient. Flow cytometric analysis of the platelet membrane glycoproteins revealed a significant decrease or absence of GP Ibα on the platelet surface, and low levels of GP V and GP IX. In subsequent immunopre-cipitation experiments, we confirmed the presence of GP V (although in significantly decreased amounts) on the platelet surface. These results indicated a defect in the GP Ibα chainGenomic DNA coding for GP Ibα was amplified, using the polymerase chain reaction (PCR). Subsequent direct sequence analysis demonstrated a homozygous deletion of T317 resulting in a frameshift deletion and predicting a substitution of Arg for Leu76. This deletion causes a shift in the reading frame, predicting a premature stop codon after 19 altered amino-acids, leading to a severily truncated molecule. The molecular genetic defect found in this patient differed from the mutations observed in three other BSS patients described in the literature. This points to a marked hetereogeneity of this disease.The single basepair deletion created a target site for the restriction enzyme Hhal. This allowed us to perform PCR-ASRA (Allele-Specific Restriction enzyme Analysis) on all available family members. Both parents and the daughter of the patient appeared to be heterozygous for the deletion, while the homozygosity of the propositus for the mutant allele was confirmed.
Parameters of Haemostasis during Acute Venous Thrombosis
Authors: Reiter W , Ehrensberger H , Steinbrückner B , Keller F 
Published: September 2018

SummaryUnderlying disorders of the coagulation system such as inhibitor deficiencies or decreased fibrinolysis are common in patients suffering from venous thrombosis. They may lead to the necessity of a lifelong prophylaxis. Prompt diagnosis is obviously to the patients benefit. We investigated 22 patients suffering from venous thromboses for the inhibitors antithrombin III (ATIII), protein C, and protein S during the first 8 to 12 days after admission to hospital and in addition after withdrawal from anticoagulant treatment after several months. At the day of admission ATIII and protein C levels were comparable to those several months later, but after 2 days they shifted downward or upward, respectively. Protein S did not shift during the period of hospitalisation, but was initially slightly lower than several months later. For inhibitors the day of admission to hospital is most suitable to take the samples. About 50% of the patients still had elevated activation markers (prothrombin fragments F1+2, thrombin-antithrombin complex TAT, and D-dimers) after several months.
Comparison of Immunological and Functional Assays for Measurement of Soluble Fibrin
Authors: Dempfle C E , Pfitzner S A , Dollman M , Huck K , Stehle G , Heene D L 
Published: September 2018

SummaryVarious assays have been developed for quantitation of soluble fibrin or fibrin monomer in clinical plasma samples, since this parameter directly reflects in vivo thrombin action on fibrinogen. Using plasma samples from healthy blood donors, patients with cerebral ischemic insult, patients with septicemia, and patients with venous thrombosis, we compared two immunologic tests using monoclonal antibodies against fibrin-specific neo-epitopes, and two functional tests based on the cofactor activity of soluble fibrin complexes in tPA-induced plasminogen activation. Test A (Enzymun®-Test FM) showed the best discriminating power among normal range and pathological samples. Test B (Fibrinostika® soluble fibrin) clearly separated normal range from pathological samples, but failed to discriminate among samples from patients with low grade coagulation activation in septicemia, and massive activation in venous thrombosis. Functional test C (Fibrin monomer test Behring) displayed good discriminating power between normal and pathological range samples, and correlated with test A (r = 0.61), whereas assay D (Coa-Set® Fibrin monomer) showed little discriminating power at values below 10 μg/ml and little correlation with other assays. Standardization of assays will require further characterization of analytes detected.
Family Studies of Type II CD36 Deficient Subjects: Linkage of a CD36 Allele to a Platelet-Specific mRNA Expression Defect(s) Causing Type II CD36 Deficiency
Authors: Kashiwagi Hirokazu , Tomiyama Yoshiaki , Kosugi Satoru , Shiraga Masamichi , Lipsky Robert H , Nagao Nobuo , Kanakura Yuzuru , Kurata Yoshiyuki , Matsuzawa Yuji 
Published: September 2018

SummaryWe performed family studies with type II CD36 deficiency. In the Mi.Y family, the proband (YII.1) and his brother (YII.2) displayed a type II deficient phenotype. In the mother(YI.2), binding of the anti CD36 monoclonal antibody, 0KM5, to both platelets and monocytes was reduced as compared to CD36 positive control cells. In the father (YI.1), while 0KM5 binding to his platelets was reduced, that of his monocytes was almost the same as normal control monocytes. Analysis of genomic DNA showed that YI.2, YII.1 and YII.2 were heterozygous for a proline90→serine mutation, and showed that both alleles of YI.1 did not have the mutation. Analysis of CD36 cDNA showed that the Pro90 form of CD36 cDNA could be detected in monocytes, but not in platelets from YII.1 and YII.2. These data indicated that YII.1 and YII.2 could be compound heterozygotes; an allele having a platelet-specific mRNA expression defect(s), which was responsible for the different CD36 expression between their platelets and monocytes, and the Ser90 allele. YI.1 was suggested to be a carrier of the platelet-specific silent allele. The platelet-specific silent allele was linked to a specific genotype of a polymorphic microsatellite sequence in the CD36 gene, supporting our hypothesis that mRNA expression defect(s) occurred at or near the CD36 gene. In a second type IICD36 deficient family, we also obtained results consistent with this hypothesis.
Mitral Valve Surgery via Partial Upper Sternotomy: Closing the Gap between Conventional Sternotomy and Right Lateral Minithoracotomy
Authors: Oezpeker Cenk , Barbieri Fabian , Hoefer Daniel , Schneider Bastian , Bonaros Nikolaos , Grimm Michael , Mueller Ludwig 
Published: September 2018

Background Minithoracotomy (MT) has gained broad acceptance for mitral valve surgery (MVS) in the last decade. In the presence of defined limitations of MT, however, full sternotomy (FS) is still widely preferred. We assume that the less investigated partial upper sternotomy (PS) will permit the gap between MT and FS in MVS to be closed. The purpose of this study is to investigate a valid less invasive alternative to MT for isolated MVS or multivalve surgery.
Methods This retrospective analysis includes data on 1,639 patients, who underwent either isolated or combined primary MVS at our department from May 2011 to August 2017. Out of these, 663 patients were operated via MT access. One-hundred three patients had been judged as not suitable for MT but feasible for PS approach in which 53.4% (n = 55) had isolated MVS and 46.6% patients (n = 48) underwent multivalve surgery. Concomitant myocardial revascularization was performed in 2.9% of the study patients (n = 3).
Results Operative, 90-day, and 1-year mortality in the PS-cohort was 0, 1.0% (n = 1), and 3.3% (n = 3), respectively. During a median follow-up time of 1,115 days (interquartile range 398–1806), all-cause mortality was 5.8% (n = 6). Operative times for cardiopulmonary-bypass and cross-clamping were 167 minutes (140–198) and 107 minutes (93–132), respectively. Median length of stay at the intensive care unit and hospital was 1 (1–2) and 7 days (7–10), respectively.
Conclusion The presented results demonstrate that there is a cohort of patients, who are not candidates for MT in MVS but may be operated successfully by an alternative less invasive approach.
Ausbildung zum ärztlichen Psychotherapeuten
Authors: Jobst A. 
Published: September 2018

Zusammenfassung
Hintergrund: Die Ausbildungslandschaft zum ärztlichen Psychotherapeuten in Deutschland ist für Ausbildungskandidaten oftmals undurchsichtig. Anforderungen und Vorgaben sind für die verschiedenen Fachrichtungen und Zusatzweiterbildungen durch die Ärztekammern geregelt. Die Ausbildung in Psychotherapie erfolgt jedoch an psychotherapeutischen Ausbildungsinstituten. Hier unterscheiden sich die Ausbildungsstrukturen zum Teil erheblich und können von den Ausbildungskandidaten selbst gewählt werden. Trotz des vielschichtigen Angebots garantiert die ärztliche psychotherapeutische Ausbildung in Deutschland im europäischen Vergleich Qualitätsstandards über gesetzliche Vorgaben. Ziel: Die spezifische Rolle der ärztlichen Psychotherapie sollte auch vor dem Hintergrund der Reform des Psychotherapeutengesetzes nicht in Vergessenheit geraten.
Pharmakokinetisches Grundverständnis als Basis der individualisierten Psychopharmakotherapie
Authors: Schwarz M. J. 
Published: September 2018

Zusammenfassung
Hintergrund: Beim Start der „Precision Medicine Initiative“ wurde das rasche und einfache Bestimmen der optimalen Medikamentendosis für jeden individuellen Patienten als großes Ziel genannt. Insbesondere in der Psychopharmakotherapie ist durch das hohe Niveau des Therapeutischen Drug-Monitorings (TDM) dieses Ziel bereits jetzt erreichbar. Eine Grundvoraussetzung für die sinnvolle und fruchtbare Anwendung von TDM ist jedoch die Grundkenntnis pharmakokinetischer Mechanismen. Methode: In diesem Beitrag werden die für die individualisierte Therapie mit Psychopharmaka relevanten Grundlagen der Pharmakokinetik dargestellt. Eng damit verknüpft ist das Thema der Pharmakogenetik; deshalb wird auch hier ein Überblick über die aktuellen internationalen Leitlinien gegeben. Ziel: Auf dieser Grundlage basierend werden die „Werkzeuge“ zur Befundinterpretation der TDM-Ergebnisse dargestellt. Fallbeispiele zeigen typische und authentische Situationen, in denen TDM hilfreich angewandt wurde. Schließlich werden in einer als Kitteltaschenkarte verwendbaren Tabelle 2 die pharmakokinetischen Schlüsselinformationen wichtiger Psychopharmaka zusammengefasst.
Striking stationarity of large-scale climate model bias patterns under strong climate change
Authors: Krinner Gerhard , Flanner Mark G. 
Published: September 2018

Significance
The typical magnitude of coupled climate model biases is similar to the magnitude of the climate change that is expected on a centennial time scale. Using climate models for assessing future climate change therefore relies on the hypothesis that these biases are stationary or vary predictably. This hypothesis, however, has not been, and cannot be, tested directly. We compare the biases of individual models with respect to a multimodel mean for two very different climate states. Our comparison shows that under very large climate change the bias patterns of key climate variables do not change substantially. This provides a justification for using state-of-the-art climate models to simulate climate change and allows extending the range of climate model applications.
How to make an artificial satellite out of a nuclear reactor. An exploration of research-technology emergence and management at INVAP*
Authors: Seijo Gustavo 
Published: September 2018

ABSTRACT
This paper analyses research-technology (RT) emergence and management at INVAP. INVAP is an Argentinean state-owned enterprise based in Bariloche, Patagonia. Most INVAP decision-makers find it challenging to develop technology to meet client-specific needs. RTs exploit interstitial boundary-crossing knowledge. Organisational technology-rooted R&D learning can be characterised as a joint, transverse, inter-departmental and inter-disciplinary process. RT-related technologies have the potential to be dis-embedded from a specific development-project and/or technological area and re-embedded in another project or area. This paper traces the historical dynamics of six RTs at INVAP. Its perspective marginalises the conventional R&D emphasis on the generation of new products and the improvement of production processes, and highlights the importance of monitoring RT emergence. It argues that technology-based product portfolio strategies can profit substantially from good RT management and planning.
A Low-Cost Pupil Center Localization Algorithm Based on Maximized Integral Voting of Circular Hollow Kernels
Authors: Ince Ibrahim Furkan , Erdem Yusuf Sait , Bulut Faruk , Sharif Md Haidar 
Published: September 2018

Abstract
Pupil center localization is an essential requirement for robust eye gaze tracking systems. In this paper, a low-cost pupil center localization algorithm is presented. The aim is to propose a computationally inexpensive algorithm with high accuracy in terms of performance and processing speed. Hence, a computationally inexpensive pupil center localization algorithm based on maximized integral voting of candidate kernels is presented. As the kernel type, a novel circular hollow kernel (CHK) is used. Estimation of pupil center is employed by applying a rule-based schema for each pixel over the eye sockets. Additionally, several features of CHK are proposed for maximizing the probability of voting for each kernel. Experimental results show promising results with 96.94% overall accuracy with around 13.89 ms computational time (71.99 fps) for a single image as an average time by using a standard PC. An extensive benchmarking study indicates that this method outperforms the learning-free algorithms and it competes with the other methods having a learning phase while their processing speed is much higher. Furthermore, this proposed learning-free system is fast enough to run on an average PC and also applicable to work with even a low-resolution webcam on a real-time video stream.
Dimensionality of mental health activities in a German sample
Authors: Hofmann Hanna , Kohlmann Carl-Walter 
Published: September 2018

Abstract
For the promotion of mental health and the reduction of mental impairment, a person’s behavior is of vital importance. Therefore, the assessment of mental health behavior is crucial in the development of suitable interventions. The present study investigates 14 self-help strategies compiled by Morgan and Jorm (Self-help strategies that are helpful for sub-threshold depression: a Delphi consensus study. J Affect Disord2009;115: 196–200) as items of a self-report scale to assess mental health promoting behavior. Dimensionality and psychometrics of mental health activities were examined in a sample of 852 German adults (76% female). After exploratory factor analyses (EFAs, n = 543), several factor structure possibilities were subsequently tested by confirmatory factor analyses (CFAs, n = 309). Based on these results, psychometric properties were calculated. Factor analyses result in a three-factor solution with the subscales positive orientation, physical engagement and emotion regulation. CFAs indicate a good model fit. The total scale showed acceptable reliability. Correlations with indicators of positive mental health were higher than with those of mental impairment. Moreover, correlations support the three-factor structure of the instrument. Women scored higher than men in the total scale, due to differences in the subscale emotion regulation. Although some modifications were performed, the results of our analyses suggest that the self-help strategies introduced by Morgan and Jorm (2009) are indeed useful items for a brief scale to assess mental health activity. The identification of the multidimensionality is an important step in supporting the work of mental health promotion.
Pelagic habitat and offspring survival in the eastern stock of Atlantic bluefin tuna
Authors: Reglero Patricia , Balbín Rosa , Abascal Franciso Javier , Medina Antonio , Alvarez-Berastegui Diego , Rasmuson Leif , Mourre Baptiste , Saber Sámar , Ortega Aurelio , Blanco Edurne , de la Gándara Fernando , Alemany Franciso Javier , Ingram G Walter , Hidalgo Manuel 
Published: September 2018

Abstract
In this manuscript, we test how an understanding of geographical variation in larval fitness in relation to temperature and habitat use could be a useful method to improve our understanding of recruitment and develop better indices of annual recruitment. On the basis of the assumption that growth and survival of tuna larvae are influenced by temperature, we have developed a potential larval survival index for Atlantic bluefin tuna (Thunnus thynnus) by combining empirical data from egg and larval rearing experiments with temperature data from hydrodynamic models. The experiments were designed to test the full range of temperature variability that bluefin larvae would experience in the field and provide a mechanistic understanding of the processes driving egg and larval survival. We then developed a biological model using the temperature-related growth expressions and a size-dependent survival function for the larvae. The biological model was applied to a time-series of spatially explicit temperature data for the western Mediterranean from the Strait of Gibraltar to 6°E, which includes the major recognized bluefin tuna eastern stock spawning area, the Balearic Sea. Our results show that areas with high probabilities of larval survival coincide with those that would be considered as optimal based on other data sources (ichthyoplankton surveys, spawning female locations from commercial fisheries data, and adult tracking data). However, evidence of spawning has been found in areas with suboptimal thermal habitats, as predicted by the model, which we discuss regarding sampling effort and salinity fronts. There was a good match between the survival index and recruitment indices from standardized CPUE fisheries data. These results have implications for our understanding of the recruitment process of the eastern stock of Atlantic bluefin tuna, since they suggest that the combined effects of temporal and spatial variability of the environment drive recruitment success, which has important implications for the management of the species.
A new electron-multiplier-tube-based beam monitor for muon monitoring at the T2K experiment
Authors: Ashida Y , Friend M , Ichikawa A K , Ishida T , Kubo H , Nakamura K G , Sakashita K , Uno W 
Published: September 2018

Abstract
Muon beam monitoring is indispensable for indirectly monitoring accelerator-produced neutrino beams in real time. Though Si photodiodes and ionization chambers have been successfully used as muon monitors at the T2K experiment, sensors that are more radiation tolerant are desired for future operation. We have investigated the electron-multiplier tube (EMT) as a new sensor for muon monitoring. Secondary electrons produced by the passage of muons at dynodes are multiplied in the tube and produce signal. Two prototype detectors were installed at the T2K muon monitor location, and various EMT properties were studied based on in situ data taken with the T2K muon beam. The signal size is as expected based on calculation, and the EMTs show a sufficiently fast time response for bunch-by-bunch beam monitoring. The spill-by-spill intensity resolution is 0.4%, better than the required value (1%). Signal linearity within $\pm$1% is achieved at proton beam powers up to 460 kW (with +250 kA focusing horn operation). A gradual signal decrease was observed during the initial exposure, due to the stabilization of dynode materials, before the response became stable within $\pm$1%. This work demonstrates that EMTs are a good candidate for future muon monitoring at T2K, and may also have other more general applications.
Cell-free prototyping strategies for enhancing the sustainable production of polyhydroxyalkanoates bioplastics
Authors: Kelwick Richard , Ricci Luca , Chee Soo Mei , Bell David , Webb Alexander J , Freemont Paul S 
Published: September 2018

Abstract
The polyhydroxyalkanoates (PHAs) are microbially-produced biopolymers that could potentially be used as sustainable alternatives to oil-derived plastics. However, PHAs are currently more expensive to produce than oil-derived plastics. Therefore, more efficient production processes would be desirable. Cell-free metabolic engineering strategies have already been used to optimize several biosynthetic pathways and we envisioned that cell-free strategies could be used for optimizing PHAs biosynthetic pathways. To this end, we developed several Escherichia coli cell-free systems for in vitro prototyping PHAs biosynthetic operons, and also for screening relevant metabolite recycling enzymes. Furthermore, we customized our cell-free reactions through the addition of whey permeate, an industrial waste that has been previously used to optimize in vivo PHAs production. We found that the inclusion of an optimal concentration of whey permeate enhanced relative cell-free GFPmut3b production by approximately 50%. In cell-free transcription–translation prototyping reactions, gas chromatography–mass spectrometry quantification of cell-free 3-hydroxybutyrate (3HB) production revealed differences between the activities of the Native ΔPhaC_C319A (1.18 ± 0.39 µM), C104 ΔPhaC_C319A (4.62 ± 1.31 µM) and C101 ΔPhaC_C319A (2.65 ± 1.27 µM) phaCAB operons that were tested. Interestingly, the most active operon, C104 produced higher levels of PHAs (or PHAs monomers) than the Native phaCAB operon in both in vitro and in vivo assays. Coupled cell-free biotransformation/transcription–translation reactions produced greater yields of 3HB (32.87 ± 6.58 µM), and these reactions were also used to characterize a Clostridium propionicum Acetyl-CoA recycling enzyme. Together, these data demonstrate that cell-free approaches complement in vivo workflows for identifying additional strategies for optimizing PHAs production.