Miracle-dz/UniFAR-FTUs huggingface dataset:
Wachstum und chronische Erkrankungen

Viele chronische Erkrankungen gehen mit Wachstumsstörungen einher. Mukoviszidose, Morbus Crohn und juvenile idiopathische Arthritis sind chronische Erkrankungen, die im Kindesalter relativ häufig auftreten und mit erheblichen Wachstumsstörungen in Zusammenhang stehen. Während eine Wachstumsstörung die erste Manifestation einer Erkrankung sein kann, ist das Wachstumsverhalten darüber hinaus ein nützliches Mass für den Schweregrad der Krankheit und das Ansprechen einer Behandlung. Der resultierende Kleinwuchs kann, abgesehen von seinem diagnostischen Wert, für die Betroffenen nicht nur inakzeptabel sein, sondern sich bei Patienten mit Erkrankungen, wie z.B. Mukoviszidose, auch nachteilig auf die physische Gesundheit auswirken. Wachstumsstörungen bei Kindern mit chronischen Erkrankungen stehen in Zusammenhang mit einer Störung der GH-IGF-1-Achse und entstehen in erster Linie durch Mangelernährung, chronische Entzündung und Langzeitbehandlung mit Kortikosteroiden. Mangelernährung hat eine starke Anpassung des endokrinen Systems zur Folge, die darauf ausgerichtet ist, Energie zu sparen, den Wachstums- und Fortpflanzungsprozessen Stoffe zu entziehen, und alternative Energiequellen für die äusserst wichtige Homöostase des Körpers bereitzustellen. Zwar wird Mangelernährung durch chronische Entzündungsprozesse noch verschlimmert, aber proinflammatorische Zytokine, wie beispielsweise Interleukin-6, Tumor-Nekrose-Faktor-α und Interleukin-1β, wirken sich auch unabhängig von der Ernährung durch die Störung der GH-IGF-Achse und die direkte Beeinflussung der Chondrogenese der ephiphysären Wachstumszone negativ auf das Wachstum aus. Die aufgrund ihrer entzündungshemmenden und immunsuppressiven Eigenschaften bei einigen chronischen Erkrankungen eingesetzten Kortikosteroide stören diese wachstumsregulierenden Mechanismen noch zusätzlich. Die wachstumshemmenden Prozesse verlangsamen wahrscheinlich die Seneszenz der Wachstumsfuge, so dass bei Genesung von der chronischen Erkrankung und Absetzen der Kortikosteroidbehandlung ein Aufholwachstum möglich ist. Die an Patienten mit Wachstumsstörungen durchgeführten Studien zum rekombinanten humanen Wachstumshormon (rhGH) deuten sowohl auf eine Verbesserung des Längenwachstums als auch auf Nutzwirkungen bezüglich der Körperzusammensetzung und des klinischen Verlaufs hin. Die Studien waren jedoch von relativ kurzer Dauer, so dass die langfristige Nutzwirkung und Sicherheit von rhGH, insbesondere bei gleichzeitiger Verabreichung von Kortikosteroiden, noch zu bewerten sind.
Regulation of Cerebral Artery Smooth Muscle Membrane Potential by Ca2+‐Activated Cation Channels

Arterial tone is dependent on the depolarizing and hyperpolarizing currents regulating membrane potential and governing the influx of Ca2+ needed for smooth muscle contraction. Several ion channels have been proposed to contribute to membrane depolarization, but the underlying molecular mechanisms are not fully understood. In this review, we will discuss the historical and physiological significance of the Ca2+‐activated cation channel, TRPM4, in regulating membrane potential of cerebral artery smooth muscle cells. As a member of the recently described transient receptor potential super family of ion channels, TRPM4 possesses the biophysical properties and upstream cellular signaling and regulatory pathways that establish it as a major physiological player in smooth muscle membrane depolarization.
Dextromethorphan Attenuates LPS‐Induced Adhesion Molecule Expression in Human Endothelial Cells

This study examines the effect of Dextromethorphan (d‐3‐methoxy‐17‐methylmorphinan; DXM), a commonly used cough‐suppressing drug, on the expression of VCAM‐1 and ICAM‐1 in human umbilical vein endothelial cells (HUVECs) stimulated with lipopolysaccharide (LPS).
Myosin Phosphatase Isoforms as Determinants of Smooth Muscle Contractile Function and Calcium Sensitivity of Force Production

The dephosphorylation of myosin by the MP causes smooth muscle relaxation. MP is also a key target of signals that regulate vascular tone and thus blood flow and pressure. Here, we review studies from the past two decades that support the hypothesis that the regulated expression of MP subunits is a critical determinant of smooth muscle responses to constrictor and dilator signals. In particular, the highly regulated splicing of the regulatory subunit Mypt1 Exon 24 is proposed to tune sensitivity to NO/cGMP‐mediated relaxation. The regulated transcription of the MP inhibitory subunit CPI‐17 is proposed to determine sensitivity to agonist‐mediated constriction. The expression of these subunits is specific in the microcirculation and varies in developmental and disease contexts. To date, the relationship between MP subunit expression and vascular function in these different contexts is correlative; confirmation of the hypothesis will require the generation of genetically engineered mice to test the role of MP subunits and their isoforms in the specificity of vascular smooth muscle responses to constrictor and dilator signals.
Bactericidal effects of non-thermal argon plasma in vitro, in biofilms and in the animal model of infected wounds.

Non-thermal (low-temperature) physical plasma is under intensive study as an alternative approach to control superficial wound and skin infections when the effectiveness of chemical agents is weak due to natural pathogen or biofilm resistance. The purpose of this study was to test the individual susceptibility of pathogenic bacteria to non-thermal argon plasma and to measure the effectiveness of plasma treatments against bacteria in biofilms and on wound surfaces. Overall, Gram-negative bacteria were more susceptible to plasma treatment than Gram-positive bacteria. For the Gram-negative bacteria Pseudomonas aeruginosa, Burkholderia cenocepacia and Escherichia coli, there were no survivors among the initial 10(5) c.f. u. after a 5 min plasma treatment. The susceptibility of Gram-positive bacteria was species- and strain-specific. Streptococcus pyogenes was the most resistant with 17 % survival of the initial 10(5) c.f. u. after a 5 min plasma treatment. Staphylococcus aureus had a strain-dependent resistance with 0 and 10 % survival from 10(5) c.f. u. of the Sa 78 and ATCC 6538 strains, respectively. Staphylococcus epidermidis and Enterococcus faecium had medium resistance. Non-ionized argon gas was not bactericidal. Biofilms partly protected bacteria, with the efficiency of protection dependent on biofilm thickness. Bacteria in deeper biofilm layers survived better after the plasma treatment. A rat model of a superficial slash wound infected with P. aeruginosa and the plasma-sensitive Staphylococcus aureus strain Sa 78 was used to assess the efficiency of argon plasma treatment. A 10 min treatment significantly reduced bacterial loads on the wound surface. A 5-day course of daily plasma treatments eliminated P. aeruginosa from the plasma-treated animals 2 days earlier than from the control ones. A statistically significant increase in the rate of wound closure was observed in plasma-treated animals after the third day of the course. Wound healing in plasma-treated animals slowed down after the course had been completed. Overall, the results show considerable potential for non-thermal argon plasma in eliminating pathogenic bacteria from biofilms and wound surfaces.
Diphenyl Phosphine Oxide‐1‐Sensitive K+ Channels Contribute to the Vascular Tone and Reactivity of Resistance Arteries From Brain and Skeletal Muscle

Many types of vascular smooth muscle cells exhibit prominent KDR currents. These KDR currents may be mediated, at least in part, by KV1.5 channels, which are sensitive to inhibition by DPO‐1. We tested the hypothesis that DPO‐1‐sensitive KDR channels regulate the tone and reactivity of resistance‐sized vessels from rat brain (MCA) and skeletal muscle (GA).
Distributed FlowVisor: a distributed FlowVisor platform for quality of service aware cloud network virtualisation

Cloud-based virtual networking environments are required to provide fine-grained quality of service (QoS) control without sacrificing scalability. However, no single approach can currently achieve these two goals simultaneously. FlowVisor is a building block to virtualise networks with fine-grained QoS support; however, scalability issues caused by the OpenFlow protocol and the centralised control model are a major concern. This study introduces a distributed FlowVisor (DFVisor) platform to address these scalability issues. The proposed DFVisor uses a layered overlay mechanism to improve network addressing space and switch capacity. DFVisor uses a distributed synchronised two-level database system with a synchronisation mechanism to enable the centralised control functions in the current FlowVisor platform in distributed control modules within the virtual network controllers. Therefore it removes a single point of failure in the network and reduces the flow setup latency without sacrificing the centralised network configuration and management capabilities. More importantly, the proposed DFVisor platform enables an advanced push-based flow setup and statistics collection mechanism to address scalability issues caused by the current pull-based flow setup and statistics collection method. A DFVisor prototype and an evaluation of this distributed synchronised two-level database are presented, and key issues for future research are discussed.
The Influence of Symtomless Degenerative Changes of the Patellofemoral Joint on Clinical Results of Medial Unicompartmental Knee Arthroplasty

Purpose: To evaluate the influence of degenerative changes in the patellofemoral joint on the clinical results of medial unicompartmental knee arthroplasty (UKA). Materials and Methods: Between January and December 2002, we operated on 180 cases of minimally invasive UKA using the Oxford phase 3. Of the 180 cases, 156 were followed up for a minimum period of 5 years. Based on intraoperative degenerative findings of the patellofemoral joint, we classified cases into 4 groups (Group I-78 cases, Group II-40 cases, Group III-27 cases, Group IV-11 cases), and the clinical data were analyzed prospectively. Results: During follow-up, which averaged 6 years and 2 months, the knee score, the knee function score, the range of knee motion and the tibiofemoral angle were improved significantly (p0.05). To date, no complication or failure involving the patellofemoral joint has been observed. Conclusion: Clinical results of UKA are satisfactory for all groups, and the severity of patellofemoral degeneration has no influence on clinical outcome. Symptomless degenerative arthritis of the patellofemoral joint is not a contraindication for medial UKA.
Utilizing Zebrafish to Identify Anti‐(Lymph)Angiogenic Compounds for Cancer Treatment: Promise and Future Challenges

Cancer metastasis which predominantly occurs through blood and lymphatic vessels, is the leading cause of death in cancer patients. Consequently, several anti‐angiogenic agents have been approved as therapeutic agents for human cancers such as metastatic renal cell carcinoma. Also, anti‐lymphangiogenic drugs such as monoclonal antibodies VGX‐100 and IMC‐3C5 have undergone phase I clinical trials for advanced and metastatic solid tumors. Although anti‐tumor‐associated angiogenesis has proven to be a promising therapeutic strategy for human cancers, this approach is fraught with toxicities and development of drug resistance. This emphasizes the need for alternative anti‐(lymph)angiogenic drugs. The use of zebrafish has become accepted as an established model for high‐throughput screening, vascular biology, and cancer research. Importantly, various zebrafish transgenic lines have now been generated that can readily discriminate different vascular compartments. This now enables detailed in vivo studies that are relevant to both human physiological and tumor (lymph)angiogenesis to be conducted in zebrafish. This review highlights recent advancements in the zebrafish anti‐vascular screening platform and showcases promising new anti‐(lymph)angiogenic compounds that have been derived from this model. In addition, this review discusses the promises and challenges of the zebrafish model in the context of anti‐(lymph)angiogenic compound discovery for cancer treatment.
Exploring a Local Linear Model Tree Approach to Car‐Following

Because car‐following (CF) models are fundamental to replicating traffic flow they have received considerable attention over the last 50 years. They are in a continuous state of improvement due to their significant role in traffic microsimulations, intelligent transportation systems, and safety engineering models. This article uses the local linear model tree (LOLIMOT) approach to model driver's CF behavior to incorporate human perceptual imperfections into a CF model. This model defines some localities in the input space. These localities are fuzzy and have overlaps with each other. Specific models for each of the localities are then defined and combined in a fuzzy manner to predict the final output. The model was developed using real world dynamic data sets. Three different data sets were used for training, testing, and validating the model. The performance of the model was compared to a number of existing CF models. The results showed very close agreement between the real data and the LOLIMOT outputs.
The effects of training triceps surae using progressive speed loading

The effects of training with simple speed loading to triceps surae was studied in healthy, normal subjects. A total of 15 subjects formed the experimental group and 13 served as the control group. After 4 weeks of a progressive increase in speed of heel raise with body weight as the constant load, there was a significant increase in the measured jumping height of the experimental group (P < 0.001). No change was found in the isokinetic peak torque measurements made at an angular velocity of 180 degrees/second. However, the static strength of soleus decreased significantly in the experimental group (P <0.05). An improvement in muscle power was therefore only shown in the jump test and not in the isokinetic measurement, which suggests the specificity of improvement to the training programme. The significant decrease in the isometric strength of soleus after training suggests that high-speed repetitive exercise may possibly inhibit the static actions of this muscle.
Effect of an intervention programme on the physical activity participation patterns among school going children in South Africa

A steady decrease in the levels of physical activity during childhood and adolescents has been noted in various parts of the world. The picture of low physical activity levels in developed countries is no different in developing countries. Children spend the majority of their day at school therefore a school setting is ideal to conduct physical activity intervention studies. The primary aim of this study was to measure the effect of an intervention programme on the physical activity participation patterns among school going children and adolescents. The conveniently selected sample from an urban independent Catholic school included all learners from grade 5 to 7 with parental consent. Baseline data included among others, patterns of physical activity participation, and support for physical activity. Physical activity was assessed with the Modifiable Activity Questionnaire for Adolescents.1 Learners were requested to indicate on how many days of the week preceding the study they participated in vigorous (VPA) and moderate activities for at least 20 min. Support for physical activity from friends and family was also measured.2 The 12-week Promoting Lifestyle activity for Youth (PLAY) programme3 was implemented at the school. Two weeks after the programme, repeat measurement of variables was collected. The mean number of sessions of VPA per week was higher after the intervention programme (3.71 days) than before (3.17 days; p<0.05) and higher levels of support from family for physical activity was reported. The mean number of sessions of moderate physical activity increased with the frequency of family and friends social support. All bivariate correlations between the family and friends social support variables and moderate physical activity were positive and some were statistically significant (p<0.05) The results of the study indicated that intervention programmes such as PLAY have the potential to increase the levels of physical activity participation and support from family for physical activity among learners.
A Wavelet Support Vector Machine‐Based Neural Network Metamodel for Structural Reliability Assessment

Wavelet neural network (WNN) has been widely used in the field of civil engineering. However, WNN can only effectively handle problems of small dimensions as the computational cost for constructing wavelets of large dimensions is prohibitive. To expand the application of WNN to higher dimensions, this article develops a new wavelet support vector machine (SVM)‐based neural network metamodel for reliability analysis. The method first develops an autocorrelation wavelet kernel SVM and then uses a set of wavelet SVMs with different resolution as the activation function of WNN. The output of network is obtained through aggregating outputs of different wavelet SVMs. The method takes advantage of the excellent capacities of SVM to handle high‐dimensional problems and of the attractive properties of wavelet to represent complex functions. Four examples are given to demonstrate the application and effectiveness of the proposed method.
Two‐Dimensional Simulation of Turning Behavior in Potential Conflict Area of Mixed‐Flow Intersections

The potential conflict area of intersection is the space where conflicting traffic flows pass through in the same signal phase. At this area, turning vehicles interact with most traffic flows, which introduce complex features including variation of trajectories and shared‐priority phenomenon. The traditional one‐dimensional simulation oversimplifies these features with lane‐based assumption. This study integrates the modified social force model with behavior decision and movement constraints to reproduce the two‐dimensional turning process. The method is framed into a three‐layered mathematical model. First, the decision layer dynamically makes decision for turning patterns. Then the operation layer uses the modified social force model to initially generate vehicle movements. Finally, the constraint layer modifies the vehicular motion with vehicle dynamics constraints, boundary of intersection and the collision avoidance rule. The proposed model is validated using trajectories of left‐turn vehicles at a real‐world mixed‐flow intersection with nonprotected signal phases, resulting in a more realistic simulation than previous methods. The distributions of decision points and travel time in simulation are compared with the empirical data in statistics. Moreover, the spatial distribution of simulated trajectories is also satisfactory.
Microcolony formation by the opportunistic pathogen Pseudomonas aeruginosa requires pyruvate and pyruvate fermentation

A hallmark of the biofilm architecture is the presence of microcolonies. However, little is known about the underlying mechanisms governing microcolony formation. In the pathogen Pseudomonas aeruginosa, microcolony formation is dependent on the two‐component regulator MifR, with mifR mutant biofilms exhibiting an overall thin structure lacking microcolonies, and overexpression of mifR resulting in hyper‐microcolony formation. Using global transcriptomic and proteomic approaches, we demonstrate that microcolony formation is associated with stressful, oxygen‐limiting but electron‐rich conditions, as indicated by the activation of stress response mechanisms and anaerobic and fermentative processes, in particular pyruvate fermentation. Inactivation of genes involved in pyruvate utilization including uspK, acnA and ldhA abrogated microcolony formation in a manner similar to mifR inactivation. Moreover, depletion of pyruvate from the growth medium impaired biofilm and microcolony formation, while addition of pyruvate significantly increased microcolony formation. Addition of pyruvate to or expression of mifR in lactate dehydrogenase (ldhA) mutant biofilms did not restore microcolony formation, while addition of pyruvate partly restored microcolony formation in mifR mutant biofilms. In contrast, expression of ldhA in mifR::Mar fully restored microcolony formation by this mutant strain. Our findings indicate the fermentative utilization of pyruvate to be a microcolony‐specific adaptation of the P. aeruginosa biofilm environment.
Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions

We examine whether the Escherichia coli chromosome is folded into a self‐adherent nucleoprotein complex, or alternately is a confined but otherwise unconstrained self‐avoiding polymer. We address this through in vivo visualization, using an inducible GFP fusion to the nucleoid‐associated protein Fis to non‐specifically decorate the entire chromosome. For a range of different growth conditions, the chromosome is a compact structure that does not fill the volume of the cell, and which moves from the new pole to the cell centre. During rapid growth, chromosome segregation occurs well before cell division, with daughter chromosomes coupled by a thin inter‐daughter filament before complete segregation, whereas during slow growth chromosomes stay adjacent until cell division occurs. Image correlation analysis indicates that sub‐nucleoid structure is stable on a 1 min timescale, comparable to the timescale for redistribution time measured for GFP–Fis after photobleaching. Optical deconvolution and writhe calculation analysis indicate that the nucleoid has a large‐scale coiled organization rather than being an amorphous mass. Our observations are consistent with the chromosome having a self‐adherent filament organization.
H2A.Z and H2B.Z double‐variant nucleosomes define intergenic regions and dynamically occupy var gene promoters in the malaria parasite Plasmodium falciparum

Histone variants are important components of eukaryotic chromatin and can alter chromatin structure to confer specialized functions. H2B variant histones are rare in nature but have evolved independently in the phyla Apicomplexa and Trypanasomatida. Here, we investigate the apicomplexan‐specific Plasmodium falciparum histone variant Pf H2B.Z and show that within nucleosomes Pf H2B.Z dimerizes with the H2A variant Pf H2A.Z and that Pf H2B.Z and Pf H2A.Z occupancy correlates in the subset of genes examined. These double‐variant nucleosomes also carry common markers of euchromatin like H3K4me3 and histone acetylation. Pf H2B.Z levels are elevated in intergenic regions across the genome, except in the var multigene family, where Pf H2A.Z/Pf H2B.Z double‐variant nucleosomes are only enriched in the promoter of the single active var copy and this enrichment is developmentally regulated. Importantly, this pattern seems to be specific for var genes and does not apply to other heterochromatic gene families involved in red blood cell invasion which are also subject to clonal expression. Thus, Pf H2A.Z/Pf H2B.Z double‐variant nucleosomes appear to have a highly specific function in the regulation of P. falciparum virulence.