Entropy production and the geometry of dissipative evolution equations.

Purely dissipative evolution equations are often cast as gradient flow structures, z ̇=K(z)DS(z), where the variable z of interest evolves towards the maximum of a functional S according to a metric defined by an operator K. While the functional often follows immediately from physical considerations (e.g.

Prospective assessment of complications on a daily basis is essential to determine morbidity and mortality in routine pediatric surgery.

Aims Of The Study: We aimed to assess postoperative complications prospectively on a daily basis and hypothesized that this would lead to an increase in the number of detected complications.

Methods: Surgical complications were assessed prospectively during a period of 8months. Systematic documentation was carried out daily during a team meeting (period S).

Upregulation of S1P1 and Rac1 receptors in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.

Purpose: Sphingolipids play a crucial role in pulmonary development. The sphingosine kinase 1 (SphK1) modulates the synthesis of sphingolipid sphingosine-1-phosphate (S1P). S1P regulates cell proliferation and angiogenesis via different receptors, S1P1, S1P2 and S1P3, which all influence the expression of Ras-related C3 botulinum toxin substrate 1 (Rac1).

The Role of Activin Receptor-Like Kinase 1 Signaling in the Pulmonary Vasculature of Experimental Diaphragmatic Hernia.

Aim: The high morbidity and mortality in newborn infants diagnosed with congenital diaphragmatic hernia (CDH) is widely recognized to be due to pulmonary hypoplasia and persistent pulmonary hypertension (PH). The underlying structural and molecular pathomechanisms causing PH are not fully understood. Recently, activin receptor-like kinase 1 (ALK-1), an endothelial cell (EC) receptor, has been implicated in the pathogenesis of PH.

Mesenchymal expression of the FRAS1/FREM2 gene unit is decreased in the developing fetal diaphragm of nitrofen-induced congenital diaphragmatic hernia.

Purpose: Developmental mutations that inhibit normal formation of extracellular matrix (ECM) in fetal diaphragms have been identified in congenital diaphragmatic hernia (CDH). FRAS1 and FRAS1-related extracellular matrix 2 (FREM2), which encode important ECM proteins, are secreted by mesenchymal cells during diaphragmatic development. The FRAS1/FREM2 gene unit has been shown to form a ternary complex with FREM1, which plays a crucial role during formation of human and rodent diaphragms.

Polyclonal Expansion of NKG2C(+) NK Cells in TAP-Deficient Patients.

Adaptive natural killer (NK) cell responses to human cytomegalovirus infection are characterized by the expansion of NKG2C(+) NK cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs). Here, we set out to study the HLA class I dependency of such NKG2C(+) NK cell expansions. We demonstrate the expansion of NKG2C(+) NK cells in patients with transporter associated with antigen presentation (TAP) deficiency, who express less than 10% of normal HLA class I levels.

[Prehospital analgesia by paramedics in Rhineland-Palatinate : Feasability, analgesic effectiveness and safety of intravenous paracetamol].

Background: In contrast to the widespread practice in life-threatening emergencies, delegation of medical pain therapy to paramedics by the medical director  of Emergency Medical Services, EMS, are still the exception in Germany. This is due to the fact that in non-life-threatening situations, the expected benefit and potential side effects of drug therapy have to be carefully weighed. In addition, in Germany federal law generally restricts the administration of opiates to physicians.

Insights into the structure and function of membrane-integrated processive glycosyltransferases.

Complex carbohydrates perform essential functions in life, including energy storage, cell signaling, protein targeting, quality control, as well as supporting cell structure and stability. Extracellular polysaccharides (EPS) represent mainly structural polymers and are found in essentially all kingdoms of life. For example, EPS are important biofilm and capsule components in bacteria, represent major constituents in cell walls of fungi, algae, arthropods and plants, and modulate the extracellular matrix in vertebrates.

Effects of late-onset and long-term captopril and nifedipine treatment in aged spontaneously hypertensive rats: Echocardiographic studies.

The purpose of the present study was to analyze the changes in blood pressure, left ventricular (LV) wall thickness and LV systolic function of aged spontaneously hypertensive rats (SHRs) either with or without antihypertensive therapy. Twenty-one SHRs aged 60.5±0.

Serologic Survey of Snowshoe Hares (Lepus americanus) in the Greater Yellowstone Area for Brucellosis, Tularemia, and Snowshoe Hare Virus.

We examined sera from snowshoe hares (Lepus americanus) livetrapped in the northern Greater Yellowstone Area (GYA), US, for antibodies to Brucella abortus, Francisella tularensis, and snowshoe hare virus (SSHV). Zero of 90, 0 of 67, and 40 of 100 samples were antibody positive for B. abortus, F.

Knockout mouse models of Hirschsprung's disease.

Purpose: Hirschsprung's disease (HSCR) is a developmental disorder of the enteric nervous system, which occurs due to the failure of neural crest cell migration. Rodent animal models of aganglionosis have contributed greatly to our understanding of the genetic basis of HSCR. Several natural or target mutations in specific genes have been reported to produce developmental defects in neural crest migration, differentiation or survival.

A molecular description of cellulose biosynthesis.

Cellulose is the most abundant biopolymer on Earth, and certain organisms from bacteria to plants and animals synthesize cellulose as an extracellular polymer for various biological functions. Humans have used cellulose for millennia as a material and an energy source, and the advent of a lignocellulosic fuel industry will elevate it to the primary carbon source for the burgeoning renewable energy sector. Despite the biological and societal importance of cellulose, the molecular mechanism by which it is synthesized is now only beginning to emerge.

Orientation behaviour of Culicoides obsoletus (Diptera: Ceratopogonidae), a relevant virus vector in northern Europe, toward host-associated odorant cues.

Some Culicoides biting midge species (Diptera: Ceratopogonidae) are biological virus vectors worldwide and have recently been associated with outbreaks of important epizootic diseases such as bluetongue and Schmallenberg in northern Europe. These diseases, which affect domestic and wild ruminants, have caused considerable economic losses. Knowledge of host preferences of these biting midges - especially of the relevant vectors of arboviruses near farms, such as Culicoides obsoletus in northern Europe - is essential to understand pathogen transmission cycles and the epidemiology of associated diseases.

Evolutionary Dynamics of the Cellulose Synthase Gene Superfamily in Grasses.

Phylogenetic analyses of cellulose synthase (CesA) and cellulose synthase-like (Csl) families from the cellulose synthase gene superfamily were used to reconstruct their evolutionary origins and selection histories. Counterintuitively, genes encoding primary cell wall CesAs have undergone extensive expansion and diversification following an ancestral duplication from a secondary cell wall-associated CesA. Selection pressure across entire CesA and Csl clades appears to be low, but this conceals considerable variation within individual clades.

Bicelles coming of age: an empirical approach to bicelle crystallization.

Biological membranes represent a unique environment in which integral membrane proteins (MPs) fold to perform diverse biological functions. In many cases, lipids support the native conformation or mediate important interactions between MPs. It is therefore imperative to develop methods that maintain this support for the structural and functional analyses of an exceedingly important class of biological macromolecules.

How Cellulose Elongates--A QM/MM Study of the Molecular Mechanism of Cellulose Polymerization in Bacterial CESA.

The catalytic mechanism of bacterial cellulose synthase was investigated by using a hybrid quantum mechanics and molecular mechanics (QM/MM) approach. The Michaelis complex model was built based on the X-ray crystal structure of the cellulose synthase subunits BcsA and BcsB containing a uridine diphosphate molecule and a translocating glucan. Our study identified an SN2-type transition structure corresponding to the nucleophilic attack of the nonreducing end O4 on the anomeric carbon C1, the breaking of the glycosidic bond C1-O1, and the transfer of proton from the nonreducing end O4 to the general base D343.

Outcome for stage II and III rectal and colon cancer equally good after treatment improvement over three decades.

Purpose: This study aimed to investigate the outcome for stage II and III rectal cancer patients compared to stage II and III colonic cancer patients with regard to 5-year cause-specific survival (CSS), overall survival, and local and combined recurrence rates over time.

Methods: This prospective cohort study identified 3,355 consecutive patients with adenocarcinoma of the colon or rectum and treated in our colorectal unit between 1981 and 2011, for investigation. The study was restricted to International Union Against Cancer (UICC) stages II and III.

On the Functional Overlap between Complement and Anti-Microbial Peptides.

Intriguingly, activated complement and anti-microbial peptides share certain functionalities; lytic, phagocytic, and chemo-attractant activities and each may, in addition, exert cell instructive roles. Each has been shown to have distinct LPS detoxifying activity and may play a role in the development of endotoxin tolerance. In search of the origin of complement, a functional homolog of complement C3 involved in opsonization has been identified in horseshoe crabs.

Neurturin influences inflammatory responses and airway remodeling in different mouse asthma models.

Neurturin (NTN) was previously described for its neuronal activities, but recently, we have shown that this factor is also involved in asthma physiopathology. However, the underlying mechanisms of NTN are unclear. The aim of this study was to investigate NTN involvement in acute bronchial Th2 responses, to analyze its interaction with airway structural cells, and to study its implication in remodeling during acute and chronic bronchial inflammation in C57BL/6 mice.

Development and in-house validation of an allergen-specific ELISA for quantification of Bet v 4 in diagnostic and therapeutic birch allergen products.

Birch (Betula) pollen is a major cause of allergy in northern and central Europe. The allergenic potency of products for diagnosis and therapy of birch pollen allergy is adjusted nearly exclusively to the major birch pollen allergen Bet v 1. Although every fifth patient is additionally sensitized to Bet v 4, both content and variability of this minor allergen in birch allergen products remain unclear due to a lack of simple and cost-effective quantitative methods.

8th GCC: consolidated feedback to US FDA on the 2013 draft FDA guidance on bioanalytical method validation.

The 8th GCC Closed Forum for Bioanalysis was held in Baltimore, MD, USA on 5 December 2013, immediately following the 2013 AAPS Workshop (Crystal City V): Quantitative Bioanalytical Methods Validation and Implementation--The 2013 Revised FDA Guidance. This GCC meeting was organized to discuss the contents of the draft revised FDA Guidance on bioanalytical method validation that was published in September 2013 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants, from seven countries, representing 46 bioanalytical CRO companies/sites.

Recommendations on incurred sample stability (ISS) by GCC.

The topic of incurred sample stability (ISS) has generated considerable discussion within the bioanalytical community in recent years. The subject was an integral part of the seventh annual Workshop on Recent Issues in Bioanalysis (WRIB) held in Long Beach, CA, USA, in April 2013, and at the Global CRO Council for Bioanalysis (GCC) meeting preceding it. Discussion at both events focused on the use of incurred samples for ISS purposes in light of results from a recent GCC survey completed by member companies.

NK cells with KIR2DS2 immunogenotype have a functional activation advantage to efficiently kill glioblastoma and prolong animal survival.

Glioblastomas (GBMs) are lethal brain cancers that are resistant to current therapies. We investigated the cytotoxicity of human allogeneic NK cells against patient-derived GBM in vitro and in vivo, as well as mechanisms mediating their efficacy. We demonstrate that KIR2DS2 immunogenotype NK cells were more potent killers, notwithstanding the absence of inhibitory killer Ig-like receptor (KIR)-HLA ligand mismatch.