bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects
Authors: de Lange Elizabeth CM 
Published: February 2013

Abstract
Despite enormous advances in CNS research, CNS disorders remain the world’s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies.
Following dosing, not only the chemical properties of the drug and blood–brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. The rate and extent of all these processes are regulated dynamically, and thus condition dependent. Therefore, heterogenious conditions such as species, gender, genetic background, tissue, age, diet, disease, drug treatment etc., result in considerable inter-individual and intra-individual variation, often encountered in CNS drug therapy.
For effective therapy, drugs should access the CNS “at the right place, at the right time, and at the right concentration”. To improve CNS therapies and drug development, details of inter-species and inter-condition variations are needed to enable target site pharmacokinetics and associated CNS effects to be translated between species and between disease states. Specifically, such studies need to include information about unbound drug concentrations which drive the effects. To date the only technique that can obtain unbound drug concentrations in brain is microdialysis. This (minimally) invasive technique cannot be readily applied to humans, and we need to rely on translational approaches to predict human brain distribution, target site kinetics, and therapeutic effects of CNS drugs.
In this review the term “Mastermind approach” is introduced, for strategic and systematic CNS drug research using advanced preclinical experimental designs and mathematical modeling. In this way, knowledge can be obtained about the contributions and variability of individual processes on the causal path between drug dosing and CNS effect in animals that can be translated to the human situation. On the basis of a few advanced preclinical microdialysis based investigations it will be shown that the “Mastermind approach” has a high potential for the prediction of human CNS drug effects.
Acute myocardial infarction is associated with endothelial glycocalyx and cell damage and a parallel increase in circulating catecholamines
Authors: Ostrowski Sisse R , Pedersen Sune H , Jensen Jan S , Mogelvang Rasmus , Johansson Pär I 
Published: February 2013

Abstract
Introduction
Excessive sympathoadrenal activation in critical illness contributes directly to organ damage, and high concentrations of catecholamines damage the vascular endothelium. This study investigated associations between potential drivers of sympathoadrenal activation, circulating catecholamines and biomarkers of endothelial damage and outcome in ST segment elevation myocardial infarction (STEMI)-patients, hypothesizing that the catecholamine surge would reflect shock degree and correlate with biomarkers of endothelial damage.

Methods
This was a prospective study of 678 consecutive STEMI-patients admitted to a single high-volume invasive heart centre for primary percutaneous coronary intervention (pPCI) from September 2006 to July 2008. Blood samples were drawn immediately before pPCI. Plasma adrenaline, noradrenaline, syndecan-1 and thrombomodulin were measured retrospectively with complete data in 571 patients (84%). Median follow-up time was 28 (IQR 23 to 34) months. Follow-up was 99.7% complete. Outcomes were all-cause and cardiovascular mortality, re-myocardial infarction and admission due to heart failure.

Results
Circulating noradrenaline and adrenaline correlated weakly but independently with syndecan-1 (rho = 0.15 and rho = 0.13, both P <0.01) and thrombomodulin (rho = 0.11 and rho = 0.17, both P <0.01), biomarkers of glycocalyx and endothelial cell damage, respectively. Considering biomarkers, patients with shock pre-pPCI had higher adrenaline and syndecan-1 and patients admitted to ICU post-pPCI had higher syndecan-1 (all P <0.05), and in the patients with shock (n = 51) catecholamines correlated strongly with thrombomodulin and syndecan-1 (rho = 0.31 to 0.42, all P <0.05). During follow-up, 78 (14%) patients died (37 cardiovascular deaths) and 65 (11%) were admitted with heart failure. By multivariate Cox proportional hazards analyses, one quartile higher plasma adrenaline was weakly but independently associated with both 30-day and long term mortality and heart failure (30-day all-cause mortality hazard ratio (95% CI) 1.39 (1.01 to 1.92), P = 0.046; 30-day heart failure 1.65 (1.17 to 2.34), P = 0.005; and long-term cardiovascular mortality 1.49 (1.08 to 2.04), P = 0.014). Furthermore, one quartile higher syndecan-1 was also weakly but independently associated with long-term all cause mortality (1.26 (1.02 to 1.57), P = 0.034).

Conclusions
In STEMI patients treated with pPCI, catecholamines correlated weakly with biomarkers of endothelial damage, with the strongest correlations and highest adrenaline and syndecan-1 levels in patients with shock. Furthermore, adrenaline and syndecan-1 were weakly but independently associated with mortality and heart failure. Acute myocardial infarction appears to cause significant endothelial cell and glycocalyx injury and a parallel increase in circulating catecholamines.
A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK
Authors: Campbell Joshua D , McDonough John E , Zeskind Julie E , Hackett Tillie L , Pechkovsky Dmitri V , Brandsma Corry-Anke , Suzuki Masaru , Gosselink John V , Liu Gang , Alekseyev Yuriy O , Xiao Ji , Zhang Xiaohui , Hayashi Shizu , Cooper Joel D , Timens Wim , Postma Dirkje S , Knight Darryl A , Lenburg Marc E , Hogg James C , Spira Avrum 
Published: February 2013

Abstract
Background
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease consisting of emphysema, small airway obstruction, and/or chronic bronchitis that results in significant loss of lung function over time.

Methods
In order to gain insights into the molecular pathways underlying progression of emphysema and explore computational strategies for identifying COPD therapeutics, we profiled gene expression in lung tissue samples obtained from regions within the same lung with varying amounts of emphysematous destruction from smokers with COPD (8 regions × 8 lungs = 64 samples). Regional emphysema severity was quantified in each tissue sample using the mean linear intercept (Lm) between alveolar walls from micro-CT scans.

Results
We identified 127 genes whose expression levels were significantly associated with regional emphysema severity while controlling for gene expression differences between individuals. Genes increasing in expression with increasing emphysematous destruction included those involved in inflammation, such as the B-cell receptor signaling pathway, while genes decreasing in expression were enriched in tissue repair processes, including the transforming growth factor beta (TGFβ) pathway, actin organization, and integrin signaling. We found concordant differential expression of these emphysema severity-associated genes in four cross-sectional studies of COPD. Using the Connectivity Map, we identified GHK as a compound that can reverse the gene-expression signature associated with emphysematous destruction and induce expression patterns consistent with TGFβ pathway activation. Treatment of human fibroblasts with GHK recapitulated TGFβ-induced gene-expression patterns, led to the organization of the actin cytoskeleton, and elevated the expression of integrin β1. Furthermore, addition of GHK or TGFβ restored collagen I contraction and remodeling by fibroblasts derived from COPD lungs compared to fibroblasts from former smokers without COPD.

Conclusions
These results demonstrate that gene-expression changes associated with regional emphysema severity within an individual's lung can provide insights into emphysema pathogenesis and identify novel therapeutic opportunities for this deadly disease. They also suggest the need for additional studies to examine the mechanisms by which TGFβ and GHK each reverse the gene-expression signature of emphysematous destruction and the effects of this reversal on disease progression.
Reversible brain inactivation induces discontinuous gas exchange in cockroaches
Authors: Matthews Philip G.D. , White Craig R. 
Published: February 2013

Summary
Many insects at rest breathe discontinuously, alternating between brief bouts of gas exchange and extended periods of breath-holding. The association between discontinuous gas exchange cycles (DGCs) and inactivity has long been recognised, leading to speculation that DGCs lie at one end of a continuum of gas exchange patterns, from continuous to discontinuous, linked to metabolic rate (MR). However, the neural hypothesis posits that it is the down-regulation of brain activity and a change in the neural control of gas exchange, rather than low MR per se, which is responsible for the emergence of DGCs during inactivity. To test this, cockroaches Nauphoeta cinerea had their brains inactivated by applying a Peltier-chilled cold probe to the head. Once brain temperature fell to 8°C cockroaches switched from a continuous to a discontinuous breathing pattern. Re-warming the brain abolished the DGC and re-established a continuous breathing pattern. Chilling the brain did not significantly reduce the cockroaches' MR and there was no association between the gas exchange pattern displayed by the insect and its MR. This demonstrates that DGCs can arise due to a decrease in brain activity and a change in the underlying regulation of gas exchange, and are not necessarily a simple consequence of low respiratory demand.
The effects of experimentally elevated traffic noise on nestling white-crowned sparrow stress physiology, immune function, and life-history
Authors: Crino Ondi L. , Johnson Erin E. , Blickley Jessica L. , Patricelli Gail L. , Breuner Creagh W. 
Published: February 2013

Summary
Roads have been associated with behavioral and physiological changes in wildlife. In birds, roads decrease reproductive success and biodiversity and increase physiological stress. Although the consequences of roads on individuals and communities have been well described, the mechanisms through which roads affect birds remain largely unexplored. Here, we examine one mechanism through which roads could affect birds: traffic noise. We exposed nestling mountain white-crowned sparrows (Zonotrichia leucophrys oriantha) to experimentally elevated traffic noise for five days during the nestling period. Following exposure to traffic noise we measured nestling stress physiology, immune function, body size, condition, and survival. Based on prior studies, we expected the traffic noise treatment to result in elevated stress hormones (glucocorticoids), and declines in immune function, body size, condition and survival. Surprisingly, nestlings exposed to traffic noise had lower glucocorticoid levels and improved condition relative to control nests. These results indicate that traffic noise does affect physiology and development in white-crowned sparrows, but not at all as predicted. Therefore, when evaluating the mechanisms through which roads affect avian populations other factors (e.g. edge effects, pollution, and mechanical vibration) may be more important than traffic noise in explaining elevated nestling stress responses in this species.
An algebraic property of Hecke operators and two indefinite theta series
Authors: Paşol Vicenţiu , Popa Alexandru A. 
Published: February 2013

Abstract
We prove an algebraic property of the elements defining Hecke operators on period polynomials
associated with modular forms, which implies that the pairing on period polynomials corresponding to the Petersson scalar product of modular forms is Hecke equivariant. As a consequence of this proof, we derive two indefinite theta series identities which can be seen as analogues of Jacobi's formula for the theta series associated with the sum of four squares.
Durchgängiges Engineering von der Anforderungserhebung bis zur Anlagenstrukturbeschreibung
Authors: Jäger Tobias , Christiansen Lars , Strube Martin , Fay Alexander 
Published: February 2013

Zusammenfassung
Dieser Beitrag beschreibt, wie das Engineering automatisierter industrieller Anlagen durch Zusammenführen von Prozess- und Anlagenstrukturbeschreibung verbessert werden kann. Durch die Integration einer semiformellen Prozessbeschreibung in die etablierte Microsoft Visio Umgebung und die Möglichkeit des Ergebnistransfers in AutomationML wird eine größtmögliche Akzeptanz dieses Ansatzes angestrebt. Die Verknüpfung der Prozessbeschreibung mit der Anlagenstrukturbeschreibung ermöglicht nicht nur ein durchgängiges Engineering, sondern auch ein durchgängiges Anforderungsmanagement.
Sense Discrimination in Five English Learner’s Dictionaries
Authors: Halas Ana 
Published: February 2013

Abstract
This paper presents the comparison of sense discrimination strategies including the structure and organization of a polysemous word entry in five English monolingual learner’s dictionaries with the aim of gaining an insight into the aspects of sense division where the given dictionaries agree and disagree. The final outcome of the analysis is the selection of features contributing to the establishment of the user friendliest sense discrimination system in a pedagogical dictionary
Application of HDMR method to reliability assessment of a single pile subjected to lateral load
Authors: Bauer Jerzy , Kozubal Janusz , Puła Wojciech , Wyjadłowski Marek 
Published: February 2013

Abstract
The paper presents an application of High Dimensional Model Representation (HDMR) to reliability assessment of a single pile subjected to lateral load. The purpose is to compare HDMR with some classical method based on response surface technique.
First 3D numerical model of the problem for finite elements computations in the ABAQUS STANDARD program has been presented. The soil model is assumed to be linear elastic. However, contacts between the sidewall and the foundation of the pile and the soil are modelled as Coulomb one with friction and cohesion.
Next the Response Surface Method is briefly reviewed in conjunction with reliability approach.
Then the High Dimensional Model Representation approach is presented. In our approach the HDMR algorithm is based on polynomial of the second degree. Finally the numerical studies have been carried out. The first series of computations demonstrate the efficiency of HDMR in comparison to neural network approach. The second series allows comparison of reliability indices resulting from three different approaches, namely neural network response surface, first-order HDMR and second-order HDMR. It has been observed that for increasing values of the length of the pile reliability indices reach similar values regardless of the method response surface applied.
Pollen morphology of Ukrainian species of the genus Pedicularis L. (Orobanchaceae Vent.)
Authors: Peregrym Olena M. , Tsymbalyuk Zoya M. , Mosyakin Sergei L. 
Published: February 2013

Abstract
Pollen grains of 10 species of Pedicularis occurring in Ukraine were investigated using light and scanning electron microscopy. Palynological data on 6 species are reported for the first time. General pollen morphology of the genus Pedicularis is presented. Three types of apertures (2-syncolpate, 3-colpate, and 3-syncolpate) and seven subtypes of sculpture (3-syncolpate pilate, 3-syncolpate microscabrate-tubeculate, 2-syncolpate microscabrate, 2-syncolpate microscabrate-tubeculate, 2-syncolpate microscabrate-tubeculate-perforate, 2-syncolpate microfoveolate, and 2-syncolpate microscabrate-perforate) are indentified. The subgenus Pedicularis is heterogeneous in its types of apertures and sculpture of the surface, which indicates the need of further taxonomic revision of the group.
The influence of surrounding vegetation on the flora of post-mining area
Authors: Kopeć Dominik , Zając Izabela , Halladin-Dąbrowska Anna 
Published: February 2013

Abstract
In 2007, extensive botanical studies were carried out in the Gagaty Sołtykowskie Reserve (Małopolska Upland, southern Poland) to compile comprehensive flora inventories n separately for a post-mining area and the surrounding forest. The main aim of the study was to assess the influence of the surrounding vegetation on the flora of a former ceramic clay mine located in the middle of a dense forest. The results show that over 30 years after closure, the former mine is now home to several valuable and protected species of vascular plants, with the rate and direction of succession determined mainly by the surrounding vegetation. Because ruderal species have no direct access to the area, non-synanthropic, indigenous species are dominant in the Gagaty Sołtykowskie Reserve (GS).
Comparative analysis of the bryophyte floras of northwest Belarus concrete fortification and the Carpathians
Authors: Sakovich Anastasia , Rykovsky Gennadij 
Published: February 2013

Abstract
The detailed research of bryophyte flora, carried out in 2008-2011 on fortifications from the times of the First World War and Second World War in Grodno district, resulted in recording 101 species, of which 95 species were true mosses (Bryophyta) and 6 species were hepatics (Marchantiophyta). Because the substratum displayed certain ecological similarity with carbonate rocks, we made comparative analysis of the species list. The total of 28 rare and very rare (in Belarus scale) bryophyte species were recorded, of which 3 species were included in the Red Data Book of Belarus; 3 species had a conservation status at the European level.
Orobanche alba subsp. alba and subsp. major (Orobanchaceae) in Poland: current distribution, taxonomy, plant communities, hosts, and seed micromorphology
Authors: Piwowarczyk Renata 
Published: February 2013

Abstract
The paper presents the current distribution of Orobanche alba subsp. major and subsp. alba in Poland, based on a critical revision of herbarium and literature data as well as results of my field studies. Most of their localities are in southeastern Poland: in the Małopolska Upland, Lublin Upland, Roztocze Hills, Polesie, Przemyśl Foothills (Pogórze Przemyskie), and Western Bieszczady Mts. These are the northernmost sites known for the species in Central Europe, so the new data extend its distribution range. Maps of distribution of both the subspecies in Poland and of subsp. major in Central Europe are included. Additionally, their seed micromorphology was compared using scanning electron microscopy (SEM). The taxonomy, biology, and ecology of both the subspecies of O. alba are also discussed.
Orobanche purpurea (Orobanchaceae) in Poland: current distribution, taxonomy, plant communities, and preferred hosts
Authors: Piwowarczyk Renata 
Published: February 2013

Abstract
The paper presents the current distribution of Orobanche purpurea s. str. (excl. O. bohemica) in Poland, based on a critical revision of herbarium and literature data as well as results of my field research. Most of the records date back to the 19th or early 20th century and are now historical. Most of them lack also herbarium documentation. Since the 1950s the species has been found in 10 new localities, only partly documented by herbarium specimens. Currently it is present in only 4 localities, in valleys of the Lower Vistula and the Lower Oder (Odra) rivers and in the Silesian-Kraków Upland (Wyżyna alπsko-Krakowska). These are some of the northernmost sites known for the species, and the new data extend its continuous distribution range. A map of its distribution in Poland is included. The taxonomy, biology, and ecology of O.purpurea are also discussed.
Crataegus and Rosa genera in the Solec Basin and southern part of the Pińczów Hummock (Southern Poland)
Authors: Sołtys-Lelek Anna 
Published: February 2013

Abstract
The Crataegus and Rosa genera are critical taxa. Because of difficulties in species identification, nobody has dealt with the distribution of these genera in the Solec Basin (Niecka Solecka) and southern part of the PiOczUw Hummock (Garb PiOczowski) thus far. The aim of this work was prepare a complete list of critical species of these genera in the study area. The floristic studies were carried out in the years 2004-2009. Nineteen species were recorded: 6 hawthorns and 13 roses. Seven species were new for the flora of the studied area (4 roses and 3 hawthorns).
New Species of Charophyta, Chara polyacantha A. Braun, in Lake Engure, Latvia
Authors: Zviedre Egita , Grinberga Laura 
Published: February 2013

Abstract
The new charophyte species for Latvia, Chara polyacantha A. Braun, was described. This species was found in Lake Engure, the third largest lake of Latvia. In 2010, C.†polyacantha covered small, approximately 25 m2 patch, growing both in a monodominant stand and mixed with C. tomentosa in the central part of the lake.
Genetic Diversity of Leafy Liverwort Species (Jungermanniidae, Marchantiophyta) in Poland: Regional Genetic Differentiation of Leafy Liverworts
Authors: Bączkiewicz Alina 
Published: February 2013

Abstract
For each of 8 species of leafy liverworts, 9-10 populations were sampled in 2-3 regions of Poland. In total, 5 regions were taken into account: the Tatra National Park, Bieszczady Mts., Białowieża Forest, Pomeranian Lake District, and Suwałki Lake District. Populations of most of the studied species did not show any correlation between genetic differentiation and geographic distances. Clear differences between regional groups of populations were found in only 2 species. The other species showed a complete or partial lack of genetic differentiation between groups of populations from various geographic regions. Generally, however, mountain populations had greater genetic diversity (HT, HS) and coefficient of genetic differentiation (GST) than lowland populations. In the Tatra National Park all the studied liverworts turned out to be more diverse than in the Bieszczady Mts. Białowieża Forest created a uniform group, standing out markedly from mountainous populations but population in this region had slightly smaller genetic diversity, then in the mountains. In the Pomeranian and Suwałki Lake Districts, genetic diversity of liverworts was significantly lower than in mountains. The decrease in diversity in these regions is a likely consequence of habitat fragmentation (causing population depletion) combined with negative effects of urban development. Habitat fragmentation results in genetic drift and inbreeding depression, which cause a decrease in genetic diversity. In the Pomeranian Lake District the level of total diversity (HT) and intra-population diversity (HS) was markedly higher than in the Suwałki Lake District. It may be linked to differences in climate, in the Suwałki Lake District climate is stronger.
Multi-Zone Models of Combustion and Heat Transfer Processes in SI Engines
Authors: Hvězda Jiří 
Published: February 2013

Shrnutí
Tato práce představuje sadu nově vyvinutých nástrojů implementovatelných do komplexních kódů pro simulaci spalovacích motorů pro zajištění výpočtů týkajících se vysokotlaké části termodynamického cyklu čtyřdobého zážehového motoru. Tento více-zónový simulační nástroj pracuje na základě jednoduché kvazi-dimenzionální metody reflektující reálnou geometrii spalovacího prostoru a používá specifický přístup k popisu chemické transformace složek.
V případech abnormálně rychlých chemických reakcí je klasické kinetické schéma adaptivně kombinováno s flexibilní metodou chemické rovnováhy pro zlepšení numerických vlastností soustavy rovnic.
Reálná 3-D geometrie spalovacího prostoru je zohledňována pomocí předem vytvořených geometrických charakteristik. Je zde prezentován nový univerzální nástroj zajišťující tato data.
Nový kód má schopnost pracovat v prediktivním stejně jako inverzním módu. Vybrané výsledky týkající se obou těchto režimů jsou prezentovány v závěru příspěvku.