bluuebunny/crossref_metadata_2025_split huggingface dataset:
M118 – A rationally engineered low-molecular-weight heparin designed specifically for the treatment of acute coronary syndromes
Authors: Qi Yi , Long Alison , Capila Ishan , Sasisekharan Ram , Guerrero Luis , Fier Ian , Roach James , Venkataraman Ganesh , Kishimoto Takashi 
Published: September 2009

SummaryThe initial choice of anticoagulant therapy administered in emergency departments for acute coronary syndromes (ACS) has important consequences for subsequent patient care, as neither unfractionated heparin (UFH) nor low-molecularweight heparin (LMWH) are ideally suited for all potential clinical treatment pathways. UFH remains widely used for surgical interventions because of the ability to rapidly reverse its anticoagulant activity. However, the unpredictable pharmacokinetic profile of UFH presents safety issues, and the low subcutaneous bioavailability limits the utility of UFH for patients who are medically managed. LMWH has superior pharmacokinetic properties, but its anticoagulant activity cannot be effectively monitored or reversed during surgery. There is an unmet medical need for a baseline anticoagulant therapy that addresses these shortcomings while retaining the beneficial properties of both UFH and LMWH. We describe here M118, a novel LMWH designed specifically for use in the treatment of ACS. M118 shows broad anticoagulant activity, including potent activity against both factor Xa (∼240 IU/mg) and thrombin (factor IIa; ∼170 IU/ mg), low polydispersity, high (78%) subcutaneous bioavailability in rabbits, and predictable subcutaneous and intravenous pharmacokinetics. Additionally, the anticoagulant activity of M118 is monitorable by standard coagulation assays and is reversible with protamine. M118 demonstrates superior activity to conventional LMWH in a rabbit model of abdominal arterial thrombosis without increasing bleeding risk, and is currently being evaluated in a phase II clinical trial evaluating efficacy and safety in patients undergoing percutaneous coronary intervention.
Direct inhibitors of coagulation proteins – the end of the heparin and low-molecular-weight heparin era for anticoagulant therapy?
Authors: Perzborn Elisabeth , Heitmeier Stefan , von Degenfeld Georges , Dittrich-Wengenroth Elke , Buchmüller Anja , Gerdes Christoph , Misselwitz Frank , Laux Volker 
Published: September 2009

SummaryHeparins, either unfractionated or low-molecular-weight (UFH and LMWHs), and vitamin K antagonists (VKAs) are currently the anticoagulants of choice for the prevention of post-operative venous thromboembolism (VTE) and for the treatment of acute venous and arterial thromboembolism. While VKAs are widely used in the US, LMWHs are the standard of care in the EU. Although efficacious, these agents are associated with a number of drawbacks, such as the risk of heparin-induced thrombocytopenia, the need for frequent coagulation monitoring in the case of UFH and VKAs, and the parenteral mode of administration in the case of heparins, which can lead to problems associated with patient compliance. There is a need for new anticoagulants that overcome these limitations. Direct, small-molecule inhibitors of coagulation proteins targeting a single enzyme in the coagulation cascade – particularly thrombin or Factor Xa – have been developed in recent years. Two agents, the direct thrombin inhibitor dabigatran and the direct Factor Xa inhibitor rivaroxaban, have recently been approved in the EU and several other countries for the prevention of VTE after total hip or knee replacement surgery. Here we will review data that suggest that the antithrombin-independent mechanism of action of these agents, particularly that of direct Factor Xa inhibitors, leads to increased efficacy with similar safety profiles compared with the antithrombin-dependent heparins. Although the end of the heparins era is not to be expected, the new anticoagulants presented in this review potentially represent the future of anticoagulation.
Detection and neutralisation of heparin by a fluorescent ruthenium compound
Authors: Szelke Helga , Harenberg Job , Krämer Roland 
Published: September 2009

SummaryHeparin and low-molecular-weight heparin (LMWH) are commonly monitored by determination of activated clotting times or chromogenic assays. Despite their wide use, these assays determine the biological activity and not the concentration of the anticoagulants. They may be inaccurate in some circumstances such as certain disease states. In addition, there is a significant interest in alternative tests for the point-of-care detection of heparin and LMWH. Their binding to small molecules for the detection in biological matrices is poorly explored. We describe here a new optical molecular probe for the detection of LMWH in serum samples. The polycationic ruthenium compound 1 is applicable to the quantification of heparin by monitoring 630 nm fluorescence. In addition, compound 1 is a rare example of a non-polymeric low molecular weight compound which neutralises the anticoagulant activity of heparin and LMWH in plasma samples. Limitation of the method is its low sensitivity currently being improved by structural modification of compound 1.
Effects of tissue factor, thrombomodulin and elevated clotting factor levels on thrombin generation in the calibrated automated thrombogram
Authors: Machlus Kellie , Colby Emily , Wu Jogin , Koch Gary , Key Nigel , Wolberg Alisa 
Published: September 2009

SummaryElevated procoagulant levels have been correlated with increased thrombin generation in vitro and with increased venous thromboembolism (VTE) risk in epidemiological studies. hrombin generation tests are increasingly being employed as a high throughput method to provide a global measure of procoagulant activity in plasma samples. The objective of this study was to distinguish the effects of assay conditions [tissue factor (TF), thrombomodulin, platelets/lipids] and factor levels on thrombin generation parameters, and determine the conditions and parameters with the highest sensitivity and specificity for detecting elevated factor levels. Thrombin generation was measured using calibrated automated thrombography (CAT) in corn trypsin inhibitor (CTI)-treated platelet-free plasma (PFP) and plateletrich plasma (PRP). Statistical analysis was performed using logarithms of observed values with analysis of variance that accounted for experiment and treatment. he relative sensitivity of lag time (LT), time to peak (TTP), peak height and endogenous thrombin potential (ETP) to elevated factors XI, IX,VIII, X, and prothrombin was as follows: PFP initiated with 1 pM TF > PFP initiated with 5 pM TF > PRP initiated with 1 pM TF. For all conditions, inclusion of thrombomodulin prolonged the LT and decreased the peak and ETP; however, addition of thrombomodulin did not increase the ability of CAT to detect elevated levels of individual procoagulant factors. In conclusion, CAT conditions differentially affected the sensitivity of thrombin generation to elevated factor levels. Monitoring the peak height and/ or ETP following initiation of clotting in PFP with 1 pM TF was most likely to detect hypercoagulability due to increased procoagulant factor levels.
The role of the vascular endothelium in arenavirus haemorrhagic fevers
Authors: Kunz Stefan 
Published: September 2009

SummaryViral haemorrhagic fevers (VHF) caused by arenaviruses are among the most devastating emerging human diseases.The most important pathogen among the arenaviruses is Lassa virus (LASV), the causative agent of Lassa fever that is endemic to West Africa. On the South American continent, the New World arenavirus Junin virus (JUNV), Machupo (MACV), Guanarito (GTOV), and Sabia virus (SABV) have emerged as causative agents of severe VHFs. Clinical and experimental studies on arenavirus VHF have revealed a crucial role of the endothelium in their pathogenesis. However, in contrast to other VHFs, haemorrhages are not a salient feature of Lassa fever and fatal cases do not show overt destruction of vascular tissue.The functional alteration of the vascular endothelium that precede shock and death in fatal Lassa fever may be due to more subtle direct or indirect effects of the virus on endothelial cells. Haemorrhagic disease manifestations and vascular involvement are more pronounced in the VHF caused by the South American haemorrhagic fever viruses. Recent studies on JUNV revealed perturbation of specific endothelial cell function, including expression of cell adhesion molecules, coagulation factors, and vasoactive mediators as a consequence of productive viral infection.These studies provided first possible links to some of the vascular abnormalities observed in patients; however, their relevance in vivo remains to be investigated.
Frogs of the genus Leptobrachella (Pelobatidae)
Authors: Dring Julian 
Published: September 2009

AbstractSix species are recognized: from Borneo, L. baluensis SMITH, L. mjobergi SMITH, L. parva sp.n. and L. brevicrus sp. n.; from the Bunguran Islands,L. natunae(GUNTHER) andL. serasanae sp. n. Calls ofthe Bornean species are described.
A new Forest Species of Phrynobatrachus (Anura: Ranidae) from Morogoro Region, Tanzania
Authors: Grandison A.G.C. , Howell K.M. 
Published: September 2009

AbstractA new species of moderate-sized Phrynobatrachus from the forests of the Uzungwe and Uluguru Mountains of southcentral Tanzania is described. It is distinguished by having dorsal asperities in both sexes and by a reddish-orange colouration on its digits and arms, this colour sometimes extending to the shoulders. The adult male lacks femoral glands and gular folds. Comparisons are made with other East African Phrynobatrachus species.
Frequency of reproduction, clutch size and clutch energy in the lizard Anguis fragilis
Authors: Patterson J.W. 
Published: September 2009

AbstractThe reproductive cycle offemale Anguisfragilis from Isle of Portland, Dorset, appears to be biennial. Fewer small females were reproducing in 1977 than in 1979 and the ratio clutch size: body size showed more variability in 1977. It is considered that the droughts in the summers of 1975 and 1976 had an adverse effect on A. fragilis reproduction in 1977. Total carcass energy in females about to give birth is much less than in females which are not reproducing that year. The ratio energy in clutch: total energy in body varies from 0.29 to 0.38.
Eine neue Art des Vipera berus-Komplexes aus der Türkei
Authors: Böhme Wolfgang , Joger Ulrich 
Published: September 2009

AbstractVipera baranin. sp. from northwestern Turkey is a member of the euro-siberian group within the genus Vipera. It is characterized by the following peculiarities: 1) Higher ventral count than V. ursinii and V. kaznakovi (145). 2) ♀ with a higher subcaudal count than V. ursinii, V. kaznakovi and V. berus (37). 3) Loreal scales and head plates divided to an extent as in the western European V. aspis (5 "loreals", 34 "intercanthals and intersupraoculars", parietals fully divided into small scales). 4) Different from V. aspis in having only one row of subocular scales between eye and supralabials. 5) The three specimens known up to now are totally melanistic, with white supralabials and a bright yellow underside of tail. The possibility ofy hybrid nature of the only preserved specimen is discussed and dimissed. As long as no further material is known, the relationships of V. barani to the other species can not be clarified.
Improving Thermal Insulation of Concrete Sandwich Buildings
Authors: Munch-Andersen Jørgen 
Published: September 2009

Increased requirement for the thermal insulation of buildings and reduction of energy consumption in order to decrease their carbon dioxide emission means that buildings only 30 years old are of a very low standard compared to today’s requirements. Therefore, there is a strong need to improve the insulation of many existing buildings. Improving insulation can be a risky business as experience has shown that different sorts of degradation will often occur after such work. On the other hand, improvement of the insulation could contribute to making a building more attractive to tenants. This article deals with good technical solutions for improving the insulation of concrete sandwich panel buildings from the 1960s and 1970s as well as how the savings in supplied energy can be estimated in a simple and accurate manner.
Zigrasite, MgZr(PO4)2(H2O)4, a new phosphate mineral from the Dunton Quarry, Newry, Oxford County, Maine, USA
Authors: Hawthorne F. C. , Ball N. A. , Nizamoff J. W. , Simmons W. B. 
Published: September 2009

AbstractZigrasite, ideally MgZr(PO4)2(H2O)4, is a new secondary phosphate mineral from the giant 1972 gem tourmaline-bearing pocket at the Dunton Quarry, Newry, Oxford County, Maine, USA. It occurs as subhedral blocky grains sometimes exceeding 1 mm in maximum dimension and perched on tourmaline. These grains are complex aggregates ofthree distinct phases, zigrasite and two unnamed phases: the Ca analogue of zigrasite, CaZr(PO4)2(H2O)4, and Zr(PO3OH)2(H2O)4. Zigrasite is associated with tourmaline, microcline, quartz, albite, beryl, amblygonite-montebrasite, childreniteeosphorite and apatite, and crystallized as one of the latest minerals during pocket formation. It is offwhite to pale yellow or light tan, translucent with a white streak and a vitreous lustre, and shows light blue to pale yellow cathodoluminescence. Mohs hardness is 3 and the measured and calculated densities are 2.76(4) and 2.66 g/cm3. The mineral has imperfect cleavage in two directions, parallel to (010) and (001), shows no parting, is brittle and has a hackly fracture. In transmitted light, it is colourless and non-pleochroic, biaxial negative with α 1.597(1), β 1.622 (1), γ 1.635 (1), with 2V(meas) = 65.5(4)º and 2V(calc.) = 71º. Zigrasite is triclinic, P , a 5.3049(2) Å, b 9.3372(4) Å, c 9.6282(5) Å, α 97.348(1)º, β 91.534(1)º, γ 90.512(4)º, V 472.79(5) Å3, Z = 2. The seven strongest lines in the X-ray powder diffraction pattern are as follows: d (Ê), I, (hkl): 9.550, 100, (001); 4.108, 70, ; 4.008, 50, (111); 4.589, 40, (110); 3.177, 40, (112); 3.569, 30, (0 2), 2.660, 30, (200),(11),(130); 3.273, 20, (12). Chemical analysis by electron microprobe gave P2O5 37.59, ZrO2 32.27, HfO2 0.34, FeO 0.20, MgO 10.37, ZnO 0.17, F 0.13, LOI 18.60, less O:F 0.05 = total 99.62 wt.%. The resulting empirical formula is (–)Σ=0.99(Zr0.99Hf0.01)Σ=1.00 P2.00O8(H2O)4 on the basis of12 O atoms with H2O = 4 per formula unit from crystal-structure analysis, and the end-member formula is MgZr(PO4)2(H2O)4.
Fluoro-sodic-ferropedrizite, NaLi2(Fe22+Al2Li)Si8O22F2, a new mineral of the amphibole group from the Sutlug River, Tuva Republic, Russia: description and crystal structure
Authors: Oberti R. , Boiocchi M. , Ball N. A. , Hawthorne F. C. 
Published: September 2009

AbstractFluoro-sodic-ferropedrizite, ideally ANaBLi2C()TSi8O22WF2, is a new mineral of the amphibole group from the Sutlug River, Tuva Republic, Russia. It occurs at the endogenic contact of a Li-pegmatite with country rocks near to a diabase dyke and formed by reaction of the pegmatitic melt with the country rock. Fluoro-sodic-ferropedrizite occurs as prismatic to acicular crystals, ranging in length from 0.1–3 cm and widths of up to 50 μm. Crystals occur inparallel to sub-parallel aggregates up to 5 mm across ina matrix of calcite and plagioclase feldspar. Crystals are pale bluish-grey with a greyish-white streak.Fluoro-sodic-ferropedrizite is brittle, has a Mohs hardness of ~6 and a splintery fracture; it is non-fluorescent with perfect {110} cleavage, no observable parting, and has a calculated density of 3.116 g cm–3. In plane-polarized light, it is pleochroic, X = pale purple-grey, Y = light grey, Z = colourless; X ^ a = 71.2º (in β acute), Y || b, Z ^ c = 83.4º (in β obtuse). Fluoro-sodic-ferropedrizite is biaxial positive, α = 1.642(1), β = 1.644(1), γ = 1.652(1); 2V(obs) = 68.0(3)º, 2V(calc) = 56.4º. Fluoro-sodic-ferropedrizite is monoclinic, space group C2/m, a = 9.3720(4) Å, b = 17.6312(8) Å, c = 5.2732(3) Å, β = 102.247(4)º, V = 851.5(2) Å3, Z = 2. The strongest ten X-ray diffraction lines in the powder patternare (d in Å ,(I),(hkl)): 8.146,(10),(110); 2.686,(9),(151); 3.008,(8),(310); 4.430,(7),(021); 2.485,(6),(02); 3.383,(4),(131); 2.876,(3),(51, 11); 2.199,(3),(12); 4.030,(2),(111) and 3.795,(2),(31). Analysis by a combination of electron microprobe and crystal-structure refinement gives SiO2 59.81, Al2O3 12.66, TiO2 0.09, FeO 10.32, MgO 5.56, MnO 0.73, ZnO 0.17, CaO 0.20, Na2O 2.81, Li2O 4.80, F 2.43, H2Ocalc 1.10, sum = 99.65 wt.%. The formula unit, calculated on the basis of 24(O,OH,F) is A(Na0.68)B(Li1.92Na0.05Ca0.03)C() T(Si7.98Al0.02)O22W(F1.03OH0.97). Crystal-structure refinement shows Li to be completely ordered at the M(3) and M(4) sites. Fluoro-sodic-ferropedrizite, ideally ANaBLi2C()TSi8O22WF2, is related to the theoretical end-member ‘sodic-pedrizite’, ANaBLi2C(Mg2Al2Li)TSi8O22W(OH)2, by the substitutions CFe2+ → CMg and WF → W(OH).
KSRP-PMR1-exosome association determines parathyroid hormone mRNA levels and stability in transfected cells
Authors: Nechama Morris , Peng Yong , Bell Osnat , Briata Paola , Gherzi Roberto , Schoenberg Daniel R , Naveh-Many Tally 
Published: September 2009

Abstract

Background
Parathyroid hormone (PTH) gene expression is regulated post-transcriptionally through the binding of the trans- acting proteins AU rich binding factor 1 (AUF1), Upstream of N-ras (Unr) and KH-type splicing regulatory protein (KSRP) to an AU rich element (ARE) in PTH mRNA 3'-UTR. AUF1 and Unr stabilize PTH mRNA while KSRP, recruiting the exoribonucleolytic complex exosome, promotes PTH mRNA decay.

Results
PTH mRNA is cleaved by the endoribonuclease polysomal ribonuclease 1 (PMR1) in an ARE-dependent manner. Moreover, PMR1 co-immunoprecipitates with PTH mRNA, the exosome and KSRP. Knock-down of either exosome components or KSRP by siRNAs prevents PMR1-mediated cleavage of PTH mRNA.

Conclusion
PTH mRNA is a target for the endonuclease PMR1. The PMR1 mediated decrease in PTH mRNA levels involves the PTH mRNA 3'-UTR ARE, KSRP and the exosome. This represents an unanticipated mechanism by which the decay of an ARE-containing mRNA is facilitated by KSRP and is dependent on both the exosome and an endoribonuclease.
Deep sequencing of Brachypodium small RNAs at the global genome level identifies microRNAs involved in cold stress response
Authors: Zhang Jingyu , Xu Yunyuan , Huan Qing , Chong Kang 
Published: September 2009

Abstract

Background
MicroRNAs (miRNAs) are endogenous small RNAs having large-scale regulatory effects on plant development and stress responses. Extensive studies of miRNAs have only been performed in a few model plants. Although miRNAs are proved to be involved in plant cold stress responses, little is known for winter-habit monocots. Brachypodium distachyon, with close evolutionary relationship to cool-season cereals, has recently emerged as a novel model plant. There are few reports of Brachypodium miRNAs.

Results
High-throughput sequencing and whole-genome-wide data mining led to the identification of 27 conserved miRNAs, as well as 129 predicted miRNAs in Brachypodium. For multiple-member conserved miRNA families, their sizes in Brachypodium were much smaller than those in rice and Populus. The genome organization of miR395 family in Brachypodium was quite different from that in rice. The expression of 3 conserved miRNAs and 25 predicted miRNAs showed significant changes in response to cold stress. Among these miRNAs, some were cold-induced and some were cold-suppressed, but all the conserved miRNAs were up-regulated under cold stress condition.

Conclusion
Our results suggest that Brachypodium miRNAs are composed of a set of conserved miRNAs and a large proportion of non-conserved miRNAs with low expression levels. Both kinds of miRNAs were involved in cold stress response, but all the conserved miRNAs were up-regulated, implying an important role for cold-induced miRNAs. The different size and genome organization of miRNA families in Brachypodium and rice suggest that the frequency of duplication events or the selection pressure on duplicated miRNAs are different between these two closely related plant species.
The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure
Authors: Song Hong-Li , Lv Sa , Liu Pei 
Published: September 2009

Abstract

Background
Spontaneous bacterial peritonitis (SBP) is a common clinical disease and one of the most severe complications of acute liver failure (ALF). Although the mechanism responsible for SBP is unclear, cytokines play an important role. The aim of this study was to investigate the effects of tumor necrosis factor-alpha (TNF-α) on the structure of the intestinal mucosa and the expression of tight junction (Zona Occludens 1; ZO-1) protein in a mouse model of ALF.

Methods
We induced ALF using D-galactosamine/lipopolysaccharide (GalN/LPS) or GalN/TNF-α and assessed the results using transmission electron microscopy, immunohistochemistry, Western blotting, ELISA and real-time quantitative PCR. The effects of administration of anti-TNF-α IgG antibody or anti-TNF-α R1 antibody before administration of GalN/LPS or GalN/TNF-α, respectively, on TNF-α were also assessed.

Results
Morphological abnormalities in the intestinal mucosa of ALF mice were positively correlated with serum TNF-α level. Electron microscopic analysis revealed tight junction (TJ) disruptions, epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was significantly decreased in both ALF models, as was the level of ZO-1 protein. Prophylactic treatment with either anti-TNF-α IgG antibody or anti-tumor necrosis factor-a receptor1 (anti-TNF-α R1) antibody prevented changes in intestinal tissue ultrastructure and ZO-1 expression.

Conclusion
TNF-α affects the structure of the intestinal mucosa, decreases expression of ZO-1, and affects the morphology of the colon in a mouse model of ALF. It also may participate in the pathophysiological mechanism of SBP complicated to ALF.
Integrating human stem cell expansion and neuronal differentiation in bioreactors
Authors: Serra Margarida , Brito Catarina , Costa Eunice M , Sousa Marcos FQ , Alves Paula M 
Published: September 2009

AbstractBackgroundHuman stem cells are cellular resources with outstanding potential for cell therapy. However, for the fulfillment of this application, major challenges remain to be met. Of paramount importance is the development of robust systems forin vitrostem cell expansion and differentiation. In this work, we successfully developed an efficient scalable bioprocess for the fast production of human neurons.ResultsThe expansion of undifferentiated human embryonal carcinoma stem cells (NTera2/cl.D1 cell line) as 3D-aggregates was firstly optimized in spinner vessel. The media exchange operation mode with an inoculum concentration of 4 × 105cell/mL was the most efficient strategy tested, with a 4.6-fold increase in cell concentration achieved in 5 days. These results were validated in a bioreactor where similar profile and metabolic performance were obtained. Furthermore, characterization of the expanded population by immunofluorescence microscopy and flow cytometry showed that NT2 cells maintained their stem cell characteristics along the bioreactor culture time.Finally, the neuronal differentiation step was integrated in the bioreactor process, by addition of retinoic acid when cells were in the middle of the exponential phase. Neurosphere composition was monitored and neuronal differentiation efficiency evaluated along the culture time. The results show that, for bioreactor cultures, we were able to increase significantly the neuronal differentiation efficiency by 10-fold while reducing drastically, by 30%, the time required for the differentiation process.ConclusionThe culture systems developed herein are robust and represent one-step-forward towards the development of integrated bioprocesses, bridging stem cell expansion and differentiation in fully controlled bioreactors.