bluuebunny/crossref_metadata_2025 huggingface dataset:
Induced pluripotent stem cell-derived endothelial cells promote angiogenesis and accelerate wound closure in a murine excisional wound healing model
Authors: Clayton Zoë E. , Tan Richard P. , Miravet Maria M. , Lennartsson Katarina , Cooke John P. , Bursill Christina A. , Wise Steven G. , Patel Sanjay
Published: July 2018

Chronic wounds are a major complication in patients with cardiovascular diseases. Cell therapies have shown potential to stimulate wound healing, but clinical trials using adult stem cells have been tempered by limited numbers of cells and invasive procurement procedures. Induced pluripotent stem cells (iPSCs) have several advantages of other cell types, for example they can be generated in abundance from patients’ somatic cells (autologous) or those from a matched donor. iPSCs can be efficiently differentiated to functional endothelial cells (iPSC-ECs). Here, we used a murine excisional wound model to test the pro-angiogenic properties of iPSC-ECs in wound healing. Two full-thickness wounds were made on the dorsum of NOD-SCID mice and splinted. iPSC-ECs (5 × 105) were topically applied to one wound, with the other serving as a control. Treatment with iPSC-ECs significantly increased wound perfusion and accelerated wound closure. Expression of endothelial cell (EC) surface marker, platelet endothelial cell adhesion molecule (PECAM-1) (CD31), and pro-angiogenic EC receptor, Tie1, mRNA was up-regulated in iPSC-EC treated wounds at 7 days post-wounding. Histological analysis of wound sections showed increased capillary density in iPSC-EC wounds at days 7 and 14 post-wounding, and increased collagen content at day 14. Anti-GFP fluorescence confirmed presence of iPSC-ECs in the wounds. Bioluminescent imaging (BLI) showed progressive decline of iPSC-ECs over time, suggesting that iPSC-ECs are acting primarily through short-term paracrine effects. These results highlight the pro-regenerative effects of iPSC-ECs and demonstrate that they are a promising potential therapy for intractable wounds.
Chemistry in disks
Authors: Semenov D. , Favre C. , Fedele D. , Guilloteau S. , Teague R. , Henning Th. , Dutrey A. , Chapillon E. , Hersant F. , Piétu V.
Published: July 2018

Context. Several sulfur-bearing molecules are observed in the interstellar medium and in comets, in strong contrast to protoplanetary disks where only CS, H2CS, and SO have been detected so far.

Aims. We combine observations and chemical models to constrain the sulfur abundances and their sensitivity to physical and chemical conditions in the DM Tau protoplanetary disk.

Methods. We obtained 0.5′′ Atacama Large Millimeter Array observations of DM Tau in Bands 4 and 6 in lines of CS, SO, SO2, OCS, CCS, H2CS, and H2S, achieving a ~5 mJy sensitivity. Using the non-Local Thermodynamical Equilibrium radiative transfer code RADEX and the forward-modeling tool DiskFit, disk-averaged CS column densities and upper limits for the other species were derived.

Results. Only CS was detected with a derived column density of ~2−6 × 1012 cm−2. We report a first tentative detection of SO2 in DM Tau. The upper limits range between ~1011 and 1014 cm−2 for the other S-bearing species. The best-fit chemical model matching these values requires a gas-phase C/O ratio of ≳1 at r ≳ 50−100 au. With chemical modeling we demonstrate that sulfur-bearing species could be robust tracers of the gas-phase C/O ratio, surface reaction rates, grain size and UV intensities.

Conclusions. The lack of detections of a variety of sulfur-bearing molecules in DM Tau other than CS implies a dearth of reactive sulfur in the gas phase, either through efficient freeze-out or because most of the elemental sulfur is in other large species, as found in comets. The inferred high CS/SO and CS/SO2 ratios require a non-solar C/O gas-phase ratio of ≳1, consistent with the recent observations of hydrocarbon rings in DM Tau. The stronger depletion of oxygen-bearing S-species compared to CS is likely linked to the low observed abundances of gaseous water in DM Tau and points to a removal mechanism of oxygen from the gas.
Hill stability in the AMD framework
Authors: Petit Antoine C. , Laskar Jacques , Boué Gwenaël
Published: July 2018

In a two-planet system, a topological boundary that is created by Sundman (1912, Acta Math., 36, 105) inequality can forbid close encounters between the two planets for an infinite time. A system is said to be Hill stable if it verifies this topological condition. Hill stability is widely used in the study of extrasolar planet dynamics. However, the coplanar and circular orbit approximation is often used. In this paper, we explain how the Hill stability can be understood in the framework of angular momentum deficit (AMD). In the secular approximation, AMD allows us to discriminate between a priori stable systems and systems for which a more in-depth dynamical analysis is required. We show that the general Hill stability criterion can be expressed as a function of only semimajor axes, masses, and total AMD of the system. The proposed criterion is only expanded in the planets-to-star mass ratio ε and not in the semimajor axis ratio, eccentricities, nor the mutual inclination. Moreover, the expansion in ε remains excellent up to values of about 10−3 even for two planets with very different mass values. We performed numerical simulations in order to highlight the sharp change of behavior between Hill stable and Hill unstable systems. We show that Hill stable systems tend to be very regular, whereas Hill unstable systems often lead to rapid planet collisions. We also note that Hill stability does not provide protection from the ejection of the outer planet.
Ultrasound Markers in Fetal Hydronephrosis to Predict Postnatal Surgery
Authors: Kiener Teresa Antonia , Wohlmuth Christoph , Schimke Christa , Brandtner Martha Georgina , Wertaschnigg Dagmar
Published: July 2018

Purpose Parents confronted with the finding of antenatal hydronephrosis (ANH) are particularly interested in whether their baby will need postnatal surgery. The objective of this study was to predict ANH requiring surgery on the basis of the fetal anteroposterior renal pelvic diameter (APRPD) and the Society for Fetal Urology (SFU) grading system.

Materials and Methods The medical records of 179 patients with the finding of ANH were reviewed retrospectively. ANH was graded according to the SFU grading system. Prenatal ultrasound examinations were correlated to postnatal outcome, which was divided into three groups: prenatal resolution, conservative management and surgical treatment.

Results 58 (32.4 %) cases were classified as prenatal resolution, 89 (49.7 %) babies were assigned to the conservative outcome group and 32 (17.9 %) patients needed surgical repair. Postnatal surgery was best predicted in the second trimester (area under the receiver operating characteristics curve: 0.839) by an APRPD cut-off of 8.3 mm (sensitivity: 77.8 %; specificity: 85.7 %; PPV of 53.9 %, NPV of 94.7 %). The combination of the parameters “progression of SFU grade” and SFU grade 3 or 4 achieved a sensitivity of 84.4 % and a specificity of 80.3 % for the prediction of surgery.

Conclusion Second-trimester APRPD is a useful parameter for predicting the risk for postnatal surgery. The SFU grade should be assessed in every prenatal ultrasound examination as some further risk estimates can be made based on its dynamics over time.
Can Ultrasound Alone Predict Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis? A Retrospective Analysis of 13 Cases, Focusing on the Stromal Area
Authors: Tajiri Kumiko , Hirokawa Mitsuyoshi , Suzuki Ayana , Takada Nami , Ota Hisashi , Oshita Maki , Fukushima Mitsuhiro , Kobayashi Kaoru , Miyauchi Akira
Published: July 2018

Papillary thyroid carcinoma with desmoid-type fibromatosis (PTC-DTF) is extremely rare. So far, only 4 cases describing the ultrasound findings of this variant have been reported. Here, we describe the ultrasound findings of 13 cases of PTC-DTF, focusing especially on the DTF area.

We retrospectively analyzed the clinical reports, ultrasound reports, and ultrasound photographs obtained from medical records at Kuma Hospital.

The patients included 8 women and 5 men with a mean age of 47.9 years. The widest dimension of the nodules ranged from 16 to 79 mm (mean: 37.5 mm). The original ultrasound reports classified the nodules as either intermediate suspicion or high suspicion. A diagnosis of PTC was suspected in 12 nodules, and anaplastic carcinoma was suspected in 1 nodule. PTC-DTF presented with an irregularly shaped nodule (100%), taller-than-wide sign (84.6%), heterogeneous echogenicity (100%), no microcalcification (76.9%), and no or mild flow signal on Doppler (75.0%). The DTF area was identified in the ultrasound photographs of 8 nodules. DTF areas were generally heterogeneous (62.5%) and more hypoechoic (71.4%) than PTC areas. Microcalcification was not observed in the DTF areas. All of the DTF areas revealed no or mild flow signal. On ultrasound elastography, the DTF areas were not stiff, and they were more elastic than the PTC areas.

It is difficult to predict PTC-DTF using ultrasound alone, and B-mode ultrasonography is more reliable than ultrasound elastography in the ultrasound diagnosis of malignant thyroid nodules.
Influencing Factors of 2D Shear Wave Elastography of the Muscle – An Ex Vivo Animal Study
Authors: Rominger Marga , Kälin Pascal , Mastalerz Monika , Martini Katharina , Klingmüller Volker , Sanabria Sergio , Frauenfelder Thomas
Published: July 2018

To evaluate measurement confounders on 2D shear wave elastography (2D-SWE) elastography of muscle.

Ex vivo, porcine muscle was examined with a GE LOGIQ E9 ultrasound machine with a 9 L linear (9 MHz) and C1-6 convex probe (operating at 2.5 or 6 MHz). The influence of different confounders on mean shear wave velocity (SWVmean) was analyzed: probes, pressure applied by probe, muscle orientation, together with the impact of different machine settings such as frequency, placement depth and size of region of interest (ROI). The mean of twelve repeated SWVmean measurements (m/s) and coefficient of variation (CV; standard deviation/mean in %) were assessed for each test configuration.

Reproducibility (CV) and maximum possible tissue depth of the linear probe were inferior to the convex probe. With the linear probe, there was a linear decrease of SWVmean with placement depth from 4.56 m/s to 1.81 m/s. A significant increase of SWVmean (p<0.001) was observed for larger ROI widths (range 3.96 m/s to 6.8 m/s). A change in the machine operation mode ('penetration' instead of 'general') led to a significant increase of SWVmean (p=0.04). SWVmean in the longitudinal direction of muscle was significantly higher than in cross section (p<0.001) (e. g. 4.56 m/s versus 3.42 m/s). An increase of linear probe pressure significantly increased muscle SWVmean from 5.29 m/s to 7.21 m/s (p<0.001).

2D-SWE of muscle is influenced by a wealth of parameters. Therefore, standardization of measurement is advisable before application in clinical research studies and routine patient assessment.
Catalytic Pauson–Khand Reaction in Ethylene Glycol–Toluene: Activity­, Selectivity, and Catalyst Recycling
Authors: Verdaguer Xavier , Riera Antoni , Cabré Albert
Published: July 2018

The use of ethylene glycol (15% v/v in toluene) as additive in the catalytic Pauson–Khand reaction (PKR) is reported. In most cases both the yield and selectivity were enhanced compared to standard protocols. Moreover, the immiscibility of ethylene glycol in toluene allowed recycling of the catalyst (which remained mainly in the ethylene glycol). The recycling allowed catalyst loading to be reduced to only 3 mol%. A gram-scale reaction was also performed, allowing the use of only 1 mol% of Co2(CO)8, the lowest amount reported so far in intermolecular cobalt-catalyzed PKR.
Distribution of the Recombinant Coagulation Factor 125I-rFVIIa in Rats
Authors: Beeby T L , Chasseaud L F , Taylor T , Thomsen M K
Published: July 2018

Recombinant human factor VIIa (rFVIIa; NovoSeven®) is a two-chain activated clotting factor that is used in the treatment of haemophilia. The distribution of radioactivity in male and pregnant and non-pregnant female rats has been examined by whole-body autoradiography (WBA) after single intravenous doses of 125I-radiolabelled rFVIIa at a dosage level of ca. 0.1 mg/kg.

Concentrations of radioactivity were highest in the blood and the highly perfused major thoracic and visceral organs and gonads. This distribution of radioactivity was generally similar in pregnant and non-pregnant females, and although radioactivity was concentrated in the foetal thyroid, it was present in other foetal tissues only at trace levels. Radioactivity in thyroid, urinary bladder and gastrointestinal tract of all rats was apparently associated with detached 125I-iodide. At early sacrifice times (up to 2 h), radioactivity was present in the bone marrow, but at later times (6-24 h) it was apparently associated with the mineralised bone structures.

The quantitative distribution of total and trichloroacetic acid precipitable radioactivity in the tissues of rats also was studied after single intravenous doses of 125I-rFVIIa and 125I-rFVII, the non-activated single chain precursor of FVIIa, which is normally present in the circulation. These studies confirmed the WBA findings and showed that the tissue distribution of 125I-rFVII and 125I-rFVIIa was similar, indicating that the distribution of rFVIIa during therapy would be similar to that produced from endogenous FVII as a physiological response to vascular injury.
Incidence and Course of Symptomatic Deep Venous Thrombosis of the Lower Extremities in a Black Caribbean Population
Authors: Nossent J C , Egelie N.C W.M
Published: July 2018

During a 5-year period 131 patients with symptomatic deep venous thrombosis of the lower extremities (DVT) were identified in a black Caribbean population. Eighty-one patients (61%) had objective evidence (ascending venography), while in 39% the diagnosis was based on clinical findings only. The overall annual incidence rate for definite DVT was 11 per 100,000 person years; there was a steep increase with age in both sexes. Proximal DVT was present in 69% of patients. Swelling (92%), pain on palpation (89%) and tenderness (87%) were the most frequent symptoms, while immobilization (43%) and varicosities (42%) were the most frequent risk factors; DVT was rare during pregnancy (1 in 15,000 deliveries). Seventeen patients (21%) developed pulmonary embolism and five patients (6.2%) died during the hospital stay (four of fatal pulmonary embolism, one due to toxic epidermolysis after venography). We conclude, that symptomatic DVT of the lower extremities has a low incidence in this black Caribbean population, but is nonetheless associated with considerable morbidity and mortality due to pulmonary embolism.
Standard and Method Independent Units for Heparin Anticoagulant Activities
Authors: Hemker H C , Béguin S
Published: July 2018

It is discussed why the current USP unit of heparin anticoagulant activity necessarily will render inaccurately the anticoagulant activities of low molecular weight heparins. It is shown that the outcome is bound to vary with the method used for comparison of the sample and the standard and with the nature of the standard used. As an alternative we define a unit of heparin in terms of anti-factor Xa- and antithrombin-activity that is independent of the heparin standard and of the assay method, but that is based upon a quantitative description of the catalytic effect of heparin on AT III mediated thrombin- and factor Xa breakdown. Expression of the results of existing anti-factor Xa- and antithrombin tests in terms of these units will allow to express heparin levels in plasma in terms of concentrations of active anticoagulant material. This approach makes it possible to separate heparin pharmacodynamics from heparin pharmacokinetics. Introduction of this unit does not require adaptation of current laboratory practice but changes the way in which the results obtained are expressed.
Facilitation of Plasminogen Activation by a Plasmin Substrate Containing a Lysyl Residue
Authors: Machovich Raymund , Owen Whyte G
Published: July 2018

The plasmin substrate, H-D-norleucyl-hexahydrotyrosyl lysine-p-nitroanilide (Spectrozyme-PL), was found to be equiva lent to 6-aminohexanoate as an enhancer of porcine and human plasminogen activation by urokinase and of removal of the 1-77 peptide of plasminogen by plasmin. Activation of plasminogen lacking kringles 1-4, on the other hand, was not influenced by Spectrozyme PL. Although the rate of activation of human plasminogen and the modification of human plasminogen by plasmin are faster by an order of magnitude than that of the activation and modification of porcine plasminogen, both reactions in the human zymogen, the hydrolysis at arg561-val562 and at lys77lys78, are accelerated by Spectrozyme PL. The findings indicate that kinetic interpretation of plasminogen activation in solutions containing substrates, where the substrate has been incorporated to inhibit feedback proteolysis by plasmin, must account for the cofactor activity as well as the inhibitory activity of the substrate.
Plasmin Potency Estimates: Influence of the Substrate Used in Assay
Authors: Philo Roger D , Gaffney Patrick J
Published: July 2018

A urokinase-activated plasmin (UK-plasmin) preparation was assayed against the International Reference Preparation for Plasmin (IRP-plasmin) using caseinolytic, fibrinolytic, fibrinogenolytic and chromogenic assay methods. The relative potency (using multi-dose bioassays) was estimated by the fibrinolytic method to be about twice that obtained by the caseinolytic, fibrinolytic and chromogenic assay methods. It was found that the UK-plasmin binds to fibrin to a greater extent than does the IRP-plasmin and this is advanced as an explanation for the discrepancy between assay methods. This difference in the binding of the two plasmins to fibrin may mean that it will be difficult to compare the fibrinolytic activities of various plasmin preparations.

It is also shown that, during thermal degradation, the IRP-plasmin loses fibrinolytic activity more rapidly than amidolytic activity.
Heparin-Releasable and Platelet Pools of Tissue Factor Pathway Inhibitor in Rabbits
Authors: Warn-Cramer Bonnie J , Maki Steven L , Rapaport Samuel I
Published: July 2018

Earlier studies from this laboratory have established that tissue factor pathway inhibitor (TFPI) functions as a natural anticoagulant protecting rabbits from intravascular coagulation triggered by the exposure of blood to small amounts of tissue factor. In addition to the TFPI circulating in plasma, humans have been shown to have heparin-releasable and platelet pools of TFPI. In order better to extrapolate from studies carried out in rabbits to an understanding of human hemostasis, we have examined the presence and extent of heparin-releasable and platelet pools of TFPI in rabbits. We find that in the rabbit the heparin-releasable pool of TFPI activity, as measured in a capacity assay, may be smaller relative to the plasma pool than in humans; that the platelet pool of TFPI activity is comparable to that of humans; and that rabbit TFPI, unlike human TFPI, has the same apparent molecular mass in all vascular pools. These studies extend our understanding of the properties of TFPI in rabbits and the appropriateness of using the rabbit for studies of TFPI relevant to human hemostasis.
Different Expression of Procoagulant Activity in Human Cancer Cells Cultured “In Vitro” or in Cells Isolated from Human Tumor Tissues
Authors: Zucchella Marisa , Pacchiarini Lucia , Tacconi Fiorenzo , Saporiti Anna , Grignani Guido
Published: July 2018

We studied in a homologous system the procoagulant activity of human tumor cells cultured “in vitro” (1402 primary melanoma, Me 7110/2 metastatic melanoma, Hep G2 hepatoma and GLC1 small cell lung carcinoma) or of cells freshly isolatedfrom different human tumor tissues.

Tumor cells cultured “in vitro” possessed and released a factor VII dependent procoagulant activity, which was inhibitedby concanavalin A and unaffected by iodoacetamide or HgCl2. The activity released by the cells of metastatic melanoma was higher than that released by the cells of the primary tumor. On the contrary, cancer cells isolated from tumor tissues possessed and released a factor VII independent activity which was inhibited by iodoacetamide or HgCl2 and was not modified by concanavalin A. Therefore, different methods for the preparation of tumor cell suspensions have to be used for the study of tumor procoagulants, since their expression depends very largely on the source of tumor cells. Furthermore, cultured human tumor cells are not an appropriate model for the “in vivo” procoagulant effect of tumor cells.
Microbubble-Induced Phospholipase C Activation Does not Correlate with Platelet Aggregation
Authors: Malmgren R , Thorsen T , Nordvik A , Holmsen H
Published: July 2018

The effect of nitrogen-(N2-)microbubbles on platelets resembles that of common platelet agonists with respect to aggregation and secretion, but is considerably slower and is poorly inhibited by aspirin. This paper reports the effect of microbubbles on platelet phospholipase C activity in gelfiltered human platelets prelabelled with [32P]Pi ([32P]-GFP). The experiments were run in the presence of an ADP scavenging system in order to rule out effects of ADP. Stimulation of [32P]-GFP for 30 min with microbubbles caused a significant reduction in single platelets (p <0.0004) and a significant increase in 32P-activity in the phosphatidic acid (PA) fraction (p <0.02). Epinephrine potentiated the microbubble-induced reduction in single platelets (p <0.05), but did not enhance the amount of 32P in the platelet [32P]PA fraction. The 32P-radioactivity in the PI-fraction increased with time to a similar extent when [32P]-GFP was stirred for 30 min in absence of microbubbles as it did after 30 min of agonist exposure. There were no significant changes in the [32P]PIP and [32P]PIP2 fractions. Aspirin abolished the microbubble-induced increase in 32P-activity in the PA fraction, but had no significant effect on the reduction in single platelets. Aspirin had a small but significant, reducing effect on platelet aggregation induced by a combination of epinephrine and microbubbles (p <0.05). With epinephrine, however, aspirin did not completely abolish the increase in [32P]-PA. It is concluded that microbubbles alone cause platelets to aggregate by a novel mechanism that operates independent of cyclooxygenase-dependent arachidonic acid metabolites and phospholipase C activation.
Generation of Tissue Factor by Patient Monocytes: Correlation to Thromboembolic Complications
Authors: Miller Carol L , Graziano Charles , Lim Robert C , Chin Milly
Published: July 2018

Thromboembolic complications are often a common pathological consequence of severe soft tissue trauma. Recent demonstration that monocytes (MØ) produce tissue factor (TF) has led to the suggestion that these TF producing MØ might play a role in coagulopathy. We have previously demonstrated that trauma patients with splenectomy develop aberrant monocyte function and this patient group is also known to be at high risk of hypercoagulability episodes. This paper is an intial report on the use of MØ TF as an indicator of and/or a correlate to clotting episodes. Monocytes isolated from the Ficoll-Hypaque purified mononuclear cells of 46 normal individuals, 17 trauma patients and 6 surgical controls were assayed at 3 day post-injury intervals for their levels of TF activity. Changes in monocyte TF activity were correlated to increases in the fractional catabolic rate (FCR) of 125I-fibrinogen. Trauma patients were retrospectively divided into those whose FCR was elevated to a level indicative of coagulopathy and those whose FCR levels were not associated with coagulation abnormalites. All trauma patients who exhibited significantly increased FCR experienced thromboembolic episodes and had monocytes whose TF activity was increased an average of 300% (X = 47 units vs X = 12 units) over surgical controls. These increases in monocyte TF activity occrured at 6-13 days post injury and preceded clinical manifestation of coagulopathy by 4-6 days. The increased monocyte TF activity demonstrated in this study was significantly correlated to detection of pathologically increased FCR (Rs = 0.850) and compared to other indices of hypercoagulability.
Long-Term Tolerance and Recovery of β-Propiolactone/Ultraviolet (βPL/UV) Treated PPSB in Chimpanzees
Authors: Stephan W , Kotitschke R , Prince A M , Brotman B
Published: July 2018

Recent experiments have shown that a preparation of PPSB (factor IX concentrate) derived from βPL/UV treated plasma was not infectious in chimpanzees with respect to hepatitis B and non-A, non-B. To answer the question whether the βPL/UV treatment influences the tolerance and efficacy of the PPSB concentrate, long-term application of PPSB-Biotest was carried out in chimpanzees. After 10 applications of 25 U factor IX/kg at weekly intervals, no signs of intolerance were observed by measurement of blood pressure during i. v. application and by means of skin-testing. Determination of coagulation factor activity during the application period revealed the same factor IX recovery at the beginning and at the end of the study.
Platelet Hypersensitivity in Acute Malaria (Plasmodium falciparum) Infection in Man
Authors: Essien E M , Ebhota M I
Published: July 2018

During acute malaria infection, platelets in human platelet-rich plasma are hypersensitive to the addition of ADP between 1.0 uM and 5.0 uM, or adrenaline 0.11 uM as aggregating agents. The mean maximum aggregation amplitude (as % of light transmission) obtained from 8 subjects in response to added ADP (1.0 uM), 39.8 ± 27 (1SD), was significantly greater than the value in 6 controls (5.2±6.7 (1SD); t = 3, 51 P <0.005). A similar pattern of response was obtained with higher ADP concentrations (2.4,4.5 or 5.0 uM) in 22 patients and 20 control subjects (89.9±14.9% vs 77.8±16.5% (1SD) t = 2.45, P <0.02). Addition of 4.5 uM ADP to patient PRP usually evoked only a single aggregation wave (fused primary and secondary waves) while the typical primary and secondary wave pattern was usually obtained from controls.

Mean plasma B-thromboglobulin (BTG) concentration in 7 patients (208.3 ± 15.6 ng/ml) was significantly higher than the value in 6 control subjects (59.2±15.7 ng/ml; t = 13.44, P <0.002).
Purification and Characterization of the Plasminogen Activator Secreted by a Rat Brain Tumor Cell Line in Culture
Authors: Bykowska K , Rijken D C , Collen D
Published: July 2018

The plasminogen activator secreted by a cultured rat brain tumor cell line (RT4-71-1) (Imada M. and Sueoka N., Develop.Biol. 69, 97-107, 1978) was purified by chromatography on zinc chelate-agarose, concanavalin A-agarose and Sephadex G-150 in the presence of 0.01% (vol/vol) Tween 80. Aprotinin was added to the culture medium to a concentration of 20 KIU per ml and to the buffers in the first two chromatographic steps to a concentration of 10 KIU per ml. Approximately 90 μg purified material was obtained from 1 1 of culture medium with a yield of 39% and a purification factor of 200. Sodium dodecylsulfate-polyacryl amide gel electrophoresis in the presence of reducing agents showed one main band with M
r of about 60,000, and a minor band with M
r about 30,000. Fibrinolytic activity was associated with the main band. The rat brain tumor plasminogen activator bound to a fibrin clot to a similar extent as human tissue plasminogen activator, whereas urokinase did not bind. In quenching experiments of the fibrinolytic activities the purified rat brain tumor plasminogen activator appeared to be immunologically related to the human tissue plasminogen activator but unrelated to urokinase.
Effects of Methylprednisolone and Hydrocortisone on Aggregation of Rabbit Platelets Induced by Arachidonic Acid and Other Aggregating Substances
Authors: Glass Frank , Lippton Howard , Kadowitz Philip J
Published: July 2018

The effects of methylprednisolone and hydrocortisone on platelet aggregation induced by arachidonic acid (AA), collagen, adenosine diphosphate (ADP), prostaglandin (PG) H2, and a stable PGH2 analog, were studied in platelet-rich plasma (PRP) from the rabbit. Incubation of either steroid in PRP inhibited AA-, collagen- and ADP-induced platelet aggregation in a concentration-related manner. The dose of methylprednisolone required to inhibit 0.02 mM AA-induced aggregation was lower than that required to inhibit either 0.08 μg/ml collagen or 0.2 μM ADP-induced aggregation. Methylprednisolone produced a dose dependent inhibition of platelet aggregation induced by PGH2 and the stable PGH2 analog. In washed platelets methylprednisolone was more effective in inhibiting AA-induced aggregation than ADP- or collagen-induced aggregation; however, the difference in effect was less than in PRP. Platelet responses to AA in PRP from rabbits treated with hydrocortisone or methylprednisolone, 100 mg/kg i.v., were inhibited in a transient manner, whereas aggregation induced by ADP under similar conditions was unchanged. Since inhibition of aggregation elicited by AA occurred at concentrations which do not influence PGH2-, PGH2 analog-, collagen- or ADP-induced aggregation, the present data suggest that the steroids may inhibit the incorporation, the release, or the metabolism of arachidonic acid in platelets. The actual mechanism of this relatively specific inhibition of AA-induced aggregation by anti-inflammatory steroids is uncertain but may be related to the membrane “stabilizing” properties of methylprednisolone and hydrocortisone.
Collagen-Induced Platelet Aggregation as Studied by Electronic Particle Size Analysis
Authors: McLean Margaret R , Hause Lawrence L
Published: July 2018

The collagen-induced response of free platelets during aggregation was measured with an electronic particle size analyzer. Aggregation was induced in platelet-rich plasma by 0.05 mg/mL collagen. The reaction was followed turbidimetrically and samples for electronic particle size analysis were obtained during aggregation.Free platelet number decreased rapidly after the addition of collagen. This decrease preceded detectable changes in transmittance and a significant reduction in free platelet number was measured during the classical lag phase. In addition, the size distribution of free platelets at variotrs times after the addition of collagen was not significantly altered indicating that large platelets are not preferentially involved in collagen-induced aggregation.
Broadband terahertz metamaterial absorber based on simple multi-ring structures
Authors: Shen Guoqing , Zhang Ming , Ji Yanping , Huang Wanxia , Yu Honglin , Shi Jianping
Published: July 2018

Single-layer metallic rings are the effective structure cell which are widely used to design single-band and multiband perfect metamaterial absorbers owning to their electromagnetic resonance. However, the absorbers based on the single-layer metallic rings have a common shortcoming, that is the narrow absorption bandwidth. To overcome the limitations, here we proposed a single-layer, flexible and broadband terahertz metamaterial absorber, which consists of four sub-cells with multiple metal rings and a metal ground plane separated by a dielectric layer. By enhancing the coupling response between adjacent metallic rings and merging the adjacent resonant peaks of multi-resonators, we experimentally observed broadband characteristics at the terahertz band. The average absorption of 88% from 0.63 to 1.34 THz and the relative absorption bandwidth of 95% at the incident angle of 15o for TE polarization. Correspondingly, for TM polarization the absorption of more than 80% from 0.61 to 1.1 THz with the relative absorption bandwidth of 80% were also observed. The results went far beyond the previous single-layer absorbers based on metal rings and were much better than the fractal-cross structure reported recently [Kenney et al., ACS Photonics 4, 2604 (2017)]. We had reason to believe that the presented terahertz metamaterial absorber with broad absorption bandwidth and simple structure can find important applications in communication, stealth, energy harvesting systems and so on.
Marangoni effect on the motion of a droplet covered with insoluble surfactant in a square microchannel
Authors: Luo Zheng Yuan , Shang Xing Long , Bai Bo Feng
Published: July 2018

Despite its significance in various applications, e.g., droplet microfluidics and chemical enhanced oil recovery, the motion of surfactant-laden droplets in non-circular microchannels remains an unsolved fundamental problem. To facilitate studies in this area, we present a systematic investigation on the motion of a droplet covered with an insoluble surfactant in a square microchannel. This work is realized via our three-dimensional front-tracking finite-difference model with integration of the convection-diffusion equation for surfactant transport on a deforming drop surface. Our results indicate significant effects of the surfactant on steady-state characteristics of droplet motion, especially the droplet-induced additional pressure loss in the channel. More particularly, the surfactant-induced reduction in drop surface tension remarkably lowers the additional pressure loss, but this effect can be fully counteracted by the effect of surface tension gradient induced Marangoni stress (i.e., to enlarge the additional pressure loss). The increasing effect of the Marangoni stress is primarily determined by two surfactant-related dimensionless parameters, i.e., the surface Peclet number and the elasticity number. The additional pressure loss significantly increases with either of them increasing. Besides, the Marangoni effect on the droplet-induced additional pressure loss also strongly depends on three other independent parameters, i.e., it is inhibited by decreasing the size ratio of the drop to the channel, increasing the viscosity ratio of the drop to the surrounding fluid, or increasing the capillary number. Finally, we discuss the mechanism of the Marangoni effect on drop motion via analyzing the distributions of the surfactant concentration and drop surface velocity on a three-dimensional drop surface.
From octopus to dendrite—Semiflexible polyelectrolyte brush condensates in trivalent counterion solution
Authors: Liu Lei , Hyeon Changbong
Published: July 2018

Interplay between counterion-mediated interaction and stiffness inherent to polymer chain can bring substantial complexity to the morphology and dynamics of polyelectrolyte brush condensates. Trivalent counterions induce collapse of flexible polyelectrolyte brushes, over a certain range of grafting density, into octopus-like surface micelles; however, if individual chains are rigid enough, the ion-mediated local nematic ordering assembles the brush chains into fractal-like dendritic condensates whose relaxation dynamics is significantly slower than that in the surface micelles. Notably, the trivalent ions condensed in the dendritic condensates are highly mobile displaying quasi-one-dimensional diffusion in parallel along the dendritic branches. Our findings in this study are potentially of great significance to understanding the response of cellular organization such as chromosomes and charged polysaccharides on membranes to the change in ionic environment.
The intersystem crossing of a cyclic (alkyl)(amino) carbene gold (i) complex
Authors: Thompson S. , Eng J. , Penfold T. J.
Published: July 2018

The intersystem crossing (ISC) mechanism of a cyclic (alkyl)(amino) carbene gold (I) complex (CMA1) is studied using quantum dynamics. A model spin-vibronic Hamiltonian is developed, which includes 10 excited states and two important nuclear degrees of freedom. The quantum dynamics reveals that ISC from S1 → T1 occurs on the tens of picosecond time scale, consistent with recent experiments. It is driven by motion along the torsional degree of freedom of the carbazole (Cz) ligand, which causes orthogonality between the donor and acceptor groups closing the gap between the initial (S1) and final (T1) states. The role of higher triplet states through spin-vibronic interactions is also discussed. Although previous calculations, evaluated in the Condon approximation, yield large ISC rates, our present dynamical treatment, taking into account the large amplitude torsional motion, increases the calculated rate by an order of magnitude improving the agreement with experiments. The model spin-vibronic Hamiltonian developed can also be used to understand the properties of related linear metal carbene compounds, facilitating molecular design.
Deformation induced frequency shifts of oscillating droplets during molten metal surface tension measurement
Authors: Xiao Xiao , Hyers Robert W. , Wunderlich Rainer K. , Fecht Hans-Jörg , Matson Douglas M.
Published: July 2018

Surface tension is an essential thermophysical property of liquids, and the oscillating droplet method is particularly effective for investigations involving reactive molten alloys. The Rayleigh equation is commonly used to evaluate surface tension from measurements of the damping frequency response of an oscillating droplet with small deformation, but non-linear effects are expected to arise for larger deformation. This work describes an improved method for interpreting frequency analysis and validates previous numerical simulation and theoretical analyses which predict a decrease in observed frequency at moderate deformation amplitude. Experimental results from microgravity tests are used to determine a correction of the Rayleigh equation to eliminate the influence of finite deformation.
Biomimetic Synthesis of Hyperjapones F-I
Authors: Lam Hiu C. , Phan Quang D. , Sumby Christopher J. , George Jonathan H.
Published: July 2018

Hyperjapones F–I are tetracyclic meroterpenoids recently isolated from Hypericum japonicum. All four of these natural products have been synthesised using oxidative, intermolecular hetero-Diels–Alder reactions to couple their common biosynthetic precursor, norflavesone, to the appropriate monoterpene building blocks: sabinene, β-pinene, and α-pinene. The synthesis of enantiomerically pure hyperjapones H and I and comparison of their optical rotations to those of the natural samples indicated that these meroterpenoids are probably biosynthesised as either racemic or scalemic mixtures.
Chemoenzymatic Syntheses of Some Analogues of the Tricarbocyclic Core of the Anti-Bacterial Agent Platencin and the Biological Evaluation of Certain of their N-Arylpropionamide Derivatives
Authors: Muhammad Rehmani N. , Chang Ee Ling , Draffan Alistair G. , Willis Anthony C. , Carr Paul D. , Banwell Martin G.
Published: July 2018

A range of structural variations on the tricarbocyclic core 2 of the anti-bacterial agent platencin 1, including those represented by compounds 14, 15, and 27, have been prepared and certain of these elaborated, through substrate-controlled enolate alkylation reactions, to analogues of the natural product. Preliminary biological evaluation of these analogues revealed that they are only weakly active anti-infective agents.
Georgian civil-military relations: hostage to confrontational politics
Authors: Darchiashvili David , Mangum Ronald Scott
Published: July 2018

The article analyzes civil-military relations and security sector transformation in Georgia since independence, and finds: 1) civilmilitary relations play an important role in internal politics, international relations and standing of the country; 2) civil-military relations fluctuate between: heads of uniformed agencies dominating the political process, or the political elite sacrificing the professionalism of the security and military establishment to power squabbles; 3) Georgia presents a case of military, intelligence and law enforcement agencies becoming hostage to confrontations of the political elite – warring factions continuously undermine the efficiency and integrity of national security for the narrow purpose of taking advantage of each other; 4) If continued, Georgia’s stability remains precarious and existing programmes of intensive cooperation with NATO and the EU will not result in security enhancement, modernization and democratization; 5) Nevertheless, the obligations for democratic security governance, vis-à-vis the international community, will eventually enable Georgia to overcome internal squabbles and undemocratic tendencies.
New lower bounds on the number of intersections of monotone Lagrangian submanifolds
Authors: Keddari Nassima
Published: July 2018

Considering a closed monotone Lagrangian submanifold

L
,

L,

we give, under some hypotheses, a lower bound on the intersection number of

L
L

with its image by a generic Hamiltonian isotopy. First for monotone Lagrangian submanifolds

L
L

which are

K

(
π
,
1
)

\mathbf {K}(\pi ,1)

and, in particular, for monotone Lagrangian submanifolds with negative sectional curvature this bound is 1+

β

1

(
L
)
.

\beta _{1}(L).

In more general cases the lower bound is weaker. We generalise some results previously obtained by L. Buhovsky in [J. Topol. Anal. 2 (2010), pp. 57–75] and P. Biran and O. Cornea in [Geom. Topol. 13 (2009), pp. 2881–2989].
Genotyping Points to Divergent Evolution of ‘CandidatusPhytoplasma asteris’ Strains Causing North American Grapevine Yellows and Strains Causing Aster Yellows
Authors: Davis Robert E. , Dally Ellen L. , Zhao Yan , Wolf Tony K.
Published: July 2018

Grapevine yellows diseases occur in cultivated grapevine (Vitis vinifera L.) on several continents, where the diseases are known by different names depending upon the identities of the causal phytoplasmas. In this study, phytoplasma strains associated with grapevine yellows disease (North American grapevine yellows [NAGY]) in vineyards of Pennsylvania were characterized as belonging to 16S ribosomal RNA (rRNA) gene restriction fragment length polymorphism group 16SrI (aster yellows phytoplasma group), subgroup 16SrI-B (I-B), and variant subgroup I-B*. The strains (NAGYI strains) were subjected to genotyping based on analyses of 16S rRNA and secY genes, and to in silico three-dimensional modeling of the SecY protein. Although the NAGYI strains are closely related to aster yellows (AY) phytoplasma strains and are classified like AY strains in subgroup I-B or in variant subgroup I-B*, the results from genotyping and protein modeling may signal ongoing evolutionary divergence of NAGYI strains from related strains in subgroup 16SrI-B.
Staphylococcus haemolyticus epididymo-orchitis and bacteraemia: a case report
Authors: Pindar Christina , Viau Roberto A.
Published: July 2018

Introduction. Although more often recognized as a culprit in female urinary tract infection, coagulase-negative staphylococci (CoNS) can cause severe genitourinary infections in men. While positive blood cultures with CoNS are usually thought to be contaminants, in the setting of a severe genito-urinary infection they can represent true infection.

Case presentation. We present the case of a 70-year-old male without a central venous catheter or urinary catheter who developed Staphylococcus haemolyticus bloodstream infection secondary to epididymo-orchitis.

Conclusion. This case highlights the importance of prompt recognition of serious CoNS infections, including bacteraemia, in the setting of CoNS genitourinary tract infections.
Characterization of Telomeric Repeat-Containing RNA (TERRA) localization and protein interactions in Primordial Germ Cells of the mouse
Authors: Brieno-Enriquez Miguel Angel , Moak Stefannie L. , Abud-Flores Anyul , Cohen Paula Elaine
Published: July 2018

Telomeres are dynamic nucleoprotein structures capping the physical ends of linear eukaryotic chromosomes. They consist of telomeric DNA repeats (TTAGGG), the shelterin protein complex, and Telomeric Repeat-Containing RNA (TERRA). Proposed TERRA functions are wide-ranging and include telomere maintenance, telomerase inhibition, genomic stability, and alternative lengthening of telomere. However, the role of TERRA in primordial germ cells (PGCs), the embryonic precursors of germ cells, is unknown. Using RNA-fluorescence in situ hybridization (RNA-FISH) we identify TERRA in PGCs soon after these cells have migrated to, and become established in, the developing gonad. RNA-FISH showed the presence of TERRA transcripts in female PGCs at 11.5, 12.5 and 13.5 days post-coitum. In male PGCs, however, TERRA transcripts are observable from 12.5 dpc. Using qPCR we evaluated chromosome-specific TERRA expression, and demonstrated that TERRA levels vary with sex and gestational age, and that transcription of TERRA from specific chromosomes is sexually dimorphic. TERRA interacting proteins were evaluated using Identification of Direct RNA Interacting Proteins (iDRiP) which identified 48 in female and 26 in male protein interactors specifically within nuclear extracts from PGCs at 13.5 dpc. We validated two different proteins the splicing factor, proline- and glutamine-rich (SFPQ) in PGCs and Non-POU domain-containing octamer-binding protein (NONO) in somatic cells. Our results show that, TERRA interacting proteins are determined by sex in both PGCs and somatic cells. Taken together, our data indicate that TERRA expression and interactome during PGC development are regulated in a dynamic fashion that is dependent on gestational age and sex.
Genetic mapping in Diversity Outbred mice identifies aTrpa1variant influencing late phase formalin response
Authors: Recla Jill M. , Bubier Jason A. , Gatti Daniel M. , Ryan Jennifer L. , Long Katie H. , Robledo Raymond F. , Glidden Nicole , Hou Guoqiang , Churchill Gary A. , Maser Richard S. , Zhang Zhong-wei , Young Erin E. , Chesler Elissa J. , Bult Carol J.
Published: July 2018

Identification of genetic variants that influence susceptibility to chronic pain is key to identifying molecular mechanisms and targets for effective and safe therapeutic alternatives to opioids. To identify genes and variants associated with chronic pain, we measured late phase response to formalin injection in 275 male and female Diversity Outbred (DO) mice genotyped for over 70 thousand SNPs. One quantitative trait locus (QTL) reached genome-wide significance on chromosome 1 with a support interval of 3.1 Mb. This locus,Nociq4(nociceptive sensitivity inflammatory QTL 4; MGI:5661503), harbors the well-known pain geneTrpa1(transient receptor potential cation channel, subfamily A, member 1).Trpa1is a cation channel known to play an important role in acute and chronic pain in both humans and mice. Analysis of DO founder strain allele effects revealed a significant effect of the CAST/EiJ allele atTrpa1, with CAST/EiJ carrier mice showing an early, but not late, response to formalin relative to carriers of the seven other inbred founder alleles (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, PWK/PhJ, and WSB/EiJ). We characterized possible functional consequences of sequence variants inTrpa1by assessing channel conductance,Trpa1/Trpv1interactions, and isoform expression. The phenotypic differences observed in CAST/EiJ relative to C57BL/6J carriers were best explained byTrpa1isoform expression differences, implicating a splice junction variant as the causal functional variant. This study demonstrates the utility of advanced, high-precision genetic mapping populations in resolving specific molecular mechanisms of variation in pain sensitivity.