Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancement of Endogenous Plasminogen Activator-induced Thrombolysis by Argatroban and APC and Its Control by TAFI, Measured in An Arterial Thrombolysis Model In Vivo Using Rat Mesenteric Arterioles

Summary Recent in vitro studies have demonstrated that thrombin inhibits fibrinolysis through thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B). We have recently shown that endogenous fibrinolysis in vivo is enhanced by activated protein C (APC) and the selective thrombin inhibitor, argatroban. The aim of the present study was to examine the role of TAFI in these fibrinolytic mechanisms in vivo using purified porcine pancreatic carboxypeptidase B (PPCPB) and a specific TAFIa inhibitor, potato tuber carboxypeptidase B inhibitor (PTCI) in a newly established arterial thrombolysis model. Non-occlusive, mural, platelet-rich thrombi were formed by helium-neon laser irradiation in rat mesenteric arterioles and thrombus size was measured by computerised image analysis. We confirmed that endogenous thrombolysis was enhanced by argatroban (2.0 mg/4 ml/kg/h) or APC (1.62 mg/2.31 ml/kg). PTCI (5.0 mg/2 ml/kg) also accelerated endogenous thrombolysis. PPCPB (3.5 mg/2 ml/kg) inhibited thrombolysis in the absence and presence of argatroban or APC. PTCI tended to further promote APC-induced thrombolysis but the differences did not reach statistical significance. The present findings were in keeping with the results of earlier studies and demonstrated that arterial, platelet-rich thrombi in vivo are degraded by naturally generated plasminogen activators. TAFI may play a significant role in the control of these mechanisms.
, INESC-ID and Instituto Superior Técnico , Universidade de Lisboa ATP-Group , Lisboa , Portugal 2780-990 Porto Salvo , Portugal fernando

Explaining cooperation between individuals is a fundamental scientific endeavour. Similarly, devising mechanisms that encourage autonomous agents to cooperate with each other is a central topic in multiagent systems. Indirect reciprocity (IR) emerged as the most elaborated mechanism of cooperation discovered, involving the moral assessment of actions, the spreading of reputations and agents that care about the social image of others. In this context, the way actions are judged and reputations are attributed depends on the socially adopted norms that define what actions (and under which contexts) are reckoned as Good or Bad. It remains an open question which norms are able to maintain high levels of cooperation in a multiagent system, composed by a finite number of agents that may often behave unpredictably. We employ computational and mathematical methods (inspired in evolutionary game theory) to explore which social norms are able to promote cooperation in a multiagent system. We seek to extend the state of art by introducing new models of IR that consider a finite number of agents that are given the opportunity to randomly explore the strategy space and that may commit errors of different nature.
Low‐Level Laser Therapy and Sodium Diclofenac in Acute Inflammatory Response Induced by Skeletal Muscle Trauma: Effects in Muscle Morphology and mRNA Gene Expression of Inflammatory Markers

Pharmacological therapy is widely used in the treatment of muscle injuries. On the other hand, low‐level laser therapy (LLLT) arises as a promising nonpharmacological treatment. The aim of this study was to analyze the effects of sodium diclofenac (topical application) and LLLT on morphological aspects and gene expression of biochemical inflammatory markers. We performed a single trauma in tibialis anterior muscle of rats. After 1 h, animals were treated with sodium diclofenac (11.6 mg g‐1 of solution) or LLLT (810 nm; continuous mode; 100 mW; 3.57 W cm−2; 1, 3 or 9 J; 10, 30 or 90 s). Histological analysis and quantification of gene expression (real‐time polymerase chain reaction—RT‐PCR) of cyclooxygenase 1 and 2 (COX‐1 and COX‐2) and tumor necrosis factor‐alpha (TNF‐α) were performed at 6, 12 and 24 h after trauma. LLLT with all doses improved morphological aspects of muscle tissue, showing better results than injury and diclofenac groups. All LLLT doses also decreased (P < 0.05) COX‐2 compared to injury group at all time points, and to diclofenac group at 24 h after trauma. In addition, LLLT decreased (P < 0.05) TNF‐α compared both to injury and diclofenac groups at all time points. LLLT mainly with dose of 9 J is better than topical application of diclofenac in acute inflammation after muscle trauma.
Acceptance for preventive genetic testing and prophylactic surgery in women with a family history of breast and gynaecological cancers

The fear of family members of patients with breast or gynaecologic cancer of developing a similar disease is often high. We investigated the acceptance for genetic testing of untested women with a positive family history and their attitude for prophylactic surgery. A total of 659 women with a familial history of breast or gynaecologic cancer were asked to answer a questionnaire regarding their interest in genetic testing for breast cancer as well as for gynaecologic carcinoma and their interest in prophylactic surgery. Genetic testing is seen to be accepted by the majority of participants: 85.0 and 77.8% chose a genetic test for breast and gynaecologic cancer, respectively. Prophylactic surgery was much less chosen; prophylactic mastectomy as well as prophylactic hysterectomy or bilateral prophylactic oophorectomy was an option only for a minority of women. Genetic testing for risk assessment of healthy women with a positive family history was observed to be accepted by a majority of participants. Prophylactic surgery was an option only for a minority and was not acceptable for most of the women.
Estimation of Circulating Immune Complexes in patients with Oral Leukoplakia and Oral Submucous Fibrosis: A Case Control Study.

PURPOSE OF THE STUDY The present study was conducted to estimate the serum levels of Circulating Immune Complexes in patients with Oral Leukoplakia ,Oral sub mucous fibrosis and normal subjects and correlate these values with the clinical grades of the diseases. MATERIALS AND METHODS The study consisted of 25 Oral Leukoplakia patients, 25 Oral sub mucous fibrosis patients and 25 Normal subjects. RESULTS The mean serum levels of CIC showed a gradual increase from normal subjects to Oral Leukoplakia patients and showed a high values in Oral sub mucous fibrosis patients. The mean serum levels of CIC also showed a gradual increase from clinical grade I to grade IV of Oral sub mucous fibrosis. CONCLUSION Serum levels of CIC may be taken as a prognostic marker for disease progression of patients with Oral Leukoplakia and Oral sub mucous fibrosis.
Reduced Efficacy of the KCC2 Cotransporter Promotes Epileptic Oscillations in a Subiculum Network Model

Pharmacoresistant epilepsy is a chronic neurological condition in which a basal brain hyperexcitability results in paroxysmal hypersynchronous neuronal discharges. Human temporal lobe epilepsy has been associated with dysfunction or loss of the potassium-chloride cotransporter KCC2 in a subset of pyramidal cells in the subiculum, a key structure generating epileptic activities. KCC2 regulates intraneuronal chloride and extracellular potassium levels by extruding both ions. Absence of effective KCC2 may alter the dynamics of chloride and potassium levels during repeated activation of GABAergic synapses due to interneuron activity. In turn, such GABAergic stress may itself affect Cl− regulation. Such changes in ionic homeostasis may switch GABAergic signaling from inhibitory to excitatory in affected pyramidal cells and also increase neuronal excitability. Possibly these changes contribute to periodic bursting in pyramidal cells, an essential component in the onset of ictal epileptic events. We tested this hypothesis with a computational model of a subicular network with realistic connectivity. The pyramidal cell model explicitly incorporated the cotransporter KCC2 and its effects on the internal/external chloride and potassium levels. Our network model suggested the loss of KCC2 in a critical number of pyramidal cells increased external potassium and intracellular chloride concentrations leading to seizure-like field potential oscillations. These oscillations included transient discharges leading to ictal-like field events with frequency spectra as in vitro. Restoration of KCC2 function suppressed seizure activity and thus may present a useful therapeutic option. These simulations therefore suggest that reduced KCC2 cotransporter activity alone may underlie the generation of ictal discharges. SIGNIFICANCE STATEMENT Ion regulation in the brain is a major determinant of neural excitability. Intracellular chloride in neurons, a partial determinant of the resting potential and the inhibitory reversal potentials, is regulated together with extracellular potassium via kation chloride cotransporters. During temporal lobe epilepsy, the homeostatic regulation of intracellular chloride is impaired in pyramidal cells, yet how this dysregulation may lead to seizures has not been explored. Using a realistic neural network model describing ion mechanisms, we show that chloride homeostasis pathology provokes seizure activity analogous to recordings from epileptogenic brain tissue. We show that there is a critical percentage of pathological cells required for seizure initiation. Our model predicts that restoration of the chloride homeostasis in pyramidal cells could be a viable antiepileptic strategy.
“Dormant” secondary metal-alkyl complexes are not omnipresent

This theoretical study was inspired by the perpetual debate over the so-called “dormancy” of the active sites in propylene polymerization, i.e., a drop in their activity after a regioerror (2,1-insertion), which was reported to occur in many (although not all) catalytic systems. To explore the range of possible situations, we have selected two homogeneous systems of fundamentally different structure: an octahedral system of C2 symmetry with a tetradentate ONNO ligand and a bridged indenyl catalyst. This choice was not accidental; it is in these two systems where the experimentalists cannot reach a consensus about dormancy. Our density-functional theory calculations explain why in certain catalytic systems both primary and secondary alkyl complexes can be equally reactive toward propylene polymerization, despite the intuitive concept of dormancy. To understand such a behavior, it was imperative to build an extensive model, including the counteranion and solvent effects. The discussion is also supplemented by our latest calculations on the classical second-generation Ziegler–Natta system.
Parallel and Distributed Computing

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Therapeutic Antibodies: What Have We Learnt from Targeting CD20 and Where Are We Going?

Therapeutic monoclonal antibodies (mAbs) have become one of the fastest growing classes of drugs in recent years and are approved for the treatment of a wide range of indications, from cancer to autoimmune disease. Perhaps the best studied target is the pan B-cell marker CD20. Indeed, the first mAb to receive approval by the Food and Drug Administration for use in cancer treatment was the CD20-targeting mAb rituximab (Rituxan®). Since its approval for relapsed/refractory non-Hodgkin’s lymphoma in 1997, rituximab has been licensed for use in the treatment of numerous other B-cell malignancies, as well as autoimmune conditions, including rheumatoid arthritis. Despite having a significant impact on the treatment of these patients, the exact mechanisms of action of rituximab remain incompletely understood. Nevertheless, numerous second- and third-generation anti-CD20 mAbs have since been developed using various strategies to enhance specific effector functions thought to be key for efficacy. A plethora of knowledge has been gained during the development and testing of these mAbs, and this knowledge can now be applied to the design of novel mAbs directed to targets beyond CD20. As we enter the “post-rituximab” era, this review will focus on the lessons learned thus far through investigation of anti-CD20 mAb. Also discussed are current and future developments relating to enhanced effector function, such as the ability to form multimers on the target cell surface. These strategies have potential applications not only in oncology but also in the improved treatment of autoimmune disorders and infectious diseases. Finally, potential approaches to overcoming mechanisms of resistance to anti-CD20 therapy are discussed, chiefly involving the combination of anti-CD20 mAbs with various other agents to resensitize patients to treatment.
Implementable Mechanisms to Coordinate Horizontal Alliances

Unprecedented changes in the economics of interaction, mainly as a result of advances in information and telecommunication technologies such as the Internet, are causing a shift toward more networked forms of organizations such as horizontal alliances-that is, alliances among firms in similar businesses that have positive externalities between them. Because the success of such horizontal alliances depends crucially on aligning individual alliance-member incentives with those of the alliance as a whole, it is important to find coordination mechanisms that achieve this alignment and are simple-to-implement. In this paper, we examine two simple coordination mechanisms for a horizontal alliance characterized by the following features: i firms in the alliance can exert effort only in their "local" markets to increase customer demand for the alliance; ii customers are mobile and a customer living in a given alliance member's local area may have a need to buy from some other alliance member; and iii the coordination rules followed by the alliance determine which firms from a large pool of potential member-firms join the alliance, and how much effort each firm joining the alliance exerts in its local market. In this horizontal alliance setup, we consider the use of two coordination mechanisms: i a linear transfer of fees between members if demand from one member's local customer is served by another member, and ii ownership of an equal share of the alliance profits generated from a royalty on each member's sales. We derive conditions on the distribution of demand externalities among alliance members to determine when each coordination mechanism should be used separately, and when the mechanisms should be used together.
A novel class of transcripts expressed with late kinetics in the absence of ICP4 spans the junction between the long and short segments of the herpes simplex virus type 1 genome

A novel family of transcripts that span the junction between the long and short segments of the herpes simplex virus type 1 genome has been identified. These transcripts, designated L/S junction-spanning transcripts (L/STs), are synthesized in abundance in a variety of cells infected with mutant viruses defective in the gene for ICP4, the major transcriptional regulatory protein of the virus. Transcription of abundant 2.3- and 8.5-kb series of L/STs was shown to initiate within the same sequences as less abundant 4.2-, 7.3-, and > 9.5-kb transcripts by Northern (RNA) blot analysis. S1 nuclease analysis revealed a single 5' terminus 28 bp downstream of a TATA box and 6 bp downstream of a consensus ICP4 binding site. The location of the transcriptional start site indicates that the promoter of the L/STs likely corresponds to the bidirectional promoter described by Bohenzky et al. (R. A. Bohenzky, A. G. Papavassiliou, I. H. Gelman, and S. Silverstein, J. Virol. 67:632-642, 1993). The L/STs accumulate with late kinetics in ICP4 mutant-infected cells and are polyadenylated. Mutant viruses encoding forms of ICP4 unable to bind the consensus site, ATCGTC, exhibited abundant expression of the L/STs, whereas mutants encoding forms of ICP4 able to bind this site expressed no detectable L/STs, suggesting that ICP4 plays a critical role in repressing L/ST expression. Their synthesis in ICP4 mutant-infected cells is inhibited by the protein synthesis inhibitor cycloheximide, indicating that they are induced either by an immediate-early viral protein other than ICP4 or by a virus-induced cellular protein. Preliminary evidence indicates that the L/STs are not present in latently infected ganglia. The abundant expression of the L/STs with late kinetics only in the absence of functional ICP4 and the sensitivity of their synthesis to cycloheximide indicate that they are not members of any of the recognized kinetic classes of herpes simplex virus type 1 transcripts but constitute a new class of viral transcript.
The effects of level of expression of a jellyfish Shaker potassium channel: a positive potassium feedback mechanism

1 When jellyfish Shaker potassium channels (jShak2) are heterologously expressed in Xenopus oocytes at different levels they demonstrate density‐dependent changes in electrical and kinetic properties of macroscopic currents. 2 The activation and inactivation properties of jShak2 channels depend on the extracellular potassium concentration. In this study we present experimental data which show that expression‐dependent changes in kinetic and electrical properties of jShak2 macroscopic currents can be explained by the positive feedback effect of dynamic accumulation of K+ in the perimembranal space.
Changes in constituents and ultrastructure of hyphal compartments during autolysis of glucose-starved Penicillium chrysogenum.

SUMMARY: The dry weight of Penicillium chrysogenum starved of an energy source decreased exponentially. The protein, RNA, DNA and endogenous respiration decreased rapidly during the first few hours of starvation and reached about 25% of their original values after 5 days starvation. The carbohydrate content of the mould only decreased after the first 2 days of starvation. About 60% of the carbon lost during autolysis was oxidized to carbon dioxide. Lysis of organelles in individual hyphal compartments occurred synchronously and did not seem to involve autophagy. Autolysis of separate compartments in the same hyphae was not synchronized. Ribosomes were rapidly degraded but membranes were particularly resistant to breakdown. Intra-hyphal hyphae were observed. In the final stages of autolysis the culture consisted largely of empty hyphal walls. A proportion of cytologically normal hyphal compartments were present at all stages, suggesting that maintenance and/or cryptic growth of some hyphae (or compartments) occurred at the expense of others.
Pulmonary Function Parameters in High-resolution Computed Tomography Phenotypes of Chronic Obstructive Pulmonary Disease

Background:Heterogeneity of clinical presentation of chronic obstructive pulmonary disease (COPD) attributes to different pathological basis. High-resolution computed tomography (HRCT) phenotypes of COPD may reflex the pathological basis of COPD indirectly by evaluating the small airway inflammation and emphysema. How the pulmonary function related with different HRCT phenotypes has not been well known. The aim was to explore the features of pulmonary function parameters in the 3 phenotypes. Methods:Sixty-three stable COPD patients were allocated in 3 groups based on HRCT findings: phenotype A (absence of emphysema, with minimal evidence of emphysema with or without bronchial wall thickening [BWT]), phenotype E (emphysema without BWT) and phenotype M (emphysema with BWT). The pulmonary function testing was also analyzed. Results:The values of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC%), FEV1% and maximum expiratory flows (MEF)50% were the highest in phenotype A (P < 0.05), so was residual volume (RV)/total lung capacity (TLC%) in phenotype E (P < 0.05). Those with MEF50/MEF25 ratio >4.0 were more prevalence in phenotype A than in E and M (odds ratio = 2.214; P < 0.05). The occurrences of RV/TLC% >40% were higher in phenotype E than in A and M (odds ratio = 3.906; P < 0.05). Receiver operating characteristic analysis showed that the cutoff value of MEF50/MEF25 ratio for identifying phenotype A was 2.5, with sensitivity 66.7% and specificity 92.9%. The cutoff value of RV/TLC% for identifying phenotype E was 57.4%, with sensitivity 75.0% and specificity 79.1%. Conclusions:The different features of pulmonary function parameters were found in various HRCT phenotypes; MEF50/MEF25 ratio could imply phenotype A, whereas RV/TLC% may be the indicator of phenotype E.
A practical guide to giant vesicles. Probing the membrane nanoregime via optical microscopy

Research on giant vesicles is becoming increasingly popular. Giant vesicles provide model biomembrane systems for systematic measurements of mechanical and rheological properties of bilayers as a function of membrane composition and temperature, as well as hydrodynamic interactions. Membrane response to external factors (for example electric fields, ions and amphiphilic molecules) can be directly visualized under the microscope. In this paper we review our current understanding of lipid bilayers as obtained from studies on giant unilamellar vesicles. Because research on giant vesicles increasingly attracts the interest of scientists from various backgrounds, we also try to provide a concise introduction for newcomers in the field. Finally, we summarize some recent developments on curvature effects induced by polymers, domain formation in membranes and shape transitions induced by electric fields.
[Studies on the antiasthmatic action of ligustilide of dang-gui, Angelica sinensis (Oliv.) Diels].

A component, ligustilide, was isolated from the essential oil of Danggui (Angelica sinensis Oliv. Diels) cultivated in Min Xian County, Gansu Province, and accounted for 0.5% of the weight of the original herb. It was shown to have remarkable antiasthmatie effect and spasmolytie action by a series of experiments. When injected into guinea pigs intraperitoneally at a dose of 0.14ml/kg, the asthmatic reaction induced by acetylcholine and histamine was immediately impeded with a potency approximately equal to the action of aminophylline (50mg/kg). Lung overflow experiment showed that an intravenous injection of ligustilide (0.08 ml/kg) into the anesthetic guinea pig caused complete or partial block of the reaction of histamine at the dose of 2～10μg/kg. Ligustilide also exhibited antispasmodic effect on isolated trachea strip of the guinea pig contracted by acetylcholine, histamine and barium chloride, and a relaxation effect on trachea strip under normal tension. Addition of propranolol did not affect those actions. The contents of cAMP and cGMP in the pulmonary and intestinal tissues of the guinea pig were not altered by treatment with ligustilide.