Miracle-dz/UniFAR-FTUs huggingface dataset:
SNAREs, HOPS and regulatory lipids control the dynamics of vacuolar actin during homotypic fusion in S. cerevisiae

Homotypic vacuole fusion requires SNAREs, the Rab Ypt7p, the tethering complex HOPS, regulatory lipids and actin. In Saccharomyces cerevisiae, actin functions at two stages of vacuole fusion. Pre-existing actin filaments are depolymerized to allow docking and assembly of the vertex ring (a microdomain enriched in proteins and lipids that mediate fusion). Actin is then polymerized late in the pathway to aid fusion. Here, we report that the fusion machinery regulates the accumulation of actin at the vertex ring. Using Cy3-labeled yeast actin to track its dynamics, we found that its vertex enrichment was abolished when actin monomers were stabilized by latrunculin-B, independent of the extent of incorporation. By contrast, stabilization of filamentous actin with jasplakinolide markedly augmented actin vertex enrichment. Importantly, agents that inhibit SNAREs, Ypt7p and HOPS inhibited the vertex enrichment of actin, demonstrating that the cytoskeleton and the fusion machinery are interdependently regulated. Actin mobilization was also inhibited by ligating ergosterol and PtdIns(3)P, whereas the ligation or modification of PtdIns(4,5)P2 augmented the vertex enrichment of actin. The proteins and lipids that regulated actin mobilization to the vertex did not affect the total incorporation of Cy3–actin, indicating that actin mobilization and polymerization activities can be dissociated during membrane fusion.
TOR1 and TOR2 Have Distinct Locations in Live Cells

ABSTRACT TOR is a structurally and functionally conserved Ser/Thr kinase found in two multiprotein complexes that regulate many cellular processes to control cell growth. Although extensively studied, the localization of TOR is still ambiguous, possibly because endogenous TOR in live cells has not been examined. Here, we examined the localization of green fluorescent protein (GFP) tagged, endogenous TOR1 and TOR2 in live S. cerevisiae cells. A DNA cassette encoding three copies of green fluorescent protein (3XGFP) was inserted in the TOR1 gene (at codon D330) or the TOR2 gene (at codon N321). The TORs were tagged internally because TOR1 or TOR2 tagged at the N or C terminus was not functional. The TOR1D330-3XGFP strain was not hypersensitive to rapamycin, was not cold sensitive, and was not resistant to manganese toxicity caused by the loss of Pmr1, all indications that TOR1-3XGFP was expressed and functional. TOR2-3XGFP was functional, as TOR2 is an essential gene and TOR2N321-3XGFP haploid cells were viable. Thus, TOR1 and TOR2 retain function after the insertion of 748 amino acids in a variable region of their noncatalytic domain. The localization patterns of TOR1-3XGFP and TOR2-3XGFP were documented by imaging of live cells. TOR1-3XGFP was diffusely cytoplasmic and concentrated near the vacuolar membrane. The TOR2-3XGFP signal was cytoplasmic but predominately in dots at the plasma membrane. Thus, TOR1 and TOR2 have distinct localization patterns, consistent with the regulation of cellular processes as part of two different complexes.
Isoform‐Targeted Regulation of Cardiac Adenylyl Cyclase

Summary: Numerous attempts have been made to develop strategies for regulating the intracellular cyclic AMP signal pharmacologically, with an intention to establish either new medical therapeutic methods or experimental tools. In the past decades, many pharmacological reagents have been identified that regulate this pathway at the level of the receptor, G protein, adenylyl cyclase, cyclic AMP, protein kinase A and phosphodiesterase. Since the cloning of adenylyl cyclase isoforms during the 1990s, investigators including ourselves have tried to find reagents that regulate the activity of this enzyme directly in an isoform‐dependent manner. The ultimate goal of developing such reagents would be to regulate the cyclic AMP signal in an organ‐dependent manner. Ourselves and other workers have reported that such reagents may vary from a simple cation to kinases. In a more recent study, using the results from crystallographic studies and computer‐assisted drug design programs, we have identified subtype‐selective regulators of adenylyl cyclase. Such regulators are mostly based upon forskolin, a diterpene compound obtained from Coleus forskolii, that acts directly on adenylyl cyclase to increase the intracellular levels of cyclic AMP. Similarly, novel reagents have been identified that inhibit a specific adenylyl cyclase isoform (e.g. type 5 adenylyl cyclase). Such reagents would potentially provide a new therapeutic strategy to treat hypertension, for example, as well as methods to selectively stimulate or inhibit this adenylyl cyclase isoform, which may be reminiscent of overexpression or knocking out of the cardiac adenylyl cyclase isoform by the use of a pharmacological method.
Positive and Negative Syndrome Scale as a long-term outcome measurement tool in patients receiving clozapine ODT- A Pilot Study

Objective This pilot, twelve-week, open-label study examined the effect of clozapine orally disintegrating tablet or ODT in patients with schizophrenia and schizoaffective disorder utilizing Positive and Negative Syndrome Scale (PANSS) as a long-term outcome measurement tool. Methods The final study sample consisted of nineteen subjects who were residents a long-term care psychiatric facility in Pomona, California. Subjects were using clozapine ODT (FazaClo®) at the most clinically effective dosage depending on their symptoms and at the discretion of the psychiatrist and psychopharm consultant. PANSS were administered at baseline, week-4, week-8 and week-12. Paired sample t-tests were used to calculate the statistical significance of the mean differences for scores at baseline and week-12. Results Mean differences from baseline indicated significant improvement on total score, as well as positive, negative, cognitive and general psychopathology subscales after twelve weeks of treatment. The greater average reduction in the negative syndrome subscale across the twelve weeks possibly illustrates the ability of clozapine ODT in improving negative symptoms, including cognitive function which is their ability to participate in their personal care and creative expressions in dance, arts, games, poetry to a greater extent their overall, quality of life and living along with the effect on positive symptoms. Conclusion Overall, clozapine proved to affect a broad range of psychopathology including cognitive functions in this schizophrenic sample.
Diasporic Synergies: Conceptualizing African Entrepreneurship Based Upon Trans-Local Networks

ABSTRACT This paper offers a theorization of African diaspora venture creation. We postulate that the motivation for forming trans-local networks – to offer security when socially vulnerable or to pursue business opportunities – mediates the relationship between the habitus of diasporic entrepreneurs and the market-orientation of their venture creation. We extend the theorization by asserting that the compositional diversity and resulting informational redundancy of the network varies depending on the motivation for its formation. This network attributes influence whether the venture is purposed to focus inwardly on the host country market, or outwardly toward contributing to the sustainability of the home country market.
Metabolic changes in deafferented central neurons of an insect, Acheta domesticus. II. Effects on cholinergic binding sites and acetylcholinesterase

Following the finding that cercal deafferentation of developing giant interneurons in the terminal abdominal ganglion (TG) of the cricket Acheta domesticus reduces TG protein metabolism within target interneuron dendrites and somata (Meyer and Edwards, 1982), it is now shown that deafferentation alters the turnover of three macromolecules associated with cholinergic transmission in the cercal sensory-giant interneuron pathway. The labeled specific ligands 3H-quinuclidinyl benzilate and 125I-alpha-bungarotoxin were used to assay populations of putative TG muscarinic and nicotinic cholinergic receptors, respectively, in control and deafferented groups of ganglia. The AChE activity of TG was also determined by assay and histochemical methods. Long-term deafferentation sustained throughout postembryonic development markedly reduces the densities of both muscarinic and nicotinic binding sites in the TG; short-term deafferentation of adult TG also leads to characteristic alterations in the properties of all three cholinergic markers within several days. Rapid changes seen in adults thus correlate with ultrastructural data demonstrating loss of afferent terminals within hours of sensory appendage removal. We propose that peripheral innervation-dependent regulatory mechanisms operate in both the developing and adult insect nervous system. Such mechanisms may influence transsynaptically the synthesis and turnover of specific macromolecules, some of which may reside on the cell surface of insect central neurons that are part of the cercal sensory- giant interneuron system.
Design of low power, wider tuning range CMOS voltage control oscillator for ultra wideband applications

This paper presents a diode varactor and MOS varactor voltage control oscillators using 0. 25μm CMOS technology, proposed for Ultra Wideband application. The VCOs are designed for 3-5GHz UWB Impulse Radio, The VCO's has -107.6 dBc/Hz and -108.8 dBc/Hz phase noise at 1 MHz offset frequency. The diode varactor VCO has a tuning range of 300 MHz and the MOS varactor VCO has a wider tuning range of 610 MHz which is very difficult to achieve. Their power consumption at the maximum oscillation frequency is 2.26 mW from a 1.2 V voltage source, with -9 dBm output power which is very low compared to the conventional VCO in similar process design.
Meta-Key: A Secure Data-Sharing Protocol Under Blockchain-Based Decentralized Storage Architecture

In this letter we propose Meta-key, a data-sharing mechanism that enables users share their encrypted data under a blockchain-based decentralized storage architecture. All the data-encryption keys are encrypted by the owner’s public key and put onto the blockchain for safe and secure storage and easy key-management. Encrypted data are stored in dedicated storage nodes and proxy re-encryption mechanism is used to ensure secure data-sharing in the untrusted environment. Security analysis of our model shows that the proxy re-encryption adopted in our system is naturally free from collusion-attack due to the specific architecture of Meta-key.
Role of NO in flow-induced remodeling of the rabbit common carotid artery.

Flow-induced changes in vessel caliber tend to restore baseline wall shear stress (WSS) and have been reported to be endothelium-dependent. To investigate the role of endothelium-derived nitric oxide (NO) in the adaptive increase in artery diameter in response to a chronic increase in blood flow, an arteriovenous fistula was constructed between the left common carotid artery (CCA) and the external jugular vein in 22 New Zealand White rabbits, and NO synthesis was inhibited in 14 animals by long-term administration of NG-nitro-L-arginine-methyl ester (L-NAME) in drinking water given for 4 weeks. The remaining 8 animals served as controls. Mean arterial blood pressure was not significantly altered by L-NAME treatment (91 +/- 2 in control versus 98 +/- 3 mm Hg in L-NAME-treated rabbits). Blood flow significantly increased in the left CCA in both groups but was lower in L-NAME-treated than control animals (106.1 +/- 10.7 versus 196.2 +/- 32.3 mL/min, P < .003). The diameter of the flow-loaded left CCA also increased significantly in both groups compared with the right CCA (2.15 +/- 0.12 and 2.54 +/- 0.1 mm, respectively, P < .02), but the increase was less in the L-NAME-treated than the control group (3.24 +/- 0.09 and 4.64 +/- 0.17 mm, respectively, P < .0001). The diameter of the anastomosed veins was also increased but to a much lesser degree in L-NAME-treated animals than in controls (4.14 +/- 0.29 versus 7.94 +/- 0.51 mm, P < .0001). As a result of artery enlargement, WSS was normalized in the flow-loaded left CCA of the control group (8.87 +/- 0.77 dynes/cm2) regardless of blood flow values. In L-NAME-treated animals, however, WSS was only partially regulated, the mean value being significantly increased (18.7 +/- 2.2 dynes/cm2, P < .006). Moreover, a highly significant positive correlation between WSS and blood flow was obtained in L-NAME-treated animals (r = .84, P < .0001). We also found remodeling of the artery wall, with a larger increase in the medial cross-sectional area associated with an increased number of smooth muscle cells, in the control group compared with the L-NAME-treated group (0.75 +/- 0.09 versus 0.49 +/- 0.04 mm2 and 4504 +/- 722 versus 2717 +/- 282 cells/mm2, P < .03). We conclude that NO plays a role in the increase of vessel caliber in response to chronic increase in blood flow. As yet unidentified additional metabolic processes appear to be necessary for a complete regulatory response.
On Variations of Perfect Equilibria

In this paper, we examine relations among various refinements of a perfect equilibrium. First, we compare two refinements of a perfect equilibrium, a strictly perfect equilibrium (SPE) and a truly perfect equilibrium (TPE). We show that true perfectness implies strict perfectness and even strict properness. We also introduce the concept of a restrictive perfect equilibrium allowing only some or all sequences of totally mixed strategies satisfying a certain property. A proper equilibrium is an example of a restrictive perfect equilibrium. Then, true perfectness imposing the most severe robustness against perturbations implies any restrictive perfectness. This proves that every TPE is proper.
Improving quality of care in people with Type 2 diabetes through the Associazione Medici Diabetologi‐annals initiative: a long‐term cost‐effectiveness analysis

The Associazione Medici Diabetologi‐annals initiative is a physician‐led quality‐of‐care improvement scheme that has been shown to improve HbA1c concentration, blood pressure, lipid profiles and BMI in enrolled people with Type 2 diabetes. The present analysis investigated the long‐term cost‐effectiveness of enrolling people with Type 2 diabetes in the Associazione Medici Diabetologi‐annals initiative compared with conventional management.
Court Leadership, Agenda Transformation, and Judicial Dissent: A European Case of a “Mysterious Demise of Consensual Norms”

The previous literature debates whether rising rates of dissent are best explained by changes in court leadership and the composition of justices or by greater judicial discretion and changes in agenda. This article examines the influential hypotheses derived from the literature in the relevant and testable European case of the Supreme Court of Norway. It shows that the rising rate of dissent in the Court in the 1990s was mainly catalyzed by fundamental changes to the Court’s discretionary power and by its newfound agenda to work more actively with the development of the law and the protection of human rights.
Identification and Characterization of Heme-interacting Proteins in the Malaria Parasite, Plasmodium falciparum*

The degradation of hemoglobin by the malaria parasite, Plasmodium falciparum, produces free ferriprotoporphyrin IX (FP) as a toxic by-product. In the presence of FP-binding drugs such as chloroquine, FP detoxification is inhibited, and the build-up of free FP is thought to be a key mechanism in parasite killing. In an effort to identify parasite proteins that might interact preferentially with FP, we have used a mass spectrometry approach. Proteins that bind to FP immobilized on agarose include P. falciparum glyceraldehyde-3-phosphate dehydrogenase (PfGAPDH), P. falciparum glutathione reductase (PfGR), and P. falciparum protein disulfide isomerase. To examine the potential consequences of FP binding, we have examined the ability of FP to inhibit the activities of GAPDH and GR from P. falciparum and other sources. FP inhibits the enzymic activity of PfGAPDH with a Ki value of 0.2 μm, whereas red blood cell GAPDH is much less sensitive. By contrast, PfGR is more resistant to FP inhibition (Ki > 25 μm) than its human counterpart. We also examined the ability of FP to inhibit the activities of the additional antioxidant enzymes, P. falciparum thioredoxin reductase, which exhibits a Ki value of 1 μm, and P. falciparum glutaredoxin, which shows more moderate sensitivity to FP. The exquisite sensitivity of PfGAPDH to FP may indicate that the glycolytic pathway of the parasite is particularly susceptible to modulation by FP stress. Inhibition of this pathway may drive flux through the pentose phosphate pathway ensuring sufficient production of reducing equivalents to counteract the oxidative stress induced by FP build-up.
Systematic in vitro and in vivo characterization of Leukemia‐inhibiting factor‐ and Fibroblast growth factor‐derived porcine induced pluripotent stem cells

Derivation and stable maintenance of porcine induced pluripotent stem cells (piPSCs) is challenging. We herein systematically analyzed two piPSC lines, derived by lentiviral transduction and cultured under either leukemia inhibitory factor (LIF) or fibroblast growth factor (FGF) conditions, to shed more light on the underlying biological mechanisms of porcine pluripotency. LIF‐derived piPSCs were more successful than their FGF‐derived counterparts in the generation of in vitro chimeras and in teratoma formation. When LIF piPSCs chimeras were transferred into surrogate sows and allowed to develop, only their prescence within the embryonic membranes could be detected. Whole‐transcriptome analysis of the piPSCs and porcine neonatal fibroblasts showed that they clustered together, but apart from the two pluripotent cell populations of early porcine embryos, indicating incomplete reprogramming. Indeed, bioinformatic analysis of the pluripotency‐related gene network of the LIF‐ versus FGF‐derived piPSCs revealed that ZFP42 (REX1) expression was absent in both piPSC‐like cells, whereas it was expressed in the porcine inner cell mass at Day 7/8. A second striking difference was the expression of ATOH1 in piPSC‐like cells, which was absent in the inner cell mass. Moreover, our gene expression analyses plus correlation analyses of known pluripotency genes identified unique relationships between pluripotency genes in the inner cell mass, which are to some extent, in the piPSC‐like cells. This deficiency in downstream gene activation and divergent gene expression may be underlie the inability to derive germ line‐transmitting piPSCs, and provides unique insight into which genes are necessary to achieve fully reprogrammed piPSCs. 84: 229–245, 2017. © 2016 Wiley Periodicals, Inc.
Chapter 7 Correlation of thromboelastometry with conventional hemostatic tests in critically ill patients with a coagulopathy treated with fresh frozen plasma

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REACTIVITY OF NATURAL AND SYNTHETIC MAGNETITES : II . ADSORPTION OF Pb ( II ) AND Zn ( II )

Two synthetic and three natural magnetite samples that were obtained from an iron ore deposit located in Central-Western Mexico, were used to investigate the magnetite surface reactivity of different particle sizes towards aqueous Pb(II) and Zn(II). From these, the synthetic samples < 50 nm [specific surface area (SSA)] = 39.3 m /g), < 5 mm (SSA = 7.3 m2/ g), and natural samples 948-fine (SSA = 7.6 m /g), 948 (SSA = 3.0 m /g) and 996 (SSA = 1.4 m /g), successfully removed Pb(II) from aqueous solutions at the investigated pH value of 5.8, but only the three first, finer magnetites removed significant aqueous Zn(II) at pH 7.0. The adsorption kinetics data were fitted using pseudo-second order and intraparticle models. The Pb(II) adsorption capacities were 140.1, 33.3, 65.4, 69.8 and 17.0 mmol/g, for samples < 50 nm, < 5 mm, 948-fine, 948 and 996, respectively, while for Zn(II) they were 159.2, 38.8 and 28.2 mmol/ g, for the first three previous samples, respectively. These adsorption capacities suggest that magnetite may play an important role as adsorbents of cationic contaminants in the environment, or that it may be used as efficient remediating agent, but it’s limited to particle sizes with specific surface areas above 3 m /g.
From LIDL − to Timed Automata ∗

LIDL is a decidable fragment of Interval Duration Logic with Located Constraints, an expressive subset of dense-time Duration Calculus. It has been claimed that, for any LIDL formula D, a timed automaton can be constructed which accepts the models of D. However, the proposed construction is incomplete and has not been proved effective. In this paper, we prove the effective construction of equivalent timed automata from LIDL formulae.
The role of chemokines and extracellular matrix components in the migration of T lymphocytes into three‐dimensional substrata

The role of chemokines and their interactions with extracellular matrix components (ECM) or the capacity of T cells to migrate into and accumulate within three‐dimensional (3D) collagen type 1 substrata was studied. We examined the influence of chemokines and fibronectin on the infiltration properties of non‐infiltrative (do not migrate into 3D substrata) and spontaneously infiltrative (migrate into 3D substrata) T‐cell lines. Infiltrative and non‐infiltrative T‐acute lymphocytic leukaemic cell lines exhibited no consistent differences with respect to the expression of various chemokine receptors or β1‐integrins. Chemokines presented inside the collagen increased the depth of migration of infiltrative T‐cell lines, but did not render non‐infiltrative T‐cell lines infiltrative, although they augmented the attachment of non‐infiltrative T‐cell lines to the upper surface of the collagen. The presence of fibronectin inside the collagen did not render non‐infiltrative T‐cell lines infiltrative, but markedly augmented the migration of ‘infiltrative’ T‐cell lines into collagen. Both infiltrative and non‐infiltrative T‐cell lines showed migratory responses to chemokines in Boyden assays (migration detected on 2D substrata). These results indicate that the process of T‐cell infiltration/migration into 3D substrata depends on a tissue penetration mechanism distinguishable from migration on 2D substrata and that the basic capacity of T cells to infiltrate is independent of chemokines and ECM components applied as attractants.