Miracle-dz/UniFAR-FTUs huggingface dataset:
A Transient N-terminal Interaction of SNAP-25 and Syntaxin Nucleates SNARE Assembly*

The SNARE proteins syntaxin, SNAP-25, and synaptobrevin play a central role during Ca2+-dependent exocytosis at the nerve terminal. Whereas syntaxin and SNAP-25 are located in the plasma membrane, synaptobrevin resides in the membrane of synaptic vesicles. It is thought that gradual assembly of these proteins into a membrane-bridging ternary SNARE complex ultimately leads to membrane fusion. According to this model, syntaxin and SNAP-25 constitute an acceptor complex for synaptobrevin. In vitro, however, syntaxin and SNAP-25 form a stable complex that contains two syntaxin molecules, one of which is occupying and possibly obstructing the binding site of synaptobrevin. To elucidate the assembly pathway of the synaptic SNAREs, we have now applied a combination of fluorescence and CD spectroscopy. We found that SNARE assembly begins with the slow and rate-limiting interaction of syntaxin and SNAP-25. Their interaction was prevented by N-terminal but not by C-terminal truncations, suggesting that for productive assembly all three participating helices must come together simultaneously. This suggests a complicated nucleation process that might be the reason for the observed slow assembly rate. N-terminal truncations of SNAP-25 and syntaxin also prevented the formation of the ternary complex, whereas neither N- nor C-terminal shortened synaptobrevin helices lost their ability to interact. This suggests that binding of synaptobrevin occurs after the establishment of the syntaxin-SNAP-25 interaction. Moreover, binding of synaptobrevin was inhibited by an excess of syntaxin, suggesting that a 1:1 interaction of syntaxin and SNAP-25 serves as the on-pathway SNARE assembly intermediate.
Smoking cessation normalizes coronary endothelial vasomotor response assessed with 15O-water and PET in healthy young smokers.

UNLABELLED Cigarette smoking is one of the risk factors of cardiovascular diseases and is related to abnormal peripheral and coronary vascular vasomotion. Coronary vascular endothelial dysfunction is caused by chronic smoking in smokers without epicardial coronary artery stenosis. The coronary endothelial vasomotion abnormality is restored by interventions such as l-arginine or vitamin C infusion. However, to our knowledge, the effect of smoking cessation on coronary vasomotor response has not been elucidated. Therefore, the aim of this study was to assess the effect of smoking cessation on coronary vasomotor response by quantitative myocardial blood flow (MBF) measurement using (15)O-water and PET. METHODS Fifteen young smokers (Brinkman index > 100; mean age +/- SD, 26 +/- 4 y) with no evidence of heart disease or cardiovascular risk factors, except for smoking, and age-matched nonsmokers (n = 12) were enrolled in this study. MBF was measured at rest, during the cold pressor test (CPT), before and at 1 and 6 mo after smoking cessation. In addition, MBF measurement during adenosine triphosphate (ATP) infusion was performed before and at 6 mo after smoking cessation. In nonsmokers, MBF was measured at rest, during ATP infusion, and during the CPT. RESULTS MBF at rest and during ATP infusion did not differ between smokers and nonsmokers (0.73 +/- 0.12 vs. 0.80 +/- 0.15 mL/g/min and 3.15 +/- 1.43 vs. 3.69 +/- 0.76 mL/g/min, respectively; P = not significant). In contrast, MBF during the CPT in smokers was lower than that in nonsmokers (0.90 +/- 0.19 vs. 1.12 +/- 0.28 mL/g/min; P < 0.05). There was no significant difference in MBF either at rest or during ATP infusion between before and after smoking cessation, but MBF during the CPT increased at 1 mo in comparison with before cessation of smoking (0.90 +/- 0.19 vs. 1.02 +/- 0.22 mL/g/min; P < 0.01). An improvement of MBF response to the CPT was preserved at 6 mo after smoking cessation. CONCLUSION Coronary vasomotor abnormality assessed by MBF response to the CPT was improved at 1 mo after smoking cessation. These findings indicate that coronary endothelial dysfunction may be reversible within 1 mo after smoking cessation in healthy young smokers.
Exemplarity and Narrativity in the Common Law Tradition: Exploring Williams v Roffey

This paper argues that for the purposes of analysing legal reasoning, exemplarity is profitably understood as a complex concept with the following dimensions: first, typicality; second, a-typicality; and third, modelling for the future. These dimensions can also be usefully thought of in temporal terms: typicality is backward-looking, atypicality is present-regarding and modelling is future-oriented. Any instance of exemplarity delicately balances these dimensions. This is equally so for any legal reasoning process, which must balance respect for the particularity of the present case, with respect for relevant past decisions and respect for the way in which the case might be used by future courts and those citizens most likely affected by the decision. The paper argues further that a useful device for balancing these dimensions is narrative. However, when we combine exemplarity and narrativity, we must be careful not to fall into the trap of thinking of narratives in a narrowly exemplary way, i.e. as tales with a moral. To combine narrativity with exemplarity usefully – for the purposes of analysing legal reasoning – narrative is best understood thinly, namely as a temporally-organised matrix of happenings that resonates emotionally with the audience. So conceived, the processes of common law reasoning is full of exemplarity and narrativity. The paper is structured into two parts: the first elaborates on the concepts of exemplarity and narrativity used in the paper, situating them in the relevant literature; the second applies those concepts to a particular common law case: Williams v Roffey (1991).
The Impact of Various Reactive Oxygen Species on the Formation of Neutrophil Extracellular Traps

The formation of neutrophil extracellular traps (NETs) depends on the generation of reactive oxygen species (ROS). Previous studies revealed that both NADPH oxidase and myeloperoxidase (MPO) are required for NET release. However, the contribution of various ROS as well as the role of mitochondria-derived ROS has not been addressed so far. In the present study we aimed to investigate in a systematic and comprehensive manner the contribution of various ROS and ROS-generating pathways to the PMA-induced NET release. By using specific inhibitors, the role of both NADPH oxidase- and mitochondria-derived ROS as well as the contribution of superoxide dismutase (SOD) and MPO on the NET release was assessed. We could demonstrate that NADPH oxidase function is crucial for the formation of NETs. In addition, we could clearly show the involvement of MPO-derived ROS in NET release. Our results, however, did not provide evidence for the role of SOD- or mitochondria-derived ROS in NET formation.
Prevalence of Batrachochytrium dendrobatidis in Xenopus Collected in Africa (1871–2000) and in California (2001–2010)

International trade of the invasive South African clawed frog (Xenopus laevis), a subclinical carrier of the fungal pathogen Batrachochytrium dendrobatis (Bd) has been proposed as a major means of introduction of Bd into naïve, susceptible amphibian populations. The historical presence of Bd in the indigenous African population of Xenopus is well documented. However, there are no reports documenting the presence of Bd in wild Xenopus populations in the US, particularly in California where introduced populations are well-established after intentional or accidental release. In this report, a survey was conducted on 178 archived specimens of 6 species of Xenopus collected in Africa from 1871–2000 and on 23 archived specimens (all wild-caught Xenopus laevis) collected in California, USA between 2001 and 2010. The overall prevalence rate of Bd in the tested Xenopus was 2.8%. The earliest positive specimen was X. borealis collected in Kenya in 1934. The overall prevalence of Bd in the X. laevis collected in California was 13% with 2 positive specimens from 2001 and one positive specimen from 2003. The positive Xenopus (3/23) collected in California were collected in 2001 (2/3) and 2003 (1/3). These data document the presence of Bd-infected wild Xenopus laevis in California. The findings reported here support the prevailing hypothesis that Bd was present as a stable, endemic infection in Xenopus populations in Africa prior to their worldwide distribution likely via international live-amphibian trade.
Selective Activation of Basal Forebrain Cholinergic Neurons Attenuates Polymicrobial Sepsis–Induced Inflammation via the Cholinergic Anti-Inflammatory Pathway

Objectives: Basal forebrain cholinergic neurons are proposed as a major neuromodulatory system in inflammatory modulation. However, the function of basal forebrain cholinergic neurons in sepsis is unknown, and the neural pathways underlying cholinergic anti-inflammation remain unexplored. Design: Animal research. Setting: University research laboratory. Subjects: Male wild-type C57BL/6 mice and ChAT-ChR2-EYFP (ChAT) transgenic mice. Interventions: The cholinergic neuronal activity of the basal forebrain was manipulated optogenetically. Cecal ligation and puncture was produced to induce sepsis. Left cervical vagotomy and 6-hydroxydopamine injection to the spleen were used. Measurements and Main Results: Photostimulation of basal forebrain cholinergic neurons induced a significant decrease in the levels of tumor necrosis factor-&agr; and interleukin-6 in the serum and spleen. When cecal ligation and puncture was combined with left cervical vagotomy in photostimulated ChAT mice, these reductions in tumor necrosis factor-&agr; and interleukin-6 were partly reversed. Furthermore, photostimulating basal forebrain cholinergic neurons induced a large increase in c-Fos expression in the basal forebrain, the dorsal motor nucleus of the vagus, and the ventral part of the solitary nucleus. Among them, 35.2% were tyrosine hydroxylase positive neurons. Furthermore, chemical denervation showed that dopaminergic neurotransmission to the spleen is indispensable for the anti-inflammation. Conclusions: These results are the first to demonstrate that selectively activating basal forebrain cholinergic neurons is sufficient to attenuate systemic inflammation in sepsis. Specifically, photostimulation of basal forebrain cholinergic neurons activated dopaminergic neurons in dorsal motor nucleus of the vagus/ventral part of the solitary nucleus, and this dopaminergic efferent signal was further transmitted by the vagus nerve to the spleen. This cholinergic-to-dopaminergic neural circuitry, connecting central cholinergic neurons to the peripheral organ, might have mediated the anti-inflammatory effect in sepsis.
3D-RISM-KH approach for biomolecular modelling at nanoscale: thermodynamics of fibril formation and beyond

As an alternative to the conventional solvation models, we propose to use the molecular theory of solvation also known as the three-dimensional reference interaction site model with the Kovalenko–Hirata closure (3D-RISM-KH) as an essential part of a multiscale approach for biomolecular modelling at nanoscale. Based on the rigorous statistical–mechanical foundation, this approach provides a natural link between different levels of coarse-graining details in the multiscale description of the solvation structure and thermodynamics, from highly localised structural solvent and bound ligand molecules to effective desolvation potentials and self-assembling nanoarchitectures. Using the 3D-RISM-KH approach, we study all stages of formation of fibrillar aggregates and amyloid fibrils. We also show that the approach is capable of predicting binding sites for the inhibitors of the pathological conversion and aggregation of prion proteins in agreement with experimental data.
COMPENSATING RESTAURANT EMPLOYEE THROUGH TIPS : AN ANTECEDENT FOR ORGANIZATIONAL COMMITMENT ?

Economic and social pressures are forcing managers to examine how people get paid and what difference it makes. The foodservice industry uses tipping as a compensation method for many of its jobs. Research on tipping has focused on role conflict, views of the parties involved in the tipping process, and the relationship of tip size and other variables (Shamir, 1983; Lynn and Lantane, 1984; Lynn, 1988; Lynn and Grassman, 1990; May, 1980; Lynn and Mynier, 1993; and Lynn, Zinkhan, and Harris, 1993). The current research takes a fresh approach from the existing research on tipping to look at the relationship between tipping as an employee’s compensation method and commitment to their organization. Data were collected from 1362 foodservice employees. The findings support that compensating employees through tips does have an effect on their commitment.
Exploring the mutual influence of self and relationship : a theory of couple identity negotiation

Relationships can shape the self-concept, draw out unique aspects of an individual’s personality, and influence individual perspectives and goals. Yet the self is not a passive player in relationships as self-related goals and motives can also influence how relationships form and develop. While the field is replete with research on the unidirectional influence between self and relationships, surprisingly little has been done on synergistic effect of combined self and relationship influences. I present a new theory of couple identity negotiation that captures how two individuals in a relationship negotiate their independent identities to form a unified couple identity. I hypothesize that the process through which an individual and his/her partner merge to create a new couple identity is crucial in determining relationship longevity and satisfaction. I draw from social identity theory (Turner et al., 1987) and identity fusion theory (Swann et al., 2009) to propose three models of couple identity negotiation: Model A involves the self being subsumed by the partner; Model B involves a negotiation wherein the self and partner both contribute to the couple identity; Model C the self subsuming the partner’s self. Study 1 tests the links between the different models to relationship outcomes, namely relationship satisfaction and commitment. Study 2 explores personality correlates of the models. Results demonstrate that couple identity negotiation models predict different levels of relationship quality. Furthermore, the models are not significantly correlated with personality variables, suggesting that the models are specific to the relationship, and are not driven solely by individual differences.
Platys: From Position to Place-Oriented Mobile Computing

The Platys project focuses on developing a high-level, semantic notion of location called place. A place, unlike a geospatial position, derives its meaning from a user’s actions and interactions in addition to the physical location where they occur. Our aim is to enable the construction of a large variety of applications that take advantage of place to render relevant content and functionality and thus, improve user experience. We consider elements of context that are particularly related to mobile computing. The main problems we have addressed to realize our place-oriented mobile computing vision, are representing places, recognizing places, engineering place-aware applications. We describe the approaches we have developed for addressing these problems and related subproblems. A key element of our work is the use of collaborative information sharing where users’ devices share and integrate knowledge about places. Our place ontology facilitates such collaboration. Declarative privacy policies allow users to specify contextual features under which they prefer to share or not share their information.
Molecular Interactions and Protein-Induced DNA Hairpin in the Transcriptional Control of Bacteriophage Ø29 DNA

Studies on the regulation of phage Ø29 gene expression revealed a new mechanism to accomplish simultaneous activation and repression of transcription leading to orderly gene expression. Two phage-encoded early proteins, p4 and p6, bind synergistically to DNA, modifying the topology of the sequences encompassing early promoters A2c and A2b and late promoter A3 in a hairpin that allows the switch from early to late transcription. Protein p6 is a nucleoid-like protein that binds DNA in a non-sequence specific manner. Protein p4 is a sequence-specific DNA binding protein with multifaceted sequence-readout properties. The protein recognizes the chemical signature of only one DNA base on the inverted repeat of its target sequence through a direct-readout mechanism. In addition, p4 specific binding depends on the recognition of three A-tracts by indirect-readout mechanisms. The biological importance of those three A-tracts resides in their individual properties rather than in the global curvature that they may induce.
Combined simplex-trust-region optimization algorithm for automated IC design

One of the basic algorithms employed in IC design automation is parametric optimization. It is used when a minimum of a so-called cost function is sought. There exist many optimization algorithms. One of the most successful ones is the Box simplex algorithm. The main drawback of this algorithm that was observed in practice is its slow progress in the last stages of the search. The paper addresses this issue by combining it with a trust-region based algorithm. The combined algorithm was implemented in the SPICE OPUS tool for circuit optimization and tested on several real-world IC design problems. The results show that the combined algorithm exhibits faster convergence and in most cases results in a lower final cost function value than the Box simplex algorithm.
Cooperation and Trust for Americans, Power and Relationship for Chinese: In Search of More Culturally Relevant Features of Negotiator Mentality

We define negotiation mentality as a negotiator’s general understanding and belief about the nature, context, and effective approaches of negotiation. In a comprehensive cross-cultural study, we investigate the etic and emic features of negotiators’ mentality. We theorize that how an individual perceives and understands a negotiation is both etic (universal) and emic (culture-specific). We developed a scale to measure negotiators’ mentality (Study 1), and examined the effects of its specific dimensions on negotiation outcomes (Study 2). In Study 1, we found three etic or universal dimensions across both Chinese and American negotiators, in addition, two emic dimensions are found among the U.S. negotiators and three emic dimensions among Chinese negotiators. In Study 2, we validated the developed scale and examined the relationships between the etic and emic dimensions and negotiation outcomes. We found that although the etic factors of cooperation and trust are relevant in predicting negotiation behaviors for both American and Chinese negotiators, their effects are much stronger for the Americans. For Chinese negotiators, the emic factors of power, relational concern, and open discussion are more powerful predictors of negotiation outcome than the etic factors of cooperation and trust. Our research contributes to cross-cultural negotiation research by establishing both etic and emic constructs and scales of negotiation mentality and shedding light on the necessity of investigating the proximal factors influencing negotiation processes and outcomes, especially the potential of emic factors in non-U.S. contexts.
Gravitational Bending of Light Near Compact Objects

A photon emitted near a compact object at an angle α with respect to the radial direction escapes to infinity at a different angle ψ > α. This bending of light is caused by a strong gravitational field. We show that, in a Schwarzschild metric, the effect is described by 1 - cos α = (1 - cos ψ)(1 - rg/R), where R/rg is the emission radius in Schwarzschild units. The formula is approximate, and it applies at R ≥ 2rg only; however, at these radii it has amazing accuracy, fully sufficient in many applications. As one application, we develop a new formulation for the light-bending effects in pulsars. It reveals the simple character of these effects and gives their quantitative description with practically no loss of accuracy (for the typical radius of a neutron star R = 3rg the error is 1%). The visible fraction of a star surface is shown to be Sv/4πR2 = [2(1 - rg/R)]-1, which is for R = 3rg. The instantaneous flux of a pulsar comes from one or two antipodal polar caps that rotate in the visible zone. The pulse produced by one blackbody cap is found to be sinusoidal (light bending impacts the pulse amplitude but not its shape). When both caps are visible, the pulse shows a plateau: the variable parts of the antipodal emissions precisely cancel each other. The pulsed fraction of blackbody emission with antipodal symmetry has an upper limit Amax = (R - 2rg)/(R + 2rg). Pulsars with A > Amax must be asymmetric.
Revealing changes in molecular composition of plant cell walls on the micron-level by Raman mapping and vertex component analysis (VCA)

At the molecular level the plant cell walls consist of a few nanometer thick semi-crystalline cellulose fibrils embedded in amorphous matrix polymers such as pectins, hemicelluloses, and lignins. The arrangement of these molecules within the cell wall in different plant tissues, cells and cell wall layers is of crucial importance for a better understanding and thus optimized utilization of plant biomass. During the last years Confocal Raman microscopy evolved as a powerful method in plant science by revealing the different molecules in context with the microstructure. In this study two-dimensional spectral maps have been acquired of micro-cross-sections of spruce (softwood) and beech (hardwood). Raman images have been derived by using univariate (band integration, height ratios) and multivariate methods [vertex component analysis (VCA)]. While univariate analysis only visualizes changes in selected band heights or areas, VCA separates anatomical regions and cell wall layers with the most different molecular structures. Beside visualization of the distinguished regions and features the underlying molecular structure can be derived based on the endmember spectra. VCA revealed that the lumen sided S3 layer has a similar molecular composition as the pit membrane, both revealing a clear change in lignin composition compared to all other cell wall regions. Within the S2 layer a lamellar structure was visualized, which was elucidated to derive from slight changes in lignin composition and content and might be due to successive but not uniform lignification during growth.