Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Receptor-attached Phosphates in Binding of Visual and Non-visual Arrestins to G Protein-coupled Receptors*

Background: The relative contribution of phosphates and active GPCR conformation is unknown. Results: Using WT and mutant arrestins and receptors, we show that phosphates are critical for arrestin binding to some GPCRs but not to others. Conclusion: The role of receptor-attached phosphates in arrestin binding varies widely depending on the arrestin-receptor combination. Significance: Distinct molecular mechanisms mediate arrestin recruitment to different GPCRs. Arrestins are a small family of proteins that regulate G protein-coupled receptors (GPCRs). Arrestins specifically bind to phosphorylated active receptors, terminating G protein coupling, targeting receptors to endocytic vesicles, and initiating G protein-independent signaling. The interaction of rhodopsin-attached phosphates with Lys-14 and Lys-15 in β-strand I was shown to disrupt the interaction of α-helix I, β-strand I, and the C-tail of visual arrestin-1, facilitating its transition into an active receptor-binding state. Here we tested the role of conserved lysines in homologous positions of non-visual arrestins by generating K2A mutants in which both lysines were replaced with alanines. K2A mutations in arrestin-1, -2, and -3 significantly reduced their binding to active phosphorhodopsin in vitro. The interaction of arrestins with several GPCRs in intact cells was monitored by a bioluminescence resonance energy transfer (BRET)-based assay. BRET data confirmed the role of Lys-14 and Lys-15 in arrestin-1 binding to non-cognate receptors. However, this was not the case for non-visual arrestins in which the K2A mutations had little effect on net BRETmax values for the M2 muscarinic acetylcholine (M2R), β2-adrenergic (β2AR), or D2 dopamine receptors. Moreover, a phosphorylation-deficient mutant of M2R interacted with wild type non-visual arrestins normally, whereas phosphorylation-deficient β2AR mutants bound arrestins at 20–50% of the level of wild type β2AR. Thus, the contribution of receptor-attached phosphates to arrestin binding varies depending on the receptor-arrestin pair. Although arrestin-1 always depends on receptor phosphorylation, its role in the recruitment of arrestin-2 and -3 is much greater in the case of β2AR than M2R and D2 dopamine receptor.
Increased Clot Formation in the Absence of Increased Thrombin Generation in Patients with Peripheral Arterial Disease: A Case–Control Study

Background In peripheral arterial disease (PAD), activation of the hemostatic system may contribute to atherosclerosis progression and atherothrombotic events. Objective This case–control study assesses the overall coagulation status in PAD patients by evaluating coagulation markers in combination with thrombin generation potential, whole blood (WB) clot formation, and fibrinolysis. Methods In blood from 40 PAD patients (n = 20 with cardiovascular event within 1 year after initial diagnosis, n = 20 without) and 40 apparently healthy controls, thrombin generation was determined in WB and platelet-poor plasma. Whole blood rotational thromboelastometry (ROTEM) measurements were triggered with tissue factor with/without tissue plasminogen activator. Results We observed increased levels of erythrocyte sedimentation rate, leukocytes, eosinophil granulocytes, vWF antigen, fibrinogen, and D-dimer in PAD patients (p < 0.05). Markers of thrombin generation potential showed no difference between patients and healthy controls. In PAD patients with event compared to patients without, WB-thrombin generation showed a lower thrombin potential when triggered with 0 and 2.5 pM tissue factor. The ROTEM clotting assay showed significantly faster clot formation and increased clot firmness in PAD patients compared to controls. No significant differences were found for parameters of clot degradation. Conclusion There are no significant differences between the thrombin generation profiles of PAD patients and healthy controls. Between PAD patients with and without cardiovascular event, the WB thrombin generation appears to differ. Mechanistically, PAD patients show an increased ability to form a stable clot in WB in comparison to healthy controls. This is most likely due to the increased fibrinogen levels related to the inflammation in atherosclerosis, confirming the importance of the inflammation-coagulation axis.
Slack in the Public Sector: A comparative analysis of a private and a public enterprise for refuse collection

There are currently strong external pressures in place to increase efficiency in the public sector. The reason for these pressures is an assumption that due to agency problems and opportunism, public enterprises have a tendency to accumulate slack, i.e. to develop lower efficiency compared to what might be achievable in the private sector. Private enterprises form the basis for comparison, and new management techniques are often transferred from the private to the public sector. This article is based on a case study involving two refuse collection enterprises: one public and one from the private sector. Both work in the same market and apply the same technology. The purpose is to investigate whether there are indications of slack in the public refuse collection enterprise, and whether the management control systems applied are suitable for controlling the level of slack. Moreover, additional focus is placed on the differences in management between the two enterprises, representing the public and private sector, respectively. The results indicate that the public refuse collection enterprise had a higher level of slack than the private enterprise, and that the management control systems were not suitable for reducing the level of slack to any significant extent. In the private enterprise, there was a higher degree of budgetary emphasis, the owners made greater demands, employees were more closely supervised and there was a greater degree of participation. In this article, we discuss whether these results may contribute towards explaining any differences in efficiency that may occur between private and public enterprises.
Macrofinancial Risks and Liquidity Preference

This paper investigates the relationship between macrofinancial volatility, derivatives usage, and liquidity preference of nonfinancial firms in the United States. It discusses theoretically how liquidity preference changes under different institutional settings created to deal with macrofinancial risks, and provides exploratory empirical analysis to measure these changes. The preliminary empirical findings suggest that the liquidity preference of nonfinancial firms in the United States, according to a specific metric, declined from the 1950s to the 1980s, but has increased since then, despite the voluminous increase in derivatives transactions since the 1970s. The theoretical discussion and the preliminary evidence lend support to claims supporting financial market regulation and raise doubts about the effectiveness of financial derivatives usage as an effective hedging mechanism.
Transferable, multiple antibiotic and mercury resistance in Atlantic Canadian isolates of Aeromonas salmonicida subsp. salmonicida is associated with carriage of an IncA/C plasmid similar to the Salmonella enterica plasmid pSN254.

OBJECTIVES The aim of this study was to examine the molecular basis for multiple antibiotic and mercury resistance in Canadian isolates of Aeromonas salmonicida subsp. salmonicida. METHODS Phenotypic and genotypic methods were employed to identify plasmid-associated antibiotic and mercury resistance genes and to determine the organization of those genes in multidrug-resistant (MDR) A. salmonicida isolates. RESULTS The MDR phenotype was transferable via conjugation using Escherichia coli, Aeromonas hydrophila and Edwardseilla tarda as recipients. Antibiotic and mercury resistance genes were carried by a conjugative IncA/C plasmid. Three distinct antibiotic resistance cassettes were characterized; first a class I integron containing an aadA7 gene encoding for an aminoglycoside-3'-adenyltransferase, the second cassette showed 99.9% nucleotide sequence homology to a cassette previously identified in the Salmonella enterica IncA/C plasmid pSN254, containing floR, tetA, sulII and strA/strB sequences. The third cassette showed 100% nucleotide sequence similarity to a transposon-like element, containing a bla(CMY-2) beta-lactamase in association with sugE and blc sequences. This element is known to be widely distributed among clinical and food-borne Salmonella and other Enterobacteriaceae throughout Asia and the United States. Mercury resistance was linked to the presence of a mer operon that showed 100% nucleotide sequence homology to the mer operon carried by plasmid pSN254. CONCLUSIONS Each MDR A. salmonicida isolate carried the same plasmid, which was related to plasmid pSN254. This is the first report of plasmid-mediated florfenicol-resistant A. salmonicida in North America. In addition, it is the first report of a plasmid-associated AmpC beta-lactamase sequence in a member of the Aeromonadaceae.
The expanding role of endoscopic skull base surgery

Abstract The endoscopic endonasal approach (EEA) is a surgical technique where a small aperture, the nostrils, can give access to the whole ventral skull base. Its principles differ from the ones of traditional skull base approaches where a wide external opening is often accompanied by a relatively small working area. Most of the results of EEAs published in the literature come from retrospective case series and the follow-up is still limited, however the consensus is that this technique is safe and effective in selected cases and when performed within dedicated skull base centres. This article sets to give an overview of the current state of endoscopic skull base surgery, based on the recent evidence and our centre's experience with nearly 2000 EEAs. The team's experience with endoscopic as well as open approaches plays a critical role in achieving satisfactory results when treating pathologies of the skull base. Guided by the principle of least neural and vascular manipulation, the team should be able to select the least traumatic route (open or endoscopic) and be able to approach the skull base from all angles.
Balancing Hydropower and Environmental Values: The Resource Management Implications of the US Electric Consumers Protection Act and the AWARE™ Software

This paper reviews the AWARE™ software distributed by the Electric Power Research Institute (EPRI). The program is designed to facilitate the Federal Energy Regulatory Commission (FERC) license renewal process for US hydropower installations. The discussion reviews the regulatory, legal, and social contexts that give rise to the creation and distribution of AWARE™. The principal legal impetus for AWARE™ is the Electric Consumer Protection Act (ECPA) of 1986 that directs FERC to give equal consideration to power and non-power resources during relicensing. The software is reviewed in this paper from several perspectives including those of natural resource economics, systems modeling, and the social context within which FERC licensing decisions are made. We examine both the software and its underlying methodology and find significant problems with each. Because of its flaws, AWARE™ does little to further ECPA's equal consideration requirement. We find that the conservation and restoration impact of ECPA for US fisheries could be seriously hampered by the widespread use of AWARE™.
Fast food and obesity in children.

In July 2003, the US National Chamber of Commerce released a report on fast food and obesity, saying: “This study finds that fast food restaurants are not a chief culprit in the fattening of America. ”1 Fast-food companies, of course, are involved in chambers of commerce across the country. The National Chamber of Commerce has on its board of directors executives from CocaCola and PepsiCo.2 With billions of dollars at stake, the food industry may find it difficult to take an objective position on their products. Typical is fare issued by the National Soft Drink Association: “… soft drinks do not cause pediatric obesity, do not reduce nutrient intake, and … Address correspondence to Kelly D. Brownell, PhD, Department of Psychology, Yale University, Box 208205, New Haven, CT 06520-8205. E-mail: kelly.brownell{at}yale.edu
FUNDAMENTAL ASPECTS OF COMMUNICATION MANAGEMENT, IN THE CASE OF PUBLIC ADMINISTRATION

Efficient communication is one the most important instruments used for the purpose of generating change inside and outside an organization. It can contribute to adjusting attitudes and the manner of approaching the present and future challenges and to changing behavioral patterns. The mission and the objectives of organizational communication are highly interrelated with organizational change and environment characteristics, in which the organization functions. The communication performed by the public administration institution outside is an institutional communication, extra-organizational, which presents the following purposes: strengthening its image, stimulating an environment of trust and affinity from the citizens (Kotler & Lee, 2007). We are of opinion that the management of communication performed by a public administration institution features three fundamental aspects, relevant for institutional communicators when designing and managing the institutional communication: communication efficiency, communication process and the implications of the new information and communication technologies (ICT) for this process.
Informality and temporary migration in Mexico.

This thesis studies two characteristics of the Mexican labour markets; informality and migration to the United States. Chapter 1 studies the impact of NAFTA on informality and wages, the former measured in a reduced form through the fraction of workers without any social or health coverage (unregistered workers). Using data on Mexican and U.S. import tariffs with the Mexican National Survey of Urban Labour (ENEU), I find that reductions in tariffs are related to reductions in unregistered labour. Unregistered labour decreases less in high import-penetration industries and more in export oriented ones. The Mexican tariffs are also negatively related to real wages, while the U.S. tariffs are negatively related to the registered-unregistered wage differentials. Chapter 2 is a joint work with Arturo Ramirez. It uses two Mexican tax reforms to test whether the unregistered sector is sensitive to changes in the tax burden. The first is the 1989 implementation of an asset tax, and the second is the 1999 elimination of accelerated depreciation allowances. The data comes from the ENEU, from which estimates of unregistration are derived; and the Annual Industrial Survey (EIA), from which the differential effects of the 1999 reform on each region and industry are implied. It is found that the response of unregistered labour to changes in taxes is heterogeneous, depending both on the economic sector and the nature of the tax policy. Lastly, chapter 3 studies the effect of temporary migration to the U.S. on labour market outcomes of Mexican workers. It uses panel data from the 1994-2002 ENEU, which is ideal for minimizing self-selection biases common to other sources. Fixed-effects estimation indicates that temporary migrants obtain higher earnings in the U.S. labour market during the period of migration. They also work longer hours and face a higher likelihood of non employment. Finally, the gains from migration are lower for more skilled workers and for those migrating from the most distant regions, relative to the U.S.
Marketing practices and Internet marketing: A study of hotels in Singapore

Singapore is renowned for its world-class airport facilities, garden city, modern and sound infrastructure, political stability and vibrant multi-racial society. It has been one of the most popular and growing tourist destinations in Asia. However, it is becoming increasingly difficult for Singapore to sustain such a high rate of growth, due to limited natural attractions and keen competition in the region. This study examines the marketing strategies adopted by local hotel establishments in the competitive hospitality industry. It also analyses the adoption and role of information technology in strategic marketing. It was found that most hotels seemed to have embraced the marketing concept, given the existence of extensive marketing plans. Although most hotels appeared to have successfully incorporated information technology into their marketing campaigns, the level of commitment seemed to be insignificant. Following a brief comparison with a similar US study, the paper concludes that there are only minor differences between US and Singapore hotels in terms of their marketing practices.
A Model of Molecular Circadian Clocks: Multiple Mechanisms for Phase Shifting and a Requirement for Strong Nonlinear Interactions

A fundamental question in the field of circadian rhythms concerns the biochemical and molecular nature of the oscillator. There is strong evidence that circadian oscillators are cell autonomous and rely on periodic gene expression. In Drosophila, Neurospora, Aplysia, and vertebrates, circadian oscillators are thought to be based on molecular autoregulatory loops composed of transcription, translation, and negative feedback by proteins on nuclear transcription. By studying a mathematical model of molecular clocks based on this general concept, the authors sought to determine which features such clocks must have to generate robust and stable oscillations and to allow entrainment by external stimuli such as light. The model produced circadian oscillations as an emergent property even though a time delay in protein synthesis and rate constants of the feedback loop were much shorter than 24 h. Along with the delay in protein production, strong nonlinear interactions in macromolecular synthesis and nuclear feedback appeared to be required for the model to show well-behaved oscillatory behavior. Realistic phase-shifting patterns induced by external stimuli could be achieved by multiple mechanisms—namely, up-and downward perturbations of protein or mRNA synthesis or degradation rates. The model makes testable predictions about interactions between clock elements and mechanisms of entrainment and may help to understand the functions of the intricate molecular interactions governing circadian rhythmogenesis.
In vivo assessment of the window of barrier opening after osmotic blood-brain barrier disruption in humans.

OBJECT Osmotic blood-brain barrier (BBB) disruption induced by intraarterial infusion of mannitol is used in conjunction with chemotherapy to treat human brain tumors. The time course to barrier closure, or the so-called therapeutic window, has been examined in animals but little information is available in humans. The authors, therefore assessed the time course to barrier closure after osmotic BBB disruption in humans. METHODS Disruption of the BBB was demonstrated using 99mTc-glucoheptonate (TcGH) single-photon emission computerized tomography (SPECT) scanning in 12 patients who were treated monthly with combination chemotherapy in conjunction with BBB disruption. The primary diagnosis was primary central nervous system lymphoma in seven patients and primitive neuroectodermal tumors in five. The TcGH (20 mCi) was injected at 1- to 480-minute intervals after osmotic BBB disruption, and patients underwent SPECT scanning after 4 hours. A total of 38 studies was performed. Good-to-excellent BBB disruption was obtained in 29 procedures and poor-to-moderate disruption was seen in the other nine studies. The TcGH indices correlated with the degree of BBB disruption as measured postprocedure on contrast-enhanced CT scans (r = 0.852). Mean baseline TcGH indices were 1.02+/-0.07. For the group of patients with good-to-excellent disruptions the mean indices at 1 minute postdisruption measured 2.19+/-0.18. After 40 minutes no significant change was noted (mean index 2.13+/-0.2). Then the indices declined more steeply and at 120 minutes after the disruption the index was 1.36+/-0.02. A very slow decline was noted between 120 and 240 minutes after mannitol infusion. At 240 minutes the barrier was still open for all good-to-excellent disruptions (index 1.33+/-0.08) but at 480 minutes the mean indices had returned to the baseline level. CONCLUSIONS Results of these in vivo human studies indicate that the time course to closure of the disrupted BBB for low-molecular-weight complexes is longer than previously estimated. The barrier is widely open during the first 40 minutes after osmotic BBB disruption and returns to baseline levels only after 6 to 8 hours following the induction of good or excellent disruption. These findings have important clinical implications for the design of therapeutic protocols.
Gfi‐1 is the transcriptional repressor of SOCS1 in acute myeloid leukemia cells

Silencing of SOCS1, a TSG, has been detected in various malignancies, including AML. However, the underlying mechanism of SOCS1 inactivation remains elusive. In this study, we explored the role of histone methylation in SOCS1 expression in AML cells. By ChIP assay, we demonstrated that G9a and SUV39H1, two enzymes catalyzing H3K9 methylation, were physically associated with the SOCS1 promoter, and treatment with chaetocin, a histone methyltransferase inhibitor, suppressed H3K9 methylation on the SOCS1 promoter and enhanced SOCS1 expression. Furthermore, knockdown of G9a and SUV39H1 by siRNA could also induce SOCS1 expression. On the other hand, SOCS1 knockdown by shRNA eliminated chaetocin‐induced cell apoptosis. To investigate further whether any transcription factor was involved in H3K9 methylation‐related SOCS1 repression, we scanned the sequences of the SOCS1 gene promoter and found two binding sites for Gfi‐1, a transcription repressor. By DNA pull‐down and ChIP assays, we showed that Gfi‐1 directly bound the SOCS1 promoter, and ectopic Gfi‐1 expression suppressed STAT5‐induced SOCS1 promoter activation. In contrast, Gfi‐1 knockdown by shRNA enhanced SOCS1 expression and inhibited STAT5 expression. Moreover, the knockdown of G9a completely rescued the repressive effect of Gfi‐1 on STAT5A‐induced SOCS1 promoter activation. Collectively, our study indicates that the expression of Gfi‐1 contributes to SOCS1 silencing in AML cells through epigenetic modification, and suppression of histone methyltransferase can provide new insight in AML therapy.
Orthodromically and antidromically evoked local field potentials in the crayfish olfactory lobe

A local field potential, consistent in form and duration, can be recorded from the olfactory lobe of crayfish following electrical stimulation of the outer flagellum of the antennule. The field potential is reversibly blocked by perfusion of the brain with low-[Ca2+] saline or -aminobutyric acid and, to a lesser extent, histamine. Paired shocks to the antennule and antidromic electrical stimulation of olfactory lobe output neurones also partially block the field potential. Comparing the field potential with simultaneously recorded intracellular responses of olfactory interneurones reveals a coincidence between excitatory and inhibitory effects in the interneurones and the appearance of identifiable components of the field potential. We interpret the field potential to reflect the response of neural elements in the olfactory lobe to orthodromic activity in the axons of the olfactory receptor neurones on the antennule. We conclude from the blocking experiments that the greater part of the field potential stems from neurones in the olfactory lobe that are postsynaptic to olfactory receptor neurones. As such, it provides a robust indication of olfactory neurone activity.