Miracle-dz/UniFAR-FTUs huggingface dataset:
Disinterested scholars or interested parties? The public's investment in self-interested universities

The university’s authority over knowledge is more tenuous than we think. The basis of university authority has been grounded, over the long history of higher education, in nothing more than ideas and values. Such ideas, however have taken institutions quite a long way. Other institutions – religious and political authorities, for example – have vied for a say over knowledge and yet the university has prevailed as the institution, arguably, that we trust the most. In the 20th century the university grew to enormous proportions and has gained significant influence. And yet it has arguably also faced more threats to both its standing and integrity than ever before.
A dog model to investigate the relationship between obstructive sleep apnoea and blood pressure regulation

SUMMARY Patients exhibiting obstructive sleep apnoea (OSA) do not display a normal circadian pattern of blood pressure. It is not clear whether this disruption of the circadian blood pressure pattern is a result of the intermittent airway obstruction during sleep or is the result of confounding factors, such as obesity and age, which are common in OSA and may independently affect blood pressure. To determine if a cause and effect relationship exists between repetitive airway obstruction during sleep and blood pressure regulation a chronically instrumented canine model of OSA has been developed. This canine model has been shown to reproduce the characteristic apnoea and hypersomnolence of human OSA. Furthermore, in this model a 12‐h nocturnal period of repetitive airway obstruction during sleep caused an increase in baseline blood pressure of more than 10 mmHg that was sustained for at least two hours following the restoration of normal airway patency. These results imply that there is a cause and effect relationship between intermittent airway obstruction during sleep and elevated blood pressure.
Six new coeliac disease loci replicated in an Italian population confirm association with coeliac disease

Background and aims: The first genome wide association study on coeliac disease (CD) and its follow-up have identified eight new loci that contribute significantly towards CD risk. Seven of these loci contain genes controlling adaptive immune responses, including IL2/IL21 (4q27), RGS1 (1q31), IL18RAP (2q11–2q12), CCR3 (3p21), IL12A (3q25–3q26), TAGAP (6q25) and SH2B3 (12q24). Methods: We selected the nine most associated single nucleotide polymorphisms to tag the eight new loci in an Italian cohort comprising 538 CD patients and 593 healthy controls. Results: Common variation in IL2/IL21, RGS1, IL12A/SCHIP and SH2B3 was associated with susceptibility to CD in our Italian cohort. The LPP and TAGAP regions also showed moderate association, whereas there was no association with CCR3 and IL18RAP. Conclusion: This is the first replication study of six of the eight new CD loci; it is also the first CD association study in a southern European cohort. Our results may imply there is a genuine population difference across Europe regarding the loci contributing to CD.
Maintenance Immunosuppression with Target-of-Rapamycin Inhibitors is Associated with a Reduced Incidence of De Novo Malignancies

Background. Immunosuppressive drug therapy has been identified as one etiological factor in the increased incidence of and deaths from malignancies in renal transplant recipients. In animal models, calcineurin inhibitors have a positive growth effect, whereas target-of-rapamycin (TOR) inhibitors have a negative growth effect on malignant cells. Methods. A multivariate analysis of posttransplant malignancies in 33,249 deceased donor primary solitary renal recipients reported by 264 kidney transplant programs to the Organ Procurement and Transplantation Network database from July 1, 1996 to December 31, 2001 was performed. Data were censored at 963 days to allow comparable follow-up time among drug treatment groups. The incidence and relative risks of any de novo malignancy (skin and solid) and for nonskin solid malignancies in patients receiving TOR inhibitors compared to patients receiving calcineurin inhibitors were the primary endpoints. Results. The incidence rates of patients with any de novo posttransplant malignancy were 0.60% with sirolimus/everolimus alone, 0.60% with sirolimus/everolimus + cyclosporine/tacrolimus, and 1.81% with cyclosporine/tacrolimus (P<0.0001); the rates with a de novo solid tumor were 0%, 0.47%, and 1.00%, respectively. In the Cox regression model the relative risk associated with sirolimus/everolimus immunosuppression for any de novo cancer was 0.39 (95% CI: 0.24–0.64; P=0.0002) and for de novo solid cancer was 0.44 (0.24–0.82; P=0.0092). Other significant risk factors were male sex, adult age group, white race, and history of a malignancy. Conclusions. Maintenance immunosuppression with the TOR inhibitor drugs, sirolimus and everolimus, is associated with a significantly reduced risk of developing any posttransplant de novo malignancy and nonskin solid malignancy.
A Metric for Quantifying Product‐Level Circularity

Circularity metrics are useful for empirically assessing the effects of a circular economy in terms of profitability, job creation, and environmental impacts. At present, however, there is no standardized method for measuring the circularity of products. We start by reviewing existing product‐level metrics in terms of validity and reliability, taking note of theoretically justified principles for aggregating different types of material flows and cycles into a single value. We then argue that the economic value of product parts may constitute a useful basis for such aggregation; describe a set of principles for using economic value as a basis for measuring product circularity; and outline a metric that utilizes this approach. Our recommendation is to use the ratio of recirculated economic value to total product value as a circularity metric, using value chain costs as an estimator. In order to protect value chain actors’ sensitive financial data and facilitate neutrality regarding outsourcing or insourcing, we suggest a means to calculate product‐level circularity based on sequential approximations of adding one product part and activity at a time. We conclude by suggesting potential avenues for further research, including ways in which the proposed metric can be used in wider assessments of the circular economy, and ways in which it may be further refined.
Alzheimer CSF biomarkers in routine clinical setting

Tabaraud F, Leman JP, Milor AM, Roussie JM, Barrière G, Tartary M, Boutros‐Toni F, Rigaud M. Alzheimer CSF biomarkers in routine clinical setting. Acta Neurol Scand: 2012: 125: 416–423. © 2011 John Wiley & Sons A/S.
Feasibility of a sustained steep Ca(2+)Gradient in the cytosol of electrically non-excitable cells.

In electrically non-excitable cells the predominant mode of calcium signaling is a biphasic rise in cytosolic calcium concentration. It results from Ca(2+)release from intracellular stores, followed by Ca(2+)influx across the plasma membrane. It has been hypothesized that prolonged calcium influx may result in a sustained local elevation of the cytosolic calcium concentration near the plasma membrane. The mathematical model presented here evaluates the cytosolic concentration of Ca(2+)as a function of time and distance from the plasma membrane. It consists of cytoplasmic calcium stores and a plasma membrane, both equipped with calcium channels and pumps, and an immobile cytoplasmic calcium buffer. The model has verified quantitatively the feasibility of a stable Ca(2+)gradient in the cytosol with high values of Ca(2+)concentration near the plasma membrane and evaluated its properties as a function of different cellular parameters. The formation of the gradient does not require special distribution of the intracellular contents, channels and pumps. However, it requires buffering of the cytosolic calcium by the intracellular stores and that the rate of calcium release from the stores near the plasma membrane be higher than in other parts of the cell. We suggest that this model can provide an adequate description of the elevated calcium plateau generally observed in electrically non-excitable cells.
Investor–State Dispute Settlement Systems in Emerging Mega‐Integration Blocs

Emerging mega-integration blocs, such as the Trans-Pacific Partnership and the Transatlantic Trade and Investment Partnership, are evolving outside of the World Trade Organization's influence. Their most contested features are their investor–state dispute settlement (ISDS) systems. This article considers basic features of the ISDS system, the expansion in the number of ISDS cases and the privileged place of corporations vis-a-vis citizens in the law-making process. The arcane private corporation-friendly ISDS system is beyond reparation and it needs to be scrapped. The existing court systems in the self-assured democracies of Europe, North America and Australia are sufficient.
Escherichia coli mutants impaired in maltodextrin transport

Wild-type Escherichia coli K-12 was found to grow equally well on maltose and on maltodextrins containing up to seven glucose residues. Three classes of mutants unable to grow on maltodextrins, but still able to grow on maltose, were investigated in detail. The first class, already known, was composed of phage lambda-resistant mutants, which lack the outer membrane protein coded by gene lamB. These mutants grow on maltose and maltotriose but not at all on maltotetraose and longer maltodextrins which cannot cross the outer membrane. A second class of mutants were affected in malE, the structural gene of the periplasmic maltose binding protein. The maltose binding proteins isolated from the new mutants were altered in their substrate binding properties, but not in a way that could account for the mutant phenotypes. Rather, the results of growth experiments and transport studies suggest that these malE mutants are impaired in their ability to transport maltodextrins across the outer membrane. This implies that the maltose binding protein (in wild-type strains) cooperates with the lambda receptor in permeation through the outer membrane. The last class of mutants described in this paper were affected in malG, or perhaps in an as yet undetected gene close to malG. They were defective in the transfer of maltodextrins from the periplasmic space to the cytoplasm but only slightly affected in the transport of maltose.
A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide

Lenalidomide is the first karyotype-selective therapeutic approved for the treatment of myelodysplastic syndromes (MDS) owing to high rates of erythroid and cytogenetic response in patients with chromosome 5q deletion [del(5q)]. Although haploinsufficiency for the RPS14 gene and others encoded within the common deleted region (CDR) have been implicated in the pathogenesis of the del(5q) phenotype, the molecular basis of the karyotype specificity of lenalidomide remains unexplained. We focused our analysis on possible haplodeficient enzymatic targets encoded within the CDR that play key roles in cell-cycle regulation. We show that the dual specificity phosphatases, Cdc25C and PP2Acα, which are coregulators of the G2-M checkpoint, are inhibited by lenalidomide. Gene expression was lower in MDS and acute myeloid leukemia (AML) specimens with del(5q) compared with those with alternate karyotypes. Lenalidomide inhibited phosphatase activity either directly (Cdc25C) or indirectly (PP2A) with corresponding retention of inhibitory phospho-tyrosine residues. Treatment of del(5q) AML cells with lenalidomide induced G2 arrest and apoptosis, whereas there was no effect in nondel(5q) AML cells. Small interfering RNA (shRNA) suppression of Cdc25C and PP2Acα gene expression recapitulated del(5q) susceptibility to lenalidomide with induction of G2 arrest and apoptosis in both U937 and primary nondel(5q) MDS cells. These data establish a role for allelic haplodeficiency of the lenalidomide inhibitable Cdc25C and PP2Acα phosphatases in the selective drug sensitivity of del(5q) MDS.
Pain reduction in patients after applying a nitrous oxide/oxygen mixture (Livopan) during photodynamic therapy: study protocol for an observational study (Livopan study)

Introduction Photodynamic therapy (PDT) is an effective treatment option for extensively photodamaged skin with multiple actinic kerastosis. However, the main drawback of PDT is the intensive pain experienced during its application, which makes it frequently necessary to interrupt or even terminate the process resulting in incomplete treatment. Several strategies for controlling pain during PDT have been studied but few effective methods are currently available. Alternative options are urgently needed. Livopan, a nitrous oxide/oxygen mixture, is indicated for the treatment of short-term pain conditions when rapid analgesic onset and offset effects are wanted. But so far, there are no studies evaluating the effect of Livopan on pain intensity during PDT. Therefore, it remains unclear whether patients benefit from this inhalation analgesia. Within the Livopan study, this issue will be evaluated for the first time. Methods and analysis The Livopan study is a prospective, single-centre, explorative, controlled, observational study to investigate the pain reduction in patients after applying a nitrous oxide/oxygen mixture (Livopan) during PDT according to the visual analogue scale in 60 patients. Ethics and dissemination Ethics approval was provided by the ethics committee of the medical faculty of the University of Heidelberg. Ethics approval number S-169/2014. Trial registration number German Clinical Trial Register (DRKS): DRKS00006054.
SHAREHOLDER RISK MEASURES

The aim of this paper is to put forward a new family of risk measures that could guide investment decisions of private companies. But at the difference of the classical approach of Artzner, Delbaen, Eber, and Heath and the subsequent extensions of this model, our risk measures are built to reflect the risk perception of shareholders rather than regulators. Instead of an axiomatic approach, we derive risk measures from the optimal policies of a shareholder value‐maximizing company. We study these optimal policies and the related risk measures that we call shareholder risk measures. We emphasize the fact that due to the specific corporate environment, in particular the limited shareholders' liability and the possibility to pay out dividends from cash reserves, these risk measures are not convex. Also, they depend on the specific economic situation of the firm, in particular its current cash level, and thus they are not translation invariant. This paper bridges the gap between two important branches of mathematical finance: risk measures and optimal dividends.
Effects of IKr and IKs heterogeneity on action potential duration and its rate dependence: a simulation study.

BACKGROUND A growing body of evidence suggests that heterogeneity of ion channel expression and electrophysiological characteristics is an important property of the ventricular myocardium. The 2 components of the delayed rectifier potassium current, IKr (rapid) and IKs (slow), play a dominant role in the repolarization of the action potential and are important determinants of its duration. METHODS AND RESULTS In this report, the effects of heterogeneities of IKr and IKs on action potential duration (APD) and its rate dependence (adaptation) are studied with the use of the LRd model of a mammalian ventricular cell. Results demonstrate the importance of IKs density variations in heterogeneity of repolarization. Cells with reduced IKs (eg, mid-myocardial M cells) display long APD and steep dependence of APD on rate. Mechanistically, accumulation of IKs activation and increased sodium calcium exchange current, INaCa, secondary to Na+ accumulation at a fast rate underlie the steep APD-rate relation of these cells. When cells are electrotonically coupled in a multicellular fiber through resistive gap junction, APD differences are reduced. The results demonstrate strong dependence of APD heterogeneity on the degree of intercellular coupling even in the normal physiological range. Highly reduced coupling maximizes APD heterogeneity. CONCLUSIONS Heterogeneity of IKs:IKr density strongly influences APD and its rate dependence. However, in the intact myocardium, the degree of gap-junction coupling may be an important factor that determines the manifestation of APD heterogeneity and dispersion of repolarization. The clinical significance of this study is in the context of repolarization abnormalities and associated arrhythmias (eg, long QT syndrome and torsade de pointes).
Effects from fine muscle and cutaneous afferents on spinal locomotion in cats

1. The effects of chemically activated fine muscle afferents (groups III and IV) and electrically activated cutaneous afferents on motoneuronal discharges were studied before and during fictive locomotion induced pharmacologically by i.v. administration of nialamide and l‐DOPA in high spinal cats. Efferent activity was recorded simultaneously from nerve filaments to ipsi‐ and contralateral extensor and flexor muscles. In addition, intracellular recordings were made from lumbar α‐motoneurones.
Collective Power to Create Political Change: Increasing the Political Efficacy and Engagement of Social Workers

ABSTRACT Because social workers are called to challenge social injustices and create systemic change to support the well-being of individuals and communities, it is essential that social workers develop political efficacy: belief that the political system can work and they can influence the system. This study explored the impact of an intensive political social work curriculum on political efficacy and planned political engagement among social work students and practitioners. The findings suggest this model of delivering a political social work curriculum effectively increases internal, external, and overall political efficacy, and that increasing political efficacy has promise for increasing future political engagement.
Deciphering Networks of Protein Interactions at the Nuclear Pore Complex*

The nuclear pore complex (NPC) gates the only known conduit for molecular exchange between the nucleus and cytoplasm of eukaryotic cells. Macromolecular transport across the NPC is mediated by nucleocytoplasmic shuttling receptors termed karyopherins (Kaps). Kaps interact with NPC proteins (nucleoporins) that contain FG peptide repeats (FG Nups) and altogether carry hundreds of different cargoes across the NPC. Previously we described a biochemical strategy to identify proteins that interact with individual components of the nucleocytoplasmic transport machinery. We used bacterially expressed fusions of glutathione S-transferase with nucleoporins or karyopherins as bait to capture interacting proteins from yeast extracts. Forty-five distinct proteins were identified as binding to one or several FG Nups and Kaps. Most of the detected interactions were expected, such as Kap-Nup interactions, but others were unexpected, such as the interactions of the multisubunit Nup84p complex with several of the FG Nups. Also unexpected were the interactions of various FG Nups with the nucleoporins Nup2p and Nup133p, the Gsp1p-GTPase-activating protein Rna1p, and the mRNA-binding protein Pab1p. Here we resolve how these interactions occur. We show that Pab1p associates nonspecifically with immobilized baits via RNA. More interestingly, we demonstrate that the Nup84p complex contains Nup133p as a subunit and binds to the FG repeat regions of Nups directly via the Nup85p subunit. Binding of Nup85p to the GLFG region of Nup116p was quantified in vitro (KD = 1.5 μm) and was confirmed in vivo using the yeast two-hybrid assay. We also demonstrate that Nup2p and Rna1p can be tethered directly to FG Nups via the importin Kap95p-Kap60p and the exportin Crm1p, respectively. We discuss possible roles of these novel interactions in the mechanisms of nucleocytoplasmic transport.
LTCC Bandpass Filter With Wide Stopband Based on Electric and Magnetic Coupling Cancellation

This paper presents a new method of using electric and magnetic coupling cancellation to extend the stopband of bandpass filters (BPFs). The mechanism is theoretically analyzed based on the lumped-element equivalent circuit. Due to the cancellation of electric and magnetic coupling between two resonators, three transmission zeros (TZs) can be generated and controlled by manipulating the coupling strength. Using the proposed method together with source-load coupling, a low temperature cofire ceramic (LTCC) BPF is designed with four TZs at the passband edges and within the stopband, resulting in high skirt selectivity and harmonic suppression. Due to the LTCC multilayer structure, the filter size is 0.054 λg*0. 045λg*0. 013λg, or 2.48 mm ×2.02 mm ×0.6 mm. The theoretical, simulated and measured results of the LTCC BPF are presented to validate the proposed design.
Labetalol: An Alpha- and Beta-Blocker

Labetalol is an investigational α- and β- adrenoreceptor antagonist. The ratio of effective β:α-blockade is approximately 7:1. Labetalol, administered intravenously or orally, has been effective in treatment of hypertension, with minimal effects on cardiac output. Labetalol will offer advantages over propranolol due to its more potent antihypertensive effects and less potent effects on left ventricular function at both rest and exercise in patients with coronary artery disease. The drug will be utilized in patients unresponsive to other β-blocking agents and in patients with congestive heart failure and concomitant hypertension, angina, or arrhythmias when other β-blockers are contraindicated. The drug appears to be safe in obstructive airway diseases and offers advantages over other β-blockers in long-term treatment after myocardial infarction.
Control of proliferation, endoreduplication and differentiation by the Arabidopsis E2Fa–DPa transcription factor

New plant cells arise at the meristems, where they divide a few times before they leave the cell‐cycle program and start to differentiate. Here we show that the E2Fa–DPa transcription factor of Arabidopsis thaliana is a key regulator determining the proliferative status of plant cells. Ectopic expression of E2Fa induced sustained cell proliferation in normally differentiated cotyledon and hypocotyl cells. The phenotype was enhanced strongly by the co‐expression of E2Fa with its dimerization partner, DPa. In endoreduplicating cells, E2Fa–DPa also caused extra DNA replication that was correlated with transcriptional induction of S phase genes. Because E2Fa–DPa transgenic plants arrested early in development, we argue that controlled exit of the cell cycle is a prerequisite for normal plant development.