Miracle-dz/UniFAR-FTUs huggingface dataset:
Influenza A Virus Panhandle Structure Is Directly Involved in RIG-I Activation and Interferon Induction

ABSTRACT Retinoic acid-inducible gene I (RIG-I) is an important innate immune sensor that recognizes viral RNA in the cytoplasm. Its nonself recognition largely depends on the unique RNA structures imposed by viral RNA. The panhandle structure residing in the influenza A virus (IAV) genome, whose primary function is to serve as the viral promoter for transcription and replication, has been proposed to be a RIG-I agonist. However, this has never been proved experimentally. Here, we employed multiple approaches to determine if the IAV panhandle structure is directly involved in RIG-I activation and type I interferon (IFN) induction. First, in porcine alveolar macrophages, we demonstrated that the viral genomic coding region is dispensable for RIG-I-dependent IFN induction. Second, using in vitro-synthesized hairpin RNA, we showed that the IAV panhandle structure could directly bind to RIG-I and stimulate IFN production. Furthermore, we investigated the contributions of the wobble base pairs, mismatch, and unpaired nucleotides within the wild-type panhandle structure to RIG-I activation. Elimination of these destabilizing elements within the panhandle structure promoted RIG-I activation and IFN induction. Given the function of the panhandle structure as the viral promoter, we further monitored the promoter activity of these panhandle variants and found that viral replication was moderately affected, whereas viral transcription was impaired dramatically. In all, our results indicate that the IAV panhandle promoter region adopts a nucleotide composition that is optimal for balanced viral RNA synthesis and suboptimal for RIG-I activation. IMPORTANCE The IAV genomic panhandle structure has been proposed to be an RIG-I agonist due to its partial complementarity; however, this has not been experimentally confirmed. Here, we provide direct evidence that the IAV panhandle structure is competent in, and sufficient for, RIG-I activation and IFN induction. By constructing panhandle variants with increased complementarity, we demonstrated that the wild-type panhandle structure could be modified to enhance RIG-I activation and IFN induction. These panhandle variants posed moderate influence on viral replication but dramatic impairment of viral transcription. These results indicate that the IAV panhandle promoter region adopts a nucleotide composition to achieve optimal balance of viral RNA synthesis and suboptimal RIG-I activation. Our results highlight the multifunctional role of the IAV panhandle promoter region in the virus life cycle and offer novel insights into the development of antiviral agents aiming to boost RIG-I signaling or virus attenuation by manipulating this conserved region.
STATISTICS IN THE PRACTICE OF MEDICINE.

PRACTICING PHYSICIANS and statisticians may not seem to have many mutual interests, but perhaps they have more in common than is apparent at first. The purpose of this article is to describe a few statistical tools and to illustrate how these tools may be useful in the practice of medicine. As a starting point, consider a fairly frequently encountered medical problem, diabetes mellitus. According to some physicians, they believe that diabetics are best maintained at slightly elevated blood-glucose levels, but others feel that they should be maintained within limits of clinical normality. Which group is right or are they both right? And what is clinical normality and how is it determined? Suppose we consider the question of clinical normality first, partly because it is relatively easy to discuss and partly because it is a portion of the problem of maintaining diabetics in control. Normal Values According to one textbook, 1
Antepartum Depressive Symptomatology Is Associated With Adverse Obstetric and Neonatal Outcomes

Objective The purpose of this study was to examine if depressive symptomatology in pregnancy is associated with adverse obstetric and neonatal outcomes. Method In a prospective observational study, 959 women were followed up longitudinally from early pregnancy to postpartum. The level of depression was measured at baseline (first antepartum visit) and in late pregnancy using the Beck Depression Inventory (BDI). Adverse obstetric and neonatal outcomes were recorded at delivery. Results Depression in late pregnancy was associated with increased risk of epidural analgesia (33% vs. 19%, p = .01, adjusted RR = 2.56, 95% CI 1.24–5.30), operative deliveries (caesarean sections and instrumental vaginal deliveries) (39% vs. 27%, p = .02, adjusted RR = 2.28, 95% CI 1.15–4.53), and admission to neonatal care unit (24% vs. 19%, p = .03, adjusted RR = 2.18, 95% CI 1.02–4.66). These effects remained significant even when controlled for potential confounders, such as antepartum complications. Conclusion Previous studies have shown that antepartum anxiety or stress was associated with growth retardation, premature delivery, and epidural analgesia. Our findings add to this body of evidence, which together suggest an adverse impact of antepartum psychological morbidity on maternal and neonatal well-being.
Resource Virtualization with Programmable Radio Processing Platform ( Invited Paper )

As wireless communication moves to all IP and packet based processing, the virtualization techniques will need to be introduced to provide common interface to higher layers which will hide the necessary details for resource reservations and sharing. In the circuit switched world the communication resources are guarantied with the allocation of channels that satisfy certain bandwidth requirements, where the allocated bandwidth is taken regardless of the actual utilization. In the IP packet based world the reservations have a soft form with statistical guaranties allowing dynamic sharing of bandwidth, while the bandwidth is requested by setting the Service Level Agreement (SLA) parameters. Setting up SLA parameters and monitoring their compliance can take complex forms, so it is advantageous to abstract the SLA related communication from the higher networking layers and shield them from the changes in the environment and system load. The virtualization is even more important for the reconfigurable and programmable devices suitable for cognitive radio applications. The changes in frequency band, modulation scheme, or other baseband and MAC protocols characteristics need to be monitored by the virtualization layer which is responsible for mapping original SLA of each flow to the new settings. We present the novel programmable radio processing platform architecture framework, Virtual Flow Pipelining – FVP, which has underlying mechanisms for per flow performance guaranties. The SLA guaranties are enforced per flow using the scheduling mechanisms that will allocate proportional share of each hardware resource to the flow. The allocations of the resource share to the flow create the Virtual Flow consisting of the sequence of processing steps on the required processing modules. The wireless protocol processing often imposes end to end latency requirements for the whole processing flow, so the resource scheduler need to take the full flow latency into account as well. General Terms Design, Economics, Experimentation
WIN51711-resistant mutants of poliovirus type 3: capsid residues important in uncoating functions.

Capsid-binding drugs that inhibit the first stage of picornaviral uncoating were used to select drug-resistant mutants of the Sabin strain of poliovirus type 3. Such mutants provide information about parts of the capsid that are important for functions blocked by the drugs, and also about pathways to drug resistance. Amino-acid substitutions allowing virus to produce progeny in the presence of drug were mapped to 13 different residues occupying three distinct locations: (I) the canyon base; (II) the lining of the drug-binding pocket; and (III) the base of the protomer. These loci might be thought of as action points for transmitting the uncoating signal from receptor, through the pocket, and to the base of the protomer. All of the mutations in a special class of drug-dependent mutants were clustered at site (III) and all were hyperlabile, i.e., uncoated spontaneously (without receptor) at growth temperature unless prevented from doing so by the presence of drug in the pocket. Thus, site (III) seems to represent a kind of thermostat which regulates the temperature at which the uncoating transition (release of VP4 to form A particles) is triggered.
The RNA-Binding Proteins Zfp36l1 and Zfp36l2 Enforce the Thymic β-Selection Checkpoint by Limiting DNA Damage Response Signaling and Cell Cycle Progression

The RNA-binding proteins Zfp36l1 and Zfp36l2 act redundantly to enforce the β-selection checkpoint during thymopoiesis, yet their molecular targets remain largely unknown. In this study, we identify these targets on a genome-wide scale in primary mouse thymocytes and show that Zfp36l1/l2 regulate DNA damage response and cell cycle transcripts to ensure proper β-selection. Double-negative 3 thymocytes lacking Zfp36l1/l2 share a gene expression profile with postselected double-negative 3b cells despite the absence of intracellular TCRβ and reduced IL-7 signaling. Our findings show that in addition to controlling the timing of proliferation at β-selection, posttranscriptional control by Zfp36l1/l2 limits DNA damage responses, which are known to promote thymocyte differentiation. Zfp36l1/l2 therefore act as posttranscriptional safeguards against chromosomal instability and replication stress by integrating pre-TCR and IL-7 signaling with DNA damage and cell cycle control.
The effects of melatonin treatment on wool production and hair follicle cycle in angora rabbits

The aims of this study were to examine the effect of melatonin treatment on (1) the quantity of wool production and fibre quality traits, (2) feed consumption and body weight and (3) hair follicle activity in the German angora rabbits. The study involved 106 male and female angora rabbits (raised under natural photoperiod), between the initial ages of 200-210 days. Half of the stock was treated with melatonin (36 mg per rabbit) either in May prior to the summer solstice, or in July subsequent to the solstice. Other animals served as untreated controls. In May two meth- ods of wool harvesting: defleecing or shearing, were tested, while in July two different intervals between wool harvests, 98 and 80 days, were compared. Skin samples were taken from May on- wards six times during the experimental period. Melatonin treatment increased significantly total wool production (by 17.7%, P < 0.01), weight of first grade wool (by 14.1%, P < 0.01), fibre length (by 5.6%, P < 0.001), wool production per day (by 17.3%, P < 0.01) and per kg of live weight (by 14.6%, P < 0.05). The melatonin treatment also led to a significant increase in feed consumption and body weight during the first weeks following melatonin treatment. Melatonin treatment did not exert any significant effect on the content of the different fibre types, or on bristle dimensions (area and diam- eter), but resulted in a 32% ( P < 0.001) increase in the number of active follicles (lateral primaries and secondaries) per hair follicle group. The date of treatment had a significant influence on the quantity of first grade wool with higher production observed only when animals are treated in July. The treat- ment proved to be more effective in the defleeced rabbits than in the shorn ones. melatonin / angora rabbit / wool production / fibre characteristic/ hair follicle activity
Physical Modeling by Directly Solving Wave PDE

We are currently developing a physical modeling method for string instruments based upon the direct solution of the string equation, rather than the simulation of travelling waves as is instead done in the Waveguide method. Although computationally heavier in comparison with Waveguides, our approach enables any physical parameter to be time-varied during playing, obtaining thus interesting effects from a musical viewpoint. Particular attention has been paid in the modeling of the bow, which is the main responsible of the peculiar timbre of bowed strings. The rosin thermal behaviour has been modelled by thresholds. Moreover, the bowing noise is simulated by adding noise to the bow force profile. The whole model runs in real time on today Wintel Workstations for bowed string of the violin or viola class. It produces good sounds not only in sustained, gently bowed articulations, but also in harsh articulations like e.g. "strappato", as well as outside the physically possible parameters zone. The model has been actually used with a primary role by the Italian Composer Michelangelo Lupone in two newly composed electronic and mixed music pieces. Glissandos of string parameters – like f.i. the internal damping and displacements of the bowing point play a main expressive role in these works. The novelty in the string equation we used is a partial third-order derivative mixed term describing the internal friction of the string, which is responsible of the frequency-dependent damping in actual strings. The free-motion analytic solutions of the corresponding PDE is discussed, together to the numerical integration method developed (based on a combination of the sinus transform, and of the well-known Stoermer rule), whose results are analysed from a timbre point of view. We also show a short comparison with Waveguides, and future improvements to continuously varying bowing point and left-hand finger position, and to reduce both asymptotic and actual computational complexity.
An oracle characterization of the counting hierarchy

Certain properties of the polynomial-time counting hierarchy (CH) introduced by K. Wagner (1986) are investigated. The closure under Boolean operations of the classes in CH is studied, and a characterization of the hierarchy in terms of nondeterministic and probabilistic machines with access to oracles is proved. The concept of lowness is extended to the classes in CH, providing a way to characterize the sets that are low for the class PP using ranking functions. Some other connections are found between ranking functions and low sets for PP, showing that if a class in the hierarchy is Hash P-rankable, then it is low for PP.<<ETX>>
Offshoring procesów opartych na wiedzy – analiza eksportu usług

Summary: This article analyzes selected factors regarding the potential of innovative economy, resources, costs and productivity of the workforce as well as investments in R&D. On this basis, an attempt was made to assess the relationship between these factors and the export of knowledge-based services, as well as the export of a group of services named as business services based on knowledge distinguished by the author. These services were considered as a sign of off-shoring of non-production processes. The empirical study made it possible to identify the factors that highly affect the country’s share in international supply networks, i.e. conducive to improve the attractiveness of the economy as a place for locating knowledge-in-tensive processes as part of offshoring.
A Stochastic Geometry Approach to the Rate of Downlink Cellular Networks over Correlated Log-Normal Shadowing

In this paper, an analytical framework to compute the average rate of downlink heterogeneous cellular networks is introduced. The framework exploits the so-called Poisson Point Process (PPP-) based abstraction model for the positions of the Base Stations (BSs), and results from stochastic geometry for other-cell interference modeling and performance analysis are used. The contribution of the present paper is twofold. 1) A simplified framework is proposed, which avoids the computation of the Meijer G-function and is applicable to arbitrary path-loss exponents. The new mathematical approach relies upon the Anderssen et al. sum of exponentials approximation for the Kohlrausch function. 2) The framework is applicable to correlated log-normal shadowing. The new mathematical approach relies upon the Owen and Steck method for the generation of equi-correlated multivariate normal distributions. The frameworks are substantiated through extensive Monte Carlo simulations, and numerical examples show that: i) for low Signal-to-Noise-Ratios (SNRs), the average rate slightly decreases if shadowing correlation increases; and ii) for high-SNRs, the average rate increases if shadowing correlation increases.
Effect of Platelet‐Activating Factor on the Process of Cellular Differentiation of Herpetomonas muscarum muscarum

ABSTRACT. The effects of platelet‐activating factor (PAF), at doses ranging from 10−6 M to 10−10 M, on cell growth and on cell differentiation of Herpetomonas muscarum muscarum were investigated. Cell differentiation was evaluated by both light and electron microscopy. At the concentrations used, PAF did not interfere with the protozoan growth. However, parasites grown in the presence of PAF (10−6 M) were significantly more differentiated than those grown in the absence of PAF, since the first day of culture. On the first two days of culture, PAF doses ranging from 10−10 M to 10−7 M, did not significantly interfere with the differentiation of these parasites, although after the third day of culture, all PAF doses used significantly increased the protozoan differentiation. Specific PAF receptor antagonists totally abrogated (WEB 2086 and WEB 2170)or significantly decreased (BN 52021) PAF effect on cell differentiation. These findings indicate PAF triggers the process of cell differentiation in Herpetomonas muscarum muscarum and suggest these parasites have receptors for PAF.
Comparison of two methods for determining in vitro postantibiotic effects of three antibiotics on Escherichia coli

The postantibiotic effect (PAE) for 10 isolates of Escherichia coli was measured by two methods after 1 h of exposure to ampicillin, ciprofloxacin, or tobramycin. The reference method involved serial colony counting to determine growth after antibiotic exposure in relation to control growth. A spectrophotometric procedure was developed with the Abbott MS-2 research system. This method measured the time to detection of growth after exposure and compared this with the time for growth detection in control chambers having the same initial colony count. A reference curve of time to growth versus log initial CFU per milliliter was used to standardize control growth. PAE was determined after exposure to antibiotic at two and six times the MIC and with inocula ranging from 10(3) to 10(9) CFU/ml. There was a statistically significant correlation between PAE measured by the spectrophotometric and the reference methods, and the residuals about the regression line were normally distributed. The mean PAE determined by both methods was statistically different for tobramycin-exposed, but not for ampicillin- or ciprofloxacin-exposed, organisms. There was a concentration-dependent PAE for ciprofloxacin and tobramycin. The PAEs for ciprofloxacin (151 min) and tobramycin (108 min) at concentrations six times the MIC were prolonged compared with those measured at two times the MIC (69 and 66 min, respectively). PAE was inversely related to the exposed inoculum for ciprofloxacin and tobramycin. The PAE for E. coli exposed to ampicillin was minimal and was not affected by either concentration or inoculum. The MS-2 method for determining PAE yields similar results, but is less laborious than the reference method.
A comparative study of tuberculosis mortality rates

The recorded mortality from tuberculosis has fallen greatly in England and Wales since the middle of the nineteenth century when records were first available. The fall in rate has not occurred uniformly in all age groups however, and one result of this is that the maximum mortality rate in males is now occurring at a much later period of life than formerly.
Perfusion MRI: the five most frequently asked clinical questions.

OBJECTIVE This article addresses questions that radiologists frequently ask when planning, performing, processing, and interpreting MRI perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and neurodegenerative diseases. Most of the impediments that have limited the use of per-fusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols.
Illicit Drugs and the Decline of the Middle Class

Empirical evidence for the U.S. suggests that the consumption of intoxicants increases in association with the socio-economic deprivation of the middle-class. To explore the underlying mechanisms, we set up a task-based labor market model with endogenous mental health status and a health care system. The decline of tasks that were historically performed by the middle class and the associated decline in relative wages and socio-economic status increases the share of mentally ill middle class workers. Mentally ill workers can mitigate their hardships by the intake of illicit drugs or by consuming health goods. We argue that explaining the drug epidemic of the U.S. middle class requires an interaction of socio-economic decline and falling opioid prices. One factor in isolation is typically insufficient. Our analysis also points to a central role of the health care system. In our model, extending mental health care could motivate the mentally ill to abstain from illicit drug consumption.
The role of networks in business model innovation : three shaping processes supporting cognitive shifts

Stakeholders and in particular customers are an important source for business model innovation. Especially for sustainable business models, stakeholder integration may radically change the business logic and help to revise the business model. In this process cognition plays a central role, challenging basic assumptions and changing the dominant logic. In this paper we explore how interactions with the network contribute to making a cognitive shift in development of a sustainable business model. We build on three cases and closely look at the commercialisation stage in which a change of cognition and redesign of the business model take place. Our findings show that network interaction changes the dominant logic in business model innovation in two ways: by triggering a cognitive shift and by contributing to business model redesign. Our main contribution is the conceptualization of three interrelated shaping processes: market approach shaping, product/service offering shaping and credibility shaping. They provide a fine-grained perspective on value creation through collaborative networks and add to the business model literature by providing a framework to study the role of networks and cognition in business model innovation. For practitioners the shaping processes may support business model redesign and building relationships to advance commercialisation of sustainability-oriented innovations.
The many faces of evil : historical perspectives

1. From Disobedience to Disorder Includes readings: The Ancient Egyptian Book of the Dead, The Old Testament, Thucydides, Seneca, Hans Jonas, Gershon Scholem 2. From Sin to Vice St Augustine, Abu Hamid Al-Ghazli, Peter Abelard, Moses Maimonides, Pope Innocent III, Aquinas, Dante, Chaucer 3. Evil as Wilfullness Luther, Calvin, Milton, Jonathan Edwards 4. Containing Lawlessness Machiavelli, Hobbes, Butler 5. The Irrationality of Waywardness Leibniz, Manderille, Voltaire, Rousseau, Kant 6. The Romanticism of Evil Goethe, Blake, Hawthorne, Baudelaire, Schopenhauer, Nietzsche 7. The Banality of Evil: The Cruelty of Everday Life Dostoyevsky, Engels, Einstein, Freud, Hannah Arendt, Michael Stocker, Amelie Rorty, Amos Oz 8. Conflict, Immorality and Crime 'War and Murder', Elizabeth Anscombe 'Political Action: The Problem of Dirty Hands', Michael Walzer 'The Nature of Immortality', Jean Hampton