Miracle-dz/UniFAR-FTUs huggingface dataset:
Model Checking Security APIs

Devices which operate on sensitive data are becoming an ever-increasing part of our lives, and we are placing a continually growing amount of trust in them. However, their ability to provide the proper level of data protection is typically only checked through analysis by hand. This method cannot be known to be complete, and as a result it can be possible to obtain data which should remain secret. It is only recently that formal methods have been applied to the analysis of such devices. We present results from the application of a model checker to the analysis of the API used by a number of security modules in Automated Teller Machine networks — IBM’s Common Cryptographic Architecture API. We show that it is capable of rediscovering all known attacks on the API, using models containing a greater set of API commands. We also analyse the set of recommendations released, in response to one of the discovered attacks, by IBM and show that, under certain assumptions, they do not prevent the attack. We use a revised set of assumptions, under which they do prevent the attack, to determine a number of our own recommendations aimed at the design and implementation of the API. Finally, we discuss various issues concerning the analysis of security APIs, based on our experiences of carrying out the work presented.
Taurine relaxes human radial artery through potassium channel opening action

The vascular actions and mechanisms of taurine were investigated in the isolated human radial artery (RA). RA rings were suspended in isolated organ baths and tension was recorded isometrically. First, a precontraction was achieved by adding potassium chloride (KCl, 45 mM) or serotonin (5-hydroxytryptamine, 5-HT, 30 µM) to organ baths. When the precontractions were stable, taurine (20, 40, 80 mM) was added cumulatively. Antagonistic effect of taurine on calcium chloride (10 µM to 10 mM)-induced contractions was investigated. Taurine-induced relaxations were also tested in the presence of the K+ channel inhibitors tetraethylammonium (1 mM), glibenclamide (10 µM) and 4-aminopyridine (1 mM). Taurine did not affect the basal tone but inhibited the contraction induced by 5-HT and KCl. Calcium chloride-induced contractions were significantly inhibited in the presence of taurine (20, 40, 80 mM) (p<0.05). The relaxation to taurine was inhibited by tetraethylammonium (p<0.05). However, glibenclamide and 4-aminopyridine did not affect taurine-induced relaxations. Present experiments show that taurine inhibits 5-HT and KCl-induced contractions in RA, and suggest that large conductance Ca2+-activated K+ channels may be involved in taurine-induced relaxation of RA.
Rapid Transient Production in Plants by Replicating and Non-Replicating Vectors Yields High Quality Functional Anti-HIV Antibody

Background The capacity of plants and plant cells to produce large amounts of recombinant protein has been well established. Due to advantages in terms of speed and yield, attention has recently turned towards the use of transient expression systems, including viral vectors, to produce proteins of pharmaceutical interest in plants. However, the effects of such high level expression from viral vectors and concomitant effects on host cells may affect the quality of the recombinant product. Methodology/Principal Findings To assess the quality of antibodies transiently expressed to high levels in plants, we have expressed and characterised the human anti-HIV monoclonal antibody, 2G12, using both replicating and non-replicating systems based on deleted versions of Cowpea mosaic virus (CPMV) RNA-2. The highest yield (approximately 100 mg/kg wet weight leaf tissue) of affinity purified 2G12 was obtained when the non-replicating CPMV-HT system was used and the antibody was retained in the endoplasmic reticulum (ER). Glycan analysis by mass-spectrometry showed that the glycosylation pattern was determined exclusively by whether the antibody was retained in the ER and did not depend on whether a replicating or non-replicating system was used. Characterisation of the binding and neutralisation properties of all the purified 2G12 variants from plants showed that these were generally similar to those of the Chinese hamster ovary (CHO) cell-produced 2G12. Conclusions Overall, the results demonstrate that replicating and non-replicating CPMV-based vectors are able to direct the production of a recombinant IgG similar in activity to the CHO-produced control. Thus, a complex recombinant protein was produced with no apparent effect on its biochemical properties using either high-level expression or viral replication. The speed with which a recombinant pharmaceutical with excellent biochemical characteristics can be produced transiently in plants makes CPMV-based expression vectors an attractive option for biopharmaceutical development and production.
Uptake and metabolism of N6-benzyladenine and 1-naphthaleneacetic acid and dynamics of indole-3-acetic acid and cytokinins in two callus lines of Actinidia deliciosa differing in growth and shoot organogenesis

Uptake, metabolism and accumulation of N 6 -benzyladenine (BA) and 1-naphthaleneacetic acid (NAA) as well as changes in endogenous indole-3-acetic acid (IAA) and several isoprenoid-type cytokinins (Cks) were characterized in two callus lines of Actinidia deliciosa cv. Hayward showing different growth and shoot organogenic responses to exogenously applied 2. 7μM NAA and 4. 4μM BA. Studies were carried out in callus 0, 1, 12, 24 and 48h after the onset of their fifth subculture on a medium containing [ 3 H]NAA or 8-[ 14 C]BA. Kiwifruit callus of line A presented high caulogenic response and lower growth that was positively associated with faster BA uptake, with transient accumulation of BA and isoprenoid-type Cks, mainly zeatin, exceeding three- and four-fold that of the non-caulogenic callus, and with values of the BA/NAA ratio exceeding 1, in fact higher than the BA/NAA ratio in the culture medium. The accumulation of BA took place in both callus lines during the first 24h of subculture and before the re-initiating of callus proliferation. The higher growth and the low or null caulogenic response shown by line B callus were correlated with faster NAA uptake, with endogenous NAA levels two-fold higher than in A calli, with higher IAA amounts and with values of the BA/NAA ratio below 1. Moreover, at 48h free NAA in both kinds of callus reached levels close to those found after 35 days of subculture. Results suggest that temporal accumulation of BA and endogenous Cks is involved in the initiation of cell division leading to callus growth, whereas the maintenance of high NAA and IAA levels are related to the support of long-term callus development. It also appears that for callus cells to become committed to shoot organogenesis, they must have a concentration of active Cks higher than a threshold value during the first 2 days of culture on fresh medium, while at the same time the concentration of auxins must not exceed a certain maximum.
Frequentist and Bayesian Pharmacometric-Based Approaches To Facilitate Critically Needed New Antibiotic Development: Overcoming Lies, Damn Lies, and Statistics

ABSTRACT Antimicrobial drug development has greatly diminished due to regulatory uncertainty about the magnitude of the antibiotic treatment effect. Herein we evaluate the utility of pharmacometric-based analyses for determining the magnitude of the treatment effect. Frequentist and Bayesian pharmacometric-based logistic regression analyses were conducted by using data from a phase 3 clinical trial of tigecycline-treated patients with hospital-acquired pneumonia (HAP) to evaluate relationships between the probability of microbiological or clinical success and the free-drug area under the concentration-time curve from time zero to 24 h (AUC0-24)/MIC ratio. By using both the frequentist and Bayesian approaches, the magnitude of the treatment effect was determined using three different methods based on the probability of success at free-drug AUC0-24/MIC ratios of 0.01 and 25. Differences in point estimates of the treatment effect for microbiological response (method 1) were larger using the frequentist approach than using the Bayesian approach (Bayesian estimate, 0.395; frequentist estimate, 0.637). However, the Bayesian credible intervals were tighter than the frequentist confidence intervals, demonstrating increased certainty with the former approach. The treatment effect determined by taking the difference in the probabilities of success between the upper limit of a 95% interval for the minimal exposure and the lower limit of a 95% interval at the maximal exposure (method 2) was greater for the Bayesian analysis (Bayesian estimate, 0.074; frequentist estimate, 0.004). After utilizing bootstrapping to determine the lower 95% bounds for the treatment effect (method 3), treatment effect estimates were still higher for the Bayesian analysis (Bayesian estimate, 0.301; frequentist estimate, 0.166). These results demonstrate the utility of frequentist and Bayesian pharmacometric-based analyses for the determination of the treatment effect using contemporary trial endpoints. Additionally, as demonstrated by using pharmacokinetic-pharmacodynamic data, the magnitude of the treatment effect for patients with HAP is large.
Multi-modality nuclear medicine imaging: artefacts, pitfalls and recommendations

Abstract Multi-modality imaging is rapidly becoming an essential tool in oncology. Clinically, the best example of multimodality imaging is seen in the rapid evolution of hybrid positron emission tomography (PET)/computed tomography (CT) and single positron emission computed tomography (SPECT)/CT scanners. However, use of multi-modality imaging is prone to artefacts and pitfalls. Important artefacts that may lead to clinical misinterpretation result from the use of CT data to correct for attenuation and the existence of mismatches between the fused images, for example due to respiratory movement. Furthermore, for institutions who proceed from a standalone PET to a hybrid PET-CT, there is an issue of interchangeability between these systems, especially for quantitative studies. Another issue is visualisation: hospital PACS is not sufficiently capable of adequately viewing integrated images. This article reviews and illustrates the most common artefacts and pitfalls that can be encountered in multi-modality nuclear medicine imaging. For correct management of oncological patients it is essential to be able to detect and correctly interpret these artefacts and pitfalls. Therefore, solutions and recommendations to these problems are provided.
Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma

There are a number of reports in literature data on the long-term outcomes of patients with multiple myeloma treated with high-dose therapy and autologous stem cell transplantation (HDT/SCT). While in general these data support the association between maximal tumor response and overall survival or progression-free survival after HDT/SCT, some trials have failed to find such correlation and there is no recent comprehensive literature analysis of this issue. We, therefore, performed a comprehensive literature review to identify prospective and retrospective studies on HDT/SCT in frontline multiple myeloma in which long-term outcomes were reported according to best tumor response observed. Following a prospectively defined search strategy we identified 21 studies (10 prospective and 11 retrospective studies) in which outcomes of 4,990 HDT/SCT patients according to their best tumor response were reported. The majority of these studies indicated a correlation between maximal response during or after HDT/SCT and long-term outcomes (overall survival and event-free/progression-free survival). The conclusions in individual studis report on the association between maximal response following induction therapy and long-term outcomes were more heterogeneous, possibly due to the low rate of complete response after standard induction therapy in each individual study. We, therefore, performed two types of meta-analyses, one based on the p-values reported for these associations in the individual studies, and one based on the primary response and outcome data provided in the individual studies. Both meta-analyses indicated highly significant associations between maximal response (complete response/near complete response/very good partial response) during or after HDT/SCT and long-term outcomes (overall survival and event-free/progression-free survival). Both meta-analyses also provided evidence of highly significant associations between maximal response following induction therapy and long-term outcomes (overall survival and event-free/progression-free survival).
Cyclic Nucleotide–Gated Channels

In voltage- and cyclic nucleotide–gated ion channels, the amino-acid loop that connects the S5 and S6 transmembrane domains, is a major component of the channel pore. It determines ion selectivity and participates in gating. In the α subunit of cyclic nucleotide–gated channels from bovine rod, the pore loop is formed by the residues R345–S371, here called R1-S27. These 24 residues were mutated one by one into a cysteine. Mutant channels were expressed in Xenopus laevis oocytes and currents were recorded from excised membrane patches. The accessibility of the substituted cysteines from both sides of the plasma membrane was tested with the thiol-specific reagents 2-aminoethyl methanethiosulfonate (MTSEA) and [2-(trimethylammonium)ethyl]methanethiosulfonate (MTSET). Residues V4C, T20C, and P22C were accessible to MTSET only from the external side of the plasma membrane, and to MTSEA from both sides of the plasma membrane. The effect of MTSEA applied to the inner side of T20C and P22C was prevented by adding 10 mM cysteine to the external side of the plasma membrane. W9C was accessible to MTSET from the internal side only. L7C residue was accessible to internal MTSET, but the inhibition was partial, ∼50% when the MTS compound was applied in the absence of cGMP and 25% when it was applied in the presence of cGMP, suggesting that this residue is not located inside the pore lumen and that it changes its position during gating. Currents from T15C and T16C mutants were rapidly potentiated by intracellular MTSET. In T16C, a slower partial inhibition took place after the initial potentiation. Current from I17C progressively decayed in inside-out patches. The rundown was accelerated by inwardly applied MTSET. The accessibility results of MTSET indicate a well-defined topology of the channel pore in which residues between L7 and I17 are inwardly accessible, residue G18 and E19 form the narrowest section of the pore, and T20, P21, P22 and V4 are outwardly accessible.
Staphylococcus aureus Protein A Promotes Immune Suppression

ABSTRACT Staphylococcus aureus is a prominent cause of human infections worldwide and is notorious for its ability to acquire resistance to antibiotics. Methicillin-resistant S. aureus (MRSA), in particular, is endemic in hospitals and is the most frequent cause of community-associated bacterial infections in the United States. Inasmuch as treatment options for severe MRSA infections are limited, there is need for a vaccine that protects against such infections. However, recent efforts to generate a staphylococcal vaccine have met with little success in human clinical trials. These failures are somewhat puzzling, since the vaccine antigens tested promote opsonophagocytosis in vitro and confer protection in animal infection models. One possibility is that the pathogen inhibits (and/or fails to elicit) the development of protective immunity in humans. Indeed, S. aureus produces numerous molecules that can potentially promote immune evasion, including protein A (SpA), an immunoglobulin (Ig)-binding protein present on the bacterial surface and freely secreted into the extracellular environment. SpA binds the Fc region of antibody and the Fab regions of the B-cell receptor, processes that are known to block opsonophagocytosis and cause B-cell death in vitro. In a recent study, Falugi et al. [F. Falugi, H. K. Kim, D. M. Missiakas, and O. Schneewind, mBio 4(5):e00575-13, 2013] showed that vaccination with spa mutant S. aureus strains lacking antibody Fc- and/or Fab-binding capacity protects against subsequent challenge with the USA300 epidemic strain. The findings provide strong support for the idea that SpA promotes S. aureus immune evasion in vivo and form the foundation for a new approach in our efforts to develop a vaccine that prevents severe S. aureus infections.
Amphibians as Indicators of Early Tertiary "Out-of-India" Dispersal of Vertebrates

Sixty-five million years ago, massive volcanism produced on the India-Seychelles landmass the largest continental lava deposit (Deccan Traps) of the past 200 million years. Using a molecular clock–independent approach for inferring dating information from molecular phylogenies, we show that multiple lineages of frogs survived Deccan Traps volcanism after millions of years of isolation on drifting India. The collision between the Indian and Eurasian plates was followed by wide dispersal of several of these lineages. This “out-of-India” scenario reveals a zoogeographical pattern that might reconcile paleontological and molecular data in other vertebrate groups.
Level crossing rate and average fade duration for pure selection and threshold selection diversity‐combining systems

Exact and closed‐form expressions for the level crossing rate and average fade duration are presented for the M‐branch Pure Selection Combining and for the two‐branch Threshold Selection Combining schemes, assuming independent branches in a Rayleigh environment. The analytical results are thoroughly validated by reducing the general case to some special cases, for which the solutions are known, and by means of simulation for the more general case. The plots presented here are also compared with those of the general solution recently published for the Equal Gain and Maximal Ratio Combining and an agreeable coherence is found. Copyright © 2001 John Wiley & Sons, Ltd.
Emergent bimodal firing patterns implement different encoding strategies during gamma-band oscillations

Upon sensory stimulation, primary cortical areas readily engage in narrow-band rhythmic activity between 30 and 90 Hz, the so-called gamma oscillations. Here we show that, when embedded in a balanced network, type-I excitable neurons entrained to the collective rhythm show a discontinuity in their firing-rates between a slow and a fast spiking mode. This jump in the spiking frequencies is characteristic to type II neurons, but is not present in the frequency-current curve (f-I curve) of isolated type I neurons. Therefore, this rate bimodality arises as an emerging network property in type I population models. We have studied the mechanisms underlying the generation of these two firing modes, in order to reproduce the spiking activity of in vivo cortical recordings, which is known to be highly irregular and sparse. We have also analyzed the relation between afferent inputs and the single unit activity, and between the latter and the local field potential (LFP) phase, in order to establish how the collective dynamics modulates the spiking activity of the individual neurons. Our results reveal that the inhibitory-excitatory balance allows two encoding mechanisms, for input rate variations and LFP phase, to coexist within the network.
Elements of a Plan-Based Theory of Speech Acts

This paper explores the truism that people think about what they say. It proposes hat, to satisfy their own goals, people often plan their speech acts to affect their listeners' beliefs, goals, and emotional states. Such language use can be modelled by viewing speech acts as operators in a planning system, thus allowing both physical and speech acts to be integrated into plans. Methodological issues of how speech acts should be defined in a plan-based theory are illustrated by defining operators for requesting and informing. Plans containing those operators are presented and comparisons are drawn with Searle's formulation. The operators are shown to be inadequate since they cannot be composed to form questions (requests to inform) and multiparty requests (requests to request). By refining the operator definitions and by identifying some of the side effects of requesting, compositional adequacy is achieved. The solution leads to a metatheoretical principle for modelling speech acts as planning operators.
Interannual variations of tropical precipitation patterns

Abstract Seasonal and annual precipitation anomalies, normalized with respect to the standard deviations, are computed for stations between 30°S and 30°N. It is established that the annual anomalies are normally distributed. Spatially averaged anomalies are computed for various regions and their representativeness confirmed. Correlations between the annual average normalized anomalies of the various regions are computed. The results show that simultaneous variations of the zonally oriented circulations of the tropical troposphere occur which are in phase with variations of the Southern Oscillation. The concurrent variations of the intensity of the zonal cells account for most of the observed interannual rainfall variations. Interannual variations in the intensity and position of the meridional Hadley cell seem to play only a minor role.
Mixotrophic basis of Atlantic oligotrophic ecosystems

Oligotrophic subtropical gyres are the largest oceanic ecosystems, covering >40% of the Earth's surface. Unicellular cyanobacteria and the smallest algae (plastidic protists) dominate CO2 fixation in these ecosystems, competing for dissolved inorganic nutrients. Here we present direct evidence from the surface mixed layer of the subtropical gyres and adjacent equatorial and temperate regions of the Atlantic Ocean, collected on three Atlantic Meridional Transect cruises on consecutive years, that bacterioplankton are fed on by plastidic and aplastidic protists at comparable rates. Rates of bacterivory were similar in the light and dark. Furthermore, because of their higher abundance, it is the plastidic protists, rather than the aplastidic forms, that control bacterivory in these waters. These findings change our basic understanding of food web function in the open ocean, because plastidic protists should now be considered as the main bacterivores as well as the main CO2 fixers in the oligotrophic gyres.
Hanf Locality and Invariant Elementary Definability

We introduce some notions of invariant elementary definability which extend the notions of first-order order-invariant definability, and, more generally, definability invariant with respect to arbitrary numerical relations. In particular, we study invariance with respect to expansions which depend not only on (an ordering of) the universe of a structure, but also on the particular relations which determine the structure; we call such expansions presentations of a structure. We establish two locality results in this context. The first is an extension of the original Hanf Locality Theorem to boolean queries which are invariantly definable over classes of locally finite structures with respect to elementary, neighborhood-bounded presentations. The second is a non-uniform version of the Fagin-Stockmeyer-Vardi Hanf Threshold Locality Theorem to boolean queries which are invariantly definable over classes of bounded degree structures with respect to elementary, neighborhood-bounded, local presentations.