Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety Evaluation of EXPAREL (DepoFoam Bupivacaine) Administered by Repeated Subcutaneous Injection in Rabbits and Dogs: Species Comparison

EXPAREL (bupivacaine extended-release liposome injection), DepoFoam bupivacaine, is in development for prolonged postsurgical analgesia. Repeat-dose toxicity studies were conducted in rabbits and dogs to compare the potential local and systemic toxicities of EXPAREL and bupivacaine HCl (Bsol), and the reversibility of any effects. Dogs tolerated much larger doses than rabbits. EXPAREL-related minimal-to-moderate granulomatous inflammation was noted at the injection sites. In recovery animals, the granulomatous inflammation was observed less frequently and was characterized by an increased number of multinucleated giant cells. These effects were considered a normal response to liposomes and nonadverse. Rabbits are more sensitive than dogs. In rabbits, convulsions were noted with EXPAREL and more frequently with Bsol; a NOAEL was not identified. In dogs, EXPAREL was well tolerated (NOAEL > 30 mg/kg/dose). The cumulative exposure of EXPAREL in these studies is well in excess of the proposed maximum single-dose exposure that is intended in humans.
Analysis of the Pathogenetic Basis for Shedding and Transmission of Ovine Gamma Herpesvirus 2

ABSTRACT Ovine herpesvirus 2 (OvHV-2), a member of the viral subfamily Gammaherpesvirinae, shares numerous similarities with human herpesvirus 8 (HHV-8). Both viruses are apathogenic in their healthy original host, may cause lymphoprolipherative diseases, cannot routinely be propagated in cell culture, and may be sexually transmitted. However, the pathways of sexual transmission of these viruses, as well as the underlying pathogenetic dynamics, are not well understood. Organs from naturally OvHV-2-infected, as well as OvHV-2-free, sheep were quantitatively analyzed for OvHV-2 by the DNA amplification techniques. The dynamics of OvHV-2 multiplication and excretion were monitored after experimental infections and, most importantly, subsequent to vasectomy. The OvHV-2 DNA load in various tissues and internal organs was not merely reflecting the viral DNA load in the bloodstream, which suggested compartmentalization of OvHV-2. Moreover, OvHV-2 DNA was detected at several portals for virus shedding, i.e., the respiratory, alimentary, and urogenital tracts. Transient OvHV-2 excretion was detected in ejaculates of experimentally infected rams. Upon vasectomy, OvHV-2 DNA reappeared in the ejaculatory plasma, but the titers did not decline after reaching a peak. Spiking and fractionation experiments revealed an inhibitory activity, associated with the spermatozoa, which was able to suppress detection of viral DNA but which was no longer present in samples from vasectomized animals. Therefore, epidemiological studies on viruses that may be transmitted by the ejaculatory pathway and for whose tracing nucleic acid amplification methods are used, i.e., OvHV-2, HHV-8, and the human immunodeficiency virus, should include vasectomized males.
Logarithmic torus amplitudes

AbstractFor the example of the logarithmic triplet theory at c = −2 the chiral vacuumtorus amplitudes are analysed. It is found that the space of these torus amplitudes isspanned by the characters of the irreducible representations, as well as a function thatcan be associated to the logarithmic extension of the vacuum representation. A fewimplications and generalisations of this result are discussed. 1. Introduction. During the last twenty years much has been understood about the struc-ture of rational conformal ﬁeld theories. Rational conformal ﬁeld theories are characterisedby the property that they have only ﬁnitely many irreducible highest weight representationsof the chiral algebra (or vertex operator algebra), and that every highest weight represen-tation is completely decomposable into irreducible representations. The structure of thesetheories is well understood: in particular, the characters of the irreducible representationstransform into one another under modular transformations [1] (see also [2]), and the modularS-matrix determines the fusion rules via the Verlinde formula [3]. (A general proof for thishas only recently been given in [4].)On the other hand, it is clear that rational conformal ﬁeld theories are rather special, andit is therefore important to understand the structure of more general classes of conformalﬁeld theories. One such class are the (rational) logarithmic theories that possess only ﬁnitelymany indecomposable representations, but for which not all highest weight representationsare completely decomposable. The name ‘logarithmic’ comes from the fact that their chiralcorrelation functions typically have logarithmic branch cuts. The ﬁrst example of a (non-rational) logarithmic conformal ﬁeld theory was found in [5] (see also [6]), and the ﬁrstrational example (that shall also concern us in this paper) was constructed in [7]; for somerecent reviews see [8, 9, 10]. From a physics point of view, logarithmic conformal ﬁeldtheories appear naturally in various models of statistical physics, for example in the theory
The effects of asymmetry on TCP performance

In this paper, we study the effects of network asymmetry on end‐to‐end TCP performance and suggest techniques to improve it. The networks investigated in this study include a wireless cable modem network and a packet radio network, both of which can form an important part of a mobile ad hoc network. In recent literature (e.g., [18]), asymmetry has been considered in terms of a mismatch in bandwidths in the two directions of a data transfer. We generalize this notion of bandwidth asymmetry to other aspects of asymmetry, such as latency and media‐access, and packet error rate, which are common in wide‐area wireless networks. Using a combination of experiments on real networks and simulation, we analyze TCP performance in such networks where the throughput achieved is not solely a function of the link and traffic characteristics in the direction of data transfer (the forward direction), but depends significantly on the reverse direction as well. We focus on bandwidth and latency asymmetries, and propose and evaluate several techniques to improve end‐to‐end performance. These include techniques to decrease the rate of acknowledgments on the constrained reverse channel (ack congestion control and ack filtering), techniques to reduce source burstiness when acknowledgments are infrequent (TCP sender adaptation), and algorithms at the reverse bottleneck router to schedule data and acks differently from FIFO (acks‐first scheduling).
An FSM based GUI test automation model

Graphical User Interfaces (GUIs) constitute a large proportion of today's software and are becoming more and more complex. Testing the correctness of GUIs and their underlying software is paramount for providing quality software products. Manual testing is extremely slow and unacceptably expensive. We present a new technique which enables the process of generating test cases and testing automation, based on an innovative model. Given a GUI based application, the set of GUI states and their running logic is modeled as a finite state machine (FSM). The efficiency of the model is formally analyzed and compared with event flow graph (EFG) model. The results show that our model is more efficient in storage.
ShareVR: Enabling Co-Located Experiences for Virtual Reality between HMD and Non-HMD Users

Virtual reality (VR) head-mounted displays (HMD) allow for a highly immersive experience and are currently becoming part of the living room entertainment. Current VR systems focus mainly on increasing the immersion and enjoyment for the user wearing the HMD (HMD user), resulting in all the bystanders (Non-HMD users) being excluded from the experience. We propose ShareVR, a proof-of-concept prototype using floor projection and mobile displays in combination with positional tracking to visualize the virtual world for the Non-HMD user, enabling them to interact with the HMD user and become part of the VR experience. We designed and implemented ShareVR based on the insights of an initial online survey (n=48) with early adopters of VR HMDs. We ran a user study (n=16) comparing ShareVRto a baseline condition showing how the interaction using ShareVR led to an increase of enjoyment, presence and social interaction. In a last step we implemented several experiences for ShareVR, exploring its design space and giving insights for designers of co-located asymmetric VR experiences.
Configuring effective navigation models and abstract test cases for web applications by analysing user behaviour

As web applications become more complex and are used more pervasively, testing demands are increasing without corresponding automated support. One promising approach to automatic test generation is statistical model‐based testing, where logged user behaviour is used to build a usage‐based model of web application navigation, from which abstract test cases are generated. Executable test cases are then created by adding parameter values to the abstract test cases. Several researchers have proposed variations of this approach; however, no one has empirically examined the tradeoffs and implications of the different ways to represent user behaviour in a navigation model and the characteristics of the test cases automatically generated from different models. This paper reports on our exploratory study of automatically generated abstract test cases and the underlying usage‐based navigation models constructed from over 19,000 user sessions across five publicly deployed web applications. Our results suggest how web testers can easily configure statistical model‐based automatic test case generators for web applications toward generating tests closely related to user behaviour or toward new navigations without using large additional test resources. Copyright © 2013 John Wiley & Sons, Ltd.
Enamel thickness and the helicoidal occlusal plane.

In the present study 38 unworn maxillary molars (M1 = 16, M2 = 12, M3 = 10) of modern humans from a Slavic necropolis were sectioned through the mesial cusps in a plane perpendicular to the cervical margin of the crown. Five slightly worn M1s and one slightly worn M3 were also used thus increasing the total sample to 44, but measurements made on the worn areas were coded as missing values. Seven measurements of enamel thickness as well as the heights of the protocone and the paracone dentine horns were recorded in order to analyze whether changes in these dimensions in anteroposterior direction can be related to the helicoidal occlusal plane. Uni- and multivariate analyses revealed that the distribution of enamel thickness within and between maxillary molars corresponds to a helicoidal occlusal wear pattern. Enamel thickness along the occlusal basin increases from anterior to posterior, which may lead to rapid development of a reverse curve of Monson in first molars when compared to posterior teeth. However, although these overall differences together with the serial, especially delayed eruption pattern of human molars, contribute to the marked expression of the helicoidal occlusal plane in Homo, differences in enamel patterning between molars indicate that a helicoidal plane is a structural feature of the orofacial skeleton. In contrast to first upper molars, second and third molars show absolutely and relatively thicker enamel under the Phase I wear facet of the paracone, i.e., the lingual slope of the paracone, than under the Phase II facet of the protocone, i.e., the buccal slope of that cusp. These proportional differences are most pronounced in M3, as evidenced by uni- and multivariate statistics. It thus appears that the pattern of enamel thickness distribution from M1 to M3 follows a trend towards providing additional tooth material in areas that are under greater functional demands, that is, corresponding to a lingual slope of wear anteriorly and to a flat or even buccal one posteriorly. In addition, the heights of the dentine horns in anteroposterior direction change in a way that lends support to the hypothesis that the axial inclination of teeth could be one of the most important factors for the development of the helicoidal occlusal plane. Finally, the changes in morphology and enamel thickness distribution from first to third upper molars found in this study suggest that molars could be "specialized" in their function, i.e., from performing proportionally more shearing anteriorly to increased crushing and grinding activities posteriorly.
Negotiation as Mutual Belief Revision

This paper presents a logical framework for negotiation based on belief revision theory. We consider that a negotiation process is a course or multiple courses of mutual belief revision. A set of AGM-style postulates are proposed to capture the rationality of competitive and cooperative behaviors of negotiation. We first show that the AGM revision and its iterated extension is a special case of negotiation function. Then we show that a negotiation function can be constructed by two related iterated belief revision functions under a certain coordination mechanism. This provides a qualitative method for constructing negotiation space and rational concessions. It also shows glimpse of how to express game-theoretical concepts in logical framework.
Temporal Dynamics of Reflexive Attention Shifts: A Dual-Stream Rapid Serial Visual Presentation Exploration

We combined a prototypical exogenous cuing procedure with rapid serial visual presentation (RSVP) to provide a precise characterization of the temporal dynamics of reflexive attention shifts. The novel paradigm thus created has several useful properties, most notably that the physical presentation of the target is neither an onset nor a unique event and that temporal precision is provided without the requirement for a speeded response. A biphasic pattern was observed, with early benefits followed by later costs (inhibition of return) at the cued location relative to the uncued location. The finding of inhibition of return in this paradigm disproves the assertion that inhibition of return is merely a reluctance to respond in the target's direction. It may be partly that, but encoding mechanisms linked to attention must also be involved.
VMAT2-Deficient Mice Display Nigral and Extranigral Pathology and Motor and Nonmotor Symptoms of Parkinson's Disease

Dopamine is transported into synaptic vesicles by the vesicular monoamine transporter (VMAT2; SLC18A2). Disruption of dopamine storage has been hypothesized to damage the dopamine neurons that are lost in Parkinson's disease. By disrupting vesicular storage of dopamine and other monoamines, we have created a progressive mouse model of PD that exhibits catecholamine neuron loss in the substantia nigra pars compacta and locus coeruleus and motor and nonmotor symptoms. With a 95% reduction in VMAT2 expression, VMAT2-deficient animals have decreased motor function, progressive deficits in olfactory discrimination, shorter latency to behavioral signs of sleep, delayed gastric emptying, anxiety-like behaviors at younger ages, and a progressive depressive-like phenotype. Pathologically, the VMAT2-deficient mice display progressive neurodegeneration in the substantia nigra (SNpc), locus coeruleus (LC), and dorsal raphe (DR) coupled with α-synuclein accumulation. Taken together, these studies demonstrate that reduced vesicular storage of monoamines and the resulting disruption of the cytosolic environment may play a role in the pathogenesis of parkinsonian symptoms and neurodegeneration. The multisystem nature of the VMAT2-deficient mice may be useful in developing therapeutic strategies that go beyond the dopamine system.
Adsorption kinetics of aromatic compounds on carbon nanotubes and activated carbons

Adsorption kinetics of two organic compounds on four types of carbonaceous adsorbents (a granular activated carbon [HD4000], an activated carbon fiber [ACF10], a single‐walled carbon nanotube [SWNT], and a multiwalled carbon nanotube [MWNT]) was examined in aqueous solutions. The times needed for the adsorption to reach apparent equilibrium on the four carbons followed the order of ACF10 > HD4000 > SWNT > MWNT. Ultrasonication of the carbon nanotubes (CNTs) accelerated their adsorption kinetics but had no effect on their equilibrium adsorption capacities. The pseudo‐second order model (PSOM) provided good fitting for the kinetic data. The fitting of kinetic data with the intraparticle diffusion model indicated that external mass transfer controls the sorption process in the organic compound–CNT systems, whereas intraparticle diffusion dominates in the sorption of organic compounds onto activated carbons. Environ. Toxicol. Chem. 2012;31:79–85. © 2011 SETAC
Task-Dependent Inhomogeneous Muscle Activities within the Bi-Articular Human Rectus Femoris Muscle

The motor nerve of the bi-articular rectus femoris muscle is generally split from the femoral nerve trunk into two sub-branches just before it reaches the distal and proximal regions of the muscle. In this study, we examined whether the regional difference in muscle activities exists within the human rectus femoris muscle during maximal voluntary isometric contractions of knee extension and hip flexion. Surface electromyographic signals were recorded from the distal, middle, and proximal regions. In addition, twitch responses were evoked by stimulating the femoral nerve with supramaximal intensity. The root mean square value of electromyographic amplitude during each voluntary task was normalized to the maximal compound muscle action potential amplitude (M-wave) for each region. The electromyographic amplitudes were significantly smaller during hip flexion than during knee extension task for all regions. There was no significant difference in the normalized electromyographic amplitude during knee extension among regions within the rectus femoris muscle, whereas those were significantly smaller in the distal than in the middle and proximal regions during hip flexion task. These results indicate that the bi-articular rectus femoris muscle is differentially controlled along the longitudinal direction and that in particular the distal region of the muscle cannot be fully activated during hip flexion.
A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition

Patient: Male, 34 Final Diagnosis: ME/CFS Symptoms: Exertion intolerance • loss of functional capacity • pain • severe fatigue Medication: — Clinical Procedure: Cardiopulmonary exercise test Specialty: Sports Medicine Objective: Unknown ethiology Background: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with profound fatigue, flu-like symptoms, pain, cognitive impairment, orthostatic intolerance, post-exertional malaise (PEM), and exacerbation of some or all of the baseline symptoms. Case Report: We report on a pair of 34-year-old monozygotic twins discordant for ME/CFS, with WELL, the non-affected twin, and ILL, the affected twin. Both twins performed a two-day cardiopulmonary exercise test (CPET), preand post-exercise blood samples were drawn, and both provided stool samples for biochemical and molecular analyses. At peak exertion for both CPETs, ILL presented lower VO2peak and peak workload compared to WELL. WELL demonstrated normal reproducibility of VO2@ventilatory/anaerobic threshold (VAT) during CPET2, whereas ILL experienced an abnormal reduction of 13% in VAT during CPET2. A normal rise in lactate dehydrogenase (LDH), creatine kinase (CK), adrenocorticotropic hormone (ACTH), cortisol, creatinine, and ferritin content was observed following exercise for both WELL and ILL at each CPET. ILL showed higher increases of resistin, soluble CD40 ligand (sCD40L), and soluble Fas ligand (sFasL) after exercise compared to WELL. The gut bacterial microbiome and virome were examined and revealed a lower microbial diversity in ILL compared to WELL, with fewer beneficial bacteria such as Faecalibacterium and Bifidobacterium, and an expansion of bacteriophages belonging to the tailed dsDNA Caudovirales order. Conclusions: Results suggest dysfunctional immune activation in ILL following exercise and that prokaryotic viruses may contribute to mucosal inflammation and bacterial dysbiosis. Therefore, a two-day CPET and molecular analyses of blood and microbiomes could provide valuable information about ME/CFS, particularly if applied to a larger cohort of monozygotic twins.
Disrupted NF- kappa B activation after partial hepatectomy does not impair hepatocyte proliferation in rats.

AIM To analyze the effects of NF- kappa B inhibition by antioxidant pyrrolidine dithiocarbamate (PDTC) or TNF inhibitor pentoxifylline (PTX) on liver regeneration after partial hepatectomy (PH). METHODS Saline, PDTC or PTX were injected 1 h before PH and rats were killed at 0.5 and 24 h after PH. Several control groups were used for comparison (injection control groups). RESULTS Compared to saline injected controls, NF- kappa B activation was absent 0.5 h after PH in rats treated with PDTC or PTX. At 24 h after PH, DNA synthesis and PCNA expression were identical in treated and control rats and thus occurred irrespectively of the status of NF- kappa B activation at 0.5 h. Signal transducer and activator of transcription 3 (Stat3) activation was observed already 0.5 h after PH in saline, PDTC or PTX group and was similar to Stat3 activation in response to injection without PH. CONCLUSION These data strongly suggest that (1) NF- kappa B p65/p50 DNA binding produced in response to PH is not a signal necessary to initiate the liver regeneration, (2) Stat3 activation is a stress response unrelated to the activation of NF- kappa B. In conclusion, NF- kappa B activation is not critically required for the process of liver regeneration after PH.
Carbon Monoxide Metabolism in Roadside Soils

Air-dried soils which were equilibrated under relative humidities greater than 93% or moistened with liquid water showed marked increases in their capacities to oxidize CO to CO2. Liquid water addition in excess of saturation resulted in lower CO oxidation rates, reflecting the limited diffusion of CO through the aqueous phase. After 35 days' storage under 100% relative humidity, the capacity for CO oxidation decreased to 21% of the value observed with a freshly collected sample. Incubation of this stored soil under an atmosphere containing 200 ppm of CO (250 mg/m3) for 21 days resulted in a sevenfold increase in CO oxidation. A correlation was noted between the CO oxidative activity and the history of previous exposure of soils to high ambient levels of CO. The organisms responsible for CO oxidation apparently comprise a small fraction of the microbial population in the soils. With a roadside soil the oxidation of CO provided the driving force for the assimilation of CO2. The stoichiometry of the oxidative and assimilatory reactions in soil was in the range of values reported from laboratory studies with CO chemoautotrophs (carboxydobacteria). It is proposed that the population and activity of CO-oxidizing microorganisms increase in response to increasing levels of CO in the environment.