Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards a Model of Face-to-Face Grounding

We investigate the verbal and nonverbal means for grounding, and propose a design for embodied conversational agents that relies on both kinds of signals to establish common ground in human-computer interaction. We analyzed eye gaze, head nods and attentional focus in the context of a direction-giving task. The distribution of nonverbal behaviors differed depending on the type of dialogue move being grounded, and the overall pattern reflected a monitoring of lack of negative feedback. Based on these results, we present an ECA that uses verbal and nonverbal grounding acts to update dialogue state.
Induction of Chronic Cardiac Insufficiency by Arteriovenous Fistula and Doxorubicin Administration

Abstract Objectives: Large animal experimental models of chronic heart failure (HF) permit repeated invasive assessment of cardiovascular function, and evaluation of new medical or surgical therapies. The existing models however fail to achieve stable and long‐term HF. The aim of this study was to create a simple and stable chronic model of HF in goat, using both arteriovenous fistula and weekly intravenous doxorubicin injections. Methods: After a preliminary experiment on four goats receiving weekly 1 to 2 mg/kg of doxorubicin, six adult female goats, having had an arteriovenous fistula without signs or symptoms of heart failure, received weekly two different dosages of doxorubicin for 13 weeks : group A (n = 3) received 0.5 mg/kg and group B (n = 3) received 1 mg/kg. After a three‐month period without medication, both groups received again 1 mg/kg for four weeks. Cardiac function was assessed by repeated electrocardiographic and echocardiographic examinations. Results: Four goats died during the medication period (one in group A, three in group B). During the period without medication a stable ventricular hypocontractility with left ventricular dilation was observed. Left ventricular dysfunction was more pronounced in group B, and was associated with clinical symptoms of HF. Conclusions: Arteriovenous fistula alone did not produce HF. Its association with doxorubicin injections provides a simple and stable chronic model of HF. This association allows reduction of the required doxorubicin dose and toxicity in animals and in the environment. Depending of the dose of doxorubicin, it is possible to obtain a model of heart dilatation and ventricular hypokinesia with or without clinical symptoms of HF, with a different mortality. (J Card Surg 2003; 18:307‐311)
A Formal Theory for the Complexity Class Associated with the Stable Marriage Problem

Subramanian defined the complexity class CC as the set of problems log-space reducible to the comparator circuit value problem. He proved that several other problems are complete for CC, including the stable marriage problem, and finding the lexicographical first maximal matching in a bipartite graph. We suggest alternative definitions of CC based on different reducibilities and introduce a two-sorted theory VCC* based on one of them. We sharpen and simplify Subramanian's completeness proofs for the above two problems and formalize them in VCC*.
Cyclin-Dependent Kinase 5 Regulates the Polarized Trafficking of Neuropeptide-Containing Dense-Core Vesicles in Caenorhabditis elegans Motor Neurons

The polarized trafficking of axonal and dendritic proteins is essential for the structure and function of neurons. Cyclin-dependent kinase 5 (CDK-5) and its activator CDKA-1/p35 regulate diverse aspects of nervous system development and function. Here, we show that CDK-5 and CDKA-1/p35 are required for the polarized distribution of neuropeptide-containing dense-core vesicles (DCVs) in Caenorhabditis elegans cholinergic motor neurons. In cdk-5 or cdka-1/p35 mutants, the predominantly axonal localization of DCVs containing INS-22 neuropeptides was disrupted and DCVs accumulated in dendrites. Time-lapse microscopy in DB class motor neurons revealed decreased trafficking of DCVs in axons and increased trafficking and accumulation of DCVs in cdk-5 mutant dendrites. The polarized distribution of several axonal and dendritic markers, including synaptic vesicles, was unaltered in cdk-5 mutant DB neurons. We found that microtubule polarity is plus-end out in axons and predominantly minus-end out in dendrites of DB neurons. Surprisingly, cdk-5 mutants had increased amounts of plus-end-out microtubules in dendrites, suggesting that CDK-5 regulates microtubule orientation. However, these changes in microtubule polarity are not responsible for the increased trafficking of DCVs into dendrites. Genetic analysis of cdk-5 and the plus-end-directed axonal DCV motor unc-104/KIF1A suggest that increased trafficking of UNC-104 into dendrites cannot explain the dendritic DCV accumulation. Instead, we found that mutations in the minus-end-directed motor cytoplasmic dynein, completely block the increased DCVs observed in cdk-5 mutant dendrites without affecting microtubule polarity. We propose a model in which CDK-5 regulates DCV polarity by both promoting DCV trafficking in axons and preventing dynein-dependent DCV trafficking into dendrites.
Prophylactic Intravenous Nimodipine Treatment in Skull Base Surgery: Pharmacokinetic Aspects

Abstract Background Nimodipine is primarily used in subarachnoid hemorrhage (SAH). Clinical trials revealed also a beneficial effect of prophylactic nimodipine treatment on cranial nerve functions following vestibular schwannoma surgery. Objective The unknown pharmacokinetics of prophylactically administered nimodipine were investigated. Methods Samples were taken from 27 patients with skull base lesions. Prophylactic intravenous nimodipine infusion was started 5.8–25.8 h (mean 17.9 h) before surgery. Nimodipine concentrations were determined in serum (intra- and postoperatively), cerebrospinal fluid (CSF) (intraoperatively), and tissue samples. Results Wide interindividual differences were observed. Mean concentrations for nimodipine were 46.9 ng/ml (SD: 6.4; min. 4.1 and max. 92.7 ng/ml) in intraoperative serum, 73.2 ng/ml (SD: 16.7; min. 6.6 and max. 253 ng/ml) in postoperative serum and 8.3 ng/ml (SD: 1.5; min. 1.0 und max. 29.7 ng/ml) in intraoperative CSF. The correlation between intra- and postoperative serum (p=0.004, r=0.560) and between intraoperative serum and CSF concentration (p=0.003, r=0.567) were statistically significant. Furthermore the correlation between intraoperative serum concentration and concentrations collected from vestibular nerves was high (r=0.711), but not statistically significant (p=0.178). Conclusions Interindividually, continously administered intravenous nimodipine produces considerably variable serum levels. Controls of nimodipine serum concentrations may be useful to optimize nimodipine medication in skull base surgery and in the management of SAH. The serum nimodipine level is a useful marker for CSF and intracranial nerve tissue concentrations of nimodipine.
Interactions between Nosema microspores and a neonicotinoid weaken honeybees (Apis mellifera)

Global pollinators, like honeybees, are declining in abundance and diversity, which can adversely affect natural ecosystems and agriculture. Therefore, we tested the current hypotheses describing honeybee losses as a multifactorial syndrome, by investigating integrative effects of an infectious organism and an insecticide on honeybee health. We demonstrated that the interaction between the microsporidia Nosema and a neonicotinoid (imidacloprid) significantly weakened honeybees. In the short term, the combination of both agents caused the highest individual mortality rates and energetic stress. By quantifying the strength of immunity at both the individual and social levels, we showed that neither the haemocyte number nor the phenoloxidase activity of individuals was affected by the different treatments. However, the activity of glucose oxidase, enabling bees to sterilize colony and brood food, was significantly decreased only by the combination of both factors compared with control, Nosema or imidacloprid groups, suggesting a synergistic interaction and in the long term a higher susceptibility of the colony to pathogens. This provides the first evidences that interaction between an infectious organism and a chemical can also threaten pollinators, interactions that are widely used to eliminate insect pests in integrative pest management.
Differential CD4 (cid:1) versus CD8 (cid:1) T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeﬁciency Virus Type 1 Vaccine Candidates Provide Comparable Efﬁcacies in Primates (cid:1) †

Poxvirus vectors have proven to be highly effective for boosting immune responses in diverse vaccine settings. Recent reports reveal marked differences in the gene expression of human dendritic cells infected with two leading poxvirus-based human immunodeﬁciency virus (HIV) vaccine candidates, New York vaccinia virus (NYVAC) and modiﬁed vaccinia virus Ankara (MVA). To understand how complex genomic changes in these two vaccine vectors translate into antigen-speciﬁc systemic immune responses, we undertook a head-to-head vaccine immunogenicity and efﬁcacy study in the pathogenic HIV type 1 (HIV-1) model of in Indian rhesus macaques. Differences in the immune responses in outbred animals were not distinguished by enzyme- linked immunospot assays, but differences were distinguished by multiparameter ﬂuorescence-activated cell sorter analysis, revealing a difference between the number of animals with both CD4 (cid:1) and CD8 (cid:1) T-cell responses to vaccine inserts (MVA) and those that elicit a dominant CD4 (cid:1) T-cell response (NYVAC). vector-induced in CD4 (cid:1) /CD8 (cid:1) T-cell
A Petri Net Theory-Based Method for Modeling Web Service-Based Systems

With the proliferation of researches on web services and their increasing applications in industries comes the opportunity to study the analysis and design method of web service-based systems systematically. Our objective is to propose a method for modeling web service-based systems to conduct the practice of developing the application systems. In this paper, we introduce the relevant research on web services. We propose a method for modeling web service-based systems. We also present the Petri net theory and take it as theoretical foundation of the modeling method. Next, we present the analysis method to assess the correctness of the model constructed by the method. Finally, we present a case study on modeling the web service-based airport emergency management information system via the modeling method and verify the correctness of the model.
National surveillance of antimicrobial resistance among Gram-positive bacteria in Saudi Arabia

Abstract Background: Antimicrobial-resistant Gram-positive bacteria are important causes of serious infections. Methods: Between January and December 2009, we examined clinical Gram-positive isolates from 24 hospitals across Saudi Arabia. Results: Among the 13750 isolates, Staphylococcus aureus (62·3%) was the commonest, followed by non-group A beta-haemolytic streptococci (14·8%), group A beta-haemolytic streptococci (7·1%), coagulase-negative staphylococci (6·6%), pneumococci (6·0%), and enterococci (3·1%). Resistance rates were high among S. aureus (methicillin-resistant S. aureus: 32%), coagulase-negative staphylococci (oxacillin: 63%) and pneumococci (penicillin G: 33%; erythromycin: 26%; ceftriaxone: 11%); low among enterococci (vancomycin: 1%) and among beta-haemolytic streptococci. Resistance rates varied between regions, but comparison was complicated by differences in antibiotics tested. Many relevant antibiotics were tested against few isolates (e.g. ampicillin, vancomycin, and high-level gentamicin versus enterococci) while unhelpful tests were widely performed (e.g. cefotaxime, ceftriaxone, and imipenem versus staphylococci. Conclusion: Resistance is widespread in staphylococci and pneumococci, but not enterococci and beta-haemolytic streptococci in Saudi Arabia. Rationalization of antibiotic panels tested is urgently needed.
Near-Neutrality, Robustness, and Epigenetics

The nearly neutral theory emphasizes the interaction of drift and weak selection in evolution. With progress of genome biology, the applicability of the nearly neutral theory has expanded. The genome-wide analyses of synonymous and nonsynonymous substitutions at protein-coding regions show prevalence of very weak selection. Many patterns of evolution of gene regulation are also in agreement with the nearly neutral prediction. Our consideration on near-neutrality expands in relation to the progress on molecular understanding of robustness and epigenetics. Both are bridges to link genotypes with phenotypes and important for understanding how weak selection and drift interact in the evolution of complex systems.
Spatial role labeling: Towards extraction of spatial relations from natural language

This article reports on the novel task of spatial role labeling in natural language text. It proposes machine learning methods to extract spatial roles and their relations. This work experiments with both a step-wise approach, where spatial prepositions are found and the related trajectors, and landmarks are then extracted, and a joint learning approach, where a spatial relation and its composing indicator, trajector, and landmark are classified collectively. Context-dependent learning techniques, such as a skip-chain conditional random field, yield good results on the GUM-evaluation (Maptask) data and CLEF-IAPR TC-12 Image Benchmark. An extensive error analysis, including feature assessment, and a cross-domain evaluation pinpoint the main bottlenecks and avenues for future research.
Pathophysiology of cardiac tamponade.

C ardiac tamponade is always life threatening and nearly always requires urgent and precise therapeutic intervention. It is perhaps unique in that appreciation of its pathophysiologic state is essential to precise diagnosis and rational treatment. Since the 19th century, investigations in experimental animals provided a basic understanding that has been continually refined by recent investigators to the point where an integrated picture of its macrophysiologic condition emerges. This review covers the resultant concepts. Procedural details of investigations can be found in the references (thus, for example, the text omits the relative merits of catheters vs flat balloons for intrapericardial pressure determination).
Renal sympathetic activation from long-term low-dose angiotensin II infusion in rabbits

Objective: Activation of renal sympathetic nerve activity (RSNA) has not been observed during long-term infusion of angiotensin II (AngII) which results in marked hypertension, despite activation of hypothalamic autonomic regions. We examined whether the function of central pathways influencing sympathetic activity is altered in conscious rabbits given a low dose of AngII that produces a modest hypertension and, therefore, limited secondary complications. Methods: Rabbits received AngII (20–30 ng/kg per min, subcutaneously) or sham treatment for 3 months at which time they were implanted with a renal sympathetic nerve electrode and the responses to airjet stress, baroreflexes and hypoxia were examined. Results: AngII infusion for 3 months increased mean arterial pressure by 16% and RSNA by 43%. Increases in RSNA during airjet stress and hypoxia (10% O2) were 35 and 65% greater in AngII-treated rabbits than sham controls, respectively. Tachycardic responses were also enhanced. Baroreflexes were shifted to the right and upward in the AngII animals but baroreflex gain was similar in the two groups, indicating near complete resetting. Greater neuronal Fos-related antigen immunoreactivity was found in the vascular organ of the lamina terminalis, paraventricular and supraoptic hypothalamic nuclei in AngII-treated rabbits compared with sham. Conclusion: Our results suggest that low-dose AngII-treatment results in marked sympathetic activation at rest and during stress and hypoxia, due to activation of specific hypothalamic pathways. These mechanisms may contribute to sympathetic activation in conditions associated with chronic activation of the renin–angiotensin system such as obesity or renovascular disease.
Lipoplex‐Loaded Microbubbles for Gene Delivery: A Trojan Horse Controlled by Ultrasound

Cationic poly(ethylene glycol)ylated (PEGylated) liposomes are one of the most important gene transfer reagents in non‐viral gene therapy. However, the low transfection efficiencies of highly PEGylated lipoplexes currently hamper their clinical use. Recently, ultrasound has been used in combination with microbubbles to enhance the uptake of genes in different cell types. However, the gene transfer efficiency still remains low in these experiments. To overcome the limitations of both techniques, we present the attachment of PEGylated lipoplexes to microbubbles via biotin–avidin–biotin linkages. Exposure of these lipoplex‐loaded microbubbles to ultrasound results in the release of unaltered lipoplexes. Furthermore, these lipoplex‐loaded microbubbles exhibit much higher transfection efficiencies than “free” PEGylated lipoplexes or naked plasmid DNA (pDNA) when combined with microbubbles and ultrasound. Interestingly, the lipoplex‐loaded microbubbles only transfect cells when exposed to ultrasound, which is promising for space‐ and time‐controlled gene transfer. Finally, this novel Trojan‐horse‐like concept can also be exploited to achieve the ultrasound‐triggered release of nanoparticles containing other therapeutic agents such as anticancer drugs.
Low‐Density Lipoprotein Receptor Gene Familial Hypercholesterolemia Variant Database: Update and Pathological Assessment

Familial hypercholesterolemia (FH) is caused predominately by variants in the low‐density lipoprotein receptor gene (LDLR). We report here an update of the UCL LDLR variant database to include variants reported in the literature and in‐house between 2008 and 2010, transfer of the database to LOVDv.2. 0 platform (https://grenada.lumc.nl/LOVD2/UCL‐Heart/home.php? select_db=LDLR) and pathogenicity analysis. The database now contains over 1288 different variants reported in FH patients: 55% exonic substitutions, 22% exonic small rearrangements (<100 bp), 11% large rearrangements (>100 bp), 2% promoter variants, 10% intronic variants and 1 variant in the 3' untranslated sequence. The distribution and type of newly reported variants closely matches that of the 2008 database, and we have used these variants (n= 223) as a representative sample to assess the utility of standard open access software (PolyPhen, SIFT, refined SIFT, Neural Network Splice Site Prediction Tool, SplicePort and NetGene2) and additional analyses (Single Amino Acid Polymorphism database, analysis of conservation and structure and Mutation Taster) for pathogenicity prediction. In combination, these techniques have enabled us to assign with confidence pathogenic predictions to 8/8 in‐frame small rearrangements and 8/9 missense substitutions with previously discordant results from PolyPhen and SIFT analysis. Overall, we conclude that 79% of the reported variants are likely to be disease causing.
Distributed Intrusion Detection in Clouds Using Mobile Agents

Cloud Computing extends an enterprise ability to meet the computing demands of its everyday operations, while offering flexibility, mobility and scalability. However, the reason that Chief Information Officers (CIOs) and their colleagues hesitate to let their business workloads to move from private Cloud into public Cloud is security. This work tries to offer a line of defense by applying Mobile Agents technology to provide intrusion detection for Cloud applications regardless of their locations. Therefore, CIOs feel safer to use Cloud to extend their on-premise infrastructure by adding capacity on demand.
Expression of human perlecan domain I as a recombinant heparan sulfate proteoglycan with 20-kDa glycosaminoglycan chains.

Recombinant forms of human perlecan domain I were secreted as proteoglycans by stably transfected human 293 cells. A recombinant domain I-only proteoglycan spanned the 95- to 265-kDa region in SDS-PAGE and appeared to be 160 kDa in denaturing gel filtration. Its glycosaminoglycan (GAG) content was approximately 67% heparan sulfate, and its average GAG chain size of 20 kDa suggested that the true molecular mass of the proteoglycan was 90 kDa. Domain I with enhanced green fluorescent protein fused to its C-terminus had an apparent molecular mass of 210-220 kDa and contained approximately 100% heparan sulfate. Its average GAG chain size (also 20 kDa) suggested a true molecular mass of 117 kDa for this proteoglycan. Its sulfate content of 53-77 mol SO2-4 per mole of protein indicated the presence of one sulfate group per 4-7 GAG sugar residues.
Martian Meteorite Launch: High-Speed Ejecta from Small Craters

We performed high-resolution computer simulations of impacts into homogeneous and layered martian terrain analogs to try to account for the ages and characteristics of the martian meteorite collection found on Earth. We found that craters as small as ∼3 kilometers can eject ∼107 decimeter-sized fragments from Mars, which is enough to expect those fragments to appear in the terrestrial collection. This minimum crater diameter is at least four times smaller than previous estimates and depends on the physical composition of the target material. Terrain covered by a weak layer such as an impact-generated regolith requires larger, therefore rarer, impacts to eject meteorites. Because older terrain is more likely to be mantled with such material, we estimate that the martian meteorites will be biased toward younger ages, which is consistent with the meteorite collection.
PROCAIN server for remote protein sequence similarity search

Sensitive and accurate detection of distant protein homology is essential for the studies of protein structure, function and evolution. We recently developed PROCAIN, a method that is based on sequence profile comparison and involves the analysis of four signals—similarities of residue content at the profile positions combined with three types of assisting information: sequence motifs, residue conservation and predicted secondary structure. Here we present the PROCAIN web server that allows the user to submit a query sequence or multiple sequence alignment and perform the search in a profile database of choice. The output is structured similar to that of BLAST, with the list of detected homologs sorted by E-value and followed by profile–profile alignments. The front page allows the user to adjust multiple options of input processing and output formatting, as well as search settings, including the relative weights assigned to the three types of assisting information. Availability: http://prodata.swmed. edu/procain/ Contact: grishin@chop.swmed. edu
Norcantharidin Induces Human Melanoma A375-S2 Cell Apoptosis through Mitochondrial and Caspase Pathways

Norcantharidin (NCTD) is the demethylated form of cantharidin, which is the active substance of mylabris. To examine the pathway of NCTD-induced A375-S2 cell death, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheyltetrazolium bromide (MTT) assay, photomicroscopical observation, DNA agarose gel electrophoresis, caspase activity assay and Western blot analysis were carried out. A375-S2 cells treated with NCTD exhibited several typical characteristics of apoptosis. The inhibitory effect of NCTD on human melanoma, A375-S2 cells, was partially reversed by the inhibitors of pan-caspase, caspase-3 and caspase-9. The activities of caspase-3 and -9 were significantly increased after treatment with NCTD at different time. The expression of inhibitor of caspase-activated DNase was decreased in a time-dependent manner, simultaneously, the ratio of Bcl-2/Bax or Bcl-xL/Bax was decreased and the expression ratio of proteins could be reversed by caspase-3 inhibitor. The expression of cytochrome c in cytosol was increased after NCTD treatment and caspase-3 inhibitor had no significant effect on the up-regulation of cytochrom c. These results suggest that NCTD induced A375-S2 cell apoptosis and the activation of caspase and mitochondrial pathway were involved in the process of NCTD-induced A375-S2 cell apoptosis.