Miracle-dz/UniFAR-FTUs huggingface dataset:
STUN: Spatio-Temporal Uncertain (Social) Networks

STUN is an extension of social networks in which the edges are characterized by spatio-temporal annotations, as well as uncertainty allowing us to express not only relationships between vertices, but when and where these relationships were true, and how certain we are that the relationships hold. We propose a STUN query language that consists of sub graphs with spatio-temporal constraints and uncertainty requirements. We then develop an index structure to store STUN graphs, together with an algorithm to answer such queries. We describe experiments with a real-world YouTube social network data set and show that our algorithm performs well on graphs with over a million edges.
Enhanced Responsiveness to Angiotensin II in Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats Is Not Associated With Alterations in Protein Kinase C

This study compares vascular smooth muscle cells from spontaneously hypertensive and normotensive Wistar-Kyoto rats with respect to protein kinase C and intracellular responses to angiotensin II (Ang II). Ang LUnduced degradation of polyphosphoinositides and accumulation of inositol di- and tris-phosphates was enhanced (∼twofold) in hypertensive-derived cells, without a change (vs. normotensive-derived cells) in half-maximally effective concentrations of Ang II. Intracellular pH (∼6.6) was comparable between both cell isolates at quiescence, but alkalinization induced by Ang II, serum, or phorbol ester was greater (Δ 0.1–0.2 pH units) for hypertensive-derived cells. For both cell types, the intracellular pH response to these agonists was prevented in the presence of Na+-H+ exchange inhibitors. S6 kinase activation induced by Ang II was enhanced (∼twofold) in hypertensive-derived cells, whereas activation in response to serum or 12–0-tetradecanoylphorbol 13-acetate did not differ significantly between the two cell types. Quantitation of protein kinase C by immunoblotting and [3H] phorbol dibutyrate binding procedures revealed no differences between the two smooth muscle cell isolates (at quiescence or in the presence of serum) with respect to either total amounts or subcellular distribution. Sensitivity of protein kinase C to phorbol ester was apparently also not different between the two cell types, as assessed from dose-dependent (phorbol ester) S6 kinase activation profiles. Phorbol ester caused a similar subcellular redistribution of [3H] phorbol dibutyrate binding in the two ceU isolates, but for both, minimal (10%) translocation occurred in response to Ang II. The data suggest that enhanced agonist responsiveness in vascular smooth muscle cells is unlikely to involve alterations in protein kinase C.
Breath Analysis in Disease Diagnosis: Methodological Considerations and Applications

Breath analysis is a promising field with great potential for non-invasive diagnosis of a number of disease states. Analysis of the concentrations of volatile organic compounds (VOCs) in breath with an acceptable accuracy are assessed by means of using analytical techniques with high sensitivity, accuracy, precision, low response time, and low detection limit, which are desirable characteristics for the detection of VOCs in human breath. “Breath fingerprinting”, indicative of a specific clinical status, relies on the use of multivariate statistics methods with powerful in-built algorithms. The need for standardisation of sample collection and analysis is the main issue concerning breath analysis, blocking the introduction of breath tests into clinical practice. This review describes recent scientific developments in basic research and clinical applications, namely issues concerning sampling and biochemistry, highlighting the diagnostic potential of breath analysis for disease diagnosis. Several considerations that need to be taken into account in breath analysis are documented here, including the growing need for metabolomics to deal with breath profiles.
Split-belt adaptation and gait symmetry in transtibial amputees walking with a hybrid EMG controlled ankle-foot prosthesis

Our ability to automatically adapt our walking pattern to the demands of our environment is central to maintaining a steady gait. Accordingly, a large effort is being made to extend and integrate this adaptability to lower-limb prostheses. To date, the main focus of this research has been on short term adaptation, such as in response to a terrain transition or a sudden change in the environment. However, long term adaptation and underlying sensorimotor learning processes are critical to optimizing walking patterns and predictively changing our gait when faced with continued perturbations. Furthermore, investigating these processes in lower-limb amputees may provide a unique window into the interplay between sensory driven adaptation and top-down cerebellar modulation of locomotor reflexes and may potentially help alleviate gait asymmetries. In the current exploratory study, we therefore investigated adaptation, sensorimotor learning, and gait symmetry in a group of transtibial amputees walking with a hybrid-EMG controlled powered prosthesis and matched controls (both groups N=3). Participants were asked to perform a split-belt walking trial during which the belt on the affected side ran at twice the speed of the contralateral belt (1.0m/s and 0.5m/s respectively). Adaptation, sensorimotor learning, and symmetry are compared to two baseline conditions. Initial results illustrate that the amputees were readily able to use the hybrid controller, modulated their EMG depending on treadmill speed, and successfully adapted their gait during split-belt walking. However, the temporal gait parameters suggest that amputees used a different adaptation technique and showed reduced sensorimotor learning, while gait symmetry was improved, in the short term, post-adaptation.
A genome‐wide DNA methylation study in azoospermia

The objective of this study was to assess genome‐wide DNA methylation in testicular tissue from azoospermic patients. A total of 94 azoospermic patients were recruited and classified into three groups: 29 patients presented obstructive azoospermia (OA), 26 displayed non‐obstructive azoospermia (NOA) and successful retrieval of spermatozoa by testicular sperm extraction (TESE+) and 39 displayed NOA and failure to retrieve spermatozoa by TESE (TESE−). An Illumina Infinium Human Methylation27 BeadChip DNA methylation array was used to establish a testicular DNA methylation pattern for each type of azoospermic patient. The OA and NOA groups were compared in terms of the relative M‐value (the log2 ratio between methylated and non‐methylated probe intensities) for each CpG site. We observed significantly different DNA methylation profiles for the NOA and OA groups, with differences at over 9000 of the 27 578 CpG sites; 212 CpG sites had a relative M‐value >3. The results highlighted 14 testis‐specific genes. Patient clustering with respect to these 212 CpG sites corresponded closely to the clinical classification. The DNA methylation patterns showed that in the NOA group, 78 of the 212 CpG sites were hypomethylated and 134 were hypermethylated (relative to the OA group). On the basis of these DNA methylation profiles, azoospermic patients could be classified as OA or NOA by considering the 212 CpG sites with the greatest methylation differences. Furthermore, we identified genes that may provide insight into the mechanism of idiopathic NOA.
The Discovery of Small-Molecule Mimicking Peptides through Phage Display

Using peptides to achieve the functional and structural mimicry of small-molecules, especially those with biological activity or clear biotechnological applications, has great potential in overcoming difficulties associated with synthesis, or unfavorable physical properties. Combinatorial techniques like phage display can aid in the discovery of these peptides even if their mechanism of mimicry is not rationally obvious.The major focus of this field has been limited to developing biotin and sugar mimetics. However, the full “mimicry” of these peptides has not yet been fully established as some bind to the target with a different mechanism than that of the natural ligand and some do not share all of the natural ligand’s binding partners. In this article, mimicry of small-molecules by phage display-discovered peptides is reviewed and their potential in biochemical and medical applications is analyzed.
Deficient long‐term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C β4 mutant mice

Long‐term depression (LTD) at parallel fibre–Purkinje cell synapse of the cerebellum is thought to be a cellular substrate for motor learning. LTD requires activation of metabotropic glutamate receptor subtype 1 (mGluR1) and its downstream signalling pathways, which invariably involves phospholipase Cβs (PLCβs). PLCβs consist of four isoforms (PLCβ1–4) among which PLCβ4 is the major isoform in most Purkinje cells in the rostral cerebellum (lobule 1 to the rostral half of lobule 6). We studied mutant mice deficient in PLCβ4, and found that LTD was deficient in the rostral but not in the caudal cerebellum of the mutant. Basic properties of parallel fibre–Purkinje cell synapses and voltage‐gated Ca2+ channel currents appeared normal. The mGluR1‐mediated Ca2+ release induced by repetitive parallel fibre stimulation was absent in the rostral cerebellum of the mutant, suggesting that their LTD lesion was due to the defect in the mGluR1‐mediated signalling in Purkinje cells. Importantly, the eyeblink conditioning, a simple form of discrete motor learning, was severely impaired in PLCβ4 mutant mice. Wild‐type mice developed the conditioned eyeblink response, when pairs of the conditioned stimulus (tone) and the unconditioned stimulus (periorbital shock) were repeatedly applied. In contrast, PLCβ4 mutant mice could not learn the association between the conditioned and unconditioned stimuli, although their behavioural responses to the tone or to the periorbital shock appeared normal. These results strongly suggest that PLCβ4 is essential for LTD in the rostral cerebellum, which may be required for the acuisition of the conditioned eyeblink response.
“Hello Emily, How Are You Today?” - Personalised Dialogue in a Toy to Engage Children.

In line with the growing interest in conversational agents as companions, we are developing a toy companion for children that is capable of engaging interactions and of developing a long-term relationship with them, and is extensible so as to evolve with them. In this paper, we investigate the importance of personalising interaction both for engagement and for long-term relationship development. In particular, we propose a framework for representing, gathering and using personal knowledge about the child during dialogue interaction.
Gaze-Contingent Multiresolutional Displays: An Integrative Review

Gaze-contingent multiresolutional displays (GCMRDs) center high-resolution information on the user's gaze position, matching the user's area of interest (AOI). Image resolution and details outside the AOI are reduced, lowering the requirements for processing resources and transmission bandwidth in demanding display and imaging applications. This review provides a general framework within which GCMRD research can be integrated, evaluated, and guided. GCMRDs (or “moving windows”) are analyzed in terms of (a) the nature of their images (i.e., “multiresolution,” “variable resolution,” “space variant,” or “level of detail”), and (b) the movement of the AOI (i.e., “gaze contingent,” “foveated,” or “eye slaved”). We also synthesize the known human factors research on GCMRDs and point out important questions for future research and development. Actual or potential applications of this research include flight, medical, and driving simulators; virtual reality; remote piloting and teleoperation; infrared and indirect vision; image transmission and retrieval; telemedicine; video teleconferencing; and artificial vision systems.
Architecting Pervasive Computing Systems for Privacy: A Survey

In pervasive computing systems, a higher number of interactions will be mediated by computers, amplifying the menace to privacy. Privacy protection in pervasive environments is still a big issue, despite the growing number of works on this subject as evidenced by this survey. In this paper, we propose a taxonomy for privacy invasion attacks, classify existing privacy enhancing technologies according to the protection provided for those attacks, and introduce a service-oriented privacy-enhanced architecture for pervasive computing.
Spontaneous emergence of large-scale cell cycle synchronization in amoeba colonies

Unicellular eukaryotic amoebae Dictyostelium discoideum are generally believed to grow in their vegetative state as single cells until starvation, when their collective aspect emerges and they differentiate to form a multicellular slime mold. While major efforts continue to be aimed at their starvation-induced social aspect, our understanding of population dynamics and cell cycle in the vegetative growth phase has remained incomplete. Here we show that cell populations grown on a substrate spontaneously synchronize their cell cycles within several hours. These collective population-wide cell cycle oscillations span millimeter length scales and can be completely suppressed by washing away putative cell-secreted signals, implying signaling by means of a diffusible growth factor or mitogen. These observations give strong evidence for collective proliferation behavior in the vegetative state.
Neurophysiological Indicators of Residual Cognitive Capacity in the Minimally Conscious State

Background. The diagnostic usefulness of electrophysiological methods in assessing disorders of consciousness (DoC) remains to be established on an individual patient level, and there is need to determine what constitutes robust experimental paradigm to elicit electrophysiological indices of covert cognitive capacity. Objectives. Two tasks encompassing active and passive conditions were explored in an event-related potentials (ERP) study. The task robustness was studied in healthy controls, and their utility to detect covert signs of command-following on an individual patient level was investigated in patients in a minimally conscious state (MCS). Methods. Twenty healthy controls and 20 MCS patients participated. The active tasks included (1) listening for a change of pitch in the subject's own name (SON) and (2) counting SON, both contrasted to passive conditions. Midline ERPs are reported. Results. A larger P3 response was detected in the counting task compared to active listening to pitch change in the healthy controls. On an individual level, the counting task revealed a higher rate of responders among both healthy subjects and MCS patients. Conclusion. ERP paradigms involving actively counting SON represent a robust paradigm in probing for volitional cognition in minimally conscious patients and add important diagnostic information in some patients.
Identification of Functional Exonic Splicing Enhancer Motifs Recognized by Individual Sr Proteins Using an in Vitro Randomization and Functional Selection Procedure, We Have Identified Three Novel Classes of Exonic Splicing Enhancers (eses) Recognized by Human Sf2/asf, Srp40, and Srp55, Respectively

These three consensus sequences occur at higher frequencies in exons than in introns and may thus help define exon–intron boundaries. They occur in clusters within regions corresponding to naturally occurring, mapped ESEs. We conclude that a remarkably diverse set of sequences can function as ESEs. The degeneracy of these motifs is consistent with the fact that exonic enhancers evolved within extremely diverse protein coding sequences and are recognized by a small number of SR proteins that bind RNA with limited sequence specificity. Pre-mRNA splicing consists of two trans-esterification reactions, which occur in a large RNA–protein complex termed the spliceosome. This high-fidelity process requires precise recognition of the intron–exon borders by the spliceosome. The poorly conserved metazoan splice sites and branch site do not provide sufficient information for this recognition. Additional intron and exon sequences are often necessary for efficient and/or accurate splicing of many higher eukaryotic pre-mRNAs. The positive exon cis-acting elements, known as exonic splicing enhancers (ESEs), are often, though not always, found in a purine-rich context. A well-studied example is the ESE in the alternative exon M2 of the mouse IgM gene. This 73-nucleotide ESE is essential for splicing of the preceding intron between exons M1 and M2. The M2 ESE can also stimulate splicing of a heterologous regulated intron of the Drosophila doublesex (dsx) gene. En-hancer activity in the context of the IgM pre-mRNA could also be obtained by insertion of certain natural or synthetic purine-rich sequences in place of the natural ESE. However, deletion of the purine-rich sequences within the M2 ESE did not abolish its activity completely (Watakabe et al. 1993; Tanaka et al. 1994). In agreement with this finding, SELEX experiments revealed that certain nonpurine-rich sequences can also function as enhancers (Tian and Kole 1995; Coulter et al. 1997). Most natural ESEs have been identified in tissue-specific or developmentally regulated exons, which typically have weak splice sites and require the ESE for exon inclusion. In some cases, ESEs are specifically recognized by one or more SR proteins In turn, SR proteins are expressed at different levels in different tissues, and their expression also appears to be regulated by alternative splicing (Jumaa et al. 1997; for review, see Cá-ceres and Krainer 1997). The SR proteins are a family of highly conserved ser-ine/arginine-rich RNA-binding proteins. They are essential splicing factors (Krainer et al. 1990b, 1991; Ge et al. 1991; Zahler et al. 1992) and also regulate …
Heparin Inhibition of Endothelial Cell Proliferation and Organization Is Dependent on Molecular Weight

Objective—Studies have shown improved survival in cancer patients treated with low molecular weight heparins (LMWHs). Tumors depend on an expanding vasculature, and heparins may affect vessel growth and function. We investigated the effect of heparins differing in Mr on selected endothelial cell properties. Methods and Results—Human umbilical vein endothelial cells were cultured with fibroblast growth factor-2 and heparins differing in Mr. Cell proliferation was assessed by [3H]thymidine incorporation, and vascular organization was assessed by in vitro assays. Maximum inhibition of 94±2% was observed with 6-kDa LMWH, greater than the inhibition seen with unfractionated heparin (58±8%) or 3-kDa LMWH (60±9%, P =0.02 for both). No inhibition of proliferation was observed with heparin tetrasaccharide, octasaccharide, or pentasaccharide (fondaparinux). Three- and 6-kDa fractions decreased endothelial tube formation in Matrigel to 58±15% and 67±9% (P <0.05), respectively, of that with fibroblast growth factor-2, whereas no inhibition was observed with unfractionated heparin, tetrasaccharide, pentasaccharide, or octasaccharide. LMWH (6 kDa) also inhibited vessel formation in a placental explant. Conclusions—Heparin inhibition of endothelial cell proliferation and organization requires a chain length of >8 saccharide units, with maximal inhibition at Mr of 6 kDa. This Mr dependence differs from that required for anticoagulant activity.
P. brasiliensis Virulence Is Affected by SconC, the Negative Regulator of Inorganic Sulfur Assimilation

Conidia/mycelium-to-yeast transition of Paracoccidioides brasiliensis is a critical step for the establishment of paracoccidioidomycosis, a systemic mycosis endemic in Latin America. Thus, knowledge of the factors that mediate this transition is of major importance for the design of intervention strategies. So far, the only known pre-requisites for the accomplishment of the morphological transition are the temperature shift to 37°C and the availability of organic sulfur compounds. In this study, we investigated the auxotrophic nature to organic sulfur of the yeast phase of Paracoccidioides , with special attention to P. brasiliensis species. For this, we addressed the role of SconCp, the negative regulator of the inorganic sulfur assimilation pathway, in the dimorphism and virulence of this pathogen. We show that down-regulation of SCONC allows initial steps of mycelium-to-yeast transition in the absence of organic sulfur compounds, contrarily to the wild-type fungus that cannot undergo mycelium-to-yeast transition under such conditions. However, SCONC down-regulated transformants were unable to sustain yeast growth using inorganic sulfur compounds only. Moreover, pulses with inorganic sulfur in SCONC down-regulated transformants triggered an increase of the inorganic sulfur metabolism, which culminated in a drastic reduction of the ATP and NADPH cellular levels and in higher oxidative stress. Importantly, the down-regulation of SCONC resulted in a decreased virulence of P. brasiliensis, as validated in an in vivo model of infection. Overall, our findings shed light on the inability of P. brasiliensis yeast to rely on inorganic sulfur compounds, correlating its metabolism with cellular energy and redox imbalances. Furthermore, the data herein presented reveal SconCp as a novel virulence determinant of P. brasiliensis.
A COMPARATIVE STUDY OF DOTHIEPIN (PROTHIADEN) AND IMIPRAMINE IN DEPRESSION

SUMMARY In a single-blind, randomised, parallel-group study comparing the efficacy and tolerability of dothiepin (50-150 mg per day) and imipramine (50-150 mg per day) for 6 weeks, involving 60 adult patients with depression, it was observed that dothiepin was comparable to imipramine in terms of efficacy as assessed by Hamilton Rating Scale for depress ion, global scale for severty of illness and clinician′s overall assessment of efficacy. Dothiepin was found to have a significantly earlier onset of anxiolytic action compared to imipramine. Dothiepin was well tolerated.
ERK2-Mediated Phosphorylation of Par3 Regulates Neuronal Polarization

Axon formation is one of the most important events in neuronal polarization and is regulated by signaling molecules involved in cytoskeletal rearrangement and protein transport. We previously found that Partition-defective 3 (Par3) is associated with KIF3A (kinesin-2) and is transported into the nascent axon in a KIF3A-dependent fashion. Par3 interacts with the Rac-specific guanine nucleotide-exchange factors (GEFs) Tiam1/2, which activate Rac1, and participates in axon formation in cultured hippocampal neurons. However, the regulatory mechanism of the Par3-KIF3A interaction is poorly understood, and the role of Par3 in neuronal polarization in vivo remains elusive. Here, we found that extracellular signal-regulated kinase 2 (ERK2) directly interacts with Par3, that ERK2 phosphorylates Par3 at Ser-1116, and that the phosphorylated Par3 accumulates at the axonal tips in a manner dependent upon ERK2 activity. The phosphorylation of Par3 by ERK2 inhibited the interaction of Par3 with KIF3A but not with the other Par3 partners, including Par6 and aPKC. The phosphomimic mutant of Par3 (Par3-S1116D) showed less binding activity with the KIF3s and slower transport in the axons. The knockdown of Par3 by RNA interference impaired neuronal polarization, which was rescued with RNAi-resistant Par3, but not with the phosphomimic Par3 mutant, in cultured rat hippocampal neurons and mouse cortical projection neurons in vivo. These results suggest that ERK2 phosphorylates Par3 and inhibits its binding with KIF3A, thereby controlling Par3 transport and neuronal polarity.