Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhaled isotretinoin (13-cis retinoic acid) is an effective lung cancer chemopreventive agent in A/J mice at low doses: a pilot study.

In previously treated head-and-neck cancer patients, p.o. administered isotretinoin (13-cis retinoic acid) reduced the occurrence of second aerodigestive tumors, including lung tumors, but side effects made chronic therapy problematic. We reasoned that inhaled isotretinoin might provide sufficient drug to the target cells for efficacy while avoiding systemic toxicity, and we proceeded with the pilot study reported here. Male A/J mice were given single i.p. doses of urethane, a common experimental lung carcinogen, or benzo[a]pyrene (BaP) or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), putative major carcinogens in tobacco smoke. The following day, exposures to isotretinoin aerosols for 45 min daily at 1.3, 20.7, or 481 microg/l were initiated. After 2 weeks, the high dose caused severe toxicity on the snout skin, necessitating a reduction of dose frequency to twice a week. As a precaution, the mid dose was reduced to three exposures per week. The weekly total deposited doses after the dose frequency reductions were calculated to be 0.24, 1.6, and 24.9 mg/kg for the low, mid, and high doses, of which 16% was estimated to be deposited in the lungs. The weekly deposited pulmonary drug doses were calculated to be 0.01, 0.07, and 1.1% of a previously reported ineffective oral dose in urethane-treated A/J mice. After 10-16 weeks, mice were sacrificed to count areas of pulmonary hyperplasia and adenomas. For all carcinogens, the mice exposed to the high isotretinoin dose showed reductions of tumor multiplicity ranging from 56 to 80% (P < 0.005). The mid dose was associated with reductions of tumor multiplicity by 67 and 88% (P < 0.005) in BaP- and NNK-treated mice, respectively, and was tolerated until approximately 12 weeks, when both these and the high-dose mice began losing weight. The low-dose mice had nonsignificant reductions of 30% (P < 0.13) and 16% (P < 0.30) for BaP- and NNK-treated mice, respectively without any evidence of side effects. For BaP- and NNK-treated mice, numbers of hyperplastic areas directly correlated to dose level and inversely to tumor number, suggesting arrested progression. Inhaled mid-dose isotretinoin caused up-regulation of lung tissue nuclear retinoic acid receptors (RARs) relative to vehicle-exposed mice, RARalpha (3.9-fold vehicle), RARbeta (3.3-fold), and RARgamma (3.7-fold), suggesting that these receptors may be useful biomarkers of retinoid activity in this system. The encouraging results from this pilot study suggest that inhaled isotretinoin merits evaluation in people at high risk for lung cancer.
The Recovery Time Course of the Endothelial Cell Glycocalyx In Vivo and Its Implications In Vitro

Compelling evidence continues to emerge suggesting that the glycocalyx surface layer on vascular endothelial cells plays a determining role in numerous physiological processes including inflammation, microvascular permeability, and endothelial mechanotransduction. Previous research has shown that enzymes degrade the glycocalyx, whereas inflammation causes shedding of the layer. To track the endogenous recovery of the glycocalyx in vivo, we used fluorescent microparticle image velocimetry (&mgr;-PIV) in mouse cremaster muscle venules to estimate the hydrodynamically relevant glycocalyx thickness 1, 3, 5, and 7 days after enzymatic or cytokine-mediated degradation of the layer. Results indicate that after acute degradation of the glycocalyx, 5 to 7 days are required for the layer to endogenously restore itself to its native hydrodynamically relevant thickness in vivo. In light of these findings, and because demonstrable evidence has emerged that standard cell culture conditions are not conducive to providing the environment and/or cellular conditions necessary to produce and maintain a physiologically relevant cell surface glycocalyx in vitro, we sought to determine whether merely the passage of time would be sufficient to promote the production of a hydrodynamically relevant glycocalyx on a confluent monolayer of human umbilical vein endothelial cells (HUVECs). Using &mgr;-PIV, we found that the hydrodynamically relevant glycocalyx was substantially absent 7 days postconfluence on HUVEC-lined cylindrical collagen microchannels maintained under standard culture conditions. Thus, it remains to be determined how a hydrodynamically relevant glycocalyx surface layer can be synthesized and maintained in culture before the endothelial cell culture model can be used to elucidate glycocalyx-mediated mechanisms of endothelial cell function.
Potential of Bioactive Glasses for Cardiac and Pulmonary Tissue Engineering

Repair and regeneration of disorders affecting cardiac and pulmonary tissues through tissue-engineering-based approaches is currently of particular interest. On this matter, different families of bioactive glasses (BGs) have recently been given much consideration with respect to treating refractory diseases of these tissues, such as myocardial infarction. The inherent properties of BGs, including their ability to bond to hard and soft tissues, to stimulate angiogenesis, and to elicit antimicrobial effects, along with their excellent biocompatibility, support these newly proposed strategies. Moreover, BGs can also act as a bioactive reinforcing phase to finely tune the mechanical properties of polymer-based constructs used to repair the damaged cardiac and pulmonary tissues. In the present study, we evaluated the potential of different forms of BGs, alone or in combination with other materials (e.g., polymers), in regards to repair and regenerate injured tissues of cardiac and pulmonary systems.
The diagnosability of the matching composition network under the comparison diagnosis model

The classical problem of diagnosability is discussed widely and the diagnosability of many well-known networks has been explored. We consider the diagnosability of a family of networks, called the matching composition network (MCN); a perfect matching connects two components. The diagnosability of MCN under the comparison model is shown to be one larger than that of the component, provided some connectivity constraints are satisfied. Applying our result, the diagnosability of the hypercube Qn, the crossed cube CQ/sub n/, the twisted cube TQ/sub n/, and the Mobius cube MQ/sub n/ can all proven to be n, for n/spl ges/4. In particular, we show that the diagnosability of the four-dimensional hypercube Q/sub 4/ is 4, which is not previously known.
Acquired inflammatory demyelinating polyneuropathies: Clinical and electrodiagnostic features

The acquired demyelinating polyneuropathies include acute (AIDP, Guillain‐Barré syndrome, GBS) and chronic (CIDP, dysproteinemic) forms which differ primarily in their temporal profile. They are inflammatory‐demyelinating diseases of the peripheral nervous system and likely have an immunologic pathogenesis. Although these neuropathies usually have a characteristic presentation, the electromyographer plays a central role in their recognition, since the demyelinating component of the neuropathy, which greatly reduces the differential diagnosis, is often first identified in the electromyography laboratory. In AIDP, the electromyographer, in addition to establishing the diagnosis, can sometimes predict the prognosis. Recognition of the chronic and dysproteinemic forms of acquired demyelinating polyneuropathy is important since they are treatable. The dysproteinemic forms also may be associated with occult systemic disorders that also may require treatment, independent of the neuropathy.
Influence of sugar as contaminant on outdoor insulation characteristics of RTV coating insulators

This paper describes the influence of sugar in contaminant to outdoor insulation characteristics of RTV coating insulator. First of all, field tests were carried out to analyze the pollution layer condition of field discharge insulators. Then RTV coating was selected to eliminate the pollution discharge, and the differences of surface condition, surface resistance and flashover voltage of RTV coating insulators between the contaminants with and without sugar were investigated in the lab. Finally, the differences of hydrophobicity transference between the RTV coating plate glass sample covered with the sugary contaminant and that covered with non-sugary contaminant were also investigated in the lab. The research results show that the sugary contamination is very absorbent and viscous, the hydrophobicity transference and the flashover voltage of RTV coating glass insulator covered with sugary contamination are worse than that covered with non-sugary contamination, but the flashover voltage is still higher 25% than that of non-RTV coating glass insulator. So it is still effective to improve outdoor insulation characteristics of glass insulator by spraying RTV coating in the sugary contamination areas.
Social selection and peer influence in an online social network

Disentangling the effects of selection and influence is one of social science's greatest unsolved puzzles: Do people befriend others who are similar to them, or do they become more similar to their friends over time? Recent advances in stochastic actor-based modeling, combined with self-reported data on a popular online social network site, allow us to address this question with a greater degree of precision than has heretofore been possible. Using data on the Facebook activity of a cohort of college students over 4 years, we find that students who share certain tastes in music and in movies, but not in books, are significantly likely to befriend one another. Meanwhile, we find little evidence for the diffusion of tastes among Facebook friends—except for tastes in classical/jazz music. These findings shed light on the mechanisms responsible for observed network homogeneity; provide a statistically rigorous assessment of the coevolution of cultural tastes and social relationships; and suggest important qualifications to our understanding of both homophily and contagion as generic social processes.
Microstructure of Welded Joints of X5CrNiCuNb16-4 (17-4 PH) Martensitic Stainlees Steel After Heat Treatment

The paper presents rezults of microstructure (LM, TEM) investigation and hardness measurments of welded joints in martensitic precipitation hardened stainless steel containing copper, subjected to heat treatment. For the aging temperature up to 540 ◦ C even for the very long times, the microstructure of the welded joints is similar to this one at lower temerature aging. After aging at 620 ◦ C a distinct change of the microstructure was observed. Non-equilibrium solidiﬁcation conditions of the weld metal, segregation and the diﬀusion of copper and the elements stablilizing the austenite cause the occurrence of the reverse transformation of the martensite into austenite as fast as just 1 hour at 620 ◦ C. TEM investigations revealed the diﬀerences in dispersion of hardening copper precipitates after aging at temperature 620 ◦ C for 1 and 4 hours.
Dioxygen and Metabolism; Dangerous Liaisons in Cardiac Function and Disease

The heart must consume a significant amount of energy to sustain its contractile activity. Although the fuel demands are huge, the stock remains very low. Thus, in order to supply its daily needs, the heart must have amazing adaptive abilities, which are dependent on dioxygen availability. However, in myriad cardiovascular diseases, “fuel” depletion and hypoxia are common features, leading cardiomyocytes to favor low-dioxygen-consuming glycolysis rather than oxidation of fatty acids. This metabolic switch makes it challenging to distinguish causes from consequences in cardiac pathologies. Finally, despite the progress achieved in the past few decades, medical treatments have not improved substantially, either. In such a situation, it seems clear that much remains to be learned about cardiac diseases. Therefore, in this review, we will discuss how reconciling dioxygen availability and cardiac metabolic adaptations may contribute to develop full and innovative strategies from bench to bedside.
Attention is Required for Maintenance of Feature Binding in Visual Working Memory

Working memory and attention are intimately connected. However, understanding the relationship between the two is challenging. Currently, there is an important controversy about whether objects in working memory are maintained automatically or require resources that are also deployed for visual or auditory attention. Here we investigated the effects of loading attention resources on precision of visual working memory, specifically on correct maintenance of feature-bound objects, using a dual-task paradigm. Participants were presented with a memory array and were asked to remember either direction of motion of random dot kinematograms of different colour, or orientation of coloured bars. During the maintenance period, they performed a secondary visual or auditory task, with varying levels of load. Following a retention period, they adjusted a coloured probe to match either the motion direction or orientation of stimuli with the same colour in the memory array. This allowed us to examine the effects of an attention-demanding task performed during maintenance on precision of recall on the concurrent working memory task. Systematic increase in attention load during maintenance resulted in a significant decrease in overall working memory performance. Changes in overall performance were specifically accompanied by an increase in feature misbinding errors: erroneous reporting of nontarget motion or orientation. Thus in trials where attention resources were taxed, participants were more likely to respond with nontarget values rather than simply making random responses. Our findings suggest that resources used during attention-demanding visual or auditory tasks also contribute to maintaining feature-bound representations in visual working memory—but not necessarily other aspects of working memory.
Smoothing of mirror substrates by thin-film deposition

Superpolished optical flats with high spatial frequency roughness below 0.1 nm have been commercially available for years. However, it is much more difficult to obtain figured optics of similar quality. We have obtained and tested the finish of figured optics from different vendors by atomic force microscopy and optical profilometry and have investigated how the substrate quality can be improved by the deposition of thin films. We have determined the growth parameters of several thin-film structures. From these parameters we can determine how the surface topography of a coated mirror differs from that of the substrate, select the best thin-film structure, and predict the possible improvement.
Trampoline: a double-sided elastic touch device for creating reliefs

Although reliefs are frequently used to add patterns to product surfaces, there is a lack of interaction techniques to model reliefs on the surface of virtual objects. We adopted the repoussé and chasing artwork techniques in an alternative interaction technique to model relief on virtual surfaces. To support this interaction technique, we developed the double-sided touchpad Trampoline that can detect the position and force of a finger touch on both sides. Additionally, Trampoline provides users with elastic feedback, as its surface consists of a stretchable fabric. We implemented a relief application with this device and the developed interaction technique. An informal user study showed that the proposed system can be a promising solution to create reliefs.
LEARNING TO PREDICT FOREST FIRES WITH DIFFERENT DATA MINING TECHNIQUES

The motivation for this study was to learn to predict forest fires in Slovenia using different data mining techniques. We used predictive models based on data from a GIS (geographical information system), the weather prediction model Aladin and MODIS satellite data. We examined three different datasets: one only for the Kras region, one for whole Primorska region and one for continental Slovenia. On these datasets we applied logistic regression and decision trees, as well as random forests, bagging and boosting of decision trees, in order to obtain predictive models of fire outbrakes. Best results in terms of predictive accuracy were obtained by bagging
Common Structural Basis for Constitutive Activity of the Ghrelin Receptor Family*

Three members of the ghrelin receptor family were characterized in parallel: the ghrelin receptor, the neurotensin receptor 2 and the orphan receptor GPR39. In transiently transfected COS-7 and human embryonic kidney 293 cells, all three receptors displayed a high degree of ligand-independent signaling activity. The structurally homologous motilin receptor served as a constitutively silent control; upon agonist stimulation, however, it signaled with a similar efficacy to the three related receptors. The constitutive activity of the ghrelin receptor and of neurotensin receptor 2 through the Gq, phospholipase C pathway was ∼50% of their maximal capacity as determined through inositol phosphate accumulation. These two receptors also showed very high constitutive activity in activation of cAMP response element-driven transcription. GPR39 displayed a clear but lower degree of constitutive activity through the inositol phosphate and cAMP response element pathways. In contrast, GPR39 signaled with the highest constitutive activity in respect of activation of serum response element-dependent transcription, in part, possibly, through G12/13 and Rho kinase. Antibody feeding experiments demonstrated that the epitope-tagged ghrelin receptor was constitutively internalized but could be trapped at the cell surface by an inverse agonist, whereas GPR39 remained at the cell surface. Mutational analysis showed that the constitutive activity of both the ghrelin receptor and GPR39 could systematically be tuned up and down depending on the size and hydrophobicity of the side chain in position VI:16 in the context of an aromatic residue at VII:09 and a large hydrophobic residue at VII:06. It is concluded that the three ghrelin-like receptors display an unusually high degree of constitutive activity, the structural basis for which is determined by an aromatic cluster on the inner face of the extracellular ends of TMs VI and VII.
Persistence and Evolution of Feline Coronavirus in a Closed Cat-Breeding Colony

Abstract Feline coronavirus (FCoV) persistence and evolution were studied in a closed cat-breeding facility with an endemic serotype I FCoV infection. Viral RNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in the feces and/or plasma of 36 of 42 cats (86%) tested. Of 5 cats, identified as FCoV shedders during the initial survey, 4 had detectable viral RNA in the feces when tested 111 days later. To determine whether this was due to continuous reinfection or to viral persistence, 2 cats were placed in strict isolation and virus shedding in the feces was monitored every 2–4 days. In 1 of the cats, virus shedding continued for up to 7 months. The other animal was sacrificed after 124 days of continuous virus shedding in order to identify the sites of viral replication. Viral mRNA was detected only in the ileum, colon, and rectum. Also in these tissues, FCoV-infected cells were identified by immunohistochemistry. These findings provide the first formal evidence that FCoV causes chronic enteric infections. To assess FCoV heterogeneity in the breeding facility and to study viral evolution during chronic infection, FCoV quasispecies sampled from individual cats were characterized by RT-PCR amplification of selected regions of the viral genome followed by sequence analysis. Phylogenetic comparison of nucleotides 7–146 of ORF7b to corresponding sequences obtained for independent European and American isolates indicated that the viruses in the breeding facility form a clade and are likely to have originated from a single founder infection. Comparative consensus sequence analysis of the more variable region formed by residues 79–478 of the S gene revealed that each cat harbored a distinct FCoV quasispecies. Moreover, FCoV appeared to be subject to immune selection during chronic infection. The combined data support a model in which the endemic infection is maintained by chronically infected carriers. Virtually every cat born to the breeding facility becomes infected, indicating that FCoV is spread very efficiently. FCoV-infected cats, however, appear to resist superinfection by closely related FCoVs.
Trends in Asymptomatic Nasopharyngeal Colonization With Streptococcus pneumoniae After Introduction of the 13-valent Pneumococcal Conjugate Vaccine in Calgary, Canada

Background: We previously reported serotype-specific trends in pneumococcal nasopharyngeal colonization soon after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in mid-2002. Our current aim is to describe later trends after PCV7 and early trends after PCV13 vaccine introduction in 2010. Methods: The Calgary Area Streptococcus pneumoniae Epidemiology Research team conducted 10 point-prevalence surveys of pneumococcal nasopharyngeal colonization in healthy children aged 12 and 18 months and 4.5 years biannually from 2003 to 2005 (previously reported) and annually in 2006, 2010, 2011 and 2012. Results: For surveys conducted during 2010–2012, the proportion colonized was 13.2% compared with 19.9% in surveys conducted during 2003–2006 (P < 0.001). Vaccination with 2 or more doses of PCV7 or PCV13, older age and recent antibiotic use reduced the odds of colonization with any pneumococcus. By 2012, 94% of all isolates were nonvaccine serotypes with 11A, 15A/B/C, 22F, 23A/B and 35B/F representing 75% of all isolates. Conclusions: Pneumococcal nasopharyngeal colonization has changed profoundly since the introduction of conjugate vaccines and overall colonization by pneumococcus has declined in recent years. By 2012, nonvaccine serotypes have nearly completely replaced vaccine serotypes. The impact on clinical disease remains to be seen.
How does temporal preparation speed up response implementation in choice tasks? Evidence for an early cortical activation.

We investigated the influence of temporal preparation on information processing. Single-pulse transcranial magnetic stimulation (TMS) of the primary motor cortex was delivered during a between-hand choice task. The time interval between the warning and the imperative stimulus varied across blocks of trials was either optimal (500 ms) or nonoptimal (2500 ms) for participants' performance. Silent period duration was shorter prior to the first evidence of response selection for the optimal condition. Amplitude of the motor evoked potential specific to the responding hand increased earlier for the optimal condition. These results revealed an early release of cortical inhibition and a faster integration of the response selection-related inputs to the corticospinal pathway when temporal preparation is better. Temporal preparation may induce cortical activation prior to response selection that speeds up the implementation of the selected response.