Miracle-dz/UniFAR-FTUs huggingface dataset:
COX-2 and BRCA1 have altered expression profile in different canine tumors.

Cancer originates from the unnatural divisions of cells that have constant mutations in the genes which are involved in cell propagation and endurance. Dogs are beloved pet animals and they suffer from many cancers like humans. Mutated BRCA1 and COX-2 abnormal gene expression have been seen in a large number of cancers previously. In this research gene sequencing and gene expression of COX-2 and BRCA1 genes in 22 different canine tumors and 25 normal canine samples were performed. All samples were collected from Punjab Province, Pakistan. The whole coding region of COX2, comprised of almost 1812bp with ten exons in dog and the hot spot N (1, 2 and 12 exons) and Cterminal (18, 19, 20, 21 and 22 exons) of BRCA1 gene which include 2024bp were included in mutational studies. There was no mutation in the coding region of COX-2 and 5’and -3’ region of BRCA1. The gene expression of COX-2 and BRCA1 in all aforementioned tumors was measured by real time qPCR. BRCA1 high grade negative expression and COX-2 positive gene expression were observed in this study. About 45% tumors showed up-regulation of COX-2 and four tumors showed highest gene expression, two CTVTs, one head tumor and one mammary tumor with fold changes 942.93, 122.79, 85.95 and 44.49 respectively. All granulomas showed down-regulation of COX-2 gene. It has been observed during this study that the loss of BRCA1 gene expression and up-regulation of the COX-2 gene may have a role in canine tumors. Altered expression of COX-2 gene in tumors may have link with the extent of aggressive tumor types. The mechanism behind the abnormal function of these genes is not clear yet, however, abnormal expression of COX-2 and BRCA1 in tumors may be associated with the most aggressive and poor prognosis of cancer types and further studies are required.
Infrequent dream recall associated with low performance but high overnight improvement on mirror‐tracing

Although sleep facilitates learning and memory, the roles of dreaming and habitual levels of recalling dreams remain unknown. This study examined if performance and overnight improvement on a rapid eye movement sleep‐sensitive visuomotor task is associated differentially with habitually high or low dream recall frequency. As a relation between dream production and visuospatial skills has been demonstrated previously, one possibility is that frequency of dream recall will be linked to performance on visuomotor tasks such as the Mirror Tracing Task. We expected that habitually low dream recallers would perform more poorly on the Mirror Tracing Task than would high recallers and would show less task improvement following a night of sleep. Fifteen low and 20 high dream recallers slept one night each in the laboratory and performed the Mirror Tracing Task before and after sleep. Low recallers had overall worse baseline performance but a greater evening‐to‐morning improvement than did high recallers. Greater improvements in completion time in low recallers were associated with Stage 2 rather than rapid eye movement sleep. Findings support the separate notions that dreaming is related to visuomotor processes and that different levels of visuomotor skill engage different sleep‐ and dream‐related consolidation mechanisms.
Autoantibodies specific for the cardiac myosin isoform are found in mice susceptible to Coxsackievirus B3-induced myocarditis.

Several mouse strains are susceptible to immunopathic myocarditis after infection with Coxsackievirus B3 (CB3). This disease is associated with autoantibodies that are directed against myosin. In this study we characterized sera from CB3-infected mice for their reactivity with three different myosin isoforms (heart, skeletal muscle, and brain myosins) and for autoantibody isotype by using an ELISA. Competitive inhibition assays and absorption studies with various myosins demonstrated the presence of two autoantibody populations in sera of susceptible A.CA and A.SW mice. The first was specific for cardiac myosin and was mainly IgG. The second antibody population cross-reacted with heart, skeletal muscle, and brain myosin and was mainly IgM. B10.PL/SgSf and B10.A/SgSf mice, which do not develop immunopathic myocarditis, produced only the IgM autoantibody population cross-reactive with all three myosin isoforms. Because the heart-specific myosin autoantibodies were found exclusively in the mouse strains that developed immunopathic myocarditis, they can be considered a serologic marker for autoimmune heart disease.
A Novel Function for the Second C2 Domain of Synaptotagmin

Synaptotagmin serves as the major Ca sensor for regulated exocytosis from neurons. While the mechanism by which synaptotagmin regulates membrane fusion remains unknown, studies using Drosophila indicate that the molecule functions as a multimeric complex and that its second C2 domain is essential for efficient excitation-secretion coupling. Here we describe biochemical data that may account for these phenomena. We report that Ca causes synaptotagmin to oligomerize, primarily forming dimers, via its second C2 domain. This effect is specific for divalent cations that can stimulate exocytosis of synaptic vesicles (Ca Ba, Sr > Mg) and occurs with an EC value of 3-10 μM Ca. In contrast, a separate Ca-dependent interaction between synaptotagmin and syntaxin, a component of the fusion apparatus, occurs with an EC value of 100 μM Ca and involves the synergistic action of both C2 domains of synaptotagmin. We propose that Ca triggers two consecutive protein-protein interactions: the formation of synaptotagmin dimers at low Ca concentrations followed by the association of synaptotagmin dimers with syntaxin at higher Ca-concentrations. Our findings, in conjunction with physiological studies, indicate that the Ca-induced dimerization of synaptotagmin is important for the efficient regulation of exocytosis by Ca.
Skin Surface Topography and Texture Analysis of Sun-Exposed Body Sites in View of Sunscreen Application

Background/Aims: To determine the roughness of the surface of human skin at highly sun-exposed anatomical sites in a wide age range in order to derive consequences for sunscreen application. Methods: The forehead, cheek, nose, shoulder, and dorsal hand of 4 age groups (0-9, 20-39, 40-59, and >60 years) were investigated by replica formation, and areal topography was determined by confocal chromatic imaging. The arithmetic mean height as a roughness parameter and the void volume of the surface profile were calculated. Results: Age and site had a significant effect on roughness. Both the dorsal hand and nose exhibited the greatest roughness over the age of 40, and the forehead of the youngest age group exhibited the smallest roughness. Differentiation between sites progressed with age, whereas roughness increased significantly with age for the dorsal hand and nose but not for the other sites. The void volume was smaller than the volume corresponding to the typically recommended amount of sunscreen application except for the cases of largest roughness. Conclusions: Different site-age combinations show significant variation of skin surface roughness. The application of sunscreen may in some instances need to be adjusted to take into account the increased roughness of highly sun-exposed anatomical sites.
Mitigation of opioid off-target effects and identification of structural drivers of opioid receptor engagement for BACE-1 small molecule inhibitors

Abstract Application of safety lead optimization screening strategies during the early stage of drug discovery led to the identification of a series of CNS-active small molecule inhibitors with opioid off-target effects, as evidenced by potent agonistic activity in functional cell-based assays for mu (MOP), kappa (KOP) and delta (DOP) opioid receptors. The translation of these effects was confirmed in vivo with the following observations: hypoactivity and decreased fecal production in rats (characteristic of MOP agonism); increased urine production in rats (characteristic of KOP agonism); and decreased intestinal transit time in mice, which was partially blocked by the MOP antagonist naloxone, demonstrating that the in vivo effects were specific for MOP. Based on the confirmation of in vitro–in vivo translatability, an in vitro screening strategy was implemented that resulted in the identification of an optimized backup molecule, devoid of in vivo off-target opioid effects. In addition, in silico modeling by docking of the various molecules to the opioid receptors allowed the identification of the structural drivers of these off-target effects, which can be applied to future chemical-design criteria. Thus, implementation of the safety lead optimization strategy described in this article demonstrates the utility and impact of such approaches on risk mitigation and identification of lead small molecules with improved safety profiles.
Sufentanil Pharmacokinetics in Pediatric Cardiovascular Patients

The pharmacokinetics of sufentanil were studied in 28 pediatric patients undergoing cardiovascular procedures. Patients were divided into four groups on the basis of age: neonates (0–1 month, n = 9), infants (1–24 months, n = 7), children (2–12 yr, n = 7), and adolescents (12–18 yr, n = 5). Sufentanil 10–15 μg/kg, was administered by IV bolus and plasma concentrations measured for up to 20 hr. A tri-exponential equation best described the time-concentration data in all patients. Clearance rate (Cl) was 6.7 ± 6.1 ml·Kg−1·min−1 (± SD) in neonates, which was significantly lower than the values of 18.1 ± 2.7, 16.9 ± 3.2, and 13.1 ± 3.6ml·kg−1min−1 observed in infants, children, and adolescents, respectively. The volume of distribution at steady state (Vdss) was 4.15 ± 1.0 L/kg in neonates, significantly greater than the values of 2.73 ± 0.5 and 2.75 ± 0.5 L/kg observed in children and adolescents, respectively. The elimination half-life (T½β) was 783 ± 346 min in neonates, significantly longer than the values of 214 ± 41, 140 ± 30, and 209 ± 23 min observed in infants, children, and adolescents, respectively. The plasma concentration of sufentanil at the time of additional anesthetic supplementation to suppress homodynamic responses to surgical stimulation was 2.51 ng/ml in neonates, significantly higher than the levels of 1.58, 1.53, and 1.56 ng/ml observed in infants, children, and adolescents, respectively. The authors conclude that age-related differences in pharmacokinetic and pharmacodynamic properties of sufentanil are evident in pediatric patients with major cardiovascular disease who are undergoing cardiovascular surgery.
Packages With Integrated 60-GHz Aperture-Coupled Patch Antennas

This paper presents balanced-fed and fork-fed aperture-coupled patch antennas and 16-element arrays suitable for broadband millimeter-wave communications. The antennas are realized in a multi-layer organic package structure, to which RF integrated circuits can be integrated. To improve antenna bandwidth and radiation efficiency, an air cavity is used, resulting in a superstrate planar patch-antenna structure. Additionally, resonating apertures are used to further increase the antenna bandwidth. Measured results at 60 GHz for the antennas show good performance in terms of peak gain (about 8 dBi for a single element and 17 dBi for a 16-element array), bandwidth ( >; 10 GHz for 10-dB return loss bandwidths are achievable), and radiation efficiency (80% for single-element from simulation).
Analytical considerations for an ISO/IEC14443 compliant SmartCard transponder

We derive and use an analytical formula to describe some aspects in the RF behaviour of Smartcard transponders at the contactless air interface. The aspects we consider contain minimum operating H-field, thermal loading, card loading and maximum load modulation depending on transponder equivalent circuit parameters. We not only consider results, but also carefully discuss the approximations and simplifications we make, which should give an understanding of the principle and thereby allow for adaptations to selected fabrication technologies among the variety of existing options.
Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary gland

Estrogen receptor (ER)-mediated gene expression plays an essential role in mammary gland morphogenesis, function, and carcinogenesis. The repressor of ER activity (REA) is an ER-interactive protein that counterbalances estrogen-induced ER transcriptional activity. Our previous study showed that genetic deletion of both REA alleles resulted in embryonic lethality. This study demonstrates that REA and ERα are coexpressed in mammary epithelial cells. REA heterozygous (REA+/−) mutant mice exhibit faster mammary ductal elongation in virgin animals, increased lobuloalveolar development during pregnancy, and delayed mammary gland involution after weaning. These morphological phenotypes of REA+/− mice are associated with significantly increased cell proliferation and ER transcriptional activities, as indicated by the estrogen response element (ERE)-luciferase reporter in the WT/ERE-Luc and REA+/−/ERE-Luc bigenic mice and by the higher expression levels of estrogen-responsive genes such as progesterone receptor and cyclin D1 in the mammary gland. Our analysis also revealed that REA is an important repressor of ER transcriptional activity in the mammary gland under natural, as well as ovariectomized and estrogen-replaced, hormonal conditions. Our results indicate that REA is a physiological modulator of ER function in the mammary gland and that its correct gene dosage is required for maintenance of normal ER activity and normal mammary gland development. Consequently, a reduction or loss of REA function may cause overactivation of ER and increase breast cancer risk in humans.
Doubly‐robust dynamic treatment regimen estimation via weighted least squares

Personalized medicine is a rapidly expanding area of health research wherein patient level information is used to inform their treatment. Dynamic treatment regimens (DTRs) are a means of formalizing the sequence of treatment decisions that characterize personalized management plans. Identifying the DTR which optimizes expected patient outcome is of obvious interest and numerous methods have been proposed for this purpose. We present a new approach which builds on two established methods: Q‐learning and G‐estimation, offering the doubly robust property of the latter but with ease of implementation much more akin to the former. We outline the underlying theory, provide simulation studies that demonstrate the double‐robustness and efficiency properties of our approach, and illustrate its use on data from the Promotion of Breastfeeding Intervention Trial.
Effects of a maximal exercise test on neurocognitive function

Objective: To examine the effects of a maximal exercise test on cognitive function in recreational athletes. Design: A repeated-measures design was used to compare baseline with post-cognitive function and fatigue symptoms after a maximal exercise test. Setting: Division 1 American Midwestern University, (Michigan State University, Michigan, USA). Participants: 102 male and female recreational athletes. Intervention: Participants in the experimental group (n = 54) were asked to perform a maximal treadmill exercise test to maximal oxygen uptake (VO2 max). Participants in the control group were asked to rest for 15 min. Main outcome measurements: All participants were administered a neuropsychological test battery called Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) before and after exercise to measure neurocognitive function and fatigue symptoms. Results: Results revealed a significant group (control, experimental)×time (baseline, post-test 1, post-test 2) interaction for verbal memory composite scores (p = 0.025). Specifically, verbal memory composite scores decreased in the experimental group from baseline to post-test 1 (p = 0.00). These values returned to baseline 3 days after the Vo2 max test (p = 0.00). Further analysis on verbal memory composite scores demonstrated significant differences on immediate recall memory (p = 0.00) and delayed recall memory (p = 0.00). No significant differences were observed for visual memory (p = 0.54), motor processing speed (p = 0.68) and reaction time (p = 0.44) composite scores between the experimental and control groups. Conclusion: The results of this study suggest that a maximal exercise test attenuated a limiting effect on cognitive function. When utilising a neuropsychological test battery to evaluate a patient who has sustained a head injury, the test should not be administered immediately after a practice or a game session.
Microarray Analysis Reveals Induction of Lipoprotein Genes in Mucoid Pseudomonas aeruginosa: Implications for Inflammation in Cystic Fibrosis

ABSTRACT The main cause of the high morbidity and mortality of cystic fibrosis (CF) is the progressive lung inflammation associated with Pseudomonas aeruginosa colonization. During the course of chronic CF infections, P. aeruginosa undergoes a conversion to a mucoid phenotype. The emergence of mucoid P. aeruginosa in CF is associated with increased inflammation, respiratory decline, and a poor prognosis. Here we show, by the use of microarray analysis, that upon P. aeruginosa conversion to mucoidy, there is a massive and preferential induction of genes encoding bacterial lipoproteins. Bacterial lipoproteins are potent agonists of Toll-like receptor 2 (TLR2) signaling. The expression of TLR2 in human respiratory epithelial cells was ascertained by Western blot analysis. Human respiratory epithelial cells responded in a TLR2-dependent manner to bacterial lipopeptides derived from Pseudomonas lipoproteins induced in mucoid strains. The TLR2 proinflammatory response was further augmented in CF cells. Thus, the excessive inflammation in CF is the result of a global induction in mucoid P. aeruginosa of lipoproteins that act as proinflammatory toxins (here termed lipotoxins) superimposed on the hyperexcitability of CF cells. Blocking the signaling cascade responding to bacterial lipotoxins may provide therapeutic benefits for CF patients.
Labels and sentiment in social media: On the role of perceived agency in online discussions of the refugee crisis

By focusing on the recent events in the Middle East, that have pushed many to flee and seek refuge in neighboring countries or in Europe, we investigate dynamics of label use in social media, the emergent patterns of labeling that can cause further disaffection and tension, and the sentiments associated with the different labels. To achieve this, we examine key labels pertaining to the refugee/migrant crisis and their usage in the user comment thread of a highly viewed and informational video of the crisis on YouTube. The use of labels indicate that migration issues are being framed not only through labels characterizing the crisis but also by their describing the individuals themselves. The sentiments associated with these labels depart from what one would normally expect; in particular, negative sentiment is attached to labels that would otherwise be deemed neutral or positive. Interestingly, both positive and negative labels exhibit increased negativity across time. Using topic modeling and sentiment analysis jointly, we discover that the latent topics of the most positive comments show more overlap than those topics of the most negative comments, which are more focused and partitioned. In terms of sentiment, we find that labels indicating some degree of perceived agency or opportunity, such as 'migrant' or 'immigrant', are embedded in less sympathetic comments than those labels indicating a need to escape war-torn regions or persecution (e.g., asylum seeker or refugee). Our study offers valuable insights into the direction of public sentiment and the nature of discussions surrounding this significant societal event, as well as the nature of online opinion sharing.
Robotic wheelchair with omni-directional vision for moving alongside a caregiver

Recently, several robotic/intelligent wheelchairs equipped with user-friendly interfaces and/or autonomous functions to fulfill set goals have been proposed. Although wheelchair users may wish to go out alone, caregivers often accompany them. Therefore, it is important to consider how to reduce the caregivers' load while supporting their activities and facilitating communication between the caregiver and wheelchair user. Hence, we have proposed a robotic wheelchair that can move alongside a caregiver by observing his/her behavior, such as body position and orientation. This form of motion enables easy communication between the wheelchair user and the caregiver. However, in our previous system, the caregiver had to set their own initial position by tapping the touchscreen displaying the distance data image captured by a laser range sensor. In this paper, therefore, we introduce a new interface we designed by incorporating an omni-directional camera so that the accompanying caregiver can easily set the initial position by tapping his/her facial image instead. Moreover, when the system loses the accompanying caregiver due to them making an unexpected motion, it promptly re-identifies the caregiver by using color appearance cues. These functions improve the usefulness of our robotic wheelchair and heighten the possibility of our wheelchair being utilized in our daily life.
Minimal subenhancer requirements for high-level polyomavirus DNA replication: a cell-specific synergy of PEA3 and PEA1 sites

The cell-specific regulation of DNA replication has important implications for the molecular strategy of cellular gene control. Mouse polyomavirus (Py) DNA replication is examined as a model of cell-specific replication control. Using an FM3A-derived mouse cell line which expresses early viral proteins (FOP cells), we determined the minimal sequence requirements for viral DNA replication. FOP cells were observed to have much simpler enhancer requirements than 3T6 and many other cells and did not need a B enhancer for high levels of DNA replication. Using these cells, we show that the individual or tandem binding sites for several unrelated trans-acting factors which are generally subfunctional as transcriptional enhancers (simian virus 40 A core, TGTGGAATG; EBP20, TGTGGTTTT; PEA1 [an AP-1 analog], GTGACTAA; PEA2, GACCGCAG; and PEA3, AGGAAG) stimulated low levels of Py DNA replication. The ordered dimeric combination of PEA3 and PEA1 factor-binding sites, however, acted synergistically to stimulate viral DNA replication to high wild-type levels. This is in contrast to prior results in which much larger enhancer sequences were necessary for high-level viral DNA replication. PEA3/PEA1-stimulated DNA replication showed a distance and orientation independence relative to the origin, which disagrees with some but not other prior analyses of enhancer-dependent DNA replication. It therefore appears that trans-acting factor-binding sites (enhansons) can generally activate DNA replication and that the AP-1 family of sites may act synergistically with other associated trans-acting factors to strongly affect Py DNA replication in specific cells.