Miracle-dz/UniFAR-FTUs huggingface dataset:
Slow Delayed Rectifier Potassium Current Blockade Contributes Importantly to Drug-Induced Long QT Syndrome

Background— Drug-induced long QT syndrome is generally ascribed to inhibition of the cardiac rapid delayed rectifier potassium current (IKr). Effects on the slow delayed rectifier potassium current (IKs) are less recognized. Triggered by a patient who carried the K422T mutation in KCNQ1 (encoding the &agr;-subunit of the IKs channel), who presented with excessive QT prolongation and high serum levels of norfluoxetine, we investigated the effects of fluoxetine and its metabolite norfluoxetine on IKs. Methods and Results— ECG data from mutation carriers and noncarriers revealed that the K422T mutation per se had mild clinical effects. Patch clamp studies, performed on HEK293 cells, showed that heterozygously expressed K422T KCNQ1/KCNE1 channels had a positive shift in voltage dependence of activation and an increase in deactivation rate. Fluoxetine and its metabolite norfluoxetine both inhibited KCNQ1/KCNE1 current, with norfluoxetine being the most potent. Moreover, norfluoxetine increased activation and deactivation rates. Computer simulations of the effects of norfluoxetine on IKs and IKr demonstrated significant action potential prolongation, to which IKs block contributed importantly. Although the effects of the mutation per se were small, additional IKs blockade by norfluoxetine resulted in more prominent QTc prolongation in mutation carriers than in noncarriers, demonstrating synergistic effects of innate and drug-induced IKs blockade on QTc prolongation. Conclusions— IKs blockade contributes importantly to drug-induced long QT syndrome, especially when repolarization reserve is reduced. Drug safety tests might have to include screening for IKs blockade.
Development and implementation of treadmill exercise testing protocols in COPD

Background: Because treadmill exercise testing is more representative of daily activity than cycle testing, we developed treadmill protocols to be used in various clinical settings as part of a two-year, multicenter, chronic obstructive pulmonary disease (COPD) trial evaluating the effect of tiotropium on exercise. Methods: We enrolled 519 COPD patients aged 64.6 ± 8.3 years with a postbronchodilator forced expiratory volume in one second (FEV1) of 1.25 ± 0.42 L, 44.3% ± 11.9% predicted. The patients performed symptom-limited treadmill tests where work rate (Ẇ) was increased linearly using speed and grade adjustments every minute. On two subsequent visits, they performed constant Ẇ tests to exhaustion at 90% of maximum Ẇ from the incremental test. Results: Mean incremental test duration was 522 ± 172 seconds (range 20–890), maximum work rate 66 ± 34 watts. For the first and second constant Ẇ tests, both at 61 ± 33 watts, mean endurance times were 317 ± 61 seconds and 341 ± 184 seconds, respectively. The mean of two tests had an intraclass correlation coefficient of 0.85 (P < 0.001). During the second constant Ẇ test, 88.2% of subjects stopped exercise because of breathing discomfort; 87.1% for Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage II, 88.5% for GOLD Stage III, and 90.2% for GOLD Stage IV. Conclusion: The symptom-limited incremental and constant work treadmill protocol was well tolerated and appeared to be representative of the physiologic limitations of COPD.
Swarm-based visual saliency for trail detection

This paper proposes a model for trail detection that builds upon the observation that trails are salient structures in the robot's visual field. Due to the complexity of natural environments, the straightforward application of bottom-up visual saliency models is not sufficiently robust to predict the location of trails. As for other detection tasks, robustness can be increased by modulating the saliency computation with top-down knowledge about which pixel-wise visual features (e.g., colour) are the most representative of the object being sought. This paper proposes the use of the object's overall layout instead, as it is a more stable and predictable feature in the case of natural trails. This novel component of top-down knowledge is specified in terms of perception-action rules, which control the behaviour of simple agents performing as a swarm to compute the saliency map of the input image. For the purpose of multi-frame evidence accumulation about the trail location, a motion compensated dynamic neural field is used. Experimental results on a large data-set reveal the ability of the model to produce a success rate of 91% at 20Hz. The model shows to be robust in situations where previous trail detectors would fail, such as when the trail does not emerge from the lower part of the image or when it is considerably interrupted.
Interaction and Feedback Regulation between STK15/BTAK/Aurora-A Kinase and Protein Phosphatase 1 through Mitotic Cell Division Cycle*

STK15 is an Aurora/Ipl-1 related serine/threonine kinase that is associated with centrosomes and induces aneuploidy when overexpressed in mammalian cells. It is well known that phosphorylation and dephosphorylation of kinases are important for regulation of their activity. But mechanisms by which STK15 activity is regulated have not been elucidated. We report that STK15 contains two functional binding sites for protein phosphatase type 1 (PP1), and the binding of these proteins is cell cycle-regulated peaking at mitosis. Activated STK15 at mitosis phosphorylates PP1 and inhibits PP1 activity in vitro. In vivo, PP1 activity co-immunoprecipitated with STK15 is also reduced. These data indicate that STK15 inhibits PP1 activity during mitosis. Also, PP1 is shown to dephosphorylate active STK15 and abolish its activity in vitro. Furthermore, we show that non-binding mutants of STK15 for PP1 are superphosphorylated, but their kinase activities are markedly reduced. Cells transfected with these non-binding mutants manifest aberrant chromosome alignment during mitosis. Our results suggest that a feedback regulation through phosphorylation/dephosphorylation events between STK15 kinase and PP1 phosphatase operates through the cell cycle. Deregulation of this balance may contribute to anomalous segregation of chromosomes during mitotic progression of cancer cells.
Evolution of stellar winds from the Sun to red giants

Abstract By performing global 1D MHD simulations, we investigate the heating and acceleration of solar and stellar winds in open magnetic field regions. Our simulation covers from photosphere to 20-60 stellar radii, and takes into account radiative cooling and thermal conduction. We do not adopt ad hoc heating function; heating is automatically calculated from the solutions of Riemann problem at the cell boundaries. In the solar wind case we impose transverse photospheric motions with velocity ~1 km/s and period between 20 seconds and 30 minutes, which generate outgoing Alfvén waves. We have found that the dissipation of Alfvén waves through compressive wave generation by decay instability is quite effective owing to the density stratification, which leads to the sufficient heating and acceleration of the coronal plasma. Next, we study the evolution of stellar winds from main sequence to red giant phases. When the stellar radius becomes ~10 times of the Sun, the steady hot corona with temperature 106 K, suddenly disappears. Instead, many hot and warm (105 – 106 K) bubbles are formed in cool (T < 2 × 104 K) chromospheric winds because of the thermal instability of the radiative cooling function; the red giant wind is not a steady stream but structured outflow.
A phase II study of gefitinib for patients with advanced HER-1 expressing synovial sarcoma refractory to doxorubicin-containing regimens.

RATIONALE Advanced synovial sarcomas (SyS) refractory to doxorubicin and ifosfamide are highly resistant to the currently available cytotoxic agents. Based on a report showing a specific overexpression of HER-1 in SyS, we investigated an HER-1 inhibitor, gefitinib, in refractory SyS. SUBJECTS AND METHODS To establish the efficacy and safety of gefitinib in HER-1 - positive SyS refractory to one or two lines of doxorubicin- and ifosfamide-based chemotherapy, a phase II study was conducted from December 2002 to October 2005 by 12 centers of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Gefitinib was given at a 500-mg/day oral dose until progression or intolerance. RESULTS Forty-eight patients were included (46 eligible). All patients had previously received chemotherapy for metastatic disease, with a median number of two lines (range, 1-4). The most frequent metastatic sites were the lungs (n = 44, 92%), lymph nodes (n = 11, 23%), and soft tissues (n = 10, 21%). The median duration of treatment was 43 days (range, 13-315). Treatment was interrupted in five patients (10%). Treatment was halted for progression in 45 (94%) patients. The best response was stable disease in 10 patients (21%). Disease progression occurred in 32 patients (70%), with a median time to disease progression of 6 weeks. Progression-free survival at 4 and 6 months was 21% and 6%, respectively. CONCLUSION The results show that gefitinib monotherapy in advanced SyS refractory to conventional chemotherapy did not demonstrate sufficient activity to warrant further investigation in this setting. This may suggest that HER-1 is not a critical protein in tumor progression in this disease.
A Modified Secure Scheme of Quantum Key Distribution Without Public Announcement Bases

This study provides a simple variation of the protocol of quantum key expansion proposed by Hwang. Some weaknesses relating to the step of public discussions for error detection are analyzed and an attack strategy, allowing the eavesdropper to get partial information about the used bases, is put forward. Using the One-Time Pad cipher, we propose a possible scheme which is secure against the presented attack.
Genetic Polymorphisms of CYP2E1 and Risk of Colorectal Adenomas in the Self Defense Forces Health Study

CYP2E1 is an enzyme involved in the metabolism of N-nitrosamines and other carcinogenic substances. Functional RsaI and 96-bp insertion polymorphisms in 5′-flanking region have drawn interest in relation to the risk of colorectal cancer. We investigated the relation of these genetic polymorphisms and colorectal adenoma, a well-established precursor lesion of colorectal cancer. Subjects were 455 cases of colorectal adenomas and 1,052 controls of normal colonoscopy among men receiving a preretirement health examination in the Self Defense Forces. Genotypes were determined by either PCR-RFLP or PCR method. Statistical adjustment was made for smoking, alcohol use, body mass index, physical activity, and others. Individuals with RsaI c2 allele showed a decreased risk of proximal colon adenomas; adjusted odds ratios (95% confidence interval) of proximal and distal adenomas for the c1/c2 or c2/c2 genotype versus c1/c1 was 0.61 (0.41-0.88) and 0.95 (0.71-1.27), respectively. CYP2E1 96-bp insertion allele was associated with an increased risk of large (≥ 5 mm) adenomas; adjusted odds ratios (95% confidence interval) of large and small adenomas for having at least one insertion allele were 1.41 (1.03-1.94) and 0.94 (0.71-1.25), respectively. A suggestive effect modification was noted for alcohol consumption on the association between RsaI polymorphism and proximal adenomas (Pinteraction = 0.09) as well as on the association between 96-bp insertion and large adenomas (Pinteraction = 0.05). These findings indicate that variation in activity and inducibility of CYP2E1 contribute to the development of colorectal carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1800–7)
Disabled women and socio-spatial 'barriers' to motherhood.

Disabled women’s social history of institutionalisation and spatial segregation has, over time and space, set them apart from mainstream society and rendered them invisible in the spaces and places of everyday life. In more contemporary times, when disabled women ‘invade’ reproductive spaces, their presence as prospective parents, ‘becoming mothers’ or mothers, is often regarded as ‘out of place’. This study hence incorporates a historical review that traces the spatial realities of disabled women’s and girl’s lives between 1796-1910 in Glasgow and Edinburgh. This reveals the development of social stereotypes and misunderstandings of disabled women’s lives and bodies, particularly their assumed asexuality and inappropriateness for undertaking reproductive or mothering roles. Disabled women’s ‘voices’ are to the fore in the contemporary chapters of the thesis, reflecting the reproductive and non-reproductive experiences of 27 disabled women resident in the Glasgow and Edinburgh areas. These narratives offer an insight into the embodied experiences of ‘disability’ in private and public space. Being placed sexually ‘off limits’, and rendered ‘out of place’ in and by reproductive or mothering environments, constitute some of the social and spatial barriers to motherhood encountered by disabled women. It is hoped that this study contributes to the process of recovering the forgotten histories and neglected experiences of disabled women, particularly in terms of their social exclusion, infantilisation and desexualisation that have reduced disabled women’s participation in child-rearing and motherhood across time and space. The chronological framework of this study reveals slow but positive changes in social attitudes towards disabled women expressing reproductive choices, raising children and creating a ‘place’ for themselves as mothers in contemporary society.
Molecular epidemiological investigation of Ascaris genotypes in China based on single‐strand conformation polymorphism analysis of ribosomal DNA

Using a single‐strand conformation polymorphism‐based approach, we investigated nucleotide variation in part of the first internal transcribed spacer (pITS‐1) of nuclear ribosomal DNA within and among a large number of Ascaris individuals from humans and pigs from six endemic regions in China, and examined the frequency of the different genotypes of Ascaris in relation to host species and geographical origin. Five different SSCP genotypes (G1–G5) were recorded for human Ascaris (n = 486), of which three (genotypes G1–G3) were detected for pig Ascaris (n = 329). Of the five Ascaris genotypes detected, genotype G1 predominantly infected humans (∼63–74%) whereas genotype G3 infected mainly pigs (∼79–86%), indicating that each of these genotypes has a particular host affiliation. In contrast, the frequencies of the other three genotypes was substantially lower for each of the two host species. The findings also suggested that the rate of cross infection of Ascaris between humans and pigs is relatively low and that gene flow between the predominant genotypes is limited, consistent with previous proposals for endemic regions in other countries. While the nature and extent of nucleotide variation in the pITS‐1 (and the proposal of host affiliated Ascaris populations) may relate to “introgression” or “lineage sorting and retention of ancentral polymorphism”, other explanations are possible. Evidence of multiple pITS‐1 sequence types in some Ascaris individuals representing particular genotypes (e.g., G2 and G5) may suggest hybridization between human‐ and pig‐affiliated Ascaris. This aspect and the species status of Ascaris (from each host species) warrant future experimental testing, employing the pig/Ascaris model and the present electrophoretic approach. *
Fusing Music and Video Modalities Using Multi-timescale Shared Representations

We propose a deep learning architecture to solve the problem of multimodal fusion of multi-timescale temporal data, using music and video parts extracted from Music Videos (MVs) in particular. We capture the correlations between music and video at multiple levels by learning shared feature representations with Deep Belief Networks (DBN). The shared representations combine information from multiple modalities for decision making tasks, and are used to evaluate matching degrees between modalities and to retrieve matched modalities using single or multiple modalities as input. Moreover, we propose a novel deep architecture to handle temporal data at multiple timescales. When processing long sequences with varying length, we propose to extract hierarchical shared representations by concatenating deep representations at different levels, and to perform decision fusion with a feed forward neural network, which takes input from predictions of local and global classifiers trained with shared representations at each level. The effectiveness of our method is demonstrated through MV classification and retrieval.
Phasic activation of ventral tegmental neurons increases response and pattern similarity in prefrontal cortex neurons

Dopamine is critical for higher neural processes and modifying the activity of the prefrontal cortex (PFC). However, the mechanism of dopamine contribution to the modification of neural representation is unclear. Using in vivo two-photon population Ca2+ imaging in awake mice, this study investigated how neural representation of visual input to PFC neurons is regulated by dopamine. Phasic stimulation of dopaminergic neurons in the ventral tegmental area (VTA) evoked prolonged Ca2+ transients, lasting ∼30 s in layer 2/3 neurons of the PFC, which are regulated by a dopamine D1 receptor-dependent pathway. Furthermore, only a conditioning protocol with visual sensory input applied 0.5 s before the VTA dopaminergic input could evoke enhanced Ca2+ transients and increased pattern similarity (or establish a neural representation) of PFC neurons to the same sensory input. By increasing both the level of neuronal response and pattern similarity, dopaminergic input may establish robust and reliable cortical representation. DOI: http://dx.doi. org/10.7554/eLife.02726. 001
Rotating Black Branes wrapped on Einstein Spaces

We present new rotating black brane solutions which solve Einstein's equations with cosmological constant Λ in arbitrary dimension d. For negative Λ, the branes naturally appear in AdS supergravity compactifications, and should therefore play some role in the AdS/CFT correspondence. The spacetimes are warped products of a four-dimensional part and an Einstein space of dimension d−4, which is not necessarily of constant curvature. As a special subcase, the solutions contain the higher dimensional generalization of the Kerr-AdS metric recently found by Hawking et al.
Draft Genome Sequence of the Virulent Avibacterium paragallinarum Serotype A Strain JF4211 and Identification of Two Toxins

ABSTRACT Avibacterium paragallinarum is an important pathogen of chicken livestock causing infectious coryza. Here, we report the draft genome sequence of the virulent A. paragallinarum serotype A strain JF4211 (2.8 Mbp and G+C content of 41%) and the two toxin operons discovered from the annotation of the genome.
Understanding ion channel biology using epitope tags: Progress, pitfalls, and promise

Epitope tags have been increasingly used to understand ion channel subunit assembly and interaction, trafficking, subcellular localization, and function in living cells. In particular, epitope tags have proven extremely useful for analyses of closely related, highly homologous channel subunits in endogenous cell contexts in vitro and in vivo, where multiple channel isoforms may be expressed. However, as the variety of epitope tags that have been used has expanded, and the use of tagged channel subunits has become increasingly sophisticated and widespread, there has also been an increase in the number of examples highlighting the potential problems associated with the use of epitope tags for ion channel studies. Described here are some of the epitope tags that have been used to study ion channel subunits, including the HA, FLAG, myc, His6, and green fluorescent protein (GFP) epitopes, as well as some of the applications and avenues of research in which they have proven advantageous. Potential pitfalls and caveats associated with the use of these epitope tags are also discussed, with an emphasis on the need to include careful characterization of epitope‐tagged channel subunits as part of their construction. Finally, potential avenues for future investigation and the development of this approach are considered. J. Cell. Physiol. 213:618–625. © 2007 Wiley‐Liss, Inc.
Illusions of filled extent : psychophysics and neuroimaging methods

The aim of this thesis is to shed light on the Oppel-Kundt, vertical-horizontal and Helmholtz’s squares illusions. Eleven psychophysics experiments and one final fMRI study were conducted in order to inform current literature regarding these illusions. Experiments 1-5 investigated the effect of the number, size and position of vertical lines on the Oppel-Kundt illusion. Whereas five vertical lines allow for veridical size judgment of a horizontal line, a relatively constant and significant Oppel-Kundt 5% effect is observed with eight to twelve vertical lines. Evidence from these experiments also demonstrates that when one vertical line crosses a horizontal, ‘bisection’ decreases the perceived size of the horizontal by 7-13%. However, no reduction in the perceived size of the horizontal line in an inverted ‘T’ configuration is observed, challenging the ‘bisection’ component of the vertical-horizontal illusion as described by Mamassian & de Montalembert (2010). Experiments 6-7 showed that the increase in the perceived size of a horizontal line in an Oppel-Kundt figure can only be partly explained in terms of repulsion between adjacent lines. Specifically, whereas the size of the Oppel-Kundt illusion is 5%, displacement of adjacent lines can only account for 0.5%. Experiments 8-11 assess Mamassian and de Montalembert’ s (2010) simple model of the vertical-horizontal illusion and propose the new ABC model consisting of three components; anisotropy, abutting and bisection which were found to affect the perceived size of lines by +7%, +9% and -7% respectively. Finally, an fMRI study was carried out to investigate whether activity in V1 can be linked to perceptual experience. Results generated revealed a significant effect in V1 associated with physical differences between visual stimuli rather than perceived differences. We concluded that intrinsic processing in V1 is not responsible for inducing illusion-related activity and it is likely that feedback from other areas dominates results of other studies. The findings of this thesis have important implications on theories of visual illusions and processing of illusory-related percepts in the brain.