Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting FLIP and Mcl‐1 using a combination of aspirin and sorafenib sensitizes colon cancer cells to TRAIL

The multikinase inhibitor sorafenib is highly effective against certain types of cancer in the clinic and prevents colon cancer cell proliferation in vitro. Non‐steroidal anti‐inflammatory drugs, such as acetylsalicylic acid (aspirin), have shown activity against colon cancer cells. The aims of this study were to determine whether the combination of aspirin with sorafenib has enhanced anti‐proliferative effects and increases recombinant human tumour necrosis factor‐related apoptosis‐inducing ligand (rhTRAIL)‐induced apoptosis in the human SW948, Lovo, Colo205, Colo320, Caco‐2 and HCT116 colon cancer cell lines. In four cell lines, aspirin strongly stimulated the anti‐proliferative effects of sorafenib (∼four‐fold enhancement) by inducing cell cycle arrest. Furthermore, combining low doses of aspirin (≤ 5 mm) and sorafenib (≤ 2.5 µm) greatly sensitized TRAIL‐sensitive and TRAIL‐resistant colon cancer cells to rhTRAIL, much more potently than either drug combined with rhTRAIL. The increase in rhTRAIL sensitivity was due to inhibition of FLIP and Mcl‐1 protein expression following aspirin and sorafenib co‐treatment, as confirmed by knock‐down studies. Next, the clinical relevance of targeting FLIP and Mcl‐1 in colon cancer was examined. Using immunohistochemistry, we found that Mcl‐1 expression was significantly increased in colon adenoma and carcinoma patient material compared to healthy colonic epithelium, similar to the enhanced FLIP expression we recently observed in colon cancer. These results underscore the potential of combining low doses of aspirin with sorafenib to inhibit proliferation and target the anti‐apoptotic proteins FLIP and Mcl‐1 in colon cancer cells. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Expression of the alpha1F calcium channel subunit by photoreceptors in the rat retina.

PURPOSE The CACNA1F gene encodes a voltage-gated calcium channel alpha1 subunit, alpha1F, which is expressed in the human retina. Mutations in this gene cause incomplete X-linked congenital stationary night blindness (CSNB2). The aim of this study was to obtain the sequence of the rat alpha1F cDNA and localize the encoded polypeptide in the rat retina. METHODS The full-length rat alpha1F sequence was compiled from sequencing of overlapping alpha1F PCR fragments amplified from rat retinal cDNA. Antiserum was raised against a human alpha1F peptide. It was found that the human alpha1F peptide used to generate the antiserum was conserved at only 11 out of 19 residues in the cloned rat sequence. Therefore, antibodies were affinity purified against either the human alpha1F peptide or the equivalent rat peptide and used for immunofluorescent staining of rat retina sections. RESULTS The rat alpha1F amino acid sequence was found to be 91% and 95% identical to the human and mouse alpha1F sequences, respectively. Antibodies affinity purified against the human alpha1F peptide stained both the outer nuclear layer (ONL) and outer plexiform layer of rat retina sections. In contrast, staining with antibodies affinity purified against the corresponding rat alpha1F peptide was restricted to the ONL. CONCLUSIONS The rat alpha1F amino acid sequence is highly homologous to the human and mouse sequences. The immunohistochemical results indicate the existence of distinct alpha1F isoforms or alpha1F-like channels, which are differentially distributed in the cell bodies and synaptic terminals of photoreceptors in the rat retina.
Hidden-Markov Factor Analysis as a spatiotemporal model for electrocorticography

We present a new approach to extracting low-dimensional neural trajectories that summarize the electrocorticographic (ECoG) signals recorded with high-channel-count electrode arrays implanted subdurally. In our approach, Hidden-Markov Factor Analysis (HMFA), a finite set of factor analyzers are used to model the relationship between the high-dimensional ECoG neural space and a low-dimensional latent neural space; the factor analyzers at different time points are in turn linked together with a hidden Markov model. The recorded ECoG signals were band-pass filtered such that our analysis was focused on a sub-band (76-100Hz) of high gamma. HMFA affords the quantization of the ECoG neural space and dimensionality reduction in a common probabilistic space. We applied this method to the ECoG recordings of 2 subjects who responded with button presses to audiovisual stimuli in an experimental task. Using a goodness-of-fit metric that measures how well the ECoG activity of each electrode can be predicted by all the other electrodes, we found that HMFA performed best when compared with Gaussian-Process Factor Analysis (GPFA) and other related spatiotemporal modeling techniques. In contradistinction to HMFA, GPFA and the other techniques integrate temporal smoothing with dimensionality reduction. We believe that this method will provide a powerful tool for relating high-channel-count ECoG signals to the perception and behavior of subjects.
A histological investigation into the correlation of central retinal artery atherosclerosis with the systemic circulation

Current research suggests that retinal arterial changes such as arteriovenous nicking and arterial narrowing are pathologically distinct from atherosclerosis. Other studies have found a positive correlation between retinal changes and systemic atherosclerosis. However, limited recent histopathologic evidence assessing atherosclerosis in the central retinal artery exists. We investigated atherosclerosis in the central retinal artery and how it correlates to atherosclerosis in the carotid and coronary arteries. Twenty‐two cadavers (12 males, 10 females) were dissected, obtaining one orbit, one carotid artery, and one coronary artery from each. The specimens were sectioned and stained for histologic analysis by light microscopy using hematoxylin and eosin, Verhoeff's elastic, and Gomori's trichrome stains. The degree of atherosclerosis was graded from absent, or I (least severe) to VIII (most severe) based on the current American Heart Association guidelines. Atherosclerotic changes were present in the central retinal, coronary, and carotid arteries. A positive correlation was found between the central retinal artery and the carotid artery (r = 0.23, P = 0.15), the central retinal artery and the coronary artery (r = 0.31, P = 0.08), and the carotid artery and the coronary artery (r = 0.45, P = 0.02). The presence of low‐grade atherosclerosis in the central retinal artery is prevalent in a population of advanced vascular disease. However, central retinal artery atherosclerotic lesion severity is poorly correlated with disease severity in the carotid and coronary arteries. Anat Rec, 297:1430–1434, 2014. © 2014 Wiley Periodicals, Inc.
Percutaneous sympathectomy of the renal arteries: the OneShot Renal Denervation System is not associated with significant vessel wall injury.

AIMS Renal artery denervation (RADN) is an emerging technique for the treatment of resistant hypertension (RH). However, the use of the available systems has been associated with vascular injury, resulting in vasospasm and vessel wall thrombosis. The OneShot System (Covidien, San Jose, CA, USA) is an irrigated radiofrequency balloon designed to reduce vessel heating and injury during RADN. METHODS AND RESULTS The aim of the present study was to evaluate the target vessel morphological features before and after renal ablation using the OneShot RADN system. In this prospective observational study, 12 renal arteries of patients underwent RADN using the OneShot™ RADN System. Pre-procedural and post-procedural optical coherence tomography (OCT) pullbacks were performed and evaluated. No evidence for vasospasm, oedema or intraluminal thrombus formation was detected. Limited arterial dissections, after RADN, occurred in three renal arteries and did not require additional treatments. A sustained reduction of office blood pressure levels was observed over six months of follow-up in all the patients. CONCLUSIONS This study demonstrates that, in a small patient population, RADN using the OneShot Renal Denervation System is not associated with arterial spasm or thrombus formation on the vessel wall.
Influence of alcohol use and family history of alcoholism on neural response to alcohol cues in college drinkers.

BACKGROUND Heavy drinkers show altered functional magnetic resonance imaging (fMRI) response to alcohol cues. Little is known about alcohol cue reactivity among college age drinkers, who show the greatest rates of alcohol use disorders. Family history of alcoholism (family history positive [FHP]) is a risk factor for problematic drinking, but the impact on alcohol cue reactivity is unclear. We investigated the influence of heavy drinking and family history of alcoholism on alcohol cue-related fMRI response among college students. METHODS Participants were 19 family history negative (FHN) light drinkers, 11 FHP light drinkers, 25 FHN heavy drinkers, and 10 FHP heavy drinkers, aged 18 to 21. During fMRI scanning, participants viewed alcohol images, nonalcohol beverage images, and degraded control images, with each beverage image presented twice. We characterized blood oxygen level-dependent (BOLD) contrast for alcohol versus nonalcohol images and examined BOLD response to repeated alcohol images to understand exposure effects. RESULTS Heavy drinkers exhibited greater BOLD response than light drinkers in posterior visual association regions, anterior cingulate, medial frontal cortex, hippocampus, amygdala, and dorsal striatum, and hyperactivation to repeated alcohol images in temporo-parietal, frontal, and insular regions (clusters > 8,127 μl, p < 0.05). FHP individuals showed increased activation to repeated alcohol images in temporo-parietal regions, fusiform, and hippocampus. There were no interactions between family history and drinking group. CONCLUSIONS Our results parallel findings of hyperactivation to alcohol cues among heavy drinkers in regions subserving visual attention, memory, motivation, and habit. Heavy drinkers demonstrated heightened activation to repeated alcohol images, which could influence continued drinking. Family history of alcoholism was associated with greater response to repeated alcohol images in regions underlying visual attention, recognition, and encoding, which could suggest aspects of alcohol cue reactivity that are independent of personal drinking. Heavy drinking and family history of alcoholism may have differential impacts on neural circuitry involved in cue reactivity.
Attitudes of Chinese chief nephrologists toward dialysis modality selection.

Peritoneal dialysis (PD) is an effective renal replacement therapy; however, its penetration rate in China is rather low. In the present study, we investigated the opinions and attitudes of Chinese chief nephrologists about dialysis modality selection. We asked 51 chief nephrologists from various university hospitals to answer 8 questions about their attitudes toward PD and about the factors that affect their selection of dialysis modality. Hemodialysis (HD) was available in all of the hospitals where the surveyed chief nephrologists worked. Peritoneal dialysis was available in 68.6% of the hospitals, and renal transplantation was available in 54.9%. Of the surveyed nephrologists, 5.9% believed that PD was more advantageous than HD, and 29.4% of them believed that HD was better. However, most of the nephrologists (64.7%) thought that the advantages of each modality depended on the individual patient and therefore that modality selection should be individualized accordingly. About 70.6% of the nephrologists expressed confidence in PD, and 88% were interested in PD. Overall, 90.2% of the nephrologists said that they would start or expand a PD program in the future. More than half of the nephrologists (52.9%) thought that the proportion of PD in China should be 30%-50%. [The actual percentage is less than 10% in most ares (58.8%) of China. ] Most nephrologists indicated that the major reasons for such low use of PD were the low profit from PD treatment and insufficient patient and professional education about PD. A few nephrologists said that peritonitis, the high PD dropout rate, and patient preference also affected the penetration of PD. Our findings suggest that many of the chief nephrologists in China are confident about PD treatment. The major obstacles to PD expansion in China are the lack of incentive (profit) for PD treatment and insufficient education for professionals and patients alike.
Tourette syndrome: Evolving concepts

Tourette syndrome is a common childhood‐onset neurobehavioral disorder characterized by multiple motor and phonic tics affecting boys more frequently than girls. Premonitory sensory urges prior to tic execution are common, and this phenomenon helps to distinguish tics from other hyperkinetic movement disorders. Tourette syndrome is commonly associated with attention deficit hyperactivity disorder, obsessive‐compulsive disorder, learning difficulties, and impulse control disorder. The pathophysiology of this complex disorder is not well understood. Involvement of basal ganglia–related circuits and dopaminergic system has been suggested by various imaging and postmortem studies. Although it is considered a genetic disorder, possibly modified by environmental factors, an intense search has thus far failed to find causative genes. Symptomatic treatment of tics chiefly utilizes various alpha adrenergic agonists, antidopaminergic drugs, topiramate, botulinum toxin, and deep brain stimulation. Habit reversal therapy and other behavioral approaches may be a reasonable option for some cases. Improved understanding of Tourette syndrome should lead to better symptomatic and more effective pathogenesis‐targeted therapies. © 2011 Movement Disorder Society
Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family.

We identified three novel transporters structurally belonging to the organic anion transporting polypeptide (OATP) family in humans. Since previously known rat oatp1 to 3 do not necessarily correspond to the human OATPs in terms of either tissue distribution or function, here we designate the newly identified human OATPs as OATP-B, -D and -E, and we rename the previously known human OATP as OATP-A. OATP-C proved to be identical with the recently reported LST1/OATP-2. Expression profiles of the five OATPs and the prostaglandin transporter PGT (a member of OATP family) in human tissues showed that OATP-C is exclusively localized in liver, OATP-A and PGT are expressed in restricted ranges of tissues, and OATP-B, -D and -E show broad expression profiles. OATP-B, -C, -D and -E exhibited transport activity for [(3)H]estrone-3-sulfate as a common substrate. OATP-C has a high transport activity with broad substrate specificity.
Clinical evaluation of a new polymerase chain reaction assay for detection of Chlamydia trachomatis in endocervical specimens

A clinical evaluation of the Amplicor polymerase chain reaction (PCR) assay for the detection of Chlamydia trachomatis in endocervical swabs (Roche Molecular Systems, Branchburg, N.J.) is described. This new clinical system used one-step sample preparation, amplification with biotinylated cryptic plasmid primer pairs (CP24-CP27), uracil-N-glycosylase (AmpErase), and a microtiter format for amplicon capture and detection. Culture with McCoy cells in duplicate 1-dram (3.697-ml) vials with fluorescent immunostaining was the reference system. Endocervical swab samples from 945 women provided 74 culture-positive specimens, of which PCR detected 71. The initial PCR result was positive for 12 additional specimens. Arbitration of the PCR-positive, culture-negative samples by PCR with major outer membrane protein primers, duplicate culture, elementary body direct fluorescent-antibody staining, and DNA extraction PCR showed that all 12 samples were positive for chlamydia, raising the number of truly positive samples from 74 to 86. After arbitration the true sensitivities of PCR and culture were 96.5 and 86%, respectively (P = 0.02). Specificities for both were 100%. For PCR, the positive and negative predictive values were 100 and 99.7%, respectively. Total test efficiency was 99.7%. A high-test-volume (121 samples) timing study with all items included in the College of American Pathologists work load method indicated that this PCR format took approximately 3 min per sample. Because of the high sensitivity, specificity, and improved ease of handling, we found PCR to be a good alternative to culture for detection of C. trachomatis.
Early events of tomato spotted wilt transcription and replication in protoplasts.

A protoplast transfection system for tomato spotted wilt tospovirus (TSWV) was established by PEG-mediated infection of tobacco protoplasts. Analysis of viral RNA synthesis revealed an asymmetric production of viral (v) and viral-complementary (vc) strands of all three genomic RNA segments and a separation in time of subgenomic transcription during the first 72 hr post infection (p.i.). Synthesis of vc-RNA was detectable 8-10 hrs prior to v-RNA production. During the first 72 h of infection the accumulation of S-RNAs exceeded M- and L-RNAs and the amount of vc-RNAs was larger than that of genomic v-RNAs. The subgenomic N-mRNA was first detected 5 hr p.i. , followed by vc-S RNA and the mRNA for the nonstructural protein (NSs) 15 hr later. The two subgenomic mRNA species of the S RNA appeared to be regulated independently from each other and from other viral mRNA species. Defective interfering (DI) elements from L RNA associated with the virus inoculum, were not preferentially replicated at the expense of full-sized L-RNA.
miR-208a as a Biomarker of Isoproterenol-induced Cardiac Injury in Sod2+/− and C57BL/6J Wild-type Mice

This investigation examined microRNA-208a (miR-208a) as a potential biomarker of isoproterenol (ISO)-induced cardiac injury in superoxide dismutase-2 (Sod2+/− ) and the wild-type mice, and the potential sensitivity of Sod2+/− mice to ISO-induced toxicity. A single intraperitoneal injection of ISO was administered to age-matched wild-type and Sod2+/− mice at 0, 80, or 160 mg/kg. Plasma miR-208a, cardiac troponin I (cTnI), and ISO systemic exposure were measured at various time points postdose. Hearts were collected for histopathology examination and for tissue expression of miR-208a and myosin heavy chain 7. ISO administration caused increases in cTnI and miR-208a plasma levels that correlated with myocardial damage; however, the magnitude of increase differed according to the types of mice. At similar ISO systemic exposure, the magnitude of cTnI was greater in wild-type mice compared to Sod2+/ − mice; however, the magnitude of miR-208a was greater in Sod2+/− mice than that of the wild-type mice. Myocardial degeneration occurred at ≥3 hr in the wild-type and ≥6 hr in Sod2+/ − mice. At ≥24 hr after ISO administration, miR-208a appeared superior to cTnI in indicating myocardial injury in both wild-type and Sod2+/− mice. Sod2+/− mice were not more sensitive than wild-type mice to ISO-induced toxicity.
Impact of Time to Treatment on Tissue-Type Plasminogen Activator–Induced Recanalization in Acute Ischemic Stroke

Background and Purpose— Although tissue-type plasminogen activator (tPA) efficacy depends on time, it is unknown whether its effect on recanalization is time dependent. Information about likelihood of successful recanalization as a function of time to treatment may improve patient selection for advanced reperfusion strategies. We aimed to identify the impact of time to treatment on tPA-induced recanalization in patients with acute ischemic stroke. Methods— Consecutive patients with intracranial acute occlusion treated with intravenous tPA underwent transcranial Doppler examination before and 1 hour after tPA administration. Patients were categorized according to occlusion localization in proximal and distal occlusion. Sequential analysis of recanalization according to time to treatment was performed for every 30-minute cutoff point. Results— Overall (n=508), 54.3% had proximal and 45.7% had distal occlusion. Median time to treatment was 171.4±61.9 minutes, and 5.9% were treated >270 minutes. Recanalization occurred in 36.1% of patients. There was no linear association between time to treatment and time to recanalization, but sequential analysis showed that patients treated >270 minutes had a lower recanalization rate. Lower National Institutes of Health Stroke Scale score on admission (odds ratio [OR], 0.305; 95% confidence interval [CI], 0.1–0.933) and time to treatment ⩽270 minutes (OR, 0.995; 95% CI, 0.99–0.999) emerged as independent predictors of recanalization. In patients with proximal occlusion, 41.8% recanalized. Time to treatment >90 minutes was associated with lower recanalization rate. However, only younger age (OR, 0.975; 95% CI, 0.952–0.999) and lower baseline National Institutes of Health Stroke Scale score (OR, 0.921; 95% CI, 0.855–0.993) independently predicted recanalization. In distal occlusion patients, male sex was the only independent predictor of recanalization (OR, 0.416; 95% CI, 0.195–0.887). None recanalized >270 minutes. Conclusions— The effect of tPA on recanalization may decrease over time. Treatment >270 minutes predicted lack of recanalization, especially in distal occlusions.
Selective Transport of α-Mannosidase by Autophagic Pathways

In the yeast Saccharomyces cerevisiae, a precursor form of aminopeptidase I (prApe1) and α-mannosidase (Ams1) are selectively transported to the vacuole through the cytoplasm-to-vacuole targeting pathway under vegetative conditions and through autophagy under starvation conditions. Atg19 plays a central role in these processes by linking Ams1 and prApe1 to Atg8 and Atg11. However, little is known about the molecular mechanisms of cargo recognition by Atg19. Here, we report structural and functional analyses of Atg19 and its paralog, Atg34. A protease-resistant domain was identified in the C-terminal region of Atg19, which was also conserved in Atg34. In vitro pulldown assays showed that the C-terminal domains of both Atg19 and Atg34 are responsible for Ams1 binding; these domains are hereafter referred to as Ams1-binding domains (ABDs). The transport of Ams1, but not prApe1, was blocked in atg19Δatg34Δ cells expressing Atg19ΔABD, indicating that ABD is specifically required for Ams1 transport. We then determined the solution structures of the ABDs of Atg19 and Atg34 using NMR spectroscopy. Both ABD structures have a canonical immunoglobulin fold consisting of eight β-strands with highly conserved loops clustered at one side of the fold. These facts, together with the results of a mutational analysis, suggest that ABD recognizes Ams1 using these conserved loops.
Multi-view coding and view synthesis for 3DTV

In this paper we analyze the current developments in 3DTV technologies concerning multi-view video coding and free-viewpoint rendering. Multi-View Coding (MVC) can be performed in several ways that influence the performance and the complexity of the system. We underline the connection between coding and free-viewpoint rendering techniques. Since the latest research shows that a better multi-view coding can be reached by using interview prediction based on view synthesis, we present our view synthesis algorithm and compare it with the MPEG standardization software. The first quality measurements, indicating the difference between our view synthesis and the MPEG algorithm, are provided and discussed.