Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of Differential Growth In Vitro by High-risk Human Papillomavirus in Human Breast Cancer Cell Lines is Associated with Caspase Dysregulation

Introduction Many viruses have been associated with human breast cancers, including Epstein-Barr and Cytomegalovirus. New evidence has revealed the frequent presence of highrisk human papillomavirus (HPV) strains HPV16 and HPV18 in breast carcinoma biopsies. These findings raise the question of whether HPV may infect developing cancers and mediate their growth and development, as was recently observed with oral cancers. The goal of this study is to test the hypothesis that these high-risk HPV strains are sufficient to significantly alter phenotypes of already transformed human breast cancer cell lines. Materials and methods A series of in vitro experiments, including proliferation, adhesion and viability assays, were used to quantify the effects of HPV16 and HPV18 on the human breast cancer cell lines, T-47D and MCF7, following transient transfection with the full length HPV virus. Normal breast and fibroblast cell lines, MCF10A and Hs27, were used as noncancerous controls. Results HPV16 and HPV18 significantly inhibited proliferation and adhesion of T-47D cells, although viability was not affected. Differential effects on proliferation were observed in MCF7 cells; HPV16 inhibited proliferation, while HPV18 stimulated proliferation. No measurable effects in adhesion or viability in MCF7 cells were observed. The phenotypic changes in T-47D and MCF7 cells were associated with changes in mRNA expression of caspase-2,-3 and -8, but not p53 or GAPDH. No measurable changes in proliferation or viability were observed following HPV transfection in the normal human breast cell line, MCF10A, or the normal human fibroblast cell line, Hs27, although adhesion was differentially affected. Conclusions Although HPV is a primary cause of virtually all cervical cancers, it is found as a concomitant infection in many other tumors. While HPV may initiate carcinogenesis in these tumors, recent studies suggest HPV may also modulate the progression or malignancy process in already transformed cancers. Determining what effects HPV has on already transformed breast cancers may therefore become an important step towards understanding the factors that will lead to more effective treatment options for a significant proportion of breast cancer patients.
Meaningful Clustered Forest: an Automatic and Robust Clustering Algorithm

We propose a new clustering technique that can be regarded as a numerical method to compute the proximity gestalt. The method analyzes edge length statistics in the MST of the dataset and provides an a contrario cluster detection criterion. The approach is fully parametric on the chosen distance and can detect arbitrarily shaped clusters. The method is also automatic, in the sense that only a single parameter is left to the user. This parameter has an intuitive interpretation as it controls the expected number of false detections. We show that the iterative application of our method can (1) provide robustness to noise and (2) solve a masking phenomenon in which a highly populated and salient cluster dominates the scene and inhibits the detection of less-populated, but still salient, clusters.
Competition Builds Trust

This paper shows that (firm-level) competition has a positive impact on (individual-level) trust. Using US statesâ€™ banking de-regulation from the mid 1970s, we first show that an increase in competition had a causal impact on trust, measured in the General Social Survey (GSS). We develop a model which explains why increased competition within a state increases trust. The model also predicts a positive correlation between trust and sectoral competitiveness in the cross-section. We explore this implication using the 2004 wave of the GSS which we match with US census of firms competition measures. The modelâ€™s predictions are strongly borne out.
Presburger Vector Addition Systems

The reachability problem for Vector Addition Systems (VAS) is a central problem of net theory. The problem is known to be decidable by inductive invariants definable in the Presburger arithmetic. When the reachability set is definable in the Presburger arithmetic, the existence of such an inductive invariant is immediate. However, in this case, the computation of a Presburger formula denoting the reachability set is an open problem. In this paper we close this problem by proving that if the reachability set of a VAS is definable in the Presburger arithmetic, then the VAS is flatable, i.e. its reachability set can be obtained by runs labeled by words in a bounded language. As a direct consequence, classical algorithms based on acceleration techniques effectively compute a formula in the Presburger arithmetic denoting the reachability set.
Inhibition of a TREK-like K+ channel current by noradrenaline requires both β1- and β2-adrenoceptors in rat atrial myocytes

Aims Noradrenaline plays an important role in the modulation of atrial electrophysiology. However, the identity of the modulated channels, their mechanisms of modulation, and their role in the action potential remain unclear. This study aimed to investigate the noradrenergic modulation of an atrial steady-state outward current (IKss). Methods and results Rat atrial myocyte whole-cell currents were recorded at 36°C. Noradrenaline potently inhibited IKss (IC50 = 0.90 nM, 42.1 ± 4.3% at 1 µM, n = 7) and potentiated the L-type Ca2+ current (ICaL, EC50 = 136 nM, 205 ± 40% at 1 µM, n = 6). Noradrenaline-sensitive IKss was weakly voltage-dependent, time-independent, and potentiated by the arachidonic acid analogue, 5,8,11,14-eicosatetraynoic acid (EYTA; 10 µM), or by osmotically induced membrane stretch. Noise analysis revealed a unitary conductance of 8.4 ± 0.42 pS (n = 8). The biophysical/pharmacological properties of IKss indicate a TREK-like K+ channel. The effect of noradrenaline on IKss was abolished by combined β1-/β2-adrenoceptor antagonism (1 µM propranolol or 10 µM β1-selective atenolol and 100 nM β2-selective ICI-118,551 in combination), but not by β1- or β2-antagonist alone. The action of noradrenaline could be mimicked by β2-agonists (zinterol and fenoterol) in the presence of β1-antagonist. The action of noradrenaline on IKss, but not on ICaL, was abolished by pertussis toxin (PTX) treatment. The action of noradrenaline on ICaL was mediated by β1-adrenoceptors via a PTX-insensitive pathway. Noradrenaline prolonged APD30 by 52 ± 19% (n = 5; P < 0.05), and this effect was abolished by combined β1-/β2-antagonism, but not by atenolol alone. Conclusion Noradrenaline inhibits a rat atrial TREK-like K+ channel current via a PTX-sensitive mechanism involving co-operativity of β1-/β2-adrenoceptors that contributes to atrial APD prolongation.
Preprocessing Reference Sensor Pattern Noise via Spectrum Equalization

Although sensor pattern noise (SPN) has been proved to be an effective means to uniquely identify digital cameras, some non-unique artifacts, shared among cameras undergo the same or similar in-camera processing procedures, often give rise to false identifications. Therefore, it is desirable and necessary to suppress these unwanted artifacts so as to improve the accuracy and reliability. In this paper, we propose a novel preprocessing approach for attenuating the influence of the non-unique artifacts on the reference SPN to reduce the false identification rate. Specifically, we equalize the magnitude spectrum of the reference SPN through detecting and suppressing the peaks according to the local characteristics, aiming at removing the interfering periodic artifacts. Combined with six SPN extractions or enhancement methods, our proposed spectrum equalization algorithm is evaluated on the Dresden image database as well as our own database, and compared with the state-of-the-art preprocessing schemes. The experimental results indicate that the proposed procedure outperforms, or at least performs comparable with, the existing methods in terms of the overall receiver operating characteristic curves and kappa statistic computed from a confusion matrix, and tends to be more resistant to JPEG compression for medium and small image blocks.
Meta Learning Shared Hierarchies

We develop a metalearning approach for learning hierarchically structured policies, improving sample efficiency on unseen tasks through the use of shared primitives---policies that are executed for large numbers of timesteps. Specifically, a set of primitives are shared within a distribution of tasks, and are switched between by task-specific policies. We provide a concrete metric for measuring the strength of such hierarchies, leading to an optimization problem for quickly reaching high reward on unseen tasks. We then present an algorithm to solve this problem end-to-end through the use of any off-the-shelf reinforcement learning method, by repeatedly sampling new tasks and resetting task-specific policies. We successfully discover meaningful motor primitives for the directional movement of four-legged robots, solely by interacting with distributions of mazes. We also demonstrate the transferability of primitives to solve long-timescale sparse-reward obstacle courses, and we enable 3D humanoid robots to robustly walk and crawl with the same policy.
SB939, a Novel Potent and Orally Active Histone Deacetylase Inhibitor with High Tumor Exposure and Efficacy in Mouse Models of Colorectal Cancer

Although clinical responses in liquid tumors and certain lymphomas have been reported, the clinical efficacy of histone deacetylase inhibitors in solid tumors has been limited. This may be in part due to the poor pharmacokinetic of these drugs, resulting in inadequate tumor concentrations of the drug. SB939 is a new hydroxamic acid based histone deacetylase inhibitor with improved physicochemical, pharmaceutical, and pharmacokinetic properties. In vitro, SB939 inhibits class I, II, and IV HDACs, with no effects on other zinc binding enzymes, and shows significant antiproliferative activity against a wide variety of tumor cell lines. It has very favorable pharmacokinetic properties after oral dosing in mice, with >4-fold increased bioavailability and 3.3-fold increased half-life over suberoylanilide hydroxamic acid (SAHA). In contrast to SAHA, SB939 accumulates in tumor tissue and induces a sustained inhibition of histone acetylation in tumor tissue. These excellent pharmacokinetic properties translated into a dose-dependent antitumor efficacy in a xenograft model of human colorectal cancer (HCT-116), with a tumor growth inhibition of 94% versus 48% for SAHA (both at maximum tolerated dose), and was also effective when given in different intermittent schedules. Furthermore, in APCmin mice, a genetic mouse model of early-stage colon cancer, SB939 inhibited adenoma formation, hemocult scores, and increased hematocrit values more effectively than 5-fluorouracil. Emerging clinical data from phase I trials in cancer patients indicate that the pharmacokinetic and pharmacologic advantages of SB939 are translated to the clinic. The efficacy of SB939 reported here in two very different models of colorectal cancer warrants further investigation in patients. Mol Cancer Ther; 9(3); 642–52
Viridans Group Streptococci Clinical Isolates: MALDI-TOF Mass Spectrometry versus Gene Sequence-Based Identification

Viridans Group Streptococci (VGS) species-level identification is fundamental for patients management. Matrix-assisted laser desorption ionization—time of flight mass spectrometry (MALDI-TOF MS) has been used for VGS identification but discrimination within the Mitis group resulted difficult. In this study, VGS identifications with two MALDI-TOF instruments, the Biotyper (Bruker) and the VITEK MS (bioMérieux) have been compared to those derived from tuf, soda and rpoB genes sequencing. VGS isolates were clustered and a dendrogram constructed using the Biotyper 3.0 software (Bruker). RpoB gene sequencing resulted the most sensitive and specific molecular method for S. pneumonia identification and was used as reference method. The sensitivity and the specificity of the VITEK MS in S. pneumonia identification were 100%, while the Biotyper resulted less specific (92.4%). In non pneumococcal VGS strains, the group-level correlation between rpoB and the Biotyper was 100%, while the species-level correlation was 61% after database upgrading (than 37% before upgrading). The group-level correlation between rpoB and the VITEK MS was 100%, while the species-level correlation was 36% and increases at 69% if isolates identified as S. mitis/S. oralis are included. The less accurate performance of the VITEK MS in VGS identification within the Mitis group was due to the inability to discriminate between S. mitis and S. oralis. Conversely, the Biotyper, after the release of the upgraded database, was able to discriminate between the two species. In the dendrogram, VGS strains from the same group were grouped into the same cluster and had a good correspondence with the gene-based clustering reported by other authors, thus confirming the validity of the upgraded version of the database. Data from this study demonstrated that MALDI-TOF technique can represent a rapid and cost saving method for VGS identification even within the Mitis group but improvements of spectra database are still recommended.
Independent Representations of Verbs and Actions in Left Lateral Temporal Cortex

Verbs and nouns differ not only on formal linguistic grounds but also in what they typically refer to: Verbs typically refer to actions, whereas nouns typically refer to objects. Prior neuroimaging studies have revealed that regions in the left lateral temporal cortex (LTC), including the left posterior middle temporal gyrus (pMTG), respond selectively to action verbs relative to object nouns. Other studies have implicated the left pMTG in action knowledge, raising the possibility that verb selectivity in LTC may primarily reflect action-specific semantic features. Here, using functional neuroimaging, we test this hypothesis. Participants performed a simple memory task on visually presented verbs and nouns that described either events (e.g., “he eats” and “the conversation”) or states (e.g., “he exists” and “the value”). Verb-selective regions in the left pMTG and the left STS were defined in individual participants by an independent localizer contrast between action verbs and object nouns. Both regions showed equally strong selectivity for event and state verbs relative to semantically matched nouns. The left STS responded more to states than events, whereas there was no difference between states and events in the left pMTG. Finally, whole-brain group analysis revealed that action verbs, relative to state verbs, activated a cluster in pMTG that was located posterior to the verb-selective pMTG clusters. Together, these results indicate that verb selectivity in LTC is independent of action representations. We consider other differences between verbs and nouns that may underlie verb selectivity in LTC, including the verb property of predication.
Evaluating the Cryotherapy for Retinopathy of Prematurity Study (CRYO-ROP).

ease than in zone 2 disease, where fortunately greater than 75% of the disease occurs. It is important to note that unfavorable outcomes as stage 5 (total retinal detachment) outnumbered stage 4B (a retinal fold extending through the macula) by a ratio of 13 to 1. The treated unfavorable results were far more common proportionately in zone 1 disease than in zone 2 disease. The results of this study proved for the first time the availability of a treatment that improved the outlook for vision significantly over the natural history of the disease. The results of the study were quickly adopted both in the United States and worldwide as the standard of care, a tribute to the meticulous planning and execution by the investigators involved in carrying it out. Treatment took a further step forward when the indirect diode laser became available and was shown in a number of observational studies to be as effective as cryotherapy and easier in application for the infant and therapist. The CRYO-ROP trial proved to be the template for studies to follow. It also furnished a cadre of ophthalmologists trained in the design and implementation of randomized trial methods and the application of the methods to other problems in pediatric ophthalmology as they arose. It stands as one of the most successful trials undertaken with support of the National Eye Institute. Submitted for Publication: November 22, 2006; accepted November 22, 2006. Correspondence: John T. Flynn, MD, Department of Ophthalmology, Harkness Eye Institute, 635 W 165th St, New York, NY 10032 (jtf38@columbia.edu). Financial Disclosure: None reported. Funding/Support: This work was supported in part by the Communities Foundation of Texas.
Expansion of Anti-Mesothelin Specific CD4+ and CD8+ T Cell Responses in Patients with Pancreatic Carcinoma

We aimed to assess the status of naturally occurring CD4+ and CD8+ T cell responses to a tumour associated antigen, Mesothelin, in patients with pancreatic carcinoma and study the effects of elevated IL-10 on Mesothelin-specific T cell responses. For that sake, short term T cell lines were generated from PBMCs of 16 healthy controls, 15 patients with benign pancreatic diseases and 25 patients with pancreatic carcinoma and Mesothelin-specific CD4+ and CD8+ T cell responses were analysed using intracellular cytokine assays for IFN-γ. Plasma levels of IL-10 and Mesothelin were measured using cytometric bead array and ELISA assay, respectively. The blocking assays were performed to assess the effects of IL-10 on Mesothelin-specific T cell responses. Here, we demonstrate that the plasma levels of Mesothelin and IL-10 are significantly increased in patients with pancreatic carcinoma. Additionally, we found that (a) Mesothelin-specific T cell responses are significantly expanded in cancer patients (p = 0.0053), (b) the multifunctional CD4+ T cell response is directed toward a broad repertoire of epitopes within the Mesothelin protein. (c) Mesothelin-specific CD4+ T cell response is directly inhibited by elevated IL-10 in cancer patients. These data provides evidence for the use of Mesothelin as an immunogen for tumour-specific T cell response.
A randomized, double-blind study to evaluate the acid-inhibitory effect of vonoprazan (20 mg and 40 mg) in patients with proton-pump inhibitor-resistant erosive esophagitis

Background: Standard treatment for patients with erosive esophagitis (EE) is proton-pump inhibitors (PPIs), but some patients are resistant to PPIs. We aimed to evaluate the acid-inhibitory effects and efficacy of a novel potassium-competitive acid blocker (vonoprazan) in patients with PPI-resistant EE. Methods This randomized, double-blind, multicenter study of vonoprazan evaluated gastric and esophageal pH over a 24-hour period as the primary endpoint and EE healing rate as the secondary endpoint. Following a 7 to 14-day run-in period (lansoprazole 30 mg treatment), patients with endoscopically confirmed PPI-resistant EE received vonoprazan 20 mg or 40 mg for 8 weeks. Results Patients were randomized to receive vonoprazan 20 mg (n = 9) or 40 mg (n = 10). Over a 24-hour period; both groups showed a significant increase from baseline in the percentage of time gastric pH ≥ 4, referred to as pH 4 holding time ratio (HTR): an increase from 73.21% to 96.46% in the 20 mg group, and from 69.97% to 100.00% in the 40 mg group. Increases from baseline in esophageal pH 4 HTRs were not significant. The 40 mg group showed greater increases in gastric and esophageal pH 4 HTRs compared with the 20 mg group, but differences between groups were not significant. After 8 weeks’ treatment, the healing rate in subjects with baseline EE grades A–D was 60.0% (3/5 patients) in the 20 mg group and 71.4% (5/7 patients) in the 40 mg group. Vonoprazan was generally well tolerated. One patient (40 mg group) experienced four treatment-emergent adverse events (TEAEs) (unrelated to study drug), leading to study discontinuation. Conclusions Vonoprazan 20 mg and 40 mg effectively inhibited gastric acid secretion over a 24-hour period with significantly increased gastric pH 4 HTR, and resulted in an EE healing rate > 60.0% in this study. Vonoprazan treatment may be valuable for patients with PPI-resistant EE
Tree visualization with tree-maps: 2-d space-filling approach

The traditional approach to representing tree structures is as a rooted, directed graph with the root node at the top of the page and children nodes below the parent node with lines connecting them (Figure 1). Knuth (1968, p. 305-313) has a long discussion about this standard representation, especially why the root is at the top and he offers several alternatives including brief mention of a space-filling approach. However, the remainder of his presentation and most other discussions of trees focus on various node and edge representations. By contrast, this paper deals with a two-dimensional (2-d) space-filling approach in which each node is a rectangle whose area is proportional to some attribute such as node size.
Down regulation of gastric and intestinal phenotypic expression in Epstein-Barr virus-associated stomach cancers.

AIMS We have previously demonstrated the importance of gastric and intestinal phenotypic expression for stomach carcinogenesis. In this study, we focused on Epstein-Barr virus (EBV)-associated stomach cancers, with special attention to Cdx2. METHODS AND RESULTS We evaluated the expression of gastric and intestinal phenotypic markers by immunohistochemistry in 35 EBV-positive [EBV (+)] and 75 EBV-negative [EBV (-)] stomach cancers in Colombia. The lesions were divided phenotypically into gastric (G), gastric-and-intestinal mixed (GI), intestinal (I), and null (N) phenotypes. In the EBV (+) cases, the lesions were divided phenotypically into 9 G (25.7%), 1 GI (2.9%), 3 I (8.6%), and 22 N (62.9%) types. Similarly, the EBV (-) lesions were also classified phenotypically as 15 G (20.0%), 19 GI (25.3%), 24 I (32.0%), and 17 N (22.7%) types. The proportion of N type EBV (+) lesions was higher than for their EBV (-) counterparts (P<0.0001). The expression of Cdx2 and MUC2 was also found to be significantly lower in EBV (+) than in EBV (-) stomach cancers (P=0.0001; P<0.0001). Cdx2 expression in the intestinal metaplastic glands present in non-neoplastic mucosa surrounding EBV (+) lesions was also significantly lower than in EBV (-) tumors (P=0.016) despite no evidence of EBV infection. CONCLUSIONS EBV (+) stomach cancers are characterized by low expression of intestinal phenotype markers, including Cdx2, and only occasional gastric phenotypic expression.
Adaptive Binarization of Historical Document Images

In this paper, we present a binarization technique specifically designed for historical document images. Existing methods for this problem focus on either finding a good global threshold or adapting the threshold for each area to remove smear, strains, uneven illumination etc. We propose a hybrid approach that first applies a global thresholding method and, then, identifies the image areas that are more likely to still contain noise. Each of these areas is re-processed separately to achieve better quality of binarization. We evaluate the proposed approach for different kinds of degradation problems. The results show that our method can handle hard cases while documents already in good condition are not affected drastically