Miracle-dz/UniFAR-FTUs huggingface dataset:
Next‐generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3‐ITD or NPM1 mutations

Systematic assessment of minimal residual disease (MRD) in acute myeloid leukemia (AML) patients has been hampered by lack of a reliable, uniform MRD marker applicable to all patients. We evaluated next‐generation sequencing (NGS) for MRD assessment in AML patients (n = 80 samples). The ability of NGS technologies to generate thousands of clonal sequences makes it possible to determine the allelic ratio of sequence variants. Using NGS, we were able to determine the allelic ratio of different FLT3‐internal tandem duplication (ITD) clones within one patient sample, in addition to resolution of FLT3‐ITD insertion site, length, and sequence in a single analysis. Furthermore, NGS allowed us to study emergence of clonal dominance. Parallel assessment of MRD by NGS and quantitative real‐time polymerase chain reaction in NPM1 mutated patients was concordant in 95% of analyzed samples (n = 38). The frequency of mutated alleles was linearly quantified by NGS. As NGS sensitivity is scalable depending on sequence coverage, it reflects a highly flexible and reliable tool to assess MRD in leukemia patients. © 2012 Wiley Periodicals, Inc.
Estrogenic Potency of Benzophenone UV Filters in Breast Cancer Cells: Proliferative and Transcriptional Activity Substantiated by Docking Analysis

The results from recent studies show that some benzophenones (BPs) and their hydroxylated metabolites can function as weak estrogens (E2) in the environment. However, little is known about the structure-activity relationship of these molecules. We have examined the effects of exposure to ten different BPs on the proliferation of estrogen receptor (ER)-positive breast cancer cells and on the transcriptional activity of E2-target genes. We analyzed two genes that are tightly linked with estrogen-mediated proliferation, the CXCL12 and amphiregulin genes and two classical estrogen-responsive genes, the pS2 and progesterone receptor. Significant differences in the BPs efficiency to induce cell proliferation and endogenous E2-target gene expressions were observed. Using ERE-, Sp1-, AP1- and C3-reporter genes that contain different ER-binding sites in their promoter, we also showed significant differences in the BPs efficiency in activation of the ER transactivation. Together, our analyzes showed that the most active molecule is 4-hydroxy-BP. Docking analysis of the interaction of BPs in the ligand-binding pocket of ERα suggests that the minimum structural requirement for the estrogenic activity of BPs is a hydroxyl (OH) group in the phenyl A-ring that allows interaction with Glu-353, Arg-394 or Phe-404, which enhances the stability between BPs and ERα. Our modeling also indicates a loss of interaction between the OH groups of the phenyl B-ring and His-524. In addition, the presence of some OH groups in the phenyl B-ring can create repulsion forces, which may constrain helix 12 in an unfavorable position, explaining the differential estrogenic effects of BPs. These results, together with our analysis of BPs for their potency in activation of cell proliferation and ER-mediated transcription, report an improved understanding of the mechanism and structure–activity relationship of BPs.
Distinct Expression Pattern of Microtubule‐Associated Protein‐2 in Human Oligodendrogliomas and Glial Precursor Cells

Microtubule-associated protein 2 (MAP2), a protein linked to the neuronal cytoskeleton in the mature central nervous system (CNS), has recently been identified in glial precursors indicating a potential role during glial development. In the present study, we systematically analyzed the expression of MAP2 in a series of 237 human neuroepithelial tumors including paraffin-embedded specimens and tumor tissue microarrays from oligodendrogliomas, mixed gliomas, astrocytomas, glioblastomas, ependymomas, as well as dysembryoplastic neuroepithelial tumors (DNT), and central neurocytomas. In addition, MAP2-immunoreactive precursor cells were studied in the developing human brain. Three monoclonal antibodies generated against MAP2A-B or MAP2A-D isoforms were used. Variable immunoreactivity for MAP2 could be observed in all gliomas with the exception of ependymomas. Oligodendrogliomas exhibited a consistently strong and distinct pattern of expression characterized by perinuclear cytoplasmic staining without significant process labeling. Tumor cells with immunoreactive bi- or multi-polar processes were mostly encountered in astroglial neoplasms, whereas the small cell component in neurocytomas and DNT was not labeled. These features render MAP2 immunoreactivity a helpful diagnostic tool for the distinction of oligodendrogliomas and other neuroepithelial neoplasms. RT-PCR, Western blot analysis, and in situ hybridization confirmed the expression of MAP2A-C (including the novel MAP2+13 transcript) in both oligodendrogliomas and astrocytomas. Double fluorescent laser scanning microscopy showed that GFAP and MAP2 labeled different tumor cell populations. In embryonic human brains, MAP2-immunoreactive glial precursor cells were identified within the subventricular or intermediate zones. These precursors exhibit morphology closely resembling the immunolabeled neoplastic cells observed in glial tumors. Our findings demonstrate MAP2 expression in astrocytic and oligodendroglial neoplasms. The distinct pattern of immunoreactivity in oligodendrogliomas may be useful as a diagnostic tool. Since MAP2 expression occurs transiently in migrating immature glial cells, our findings are in line with an assumed origin of diffuse gliomas from glial precursors.
Apical Organelle Discharge by Cryptosporidium parvum Is Temperature, Cytoskeleton, and Intracellular Calcium Dependent and Required for Host Cell Invasion

ABSTRACT The apical organelles in apicomplexan parasites are characteristic secretory vesicles containing complex mixtures of molecules. While apical organelle discharge has been demonstrated to be involved in the cellular invasion of some apicomplexan parasites, including Toxoplasma gondii and Plasmodium spp. , the mechanisms of apical organelle discharge by Cryptosporidium parvum sporozoites and its role in host cell invasion are unclear. Here we show that the discharge of C. parvum apical organelles occurs in a temperature-dependent fashion. The inhibition of parasite actin and tubulin polymerization by cytochalasin D and colchicines, respectively, inhibited parasite apical organelle discharge. Chelation of the parasite's intracellular calcium also inhibited apical organelle discharge, and this process was partially reversed by raising the intracellular calcium concentration by use of the ionophore A23187. The inhibition of parasite cytoskeleton polymerization by cytochalasin D and colchicine and the depletion of intracellular calcium also decreased the gliding motility of C. parvum sporozoites. Importantly, the inhibition of apical organelle discharge by C. parvum sporozoites blocked parasite invasion of, but not attachment to, host cells (i.e., cultured human cholangiocytes). Moreover, the translocation of a parasite protein, CP2, to the host cell membrane at the region of the host cell-parasite interface was detected; an antibody to CP2 decreased the C. parvum invasion of cholangiocytes. These data demonstrate that the discharge of C. parvum sporozoite apical organelle contents occurs and that it is temperature, intracellular calcium, and cytoskeleton dependent and required for host cell invasion, confirming that apical organelles play a central role in C. parvum entry into host cells.
Improving topological ATPG with symbolic techniques

This paper presents a new approach to Automatic Test Pattern Generation for sequential circuits. Traditional topological algorithms nowadays are able to deal with very large circuits, but often fail when highly sequential subnetworks are found. On the other hand, symbolic techniques based on Binary Decision Diagrams proved themselves very efficient on small or medium circuits, no matter their sequential complexity. A state-of-the-art structural ATPG is extended by identifying some critical areas in the circuit and resorting to symbolic techniques when such areas need to be considered. Experimental results prove that the combined approach considerably enhances fault coverage while reducing CPU time when compared to a purely topological approach.
Development of the Lower Sacramento Valley Flood-Control System: Historical Perspective

Natural physical conditions and the politics of flood management provide the historical context for structural flood control that underlies modern flood hazards in the Sacramento Valley. The valley is a broad, low plain with backswamp basins that were frequently inundated prior to Anglo-American settlement, continuing until the modern flood-control system was established. Early attempts to emulate the Mississippi River single-channel levee strategy failed repeatedly in the Sacramento Valley due to high flow variability, mining sedimentation, lack of a coordinated levee system, and the inability of the main channels to carry most of the flood flows. Hydraulic mining caused massive sedimentation in major east-side tributaries, such as the Feather, Yuba, Bear, and American Rivers, and in the Sacramento River below the Feather River confluence. This sedimentation led to a flood-control design that relied on levees with narrow cross-channel spacings to promote channel scour and facilitate navigation. Even with.
Ribosomal Protein L11 Negatively Regulates Oncoprotein MDM2 and Mediates a p53-Dependent Ribosomal-Stress Checkpoint Pathway

ABSTRACT The gene encoding p53 mediates a major tumor suppression pathway that is frequently altered in human cancers. p53 function is kept at a low level during normal cell growth and is activated in response to various cellular stresses. The MDM2 oncoprotein plays a key role in negatively regulating p53 activity by either direct repression of p53 transactivation activity in the nucleus or promotion of p53 degradation in the cytoplasm. DNA damage and oncogenic insults, the two best-characterized p53-dependent checkpoint pathways, both activate p53 through inhibition of MDM2. Here we report that the human homologue of MDM2, HDM2, binds to ribosomal protein L11. L11 binds a central region in HDM2 that is distinct from the ARF binding site. We show that the functional consequence of L11-HDM2 association, like that with ARF, results in the prevention of HDM2-mediated p53 ubiquitination and degradation, subsequently restoring p53-mediated transactivation, accumulating p21 protein levels, and inducing a p53-dependent cell cycle arrest by canceling the inhibitory function of HDM2. Interference with ribosomal biogenesis by a low concentration of actinomycin D is associated with an increased L11-HDM2 interaction and subsequent p53 stabilization. We suggest that L11 functions as a negative regulator of HDM2 and that there might exist in vivo an L11-HDM2-p53 pathway for monitoring ribosomal integrity.
A survey of emerging approaches to spam filtering

From just an annoying characteristic of the electronic mail epoch, spam has evolved into an expensive resource and time-consuming problem. In this survey, we focus on emerging approaches to spam filtering built on recent developments in computing technologies. These include peer-to-peer computing, grid computing, semantic Web, and social networks. We also address a number of perspectives related to personalization and privacy in spam filtering. We conclude that, while important advancements have been made in spam filtering in recent years, high performance approaches remain to be explored due to the large scale of the problem.
Supporting Uncompressed HD Video Streaming without Retransmissions over 60GHz Wireless Networks

Uncompressed HD (high-definition) video delivery over wireless personal area networks (WPANs) is a challenging problem because of the limited bandwidth and variations in channel. The most straight forward technique to recover from channel errors is to retransmit corrupted packets. However, retransmissions introduce significant delay/jitter and require additional bandwidth. Therefore, retransmissions may be unsuitable for uncompressed video streaming. In this paper, we develop, simulate, and evaluate an millimeter- wave (mmWave) system for supporting uncompressed video streams up to 3-Gbps without any retransmissions. New features of the mmWave system incorporates: (i) UEP (unequal error protection) where different video bits (MSBs and LSBs) are protected differently, (ii) a multiple-CRC to determine whether MSB or/and LSB portions are in error, (iii) RS code swapping (RSS), an error concealment scheme which can conceal some errors in video pixels. Simulations using real uncompressed HD images indicate that the proposed mmWave system can maintain good average PSNR (peak-signal-to-noise-ratio) under poor channel conditions, achieving what is generally accepted as a good picture quality with PSNR values greater than 40 dB. Moreover, the proposed system results in less fluctuating PSNR values.
Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis.

BACKGROUND Invasive candidiasis is an important cause of morbidity and mortality among patients with health care-associated infection. The echinocandins have potent fungicidal activity against most Candida species, but there are few data comparing the safety and efficacy of echinocandins in the treatment of invasive candidiasis. METHODS This was an international, randomized, double-blind trial comparing micafungin (100 mg daily) and micafungin (150 mg daily) with a standard dosage of caspofungin (70 mg followed by 50 mg daily) in adults with candidemia and other forms of invasive candidiasis. The primary end point was treatment success, defined as clinical and mycological success at the end of blinded intravenous therapy. RESULTS A total of 595 patients were randomized to one the treatment groups and received at least 1 dose of study drug. In the modified intent-to-treat population, 191 patients were assigned to the micafungin 100 mg group, 199 to the micafungin 150 mg group, and 188 to the caspofungin group. Demographic characteristics and underlying disorders were comparable across the groups. Approximately 85% of patients had candidemia; the remainder had noncandidemic invasive candidiasis. At the end of blinded intravenous therapy, treatment was considered successful for 76.4% of patients in the micafungin 100 mg group, 71.4% in the micafungin 150 mg group, and 72.3% in the caspofungin group. The median time to culture negativity was 2 days in the micafungin 100 mg group and the caspofungin group, compared with 3 days in the micafungin 150 mg groups. There were no significant differences in mortality, relapsing and emergent infections, or adverse events between the study arms. CONCLUSIONS Dosages of micafungin 100 mg daily and 150 mg daily were noninferior to a standard dosage of caspofungin for the treatment of candidemia and other forms of invasive candidiasis.
Molecular and Cellular Organization of the Taste System in the Drosophila Larva

We examine the molecular and cellular basis of taste perception in the Drosophila larva through a comprehensive analysis of the expression patterns of all 68 Gustatory receptors (Grs). Gr-GAL4 lines representing each Gr are examined, and 39 show expression in taste organs of the larval head, including the terminal organ (TO), the dorsal organ (DO), and the pharyngeal organs. A receptor-to-neuron map is constructed. The map defines 10 neurons of the TO and DO, and it identifies 28 receptors that map to them. Each of these neurons expresses a unique subset of Gr-GAL4 drivers, except for two neurons that express the same complement. All of these neurons express at least two drivers, and one neuron expresses 17. Many of the receptors map to only one of these cells, but some map to as many as six. Conspicuously absent from the roster of Gr-GAL4 drivers expressed in larvae are those of the sugar receptor subfamily. Coexpression analysis suggests that most larval Grs act in bitter response and that there are distinct bitter-sensing neurons. A comprehensive analysis of central projections confirms that sensory information collected from different regions (e.g., the tip of the head vs the pharynx) is processed in different regions of the suboesophageal ganglion, the primary taste center of the CNS. Together, the results provide an extensive view of the molecular and cellular organization of the larval taste system.
A Spatio-spectral Data Fusion Method for the Detection of Urban Areas in optical High Resolution Images by a Novel MRF Model

In this paper, a novel Markov Random Field (MRF) model is proposed for the classification of high spatial resolution data. The key idea is that each thematic class can be described by a set of clusters, which represent spectral subclasses related to material responses. Accordingly, the proposed MRF model describes the contextual information by using the relationship between the (user-defined) thematic classes and the clusters extracted by a clustering procedure. This approach permits one to avoid penalizing configurations of cluster labels of neighboring pixels that correspond to the same thematic label. The proposed model has been validated on a real data set acquired by an IKONOS sensor.
Real and nominal rigidities in price setting: A bayesian analysis using aggregate data

This paper uses the Bayesian approach to solve and estimate a New Keynesian model augmented by a generalized Phillips curve, in which the shape of the price reset hazards can be identiÂ…ed using aggregate data. My empirical result shows that a constant hazard function is easily rejected by the data. The empirical hazard function for post-1983 periods in the U.S. is consistent with micro evidence obtained using data from similar periods. The hazard for pre-1983 periods, however, exhibits a remarkable increasing pattern, implying that pricing decisions are characterized by both time- and state-dependent aspects. Additionally, real rigidity plays an important role, but not as big a role as found in empirical studies using limited information methods.
Individual Differences in Motivation to Participate in Online Panels

The majority of online research is now conducted via discontinuous online access panels, which promise high response rates, sampling control, access to populations that are hard to reach, and detailed information about respondents. To sustain a critical mass of respondents, overcome panel attrition and recruit new panel members, marketers must understand how they can predict and explain what motivates people to participate repeatedly in online surveys. Using the newly developed survey participation inventory (SPI) measure, we identify three clusters of participants, characterised as voicing assistants, reward seekers and intrinsics. Our results suggest that most online surveys are filled out by intrinsically motivated respondents that show higher participation rates, response effort and performance; incentives do not offer an important response motive.
Body Location Independent Activity Monitoring

Human Activity Recognition (HAR) is increasingly common in peopleâs daily lives, being applied in health areas, sports and safety. Because of their high computational power, small size and low cost, smartphones and wearable sensors are suitable to monitor userâs daily living activities. However, almost all existing systems require devices to be worn in certain positions, making them impractical for long-term activity monitoring, where a change in position can lead to less accurate results. This work describes a novel algorithm to detect human activity independent of the sensor placement. Taking into account the battery consumption, only two sensors were considered: the accelerometer (ACC) and the barometer (BAR), with a sample frequency of 30 and 5 Hz, respectively. The signals obtained were then divided into 5 seconds windows. The dataset used is composed of 25 subjects, with more than 7 hours of recording. Daily living activities were performed with the smartphone worn in 12 different positions. From each window a set of statistical, temporal and spectral features were extracted and selected. During the classification process, a decision tree was trained and evaluated using a leave one user out cross validation. The developed framework achieved an accuracy of 94.5±6.8 %, regardless the subject and deviceâs position. This solution may be applied to elderly monitoring, as a rehabilitation tool in physiotherapy fields and also to be used by ordinary users, who just want to check their daily level of physical activity.
Comparison of cell migration mechanical strategies in three-dimensional matrices: a computational study

Cell migration on a two-dimensional flat surface has been extensively studied and is generally characterized by a front-protrusion–rear-contraction process. In a three-dimensional (3D) environment, on the other hand, cells adopt multiple migration strategies depending on the cell type and the properties of the extracellular matrix (ECM). By using computer simulations, we find that these migration strategies can be classified by various spatial–temporal dynamics of actin protrusion, actin–myosin contraction and actin–ECM adhesion. We demonstrate that if we include or exclude proteolysis of ECM, and vary adhesion dynamics and spatial distributions of protrusion, contraction and adhesion, our model can reproduce six experimentally observed motility modes: mesenchymal, chimneying, amoeboid, blebbing, finger-like protrusion and rear-squeezing cell locomotory behaviours. We further find that the mode of the cell motility evolves in response to the ECM density and adhesion detachment rate. The model makes non-trivial predictions about cell speed as a function of the adhesion strength, and ECM elasticity and mesh size.
Image Text Detection Using a Bandlet-Based Edge Detector and Stroke Width Transform

In this paper, we propose a text detection method based on a feature vector generated from connected components produced via the stroke width transform. Several properties, such as variant directionality of gradient of text edges, high contrast with background, and geometric properties of text components jointly with the properties found by the stroke width transform are considered in the formation of feature vectors. Then, k-means clustering is performed by employing the feature vectors in a bid to distinguish text and non-text components. Finally, the obtained text components are grouped and the remaining components are discarded. Since the stroke width transform relies on a precise edge detection scheme, we introduce a novel bandlet-based edge detector which is quite effective at obtaining text edges in images while dismissing noisy and foliage edges. Our experimental results indicate a high performance for the proposed method and the effectiveness of our proposed edge detector for text localization purposes.
Rhinovirus infections

One hundred and seventy-five rhinoviruses were isolated from 4·4% of patients in the general practice survey and 44 from 1·8% of children in the hospital survey. Isolations were made at all times of the year and although isolated most frequently from cases of common cold rhinoviruses were also found in association with other respiratory syndromes.