Extreme Value Distribution Based Gene Selection Criteria for Discriminant Microarray Data Analysis Using Logistic Regression

One important issue commonly encountered in the analysis of microarray data is to decide which and how many genes should be selected for further studies. For discriminant microarray data analyses based on statistical models, such as the logistic regression models, gene selection can be accomplished by a comparison of the maximum likelihood of the model given the real data, $\hat{L}(D|M)$, and the expected maximum likelihood of the model given an ensemble of surrogate data with randomly permuted label, $\hat{L}(D_0|M)$. Typically, the computational burden for obtaining $\hat{L}(D_0|M)$ is immense, often exceeding the limits of computing available resources by orders of magnitude. Here, we propose an approach that circumvents such heavy computations by mapping the simulation problem to an extreme-value problem. We present the derivation of an asymptotic distribution of the extreme-value as well as its mean, median, and variance. Using this distribution, we propose two gene selection criteria, and we apply them to two microarray datasets and three classification tasks for illustration.Comment: to be published in Journal of Computational Biology (2004

The role of adenosine, adenosine receptors and transporters in the modulation of cell death

Ph.DDOCTOR OF PHILOSOPH

Understanding Taxi Drivers’ Multi-day Cruising Patterns

This study investigates taxi drivers’ multi-day cruising behaviours with GPS data collected in Shenzhen, China. By calculating the inter-daily variability of taxi drivers’ cruising behaviours, the multi-day cruising patterns are investigated. The impacts of learning feature and habitual feature on multi-day cruising behaviours are determined. The results prove that there is variability among taxis’ day-to-day cruising behaviours, and the day-of-week pattern is that taxi drivers tend to cruise a larger area on Friday, and a rather focused area on Monday. The findings also indicate that the impacts of learning feature and habitual feature are more obvious between weekend days than among weekdays. Moreover, learning feature between two sequent weeks is found to be greater than that within one week, while the habitual feature shows recession over time. By revealing taxis\u27 day-to-day cruising pattern and the factors influencing it, the study results provide us with crucial information in predicting taxis\u27 multi-day cruising locations, which can be applied to simulate taxis\u27 multi-day cruising behaviour as well as to determine the traffic volume derived from taxis\u27 cruising behaviour. This can help us in planning of transportation facilities, such as stop stations or parking lots for taxis. Moreover, the findings can be also employed in predicting taxis\u27 adjustments of multi-day cruising locations under the impact of traffic management strategies

Effect of long noncoding RNA FLJ30679 on proliferation and migration of oral squamous cell carcinoma cells

Background and purpose: Long noncoding RNA (lncRNA) can regulate gene transcription, mRNA shear, stabilization and translation, and it is an important regulatory factor in a variety of biological processes. This study aimed to investigate the expression and clinical features of lncRNA FLJ30679 in oral squamous cell carcinoma (OSCC) and its effect on the malignant biological behavior of OSCC. Methods: The expression of FLJ30679 in head and neck squamous cell carcinoma (HNSCC) tissues and normal tissues was analyzed by the UCSC Xena database for expression and prognosis. The expression of FLJ30679 in OSCC cell lines was detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). The subcellular localization of FLJ30679 in OSCC cells was detected by RNA nuclear-cytoplasmic fractionation assays. FLJ30679 Smart Silencer was used to establish the FLJ30679 knockdown group (SS-FLJ30679), and overexpression plasmid of FLJ30679 was used to establish FLJ30679 overexpression group (FLJ30679). The effects of altered FLJ30679 expression on the proliferative and migration capacity of OSCC cells were examined by cell counting kit-8 (CCK-8) and transwell migration assays. RTFQ-PCR and Western blot were used to determine the effect of altered FLJ30679 expression on the expression of epithelial-mesenchymal transition (EMT)-related genes in OSCC cells. The effects of altered FLJ30679 expression on the phosphoinositide 3-kinase (PI3K)/protein kinase (AKT) pathway were detected by Western blot. Results: Online query of database showed that FLJ30679 expression was higher in HNSCC tissues compared to normal tissues (P<0.01). HNSCC patients with higher FLJ30679 expression had lower overall survival (P<0.01). The RTFQ-PCR results showed that FLJ30679 was expressed at a higher level in six OSCC cell lines compared with normal cells, and was predominantly localized in the nucleus. The ability of OSCC cells in the SS-FLJ30679 group to proliferate and migrate was significantly lower compared with the SS-NC group (P<0.01). OSCC cells in the FLJ30679 overexpression group had significantly higher proliferative and migratory capacities than those in the vector group (P<0.001). RTFQ-PCR and Western blot results showed that FLJ30679 knockdown resulted in upregulation of mRNA and protein expression levels of E-cadherin (P<0.01) and downregulation of mRNA and protein expression levels of N-cadherin and vimentin (P<0.01). FLJ30679 overexpression resulted in downregulation of protein expression levels of E-cadherin (P<0.01) and upregulation of mRNA and protein expression levels of N-cadherin and vimentin (P<0.05). Western blot results showed that knockdown of FLJ30679 resulted in decreased protein expression levels of phosphorylated-PI3K (p-PI3K) and phosphorylated-AKT (p-AKT) (P<0.001), and overexpression of FLJ30679 resulted in increased protein expression levels of p-PI3K and p-AKT (P<0.01). Conclusion: The expression of FLJ30679 was increased in OSCC tissues and cells. It promoted the proliferation and migration ability of OSCC cells, which may be caused by FLJ30679 promoting EMT via PI3K/AKT pathway

Characterization of ultra-deeply buried middle Triassic Leikoupo marine carbonate petroleum system (!) in the Western Sichuan depression, China

Ultra-deeply buried (>5000 m) marine carbonate reservoirs have gradually become important exploration targets. This research focuses on providing an understanding of the basic elements of the ultra-deeply buried Middle Triassic Leikoupo marine carbonate petroleum system within the Western Sichuan Depression, China. Comprehensive analyses of organic geochemistry, natural gas, and C–H–He–Ne–Ar isotope compositions suggest that the reservoir is charged with compound gases from four source rock units including the Permian Longtan, Middle Triassic Leikoupo, Late Triassic Maantang and Xiaotangzi formations. Approximately a 50-m thick outcrop and 100-m length of drilling cores were examined in detail, and 108 samples were collected from six different exploration wells in order to conduct petrographic and petrophysical analyses. Thin-section and scanning electron microscope (SEM) observations, helium porosity and permeability measurements, mercury injection capillary pressure (MICP) analysis, and wire-line logging (5,500–6,900 m) indicate that the reservoir lithologies include argillaceous algal limestones, dolograinstones, crystalline dolostones, and microbially-derived stromatolitic and thrombolitic dolostones. Reservoir properties exhibit extreme heterogeneity due to different paleogeographic environmental controls and mutual interactions between constructive (e.g., epigenetic paleo-karstification, burial dissolution, structural movement, pressure-solution and dolomitization) and destructive (e.g., physical/chemical compaction, cementation, infilling, recrystallization, and replacement) diagenetic processes. An unconformity-related epigenetic karstification zone was identified in the uppermost fourth member of the Leikoupo Formation, which has developed secondary solution-enhanced pores, vugs, and holes that resulted in higher porosity (1.8–14.2%) and permeability (0.2–7.7 mD). The homogeneity and tightness of the reservoir increases with depth below the unconformity, and it is characterized by primary intergranular and intracrystalline pores, solution pores, fractures, stylolites, and micropores with a lower helium porosity (0.6–4.1%) and permeability (0.003–125.2 mD). Regional seals consist of the Late Triassic Xujiahe Formation, comprised of ~300 m of mudstones that are overlain by ~5,000-m thick of Jurassic to Quaternary continental argillaceous overburden rocks. Effective traps are dominated by a combination of structural-stratigraphic types. Paleo- reservoir crude oil cracking, wet-gases, and dry-gases from three successive hydrocarbon generation processes supplied the sufficient hydrocarbon resources. The homogenization temperatures of the hydrocarbon-associated aqueous fluid inclusions range from 98–130 °C and 130–171 °C, which suggests hydrocarbon charging occurred between 220–170 Ma and 130–90 Ma, respectively. One-dimensional basin evolution models combined with structural geologic and seismic profiles across wells PZ1-XQS1-CK1-XCS1-TS1 show that hydrocarbon migration and entrapment mainly occurred via the unconformity and interconnected fault-fracture networks with migration and charging driven by formation overpressure, abnormal fluid flow pressure, and buoyancy forces during the Indosinian and Yanshanian orogenies, with experiencing additional transformation occurring during the Himalayan orogeny. The predicted estimated reserves reached ~300 × 109 m3. The results provide excellent scientific implications for similar sedimentary basin studies, it is believed that abundant analogous deeply buried marine carbonate hydrocarbon resources yet to be discovered in China and elsewhere worldwide in the near future

Adsorption Behavior of Iodine by Novel Covalent Organic Polymers Constructed Through Heterostructural Mixed Linkers

The efficient capture and storage radioactive iodine (129I or 131I) formed during the extensive use of nuclear energy is of paramount importance. Therefore, it is a great deal to design and empolder new adsorbents for effectively disposing of iodine from nuclear waste. In this work, we presented a novel covalent organic polymer (JLUE-COP-3) constructed through heterostructural mixed linkers with perforated porousness, plenty of π-conjugated phenyl rings and functional –CO–NH– and –SO3H groups to iodine adsorption process. After fully characterizing the morphology and structure, the adsorption behavior of iodine by the resultant polymers were explored in detail. The external adsorption behavior was determined to obey the pseudo-second order kinetic model according to the kinetic analysis. The maximum liquid adsorption capacity was obtained to reach 153.85 mg/g at 298 K, which was evaluated by the Langmuir isotherm model. In addition, the negative attributes of ΔG° as well as the positive attributes of ΔH° and ΔS° at three temperatures indicated the nature of the iodine adsorption over JLUE-COP-3 was spontaneous and endothermic. The current study could look forward to making great contributions to the facile fabrication of late-model three-component POP materials and their applications in treatment of nuclear waste

DL3DV-10K: A Large-Scale Scene Dataset for Deep Learning-based 3D Vision

We have witnessed significant progress in deep learning-based 3D vision, ranging from neural radiance field (NeRF) based 3D representation learning to applications in novel view synthesis (NVS). However, existing scene-level datasets for deep learning-based 3D vision, limited to either synthetic environments or a narrow selection of real-world scenes, are quite insufficient. This insufficiency not only hinders a comprehensive benchmark of existing methods but also caps what could be explored in deep learning-based 3D analysis. To address this critical gap, we present DL3DV-10K, a large-scale scene dataset, featuring 51.2 million frames from 10,510 videos captured from 65 types of point-of-interest (POI) locations, covering both bounded and unbounded scenes, with different levels of reflection, transparency, and lighting. We conducted a comprehensive benchmark of recent NVS methods on DL3DV-10K, which revealed valuable insights for future research in NVS. In addition, we have obtained encouraging results in a pilot study to learn generalizable NeRF from DL3DV-10K, which manifests the necessity of a large-scale scene-level dataset to forge a path toward a foundation model for learning 3D representation. Our DL3DV-10K dataset, benchmark results, and models will be publicly accessible at https://dl3dv-10k.github.io/DL3DV-10K/

Multilevel defects in the hematopoietic niche in essential thrombocythemia

The role of the bone marrow niche in essential thrombocythemia (ET) remains unclear. Here, we observed multilevel defects in the hematopoietic niche of patients with JAK2V617F-positive ET, including functional deficiency in mesenchymal stromal cells (MSC), immune imbalance, and sympathetic-nerve damage. Mesenchymal stromal cells from patients with JAK2V617F-positive essential thrombocythemia had a transformed transcriptome. In parallel, they showed enhanced proliferation, decreased apoptosis and senescence, attenuated ability to differentiate into adipocytes and osteocytes, and insufficient support for normal hematopoiesis. Additionally, they were inefficient in suppressing immune responses. For instance, they poorly inhibited proliferation and activation of CD4-positive T cells and the secretion of the inflammatory factor soluble CD40-ligand. They also poorly induced formation of mostly immunosuppressive T-helper 2 cells (Th2) and the secretion of the anti-inflammatory factor interleukin-4 (IL-4). Furthermore, we identified WDR4 as a potent protein with low expression and which was correlated with increased proliferation, reduced senescence and differentiation, and insufficient support for normal hematopoiesis in MSC from patients with JAK2V617F-positive ET. We also observed that loss of WDR4 in MSC cells downregulated the interleukin-6 (IL-6) level through the ERK–GSK3β–CREB signaling based on our in vitro studies. Altogether, our results show that multilevel changes occur in the bone marrow niche of patients with JAK2V617F-positive ET, and low expression of WDR4 in MSC may be critical for inducing hematopoietic related changes

Prediction of Biological Functions on Glycosylation Site Migrations in Human Influenza H1N1 Viruses

Protein glycosylation alteration is typically employed by various viruses for escaping immune pressures from their hosts. Our previous work had shown that not only the increase of glycosylation sites (glycosites) numbers, but also glycosite migration might be involved in the evolution of human seasonal influenza H1N1 viruses. More importantly, glycosite migration was likely a more effectively alteration way for the host adaption of human influenza H1N1 viruses. In this study, we provided more bioinformatics and statistic evidences for further predicting the significant biological functions of glycosite migration in the host adaptation of human influenza H1N1 viruses, by employing homology modeling and in silico protein glycosylation of representative HA and NA proteins as well as amino acid variability analysis at antigenic sites of HA and NA. The results showed that glycosite migrations in human influenza viruses have at least five possible functions: to more effectively mask the antigenic sites, to more effectively protect the enzymatic cleavage sites of neuraminidase (NA), to stabilize the polymeric structures, to regulate the receptor binding and catalytic activities and to balance the binding activity of hemagglutinin (HA) with the release activity of NA. The information here can provide some constructive suggestions for the function research related to protein glycosylation of influenza viruses, although these predictions still need to be supported by experimental data

Two Glycosylation Sites in H5N1 Influenza Virus Hemagglutinin That Affect Binding Preference by Computer-Based Analysis

Increasing numbers of H5N1 influenza viruses (IVs) are responsible for human deaths, especially in North Africa and Southeast Asian. The binding of hemagglutinin (HA) on the viral surface to host sialic acid (SA) receptors is a requisite step in the infection process. Phylogenetic analysis reveals that H5N1 viruses can be divided into 10 clades based on their HA sequences, with most human IVs centered from clade 1 and clade 2.1 to clade 2.3. Protein sequence alignment in various clades indicates the high conservation in the receptor-binding domains (RBDs) is essential for binding with the SA receptor. Two glycosylation sites, 158N and 169N, also participate in receptor recognition. In the present work, we attempted to construct a serial H5N1 HA models including diverse glycosylated HAs to simulate the binding process with various SA receptors in silico. As the SA-α-2,3-Gal and SA-α-2,6-Gal receptor adopted two distinctive topologies, straight and fishhook-like, respectively, the presence of N-glycans at 158N would decrease the affinity of HA for all of the receptors, particularly SA-α-2,6-Gal analogs. The steric clashes of the huge glycans shown at another glycosylation site, 169N, located on an adjacent HA monomer, would be more effective in preventing the binding of SA-α-2,3-Gal analogs