Miracle-dz/UniFAR-FTUs huggingface dataset:
Tyr-94 Phosphorylation Inhibits Pyruvate Dehydrogenase Phosphatase 1 and Promotes Tumor Growth*

Background: How oncogenic signals attenuate mitochondrial function and promote the switch to glycolysis remains unclear. Results: Tyr-94 phosphorylation inhibits mitochondrial PDP1 and is important for the glycolytic switch and tumor growth. Conclusion: Phosphorylation at different tyrosine residues inhibits PDP1 through independent mechanisms to promote the Warburg effect. Significance: These data provide novel insights into the molecular mechanisms underlying the Warburg effect. Many cancer cells rely more on aerobic glycolysis (the Warburg effect) than mitochondrial oxidative phosphorylation and catabolize glucose at a high rate. Such a metabolic switch is suggested to be due in part to functional attenuation of mitochondria in cancer cells. However, how oncogenic signals attenuate mitochondrial function and promote the switch to glycolysis remains unclear. We previously reported that tyrosine phosphorylation activates and inhibits mitochondrial pyruvate dehydrogenase kinase (PDK) and phosphatase (PDP), respectively, leading to enhanced inhibitory serine phosphorylation of pyruvate dehydrogenase (PDH) and consequently inhibition of pyruvate dehydrogenase complex (PDC) in cancer cells. In particular, Tyr-381 phosphorylation of PDP1 dissociates deacetylase SIRT3 and recruits acetyltransferase ACAT1 to PDC, resulting in increased inhibitory lysine acetylation of PDHA1 and PDP1. Here we report that phosphorylation at another tyrosine residue, Tyr-94, inhibits PDP1 by reducing the binding ability of PDP1 to lipoic acid, which is covalently attached to the L2 domain of dihydrolipoyl acetyltransferase (E2) to recruit PDP1 to PDC. We found that multiple oncogenic tyrosine kinases directly phosphorylated PDP1 at Tyr-94, and Tyr-94 phosphorylation of PDP1 was common in diverse human cancer cells and primary leukemia cells from patients. Moreover, expression of a phosphorylation-deficient PDP1 Y94F mutant in cancer cells resulted in increased oxidative phosphorylation, decreased cell proliferation under hypoxia, and reduced tumor growth in mice. Together, our findings suggest that phosphorylation at different tyrosine residues inhibits PDP1 through independent mechanisms, which act in concert to regulate PDC activity and promote the Warburg effect.
A structure-based model for ligand binding and dimerization of EGF receptors.

On the basis of the 3D structures of the extracellular ligand-binding domains of the epidermal growth factor (EGF) receptor (EGFR) and ErbB3, a mechanism has been proposed for how the extracellular region of the EGFR is maintained in an autoinhibited configuration and for how EGF binding induces EGFR dimerization and activation. We have attempted to derive a mathematical model for EGF binding to the EGFR and for ligand-induced receptor dimerization and activation that uses this structural information and can explain the characteristic concave-up curvilinear Scatchard plots seen when EGF binding to intact EGFR is studied in living cells. We show that these curvilinear plots cannot be accounted for by simply ascribing different affinities to the autoinhibited and extended (dimeric) configurations of the receptor seen in structural studies. Concave-up plots can only be obtained by including in the mathematical model an additional binding event in which occupied EGFR dimers bind to an "external site. " The external site may represent receptor interactions with coated-pit regions in the cell membrane or with other cellular components involved in receptor endocytosis and turnover. We conclude in this study and in the accompanying article that the active extended EGFR configuration binds EGF 5- to 20-fold more strongly than the autoinhibited monomeric receptor configuration. However, these extended receptors do not correspond directly with the "high-affinity" EGF-binding sites seen in EGF-binding studies on intact cells.
EXTRACTING TASK-RELATED COMPONENTS IN FUNCTIONAL MRI

To extract consistently and transiently task-related component maps, a novel ICA paradigm, the ICA with reference (ICA-R), is proposed. ICA-R produces only component maps corresponding to the input stimuli which are used as reference signals in the learning paradigm, and all activations corresponding to a particular stimulus are located in a single component map. Computational and memory requirements of ICA-R are much less than those required by spatial ICA or temporal ICA.
Green Support and the Use of Information Technology Products

Nowadays people need technology in their daily life. This fact involves endless manufacturing of IT products. It increases the environmental problem. Concerned parties know that green IT products and green businesses are eco-saviors. The problem is lack of the green knowledge. This paper proposes and tests a framework that predict consumer intentions to support eco-friendly IT products and businesses. Structural equation modeling techniques was employed for hypothesis testing. The result suggests that to gain support from consumers, there are five criteria: belief in the benefits of a green IT, voluntary spending extra price, green-labels recognition, environmental concerns and influence from green policies/culture. However, social influence was insignificant in the intention to support green IT products. Increasing educational experiences and age strengthen the skepticism about the green IT benefits. The resources sacrifices become stronger with the higher educational experience. The influence of environmental concern is strengthener along with age.
Spatial‐temporal patterns of seismic tremors in northern Cascadia

[1] We study in detail the two consecutive episodic tremor-and-slip (ETS) events that occurred in the northern Cascadia subduction zone during 2003 and 2004. For both sequences, the newly developed Source-Scanning Algorithm (SSA) is applied to seismic waveform data from a dense regional seismograph array to determine the precise locations and origin times of seismic tremors. In map view, the majority of the tremors occurred in a limited band bounded approximately by the surface projections of the 30-km and 50-km depth contours of the plate interface. The horizontal migration of tremor occurrence is from southeast to northwest with an average speed of 5 km/d. In cross section, tremors in both sequences span a depth range of over 40 km across the interface, with the majority occurring in the overriding continental crust. In particular, 50-55% of them are located within 2.5 km from the strong seismic reflector bands above the plate interface. The lack of vertical migration implies that a slow diffusion process in the vertical direction cannot be responsible for tremor occurrences. The source spectra of tremors clearly lack high-frequency content (>5 Hz) relative to local earthquakes. We propose two possible models to explain the relationship between slip and tremors. The first one regards ETS tremors as the manifestation of hydroseismogenic processes in response to the temporal strain variation associated with the episodic slip along the lower portion of the plate interface downdip from the locked zone. In the second model, tremors and slip are associated with the same process along the same structure in a distributed deformation zone across the plate interface. Neither model can be dismissed conclusively at this stage.
Propagation Over Parabolic Terrain: Asymptotics and Comparison to Data

Analysis of radio propagation over varying, clutter-covered terrain was carried out aiming at prediction of power received by a terminal immersed in clutter, with the transmitter placed above clutter. The need for such prediction arises, for example, in planning and assessing coverage and interference in radio communications. Following a general formulation of the problem, particular solutions were found when the terrain has constant curvature. Asymptotic evaluation yielded compact expressions both for parabolic valleys and ridges. In both cases, ray-optical term dominated for short ranges, while a single mode dominated at large ranges. Strong focusing was found to occur in valleys, while ridges produced strong blockage beyond the ¿horizon¿. The resulting procedure for predicting pathloss over varying terrain is therefore to apply the formulae using the terrain curvature extracted from terrain files. In comparison to measured power across a valley, mean errors of less than 1 dB were found, a marked improvement over standard terrain-unaware models that produce a mean error of 30 dB.
Fast and Effective Geometric K-Nearest Neighbors Multi-frame Super-Resolution

Multi-frame super-resolution is possible when there is motion and non-redundant information from a sequence of low-resolution input images. Remote sensors, surveillance videos and modern mobile phones are examples of devices able to easily gather multiple images of a same scene. However, combining a large number of frames into a higher resolution image may not be computationally feasible by complex super-resolution techniques. We discuss herein a set of simple and effective high-performance algorithms to fastly super-resolve several low-resolution images in an always-on low-power environment, with possible applications in mobile computing, forensics, and biometrics. The algorithms rely on geometric k-nearest neighbors to decide which information to consider in each high-resolution pixel, have a low memory footprint and run in linear time as we increase the number of low-resolution input images. Finally, we suggest a minimum number of input images for multi-frame super-resolution, considering that we expect a good response as fast as possible.
Multi-Modal 2D and 3D Biometrics for Face Recognition

Results are presented for the largest experimental study to date that investigates the comparison and combination of 2D and 3D face data for biometric recognition. To our knowledge, this is also the only such study to incorporate significant time lapse between gallery and probe image acquisition. Recognition results are presented for gallery and probe datasets of 166 subjects imaged in both 2D and 3D, with six to thirteen weeks time lapse between gallery and probe images of a given subject. Using a PCA-based approach tuned separately for 2D and for 3D, we find no statistically significant difference between the rank-one recognition rates of 83.1% for 2D and 83.7% for 3D. Using a certainty-weighted sum-of-distance approach to combining 2D and 3D, we find a multimodal rank-one recognition rate of 92.8%, which is statistically significantly greater than either 2D or 3D alone.
Shared genetic regulatory networks for cardiovascular disease and type 2 diabetes in multiple populations of diverse ethnicities in the United States

Cardiovascular diseases (CVD) and type 2 diabetes (T2D) are closely interrelated complex diseases likely sharing overlapping pathogenesis driven by aberrant activities in gene networks. However, the molecular circuitries underlying the pathogenic commonalities remain poorly understood. We sought to identify the shared gene networks and their key intervening drivers for both CVD and T2D by conducting a comprehensive integrative analysis driven by five multi-ethnic genome-wide association studies (GWAS) for CVD and T2D, expression quantitative trait loci (eQTLs), ENCODE, and tissue-specific gene network models (both co-expression and graphical models) from CVD and T2D relevant tissues. We identified pathways regulating the metabolism of lipids, glucose, and branched-chain amino acids, along with those governing oxidation, extracellular matrix, immune response, and neuronal system as shared pathogenic processes for both diseases. Further, we uncovered 15 key drivers including HMGCR, CAV1, IGF1 and PCOLCE, whose network neighbors collectively account for approximately 35% of known GWAS hits for CVD and 22% for T2D. Finally, we cross-validated the regulatory role of the top key drivers using in vitro siRNA knockdown, in vivo gene knockout, and two Hybrid Mouse Diversity Panels each comprised of >100 strains. Findings from this in-depth assessment of genetic and functional data from multiple human cohorts provide strong support that common sets of tissue-specific molecular networks drive the pathogenesis of both CVD and T2D across ethnicities and help prioritize new therapeutic avenues for both CVD and T2D.
Replication of Poliovirus Requires Binding of the Poly(rC) Binding Protein to the Cloverleaf as Well as to the Adjacent C-Rich Spacer Sequence between the Cloverleaf and the Internal Ribosomal Entry Site

ABSTRACT The 5′ nontranslated region of poliovirus RNA contains two highly structured regions, the cloverleaf (CL) and the internal ribosomal entry site (IRES). A cellular protein, the poly(rC) binding protein (PCBP), has been reported to interact with the CL either alone or in combination with viral protein 3CDpro. The formation of the ternary complex is essential for RNA replication and, hence, viral proliferation. PCBP also interacts with stem-loop IV of the IRES, an event critical for the initiation of cap-independent translation. Until recently, no special function was assigned to a spacer region (nucleotides [nt] 89 to 123) located between the CL and the IRES. However, on the basis of our discovery that this region strongly affects the neurovirulent phenotype of poliovirus, we have embarked upon genetic and biochemical analyses of the spacer region, focusing on two clusters of C residues (C93-95 and C98-100) that are highly conserved among entero- and rhinoviruses. Replacement of all six C residues with A residues had no effect on translation in vitro but abolished RNA replication, leading to a lethal growth phenotype of the virus in HeLa cells. Mutation of the first group of C residues (C93-95) resulted in slower viral growth, whereas the C98-100A change had no significant effect on viability. Genetic analyses of the C-rich region by extensive mutagenesis and analyses of revertants revealed that two consecutive C residues (C94-95) were sufficient to promote normal growth of the virus. However, there was a distinct position effect of the preferred C residues. A 142-nt-long 5′-terminal RNA fragment including the CL and spacer sequences efficiently bound PCBP, whereas no PCBP binding was observed with the CL (nt 1 to 88) alone. Binding of PCBP to the 142-nt fragment was completely ablated after the two C clusters in the spacer were mutated to A clusters. In contrast, the same mutations had no effect on the binding of 3CDpro to the 142-nt RNA fragment. Stepwise replacement of the C residues with A residues resulted in impaired replication that covaried with weaker binding of PCBP in vitro. We conclude that PCBP has little, if any, binding affinity for the CL itself (nt 1 to 88) but requires additional nucleotides downstream of the CL for its function as an essential cofactor in poliovirus RNA replication. These data reveal a new essential function of the spacer between the CL and the IRES in poliovirus proliferation.
The Degree Theorem in Higher Rank

Let N be any closed, Riemannian manifold. In this paper we prove that, for most locally symmetric, nonpositively curved Riemannian manifolds M , and for every continuous map f : N → M , the map f is homotopic to a smooth map with Jacobian bounded by a universal constant, depending (as it must) only on Ricci curvature bounds of N . From this we deduce an extension of Gromov’s Volume Comparison Theorem for negatively curved manifolds to (most) nonpositively curved, locally symmetric manifolds.
Multitemperature Blackbody Spectrum of a Thin Accretion Disk around a Kerr Black Hole: Model Computations and Comparison with Observations

We use a ray-tracing technique to compute the observed spectrum of a thin accretion disk around a Kerr black hole. We include all relativistic effects such as frame-dragging, Doppler boost, gravitational redshift, and bending of light by the gravity of the black hole. We also include self-irradiation of the disk as a result of light deflection. Assuming that the disk emission is locally blackbody, we show how the observed spectrum depends on the spin of the black hole, the inclination of the disk, and the torque at the inner edge of the disk. We find that the effect of a nonzero torque on the spectrum can, to a good approximation, be absorbed into a zero-torque model by adjusting the mass accretion rate and the normalization. We describe a computer model, called KERRBB, which we have developed for fitting the spectra of black hole X-ray binaries. Using KERRBB within the X-ray data reduction package XSPEC, and assuming a spectral hardening factor fcol = 1.7, we analyze the spectra of three black hole X-ray binaries: 4U 1543-47, XTE J1550-564, and GRO J1655-40. We estimate the spin parameters of the black holes in 4U 1543-47 and GRO J1655-40 to be a/M ∼ 0.6 and ∼0.6-0.7, respectively. If fcol ∼ 1.5-1.6, as in a recent study, then we find a/M ∼ 0.7-0.8 and ∼0.8-0.9, respectively. These estimates are subject to additional uncertainties in the assumed black hole masses, distances, and disk inclinations.
On Generalization and Regularization in Deep Learning

Why do large neural network generalize so well on complex tasks such as image classification or speech recognition? What exactly is the role regularization for them? These are arguably among the most important open questions in machine learning today. In a recent and thought provoking paper [C. Zhang et al.] several authors performed a number of numerical experiments that hint at the need for novel theoretical concepts to account for this phenomenon. The paper stirred quit a lot of excitement among the machine learning community but at the same time it created some confusion as discussions on this http URL testifies. The aim of this pedagogical paper is to make this debate accessible to a wider audience of data scientists without advanced theoretical knowledge in statistical learning. The focus here is on explicit mathematical definitions and on a discussion of relevant concepts, not on proofs for which we provide references.
Chromosome Number Changes Associated with Speciation in Sedges: a Phylogenetic Study in Carex section Ovales (Cyperaceae) Using AFLP Data

Phylogenetic analysis of amplified fragment length polymorphisms (AFLP) was used to infer patterns of morphologic and chromosomal evolution in an eastern North American group of sedges (ENA clade I of Carex sect. Ovales). Distance analyses of AFLP data recover a tree that is topologically congruent with previous phylogenetic estimates based on nuclear ribosomal DNA (nrDNA) sequences and provide support for four species groups within ENA clade I. A maximum likelihood method designed for analysis of restriction site data is used to evaluate the strength of support for alternative topologies. While there is little support for the precise placement of the root, the likelihood of topologies in which any of the four clades identified within the ENA clade I is forced to be paraphyletic is much lower than the likelihood of the optimal tree. Chromosome counts for a sampling of species from throughout sect. Ovales are mapped onto the tree, as well as counts for all species in ENA clade I. Parsimony reconstruction of ancestral character states suggest that: (1) Heilborn's hypothesis that more highly derived species in Carex have higher chromosome counts does not apply within sect. Ovales, (2) the migration to eastern North America involved a decrease in average chromosome count within sect. Ovales, and (3) intermediate chromosome counts are ancestral within ENA clade I. A more precise understanding of chromosomal evolution in Carex should be possible using likelihood analyses that take into account the intraspecific polymorphism and wide range of chromosome counts that characterize the genus.
Leg elevation and wrapping in the prevention of hypotension following spinal anaesthesia for elective Caesarean section

Ninety‐seven parturients undergoing elective Caesarean section were allocated randomly to have their legs elevated to approximately 30° on pillows or elevated and wrapped with elasticated Esmarch bandages or neither (controls) following spinal anaesthesia. All patients received intravenous crystalloid (20 ml.kg−1 over 20 min) prior to spinal injection and were placed in the left lateral tilt position. Significant hypotension was treated with intravenous ephedrine in 5 mg bolus doses. Leg wrapping resulted in a significant reduction in the incidence ofpostspinal hypotension in comparison to the control group (18% compared to 53%, p = 0.004). This represents a five‐fold reduction in the likelihood ofpostspinal hypotension (odds ratio 5.3, 95% CI 1.7–16.3). Leg elevation alone did not significantly reduce the incidence of hypotension (39%). There was no significant difference in the time of onset of hypotension between the groups. For those patients requiring ephedrine, there was no significant difference in mean dose requirements between the groups. The use of leg compression immediately postspinal provides a simple means of reducing the accompanying hypotension and should be used more widely.
Prophylactic and therapeutic vaccines for obesity

Chronic diseases such as obesity and diabetes are major causes of death and disability throughout the world. Many causes are known to trigger these chronic diseases, and infectious agents such as viruses are also pathological factors. In particular, it is considered that adenovirus 36 infections may be associated with obesity. If this is the case, a vaccine against adenovirus 36 may be a form of prophylaxis to combat obesity. Other types of therapeutic vaccines to combat obesity are also being developed. Recently, hormones such as glucagon-like peptide-1, ghrelin, and peptide YY have been studied as treatments to prevent obesity. This review describes the ongoing development of therapeutic vaccines to treat obesity, and the possibility of using inactivated adenovirus 36 as a vaccine and an anti-obesity agent.
Visual Versus Quantitative Assessment of Intratumor 18F-FDG PET Uptake Heterogeneity: Prognostic Value in Non–Small Cell Lung Cancer

The goal of this study was to compare visual assessment of intratumor 18F-FDG PET uptake distribution with a textural-features (TF) automated quantification and to establish their respective prognostic value in non–small cell lung cancer (NSCLC). Methods: The study retrospectively included 102 consecutive patients. Only primary tumors were considered. Intratumor heterogeneity was visually scored (3-level scale [Hvisu]) by 2 nuclear medicine physicians. Tumor volumes were automatically delineated, and heterogeneity was quantified with TF. Mean and maximum standardized uptake value were also included. Visual interobserver agreement and correlations with quantitative assessment were evaluated using the κ test and Spearman rank (ρ) coefficient, respectively. Association with overall survival and recurrence-free survival was investigated using the Kaplan–Meier method and Cox regression models. Results: Moderate correlations (0.4 < ρ < 0.6) between TF parameters and Hvisu were observed. Interobserver agreement for Hvisu was moderate (κ = 0.64, discrepancies in 27% of the cases). High standardized uptake value, large metabolic volumes, and high heterogeneity according to TF were associated with poorer overall survival and recurrence-free survival and remained an independent prognostic factor of overall survival with respect to clinical variables. Conclusion: Quantification of 18F-FDG uptake heterogeneity in NSCLC through TF was correlated with visual assessment by experts. However, TF also constitutes an objective heterogeneity quantification, with reduced interobserver variability, and independent prognostic value potentially useful for patient stratification and management.