Miracle-dz/UniFAR-FTUs huggingface dataset:
KSR1 and EPHB4 Regulate Myc and PGC1β To Promote Survival of Human Colon Tumors

ABSTRACT Identification and characterization of survival pathways active in tumor cells but absent in normal tissues provide opportunities to develop effective anticancer therapies with reduced toxicity to the patient. We show here that, like kinase suppressor of Ras 1 (KSR1), EPH (erythropoietin-producing hepatocellular carcinoma) receptor B4 (EPHB4) is aberrantly overexpressed in human colon tumor cell lines and selectively required for their survival. KSR1 and EPHB4 support tumor cell survival by promoting the expression of downstream targets, Myc and the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1β (PGC1β). While KSR1 promotes the aberrant expression of Myc and the PGC1β protein via a posttranscriptional mechanism, EPHB4 has a greater effect on Myc and PGC1β expression via its ability to elevate mRNA levels. Subsequent analysis of the posttranscriptional regulation demonstrated that KSR1 promotes the translation of Myc protein. These findings reveal novel KSR1- and EPHB4-dependent signaling pathways supporting the survival of colorectal cancer cells through regulation of Myc and PGC1β, suggesting that inhibition of KSR1 or EPHB4 effectors may lead to selective toxicity in colorectal tumors.
The MicroRNA 29 Family Promotes Type II Cell Differentiation in Developing Lung

ABSTRACT Lung alveolar type II cells uniquely synthesize surfactant, a developmentally regulated lipoprotein that is essential for breathing. Expression of the gene (SFTPA) encoding the major surfactant protein, SP-A, in midgestation human fetal lung (HFL) is dramatically induced by cyclic AMP (cAMP). cAMP induction of SP-A expression is repressed by transforming growth factor β (TGF-β) and by hypoxia. In this study, we found that expression of the microRNA 29 (miR-29) family was significantly upregulated in epithelial cells isolated from mouse fetal lung during late gestation and in epithelial cells isolated from HFL explants during type II cell differentiation in culture. miR-29 expression in cultured HFL epithelial cells was increased by cAMP and inhibited by hypoxia, whereas the miR-29 target, TGF-β2, was coordinately decreased. Knockdown of the miR-29 family in cultured HFL type II cells blocked cAMP-induced SP-A expression and accumulation of surfactant-containing lamellar bodies, suggesting their physiological relevance. This occurred through derepression of TGF-β signaling. Notably, cAMP increased binding of endogenous thyroid transcription factor 1 (TTF-1/Nkx2.1) to the miR-29ab1 promoter in HFL type II cells, and TTF-1 increased miR-29ab1 promoter-driven luciferase activity in cotransfection assays. Together, these findings identify miR-29 family members as TTF-1-driven mediators of SP-A expression and type II cell differentiation through repression of TGF-β signaling.
Freud-1/Aki1, a Novel PDK1-Interacting Protein, Functions as a Scaffold To Activate the PDK1/Akt Pathway in Epidermal Growth Factor Signaling

ABSTRACT The phosphoinositide 3-kinase (PI3K)/3-phosphoinositide-dependent protein kinase 1 (PDK1)/Akt pathway regulates various cellular functions, especially cell survival and cell cycle progression. In contrast to other survival pathways, there have been few reports of scaffold proteins that regulate signaling cascade specificity in this pathway. Here we identify a 5′ repressor element under dual-repression binding protein 1 (Freud-1)/Akt kinase-interacting protein 1 (Aki1) as a novel scaffold for the PDK1/Akt pathway. Freud-1/Aki1 (also known as CC2D1A) expression induced formation of a PDK1/Akt complex and regulated Akt activation in a concentration-dependent biphasic manner. Freud-1/Aki1 also associated with epidermal growth factor (EGF) receptor in response to EGF stimulation and was required for Akt activation induced by EGF, but not by insulin-like growth factor 1. Freud-1/Aki1 gene silencing decreased Akt kinase activity, resulting in induction of apoptosis and increased sensitivity toward chemotherapeutic agents. Our results suggest that Freud-1/Aki1 is a novel receptor-selective scaffold protein for the PDK1/Akt pathway and present a new activation mechanism of Akt.
Genetic Demonstration of a Redundant Role of Extracellular Signal-Regulated Kinase 1 (ERK1) and ERK2 Mitogen-Activated Protein Kinases in Promoting Fibroblast Proliferation

ABSTRACT The extracellular signal-regulated kinase 1 and 2 (ERK1/2) mitogen-activated protein (MAP) kinase signaling pathway plays an important role in the proliferative response of mammalian cells to mitogens. However, the individual contribution of the isoforms ERK1 and ERK2 to cell proliferation control is unclear. The two ERK isoforms have similar biochemical properties and recognize the same primary sequence determinants on substrates. On the other hand, analysis of mice lacking individual ERK genes suggests that ERK1 and ERK2 may have evolved unique functions. In this study, we used a robust genetic approach to analyze the individual functions of ERK1 and ERK2 in cell proliferation using genetically matched primary embryonic fibroblasts. We show that individual loss of either ERK1 or ERK2 slows down the proliferation rate of fibroblasts to an extent reflecting the expression level of the kinase. Moreover, RNA interference-mediated silencing of ERK1 or ERK2 expression in cells genetically disrupted for the other isoform similarly reduces cell proliferation. We generated fibroblasts genetically deficient in both Erk1 and Erk2. Combined loss of ERK1 and ERK2 resulted in a complete arrest of cell proliferation associated with G1 arrest and premature replicative senescence. Together, our findings provide compelling genetic evidence for a redundant role of ERK1 and ERK2 in promoting cell proliferation.
OFDM and externally modulated multi-mode fibers in radio over fiber sy

Performance of wireless local area networks (WLANs) over fiber systems is investigated under multipath fading for different graded index fiber profiles and optical system imperfections. The effect of OFDM cyclic prefix to the multimode fiber dispersion is investigated for the first time. Comparison of the WLAN over fiber systems operating at 5 GHz and 60 GHz is presented. External modulators, namely Mach Zehnder external modulators, are employed in the system architecture. Wireless and optical impairments are attacked together and solved in a collaborative and efficient manner
Three-dimensional perception improvement using sharpness adjustment and hardware implementation

This paper presents a stereoscopic perception improvement algorithm using depth-adaptive sharpness adjustment in 3D video sequences and shows the FPGA implementation results. The first step of the proposed algorithm is to estimate the depth information of an input stereo video on a block basis. Second, the objects in the input video are segmented according to their depths. Third, the sharpness of the foreground objects is enhanced and the background objects are maintained or weakened. The simulation results show that the proposed algorithm can improve stereoscopic perception without intentional depth adjustment. In addition, we designed the hardware architecture of the proposed algorithm, and implemented it on a general-purpose FPGA board.
Group IVA Cytosolic Phospholipase A2 Regulates the G2-to-M Transition by Modulating the Activity of Tumor Suppressor SIRT2

ABSTRACT The G2-to-M transition (or prophase) checkpoint of the cell cycle is a critical regulator of mitotic entry. SIRT2, a tumor suppressor gene, contributes to the control of this checkpoint by blocking mitotic entry under cellular stress. However, the mechanism underlying both SIRT2 activation and regulation of the G2-to-M transition remains largely unknown. Here, we report the formation of a multiprotein complex at the G2-to-M transition in vitro and in vivo. Group IVA cytosolic phospholipase A2 (cPLA2α) acts as a bridge in this complex to promote binding of SIRT2 to cyclin A-Cdk2. Cyclin A-Cdk2 then phosphorylates SIRT2 at Ser331. This phosphorylation reduces SIRT2 catalytic activity and its binding affinity to centrosomes and mitotic spindles, promoting G2-to-M transition. We show that the inhibitory effect of cPLA2α on SIRT2 activity impacts various cellular processes, including cellular levels of histone H4 acetylated at K16 (Ac-H4K16) and Ac-α-tubulin. This regulatory effect of cPLA2α on SIRT2 defines a novel function of cPLA2α independent of its phospholipase activity and may have implications for the impact of SIRT2-related effects on tumorigenesis and age-related diseases.
Chromatin Structure Is Implicated in “Late” Elongation Checkpoints on the U2 snRNA and β-Actin Genes

ABSTRACT The negative elongation factor NELF is a key component of an early elongation checkpoint generally located within 100 bp of the transcription start site of protein-coding genes. Negotiation of this checkpoint and conversion to productive elongation require phosphorylation of the carboxy-terminal domain of RNA polymerase II (pol II), NELF, and DRB sensitivity-inducing factor (DSIF) by positive transcription elongation factor b (P-TEFb). P-TEFb is dispensable for transcription of the noncoding U2 snRNA genes, suggesting that a NELF-dependent checkpoint is absent. However, we find that NELF at the end of the 800-bp U2 gene transcription unit and RNA interference-mediated knockdown of NELF causes a termination defect. NELF is also associated 800 bp downstream of the transcription start site of the β-actin gene, where a “late” P-TEFb-dependent checkpoint occurs. Interestingly, both genes have an extended nucleosome-depleted region up to the NELF-dependent control point. In both cases, transcription through this region is P-TEFb independent, implicating chromatin in the formation of the terminator/checkpoint. Furthermore, CTCF colocalizes with NELF on the U2 and β-actin genes, raising the possibility that it helps the positioning and/or function of the NELF-dependent control point on these genes.
A visually salient approach to recognize vehicles based on hierarchical architecture

In order to recognize multi-class vehicles, traditional methods are typically based on license plates and frontal images of vehicles. These methods rely heavily on specific datasets and thus are not applicable in real-world tasks. In this paper, we propose a novel method based on a hierarchical model, HMAX, which simulates visual architecture of primates for object recognition. It can extract features of shift-invariance and scale-invariance by Gabor filtering, template matching, and max pooling. In particular, we adopt a model of saliency-based visual attention to detect salient patches for template matching, also we drop inefficient features via an all-pairs linear SVM. During experiments, high accuracy and great efficiency are achieved on a dataset which has 31 types and over 1400 vehicle images with varying scales, orientations, and colors. With comparisons with Original-HMAX, Salient-HMAX, and Sifted-HMAX model, our method achieves classifying accuracy at 92% and time for each image at around 1.5s, while reduces 73% of the time consumed by original HMAX model.
SRSF2 Is Essential for Hematopoiesis, and Its Myelodysplastic Syndrome-Related Mutations Dysregulate Alternative Pre-mRNA Splicing

ABSTRACT Myelodysplastic syndromes (MDS) are a group of neoplasms characterized by ineffective myeloid hematopoiesis and various risks for leukemia. SRSF2, a member of the serine/arginine-rich (SR) family of splicing factors, is one of the mutation targets associated with poor survival in patients suffering from myelodysplastic syndromes. Here we report the biological function of SRSF2 in hematopoiesis by using conditional knockout mouse models. Ablation of SRSF2 in the hematopoietic lineage caused embryonic lethality, and Srsf2-deficient fetal liver cells showed significantly enhanced apoptosis and decreased levels of hematopoietic stem/progenitor cells. Induced ablation of SRSF2 in adult Mx1-Cre Srsf2flox/flox mice upon poly(I):poly(C) injection demonstrated a significant decrease in lineage− Sca+ c-Kit+ cells in bone marrow. To reveal the functional impact of myelodysplastic syndromes-associated mutations in SRSF2, we analyzed splicing responses on the MSD-L cell line and found that the missense mutation of proline 95 to histidine (P95H) and a P95-to-R102 in-frame 8-amino-acid deletion caused significant changes in alternative splicing. The affected genes were enriched in cancer development and apoptosis. These findings suggest that intact SRSF2 is essential for the functional integrity of the hematopoietic system and that its mutations likely contribute to development of myelodysplastic syndromes.
The big data between your ears: Human inspired heuristics for forgetting in databases

Inspired by explanations of human forgetting, the primary research question that motivates this research is whether databases can be manipulated to resemble human long term memory in performance. We hypothesize that selective degradation of a database using different heuristics proposed as explanations of human forgetting, produce different recall results. Furthermore, we explore how these results resemble human performance by mapping performance to five memory phenomena that typify human forgetting. For this research we implemented the artificial long term memory of a fictitious character, Mr. Alfred Polly, using the Ardemia modelling architecture, which is built on a relational database management system. The experimental investigation of three versions of Mr. Polly's selectively degraded artificial memory revealed that forgetting heuristics produce query results that resemble human forgetting. The implication of this study is that big data algorithms inspired by “human forgetting inspired heuristics” can be a tool for shrinking and managing large data using attributes or metadata.
The Headpiece Domain of Dematin Regulates Cell Shape, Motility, and Wound Healing by Modulating RhoA Activation

ABSTRACT RhoA is known to participate in cytoskeletal remodeling events through several signaling pathways, yet the precise mechanism of its activation remains unknown. Here, we provide the first evidence that dematin functions upstream of RhoA and regulates its activation. Primary mouse embryonic fibroblasts were generated from a dematin headpiece domain null (HPKO) mouse, and the visualization of the actin morphology revealed a time-dependent defect in stress fiber formation, membrane protrusions, cell motility, and cell adhesion. Rescue experiments using RNA interference and transfection assays revealed that the observed phenotypes are due to a null effect and not a gain of function in the mutant fibroblasts. In vivo wounding of adult HPKO mouse skin showed a decrease in wound healing (reepithelialization and granulation) compared to the wild-type control. Biochemical analysis of the HPKO fibroblasts revealed a sustained hyperphosphorylation of focal adhesion kinase (FAK) at tyrosine 397 as well as a twofold increase in RhoA activation. Inhibition of both RhoA and FAK signaling using C3 toxin and FRNK (focal adhesion kinase nonrelated kinase), respectively, revealed that dematin acts upstream of RhoA. Together, these results unveil a new function of dematin as a negative regulator of the RhoA activation pathway with physiological implications for normal and pathogenic signaling pathways.
Emotion classification of EEG brain signal using SVM and KNN

Affective computing research field is growing in large scale with the frequent development of human-computer applications. These applications use information of mental or affective conditions of desired subjects to train their brain responses. Facial impressions, text physiology, vocal and other information about the subjects are used in the classification algorithms. However, the classification frameworks for EEG brain signals have been used infrequently due to the lack of a complete theoretical framework. Therefore, we present here an analysis of two different classification methods which are SVM and KNN. Four different types of emotional stimulus were presented to each subject. After preprocessing of raw EEG data, we employed Hjorth parameters for feature extraction of all EEG channels at each epoch. Five male subjects were selected in this experiment. Our results show that the emotion recognition from EEG brain signals might be possible.
Myristoylation and Membrane Binding Regulate c-Src Stability and Kinase Activity

ABSTRACT Myristoylation is critical for membrane association of Src kinases, but a role for myristate in regulating other aspects of Src biology has not been explored. In the c-Abl tyrosine kinase, myristate binds within a hydrophobic pocket at the base of the kinase domain and latches the protein into an autoinhibitory conformation. A similar pocket has been predicted to exist in c-Src, raising the possibility that Src might also be regulated by myristoylation. Here we show that in contrast to the case for c-Abl, myristoylation exerts a positive effect on c-Src kinase activity. We also demonstrate that myristoylation and membrane binding regulate c-Src ubiquitination and degradation. Nonmyristoylated c-Src exhibited reduced kinase activity but had enhanced stability compared to myristoylated c-Src. We then mutated critical residues in the predicted myristate binding pocket of c-Src. Mutation of L360 and/or E486 had no effect on c-Src membrane binding or localization. However, constructs containing a T456A mutation were partially released from the membrane, suggesting that mutagenesis could induce c-Src to undergo an artificial myristoyl switch. All of the pocket mutants exhibited decreased kinase activity. We concluded that myristoylation and the pocket residues regulate c-Src, but in a manner very different from that for c-Abl.
Buffer Control to Support a Seamless Stream Handoff in a WLAN that Employs Simulcast Streaming

This paper studies the buffer control issues that are related to supporting a seamless stream handoff in a WLAN environment that employs simulcast streaming. We analyze the impacts of the handoff disruption period and inter-AR synchronization variance. We also derive theoretical results that concern how a seamless stream handoff can be guaranteed in terms of the minimum buffer and backlog requirements. Based on the results, an MH-controlled-AR-pushed buffer control scheme is proposed and its cooperation with FMIPv6 is also discussed. The simulation results confirm the effectiveness of our scheme. In general, the deployment of a few-hundred-millisecond video-clip buffer in ARs and MHs is sufficient to achieve the seamless stream handoff most of the time, subject to fairly relaxed constraints of the inter-AR synchronization variance (ranging plusmn 150 ms) and handoff disruption period (around 50 ms).
Psy2 Targets the PP4 Family Phosphatase Pph3 To Dephosphorylate Mth1 and Repress Glucose Transporter Gene Expression

ABSTRACT The reversible nature of protein phosphorylation dictates that any protein kinase activity must be counteracted by protein phosphatase activity. How phosphatases target specific phosphoprotein substrates and reverse the action of kinases, however, is poorly understood in a biological context. We address this question by elucidating a novel function of the conserved PP4 family phosphatase Pph3-Psy2, the yeast counterpart of the mammalian PP4c-R3 complex, in the glucose-signaling pathway. Our studies show that Pph3-Psy2 specifically targets the glucose signal transducer protein Mth1 via direct binding of the EVH1 domain of the Psy2 regulatory subunit to the polyproline motif of Mth1. This activity is required for the timely dephosphorylation of the downstream transcriptional repressor Rgt1 upon glucose withdrawal, a critical event in the repression of HXT genes, which encode glucose transporters. Pph3-Psy2 dephosphorylates Mth1, an Rgt1 associated corepressor, but does not dephosphorylate Rgt1 at sites associated with inactivation, in vitro. We show that Pph3-Psy2 phosphatase antagonizes Mth1 phosphorylation by protein kinase A (PKA), the major protein kinase activated in response to glucose, in vitro and regulates Mth1 function via putative PKA phosphorylation sites in vivo. We conclude that the Pph3-Psy2 phosphatase modulates Mth1 activity to facilitate precise regulation of HXT gene expression by glucose.
Fathers' involvement in antenatal screening: midwives' views

Research on fathers' roles in antenatal screening has grown in recent years. Such research has emphasized the increasing importance of men's roles as supporters of pregnant partners undergoing screening, and as potential fathers interested in the wellbeing of their baby. Despite this increasing attention to men's roles in screening, existing research has tended to concentrate on seeking the views of those whose partners are undergoing screening. The views of professionals involved in screening are seldom explored. Drawing on a small scale empirical study with midwives in a northern city in the UK this article seeks to develop an understanding of men's participation in screening from a professional perspective. The article will highlight a number of interesting issues on this subject from attendance at screening to issues of paternity. The article concludes by emphasizing the importance of midwives' contributions, making suggestions for further research in this area.
A K-Nearest-Neighbor-Pooling method for graph matching

In the real-word matching, deformation, outliers and other emerging variations are inseparable conditions which make matching increasingly difficult. One way to solve this challenging problem is raising an effective graph matching method which is flexible to non-rigid objects. As a good structure representation, graph can nicely describe objects with meaningful information. Meanwhile, feature pooling plays a central role in feature sparsification. In this paper, we introduce a K-Nearest-Neighbor-Pooling Matching (KNNPM) method, which adopts feature pooling into the graph matching framework with lower solving complexity. The proposed algorithm evaluates each candidate matching with different weights on its k-nearest neighbors (KNN) by taking locality as well as sparsity into consideration. It also has wide range of applicability with generality in nowadays computer vision. In addition, our comparative and extensive experiments show the robustness and great improvements in matching accuracy.
The TSC1-TSC2 Complex Is Required for Proper Activation of mTOR Complex 2

ABSTRACT The mammalian target of rapamycin (mTOR) is a protein kinase that forms two functionally distinct complexes important for nutrient and growth factor signaling. Both complexes phosphorylate a hydrophobic motif on downstream protein kinases, which contributes to the activation of these kinases. mTOR complex 1 (mTORC1) phosphorylates S6K1, while mTORC2 phosphorylates Akt. The TSC1-TSC2 complex is a critical negative regulator of mTORC1. However, how mTORC2 is regulated and whether the TSC1-TSC2 complex is involved are unknown. We find that mTORC2 isolated from a variety of cells lacking a functional TSC1-TSC2 complex is impaired in its kinase activity toward Akt. Importantly, the defect in mTORC2 activity in these cells can be separated from effects on mTORC1 signaling and known feedback mechanisms affecting insulin receptor substrate-1 and phosphatidylinositol 3-kinase. Our data also suggest that the TSC1-TSC2 complex positively regulates mTORC2 in a manner independent of its GTPase-activating protein activity toward Rheb. Finally, we find that the TSC1-TSC2 complex can physically associate with mTORC2 but not mTORC1. These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2, which through different mechanisms promotes Akt activation.