Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of mitochondria distribution by RhoA and formins

The distribution of mitochondria is strictly controlled by the cell because of their vital role in energy supply, regulation of cytosolic Ca2+ concentration and apoptosis. We employed cultured mammalian CV-1 cells and Drosophila BG2-C2 neuronal cells with enhanced green fluorescent protein (EGFP)-tagged mitochondria to investigate the regulation of their movement and anchorage. We show here that lysophosphatidic acid (LPA) inhibits fast mitochondrial movements in CV-1 cells acting through the small GTPase RhoA. The action of RhoA is mediated by its downstream effectors: formin-homology family members mDia1 in mammalian cells and diaphanous in Drosophila. Overexpression of constitutively active mutant forms of formins leads to dramatic loss of mitochondrial motility and to their anchorage to actin microfilaments. Conversely, depletion of endogenous diaphanous protein in BG2-C2 cells by RNA interference (RNAi) stimulates the mitochondrial movement. These effects are not simply explained by increased cytoplasm viscosity resulting from an increased F-actin concentration since stimulators of Arp2/3-dependent actin polymerization and jasplakinolide do not cause inhibition. The observed effects are highly specific to mitochondria since perturbations of diaphanous or mDia1 have no effect on movement of other membrane organelles. Thus, mitochondrial movement is controlled by the small GTPase RhoA and this control is mediated by formins.
Characteristics of gastric cancer detected within 1 year after successful eradication of Helicobacter pylori

Gastric cancers are sometimes diagnosed in patients who have successfully undergone Helicobacter pylori (H. pylori) eradication. We analyzed the clinicopathological features of gastric cancers detected after eradication to clarify their characteristics. We reviewed 31 patients with 34 cases of gastric cancer detected after successful H. pylori eradication. Clinicopathological characteristics analyzed included interval since eradication, interval since last endoscopy, tumor size, and depth of invasion. Patients were classified into two groups: early detection (<1 year since eradication) and delayed detection (≥1 year since eradication). The interval since last endoscopy was significantly shorter in the early detection group than in the delayed detection group. However, gastric cancers were significantly larger and more invasive in the early detection group than in the delayed detection group. In conclusion, diligent endoscopy is necessary during the first year after successful H. pylori eradication. (The University Hospital Medical Information Network clinical trial registration number is UMIN000018541.)
A Topological Characterization of Medium-Dependent Essential Metabolic Reactions

Metabolism has frequently been analyzed from a network perspective. A major question is how network properties correlate with biological features like growth rates, flux patterns and enzyme essentiality. Using methods from graph theory as well as established topological categories of metabolic systems, we analyze the essentiality of metabolic reactions depending on the growth medium and identify the topological footprint of these reactions. We find that the typical topological context of a medium-dependent essential reaction is systematically different from that of a globally essential reaction. In particular, we observe systematic differences in the distribution of medium-dependent essential reactions across three-node subgraphs (the network motif signature of medium-dependent essential reactions) compared to globally essential or globally redundant reactions. In this way, we provide evidence that the analysis of metabolic systems on the few-node subgraph scale is meaningful for explaining dynamic patterns. This topological characterization of medium-dependent essentiality provides a better understanding of the interplay between reaction deletions and environmental conditions.
Regulation of DNA Repair Mechanism in Human Glioma Xenograft Cells both In Vitro and In Vivo in Nude Mice

Background Glioblastoma Multiforme (GBM) is the most lethal form of brain tumor. Efficient DNA repair and anti-apoptotic mechanisms are making glioma treatment difficult. Proteases such as MMP9, cathepsin B and urokinase plasminogen activator receptor (uPAR) are over expressed in gliomas and contribute to enhanced cancer cell proliferation. Non-homologous end joining (NHEJ) repair mechanism plays a major role in double strand break (DSB) repair in mammalian cells. Methodology/Principal Findings Here we show that silencing MMP9 in combination with uPAR/cathepsin B effects NHEJ repair machinery. Expression of DNA PKcs and Ku70/80 at both mRNA and protein levels in MMP9-uPAR (pMU) and MMP9-cathepsin B (pMC) shRNA-treated glioma xenograft cells were reduced. FACS analysis showed an increase in apoptotic peak and proliferation assays revealed a significant reduction in the cell population in pMU- and pMC-treated cells compared to untreated cells. We hypothesized that reduced NHEJ repair led to DSBs accumulation in pMU- and pMC-treated cells, thereby initiating cell death. This hypothesis was confirmed by reduced Ku70/Ku80 protein binding to DSB, increased comet tail length and elevated γH2AX expression in treated cells compared to control. Immunoprecipitation analysis showed that EGFR-mediated lowered DNA PK activity in treated cells compared to controls. Treatment with pMU and pMC shRNA reduced the expression of DNA PKcs and ATM, and elevated γH2AX levels in xenograft implanted nude mice. Glioma cells exposed to hypoxia and irradiation showed DSB accumulation and apoptosis after pMU and pMC treatments compared to respective controls. Conclusion/Significance Our results suggest that pMU and pMC shRNA reduce glioma proliferation by DSB accumulation and increase apoptosis under normoxia, hypoxia and in combination with irradiation. Considering the radio- and chemo-resistant cancers favored by hypoxia, our study provides important therapeutic potential of MMP9, uPAR and cathepsin B shRNA in the treatment of glioma from clinical stand point.
Influence of N-Terminal Domain Histidine and Proline Residues on the Substrate Selectivities of Human UDP-Glucuronosyltransferase 1A1, 1A6, 1A9, 2B7, and 2B10

An N-terminal domain histidine [corresponding to position 39 of UDP-glucuronosyltransferase (UGT) 1A1] is conserved in all UGT1A and UGT2B subfamily proteins except UGT1A4 (Pro-40) and UGT2B10 (Leu-34). Unlike most UGT1A and UGT2B xenobiotic-metabolizing enzymes, UGT1A4 and UGT2B10 lack the ability to glucuronidate 4-methylumbelliferone (4MU) and 1-naphthol (1NP), both planar phenols, and naproxen (a carboxylic acid). However, only UGT1A4 glucuronidates the tertiary amines lamotrigine (LTG) and trifluoperazine (TFP). In this study, we sought to elucidate the influence of specific N-terminal histidine and proline residues on UGT enzyme substrate selectivity. The conserved N-terminal domain histidine of UGT1A1, UGT1A6, UGT1A9, and UGT2B7 was mutated to proline and leucine 34 of UGT2B10 was substituted with histidine, and the capacity of the wild-type and mutant proteins to glucuronidate 4MU, 1NP, LTG, TFP, and naproxen was characterized. Whereas UGT1A1(H39P), UGT1A6(H38P), and UGT1A9(H37P) lacked the ability to metabolize 4MU, 1NP, and naproxen, all glucuronidated LTG. Km values for UGT1A1(H39P) and UGT1A9(H37P) were 774 and 3812 μM, respectively, compared with 1579 μM for UGT1A4. UGT1A1(H39P) also glucuronidated TFP with a Vmax/Km value comparable to that of UGT1A4. In contrast to the wild-type enzyme, UGT2B10(L34H) glucuronidated 4MU and 1NP with respective Km values of 260 and 118 μM. UGT2B7(H35P) lacked activity toward all substrates. The data confirm a pivotal role for an N-terminal domain proline in the glucuronidation of the tertiary amines LTG and TFP by UGT1A subfamily proteins, whereas glucuronidation reactions involving proton abstraction generally, although not invariably, require a histidine at the equivalent position in both UGT1A and UGT2B enzymes.
Preattentive co-saliency detection

This paper presents a new algorithm to solve the problem of co-saliency detection, i.e., to find the common salient objects that are present in both of a pair of input images. Unlike most previous approaches, which require correspondence matching, we seek to solve the problem of co-saliency detection under a preattentive scheme. Our algorithm does not need to perform the correspondence matching between the two input images, and is able to achieve co-saliency detection before the focused attention occurs. The joint information provided by the image pair enables our algorithm to inhibit the responses of other salient objects that appear in just one of the images. Through experiments we show that our algorithm is effective in localizing the co-salient objects inside input image pairs.
Finite-SNR Diversity-Multiplexing Tradeoff and Optimum Power Allocation in Bidirectional Cooperative Networks

This paper focuses on analog network coding (ANC) and time division broadcasting (TDBC) which are two major protocols used in bidirectional cooperative networks. Lower bounds of the outage probabilities of those two protocols are derived first. Those lower bounds are extremely tight in the whole signal-to-noise ratio (SNR) range irrespective of the values of channel variances. Based on those lower bounds, finite-SNR diversity-multiplexing tradeoffs of the ANC and TDBC protocols are obtained. Secondly, we investigate how to efficiently use channel state information (CSI) in those two protocols. Specifically, an optimum power allocation scheme is proposed for the ANC protocol. It simultaneously minimizes the outage probability and maximizes the total mutual information of this protocol. For the TDBC protocol, an optimum method to combine the received signals at the relay terminal is developed under an equal power allocation assumption. This method minimizes the outage probability and maximizes the total mutual information of the TDBC protocol at the same time.
Description Trees for Some Families of Planar Maps

In this paper, we introduce description trees, to give a general framework for the recursive decompositions of several families of planar maps studied by W.T. Tutte. These trees reeect the combinatorial structure of the decompositions and carry out various combi-natorial parameters. We also introduce left regular trees as canonical representants of some new conjugacy classes on planted plane trees. We give an enumeration formula for these trees. In several cases the combination of these two ingredients yields a purely combinatorial proof of some elegant formulae of W.T. Tutte and gives uniform random generation algorithms for the corresponding planar maps. Rsum Dans cet article, nous introduisons des arbres de description pour coder la dcomposi-tion rcursive de plusieurs familles de cartes planaires tudies par W.T. Tutte. Ces arbres reetent la structure combinatoire de la dcomposition et portent diirents paramtres com-binatoires. Nous introduisons aussi les arbres rguliers gauches qui sont des repr esentants canoniques de nouvelles classes de conjugauisons d'arbre plan plant es. Nous donnons une formule d'numration pour ces arbres. Dans plusieurs cas la combinaison de ces deux ingrdients aboutit la preuve combinatoire de certaines formules de W.T. Tutte et donne des algorithmes de gnration alatoire uniforme pour les cartes planaires associes.
Opacity and cyclicity

Cyclic phonology-morphology interactions and opacity have been dealt with in strictly parallelist OT by introducing new constraint types, including Base-Output constraints and Sympathy. An alternative OT approach to the phonology-morphology interface is a constraint-based version of Lexical Phonology and Morphology (LPM), in which stems, words, and sentences are subject to separate, serially related OT constraint systems. I show that OT-based LPM provides a superior account of the cyclic morphology/phonology interaction in Levantine data from which Kenstowicz and Kager drew support for Base-Output constraints, and that the same account explains the derivational opacity phenomena for which Sympathy theory provides a purely descriptive solution.
Theoretical Methods of Domain Structures in Ultrathin Ferroelectric Films: A Review

This review covers methods and recent developments of the theoretical study of domain structures in ultrathin ferroelectric films. The review begins with an introduction to some basic concepts and theories (e.g., polarization and its modern theory, ferroelectric phase transition, domain formation, and finite size effects, etc.) that are relevant to the study of domain structures in ultrathin ferroelectric films. Basic techniques and recent progress of a variety of important approaches for domain structure simulation, including first-principles calculation, molecular dynamics, Monte Carlo simulation, effective Hamiltonian approach and phase field modeling, as well as multiscale simulation are then elaborated. For each approach, its important features and relative merits over other approaches for modeling domain structures in ultrathin ferroelectric films are discussed. Finally, we review recent theoretical studies on some important issues of domain structures in ultrathin ferroelectric films, with an emphasis on the effects of interfacial electrostatics, boundary conditions and external loads.
Class Prior Estimation from Positive and Unlabeled Data

We consider the problem of learning a classifier using only positive and unlabeled samples. In this setting, it is known that a classifier can be successfully learned if the class prior is available. However, in practice, the class prior is unknown and thus must be estimated from data. In this paper, we propose a new method to estimate the class prior by partially matching the class-conditional density of the positive class to the input density. By performing this partial matching in terms of the Pearson divergence, which we estimate directly without density estimation via lower-bound maximization, we can obtain an analytical estimator of the class prior. We further show that an existing class prior estimation method can also be interpreted as performing partial matching under the Pearson divergence, but in an indirect manner. The superiority of our direct class prior estimation method is illustrated on several benchmark datasets.
On Test Case Distributions of Adaptive Random Testing

Adaptive Random Resting (ART) has recently been proposed as an approach to enhancing the fault-detection effectiveness of Random Testing (RT). The basic principle of ART is to enforce randomly selected test cases as evenly spread over the input domain as possible. Many ART methods have been proposed to evenly spread test cases in different ways, but no comparison has been made among these methods in terms of their test case distributions. In this paper, we conduct a comprehensive investigation on test case distributions of various ART methods. Our work shows many interesting aspects related to ART's performance and its test case distribution. Furthermore, it points out a new research direction on enhancing ART.
Predictors of Love Attitudes: The Contribution of Cultural Orientation, Gender Attachment Style, Relationship Length and Age in Participants From the UK and Hong Kong

The aim of this research was to explore whether a model including psychological predictors at the individual, interpersonal and cultural level could predict romantic attitudes. Attachment style, cultural orientation, gender, and relationship length were tested as predictors for each of the six love styles conceptualized by Lee (1977). Adults from Britain (N = 56) and Hong Kong (N = 52) who were in a romantic relationship completed four self-report measures; a demographic questionnaire, The Individualism and Collectivism Scale (IC-S), The Experiences in Close Relationship Scale-Short Form (ECR-S) and The Love Attitude Scale short form (LAS). The model successfully predicted each love style and in one case (Mania) accounted for 52% of the variance in this love style. Each love attitude had a different profile, and no one predictor dominated any one style which supports Lee’s original idea that the styles are qualitatively different.
Intelligent in-pipe machine adjustable to inner pipe diameter

The paper concerns to area of in-pipe locomotion. Traditional conceptions of in-pipe machines tend to wheels slipping or self-blocking. Several design stages of improved in-pipe machine are shown. Design of in-pipe machine coming from conception of computer controlled electromechanical device. Final design solution will be able to locomote inside pipe with variation of inner diameter in range from 100 to 200 mm with automatically adjustment to pipe diameter.
On the passage from atomistic systems to nonlinear elasticity theory for general multi-body potentials with p-growth

We derive continuum limits of atomistic models in the realm of nonlinear elasticity theory rigorously as the interatomic distances tend to zero. In particular we obtain an integral functional acting on the deformation gradient in the continuum theory which depends on the underlying atomistic interaction potentials and the lattice geometry. The interaction potentials to which our theory applies are general finite range models on multilattices which in particular can also account for multi-pole interactions and bond-angle dependent contributions. Furthermore, we discuss the applicability of the Cauchy-Born rule. Our class of limiting energy densities consists of general quasiconvex functions and the class of linearized limiting energies consistent with the Cauchy-Born rule consists of general quadratic forms not restricted by the Cauchy relations.
Pituitary Tumor-Transforming Gene 1 Is Expressed in Primary Ductal Breast Carcinoma, Lymph Node Infiltration, and Distant Metastases

Despite the advances that have been made in the fields of molecular and cell biology, there is still considerable debate explaining how the breast cancer cells progress through carcinogenesis and acquire their metastatic ability. The lack of preventive methods and effective therapies underlines the pressing need to identify new biomarkers that can aid early diagnosis and may be targets for effective therapeutic strategies. In this study we explore the pituitary tumor-transforming gene 1 (PTTG1) expression in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Three human cell lines, 184B5 derived from normal mammary epithelium, HCC70 from a primary ductal carcinoma, and MDA-MB-361 from a breast metastasis, were used for quantifying PTTG1 mRNA expression. The PTTG1 immunohistochemical expression was carried out on specimens taken from eight patients with invasive ductal breast cancer who underwent surgical treatment and followup for five years retrospectively selected. The study demonstrated that PTTG1 is expressed gradually in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Our findings suggest that the immunohistochemical evaluation of PTTG1 expression might be a powerful biomarker of recognition and quantification of the breast cancer cells in routine pathological specimens and a potential target for developing an effective immunotherapeutic strategy for primary and metastatic breast cancer.
Cross-frequency coupling supports multi-item working memory in the human hippocampus

Recent findings indicate that the hippocampus supports not only long-term memory encoding but also plays a role in working memory (WM) maintenance of multiple items; however, the neural mechanism underlying multi-item maintenance is still unclear. Theoretical work suggests that multiple items are being maintained by neural assemblies synchronized in the gamma frequency range (25–100 Hz) that are locked to consecutive phase ranges of oscillatory activity in the theta frequency range (4–8 Hz). Indeed, cross-frequency coupling of the amplitude of high-frequency activity to the phase of slower oscillations has been described both in animals and in humans, but has never been linked to a theoretical model of a cognitive process. Here we used intracranial EEG recordings in human epilepsy patients to test pivotal predictions from theoretical work. First, we show that simultaneous maintenance of multiple items in WM is accompanied by cross-frequency coupling of oscillatory activity in the hippocampus, which is recruited during multi-item WM. Second, maintenance of an increasing number of items is associated with modulation of beta/gamma amplitude with theta band activity of lower frequency, consistent with the idea that longer cycles are required for an increased number of representations by gamma cycles. This effect cannot be explained by a difference in theta or beta/gamma power. Third, we describe how the precision of cross-frequency coupling predicts individual WM performance. These data support the idea that working memory in humans depends on a neural code using phase information.
Targeting Angiotensin II Type-1 Receptor (AT1R) Inhibits the Harmful Phenotype of Plasmodium-Specific CD8+ T Cells during Blood-Stage Malaria

CD8+ T-cell response is critical in the pathogenesis of cerebral malaria during blood-stage. Our group and other have been shown that angiotensin II (Ang II) and its receptor AT1 (AT1R), a key effector axis of renin-angiotensin system (RAS), have immune regulatory effects on T cells. Previously, we showed that inhibition of AT1R signaling protects mice against the lethal disease induced by Plasmodium berghei ANKA infection However, most of the Ang II/AT1R actions were characterized by using only pharmacological approaches, the effects of which may not always be due to a specific receptor blockade. In addition, the mechanisms of action of the AT1R in inducing the pathogenic activity of Plasmodium-specific CD8+ T cells during blood-stage were not determined. Here, we examined how angiotensin II/AT1R axis promotes the harmful response of Plasmodium-specific CD8+ T-cell during blood-stage by using genetic and pharmacological approaches. We evaluated the response of wild-type (WT) and AT1R−/− Plasmodium-specific CD8+ T cells in mice infected with a transgenic PbA lineage expressing ovalbumin; and in parallel infected mice receiving WT Plasmodium-specific CD8+ T cells were treated with losartan (AT1R antagonist) or captopril (ACE inhibitor). Both, AT1R−/− OT-I cells and WT OT-I cells from losartan- or captopril-treated mice showed lower expansion, reduced IL-2 production and IL-2Rα expression, lower activation (lower expression of CD69, CD44 and CD160) and lower exhaustion profiles. AT1R−/− OT-I cells also exhibit lower expression of the integrin LFA-1 and the chemokine receptors CCR5 and CXCR3, known to play a key role in the development of cerebral malaria. Moreover, AT1R−/− OT-I cells produce lower amounts of IFN-γ and TNF-α and show lower degranulation upon restimulation. In conclusion, our results show the pivotal mechanisms of AT1R-induced harmful phenotype of Plasmodium-specific CD8+ T cells during blood-stage malaria.
MEMS based IMU for tilting measurement: Comparison of complementary and kalman filter based data fusion

This research investigates real time tilting measurement using Micro-Electro-Mechanical-system (MEMS) based inertial measurement unit (IMU). Accelerometers suffer from errors caused by external accelerations that sums to gravity and make accelerometers based tilting sensing unreliable and inaccurate. Gyroscopes can offset such drawbacks but have data drifting problems. This paper presents a study on complementary and Kalman filter for tilting measurement using MEMS based IMU. The complementary filter algorithm uses low-pass filter and high-pass filter to deal with the data from accelerometer and gyroscope while Kalman filter takes the tilting angle and gyroscope bias as system states, combining the angle derived from the accelerometer to estimate the tilting angle. The study carried out both static and dynamic experiments. The results showed that both Complementary and Kalman filter were less sensitive to variations and almost no signal coupling phenomenon and able to obtain smooth and accurate results.