Miracle-dz/UniFAR-FTUs huggingface dataset:
Ion access pathway to the transmembrane pore in P2X receptor channels

P2X receptors are trimeric cation channels that open in response to the binding of adenosine triphosphate (ATP) to a large extracellular domain. The x-ray structure of the P2X4 receptor from zebrafish (zfP2X4) receptor reveals that the extracellular vestibule above the gate opens to the outside through lateral fenestrations, providing a potential pathway for ions to enter and exit the pore. The extracellular region also contains a void at the central axis, providing a second potential pathway. To investigate the energetics of each potential ion permeation pathway, we calculated the electrostatic free energy by solving the Poisson-Boltzmann equation along each of these pathways in the zfP2X4 crystal structure and a homology model of rat P2X2 (rP2X2). We found that the lateral fenestrations are energetically favorable for monovalent cations even in the closed-state structure, whereas the central pathway presents strong electrostatic barriers that would require structural rearrangements to allow for ion accessibility. To probe ion accessibility along these pathways in the rP2X2 receptor, we investigated the modification of introduced Cys residues by methanethiosulfonate (MTS) reagents and constrained structural changes by introducing disulfide bridges. Our results show that MTS reagents can permeate the lateral fenestrations, and that these become larger after ATP binding. Although relatively small MTS reagents can access residues in one of the vestibules within the central pathway, no reactive positions were identified in the upper region of this pathway, and disulfide bridges that constrain movements in that region do not prevent ion conduction. Collectively, these results suggest that ions access the pore using the lateral fenestrations, and that these breathe as the channel opens. The accessibility of ions to one of the chambers in the central pathway likely serves a regulatory function.
Banks' Equity Capital Frictions, Capital Ratios, and Interest Rates: Evidence from Spanish Banks

Banks’ choices on their economic capital factor into the cost of funds and are key to the assessment of the social cost from higher equity capital ratios set by Basel III. We model the determinants of equity capital and the influence of its ratios on the interest rates of bank loans by using data from Spanish banks. The results show that a combination of valuemaximization choices and inertial earnings retentions determine equity capital and that the inertia component is more important to savings banks than to commercial banks. We also find that loans’ interest rates increase with equity capital and the increase is higher during the adjustment period than in the steady state.
Histone H3 Exerts a Key Function in Mitotic Checkpoint Control

ABSTRACT It has been firmly established that many interphase nuclear functions, including transcriptional regulation, are regulated by chromatin and histones. How mitotic progression and quality control might be influenced by histones is less well characterized. We show that histone H3 plays a crucial role in activating the spindle assembly checkpoint in response to a defect in mitosis. Prior to anaphase, all chromosomes must attach to spindles emanating from the opposite spindle pole bodies. The tension between sister chromatids generated by the poleward pulling force is an integral part of chromosome biorientation. Lack of tension due to erroneous attachment activates the spindle assembly checkpoint, which corrects the mistakes and ensures segregation fidelity. A histone H3 mutation impairs the ability of yeast cells to activate the checkpoint in a tensionless crisis, leading to missegregation and aneuploidy. The defects in tension sensing result directly from an attenuated H3-Sgo1p interaction essential for pericentric recruitment of Sgo1p. Reinstating the pericentric enrichment of Sgo1p alleviates the mitotic defects. Histone H3, and hence the chromatin, is thus a key factor transmitting the tension status to the spindle assembly checkpoint.
Capsaicin Mediates Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells via Stabilizing and Activating p53

Capsaicin is the major pungent ingredient in red peppers which is world widely consumed. Except its potent pain relieving efficacy as reported, capsaicin also exerted its antitumor activity in several tumor models. Here, we reported that capsaicin had a profound anti-proliferative effect on human colon cancer cells via inducing cell cycle G0/G1 phase arrest and apoptosis, which was associated with an increase of p21, Bax and cleaved PARP. The underlying mechanism of capsaicin's antitumor potency was mainly attributed to the stabilization and activation of p53. Capsaicin substantially prolonged the half-life of p53 and significantly elevated the transcriptional activity of p53. Through suppressing the interaction between p53 and MDM2, MDM2-mediated p53 ubiquitination was remarkably decreased after capsaicin treatment, which resulted in the stabilization and accumulation of p53. The results of p53-shRNA experiment further demonstrated that p53 knockdown severely impaired the sensitivity of tested cells to capsaicin, G0/G1 phase arrest and the apoptosis induced by capsaicin in p53-knockdown cells was also dramatically decreased, implicating the important role of p53 played in capsaicin's antitumor activity. In summary, our data suggested that capsaicin, or a related analogue, may have a role in the management of human colon cancer.
Clinical and prognostic implications of β1, 6‐N‐acetylglucosaminyltransferase V in patients with gastric cancer

Aberrant β1, 6‐N‐acetylglucosaminyltransferase V (MGAT5) expression in malignant tissues has been reported to be involved in the development of various cancers and their progression, through altering N‐glycan branching. We aimed to investigate the clinical and prognostic values of MGAT5 and improve the risk stratification in patients with gastric cancer. MGAT5 expression was retrospectively analyzed by immunohistochemistry in three independent sets comprising 313 patients from China with gastric adenocarcinoma. Results were assessed for association with clinical features and overall survival using Kaplan–Meier analysis. Prognostic values of MGAT5 expression and clinical outcomes were evaluated by Cox regression analysis. A molecular prognostic stratification scheme incorporating MGAT5 expression was determined in patients with late‐stage gastric cancer by using receiver operating characteristic analysis. The results show that low intratumoral MGAT5 density, which was associated with poor differentiation, N classification, TNM stage, and Kiel stage, was an independent prognosticator for poor overall survival. The combination of intratumoral MGAT5 expression and TNM or Kiel staging systems had a better predictive power for overall survival. Applying the prognostic value of intratumoral MGAT5 density to TNM stage III+IV and Kiel stage IIIB+IV groups showed a better risk stratification for overall survival in patients with late‐stage gastric cancer. In conclusion, integrating intratumoral MGAT5 density that was recognized as an independent prognostic marker into current clinical staging systems significantly improved prognostic stratification of patients with late‐stage gastric cancer. This refined risk stratification scheme might aid in appropriate therapeutic options and ultimately improve the outcomes of patients with advanced‐stage disease.
Is prospective memory related to depression and anxiety? A hierarchical MPT modelling approach

Prospective memory (PM) refers to remembering to perform an action in the future. One hundred and twenty-nine students completed a laboratory event–based PM task as well as depression and anxiety questionnaires. The data were analysed with the beta-MPT version of the multinomial processing tree model of event-based PM. Thereby, the prospective and retrospective components of PM were estimated for each participant and were then correlated with depression and anxiety. State anxiety was negatively correlated with the prospective component of PM. Neither depression nor trait anxiety were related to either component of PM.
Application of Fault Tree Analysis and Fuzzy Neural Networks to Fault Diagnosis in the Internet of Things (IoT) for Aquaculture

In the Internet of Things (IoT) equipment used for aquaculture is often deployed in outdoor ponds located in remote areas. Faults occur frequently in these tough environments and the staff generally lack professional knowledge and pay a low degree of attention in these areas. Once faults happen, expert personnel must carry out maintenance outdoors. Therefore, this study presents an intelligent method for fault diagnosis based on fault tree analysis and a fuzzy neural network. In the proposed method, first, the fault tree presents a logic structure of fault symptoms and faults. Second, rules extracted from the fault trees avoid duplicate and redundancy. Third, the fuzzy neural network is applied to train the relationship mapping between fault symptoms and faults. In the aquaculture IoT, one fault can cause various fault symptoms, and one symptom can be caused by a variety of faults. Four fault relationships are obtained. Results show that one symptom-to-one fault, two symptoms-to-two faults, and two symptoms-to-one fault relationships can be rapidly diagnosed with high precision, while one symptom-to-two faults patterns perform not so well, but are still worth researching. This model implements diagnosis for most kinds of faults in the aquaculture IoT.
Leadership with commitment to mixed strategies

A basic model of commitment is to convert a game in strategic form into a “leadership game” where one player commits to a strategy to which the other player chooses a best response, with payoffs as in the original game. This paper studies subgame perfect equilibria of such leadership games for the mixed extension of a finite game, where the leader commits to a mixed strategy. In a generic two-player game, the leader payoff is unique and at least as large as any Nash payoff in the original simultaneous game. In non-generic two-player games, which are completely analyzed, the leader payoffs may form an interval, which as a set of payoffs is never worse than the Nash payoffs for the player who has the commitment power. Furthermore, the set of payoffs to the leader is also at least as good as the set of correlated equilibrium payoffs. These observations no longer hold in leadership games with three or more players. The possible payoffs to the follower are shown to be arbitrary compared to the simultaneous game or the game where the players switch their roles of leader and follower. Curiously, the follower payoff is not so arbitrary in typical
Adaptive Image Restoration and Segmentation Method Using Different Neighborhood Sizes

The image restoration methods based on the Bayesian’s framework and Markov random fields (MRF) have been widely used in the image-processing field. The basic idea of all these methods is to use calculus of variation and mathematical statistics to average or estimate a pixel value by the values of its neighbors. After applying this averaging process to the whole image a number of times, the noisy pixels, which are abnormal values, are filtered out. Based on the Tea-trade model, which states that the closer the neighbor, more contribution it makes, almost all of these methods use only the nearest four neighbors for calculation. In our previous research [1, 2], we extended the research on CLRS (image restoration and segmentation by using competitive learning) algorithm to enlarge the neighborhood size. The results showed that the longer neighborhood range could improve or worsen the restoration results. We also found that the autocorrelation coefficient was an important factor to determine the proper neighborhood size. We then further realized that the computational complexity increased dramatically along with the enlargement of the neighborhood size. This paper is to further the previous research and to discuss the tradeoff between the computational complexity and the restoration improvement by using longer neighborhood range. We used a couple of methods to construct the synthetic images with the exact correlation coefficients we want and to determine the corresponding neighborhood size. We constructed an image with a range of correlation coefficients by blending some synthetic images. Then an adaptive method to find the correlation coefficients of this image was constructed. We restored the image by applying different neighborhood CLRS algorithm to different parts of the image according to its correlation coefficient. Finally, we applied this adaptive method to some real-world images to get improved restoration results than by using single neighborhood size. This method can be extended virtually on all the methods based on MRF framework and result in improved algorithms.
Expression of purinergic receptor P2Y4 in Schwann cell following nerve regeneration.

OBJECTIVE Emerging evidences suggested an important role of purinergic receptor P2Y4 in nerve system. The present study aims to investigate the localization and possible function of P2Y4 receptor in recurrent laryngeal nerve (RLN) following regeneration. METHODS Right RLN of fifty Sprague-Dawley rats was cut and immediately repaired with PLGA/chitosan nerve conduit. Immunofluorescence, real-time qPCR and Western blot were used to detect the expression alterations of P2Y4 receptor. RESULTS Weak immunostaining signals of P2Y4 receptor were located on the plasmalemma of Schwann cell (SC) with regular arrangement of axons in normal RLN. On the post-injury 4th day, the sprouting axons regrowed along the degenerated SCs intensively expressing P2Y4 receptor. On the post-injury 7th day, the regenerating axons existed in multicellular cords of P2Y4 receptor-positive SCs occupying the nerve gap. On the post-injury 14th day, the axons grew along the bands of P2Y4 receptor-positive SCs exhibiting the regularly parallel distribution. On the post-injury 30th day, mild immunostaining signals of P2Y4 receptor still existed on SC surface, and the regenerated axons were located inside the remodeled endoneurium tube. In accordance with immunofluorescence findings, the transcription and protein expression levels of P2Y4 were significantly increased after the injury and the peak value appeared on the post-injury 7th day, compared to control group (P < 0.05). CONCLUSION Data from the present study suggested a potential role of P2Y4 receptors in functional modulation of SCs in the regeneration of RLN.
Oxidative Stress in Asthma

Asthma is a chronic inflammatory lung disease that results in airflow limitation, hyperreactivity, and airway remodeling. There is strong evidence that an imbalance between the reducing and oxidizing systems favoring a more oxidative state is present in asthma. Endogenous and exogenous reactive oxygen species, such as superoxide anion, hydroxyl radical, hypohalite radical, and hydrogen peroxide, and reactive nitrogen species, such as nitric oxide, peroxynitrite, and nitrite, play a major role in the airway inflammation and are determinants of asthma severity. Asthma is also associated with decreased antioxidant defenses, such as superoxide dismutase, catalase, and glutathione. In this review, we will summarize the current knowledge and discuss the current and future strategies for the modulation of oxidative stress in asthma.
Physcion, a natural anthraquinone derivative, enhances the gene expression of leaf-specific thionin of barley against Blumeria graminis.

BACKGROUND Physcion is a key active ingredient of the ethanol extract from roots of Chinese rhubarb (Rheum officinale Baill.) that has been commercialised in China for controlling powdery mildews. The biological mechanism of action of physcion against the barley powdery mildew pathogen was studied using bioassay and microarray methods. RESULTS Bioassay indicated that physcion did not directly affect conidial germination of Blumeria graminis Speer f. sp. hordei Marchal, but significantly inhibited conidial germination in vivo. Challenge inoculation indicated that physcion induced localised resistance rather than systemic resistance against powdery mildew. Gene expression profiling of physcion-treated barley leaves detected four upregulated and five downregulated genes (ratio >or= 2.0 and P-value < 0.05) by using an Affymetrix Barley GeneChip. The five upregulated probe sequences blasted to the same barley leaf-specific thionin gene, with significant changes varying from 4.26 to 19.91-fold. All downregulated genes were defence-related, linked to peroxidase, oxalate oxidase, bsi1 protein and a pathogenesis-related protein. These changes varied from - 2.34 to - 2.96. Quantitative real-time PCR data confirmed that physcion enhanced the gene expression of leaf-specific thionin of barley. CONCLUSION Results indicated that physcion controls powdery mildew mainly through changing the expression of defence-related genes, and especially enhancing expression of leaf-specific thionin in barley leaves.
Cultural Differences in Asymmetric Beliefs of Interpersonal Knowledge in Vertical and Horizontal Relationships

ABSTRACT Previous studies have reported that our interpersonal knowledge shows an asymmetry; that is, we tend to believe that we know and understand other people's thoughts and feelings better than other people know and understand our own thoughts and feelings. In the present study, the authors compared American (114 men, 192 women) and Korean (99 men and 98 women) students to examine whether the asymmetry is greater in collectivistic than in individualistic culture in two types of relationships: horizontal (with best friends) and vertical (with parents). On all three items—Know, Understand, and Visibility—asymmetry was found for both horizontal and vertical relationships. Further, the Understand and Visibility items showed greater asymmetry for the Korean group than for the American group. It was concluded that asymmetry is greater in collectivistic than in individualistic culture. The cultural differences can be explained by self-consistency, sensitivity to social consequences, parent–child interaction, and living arrangement.
Clinical Presentation of Endometrioid Epithelial Ovarian Cancer with Concurrent Endometriosis: A Multicenter Retrospective Study

Background: Endometrioid epithelial ovarian cancer (EEOC) is frequently diagnosed in conjunction with endometriosis and is suggested to arise during the process of endometriosis. This study evaluates the clinical manifestations, including endometriosis-related symptoms and their relationships according to the coexistence of endometriosis. Methods: Using medical records, a retrospective analysis was conducted on 221 patients treated for EEOC at four tertiary educational hospitals between 2000 and 2008. The initial presenting symptoms, particularly those related to endometriosis, were examined in relation to the coexistence of endometriosis or other clinical variables. Results: Endometriosis was identified in 82 (37.1%) of the 221 patients with EEOC. The most common symptoms were pelvic pain followed by gastrointestinal symptoms, palpable mass, abdominal distension, vaginal bleeding, and newly developed or exacerbated dysmenorrhea (18.1%) and dyspareunia (13.6%). Notably, dysmenorrhea and dyspareunia were frequently observed in patients with endometriosis. Among 210 patients identified with pretreatment serum CA-125, 54 (25.7%) displayed normal CA-125 levels (<35 units/mL) and 23.3% and 29.9% of patients without and with endometriosis had normal CA-125 levels, respectively (P = 0.381). Additionally, 32.6% of the patients with early-stage EEOC displayed normal CA-125 levels. Conclusions: In this large series of patients with EEOC, the main presenting symptoms were pelvic pain followed by gastrointestinal symptoms, palpable mass, abdominal distension, vaginal bleeding, and newly developed or exacerbated dysmenorrhea and dyspareunia. Dyspareunia and dysmenorrhea were more frequently detected in patients with endometriosis. Normal CA-125 levels cannot be applied as a marker to exclude EEOC, particularly at the early stages. Cancer Epidemiol Biomarkers Prev; 19(2); 398–404
Targeted therapeutics for multiple myeloma: The arrival of a risk-stratified approach

Multiple myeloma (MM) remains an incurable hematologic malignancy characterized by frequent early responses, inevitably followed by treatment relapse. Until recently, few effective therapies existed. Indeed, the use of alkylating agents and corticosteroids had remained the treatment of choice for almost four decades. Several novel agents for MM have now become available, including the immunomodulatory drugs thalidomide and lenalidomide, as well as the proteasome inhibitor bortezomib. Each of these agents is undergoing extensive clinical evaluation in combination with other therapies to produce unprecedented response rates in newly diagnosed and relapsed MM. Nevertheless, relapse remains universal and further therapeutics with broad activity are required. Importantly, it has become clear that pivotal genetic events are the primary harbingers of clinical outcome and novel targeted therapy approaches using existing approved drugs or novel agents, which address that disrupted signaling pathways are now in various stages of clinical testing. It seems increasingly likely that novel drug combinations, which together turn off these critical Achilles heels, will become the standard of care and that treatment will become increasingly personalized and guided by genetic testing and prognostic factors. [Mol Cancer Ther 2007;6(3):802–10]
Emulating Asymmetric MPSoCs on the Intel SCC Many-Core Processor

The Single-chip Cloud Computer (SCC) is a 48-core experimental processor created by Intel Labs targeting the manycore research community. It has extensive frequency and voltage scaling support as well as on board power monitors. In this paper we present a detailed study of the power properties of the SCC. Then, we show how the SCC can be used as a substrate to emulate asymmetric multi processor systems on chip (MPSoCs) to be used for studying power/performance trade-offs.