Miracle-dz/UniFAR-FTUs huggingface dataset:
2-Methoxyestradiol Inhibits Intracerebral Hemorrhage- Induced Angiogenesis in Rats.

AIM Angiogenesis occurs after intracerebral hemorrhage (ICH). Hypoxia-inducible factor-1? (HIF-1? ) is a critical regulator of angiogenesis. However, its role in the central nervous system remains controversial. 2-Methoxyestradiol (2ME2), a natural metabolite of estrogen, is known to inhibit HIF-1? In the present study, we investigated the effect of 2ME2 in a rat model of ICH-induced angiogenesis. MATERIAL AND METHODS Sprague-Dawley male rats (n=50) were randomly divided into 5 groups: Sham operated group; ICH; ICH+2ME2; and ICH+Vehicle groups. ICH model was induced by stereotactic injection of collagenase type VII into the right globus pallidus. 2ME2 or vehicle (10% dimethyl sulfoxide) was administered intraperitoneally 10 min after ICH. Angiogenesis and expression of HIF-1? was evaluated by immunohistochemistry, quantitative real time-reverse transcription polymerase chain reaction and western blot, respectively. RESULTS Proliferating cell nuclear antigen (PCNA)-labeled nuclei were detected in cerebral endothelial cells (ECs) around the hematoma. The labeling peaked at 14 days post-ICH. HIF-1? -immunoreactive microvessels with dilated outline were detected in the perihematomal tissues. The vessels extended into the clot from the surrounding tissues from day 7 onwards. HIF-1? protein levels increased, while no change was observed in HIF-1? mRNA expression after ICH. 2ME2 decreased the PCNA-labeled nuclei in cerebral ECs and down-regulated the expression of HIF-1? protein as well, while it had little effect on the mRNA expression of HIF-1? CONCLUSION HIF-1? inhibitor, 2ME2, inhibited post-ICH angiogenesis by suppressing HIF-1? expression, thus exerting detrimental effects in ICH.
Spatial–degree of freedom improvement of interference alignment in multi-input, multi-output interference channels

As we know, the degree of freedom approximates the capacity of a network. To improve the achievable degree of freedom in the K-user interference network, we propose a rank minimization interference minimization algorithm. Unlike the existing methods concentrating on the promotion of degree of freedom, our rank optimization method works directly with the interference matrix rather than its projection using the receive beamformers. Moreover, we put the trace constraint of the square root of desired matrix into the rank optimization to prevent the received signal-to-interference-plus-noise ratio from reduction. The decoders are designed through a weight interference leakage minimization method. Considering that the practical obtainable signal-to-noise ratio may be limited, we improve the design of decoders in rank minimization interference minimization, and propose the rank minimization rate maximization. Rank minimization rate maximization aims to reduce the impact of interference on undesired users as much as possible while improving the desired data rate. Simulation results show that rank minimization interference minimization algorithm can provide more interference-free dimensions for desired signals than other rank minimization methods. Rank minimization rate maximization outperforms rank minimization interference minimization at low-to-moderate signal-to-noise ratios, and its performance gets closer to rank minimization interference minimization with the increase in signal-to-noise ratio. Furthermore, in an improper system, rank minimization rate maximization still performs well.
Biodistribution of gold nanoparticles in BBN-induced muscle-invasive bladder cancer in mice

Bladder-sparing options are being developed for muscle-invasive bladder cancer in place of radical cystectomy, including the combination of chemotherapy and radiation therapy. We reasoned that improving the radiotherapy component of chemoradiation could improve the control of locally advanced disease. Previously, we showed that gold nanoparticles (AuNPs) are potent enhancers of radiation therapy. We hypothesized that if AuNPs were to preferentially localize to bladder tumors, they may be used to enhance the radiation component of muscle-invasive bladder tumor therapy. Mice were treated with the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 17, 20, and 22 weeks – long enough to induce muscle-invasive tumors. Mice were then anesthetized and injected intravenously with 1.9 nm AuNPs of which most were rapidly cleared from the blood and excreted after a 30–50 minute residence time in the bladder. We found AuNPs distributed throughout the bladder wall, but most of the AuNPs were associated with the stroma surrounding the tumor cells or extracellular keratin produced by the tumor cells. There were relatively few AuNPs in the tumor cells themselves. The AuNPs therefore localized to tumor-associated stroma and this tumor specificity might be useful for specific X-ray dose enhancement therapy of muscle-invasive bladder carcinomas.
Tumorigenic proteins upregulated in the MYCN-amplified IMR-32 human neuroblastoma cells promote proliferation and migration

Childhood neuroblastoma is one of the most common types of extra-cranial cancer affecting children with a clinical spectrum ranging from spontaneous regression to malignant and fatal progression. In order to improve the clinical outcomes of children with high-risk neuroblastoma, it is crucial to understand the tumorigenic mechanisms that govern its malignant behaviors. MYCN proto-oncogene, bHLH transcription factor (MYCN) amplification has been implicated in the malignant, treatment-evasive nature of aggressive, high-risk neuroblastoma. In this study, we used a SILAC approach to compare the proteomic signatures of MYCN-amplified IMR-32 and non-MYCN-amplified SK-N-SH human neuroblastoma cells. Tumorigenic proteins, including fatty-acid binding protein 5 (FABP5), L1-cell adhesion molecule (L1-CAM), baculoviral IAP repeat containing 5 [BIRC5 (survivin)] and high mobility group protein A1 (HMGA1) were found to be significantly upregulated in the IMR-32 compared to the SK-N-SH cells and mapped to highly tumorigenic pathways including, MYC, MYCN, microtubule associated protein Tau (MAPT), E2F transcription factor 1 (E2F1), sterol regulatory element binding transcription factor 1 or 2 (SREBF1/2), hypoxia-inducible factor 1α (HIF-1α), Sp1 transcription factor (SP1) and amyloid precursor protein (APP). The transcriptional knockdown (KD) of MYCN, HMGA1, FABP5 and L1-CAM significantly abrogated the proliferation of the IMR-32 cells at 48 h post transfection. The early apoptotic rates were significantly higher in the IMR-32 cells in which FABP5 and MYCN were knocked down, whereas cellular migration was significantly abrogated with FABP5 and HMGA1 KD compared to the controls. Of note, L1-CAM, HMGA1 and FABP5 KD concomitantly downregulated MYCN protein expression and MYCN KD concomitantly downregulated L1-CAM, HMGA1 and FABP5 protein expression, while survivin protein expression was significantly downregulated by MYCN, HMGA1 and FABP5 KD. In addition, combined L1-CAM and FABP5 KD led to the concomitant downregulation of HMGA1 protein expression. On the whole, our data indicate that this inter-play between MYCN and the highly tumorigenic proteins which are upregulated in the malignant IMR-32 cells may be fueling their aggressive behavior, thereby signifying the importance of combination, multi-modality targeted therapy to eradicate this deadly childhood cancer.
Pharmacological and molecular approaches for the treatment of β‐hemoglobin disorders

β‐hemoglobin disorders, such as β‐thalassemia and sickle cell anemia are among the most prevalent inherited genetic disorders worldwide. These disorders are caused by mutations in the gene encoding hemoglobin‐β (HBB), a vital protein found in red blood cells (RBCs) that carries oxygen from lungs to all parts of the human body. As a consequence, there has been an enduring interest in this field in formulating therapeutic strategies for the treatment of these diseases. Currently, there is no cure available for hemoglobin disorders, although, some patients have been treated with bone marrow transplantation, whose scope is limited because of the difficulty in finding a histocompatible donor and also due to transplant‐associated clinical complications that can arise during the treatment. On account of these constraints, reactivation of fetal hemoglobin (HbF) synthesis holds immense promise and is a viable strategy to alleviate the symptoms of β‐hemoglobin disorders. Development of new genomic tools has led to the identification of important natural genetic modifiers of hemoglobin switching which include BCL11A, KLF1, HBSIL‐MYB, LRF, LSD1, LDB1, histone deacetylases 1 and 2 (HDAC1 and HDAC2). miRNAs are also promising therapeutic targets for development of more effective strategies for the induction of HbF production. Many new small molecule pharmacological inducers of HbF production are already under pre‐clinical and clinical development. Furthermore, recent advancements in gene and cell therapy includes targeted genome editing and iPS cell technologies, both of which utilizes a patient's own cells, are emerging as extremely promising approaches for significantly reducing the burden of β‐hemoglobin disorders.
Carbon Steel Corrosion Induced by Microbial Community in Soil Environment and Its Analysis

To obtain the knowledge about the corrosion ability and its mechanism as a target the soil environment microorganisms, lake mud was cultured with metallic iron. As a result, corrosion of carbon steel was observed with sulfate reduction and methane producing activity in brackish medium with lactate as substrate. The next-generation sequencing technologies revealed microbial community varies greatly between environmental samples (inoculated sample) and cultured sample. Particularly, Desulfovibrio species and Clostridia class, that sulfate reducing ability have been reported, became dominant. Inhibition test of sulfate reducing bacteria and methane producing archaea suggested that sulfate reducing bacteria plays a major role for this corrosion, and methane producing archaea enhanced corrosion activity by the coexistence of sulfate reducing bacteria.
The use of Bioptron light (polarized, polychromatic, non-coherent) therapy for the treatment of acute ankle sprains

Abstract Purpose The purpose of this study was to investigate the efficacy of Bioptron light therapy for the treatment of acute ankle sprains. Method A parallel group, single-blind, controlled study was carried out in patients with grade II acute ankle sprains. Patients were randomly allocated into two treatment groups (n = 25 for each). Both groups received cryotherapy, and the test group also received Bioptron light therapy. All treatments were performed daily for 5 d. Evaluations included self-reported pain via a visual analogue scale, degree of ankle edema, and ankle range of motion via goniometry carried out before the treatment and at the end of the treatment. Results The test group showed the largest magnitude of improvement for all evaluations at treatment five, and the between-group differences observed were statistically significant (p < 0.0005 for each). Conclusions These data provide preliminary evidence of the efficacy of Bioptron light therapy supplemented with cryotherapy for the treatment of acute ankle sprains; however, larger studies are required to confirm these results. Implications for Rehabilitation Ankle sprains are common acute injuries among professional and recreational sports players but also among people in general. Cryotherapy is the first-standard treatment of acute ankle sprains. Phototherapy such as Bioptron light has been recommended supplement to cryotherapy to reduce the symptoms of ankle sprains. The results of the present trial showed that using BIOPTRON LIGHT and cryotherapy the rehabilitation period of acute ankle sprains can be reduced.
Mapping the Invocation Structure of Online Political Interaction

The surge in political information, discourse, and interaction has been one of the most important developments in social media over the past several years. There is rich structure in the interaction among different viewpoints on the ideological spectrum. However, we still have only a limited analytical vocabulary for expressing the ways in which these viewpoints interact. In this paper, we develop network-based methods that operate on the ways in which users share content; we construct invocation graphs on Web domains showing the extent to which pages from one domain are invoked by users to reply to posts containing pages from other domains. When we locate the domains on a political spectrum induced from the data, we obtain an embedded graph showing how these interaction links span different distances on the spectrum. The structure of this embedded network, and its evolution over time, helps us derive macro-level insights about how political interaction unfolded through 2016, leading up to the US Presidential election. In particular, we find that the domains invoked in replies spanned increasing distances on the spectrum over the months approaching the election, and that there was clear asymmetry between the left-to-right and right-to-left patterns of linkage.
Stable-isotope analysis: a neglected tool for placing parasites in food webs

Abstract Parasites are often overlooked in the construction of food webs, despite their ubiquitous presence in almost every type of ecosystem. Researchers who do recognize their importance often struggle to include parasites using classical food-web theory, mainly due to the parasites' multiple hosts and life stages. A novel approach using compound-specific stable-isotope analysis promises to provide considerable insight into the energetic exchanges of parasite and host, which may solve some of the issues inherent in incorporating parasites using a classical approach. Understanding the role of parasites within food webs, and tracing the associated biomass transfers, are crucial to constructing new models that will expand our knowledge of food webs. This mini-review focuses on stable-isotope studies published in the past decade, and introduces compound-specific stable-isotope analysis as a powerful, but underutilized, newly developed tool that may answer many unresolved questions regarding the role of parasites in food webs.
Ciliary neurotrophic factor enhances neuronal survival in embryonic rat hippocampal cultures

First described as a survival factor for chick ciliary ganglion neurons, ciliary neurotrophic factor (CNTF) has recently been shown to promote survival of chick embryo motor neurons. We now report neurotrophic effects of CNTF toward three populations of rat hippocampal neurons, the first demonstration of effects of CNTF upon rodent CNS neurons in culture. CNTF elicited an increase in the neurofilament content of hippocampal cultures prepared from embryonic day 18 (E18) rat brain. This was accompanied by increases of 2-, 28-, and 3-fold in the number of GABAergic, cholinergic, and calbindin- immunopositive cells, respectively. CNTF totally prevented the 67% loss of GABAergic neurons that occurred in control cultures over 8 d. CNTF also increased high-affinity GABA uptake and glutamic acid decarboxylase activity. Effects of CNTF were in all cases dose dependent, with maximal stimulation at approximately 100 pg/ml. When addition was delayed for 3 d, CNTF failed to elicit increases either in the number of cholinergic neurons or in GABA uptake.
Frame Transmission Efficiency-Based Cross-Layer Congestion Notification Scheme in Wireless Ad Hoc Networks

Different from the traditional wired network, the fundamental cause of transmission congestion in wireless ad hoc networks is medium contention. How to utilize the congestion state from the MAC (Media Access Control) layer to adjust the transmission rate is core work for transport protocol design. However, recent works have shown that the existing cross-layer congestion detection solutions are too complex to be deployed or not able to characterize the congestion accurately. We first propose a new congestion metric called frame transmission efficiency (i.e., the ratio of successful transmission delay to the frame service delay), which describes the medium contention in a fast and accurate manner. We further present the design and implementation of RECN (ECN and the ratio of successful transmission delay to the frame service delay in the MAC layer, namely, the frame transmission efficiency), a general supporting scheme that adjusts the transport sending rate through a standard ECN (Explicit Congestion Notification) signaling method. Our method can be deployed on commodity switches with small firmware updates, while making no modification on end hosts. We integrate RECN transparently (i.e., without modification) with TCP on NS2 simulation. The experimental results show that RECN remarkably improves network goodput across multiple concurrent TCP flows.
Efficient Bayesian Species Tree Inference under the Multispecies Coalescent

&NA; We develop a Bayesian method for inferring the species phylogeny under the multispecies coalescent (MSC) model. To improve the mixing properties of the Markov chain Monte Carlo (MCMC) algorithm that traverses the space of species trees, we implement two efficient MCMC proposals: the first is based on the Subtree Pruning and Regrafting (SPR) algorithm and the second is based on a node‐slider algorithm. Like the Nearest‐Neighbor Interchange (NNI) algorithm we implemented previously, both new algorithms propose changes to the species tree, while simultaneously altering the gene trees at multiple genetic loci to automatically avoid conflicts with the newly proposed species tree. The method integrates over gene trees, naturally taking account of the uncertainty of gene tree topology and branch lengths given the sequence data. A simulation study was performed to examine the statistical properties of the new method. The method was found to show excellent statistical performance, inferring the correct species tree with near certainty when 10 loci were included in the dataset. The prior on species trees has some impact, particularly for small numbers of loci. We analyzed several previously published datasets (both real and simulated) for rattlesnakes and Philippine shrews, in comparison with alternative methods. The results suggest that the Bayesian coalescent‐based method is statistically more efficient than heuristic methods based on summary statistics, and that our implementation is computationally more efficient than alternative full‐likelihood methods under the MSC. Parameter estimates for the rattlesnake data suggest drastically different evolutionary dynamics between the nuclear and mitochondrial loci, even though they support largely consistent species trees. We discuss the different challenges facing the marginal likelihood calculation and transmodel MCMC as alternative strategies for estimating posterior probabilities for species trees. [Bayes factor; Bayesian inference; MCMC; multispecies coalescent; nodeslider; species tree; SPR. ]
Neuroplasticity of selective attention: Research foundations and preliminary evidence for a gene by intervention interaction

Significance Selective attention is the ability to select and preferentially process specific information while simultaneously suppressing the processing of irrelevant, competing distractors. It is a fundamental ability linked to various cognitive skills and academic achievement. We describe the foundations and history of our research program, which spans from basic research on neural mechanisms and neuroplasticity of selective attention to translational research aimed at designing interventions to improve selective attention. We also present preliminary evidence for gene × intervention interactions in neural mechanisms of selective attention in children from lower socioeconomic status backgrounds. This program of research demonstrates the marked malleability of neural systems for selective attention and highlights the potential for changes in selective attention as a function of intervention. This article reviews the trajectory of our research program on selective attention, which has moved from basic research on the neural processes underlying selective attention to translational studies using selective attention as a neurobiological target for evidence-based interventions. We use this background to present a promising preliminary investigation of how genetic and experiential factors interact during development (i.e., gene × intervention interactions). Our findings provide evidence on how exposure to a family-based training can modify the associations between genotype (5-HTTLPR) and the neural mechanisms of selective attention in preschool children from lower socioeconomic status backgrounds.
Mechanisms of Vesicular Stomatitis Virus Inactivation by Protoporphyrin IX, Zinc-Protoporphyrin IX, and Mesoporphyrin IX

ABSTRACT Virus resistance to antiviral therapies is an increasing concern that makes the development of broad-spectrum antiviral drugs urgent. Targeting of the viral envelope, a component shared by a large number of viruses, emerges as a promising strategy to overcome this problem. Natural and synthetic porphyrins are good candidates for antiviral development due to their relative hydrophobicity and pro-oxidant character. In the present work, we characterized the antiviral activities of protoprophyrin IX (PPIX), Zn-protoporphyrin IX (ZnPPIX), and mesoporphyrin IX (MPIX) against vesicular stomatitis virus (VSV) and evaluated the mechanisms involved in this activity. Treatment of VSV with PPIX, ZnPPIX, and MPIX promoted dose-dependent virus inactivation, which was potentiated by porphyrin photoactivation. All three porphyrins inserted into lipid vesicles and disturbed the viral membrane organization. In addition, the porphyrins also affected viral proteins, inducing VSV glycoprotein cross-linking, which was enhanced by porphyrin photoactivation. Virus incubation with sodium azide and α-tocopherol partially protected VSV from inactivation by porphyrins, suggesting that singlet oxygen (1O2) was the main reactive oxygen species produced by photoactivation of these molecules. Furthermore, 1O2 was detected by 9,10-dimethylanthracene oxidation in photoactivated porphyrin samples, reinforcing this hypothesis. These results reveal the potential therapeutic application of PPIX, ZnPPIX, and MPIX as good models for broad antiviral drug design.
Revealed in Tumors by Dynamic Contrast-Enhanced MRI Interstitial Fluid Pressure and Associated Lymph Node Metastasis

Elevated interstitial fluid pressure (IFP) in tumors can cause metastatic dissemination and treatment resistance, but its study poses a challenge because of a paucity of noninvasive imaging strategies. In this study, we address this issue by reporting the development of a noninvasive tool to assess tumor IFP and interstitial hypertension-induced lymph node metastasis. Using mouse xenograft models of several types of human cancer, we used gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as a contrast agent for dynamic contrastenhancedMRI (DCE-MRI). Immediately after Gd-DTPA administration, a high-signal-intensity rim was observed in the tumor periphery, which moved outward with time. Assuming the velocity of Gd-DTPA to be equal to the fluid flow velocity, we used a simple model of peritumoral interstitial fluid flow to calculate the fluid flow velocity at the tumor surface (v0) based on the rimmovement. Significant positive correlations were found between v0 and IFP in all tumor xenografts.Moreover, the primary tumors ofmetastasis-positivemice displayed higher IFP and v0 than the primary tumors of metastasis-negative mice. Findings were confirmed in cervical cancer patients with pelvic lymph node metastases, where we found v0 to be higher compared with patients without lymph node involvement (P < 0.00001). Together, these findings establish that Gd-DTPA-based DCE-MRI can noninvasively visualize tumor IFP, and they reveal the potential for v0 determined by this method to serve as a novel general biomarker of tumor aggressiveness. Cancer Res; 72(19); 4899–908. 2012 AACR.