Miracle-dz/UniFAR-FTUs huggingface dataset:
Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality

Objectives Drug repurposing, which finds new indications for existing drugs, has received great attention recently. The goal of our work is to assess the feasibility of using electronic health records (EHRs) and automated informatics methods to efficiently validate a recent drug repurposing association of metformin with reduced cancer mortality. Methods By linking two large EHRs from Vanderbilt University Medical Center and Mayo Clinic to their tumor registries, we constructed a cohort including 32 415 adults with a cancer diagnosis at Vanderbilt and 79 258 cancer patients at Mayo from 1995 to 2010. Using automated informatics methods, we further identified type 2 diabetes patients within the cancer cohort and determined their drug exposure information, as well as other covariates such as smoking status. We then estimated HRs for all-cause mortality and their associated 95% CIs using stratified Cox proportional hazard models. HRs were estimated according to metformin exposure, adjusted for age at diagnosis, sex, race, body mass index, tobacco use, insulin use, cancer type, and non-cancer Charlson comorbidity index. Results Among all Vanderbilt cancer patients, metformin was associated with a 22% decrease in overall mortality compared to other oral hypoglycemic medications (HR 0.78; 95% CI 0.69 to 0.88) and with a 39% decrease compared to type 2 diabetes patients on insulin only (HR 0.61; 95% CI 0.50 to 0.73). Diabetic patients on metformin also had a 23% improved survival compared with non-diabetic patients (HR 0.77; 95% CI 0.71 to 0.85). These associations were replicated using the Mayo Clinic EHR data. Many site-specific cancers including breast, colorectal, lung, and prostate demonstrated reduced mortality with metformin use in at least one EHR. Conclusions EHR data suggested that the use of metformin was associated with decreased mortality after a cancer diagnosis compared with diabetic and non-diabetic cancer patients not on metformin, indicating its potential as a chemotherapeutic regimen. This study serves as a model for robust and inexpensive validation studies for drug repurposing signals using EHR data.
Relationship between Pericytes and Endothelial Cells in Retinal Neovascularization: A Histological and Immunofluorescent Study of Retinal Angiogenesis

Purpose To evaluate the relationship between pericytes and endothelial cells in retinal neovascularization through histological and immunofluorescent studies. Methods C57BL/6J mice were exposed to hyperoxia from postnatal day (P) 7 to P12 and were returned to room air at P12 to induce a model of oxygen-induced retinopathy (OIR). The cross sections of enucleated eyes were processed with hematoxylin and eosin. Immunofluorescent staining of pericytes, endothelial cells, and N-cadherin was performed. Microfluidic devices were fabricated out of polydimethylsiloxane using soft lithography and replica molding. Human retinal microvascular endothelial cells, human brain microvascular endothelial cells, human umbilical vein endothelial cells and human placenta pericyte were mixed and co-cultured. Results Unlike the three-layered vascular plexus found in retinal angiogenesis of a normal mouse, angiogenesis in the OIR model is identified by the neovascular tuft extending into the vitreous. Neovascular tufts and the three-layered vascular plexus were both covered with pericytes in the OIR model. In this pathologic vascularization, N-cadherin, known to be crucial intercellular adhesion molecule, was also present. Further evaluation using the microfluidic in vitro model, successfully developed a microvascular network of endothelial cells covered with pericytes, mimicking normal retinal angiogenesis within 6 days. Conclusions Pericytes covering endothelial cells were observed not only in vasculature of normal retina but also pathologic neovascularization of OIR mouse at P17. Factors involved in the endothelial cell-pericyte interaction can be evaluated as an attractive novel treatment target. These future studies can be performed using microfluidic systems, which can shorten the study time and provide three-dimensional structural evaluation.
Ultracompact variable optical attenuator based on photonic crystal waveguide

We demonstrated and fabricated a 20μm-long ultra-compact variable optical attenuator based on thermo-optical effect with slow light photonic crystal waveguide (PCWG). In simulation, we optimize the line-defect width and radius/period ratio (r/a) of the PCWG for deep photonic band gap and large slope photonic band edge. An r/a=140nm/410nm W1 PCWG is selected for its -60dB depth and 36dB variable attenuation range when the tunable refractive index change is 0.01. We also study different shapes of micro-heaters for low power consumption and high heat transfer efficiency. A 24.6mW and 75.9% heat transfer efficiency are achieved in a 2μm-wide right-angle-shaped micro-heater. In experiment, A 4.6nm red shift at the cutoff wavelength of the fundamental mode and a 10dB tunable attenuation range are achieved through tuning the temperature of the W1 PCWG by an 4. 7μm-wide aluminum micro-heater with a maximum power consumption as low as 30.7mW.
Asymptotically tight bounds for performing BMMC permutations on parallel disk systems

This paper presents asymptotically equal lower and upper bounds for the number of parallel I/O operations required to perform bit-matrix-multiply/complement (BMMC) permutations on the Parallel Disk Model proposed by Vitter and Shriver. A BMMC permutation maps a source index to a target index by an affine transformation over GF (2), where the source and target indices are treated as bit vectors. The class of BMMC permutations includes many common permutations, such as matrix transposition (when dimensions are powers of 2), bit-reversal permutations, vectorreversal permutations, hypercube permutations, matrix reblocking, Gray-code permutations, and inverse Gray-code permutations. The upper bound improves upon the asymptotic bound in the previous best known BMMC algorithm and upon the constant factor in the previous best known bit-permute/complement (BPC) permutation algorithm. The algorithm achieving the upper bound uses basic linear-algebra techniques to factor the characteristic matrix for the BMMC permutation into a product of factors, each of which characterizes a permutation that can be performed in one pass over the data. The factoring uses new subclasses of BMMC permutations: memoryload-dispersal (MLD) permutations and their inverses. These subclasses extend the catalog of one-pass permutations. Although many BMMC permutations of practical interest fall into subclasses that might be explicitly invoked within the source code, this paper shows how to quickly detect whether a given vector of target addresses specifies a BMMC permutation. Thus, one can determine efficiently at run time whether a permutation to be performed is BMMC and then avoid the general-permutation algorithm and save parallel I/Os by using the BMMC permutation algorithm herein.
Video Streaming issues and Techniques over MANETs

Video streaming in MANETs is most Challenging issue and it mainly affected by these factors like node mobility, dynamic change in topology, multi path shadowing and fading, collusion, interference and many more. The dynamic change in topology causes periodic connectivity which results in large packet loss. Video streaming in real time requires special techniques that can overcome the losses of packets in the unreliable networks. Developments in mobile devices and wireless networking provide the technical platform for video streaming over mobile ad hoc networks (MANETs). And efforts to realize video streaming over MANETs have met many challenges, which are addressed by several different techniques. Here in this paper we have studied and reviewed many issues and different techniques present for video streaming over MANETs. This paper contain work done in the field of video streaming in MANETs and guide newcomers who are willing to work in video streaming in MANETs field. Keywords-Video streaming ,MANETs , cross layer design, MDC, Multipath routing.
Van Der Pauw method for measuring resistivities of anisotropic layers printed on textile substrates

Electrically conducting layers have been screen printed on woven textile substrates. Using the Van Der Pauw method for electrical resistivity measurements in thin layers, it was observed that the screen-printed layers showed anisotropic behavior. In order to be able to interpret the measurements correctly, a mathematical analysis of the measuring method has been established. From the experimental results one is then able to find the relation between the electrical resistivity in the warp versus the weft direction.
Hoeffding Bounds vs . Empirical

Sampling is a popular way of scaling up machine learning algorithms to large datasets. The question often is how many samples are needed. Adaptive stopping algorithms monitor the performance in an online fashion and they can stop early, saving valuable resources. We consider problems where probabilistic guarantees are desired and demonstrate how recently-introduced empirical Bernstein bounds can be used to design stopping rules that are efficient. We provide upper bounds on the sample complexity of the new rules, as well as empirical results on model selection and boosting in the filtering setting.
Association between Body Mass Index and Cognitive Function among Chinese Nonagenarians/Centenarians

Aims: We examined the individual association between body mass index (BMI) and cognitive function among the very elderly. Methods: The present study analyzed data from a survey that was conducted on all residents aged 90 years or more from a district which had 2,311,709 inhabitants in 2005. The subjects were divided into 4 groups according to quartiles of BMI (<16.6, 16.6–18.9, 18.9–21.1 and >21.1), and according to classification criteria of underweight, normal weight, overweight and obesity in BMI (<18.5, 18.5–23.0, 23.0–27.5 and >27.5), respectively. Results: The subjects included in the statistical analysis were 211 men and 427 women. Those in the 3rd quartile of BMI (18.9–21.1) had higher cognitive function scores (p < 0.001) and were less likely to present possible dementia (p = 0.016) than the others. However, there was no difference in cognitive function scores (p = 0.350) or prevalence of possible dementia (p = 0.263) among obesity, overweight, normal weight and underweight groups. Conclusions: Concerning longevity in Chinese, there is an association between BMI and cognitive function. BMI of around 20 (18.9–21.1) is associated with the lowest risk of prevalence of possible dementia and the highest cognitive function scores.
Viral Infection Identifies Micropeptides Differentially Regulated in smORF-Containing lncRNAs

Viral infection leads to a robust cellular response whereby the infected cell produces hundreds of molecular regulators to combat infection. Currently, non-canonical components, e.g., long noncoding RNAs (lncRNAs) have been added to the repertoire of immune regulators involved in the antiviral program. Interestingly, studies utilizing next-generation sequencing technologies show that a subset of the >10,000 lncRNAs in the mammalian genome contain small open reading frames (smORFs) associated with active translation, i.e., many lncRNAs are not noncoding. Here, we use genome-wide high-throughput methods to identify potential micropeptides in smORF-containing lncRNAs involved in the immune response. Using influenza as a viral infection model, we performed RNA-seq and ribosome profiling to track expression and translation of putative lncRNAs that may encode for peptides and identify tens of potential candidates. Interestingly, many of these peptides are highly conserved at the protein level, strongly suggesting biological relevance and activity. By perusing publicly available data sets, four potential peptides of interest seem common to stress induction and/or are highly conserved; potential peptides from the MMP24-AS1, ZFAS1, RP11-622K12.1, and MIR22HG genes. Interestingly, using an antibody against the potential peptide encoded by MIR22HG RNA, we show that the peptide is stably expressed in the absence of infection, and upregulated in response to infection, corroborating the prediction of the ribosome profiling results. These data show the utility of perturbation approaches in identifying potentially relevant novel molecules encoded in the genome.
MONITORING THERMAL-SHOCK DAMAGE IN CERAMIC MATERIALS BY MEANS OF ACOUSTIC EMISSION

The basic principles of acoustic emission technique was introduced. Thermal shock damage strength degrade and microcrack propagation in mullite aluminum titanate ceramic material during quenching in oil was monitored by appling the acoustic emission technique. The results show the acoustic emission signal of microcrack propagation induced by thermal stress is in agreement with the variation of the residual strength.
Clinicopathological significance of platelet-derived growth factor B, platelet-derived growth factor receptor-β, and E-cadherin expression in gastric carcinoma

Aim of the study Platelet-derived growth factor B (PDGF-B), a vital growth factor which can induce angiogenesis and epithelial-mesenchymal transition (EMT), is important in the metastasis of many tumors. However, the roles of PDGF-B in gastric carcinoma are largely unknown. We investigated the correlation between PDGF-B, PDGFR-β and E-cadherin expression with the clinical features of gastric carcinoma patients to evaluate the relationship between PDGF-B signaling, E-cadherin and metastasis of gastric carcinoma, the correlation between PDGF-B and E-cadherin expression to assess the roles of PDGF-B signaling in metastasis of gastric carcinoma. Material and methods We detected expressions of PDGF-B, PDGFR-β and E-cadherin in gastric carcinoma tissues and normal gastric mucosa tissues of 64 patients with gastric carcinoma who had undergone surgical resection, and investigated their relationships with clinical features and the relationships between PDGF-B and E-cadherin expression in gastric carcinoma. Results In surgical specimens, tumor cells expressed PDGF-B, and PDGFR-β was expressed by tumor stromal cells. E-cadherin was expressed by both tumor cells and normal gastric mucosa cells. Expressions of PDGF-B and PDGFR-β were increased in gastric carcinoma tissues (p < 0.05) and were positively correlated with the depth of cancer invasion, lymph node metastasis and TNM stage (p < 0.05). The expression of E-cadherin was reduced in gastric carcinoma tissues (p < 0.05) and was negatively correlated with the depth of cancer invasion, lymph node metastasis and TNM stage (p < 0.05). The correlation between PDGF-B and E-cadherin expression was negative (p < 0.05). Conclusion Our data indicate that either the overexpression of PDGF-B and PDGFR-β or the underexpression of E-cadherin is correlated with cancer progression and lymphogenous metastasis of gastric carcinoma. The PDGF-B signal pathway might induce EMT by down-regulating expression of E-cadherin to promote metastasis of gastric carcinoma.
Switches in Genomic GC Content Drive Shifts of Optimal Codons under Sustained Selection on Synonymous Sites

Abstract The major codon preference model suggests that codons read by tRNAs in high concentrations are preferentially utilized in highly expressed genes. However, the identity of the optimal codons differs between species although the forces driving such changes are poorly understood. We suggest that these questions can be tackled by placing codon usage studies in a phylogenetic framework and that bacterial genomes with extreme nucleotide composition biases provide informative model systems. Switches in the background substitution biases from GC to AT have occurred in Gardnerella vaginalis (GC = 32%), and from AT to GC in Lactobacillus delbrueckii (GC = 62%) and Lactobacillus fermentum (GC = 63%). We show that despite the large effects on codon usage patterns by these switches, all three species evolve under selection on synonymous sites. In G. vaginalis, the dramatic codon frequency changes coincide with shifts of optimal codons. In contrast, the optimal codons have not shifted in the two Lactobacillus genomes despite an increased fraction of GC-ending codons. We suggest that all three species are in different phases of an on-going shift of optimal codons, and attribute the difference to a stronger background substitution bias and/or longer time since the switch in G. vaginalis. We show that comparative and correlative methods for optimal codon identification yield conflicting results for genomes in flux and discuss possible reasons for the mispredictions. We conclude that switches in the direction of the background substitution biases can drive major shifts in codon preference patterns even under sustained selection on synonymous codon sites.
Deoxycorticosterone acetate-salt hypertension activates placental growth factor in the spleen to couple sympathetic drive and immune system activation

Aims Chronic increase of mineralocorticoids obtained by administration of deoxycorticosterone acetate (DOCA) results in salt-dependent hypertension in animals. Despite the lack of a generalized sympathoexcitation, DOCA-salt hypertension has been also associated to overdrive of peripheral nervous system in organs typically targeted by blood pressure (BP), as kidneys and vasculature. Aim of this study was to explore whether DOCA-salt recruits immune system by overactivating sympathetic nervous system in lymphoid organs and whether this is relevant for hypertension. Methods and results To evaluate the role of the neurosplenic sympathetic drive in DOCA-salt hypertension, we challenged splenectomized mice or mice with left coeliac ganglionectomy with DOCA-salt, observing that they were both unable to increase BP. Then, we evaluated by immunofluorescence and ELISA levels of the placental growth factor (PlGF) upon DOCA-salt challenge, which significantly increased the growth factor expression, but only in the presence of an intact neurosplenic sympathetic drive. When PlGF KO mice were subjected to DOCA-salt, they were significantly protected from the increased BP observed in WT mice under same experimental conditions. In addition, absence of PlGF hampered DOCA-salt mediated T cells co-stimulation and their consequent deployment towards kidneys where they infiltrated tissue and provoked end-organ damage. Conclusion Overall, our study demonstrates that DOCA-salt requires an intact sympathetic drive to the spleen for priming of immunity and consequent BP increase. The coupling of nervous system and immune cells activation in the splenic marginal zone is established through a sympathetic-mediated PlGF release, suggesting that this pathway could be a valid therapeutic target for hypertension.
Whole-Genome Sequence of Phage-Resistant Strain Escherichia coli DH5α

ABSTRACT The genomes of many strains of Escherichia coli have been sequenced, as this organism is a classic model bacterium. Here, we report the genome sequence of Escherichia coli DH5α, which is resistant to a T4 bacteriophage (CCTCC AB 2015375), while its other homologous E. coli strains, such as E. coli BL21, DH10B, and MG1655, are not resistant to phage invasions. Thus, understanding of the genome of the DH5α strain, along with comparative analysis of its genome sequence along with other sequences of E. coli strains, may help to reveal the bacteriophage resistance mechanism of E. coli.
Explaining Recommendations by Means of User Reviews

The ﬁeld of recommender systems has seen substantial progress in recent years in terms of algorithmic sophistication and quality of recommendations as measured by standard accuracy metrics. Yet, the systems mainly act as black boxes for the user and are limited in their capability to explain why certain items are recommended. This is particularly true when using abstract models which do not easily lend themselves for providing explanations. In many cases, however, recommendation methods are employed in scenarios where users not only rate items, but also provide feedback in the form of tags or written product reviews. Such user-generated content can serve as a useful source for deriving explanatory information that may increase the user’s understanding of the underlying criteria and mechanisms that led to the results. In this paper, we describe a set of developments we undertook to couple such textual content with common recommender techniques. These developments have moved from integrating tags into collaborative ﬁltering to employing topics and sentiments expressed in reviews to increase transparency and to give users more control over the recommendation process. Furthermore, we describe our current research goals and a ﬁrst concept concerning extraction of more complex argumentative explanations from textual reviews and presenting them to users.
A Particle Swarm Optimization Approach to Multi Criteria Recommender System Utilizing Effective Similarity Measures

Recommender system (RS), a web personalization tool, attempts to generate suitable recommendations to users based on their preferences. Generally, recommender system works on overall ratings but these ratings do not reflect the actual user preferences. Therefore, incorporation of multiple criteria ratings into RS can capture the user preferences accurately and produce effective recommendations to users. Multi criteria recommender systems (MCRS) generate recommendations to users based on the aggregation of similarities computed on multiple criteria using collaborative filtering. However, capturing optimal weights of various users on different criteria in the process of similarity aggregation is a major concern. Further selection of appropriate similarity measure is another challenge for employing collaborative filtering. Our work in this paper is an attempt towards developing multi criteria recommender systems by utilizing various similarity measures and particle swarm optimization to learn optimal weights. Experimental results reveal that our proposed approaches outperform other traditional approaches.
Wedelolactone, an Anti-inflammatory Botanical, Interrupts c-Myc Oncogenic Signaling and Synergizes with Enzalutamide to Induce Apoptosis in Prostate Cancer Cells

The c-Myc gene encodes an oncoprotein transcription factor that is frequently upregulated in almost all cancer types and is the subject of intense investigation for management of cancer because of its pleiotropic effects controlling a spectrum of cellular functions. However, due of its nonenzymatic nature, development of suitable strategies to block its protein–protein or protein–DNA interaction is challenging. Thus, c-Myc has been recognized as an elusive molecular target for cancer control, and various approaches are in development to inhibit c-Myc transcriptional activity. We observed that wedelolactone (WDL), an anti-inflammatory botanical compound, severely downregulates the expression of c-Myc mRNA in prostate cancer cells. Moreover, WDL dramatically decreases the protein level, nuclear accumulation, DNA-binding, and transcriptional activities of c-Myc. c-Myc is a transforming oncogene widely expressed in prostate cancer cells and is critical for maintaining their transformed phenotype. Interestingly, WDL was found to strongly affect the viability of Myc-activated prostate cancer cells and completely block their invasion as well as soft agar colony formation in vitro. WDL was also found to downregulate c-Myc in vivo in nude mice xenografts. Moreover, WDL synergizes with enzalutamide to decrease the viability of androgen-sensitive prostate cancer cells via induction of apoptosis. These findings reveal a novel anticancer mechanism of the natural compound WDL, and suggest that the oncogenic function of c-Myc in prostate cancer cells can be effectively downregulated by WDL for the development of a new therapeutic strategy against Myc-driven prostate cancer. Mol Cancer Ther; 15(11); 2791–801. ©2016 AACR.