Miracle-dz/UniFAR-FTUs huggingface dataset:
Antitumor Activity of NK012 Combined with Cisplatin against Small Cell Lung Cancer and Intestinal Mucosal Changes in Tumor-Bearing Mouse after Treatment

Purpose: To investigate the advantages of treatment with the SN-38–incorporating polymeric micelles NK012 over CPT-11 in combination with cisplatin [cis-dichlorodiammineplatinum (II) (CDDP)] in mice bearing a small cell lung cancer xenograft in terms of antitumor activity and toxicity, particularly intestinal toxicity. Experimental Design: Cytotoxic effects were evaluated in human small cell lung cancer cell lines [H69, H82, and vascular endothelial growth factor (VEGF)–secreting cells (SBC-3/VEGF and its mock transfectant SBC-3/Neo)]. In vivo antitumor effects were evaluated in SBC-3/Neo–bearing and SBC-3/VEGF–bearing mice after NK012/CDDP or CPT-11/CDDP administration on days 0, 7, and 14. Drug distribution was analyzed by high-performance liquid chromatography or fluorescence microscopy, and the small intestine was pathologically examined. Results: The in vitro growth-inhibitory effects of NK012 were 198- to 532-fold more potent than those of CPT-11. A significant difference in the relative tumor volume on day 30 was found between NK012/CDDP and CPT-11/CDDP treatments (P = 0.0058). Inflammatory changes in the small intestinal mucosa were rare in all NK012-treated mice but were commonly observed in CPT-11–treated mice. Moreover, a large amount of CPT-11 was excreted into the feces and high CPT-11 concentration was detected in the small intestinal epithelium. On the other hand, a small amount of NK012 was found in the feces and NK012 was weakly and uniformly distributed in the mucosal interstitium. Conclusions: NK012/CDDP combination may be a promising candidate regimen against lung cancer without severe diarrhea toxicity and therefore warrants further clinical evaluation.
Glaucoma Viral Vector Effects on Exoenzyme C 3 Transferase – Mediated Actin Disruption and on Outflow Facility

Citation: Slauson SR, Peters DM, Schwinn MK, Kaufman PL, Gabelt BT, Brandt CR. Viral vector effects on exoenzyme C3 transferase–mediated actin disruption and on outflow facility. Invest Ophthalmol Vis Sci. 2015;56:2431–2438. DOI:10.1167/ iovs.14-15909 PURPOSE. Purified Clostridium botulinum exoenzyme C3 transferase (C3) effects on the actin cytoskeleton in human trabecular meshwork cells (HTM) and on the outflow facility response in monkey organ-cultured anterior segments (MOCAS) were determined in the presence or absence of viral vectors.
Improving the performance of Q-learning using simultanouse Q-values updating

Q-learning is a one of the best model-free reinforcement learning algorithms. The goal is to find an estimate of the optimal action-value function called Q-value function. The Q-value function is defined as the expected sum of future rewards obtained by taking an action in the current state. The main drawback of Q-learning is that the learning process is expensive for the agent, specially, in the beginning steps. Because, every state-action pair should be visited frequently in order to converge to the optimal policy. In this paper, the concept of opposite action is used to improve the performance of the Q-learning algorithm, especially, in the beginning steps of the learning. Opposite actions suggest updating two Q-values, simultaneously. The agent will update Q-value for each action and corresponding opposite action and thus increasing the speed of learning. The novel Q-learning method based on the concept of opposite action is simulated for the famous test-bed grid world problem. The results show the ability of the proposed method to improve the learning process.
Intensive chemotherapy with cyclophosphamide, doxorubicin, high‐dose methotrexate/ifosfamide, etoposide, and high‐dose cytarabine (CODOX‐M/IVAC) for human immunodeficiency virus–associated Burkitt lymphoma

In the era of highly active antiretroviral therapy (HAART), standard‐dose chemotherapy for human immunodeficiency virus (HIV)‐associated diffuse large B‐cell lymphoma is becoming the standard of care. In contrast, the safety and efficacy of intensive regimens have not been established for Burkitt lymphoma (BL), a highly aggressive lymphoma for which moderate‐dose chemotherapy is substandard in the HIV‐negative population.
A Novel Pathway-Based Approach Improves Lung Cancer Risk Prediction Using Germline Genetic Variations

Background: Although genome-wide association studies (GWAS) have identified many genetic variants that are strongly associated with lung cancer, these variants have low penetrance and serve as poor predictors of lung cancer in individuals. We sought to increase the predictive value of germline variants by considering their cumulative effects in the context of biologic pathways. Methods: For individuals in the Environment and Genetics in Lung Cancer Etiology study (1,815 cases/1,971 controls), we computed pathway-level susceptibility effects as the sum of relevant SNP variant alleles weighted by their log-additive effects from a separate lung cancer GWAS meta-analysis (7,766 cases/37,482 controls). Logistic regression models based on age, sex, smoking, genetic variants, and principal components of pathway effects and pathway–smoking interactions were trained and optimized in cross-validation and further tested on an independent dataset (556 cases/830 controls). We assessed prediction performance using area under the receiver operating characteristic curve (AUC). Results: Compared with typical binomial prediction models that have epidemiologic predictors (AUC = 0.607) in addition to top GWAS variants (AUC = 0.617), our pathway-based smoking-interactive multinomial model significantly improved prediction performance in external validation (AUC = 0.656, P < 0.0001). Conclusions: Our biologically informed approach demonstrated a larger increase in AUC over nongenetic counterpart models relative to previous approaches that incorporate variants. Impact: This model is the first of its kind to evaluate lung cancer prediction using subtype-stratified genetic effects organized into pathways and interacted with smoking. We propose pathway–exposure interactions as a potentially powerful new contributor to risk inference. Cancer Epidemiol Biomarkers Prev; 25(8); 1208–15. ©2016 AACR.
A novel 3D liver organoid system for elucidation of hepatic glucose metabolism

Hepatic glucose metabolism is a key player in diseases such as obesity and diabetes as well as in antihyperglycemic drugs screening. Hepatocytes culture in two‐dimensional configurations is limited in vitro model for hepatocytes to function properly, while truly practical platforms to perform three‐dimensional (3D) culture are unavailable. In this work, we present a practical organoid culture method of hepatocytes for elucidation of glucose metabolism under nominal and stress conditions. Employing this new method of culturing cells within a hollow fiber reactor, hepatocytes were observed to self‐assemble into 3D spherical organoids with preservation of tight junctions and display increased liver‐specific functions. Compared to both monolayer culture and sandwich culture, the hepatocyte organoids displayed higher intracellular glycogen content, glucose consumption, and gluconeogenesis and approached the in vivo values, as also confirmed by gene expression of key enzymes. Moreover, hepatocyte organoids demonstrated more realistic sensitivity to hormonal challenges with insulin, glucagon, and dexamethasone. Finally, the exposure to high glucose demonstrated toxicities including alteration of mitochondrial membrane potential, lipid accumulation, and reactive oxygen species formation, similar to the in vivo responses, which was not captured by monolayer cultures. Collectively, hepatocyte organoids mimicked the in vivo functions better than hepatocyte monolayer and sandwich cultures, suggesting suitability for applications such as antihyperglycemic drugs screening. Biotechnol. Bioeng. 2012; 109:595–604. © 2011 Wiley Periodicals, Inc.
Antibodies to Complement Receptor 3 Treat Established Inflammation in Murine Models of Colitis and a Novel Model of Psoriasiform Dermatitis

Prior studies indicated the ability of Abs to complement receptor 3 (CR3, CD11b/CD18) to suppress the production of IL-12 from immune cells. Therefore, we tested the ability of an anti-CR3 Ab (clone M1/70) to treat established IL-12-dependent Th1-mediated inflammation in murine models. Systemic administration of anti-CR3 significantly ameliorated established intestinal inflammation following the intrarectal administration of trinitrobenzene sulfonic acid (TNBS-colitis), as well as colitis and skin inflammation in C57BL/10 RAG-2−/− mice reconstituted with CD4+CD45RBhigh T cells. The hyperproliferative skin inflammation in this novel murine model demonstrated many characteristics of human psoriasis, and was prevented by the adoptive transfer of CD45RBlow T cells. In vitro and in vivo studies suggest that anti-CR3 treatment may act, at least in part, by directly inhibiting IL-12 production by APCs. Administration of anti-CR3 may be a useful therapeutic approach to consider for the treatment of inflammatory bowel disease and psoriasis in humans.
Carbamylcholine‐ and 5‐hydroxytryptamine‐induced contraction in rat isolated airways: inhibition by calcitonin gene‐related peptide

1 The effects of rat and human α‐calcitonin gene‐related peptide (α‐CGRP) were investigated in isolated smooth muscle preparations obtained from three levels of the rat respiratory tract. 2 Neither peptide (10−10–10−6m) had any effect on resting tension or on carbamylcholine (10−6m)‐induced tone of trachea or main bronchus. In contrast, CGRP sometimes reduced spontaneous or carbamylcholine‐induced tone of lung parenchymal strips. 3 CGRP produced a significant rightward shift of the log concentration‐response curves to carbamylcholine and 5‐hydroxytryptamine (5‐HT) in the main bronchus. A rightward shift was also seen in trachea and parenchymal strips but this did not achieve the level of significance. The maximal response to 5‐HT was reduced in the main bronchus and lung parenchyma whereas the maximal contraction to carbamylcholine was decreased in parenchymal strip only. 4 In all three airway preparations, CGRP caused concentration‐dependent inhibition of responses elicited by challenges with 10−7m carbamylcholine or 5 × 10−7m 5‐HT. The inhibitory effect of the peptide was inversely related to the size of the airways: the smaller the calibre, the greater the inhibition. 5 The inhibitory action of CGRP was not modified by pretreatment with tetrodotoxin (10−6m), propranolol (10−6m) or indomethacin (10−6m). 6 The results strongly suggest that (a) CGRP has a nonspecific inhibitory action on airway smooth muscle cells, (b) CGRP may act as a potent inhibitor of responses elicited by bronchoconstrictor substances and (c) its inhibitory activity may be most powerfully expressed in peripheral regions of the respiratory tract.
Quantitative Characterization of Code Switching Patterns in Complex Multi-Party Conversations: A Case Study on Hindi Movie Scripts

In this paper, we present a framework for quantitative characterization of code-switching patterns in multi-party conversations, which allows us to compare and contrast the socio-cultural and functional aspects of code-switching within a set of cultural contexts. Our method applies some of the proposed metrics for quan-tiﬁcation of code-switching (Gamback and Das, 2016; Guzman et al., 2017) at the level of entire conversations, dyads and participants. We apply this technique to analyze the conversations from 18 recent Hindi movies. In the process, we are able to tease apart the use of code-switching as a device for establishing identity, socio-cultural contexts of the characters and the events in a movie.
Chromosomal Complementation Using Tn7 Transposon Vectors in Enterobacteriaceae

ABSTRACT Genetic complementation in many bacteria is commonly achieved by reintroducing functional copies of the mutated or deleted genes on a recombinant plasmid. Chromosomal integration systems using the Tn7 transposon have the advantage of providing a stable single-copy integration that does not require selective pressure. Previous Tn7 systems have been developed, although none have been shown to work effectively in a variety of enterobacteria. We have developed several mini-Tn7 and transposase vectors to provide a more versatile system. Transposition of Tn7 at the chromosomal attTn7 site was achieved by a classical conjugation approach, wherein the donor strain harbored the mini-Tn7 vector and the recipient strain possessed the transposase vector. This approach was efficient for five different pathogenic enterobacterial species. Thus, this system provides a useful tool for single-copy complementation at an episomal site for research in bacterial genetics and microbial pathogenesis. Furthermore, these vectors could also be used for the introduction of foreign genes for use in biotechnology applications, vaccine development, or gene expression and gene fusion constructs.
Adaptive array processing MLSE receivers for TDMA digital cellular/PCS communications

Array processing is a promising approach for improving quality, coverage, and capacity in digital cellular communication systems. By combining array processing with maximum likelihood sequence estimation (MLSE), intersymbol interference (ISI) introduced by multipath propagation can be mitigated as well. Novel symbol-spaced and fractionally spaced adaptive array processing MLSE receivers are developed for both diversity and phased array antenna configurations. The practical issues of synchronization and channel estimation are addressed. A novel approach to automatic frequency error correction (AFC) is proposed and is shown to be critical when cancelling cochannel interference. Performance is evaluated for the reverse link of the IS-136 TDMA-based digital cellular system. Substantial improvements are obtained over conventional antenna configurations for receiver sensitivity (2.5-4 dB) and over traditional antenna combining when cochannel interference is present (0.5-25 dB).
Resistance to change in a North Midlands parish

This study is a sociological account of the relative failure of a Roman Catholic parish in the North Midlands to implement the changes in parish life implied by the documents of The Second Vatican Council (1962 - 1965). Initial observation suggested resistance to liturgical, pastoral and ministerial changes On the basis of a critical sociology developed along the lines of a Giddensian critique of both structuralism and phenomenology the following elements were identified by the processes of enumerative and analytic induction: 1) resistance both ideational and practical on the part of the majority of nuclear parishioners of (St Margaret's, Acton), to the process of sacral transformation evident elsewhere, whereby objects formerly hierophanized are desacralised in favour of newly sacralised phenomena; 2) the knowledgeability of social actors as they draw on the rules and resources of the Church and society in the context of the unintended outcomes of their predecessors' actions; 3) the ideological distortions in communication between priest and people; 4) the processes whereby the rules and resources referred to in (2) above are drawn on asymmetrically by hegemonic groups in ways which create forms of exploitative domination in the parish; 5) the historical structuring of religious praxis, specifically the influence of the nineteenth century Catholic revival in (Saxonshire); 6) the relative geographical and social immobility of the Catholic population in (Acton) and the fairly restricted religious socialization of active parishioners. Note: Pseudonyms have been used in this study. On this page and in Chapter 3 brackets have been used to indicate this. The practice is intended to protect the interests of the subjects of the research.
TARMan: Topology-aware reliability management for softwarized network systems

The recent networking paradigm shifts towards the virtualization and softwarization of network functions, controls, and applications that are promising; they optimize costs and processes while bringing new value to the infrastructures. However, the centralized reliability management in softwarization architecture poses both scalability and latency challenges. In this paper, we design and build a novel topology-aware network reliability management framework that enhances the efficiency of network discovery (Link Layer Discovery Protocol (LLDP)) mechanisms and introduces a three-tier-based algorithm that the controller utilizes to calculate the LLDP-discovery frequency. A novel impact based per target LLDP-discovery approach enables fast failure detection and recovery for the important targets. A prototype is implemented on Cisco's OpenDayLight (ODL). Extensive Mininet experiment results validate that the tier-based LLDP message algorithm enables effective decision making tools for the network reliability management framework.
THE POWER OF PERSONALITY *

* An address delivered tlhe annuial meeting of the Osler Club, on July 12th, 1929. a crowd are the sum of those of its individual memiibers, not merely of the cogs or teethl of a machine. There is no level at wllicli personality begins, no sharp line between Socrates, Julius Caesar, and the tramp upon the high road, only a series of imperceptible gradations. Happily for us, we do not recognize the repercussions of oiur personalities as we walk througlh life, nor the extent to wliclh even the most insignificant of us influences his neighbours. Did we do so we should be tempted to take refuge in a Tra.lppist monastery. People of outstanding personality, the fernmenit folk, difer widely amonigst themiselves, anid varlious factoirs go to their making. Ability, I take it, they must possess, and wisdom; the gift of expression, a clear brain, a ready tongue. A senlse of humour, one of Nature's clhoicest gifts, can hiairdly be dispensed with, and, amonig the essentials also, lhuman sympathy and interest in the work and aims of others. Each one of u.s, when he casts hiis thlouights baclkwards overhis own life, recalls a few people who have influienced him powerfully eitlher for good orevil; but it isiupoln tlhe former that our miemory likes to dwelW. We recall the schoolmaster who awakened our interest in whathas been our life's work; he who by a word of encouragement spokeni in good season helped to give us confidence, and slhowed us that one personi at least believed that there was something in us. Another may have succeeded in interesting us in subjects for wlhich we had no aptitude-classics perhaps-anid who seems to walk beside us when we tread the streets of Athens or of Rome. No doubt as we grow older thesepeople tend to grow in stature in our memory, but tlley undoubtedly possessed striking personialitv, anid sowed a grain of mustard seed which has produced a tree. Any miiani who teaches others caninot be a really good teacher unksshe exerts some such influence; the lecturer must interest himself as well as hiis hearers. Probably each one of the elders of ushlas been told, by somiie former pupil, that hehas ni,ever forgotteni something which we said many years ago. We hopethatho will recall one of our choice but forgotteln aphorisms, but it usually turnils out to be a platitude to which lie has clung so long. Apalrt from its personal magnietism, a striking personality may be reflected anid, so to speak, crystallized by a great writer or biographer. How else is it that we so clearly recognize that which distinguishes Elijah froi Elisha, and Queenl Elizabeth from Kinig Henry VII. Plato has beeni able to hand down to all time hiis own mental picture ofthe personiality of Socrates, anid Boswell. reflects for us that of Sam uel Johnson.
Temperature-Controlled Radiofrequency Tissue Volume Reduction in the Human Soft Palate

OBJECTIVE: To validate the use of temperature-controlled radiofrequency energy applied to the soft palate in a multicenter setting for reduction of snoring in a minimally morbid manner. METHODS: Prospective, nonrandomized multicenter study of 113 patients who had a respiratory disturbance index less than 15 and minimum oxygen saturation not less than 85% and who were seeking treatment for habitual disruptive snoring. Patients were given either single or multiple lesions to the soft palate during each treatment session. RESULTS: Patients received 1978 J on average with an overall average of 2.4 treatments. Snoring scores went from an average of 7.8 (visual analog scale [VAS], 0–10) pretreatment to 3.2 posttreatment. Pain was minimal, averaging 1.7 (VAS 0–10) on days 1 to 6. Complications were few and transient, and mild. CONCLUSIONS: The multiple lesion protocol was the most successful; reducing snoring from 7.6 to 2.7, on a VAS with an average of 1232 J delivered over 1.6 treatments. Temperature-controlled radiofrequency was found to be a minimally invasive, well-tolerated procedure that was safe and efficacious in this study group.
The impact of psychological distress on exacerbation rates in COPD

Background: Exacerbations are common in chronic obstructive pulmonary disease (COPD) and contribute significantly to COPD morbidity and mortality. COPD is also associated with high levels of psychological distress, which has been shown to be associated with higher exacerbation rates. However, the existing literature on the association between psychological distress and exacerbation risk remains largely misunderstood. Objectives: To critically review the current literature on the association between psychological distress (defined as anxiety and depressive symptoms or anxiety and depressive disorders) and COPD exacerbations in COPD patients, to highlight the limitations of the existing literature, and to provide recommendations for future research. Methods: A critical review of English-language peer-reviewed longitudinal and retrospective studies was conducted. The Ovid portal to Medline, EMBASE, and PsycINFO databases were accessed. Results: Some acceptable evidence suggested that psychological distress confers greater risk for exacerbations, more specifically symptom-based exacerbations or those treated in the patient’s own environment. However, most studies showed an absence of a positive association, especially with exacerbations leading to hospitalization. Conclusions: Methodological weaknesses and the use of a wide range of psychological tools mean that there is an inconsistent association between psychological distress and exacerbations in the current literature. However, psychological distress may confer greater risk for symptom-based rather than event-based defined exacerbations. Further studies are needed to more comprehensively assess the question, particularly in light of the high levels of both anxiety and depression in COPD patients.