Miracle-dz/UniFAR-FTUs huggingface dataset:
Improving penetration in tumors with nanoassemblies of phospholipids and doxorubicin.

BACKGROUND Drug delivery and penetration into neoplastic cells distant from tumor vessels is critical for the effectiveness of solid tumor chemotherapy. We hypothesized that 10- to 20-nm nanoassemblies of phospholipids containing doxorubicin would improve the drug's penetration, accumulation, and antitumor activity. METHODS Doxorubicin was incorporated into polyethylene glycol-phosphatidylethanolamine (PEG-PE) block copolymer micelles by a self-assembly procedure to form nanoassemblies of doxorubicin and PEG-PE. In vitro cytotoxicity of micelle-encapsulated doxorubicin (M-Dox) against A549 human non-small-cell lung carcinoma cells was examined using the methylthiazoletetrazolium assay, and confocal microscopy, total internal reflection fluorescence microscopy, and flow cytometry were used to examine intracellular distribution and the cellular uptake mechanism. C57Bl/6 mice (n = 10-40 per group) bearing subcutaneous or pulmonary Lewis lung carcinoma (LLC) tumors were treated with M-Dox or free doxorubicin, and tumor growth, doxorubicin pharmacokinetics, and mortality were compared. Toxicity was analyzed in tumor-free mice. All statistical tests were two-sided. RESULTS Encapsulation of doxorubicin in PEG-PE micelles increased its internalization by A549 cells into lysosomes and enhanced cytotoxicity. Drug-encapsulated doxorubicin was more effective in inhibiting tumor growth in the subcutaneous LLC tumor model (mean tumor volumes in mice treated with 5 mg/kg M-Dox = 1126 mm3 and in control mice = 3693 mm3, difference = 2567 mm3, 95% confidence interval [CI] = 2190 to 2943 mm3, P<.001) than free doxorubicin (mean tumor volumes in doxorubicin-treated mice = 3021 mm3 and in control mice = 3693 mm3, difference = 672 mm3, 95% CI = 296 to 1049 mm3, P = .0332, Wilcoxon signed rank test). M-Dox treatment prolonged survival in both mouse models and reduced metastases in the pulmonary model; it also reduced toxicity. CONCLUSIONS We have developed a novel PEG-PE-based nanocarrier of doxorubicin that increased cytotoxicity in vitro and enhanced antitumor activity in vivo with low systemic toxicity. This drug packaging technology may provide a new strategy for design of cancer therapies.
Significance of the prognostic nutritional index in patients with esophageal squamous cell carcinoma

Background The prognostic nutritional index (PNI) is related to the prognosis in many cancers; however, its role in esophageal cancer is still controversial. Further, controversy exists concerning the optimal cut-off points for PNI to predict survival. The aim of this study was to determine the prognostic value of PNI and propose the optimal cut-off points for PNI in predicting cancer-specific survival (CSS) in esophageal squamous cell carcinoma (ESCC). Methods This retrospective study included 375 patients who underwent esophagectomy for ESCC. The PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). With the help of the fit line on the scatter plot, we classified the patients into three categories according to the PNI, ie, >52, 42–52, and <42. Results Our study showed that PNI was associated with tumor length (P=0.007), T grade (P=0.001), and N staging (P<0.001). The 5-year CSS in patients with PNI <42, 42–52, and >52 were 11.0%, 39.1%, and 55.2%, respectively (P<0.001). Multivariate analysis showed that PNI was a significant predictor of CSS (42–52 versus >52, P=0.011; <42 versus PNI >52, P<0.001). Conclusion PNI is a predictive factor for long-term survival in ESCC. The survival rate of ESCC can be discriminated between three groups, ie, PNI <42, 42–52, and >52.
Principal-agent and Peer Relationships in Tournaments

Effort provision in tournaments may depend on both social preferences towards the competitor and social preferences towards the principal who designed the tournament. In a laboratory experiment, we analyze agents' behavior in different tournament settings that vary the distribution of the prize between agents. The principal chooses between a low and a high guaranteed payment. Standard economic theory predicts the same effort provision in all situations. Instead, our results show that both the generosity of the principal and the strict separation between winner and loser increase the effort level in tournaments. Moreover, agents focus their preferences either on the principal or on the agent. Copyright © 2014 John Wiley & Sons, Ltd.
The Effects of Social Status and Culture on Delay Discounting†

People generally tend to discount future outcomes in favor of smaller but immediate gains (i.e., delay discounting). This study examines the hypothesis that culture and social status moderate this tendency, as well as the alternative hypothesis that social status and culture influence delay discounting independently of each other. American and Japanese adults were asked to choose receiving hypothetical monetary rewards either immediately or receiving rewards of different amounts with a delay of 1 year. The results replicated previous findings and supported the alternative hypothesis. Delay discounting was lower when subjective socioeconomic status (i.e., an individual’s perception of her or his social rank) was higher. Also, the Japanese were less likely to discount future rewards than the Americans. However, there was no interaction between social status and culture in influencing the rates of delay discounting.
BOUNDED GAPS BETWEEN PRIMES

Recently, Yitang Zhang proved the existence of a finite bound B such that there are infinitely many pairs pn, pn 1 of consecutive primes for which pn 1 pn ¤ B. This can be seen as a massive breakthrough on the subject of twin primes and other delicate questions about prime numbers that had previously seemed intractable. In this article we will discuss Zhang’s extraordinary work, putting it in its context in analytic number theory, and sketch a proof of his theorem. Zhang even proved the result with B 70 000 000. A co-operative team, polymath8, collaborating only on-line, has been able to lower the value of B to 4680, and it seems plausible that these techniques can be pushed somewhat further, though the limit of these methods seem, for now, to be B 12.
Salmonella enterica serovar Typhi has a 4.1 kb genetic island inserted within the sapABCDF operon that causes loss of resistance to the antimicrobial peptide protamine.

OBJECTIVES To investigate the association between the presence of a genetic island inserted within the sapABCDF operon of Salmonella Typhi and the susceptibility to antimicrobial peptides. METHODS Genetics and bioinformatics approaches were used to study the genomic organization of the sap operon of Salmonella Typhi and several serovars of Salmonella enterica. PCR was used to confirm the information obtained from these analyses. Deletion of the entire genetic island of Salmonella Typhi was achieved by the red swap method. RT-PCR amplification and antimicrobial peptide susceptibility tests were used to evaluate expression of the sap genes and bacterial resistance to protamine. RESULTS Inspection of the genomes of Salmonella Typhi and 10 serovars of Salmonella enterica showed an insertion of a genetic island located between the sapB and sapC genes of the sap operon. This genetic element was referred to as GICT18/1. Unlike Salmonella Typhimurium, the bacterial susceptibility to protamine is increased in Salmonella Typhi wild-type. Deletion of GICT18/1 resulted in protamine susceptibility levels similar to those of Salmonella Typhimurium, suggesting that restoration of the sap operon occurred in the Salmonella Typhi Delta GICT18-1 mutant strain. RT-PCR experiments supported this assumption because an amplicon containing a fragment of sapD-sapF was detected in Salmonella Typhi Delta GICT18/1, whereas it was not detected in Salmonella Typhi wild-type. CONCLUSIONS The presence of GICT18/1 seems to be a natural feature of Salmonella Typhi. This genetic island is found only in 10 out of 32 Salmonella enterica serovars included in this study. Removal of GICT18/1 has an impact in the susceptibility of Salmonella Typhi to the antimicrobial peptide protamine.
Synergistic Effects of Hypofibrinolysis and Genetic and Acquired Risk Factors on the Risk of a First Venous Thrombosis

Background Previously, we demonstrated that hypofibrinolysis, a decreased capacity to dissolve a blood clot as measured with an overall clot lysis assay, increases the risk of venous thrombosis. Here, we investigated the combined effect of hypofibrinolysis with established risk factors associated with hypercoagulability. Methods and Findings Fibrinolytic potential was determined with a plasma-based clot lysis assay in 2,090 patients with venous thrombosis and 2,564 control participants between 18 and 70 y of age enrolled in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based case-control study on venous thrombosis. Participants completed a standardized questionnaire on acquired risk factors. Hypofibrinolysis alone, i.e., clot lysis time (CLT) in the fourth quartile (longest CLT) (in absence of the other risk factor of interest) increased thrombosis risk about 2-fold relative to individuals with CLT in the first quartile (shortest CLT). Oral contraceptive use in women with CLT in the first quartile gave an odds ratio (OR) of 2.6 (95% confidence interval [CI] 1.6 to 4.0), while women with hypofibrinolysis who used oral contraceptives had an over 20-fold increased risk of venous thrombosis (OR 21.8, 95% CI 10.2 to 46.7). For immobilization alone the OR was 4.3 (95% CI 3.2 to 5.8) and immobilization with hypofibrinolysis increased the risk 10.3-fold (95% CI 7.7 to 13.8). Factor V Leiden alone increased the risk 3.5-fold (95% CI 2.3 to 5.5), and hypofibrinolysis in factor V Leiden carriers gave an OR of 8.1 (95% CI 5.3 to 12.3). The combination of hypofibrinolysis and the prothrombin 20210A mutation did not synergistically increase the risk. All ORs and 95% CIs presented are relative to individuals with CLT in the first quartile and without the other risk factor of interest. Conclusions The combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks.
Chemical rival recognition decreases aggression levels in male Iberian wall lizards, Podarcis hispanica

In an agonistic interaction, the assessment of the probable outcome of future encounters with the same individuals may be the best way of decreasing costs of fighting, but this may only be accomplished if animals are able to recognize individual conspecifics. We staged encounters between male lizards, Podarcis hispanica, to examine whether odoriferous cues are involved in rival recognition during agonistic interactions. We experimen- tally manipulated the odour of intruding males, creating familiar males with their own odour or bearing odours of unfamiliar males, and unfamiliar males bearing unfamil- iar odours or odours of familiar males. The results showed that when familiar males were impregnated with scents from unfamiliar males, they elicited an aggressive response by resident unmanipulated males similar to that observed for a new unfamiliar male with unfamiliar odour. This suggests that resident males were unable to recognize familiar males when their own scents were removed. In contrast, responding males were less aggres- sive towards familiar males impregnated with their own odour and towards unfamiliar males impregnated with scents of familiar males, suggesting that when two males have already interacted, their scents become familiar for both males, and that the detection in successive encoun- ters of the familiar scent suffices to reduce the aggres- sive response of territorial males. Therefore, recognition mechanisms based on chemical cues during agonistic en- counters may contribute to reducing the intensity and the costs of fighting in P. hispanica and may play an impor- tant role in the organization of their social system.
Emotion as a Mode of Engagement: A Critical Defense of Ben-Ze’ev’s Social Theory of Emotions

What is an emotion, and what does an emotional reaction signify? In this thesis I critically defend Aaron Ben-Ze’ev’s theory of emotion as a mode of social engagement. Building on the idea that an emotional reaction is the opposite of indifference, emotions express one’s concerns. They are most intense with regard to the shifting dynamics of personal relationships and social status. Thus, in order to think well about social and personal issues, attention to emotional views of the world is paramount. The social concern of emotion opens what may seem private about our reactions to an interpersonal reading. Emotions are contrasted with an intellectual form of engagement, the latter being characterized by deliberative thinking, which focuses on generalities and stable patterns. Emotions, on the other hand, are more closely aligned with action tendencies and tend to disrupt detached styles of thinking by narrowing one’s focus to the emotion’s target. Because emotions express one’s concerns, Ben-Ze’ev argues that they tend to sincerely express our “profound values,” a view which I argue against. Building on Diane Meyers’s conception of the five-dimensional self, I argue that emotions are a source of deeply held convictions, but avoid conflating this with notions of sincerity. Instead, emotional concerns can be integrated into the cultivation of personal autonomy, in terms of self-definition and selfdiscovery. I apply this conception of emotion to the popular concept of emotional intelligence, and argue that emotional intelligence involves a capacity to handle with skill the emerging and chaotic urgency of emotional reactions. EMOTION AS A MODE OF ENGAGEMENT iii
Incorporating Covariates into Standard Line Transect Analyses

Summary. An implicit assumption of standard line transect methodology is that detection probabilities depend solely on the perpendicular distance of detected objects to the transect line. Heterogeneity in detection probabilities is commonly minimized using stratification, but this may be precluded by small sample sizes. We develop a general methodology which allows the effects of multiple covariates to be directly incorporated into the estimation procedure using a conditional likelihood approach. Small sample size properties of estimators are examined via simulations. As an example the method is applied to eastern tropical Pacific dolphin sightings data.
Within- and Across-Species Responses of Plant Traits and Litter Decomposition to Elevation across Contrasting Vegetation Types in Subarctic Tundra

Elevational gradients are increasingly recognized as a valuable tool for understanding how community and ecosystem properties respond to climatic factors, but little is known about how plant traits and their effects on ecosystem processes respond to elevation. We studied the response of plant leaf and litter traits, and litter decomposability across a gradient of elevation, and thus temperature, in subarctic tundra in northern Sweden for each of two contrasting vegetation types, heath and meadow, dominated by dwarf shrubs and herbaceous plants respectively. This was done at each of three levels; across species, within individual species, and the plant community using a community weighted average approach. Several leaf and litter traits shifted with increasing elevation in a manner consistent with greater conservation of nutrients at all three levels, and the most consistent response was an increase in tissue N to P ratio. However, litter decomposition was less directly responsive to elevation because the leaf and litter traits which were most responsive to elevation were not necessarily those responsible for driving decomposition. At the community level, the response to elevation of foliar and litter traits, and decomposability, varied greatly among the two vegetation types, highlighting the importance of vegetation type in determining ecological responses to climatic factors such as temperature. Finally our results highlight how understanding the responses of leaf and litter characteristics of functionally distinct vegetation types, and the processes that they drive, to temperature helps provide insights about how future climate change could affect tundra ecosystems.
Synchronization and observers for nonlinear discrete time systems

A method is described for the synchronization of nonlinear discrete time dynamics. The methodology consists of constructing observer-receiver dynamics that exploit at each time instant the drive signal and buffered past values of the drive signal. In this way, the method can be viewed as a dynamic reconstruction mechanism, in contrast to existing static inversion methods from the theory of dynamical systems.
Boosting Prediction of Geo-location for Web Images Through Integrating Multiple Knowledge Sources

Estimating geographical information of a given photo is a challenging task due to the massive spread of candidate locations on the earth. With the help of freely available geo-tagged Web images, the problem can be addressed by propagating geo-coordinates (latitude and longitude) of geo-related training data, which is obtained using document retrieval techniques. The state-of-the-art approach adopts language modeling technique to estimate the probability distribution of image associated tags in a local region. Under this framework, we propose to differentiate the tags based on the knowledge explored from multiple sources. Finally, a set of geo-informative tags are identified and further emphasized during the model learning and geo-location prediction. In addition, accurate geo-coordinates are estimated by incorporating the image visual information. Experiments on a large-scale geo-tagged Flickr image dataset demonstrate the effectiveness of proposed method at different levels of evaluation granularity.
Community Management of Acute Malnutrition in the Developing World

Globally, acute malnutrition triggers more than 50% of childhood mortality in children under 5 years old, which implies that about 3.5 million children die of malnutrition each year. Prior to the advent of ready-to-use therapeutic food (RUTF), the management of acute malnutrition was limited to hospitals, resulting in low coverage rates with high mortality, as malnourished cases were indentified at later stages often plagued with complications. However, current availability of RUTF has enabled malnourished children to be treated at communities. Further, because RUTF is dehydrated and sealed, it has the added advantage of a lower risk of bacterial contamination, thereby prolonging its storage life at room temperature. Recent data indicate that Community Management of Acute Malnutrition (CMAM) is as cost effective as other high-impact public health measures such as oral rehydration therapy for acute diarrheal diseases, vitamin A supplementation, and antibiotic treatment for acute respiratory infections. Despite the high efficacy of CMAM programs, CMAM still draws insufficient attention for global implementation, suggesting that CMAM programs should be integrated into local or regional routine health systems. Knowledge gaps requiring further research include: the definition of practical screening criteria for malnourished children at communities, the need for systematic antibiotic therapy during malnutrition treatment, and the dietary management of severe malnutrition in children below 6 months of age.
Nonlinear ICA of Temporally Dependent Stationary Sources

We develop a nonlinear generalization of independent component analysis (ICA) or blind source separation, based on temporal dependencies (e.g. autocorrelations). We introduce a nonlinear generative model where the independent sources are assumed to be temporally dependent, non-Gaussian, and stationary, and we observe arbitrarily nonlinear mixtures of them. We develop a method for estimating the model (i.e. separating the sources) based on logistic regression in a neural network which learns to discriminate between a short temporal window of the data vs. a temporal window of temporally permuted data. We prove that the method estimates the sources for general smooth mixing nonlinearities, assuming the sources have sufficiently strong temporal dependencies, and these dependencies are in a certain way different from dependencies found in Gaussian processes. For Gaussian (and similar) sources, the method estimates the nonlinear part of the mixing. We thus provide the first rigorous and general proof of identifiability of nonlinear ICA for temporally dependent sources, together with a practical method for its estimation.
Human cochlear expressed sequence tags provide insight into cochlear gene expression and identify candidate genes for deafness.

To identify candidate genes for human hearing disorders and to understand better human hearing at the molecular level, we constructed a human cochlear cDNA library. An aliquot of the unsubtracted cochlear library was contributed to the IMAGE Consortium at Lawrence Livermore National Laboratory for the generation of expressed sequence tags (ESTs) by the Merck/WashU EST project. Over 4000 ESTs were developed from the cochlear cDNA library and deposited in the GenBank EST database. Sequence clustering shows that the majority of clones are in low copy numbers, demonstrating the high complexity of the library. The sequences of 1388 cochlear ESTs (33%) match 517 known human genes. Among these are genes previously shown to cause both syndromic and non-syndromic hearing loss. A number of the cochlear ESTs show high homology to non-human genes, suggesting new gene family members or human homologs of animal genes. We also report the chromosomal map positions of 437 cochlear ESTs. These provide positional candidate genes for 18 different non-syndromic hearing disorders. A Human Cochlear EST Database web site (http://www.bwh.partners. org/pathology ) has been created to provide access to the cochlear clone data for gene discovery investigations.