Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene set analysis: limitations in popular existing methods and proposed improvements

MOTIVATION Gene set analysis is the analysis of a set of genes that collectively contribute to a biological process. Most popular gene set analysis methods are based on empirical P-value that requires large number of permutations. Despite numerous gene set analysis methods developed in the past decade, the most popular methods still suffer from serious limitations. RESULTS We present a gene set analysis method (mGSZ) based on Gene Set Z-scoring function (GSZ) and asymptotic P-values. Asymptotic P-value calculation requires fewer permutations, and thus speeds up the gene set analysis process. We compare the GSZ-scoring function with seven popular gene set scoring functions and show that GSZ stands out as the best scoring function. In addition, we show improved performance of the GSA method when the max-mean statistics is replaced by the GSZ scoring function. We demonstrate the importance of both gene and sample permutations by showing the consequences in the absence of one or the other. A comparison of asymptotic and empirical methods of P-value estimation demonstrates a clear advantage of asymptotic P-value over empirical P-value. We show that mGSZ outperforms the state-of-the-art methods based on two different evaluations. We compared mGSZ results with permutation and rotation tests and show that rotation does not improve our asymptotic P-values. We also propose well-known asymptotic distribution models for three of the compared methods. AVAILABILITY AND IMPLEMENTATION mGSZ is available as R package from cran.r-project.org.
In Vivo Role of p38 Mitogen-Activated Protein Kinase in Mediating the Anti-inflammatory Effects of CpG Oligodeoxynucleotide in Murine Asthma1

DNA containing unmethylated CpG motifs is intrinsically immunostimulatory, inducing the production of a variety of cytokines and chemokines by immune cells. The strong Th1 response triggered by CpG oligodeoxynucleotide (ODN) inhibits the development of Th2-mediated allergic asthma in mice. This work documents that CpG ODN-induced IL-12 production plays a critical role in this process, because intrapulmonary CpG ODN inhibits allergic inflammation in wild-type but not IL-12−/− mice. CpG ODN rapidly localized to alveolar macrophages (AM), thereby triggering the phosphorylation of p38 mitogen-activated protein kinase (MAP kinase). AM cultured with CpG but not control ODN up-regulated IL-12 p40 expression and release, and these effects were blocked by the highly specific p38 MAP kinase inhibitor SB202190. Intrapulmonary administration of this inhibitor blocked the ability of CpG ODN to produce IL-12 in the lungs and reversed the anti-inflammatory effects of CpG ODN on allergic lung inflammation. These findings indicate that IL-12 production by AM is stimulated by intrapulmonary CpG ODN administration through a p38 MAP kinase-dependent process, and IL-12 is a key cytokine that mediates CpG ODN-induced protection against allergic lung inflammation.
Evolution of Signaling in a Multi-Robot System: Categorization and Communication

Communication is of central importance in collective robotics, as it is integral to the switch from solitary to social behavior. In this article, we study emergent communication behaviors that are not predetermined by the experimenter, but are shaped by artificial evolution, together with the rest of the behavioral repertoire of the robots. In particular, we describe a set of experiments in which artificial evolution is used as a means to engineer robot neuro-controllers capable of guiding groups of robots in a categorization task by producing appropriate actions. The categorization is a result of how robots' sensory inputs unfold in time, and, more specifically, of the integration over time of sensory input. In spite of the absence of explicit selective pressure (coded into the fitness function), which would favor signaling over non-signaling groups, communicative behavior emerges. Post-evaluation analyses illustrate the adaptive function of the evolved signals and show that these signals are tightly linked to the behavioral repertoire of the agents. Signals evolve because communication enhances group performance, revealing a “hidden” benefit for social behavior. This benefit is related to obtaining robust and fast decision-making mechanisms. More generally, we show how processes requiring the categorization of noisy dynamical information might be improved by social interactions mediated by communication. In a further series of experiments, we successfully download evolved controllers onto real s-bots. We discuss the challenges involved in porting neuro-controllers displaying time-based decision-making processes onto real robots. Finally, the beneficial effect of communication is shown to transfer to the case of a real robot, and the robustness of the behavior against inter-robot differences is discussed.
The Psychology of Word Use in Depression Forums in English and in Spanish: Texting Two Text Analytic Approaches

The present studies demonstrate two computerized approaches to examining the expression of depression on the Internet. Study 1 observed linguistic markers of depression in English and Spanish forums. English and Spanish posts by depressed (N=160) and non-depressed individuals (N=160) were collected from Internet forums using bulletin board systems (bbs). A computer program (LIWC2001) was used to compare linguistic categories across groups within the English and Spanish language. Study 2 analyzed the themes people use when talking about their depression in forums in English and Spanish. Posts by English speaking (N=404) and Spanish speaking depressed people (N=400) were collected from bbs. An automated inductive approach to content analysis was used to compare how the expression of depression varies across cultures. The results for Study 1 showed that linguistic cues previously associated with depression were found to be higher in depressed than in non-depressed posts in English and Spanish. Study 2 showed that depressed people who wrote in Spanish were more likely to mention relational concerns than depressed people who wrote in English, who were more likely to mention medicinal concerns. Implications for informational and support needs and concerns in psychotherapy vs. online support across cultures are addressed and discussed.
Polynomial Multiplication over Finite Fields Using Field Extensions and Interpolation

A method for polynomial multiplication over finite fields using field extensions and polynomial interpolation is introduced. The proposed method uses polynomial interpolation as Toom-Cook method together with field extensions. Furthermore, the proposed method can be used when Toom-Cook method cannot be applied directly. Explicit formulae improving the previous results in many cases are obtained.
Application of next-generation sequencing technologies in virology

The progress of science is punctuated by the advent of revolutionary technologies that provide new ways and scales to formulate scientific questions and advance knowledge. Following on from electron microscopy, cell culture and PCR, next-generation sequencing is one of these methodologies that is now changing the way that we understand viruses, particularly in the areas of genome sequencing, evolution, ecology, discovery and transcriptomics. Possibilities for these methodologies are only limited by our scientific imagination and, to some extent, by their cost, which has restricted their use to relatively small numbers of samples. Challenges remain, including the storage and analysis of the large amounts of data generated. As the chemistries employed mature, costs will decrease. In addition, improved methods for analysis will become available, opening yet further applications in virology including routine diagnostic work on individuals, and new understanding of the interaction between viral and host transcriptomes. An exciting era of viral exploration has begun, and will set us new challenges to understand the role of newly discovered viral diversity in both disease and health.
Lightweight Dual Stream Network With Knowledge Distillation for RGB-D Scene Parsing

Significant progress has been made in the field of indoor scene parsing. The increasing demand for lightweight networks is due to the limited hardware capacity of mobile devices. However, there has been a lack of research on the design of lightweight networks for indoor scene parsing. Therefore, we propose lightweight dual stream network (LDSNet) with knowledge distillation (KD) for RGB-D indoor scene parsing. Initially, we developed a two-stream network with three versions (LDSNet-tiny*, LDSNet-small*, and LDSNet-base, where* represents the model after KD) for different scenarios. In the main stream, we designed an integrated joint enhancement module that captures valuable information from both RGB and depth features. This information is then processed by the cascading integration module to generate the final map. To improve the performance of the model, we included an auxiliary extraction module in the auxiliary stream to specifically extract feature information for KD. During the training process, we used hierarchical context loss to distill features and obtain LDSNet-tiny* and LDSNet-small*. We conducted experiments on the NYUDv2 and SUN RGB-D datasets, which demonstrated that our LDSNet-base achieves superior results, while LDSNet-tiny* and LDSNet-small* also exhibit satisfactory performance.
Modeling Coverage for Neural Machine Translation

Attention mechanism has enhanced state-of-the-art Neural Machine Translation (NMT) by jointly learning to align and translate. It tends to ignore past alignment information, however, which often leads to over-translation and under-translation. To address this problem, we propose coverage-based NMT in this paper. We maintain a coverage vector to keep track of the attention history. The coverage vector is fed to the attention model to help adjust future attention, which lets NMT system to consider more about untranslated source words. Experiments show that the proposed approach significantly improves both translation quality and alignment quality over standard attention-based NMT.
Multiobjective evolutionary algorithm with many tables for purely ab initio protein structure prediction

This article focuses on the development of an approach for ab initio protein structure prediction (PSP) without using any earlier knowledge from similar protein structures, as fragment‐based statistics or inference of secondary structures. Such an approach is called purely ab initio prediction. The article shows that well‐designed multiobjective evolutionary algorithms can predict relevant protein structures in a purely ab initio way. One challenge for purely ab initio PSP is the prediction of structures with β‐sheets. To work with such proteins, this research has also developed procedures to efficiently estimate hydrogen bond and solvation contribution energies. Considering van der Waals, electrostatic, hydrogen bond, and solvation contribution energies, the PSP is a problem with four energetic terms to be minimized. Each interaction energy term can be considered an objective of an optimization method. Combinatorial problems with four objectives have been considered too complex for the available multiobjective optimization (MOO) methods. The proposed approach, called “Multiobjective evolutionary algorithms with many tables” (MEAMT), can efficiently deal with four objectives through the combination thereof, performing a more adequate sampling of the objective space. Therefore, this method can better map the promising regions in this space, predicting structures in a purely ab initio way. In other words, MEAMT is an efficient optimization method for MOO, which explores simultaneously the search space as well as the objective space. MEAMT can predict structures with one or two domains with RMSDs comparable to values obtained by recently developed ab initio methods (GAPFCG, I‐PAES, and Quark) that use different levels of earlier knowledge. © 2013 Wiley Periodicals, Inc.
A Sound and Practical Approach to Quantifying Security Risk in Enterprise Networks ∗

Mitigation of security risk is an important task in enterpri se network security management. However it is presently a skill ac quired by individual experience, more an art than a science. Th biggest challenge in the problem is a quantitative model tha t objectively measures the likelihood a breach can be accomplis hed. This paper presents a sound and practical approach to such a quantitative model. We utilize existing work in attack grap hs and individual vulnerability metrics, such as CVSS, and apply p robabilistic reasoning to produce a sound risk measurement. Th e problem requires a careful coordination of attack graph dat a to account for cyclic and shared dependencies. We recognize th at networks commonly have many host interconnections and network privileges could be gained in many ways. This factor lea ds to cycles in an attack graph, which must be identified and prop erly treated when measuring risk to prevent distortion of th e results. We also recognize that multiple attack paths leading to the same network privilege will often share some dependencies a nd so a valid assessment cannot simply treat these paths as inde pendent. Our approach is provably sound and ensures that shared dependencies have a proportional effect on the final calculati on, and that cycles are handled correctly so that privileges are eva luated without any self-referencing effect. We also present preli minary experimental results on our algorithm and identify directi ons for future improvement.
IL-6 Alters Osteocyte Signaling toward Osteoblasts but Not Osteoclasts

Mechanosensitive osteocytes regulate bone mass in adults. Interleukin 6 (IL-6), such as present during orthodontic tooth movement, also strongly affects bone mass, but little is known about the effect of IL-6 on osteocyte function. Therefore we aimed to determine in vitro whether IL-6 affects osteocyte mechanosensitivity, and osteocyte regulation of osteoclastogenesis and osteoblast differentiation. MLO-Y4 osteocytes were incubated with/without IL-6 (1 or 10 pg/mL) for 24 hr. Subsequently, osteocytes were subjected to mechanical loading by pulsating fluid flow (PFF) for 1 hr. Mouse osteoclast precursors were cultured for 7 days on top of IL-6-treated osteocytes. Conditioned medium from osteocytes treated with/without IL-6 was added to MC3T3-E1 pre-osteoblasts for 14 days. Exogenous IL-6 (10 pg/mL) did not alter the osteocyte response to PFF. PFF significantly enhanced IL-6 production by osteocytes. IL-6 enhanced Rankl expression but reduced caspase 3/7 activity by osteocytes, and therefore did not affect osteocyte-stimulated osteoclastogenesis. Conditioned medium from IL-6-treated osteocytes reduced alkaline phosphatase (ALP) activity and Runx2 expression in osteoblasts, but increased expression of the proliferation marker Ki67 and osteocalcin. Our results suggest that IL-6 is produced by shear-loaded osteocytes and that IL-6 may affect bone mass by modulating osteocyte communication toward osteoblasts.
Exploring family demography in Asia through the lens of fertility preferences

From the standpoint of global population dynamics, the domain of this volume is of indisputable importance. The large set of countries that collectively comprise “Asia” at present contain a majority of the global population (60% in 2015) and this will continue to be the case at mid-century (54% in 2050 according to United Nations projections (United Nations Population Division 2017)). That population levels and trends are heavily determined by levels and trends in fertility is a firmly established demographic truth, indeed fertility stands as one of the three elements in the demographic balancing equation (the other two being mortality and migration). Fertility is fundamental to population dynamics – about this there can be no dispute. Total fertility rates (TFR) are the “headline” figures so often referred to. The variation across the region, as shown in Figure 1.1, is immense (Gietel-Basten 2018). Indeed, one can argue that Asia has some of both the highest and lowest TFRs in the world. But what about fertility desires, the theme of this volume? Should fertility desires be viewed as a central driver of fertility levels and trends, or as an epiphenomenon, i.e. simply a mediating factor through which the more fundamental determinants operate? In fact, these two stances are not incompatible, indeed canonical fertility theory encompasses both. Notably, the influential Easterlin Synthesis Framework (Easterlin 1975) accords considerable determining power to fertility desires but is also explicit that desires serve to mediate the causal effects of cultural, social and economic variables (see also National Academy of Sciences, Panel on Fertility Determinants 1983). More autonomy to fertility desires is posited by Coale in his three preconditions for fertility decline (Coale 1973), and this is the case to an even greater extent in the various “ideational” explanations derived from the empirical research of Coale and his collaborators on the European fertility decline (see, e.g., Lesthaeghe 1983, Watkins 1986, Cleland and Wilson 1987).
Non-Pegylated Liposomal Doxorubicin-Cyclophosphamide in Sequential Regimens with Taxanes as Neoadjuvant Chemotherapy in Breast Cancer Patients

Purpose: Chemotherapy regimens containing anthracyclines and taxanes represent the landmark of neoadjuvant systemic therapy of breast cancer. In advanced breast cancer patients liposomal anthracyclines (LA) have shown similar efficacy and less cardiac toxicity when compared to conventional anthracyclines. We performed this retrospective analysis in order to evaluate the efficacy and tolerability of neoadjuvant regimens including LA outside of clinical trials in routine clinical practice. Methods: Fifty operable or locally advanced, HER2 negative, breast cancer patients were retrospectively identified in 5 Italian cancer centres. Nineteen patients had received 4 cycles of non-pegylated liposomal doxorubicin (NPLD) and cyclophosphamide, followed by 4 cycles of docetaxel, every 3 weeks. In 25 patients the reverse sequence was employed, and a third subgroup of 6 patients received 4 cycles of NPLD/cyclophosphamide every 3 weeks followed by 4 cycles of weekly carboplatin and paclitaxel. Results: We observed 10 pathological complete responses (pCR) (20.0%, 95%CI, 9% to 31%), and 35 (70%, 95%CI, 57.3% to 82.7%) partial responses (pPR), whereas no patients progressed onto therapy. In the small subset of triple negative tumors the pCR rate was 37.5%, and in tumors expressing ER and/or PgR it was 16.7%. A pCR rate of 26.5% was observed in tumors with high Ki-67, whereas in tumors with low Ki-67 only one (6.2%) pCR was observed (p=0.14). Treatments were well tolerated. The most common toxicities were myelosuppression and palmar-plantar erytrodysesthesia; 4 asymptomatic and transient LVEF decrease have been recorded, without any case of clinical cardiotoxicity. Conclusions: NPLD-cyclophosphamide and taxanes sequential regimens were proven effective and well tolerated in breast cancer patients with contra-indication to conventional anthracyclines undergoing neoadjuvant chemotherapy, even outside of clinical trials in everyday clinical practice.
Lesser black-backed gull distribution in and around the Thornton Bank offshore wind farm using GPS logger data,

We analysed GPS data of lesser black-backed gulls (Larus fuscus) caught and tagged in the colonies at Ostend and Zeebrugge. After exploring general patterns in at-sea presence and behaviour, we performed three modelling exercises to study the response of lesser blackbacked gulls towards the C-Power turbines at the Thornton Bank offshore wind farm (OWF) in more detail. These exercises confirmed that much more time was spent roosting on outer than on inner turbines. Next, we found a significant and gradual increase in the number of logs of flying birds going from the centre of the wind farm up to 2000 m from the wind farm edge, beyond which the response seemed to stabilise. For non-flying birds too, the model predicted a minimum number of logs in the centre of the wind farm and a flattening of the smoother at about 2000 m, yet with a highly increased presence right at the wind farm’s edge, representing birds roosting on the outer turbine foundations. The last model, aiming to assess temporal variation in the presence of lesser black-backed gulls in and around the Thornton Bank OWF, showed that the birds were increasingly wary of entering the wind farm during times of strong winds with fast moving rotor blades. The results of this study illustrate that the response of lesser blackbacked gulls towards OWFs can be subject to both temporal and (within-OWF) spatial variation, which in turn can be of high value in refining collision risk modelling.
The fraction of galaxies that contain active nuclei and their accretion rates

We investigate the relationship between the present-day optical luminosity function of galaxies and the X-ray luminosity function of Seyfert 1s to determine the fraction of galaxies that host Seyfert 1 nuclei and their Eddington ratios. The local type 1 active galactic nuclei (AGN) X-ray luminosity function is well reproduced if similar to1 per cent of all galaxies are type 1 Seyferts which have Eddington ratios of similar to 10(-3). However, in such a model the X-ray luminosity function is completely dominated by AGN in E and S0 galaxies, contrary to the observed mix of Seyfert host galaxies. To obtain a plausible mix of AGN host galaxy morphologies requires that the most massive black holes in E and S0 galaxies accrete with lower Eddington ratios, or have a lower incidence of Seyfert activity, than the central black holes of later-type galaxies.
Reliabilism and the Value of Knowledge

1. W EAK K NOWLEDGE I S M ERE T RUE B ELIEF It is a widely accepted doctrine in epistemology that knowledge has greater value than mere true belief. But although epistemologists regularly pay homage to this doctrine, evidence for it is shaky. Is it based on evidence that ordinary people on the street make evaluative comparisons of knowledge and true belief, and consistently rate the former ahead of the latter? Do they reveal such a preference by some sort of persistent choice behavior? Neither of these scenarios is observed. Rather, epistemologists come to this conclusion because they have some sort of conception or theory of what knowledge is, and they find reasons why people should rate knowledge, so understood, ahead of mere true belief. But what if these epistemological theories are wrong? Then the assumption that knowledge is more valuable than true belief might be in trouble. We don't wish to take a firm position against the thesis that knowledge is more valuable than true belief. But we begin this paper by arguing that there is one sense of 'know' under which the thesis cannot be right. In particular, there seems to be a sense of 'know' in which it means, simply, 'believe truly. ' If this is correct, then knowledge—in this weak sense of the term—cannot be more valuable than true belief. What evidence is there for a weak sense of 'knowledge' in which it is equivalent to 'true belief'? Knowledge seems to contrast with ignorance. Not only do knowledge and ignorance contrast with one another but they seem to exhaust the alternatives, at least for a specified person and fact. Given a true proposition p, Diane either knows p or is ignorant of it. The same point can be expressed using rough synonyms of 'know. ' Diane is either aware of (the fact that) p or is ignorant of it. She is either cognizant of po r ignorant of it. She eitherpossesses the information that p or she is uninformed (ignorant) of it. To illustrate these suggestions, consider a case discussed by John Hawthorne (2002). If I ask you how many people in the room know that Vienna is the capital of Austria, you will tally up the number of people in the room who possess the information that Vienna is the capital of Austria. Everyone in the room who