Miracle-dz/UniFAR-FTUs huggingface dataset:
Bypassing STAT3-mediated inhibition of the transcriptional regulator ID2 improves the antitumor efficacy of dendritic cells

Blocking tumor-derived cytokine signaling in dendritic cells enables engineered dendritic cells to function as an antitumor vaccine. Engineering antitumor activity Dendritic cells are critical mediators of the immune response to infection. Despite their potential, antitumor vaccines based on injecting dendritic cells have not been effective. Using mouse models of melanoma, Li et al. found that tumor cells release cytokines that suppress the ability of tumor-infiltrating dendritic cells to mount an antitumor response. The cytokines released from melanoma cells activated the transcription factor STAT3, which repressed the expression of the gene encoding the transcription regulator ID2. Constitutively expressing ID2 dampened production of proinflammatory cytokines in dendritic cells and promoted dendritic cell–mediated immunostimulatory lymphocyte responses. Vaccination experiments in tumor-bearing mice suggested that engineering dendritic cells to overcome or prevent the tumor-derived cytokine response in the injected dendritic cells, by either deleting STAT3 or overexpressing ID2, might prove an effective immunotherapy strategy in cancer patients. Despite the potent ability of dendritic cells (DCs) to stimulate lymphocyte responses and host immunity, granulocyte-macrophage colony-stimulating factor–derived DCs (GM-DCs) used as antitumor vaccines have demonstrated relatively modest success in cancer immunotherapy. We found that injecting GM-DCs into melanoma tumors in mice, or culturing GM-DCs with melanoma-secreted cytokines or melanoma-conditioned medium, rapidly suppressed DC-intrinsic expression of the gene encoding inhibitor of differentiation 2 (ID2), a transcriptional regulator. Melanoma-associated cytokines repressed Id2 transcription in murine DCs through the activation of signal transducer and activator of transcription 3 (STAT3). Enforced expression of ID2 in GM-DCs (ID2–GM-DCs) suppressed their production of the proinflammatory cytokine tumor necrosis factor–α (TNF-α). Vaccination with ID2–GM-DCs slowed the progression of melanoma tumors and enhanced animal survival, which was associated with an increased abundance of tumor-infiltrating interferon-γ–positive CD4+ effector and CD8+ cytotoxic T cells and a decreased number of tumor-infiltrating regulatory CD4+ T cells. The efficacy of the ID2–GM-DC vaccine was improved by combinatorial treatment with a blocking antibody to programmed cell death protein–1 (PD-1), a current immunotherapy that overcomes suppressive immune checkpoint signaling. Collectively, our data reveal a previously unrecognized STAT3-mediated immunosuppressive mechanism in DCs and indicate that DC-intrinsic ID2 promotes tumor immunity by modulating tumor-associated CD4+ T cell responses. Thus, inhibiting STAT3 or overexpressing ID2 selectively in DCs may improve the efficiency of DC vaccines in cancer therapy.
Exploring the structural regularities in networks

In this paper, we consider the problem of exploring structural regularities of networks by dividing the nodes of a network into groups such that the members of each group have similar patterns of connections to other groups. Specifically, we propose a general statistical model to describe network structure. In this model, a group is viewed as a hidden or unobserved quantity and it is learned by fitting the observed network data using the expectation-maximization algorithm. Compared with existing models, the most prominent strength of our model is the high flexibility. This strength enables it to possess the advantages of existing models and to overcome their shortcomings in a unified way. As a result, not only can broad types of structure be detected without prior knowledge of the type of intrinsic regularities existing in the target network, but also the type of identified structure can be directly learned from the network. Moreover, by differentiating outgoing edges from incoming edges, our model can detect several types of structural regularities beyond competing models. Tests on a number of real world and artificial networks demonstrate that our model outperforms the state-of-the-art model in shedding light on the structural regularities of networks, including the overlapping community structure, multipartite structure, and several other types of structure, which are beyond the capability of existing models.
A meta-analysis testing eusocial co-option theories in termite gut physiology and symbiosis

ABSTRACT The termite gut accomplishes key physiologic functions that underlie termite symbiosis and sociality. However, potential candidate functions of the host-symbiont holobiome have not yet been explored across seemingly divergent processes such as digestion, immunity, caste differentiation, and xenobiotic tolerance. This study took a meta-analysis approach for concurrently studying host and symbiont gut metatranscriptome responses of the lower termite Reticulitermes flavipes, which has ancestral characteristics and hosts a diverse mix of eukaryotic and bacterial symbionts. Thirteen treatments were compared from 5 categories (dietary, social, hormonal, immunological, and xenobiotic), revealing 3 main insights. First, each of the 5 tested colonies had distinct magnitudes of transcriptome response, likely as a result of unique symbiont profiles, which highlights the uniqueness of individual termite colonies. Second, after normalization to standardize colony response magnitudes, unique treatment-linked metatranscriptome topologies became apparent. Third, despite colony and topology differences, 4 co-opted master genes emerged that were universally responsive across diverse treatments. These master genes encode host functions related to protein translation and symbiont functions related to protein degradation and pore formation in microbial cell walls. Three of the 4 master genes were from co-evolved protist symbionts, highlighting potentially co-evolved roles for gut symbiota in coordinating functional responses of the collective host-symbiont holobiome. Lastly, for host genes identified, these results provide annotations of recent termite genome sequences. By revealing conserved domain genes, as well as apparent roles for gut symbiota in holobiome regulation, this study provides new insights into co-opted eusocial genes and symbiont roles in termite sociobiology.
Context-aware Path Ranking for Knowledge Base Completion

Knowledge base (KB) completion aims to infer missing facts from existing ones in a KB. Among various approaches, path ranking (PR) algorithms have received increasing attention in recent years. PR algorithms enumerate paths between entity pairs in a KB and use those paths as features to train a model for missing fact prediction. Due to their good performances and high model interpretability, several methods have been proposed. However, most existing methods suffer from scalability (high RAM consumption) and feature explosion (trains on an exponentially large number of features) problems. This paper proposes a Context-aware Path Ranking (C-PR) algorithm to solve these problems by introducing a selective path exploration strategy. C-PR learns global semantics of entities in the KB using word embedding and leverages the knowledge of entity semantics to enumerate contextually relevant paths using bidirectional random walk. Experimental results on three large KBs show that the path features (fewer in number) discovered by C-PR not only improve predictive performance but also are more interpretable than existing baselines.
Effect of tip geometry and crystallinity on two photon excited luminescence and laser scattering of single gold nanorods

A fascinating feature of noble metal nanoparticles is their surface plasmon resonance (SPR) mediated photoluminecence property. Under resonant excitation, collective oscillations of the surface electrons within the nanoparticles are formed, generating large electromagnetic near fields, which have been used to enhance surface enhanced raman scattering (SERS), and two photon luminescent (TPL) generations. Moreover due to their anisotropic physical structure, elongated nanoparticles such as gold nanorods have two plasmon modes (transverse and longitudinal), of which the latter (LSPR) has stronger SPR absorption in the near-infrared region of the electromagnetic spectrum which makes gold nanorods particularly attractive as bio-labelling agents. In TPL, the excitation laser energy is coupled to the longitudinal surface plasmon resonance (LSPR) of the nanorods which results in the increase of the luminescence efficiency even more that of flurescence dye molecules or semiconductor quantum dots. In this thesis, we systematically study the intrinsic radiative features (scattering and TPL) of gold nanorods at a single particle level. Two fundamental questions that we ask in this thesis are: how does the geometry of nanorods enhance the strength of their TPL generation? And how does the substrate affect SPR mediated scattering and TPL properties of EBL (electron beam lithography) fabricated gold nanorods?
The ecological importance of severe wildfires: some like it hot.

Many scientists and forest land managers concur that past fire suppression, grazing, and timber harvesting practices have created unnatural and unhealthy conditions in the dry, ponderosa pine forests of the western United States. Specifically, such forests are said to carry higher fuel loads and experience fires that are more severe than those that occurred historically. It remains unclear, however, how far these generalizations can be extrapolated in time and space, and how well they apply to the more mesic ponderosa pine systems and to other forest systems within the western United States. I use data on the pattern of distribution of one bird species (Black-backed Woodpecker, Picoides arcticus) as derived from 16465 sample locations to show that, in western Montana, this bird species is extremely specialized on severely burned forests. Such specialization has profound implications because it suggests that the severe fires we see burning in many forests in the Intermountain West are not entirely "unnatural" or "unhealthy. " Instead, severely burned forest conditions have probably occurred naturally across a broad range of forest types for millennia. These findings highlight the fact that severe fire provides an important ecological backdrop for fire specialists like the Black-backed Woodpecker, and that the presence and importance of severe fire may be much broader than commonly appreciated.
Notes on linear systems and frequency responses

We show that not all continuous multidimensional linear shift‐invariant systems are characterized by their frequency responses (even when they exist), but that the members of a certain important large family of multidimensional linear systems are completely characterized by their suitably defined frequency responses. Copyright © 2005 John Wiley & Sons, Ltd.
Clinical Interventions in Aging Dovepress Cantab Object Recognition and Language Tests to Detect Aging Cognitive Decline: an Exploratory Comparative Study

Objective: The recognition of the limits between normal and pathological aging is essential to start preventive actions. The aim of this paper is to compare the Cambridge Neuropsychologi-cal Test Automated Battery (CANTAB) and language tests to distinguish subtle differences in cognitive performances in two different age groups, namely young adults and elderly cognitively normal subjects. Method: We selected 29 young adults (29.9±1.06 years) and 31 older adults (74.1±1.15 years) matched by educational level (years of schooling). All subjects underwent a general assessment and a battery of neuropsychological tests, including the Mini Mental State Examination, visuospatial learning, and memory tasks from CANTAB and language tests. Cluster and dis-criminant analysis were applied to all neuropsychological test results to distinguish possible subgroups inside each age group. Results: Significant differences in the performance of aged and young adults were detected in both language and visuospatial memory tests. Intragroup cluster and discriminant analysis revealed that CANTAB, as compared to language tests, was able to detect subtle but significant differences between the subjects. Conclusion: Based on these findings, we concluded that, as compared to language tests, large-scale application of automated visuospatial tests to assess learning and memory might increase our ability to discern the limits between normal and pathological aging.
Bias-Correction Techniques Alone Cannot Determine Whether Ego Depletion is Different from Zero: Commentary on Carter, Kofler, Forster, & McCullough, 2015

Carter, Kofler, Forster, & McCullough (2015) conducted a bias-corrected meta-analysis of the so-called ego depletion effect to determine its real size and robustness. Their efforts have raised awareness of how badly meta-analyses can mislead when the articles that go into them are products of publication bias. Despite our genuine enthusiasm for their work, we worry that in their zeal to correct the record of publication bias, they have drawn too heavily on largely untested statistical techniques that can be insensitive and sometimes misleading. We tested a set of bias-correction techniques, including those favored by Carter and colleagues, by simulating 40,000 meta-analyses in a range of situations that approximate what is found in the ego depletion literature, most notably the presence of heterogeneous effects filtered by publication bias. Our simulations revealed that not one of the bias-correction techniques revealed itself superior in all conditions, with corrections performing adequately in some situations but inadequately in others. Such a result implies that meta-analysts ought to present a range of possible effect sizes and to consider them all as being possible. The problem with the ego depletion literature is that the bias-corrected estimates for the overall effect do not converge, with estimates ranging from g=0 to g=0.24 to g=0.26. Despite our admiration for this program of meta-research, we suggest that bias-corrected meta-analyses cannot yet resolve whether the overall ego depletion is different from zero or not.
Observation of high-frequency waves during strong tearing mode activity in FTU plasmas without fast ions

MHD spectroscopy in FTU has revealed high frequency (HF) oscillations between 30 and 70 kHz that accompany the development of large m0 = −2, n0 = −1 islands in ohmic plasmas. This frequency range is one order of magnitude above the island rotation frequency, one order of magnitude below the first toroidal gap in the Alfvén continuum and of the same order of the low frequency gap introduced by finite beta effects. The HF spectrum is organized in pairs of modes with opposite toroidal numbers, n = 1 and n = −1 for the stronger ones, which form standing waves in the island rest frame. The poloidal structure of HF modes is |m| = 2 for the main lines. HF lines appear when the level of poloidal field perturbation produced by the island at the plasma edge exceeds 0.2%. The absence of energetic ions in FTU ohmic plasmas, the strict correlation between HF and tearing modes and the existence of a threshold indicate that HF modes tap their energy from the tearing mode by a non-linear coupling mechanism.
Randoms in my bedroom: Negotiating privacy and unsolicited contact on social network sites

The immense popularity of social network sites such as MySpace and Facebook has caused a significant shift in the way social interactions occur on the internet. Online interaction is no longer the sole domain of people seeking contact but rather it has become a key medium for maintaining and strengthening social relationships. This article draws on empirical research investigating emerging social practices being developed by young Australian internet users on social network sites. Consistent with other current research, this article argues that social network sites are increasingly regarded as private spaces where young people are ‘hanging out’ and articulating or playing with notions of identity and belonging. Some social networks have even been likened to bedrooms for teenagers, or are arguably replacing shopping centres and parks as spaces for casual youth interaction. Based on empirical research, this article tests these metaphors and suggests measures to strengthen their validity. As multiple social relationships are collapsed under the banner of Friendship on social network sites, important issues about privacy and audience management need to be addressed. What constitutes ‘Friendship’ in the Facebook era? How do young people deal with unsolicited contact in these private spaces? This article argues that young users of social network sites on the Gold Coast in Australia are, consistent with research being conducted throughout the world, developing increasingly complex strategies for managing
Supervisor-Employee Power Distance Incompatibility, Gender Similarity, and Relationship Conflict: A Test of Interpersonal Interaction Theory

According to interpersonal interaction theory, relational harmony surfaces when two individuals have compatible interaction styles. Building from this theory, we propose that supervisor-employee power distance orientation incompatibility will be related to employees’ experience of higher levels of relationship conflict with their supervisors. Additionally, we propose an asymmetrical incongruence effect such that relationship conflict will be highest when supervisors are high in power distance and employees are low in power distance. Furthermore, we address calls in interpersonal interaction research for more direct attention to the social context of the dyadic interaction and explore the moderating effects of supervisor-employee gender (dis)similarity on the relationship between this incompatibility and conflict. We propose that supervisor-employee gender dissimilarity (e.g., male-female or female-male pairs) acts as a conditional moderator, neutralizing the power distance incongruence effect and the asymmetrical incongruence effect. Using 259 supervisor-employee dyads in the physical therapy industry, the hypotheses were generally supported. Theoretical and practical implications regarding the unique benefits of power distance compatibility and gender diversity in supervisor-employee dyads are discussed.
Occupational Cognitive Failure and Its Relationship With Unsafe Behaviors and Accidents

Objectives. The aim of this study was to assess the relationship between occupational cognitive failures (OCFs) and unsafe behaviors, accidents and driving offences among municipal bus drivers in Tehran, Iran. Methods. Systematic random sampling was used to select 190 drivers from 3 transport and traffic Tehran districts. Data were collected with the occupational cognitive failure questionnaire (OCFQ), the driver behavior questionnaire and a data collection form. Results. The mean (SD) numbers of driving-related offences and road traffic accidents were 1.5 (2.6) and 0.37 (1.0), respectively. The mean (SD) numbers of deliberate driving violations, unintended violations, driving slips and mistakes were 6.97 (5.5), 1.61 (1.5), 13.6 (9.0) and 4.53 (3.28), respectively. The mean (SD) number of the OCFs was 28.9 (20.5). A significant correlation was found between occupational cognitive error and unsafe driving behavior subscales. The stepwise logistic regression results showed that, while controlling the effects of confounding factors, the OCF predicts 6%, 9%, 15% and 9% of deliberate violations, unintended violations, driving slips and driving mistakes, respectively. Conclusion. The results of this study show that the score of the OCFQ is a predictor of unsafe driving behaviors and its subscales.
Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer's disease

Cardiorespiratory fitness (CRF) has been shown to be related to brain health in older adults. In individuals at risk for developing Alzheimer's disease (AD), CRF may be a modifiable risk factor that could attenuate anticipated declines in brain volume and episodic memory. The objective of this study was to determine the association between CRF and both hippocampal volume and episodic memory in a cohort of cognitively healthy older adults with familial and/or genetic risk for Alzheimer's disease (AD).
Brain structural alterations associated with dysfunctional cognitive control of pain in patients with low back pain

Recent evidence has shown that chronic back pain (CBP) can lead to functional alterations in the circuitry underlying the cognitive control of pain. Thought suppression (TS) is a common type of cognitive control of pain. Previous research has shown that TS has paradoxical effects that may increase the awareness of pain. Pain‐related TS may also increase individuals’ attention to pain, which may also increase pain sensation, but thus far, the relationship between pain‐related TS and structural brain alterations is unknown.
FEN1 promotes tumor progression and confers cisplatin resistance in non‐small‐cell lung cancer

Lung cancer is one of the leading causes of cancer mortality worldwide. The therapeutic effect of chemotherapy is limited due to the resistance of cancer cells, which remains a challenge in cancer therapeutics. In this work, we found that flap endonuclease 1 (FEN1) is overexpressed in lung cancer cells. FEN1 is a major component of the base excision repair pathway for DNA repair systems and plays important roles in maintaining genomic stability through DNA replication and repair. We showed that FEN1 is critical for the rapid proliferation of lung cancer cells. Suppression of FEN1 resulted in decreased DNA replication and accumulation of DNA damage, which subsequently induced apoptosis. Manipulating the amount of FEN1 altered the response of lung cancer cells to chemotherapeutic drugs. A small‐molecule inhibitor (C20) was used to target FEN1 and this enhanced the therapeutic effect of cisplatin. The FEN1 inhibitor significantly suppressed cell proliferation and induced DNA damage in lung cancer cells. In mouse models, the FEN1 inhibitor sensitized lung cancer cells to a DNA damage‐inducing agent and efficiently suppressed cancer progression in combination with cisplatin treatment. Our study suggests that targeting FEN1 may be a novel and efficient strategy for a tumor‐targeting therapy for lung cancer.