Miracle-dz/UniFAR-FTUs huggingface dataset:
Fractionated exposure to low doses of ionizing radiation results in accumulation of DNA damage in mouse spleen tissue and activation of apoptosis in a p53/Atm-independent manner

Abstract Purpose: While the effects of high doses of ionizing radiation (IR) are relatively well characterized, the molecular mechanisms underlying cellular responses to prolonged exposure to low doses of radiation remain largely under-investigated. Materials and methods: Here, we addressed the DNA damage and apoptotic response in the spleen tissue of C57BL/6 male mice after fractionated exposure to X-rays within the 0.1–0.5 Gy dose range. Results: The response to initial exposure to 0.1 Gy of IR was characterized by increased DNA damage and elevated levels of apoptosis. Subsequent exposures (cumulative doses of 0.2 and 0.3 Gy) resulted in adaptive response-like changes, represented as increased proliferation and apoptotic response. Cumulative doses of 0.4 and 0.5 Gy were characterized by accumulation of DNA damage and reactivation of apoptosis and apoptosis-related proteins. Additionally, spleen cells with irreversible damage caused by radiation can undergo apoptosis via activation of p38, which does not necessarily involve the Atm/p53 pathway. Conclusions: Fractionated exposure to low doses of X-rays resulted in accumulation of DNA damage in the murine spleen and induction of apoptotic response in p53/Atm-independent manner. Further studies are needed to understand the outcomes and molecular mechanisms underlying cellular responses and early induction of p38 in response to prolonged exposure to IR.
Infectious Epstein-Barr Virus Lacking Major Glycoprotein BLLF1 (gp350/220) Demonstrates the Existence of Additional Viral Ligands

ABSTRACT The binding of the viral major glycoprotein BLLF1 (gp350/220) to the CD21 cellular receptor is thought to play an essential role during infection of B lymphocytes by the Epstein-Barr virus (EBV). However, since CD21-negative cells have been reported to be infectible with EBV, additional interactions between viral and cellular molecules seem to be probable. Based on a recombinant genomic EBV plasmid, we deleted the gene that encodes the viral glycoprotein BLLF1. We tested the ability of the viral mutant to infect different lymphoid and epithelial cell lines. Primary human B cells, lymphoid cell lines, and nearly all of the epithelial cell lines that are susceptible to wild-type EBV infection could also be successfully infected with the viral mutant in vitro, although the efficiency of infection with BLLF1-negative virus was clearly lower than the one observed with wild-type EBV. Our studies show that the interaction between BLLF1 and CD21 is not absolutely required for the infection of lymphocytes and epithelial cells, indicating that viral molecules other than BLLF1 can mediate the binding of EBV to its target cells. In this context, our results further suggest the hypothesis that additional cellular molecules, apart from CD21, allow virus entry into these cells.
Multipartite Pooling for Deep Convolutional Neural Networks

We propose a novel pooling strategy that learns how to adaptively rank deep convolutional features for selecting more informative representations. To this end, we exploit discriminative analysis to project the features onto a space spanned by the number of classes in the dataset under study. This maps the notion of labels in the feature space into instances in the projected space. We employ these projected distances as a measure to rank the existing features with respect to their specific discriminant power for each individual class. We then apply multipartite ranking to score the separability of the instances and aggregate one-versus-all scores to compute an overall distinction score for each feature. For the pooling, we pick features with the highest scores in a pooling window instead of maximum, average or stochastic random assignments. Our experiments on various benchmarks confirm that the proposed strategy of multipartite pooling is highly beneficial to consistently improve the performance of deep convolutional networks via better generalization of the trained models for the test-time data.
Antimony-Resistant Leishmania donovani Exploits miR-466i To Deactivate Host MyD88 for Regulating IL-10/IL-12 Levels during Early Hours of Infection

Infection with antimony-resistant Leishmania donovani (SbRLD) induces aggressive pathology in the mammalian hosts as compared with ones with antimony-sensitive L. donovani (SbSLD) infection. SbRLD, but not SbSLD, interacts with TLR2/TLR6 to induce IL-10 by exploiting p50/c-Rel subunits of NF-κB in infected macrophages (Mϕs). Most of the TLRs exploit the universal adaptor protein MyD88 to activate NF-κB. We now show that infection of Mϕs from MyD88−/− mice with SbRLD gave rise to significantly higher intracellular parasite number coupled with elevated IL-10/IL-12 ratio in the culture supernatant as compared with infection in wild type (WT) Mϕs. Τhese attributes were not seen with SbSLD in similar experiments. Further, SbRLD infection upregulated miR-466i, which binds with 3′-untranslated region, leading to the downregulation of MyD88. Infection of MyD88−/− Mϕ or IL-12−/− Mϕ with SbRLD induced IL-10 surge at 4 h, whereas the same in WT Mϕ started from 12 h. Thus, absence of IL-12 in MyD88−/− mice favored early binding of NF-κB subunits to the IL-10 promoter, resulting in IL-10 surge. Infection of MyD88−/− mice with SbRLD showed significantly higher organ parasites coupled with ill-defined and immature hepatic granulomas, whereas in WT mice there were less organ parasites and the granulomas were well defined. From the survival kinetics it was observed that SbRLD-infected MyD88−/− mice died by 60 d postinfection, whereas the WT mice continued to survive. Our results demonstrate that SbRLD has evolved a unique strategy to evade host antileishmanial immune repertoire by manipulating host MyD88 to its advantage.
Mortgage Shoppers: How Much Do They Save?

Survey evidence suggests that many U.S. and European consumers do not spend a lot of time comparing mortgage products. We show, however, that mortgage shopping is associated with a substantial monetary payoff, using a unique data set from a website where borrowers (not the lenders) can post their complete set of received mortgage rate offers. A borrower who shops for five mortgage offers is able to save 7,078 euros in net present value on average. The potential savings suggest suboptimal mortgage shopping as the opportunity cost of time to renegotiate additional quotes is unlikely to be that high.
Perils of Partialing Redux: The Case of the Dark Triad

The Dark Triad (DT) is a collection of overlapping aversive personality profiles constituting psychopathy, narcissism, and Machiavellianism. Debates remain regarding the optimal way to examine the unique outcomes associated with each construct, with several scholars advocating partialing these profiles in multiple regression analyses (i.e., removing their shared variance). The present paper details the pitfalls inherent in this approach by comparing the convergence and divergence of relations derived from raw and residualized DT composite scores. In Sample 1 (N = 393), DT scores were examined to determine the extent to which their raw and residualized components manifested similar relationships with the Five-Factor Model and the DSM–5 Section III personality disorder traits. In Sample 2 (N = 542), the same approach was taken in relation to an array of associated behaviors (e.g., antisocial behavior, promiscuity). Findings from Samples 1 and 2 demonstrate that the use of residualized (vs. raw) coefficients presents important interpretative challenges for both narcissism and Machiavellianism. This study illustrates the substantial interpretive difficulties that can arise when using findings from residualized analyses (e.g., multiple regression) to build nomological networks around Dark Triad constructs. We argue that bivariate relations be given preferential treatment, given their more direct ties to the assessments, and that if multivariate approaches are to be used, they must be accompanied by strong theory about the components of DT constructs.
Digital perfusion phantoms for visual perfusion validation.

OBJECTIVE Despite the increasingly broad use of perfusion applications, we still have no generally accessible means for their verification: The common sense of perfusion maps and "bona fides" of perfusion software vendors remain the only grounds for acceptance. Thus, perfusion applications are one of a very few clinical tools considerably lacking practical objective hands-on validation. MATERIALS AND METHODS To solve this problem, we introduce digital perfusion phantoms (DPPs)--numerically simulated DICOM image sequences specifically designed to have known perfusion maps with simple visual patterns. Processing DPP perfusion sequences with any perfusion algorithm or software of choice and comparing the results with the expected DPP patterns provide a robust and straightforward way to control the quality of perfusion analysis, software, and protocols. RESULTS The deviations from the expected DPP maps, observed in each perfusion software, provided clear visualization of processing differences and possible perfusion implementation errors. CONCLUSION Perfusion implementation errors, often hidden behind real-data anatomy and noise, become very visible with DPPs. We strongly recommend using DPPs to verify the quality of perfusion applications.
Bidirectional Negative Regulation of Human T and Dendritic Cells by CD47 and Its Cognate Receptor Signal-Regulator Protein-α: Down-Regulation of IL-12 Responsiveness and Inhibition of Dendritic Cell Activation1

Proinflammatory molecules, including IFN-γ and IL-12, play a crucial role in the elimination of causative agents. To allow healing, potent anti-inflammatory processes are required to down-regulate the inflammatory response. In this study, we first show that CD47/integrin-associated protein, a ubiquitous multispan transmembrane protein highly expressed on T cells, interacts with signal-regulator protein (SIRP)-α, an immunoreceptor tyrosine-based inhibition motif-containing molecule selectively expressed on myelomonocytic cells, and next demonstrate that this pair of molecules negatively regulates human T and dendritic cell (DC) function. CD47 ligation by CD47 mAb or L-SIRP-α transfectants inhibits IL-12R expression and down-regulates IL-12 responsiveness of activated CD4+ and CD8+ adult T cells without affecting their response to IL-2. Human CD47-Fc fusion protein binds SIRP-α expressed on immature DC and mature DC. SIRP-α engagement by CD47-Fc prevents the phenotypic and functional maturation of immature DC and still inhibits cytokine production by mature DC. Finally, in allogeneic MLR between mDC and naive T cells, CD47-Fc decreases IFN-γ production after priming and impairs the development of a Th1 response. Therefore, CD47 on T cells and its cognate receptor SIRP-α on DC define a novel regulatory pathway that may be involved in the maintenance of homeostasis by preventing the escalation of the inflammatory immune response.
Unified service conflict control in IMS

Service conflict is one of the major obstacles for rapid introduction of new services in telecommunication networks. Though many contributions have been proposed to tackle this issue, they are typically incapable of detecting multifarious conflicts in a universal way and lack enough adaptability to learn about new emerging conflicts, both of which limit their successes. In this paper, based on comprehensive analysis of requirements for IP multimedia system (IMS) service conflict control, and the similarities between conflict control system and Artificial Immune System(AIS), an artificial-immune-based online system, named Unified Control of IMS Service Conflicts (UCISC), is proposed. By exploiting some AIS mechanisms including immune recognition, clonal selection and self tolerance, UCISC has the capability to detect and resolve various IMS conflicts uniformly. New conflicts can also be learned gradually. Case studies on the both well-known conflicts in legacy networks and new emerging IMS conflicts are conducted to evaluate the feasibility and validity of the proposed system.
Sleep in the Acute Phase of Severe Traumatic Brain Injury

Background and Objectives. The onset of pervasive sleep-wake disturbances associated with traumatic brain injury (TBI) is poorly understood. This study aimed to (a) determine the feasibility of using polysomnography in patients in the acute, hospitalized stage of severe TBI and (b) explore sleep quality and sleep architecture during this stage of recovery, compared to patients with other traumatic injuries. Methods. A cross-sectional case-control design was used. We examined the sleep of 7 patients with severe TBI (17-47 years; 20.3 ± 15.0 days postinjury) and 6 patients with orthopedic and/or spinal cord injuries (OSCI; 19-58 years; 16.9 ± 4.9 days postinjury). One night of ambulatory polysomnography was performed at bedside. Results. Compared to OSCI patients, TBI patients showed a significantly longer duration of nocturnal sleep and earlier nighttime sleep onset. Sleep efficiency was low and comparable in both groups. All sleep stages were observed in both groups with normal proportions according to age. Conclusion. Patients in the acute stage of severe TBI exhibit increased sleep duration and earlier sleep onset, suggesting that the injured brain enhances sleep need and/or decreases the ability to maintain wakefulness. As poor sleep efficiency could compromise brain recovery, further studies should investigate whether strategies known to optimize sleep in healthy individuals are efficacious in acute TBI. While there are several inherent challenges, polysomnography is a useful means of examining sleep in the early stage of recovery in patients with severe TBI.
Effects of Gender Marking in Pronominal Coindexation

The naming latency of a pronoun was measured when a single previously presented name in a discourse either agreed or did not agree with the pronoun in gender and person. An effect of agreement was found both under conditions in which subjects were likely to have engaged in strategic processing of the pronoun (Experiment 1) and under conditions in which this was unlikely (Experiment 3). The effect of gender agreement was also investigated when two noun phrases were present in the discourse. The results continued to show an immediate effect of gender agreement (naming latencies increased when a pronoun did not agree with one of two previously presented nouns) under experimental conditions likely to engender strategic processing (Experiment 2). This last effect was not significant under experimental conditions that were not likely to engender strategic processing (Experiment 3). The results are discussed in terms of models of the process of identifying the referent of a pronoun in a discourse.
Sumoylation of the Epstein-Barr Virus BZLF1 Protein Inhibits Its Transcriptional Activity and Is Regulated by the Virus-Encoded Protein Kinase

ABSTRACT The Epstein-Barr virus (EBV) immediate-early protein BZLF1 (Z) mediates the switch between latent and lytic EBV infection. Z not only activates early lytic viral gene transcription but also plays a direct role in lytic viral genome replication. Although a small fraction of Z is known to be sumoylated, the effects of this posttranslational modification on various different Z functions have not been well defined. In this report, we show that only the lysine at amino acid residue 12 is required for the sumoylation of Z, and that Z can be sumoylated by SUMO isoforms 1, 2, and 3. We also demonstrate that the sumo-defective Z mutants ZK12A and ZK12R have enhanced transcriptional activity. The sumoylated and nonsumoylated forms of Z were found to have a similar cellular location, both being localized primarily within the nuclear matrix. The Z sumo-defective mutants were, however, partially defective for disrupting promyelocytic leukemia (PML) bodies compared to the ability of wild-type Z. In addition, we show that lytic viral genome replication does not require the sumoylation of Z, although a Z mutant altered at both amino acids 12 and 13 is replication defective. Furthermore, we show that the sumoylation of Z is greatly increased (from less than 1 to about 11%) in lytically induced 293 cells infected with an EBV mutant virus deleted for the EBV-encoded protein kinase (EBV-PK) compared to that of 293 cells infected with wild-type EBV, and that the overexpression of EBV-PK leads to the reduced sumoylation of Z in EBV-negative cells. Our results suggest that the sumoylation of Z helps to promote viral latency, and that EBV-PK inhibits Z sumoylation during viral reactivation.
Confocal microscopy for the analysis of siRNA delivery by polymeric nanoparticles

Clinical applications of genetic therapies, including delivery of short, interfering RNAs (siRNAs) for RNA interference (RNAi), are limited due to the difficulty of delivering nucleic acids to specific cells of interest while at the same time minimizing toxicity and immunogenicity. The use of cationic polymers to deliver nucleic acid therapeutics has the potential to address these complex issues but is currently limited by low‐delivery efficiencies. Although cell culture studies have shown that some polymers can be used to deliver siRNAs and achieve silencing, it is still not clear what physical or chemical properties are needed to ensure that the polymers form active polymer‐siRNA complexes. In this study, we used multicolor fluorescence confocal microscopy to analyze the cellular uptake of siRNAs delivered by novel propargyl glycolide polymeric nanoparticles (NPs). Delivery by these vehicles was compared with delivery by linear polyethyleneimine (LPEI) and Lipofectamine 2000 (LF2K), which are both known as effective delivery vehicles for siRNAs. Our results showed that when LF2K and LPEI were used, large quantities of siRNA were delivered rapidly, presumably overwhelming the basal levels of mRNA to initiate silencing. In contrast, our novel polymeric NPs showed delivery of siRNAs but at concentrations that were initially too low to achieve silencing. Nonetheless, the exceptionally low cytotoxicity of our NPs, and the simplicity with which they can be modified, makes them good candidates for further study to optimize their delivery profiles and, in turn, achieve efficient silencing. Microsc. Res. Tech. 73:878–885, 2010. © 2010 Wiley‐Liss, Inc.
Impact of WNT signaling on tissue lineage differentiation in the early mouse embryo

WNT signaling activity is involved in the regulation of many cellular functions, including proliferation, migration, cell fate specification, maintenance of pluripotency and induction of tumorigenicity. Here we summarize recent progress towards understanding the regulation of canonical WNT/β‐catenin signaling activity through feedback regulatory loops involving the ligands, agonists and antagonists, the availability of intracellular pools of active β‐catenin and the cross‐regulation of the WNT activity by β‐catenin independent pathway. We also review recent findings on the role of WNT/β‐catenin signaling in tissue lineage differentiation during embryogenesis and the maintenance and self renewal of embryo‐derived stem cells in vitro.
Asymmetric impact of monetary surprises on exchange rate

ABSTRACT This paper examines the asymmetric response of exchange rate to monetary surprises. After controlling the type, direction and origin of the news as well as business cycle phase, a new asymmetry is found in the response of the exchange rate to news surprises. In specific, the US Dollar depreciates against major currencies as the response to the negative monetary surprises in the 2001 recession, while the Dollar appreciates responding to similar negative monetary surprises during the 2008 recession. The paper further explores possible causes and finds that time-varying status of the currency with higher financial returns may contribute to the new asymmetry.
Scatter correction in digital mammography based on image deconvolution

X-ray scatter is a major cause of nonlinearity in densitometry measurements using digital mammography. Previous scatter correction techniques have primarily used a single scatter point spread function to estimate x-ray scatter. In this study, a new algorithm to correct x-ray scatter based on image convolution was implemented using a spatially variant scatter point spread function which is energy and thickness dependent. The scatter kernel was characterized in terms of its scattering fraction (SF) and scatter radial extent (k) on uniform Lucite phantoms with thickness of 0.8–8.0 cm. The algorithm operates on a pixel-by-pixel basis by grouping pixels of similar thicknesses into a series of mask images that are individually deconvolved using Fourier image analysis with a distinct kernel for each image. The algorithm was evaluated with three Lucite step phantoms and one anthropomorphic breast phantom using a full-field digital mammography system at energies of 24, 28, 31 and 49 kVp. The true primary signal was measured with a multi-hole collimator. The effect on image quality was also evaluated. For all 16 studies, the average mean percentage error in estimating the true primary signal was found to be −2.13% and the average rms percentage error was 2.60%. The image quality was seen to improve at every energy up to 25% at 49 kVp. The results indicate that a technique based on a spatially variant scatter point spread function can accurately estimate x-ray scatter.
Identification of an outer membrane protein involved in utilization of hemoglobin-haptoglobin complexes by nontypeable Haemophilus influenzae

A recombinant plasmid containing a 6.5-kb fragment of nontypeable Haemophilus influenzae (NTHI) chromosomal DNA was shown to confer a hemoglobin-haptoglobin-binding phenotype on Escherichia coli. Use of a mini-Tn10kan transposon for random insertion mutagenesis of this recombinant plasmid allowed localization of the NTHI DNA responsible for this hemoglobin-haptoglobin-binding phenotype to a 3.5-kb PstI-XhoI fragment within the 6.5-kb NTHI DNA insert. When this mutagenized NTHI DNA fragment was used to transform the wild-type NTHI strain, the resultant kanamycin-resistant mutant exhibited significantly decreased abilities to bind hemoglobin-haptoglobin and utilize it as a source of heme for aerobic growth in vitro. This mutant also lacked expression of a 115-kDa outer membrane protein that was present in the wild-type parent strain. Transformation of this mutant with wild-type NTHI chromosomal DNA restored the abilities to bind and utilize hemoglobin-haptoglobin and to express the 115-kDa outer membrane protein. Nucleotide sequence analysis of the relevant NTHI DNA revealed the presence of a gene, designated hhuA, that encoded a predicted 117,145-Da protein. The HhuA protein exhibited features typical of a TonB-dependent outer membrane receptor and had significant identity with the hemoglobin receptors of both Haemophilus ducreyi and Neisseria meningitidis.