Miracle-dz/UniFAR-FTUs huggingface dataset:
Thioredoxin-1 Promotes Anti-Inflammatory Macrophages of the M2 Phenotype and Antagonizes Atherosclerosis

Objective—Oxidative stress is believed to play a key role in cardiovascular disorders. Thioredoxin (Trx) is an oxidative stress-limiting protein with anti-inflammatory and antiapoptotic properties. Here, we analyzed whether Trx-1 might exert atheroprotective effects by promoting macrophage differentiation into the M2 anti-inflammatory phenotype. Methods and Results—Trx-1 at 1 &mgr;g/mL induced downregulation of p16INK4a and significantly promoted the polarization of anti-inflammatory M2 macrophages in macrophages exposed to interleukin (IL)-4 at 15 ng/mL or IL-4/IL-13 (10 ng/mL each) in vitro, as evidenced by the expression of the CD206 and IL-10 markers. In addition, Trx-1 induced downregulation of nuclear translocation of activator protein-1 and Ref-1, and significantly reduced the lipopolysaccharide-induced differentiation of inflammatory M1 macrophages, as indicated by the decreased expression of the M1 cytokines, tumor necrosis factor-&agr; and monocyte chemoattractant protein-1. Consistently, Trx-1 administered to hyperlipoproteinemic ApoE2.Ki mice at 30 &mgr;g/30 g body weight challenged either with lipopolysaccharide at 30 &mgr;g/30 g body weight or with IL-4 at 500 ng/30 g body weight significantly induced the M2 phenotype while inhibiting differentiation of macrophages into the M1 phenotype in liver and thymus. ApoE2.Ki mice challenged once weekly with lipopolysaccharide for 5 weeks developed severe atherosclerotic lesions enriched with macrophages expressing predominantly M1 over M2 markers. In contrast, however, daily injections of Trx-1 shifted the phenotype pattern of lesional macrophages in these animals to predominantly M2 over M1, and the aortic lesion area was significantly reduced (from 100%±18% to 62.8%±9.8%; n=8; P<0.01). Consistently, Trx-1 colocalized with M2 but not with M1 macrophage markers in human atherosclerotic vessel specimens. Conclusion—The ability of Trx-1 to promote differentiation of macrophages into an alternative, anti-inflammatory phenotype may explain its protective effects in cardiovascular diseases. These data provide novel insight into the link between oxidative stress and cardiovascular diseases.
NTT's QA Systems for NTCIR QAC-1

In this paper, we describe two Question Answering systems that participated in the NTCIR QAC task. The first system, SAIQA-Ii, follows a standard worddistance approach. This system was designed to output the top five candidates and participated in TASK-1. The second system, SAIQA-Is, employs a logic-based approach. This system was designed to output only the most likely candidates and participated in TASK-1 through TASK-3. The evaluation results showed that SAIQA-Ii’s word-distance approach was more suitable for TASK-1 than SAIQA-Is’s; however, SAIQAIs’s logic-based approach was promising in TASK-2 and TASK-3.
Feline calicivirus p32, p39 and p30 proteins localize to the endoplasmic reticulum to initiate replication complex formation

In common with other positive-strand RNA viruses, replication of feline calicivirus (FCV) results in rearrangement of intracellular membranes and production of numerous membrane-bound vesicular structures on which viral genome replication is thought to occur. In this study, bioinformatics approaches have identified three of the FCV non-structural proteins, namely p32, p39 and p30, as potential transmembrane proteins. These proteins were able to target enhanced cyan fluorescent protein to membrane fractions where they behaved as integral membrane proteins. Immunofluorescence microscopy of these proteins expressed in cells showed co-localization with endoplasmic reticulum (ER) markers. Further electron microscopy analysis of cells co-expressing FCV p39 or p30 with a horseradish peroxidase protein containing the KDEL ER retention motif demonstrated gross morphological changes to the ER. Similar reorganization patterns, especially for those produced by p30, were observed in naturally infected Crandel–Rees feline kidney cells. Together, the data demonstrate that the p32, p39 and p30 proteins of FCV locate to the ER and lead to reorganization of ER membranes. This suggests that they may play a role in the generation of FCV replication complexes and that the endoplasmic reticulum may represent the potential source of the membrane vesicles induced during FCV infection.
R‐form LPS, the master key to the activation ofTLR4/MD‐2‐positive cells

Lipopolysaccharide (endotoxin, LPS) is a major recognition marker for the detection of gram‐negative bacteria by the host and a powerful initiator of the inflammatory response to infection. Using S‐ and R‐form LPS from wild‐type and R‐mutants of Salmonella and E. coli, we show that R‐form LPS readily activates mouse cells expressing the signaling receptor Toll‐like receptor 4/myeloid differentiation protein 2 (TLR4/MD‐2), while the S‐form requires further the help of the LPS‐binding proteins CD14 and LBP, which limits its activating capacity. Therefore, the R‐form LPS under physiological conditions recruits a larger spectrum of cells in endotoxic reactions than S‐form LPS. We also show that soluble CD14 at high concentrations enables CD14‐negative cells to respond to S‐form LPS. The presented in vitro data are corroborated by an in vivo study measuring TNF‐α levels in response to injection of R‐ and S‐form LPS in mice. Since the R‐form LPS constitutes ubiquitously part of the total LPS present in all wild‐type bacteria its contribution to the innate immune response and pathophysiology of infection is much higher than anticipated during the last half century.
The geometric maximum traveling salesman problem

We consider the traveling salesman problem when the cities are points in &##x211D;<sup><i>d</i></sup> for some fixed <i>d</i> and distances are computed according to geometric distances, determined by some norm. We show that for any polyhedral norm, the problem of finding a tour of <i>maximum</i> length can be solved in polynomial time. If arithmetic operations are assumed to take unit time, our algorithms run in time <i>O</i>(<i>n</i><sup><i>f</i>−2</sup> log <i>n</i>), where <i>f</i> is the number of facets of the polyhedron determining the polyhedral norm. Thus, for example, we have <i>O</i>(<i>n</i><sup>2</sup> log <i>n</i>) algorithms for the cases of points in the plane under the Rectilinear and Sup norms. This is in contrast to the fact that finding a <i>minimum</i> length tour in each case is NP-hard. Our approach can be extended to the more general case of <i>quasi-norms</i> with a not necessarily symmetric unit ball, where we get a complexity of <i>O</i>(<i>n</i><sup>2<i>f</i>−2</sup> log <i>n</i>). For the special case of two-dimensional metrics with <i>f</i> = 4 (which includes the Rectilinear and Sup norms), we present a simple algorithm with <i>O</i>(<i>n</i>) running time. The algorithm does not use any indirect addressing, so its running time remains valid even in comparison based models in which sorting requires Ω(<i>n</i> log <i>n</i>) time. The basic mechanism of the algorithm provides some intuition on why polyhedral norms allow fast algorithms.Complementing the results on simplicity for polyhedral norms, we prove that, for the case of Euclidean distances in &##x211D;<sup><i>d</i></sup> for <i>d</i> ≥ 3, the Maximum TSP is NP-hard. This sheds new light on the well-studied difficulties of Euclidean distances.
Dietary omega-3 fatty acids attenuate myocardial arrhythmogenic factors and propensity of the heart to lethal arrhythmias in a rodent model of human essential hypertension

Objective: Hypertension-induced myocardial remodeling is known to be associated with increased risk for malignant arrhythmias and alterations in electrical coupling protein, connexin-43 (Cx43), may be involved. We investigated whether omega-3 fatty acids intake affects abnormalities of Cx43 as well as protein kinase C (PKC) signaling and myosin heavy chain (MyHC) profile at the early and late stage of hypertension in the context of the heart's susceptibility to ventricular fibrillation and ability to restore sinus rhythm. Methods: Untreated young and old male spontaneously hypertensive rats (SHRs) and age-matched normotensive rats were compared with animals supplemented by omega-3 (eicosapentaneoic acid + docosahexaneoic acid, 200 mg/kg body weight/day) for 2 months. Left ventricular tissues were taken for examination of subcellular integrity of gap junctions, Cx43 mRNA and protein expression, PKC&egr; and PKC&dgr; as well as MyHC determination. Electrically inducible ventricular fibrillation and sinus rhythm restoration (SRR) were examined on Langedorff-perfused heart preparation. Results: Omega-3 intake significantly reduced cardiovascular risk factors, suppressed inducible ventricular fibrillation, and facilitated SRR in hypertensive rats. Supplementation attenuated lateralization and internalization of Cx43, suppressed elevated Cx43 mRNA, enhanced total Cx43 protein expression and/or expression of its functional phosphorylated forms as well as the expression of cardioprotective PKC-&egr; and suppressed pro-apoptotic PKC-&dgr; isoform. Moreover, the omega-3 diet normalized MyHC profiles in SHR at early stage of disease and old nonhypertensive rats, but failed to do so in old SHR at late stage of disease. Conclusion: Findings suggest that amelioration of myocardial Cx43-related abnormalities, positive modulation of PKC pathways, and normalization of MyHC can significantly contribute to the antiarrhythmic effects of omega-3 in rat model mimicking human essential hypertension. Our results support the prophylactic use of omega-3 to minimize cardiovascular risk and sudden arrhythmic death.
Nucleotide sequence of the leukotoxin gene from Actinobacillus actinomycetemcomitans: homology to the alpha-hemolysin/leukotoxin gene family

The leukotoxin produced by Actinobacillus actinomycetemcomitans has been implicated in the etiology of localized juvenile periodontitis. To initiate a genetic analysis into the role of this protein in disease, we have cloned its gene, lktA. We now present the complete nucleotide sequence of the lktA gene from A. actinomycetemcomitans. When the deduced amino acid sequence of the leukotoxin protein was compared with those of other proteins, it was found to be homologous to the leukotoxin from Pasteurella haemolytica and to the alpha-hemolysins from Escherichia coli and Actinobacillus pleuropneumoniae. Each alignment showed at least 42% identity. As in the other organisms, the lktA gene of A. actinomycetemcomitans was linked to another gene, lktC, which is thought to be involved in the activation of the leukotoxin. The predicted LktC protein was related to the leukotoxin/hemolysin C proteins from the other bacteria, since they shared a minimum of 49% amino acid identity. Surprisingly, although actinobacillus species are more closely related to pasteurellae than to members of the family Enterobacteriaciae, LktA and LktC from A. actinomycetemcomitans shared significantly greater sequence identity with the E. coli alpha-hemolysin proteins than with the P. haemolytica leukotoxin proteins. Despite the overall homology to the other leukotoxin/hemolysin proteins, the LktA protein from A. actinomycetemcomitans has several unique properties. Most strikingly, it is a very basic protein with a calculated pI of 9.7; the other toxins have estimated pIs around 6.2. The unusual features of the A. actinomycetemcomitans protein are discussed in light of the different species and target-cell specificities of the hemolysins and the leukotoxins.
Performance Related Factors Are the Main Determinants of the von Willebrand Factor Response to Exhaustive Physical Exercise

Background Physical stress triggers the endothelium to release von Willebrand Factor (VWF) from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise. Methods 105 healthy individuals (18–35 years) were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag) levels, VWF collagen binding (VWF:CB) levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599), Syntaxin-2 (STX2, rs7978987) and VWF (promoter, rs7965413) were determined. Results The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8–1.1] and increased with 47% [IQR 25–73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1–1.8] (p<0.0001). VWF:CB levels and ADAMTS13 activity both also increased after exhaustive exercise (median increase 43% and 12%, both p<0.0001). The strongest determinants of the VWF:Ag level increase are performance related (p<0.0001). We observed a gender difference in VWF:Ag response to exercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001), which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase. Conclusions VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter.
Hair follicle renewal: organization of stem cells in the matrix and the role of stereotyped lineages and behaviors

Hair follicles (HFs) are renewed via multipotent stem cells located in a reservoir (the bulge); however, little is known about how they generate multi-tissue HFs from a proliferative zone (the matrix). To address this issue, we temporally induced clonal labeling during HF growth. Challenging the prevailing hypothesis, we found that the matrix contains restricted self-renewing stem cells for each inner structure. These cells are located around the dermal papilla forming a germinative layer. They occupy different proximodistal sectors and produce differentiated cells along the matrix radial axis via stereotyped lineages and cell behavior. By contrast, the outer layer of HFs displays a mode of growth involving apoptosis that coordinates the development of outer and inner structures. HF morphology is therefore determined by the organization of cell fates along the proximodistal axis and by cell behavior along the radial (lateral) axis in the matrix. Thus, our studies suggest that fate and behavior are organized by two systems (uncoupled), and this uncoupling may represent a fundamental way to simplify morphogenesis.
Composition of Musical Sound Expressing an Emotion of Robot Based on Musical Factors

In human-robot interaction, how to express robot's emotion to human is an important issue. In this paper, we have proposed the music as a medium expressing robot's emotion. Since emotions and the feelings from music are somewhat subjective, we have composed the music considering musical factors to reduce ambiguity. As an earlier work, we composed the music for happy, sad, fear, and dislike. We analyzed their musical factors and explained the motives of composition. To validate the effect of the composed music for happy, sad, fear, and dislike, we have conducted experiments and compared the results with that on robot's facial expression. The results showed that the composed music is very effective in conveying emotions. In addition, the results showed better emotion expression when music and facial expression were simultaneously presented.
Crystal Structure of SEDL and Its Implications for a Genetic Disease Spondyloepiphyseal Dysplasia Tarda*

SEDL is an evolutionarily highly conserved protein in eukaryotic organisms. Deletions or point mutations in theSEDL gene are responsible for the genetic disease spondyloepiphyseal dysplasia tarda (SEDT), an X-linked skeletal disorder. SEDL has been identified as a component of the transport protein particle (TRAPP), critically involved in endoplasmic reticulum-to-Golgi vesicle transport. Herein, we report the 2.4 Å resolution structure of SEDL, which reveals an unexpected similarity to the structures of the N-terminal regulatory domain of two SNAREs, Ykt6p and Sec22b, despite no sequence homology to these proteins. The similarity and the presence of unusually many solvent-exposed apolar residues of SEDL suggest that it serves regulatory and/or adaptor functions through multiple protein-protein interactions. Of the four known missense mutations responsible for SEDT, three mutations (S73L, F83S, V130D) map to the protein interior, where the mutations would disrupt the structure, and the fourth (D47Y) on a surface at which the mutation may abrogate functional interactions with a partner protein.
Young Age Is Associated with Increased Locoregional Recurrence in Node-Positive Breast Cancer with Luminal Subtypes

Purpose The effects of biological subtypes within breast cancer on prognosis are influenced by age at diagnosis. We investigated the association of young age with locoregional recurrence (LRR) between patients with luminal subtypes versus those with nonluminal subtypes. Materials and Methods Medical records of 524 breast cancer patients with positive lymph nodes between 1999 and 2010 were reviewed retrospectively. All patients received curative surgery and adjuvant chemotherapy based on contemporary guidelines. Radiation was delivered for patients who underwent breast conserving surgery or those who had four or more positive lymph nodes after mastectomy. Adjuvant hormone therapy was administered to 413 patients with positive hormone receptors according to their menstrual status. Results During median follow-up of 84 months, the 10-year locoregional recurrence-free survival rate (LRRFS) was 84.3% for all patients. Patients < 40 years showed significantly worse 10-year LRRFS than those ≥ 40 years (73.2% vs. 89.0%, respectively; p=0.01). The negative effect of young age on LRRFS was only observed in luminal subtypes (69.7% for < 40 years vs. 90.8% for ≥ 40 years; p < 0.01). Multivariate analysis using luminal subtypes ≥ 40 years as a reference revealed luminal subtypes < 40 years were significantly associated with increased risk of LRR (hazard ratio, 2.33; p < 0.01). Conclusion Young breast cancer patients with positive lymph nodes had a higher risk of LRR than those aged ≥ 40 years. This detrimental effect of young age on LRR was confined in luminal subtypes.
Augmenting web search surrogates with images

While images are commonly used in search result presentation for vertical domains such as shopping and news, web search results surrogates remain primarily text-based. In this paper, we present results of two large-scale user studies to examine the effects of augmenting text-based surrogates with images extracted from the underlying webpage. We evaluate effectiveness and efficiency at both the individual surrogate level and at the results page level. Additionally, we investigate the influence of two factors: the goodness of the image in terms of representing the underlying page content, and the diversity of the results on a results page. Our results show that at the individual surrogate level, good images provide only a small benefit in judgment accuracy versus text-only surrogates, with a slight increase in judgment time. At the results page level, surrogates with good images had similar effectiveness and efficiency compared to the text-only condition. However, in situations where the results page items had diverse senses, surrogates with images had higher click precision versus text-only ones. Results of these studies show tradeoffs in the use of images in web search surrogates, and highlight particular situations where they can provide benefits.
Sequence determinants of breakpoint location during HIV-1 intersubtype recombination

Retroviral recombination results from strand switching, during reverse transcription, between the two copies of genomic RNA present in the virus. We analysed recombination in part of the envelope gene, between HIV-1 subtype A and D strains. After a single infection cycle, breakpoints clustered in regions corresponding to the constant portions of Env. With some exceptions, a similar distribution was observed after multiple infection cycles, and among recombinant sequences in the HIV Sequence Database. We compared the experimental data with computer simulations made using a program that only allows recombination to occur whenever an identical base is present in the aligned parental RNAs. Experimental recombination was more frequent than expected on the basis of simulated recombination when, in a region spanning 40 nt from the 5′ border of a breakpoint, no more than two discordant bases between the parental RNAs were present. When these requirements were not fulfilled, breakpoints were distributed randomly along the RNA, closer to the distribution predicted by computer simulation. A significant preference for recombination was also observed for regions containing homopolymeric stretches. These results define, for the first time, local sequence determinants for recombination between divergent HIV-1 isolates.
Whartonacarus floridensis sp. nov. (Acari: Trombiculidae), with a Taxonomic Review and the First Record of Whartonacarus Chiggers in the Continental United States

ABSTRACT Among several unusual species collected during surveillance of ectoparasites on wildlife hosts in the southeastern United States and Caribbean Region, the larvae of a new species of Whartonacarus were encountered in 2003 on a cattle egret, Bubulcus ibis (L.), in the Florida Keys. This is the first record for a member of Whartonacarus in the continental United States. The mite is described and named as Whartonacarus floridensis Mertins, and the possible significance of this discovery with respect to the “tropical bont tick,” Amblyomma variegatum (F.), is discussed. A brief taxonomic review of Whartonacarus raises questions about the putative synonymy of Whartonacarus nativitatis (Hoffmann) and Whartonacarus thompsoni (Brennan) and suggests that Whartonacarus shiraii (Sasa et al.) may include two distinct taxa. Whartonacarus is redefined, and a revised key to the known taxa is provided. Toritrombicula oceanica Brennan & Amerson is placed in the genus Whartonacarus. Also, Whartonacarus palenquensis (Hoffman) is rejected as a member of this genus and placed in its own new genus, Longisetacarus Mertins.
Predictions, perception, and a sense of self

In recent years there has been a paradigm shift in theoretical neuroscience in which the brain—as a passive processor of sensory information—is now considered an active organ of inference, generating predictions and hypotheses about the causes of its sensations. In this commentary, we try to convey the basic ideas behind this perspective, describe their neurophysiologic underpinnings, and highlight the potential importance of this formulation for clinical neuroscience. The formalism it provides—and the implementation of active inference in the brain—may have the potential to reveal aspects of functional neuroanatomy that are compromised in conditions ranging from Parkinson disease to schizophrenia. In particular, many neurologic and neuropsychiatric conditions may be understandable in terms of a failure to modulate the postsynaptic gain of neuronal populations reporting prediction errors during action and perception. From the perspective of the predictive brain, this represents a failure to encode the precision of—or confidence in—sensory information. We propose that the predictive or inferential perspective on brain function offers novel insights into brain diseases.