Miracle-dz/UniFAR-FTUs huggingface dataset:
DC-SIGN Induction in Alveolar Macrophages Defines Privileged Target Host Cells for Mycobacteria in Patients with Tuberculosis

Background Interplays between Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) in human and host professional phagocytes, namely macrophages (Mφs) and dendritic cells (DCs), are central to immune protection against TB and to TB pathogenesis. We and others have recently shown that the C-type lectin dendritic cell–specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN; CD209) mediates important interactions between mycobacteria and human monocyte-derived DCs (MoDCs) in vitro. Methods and Findings In order to explore the possible role of DC-SIGN in M. tuberculosis infection in vivo, we have analysed DC-SIGN expression in broncho-alveolar lavage (BAL) cells from patients with TB (n = 40) or with other non-mycobacterial lung pathologies, namely asthma (n = 14) and sarcoidosis (n = 11), as well as from control individuals (n = 9). We show that in patients with TB, up to 70% of alveolar Mφs express DC-SIGN. By contrast, the lectin is barely detected in alveolar Mφs from all other individuals. Flow cytometry, RT-PCR, and enzyme-linked immunosorbent assay analyses of BAL-derived fluids and cells indicated that M. tuberculosis infection induces DC-SIGN expression in alveolar Mφs by a mechanism that is independent of Toll-like receptor-4, interleukin (IL)-4, and IL-13. This mechanism most likely relies on the secretion of soluble host and/or mycobacterial factors that have yet to be identified, as both infected and uninfected bystander Mφs were found to express DC-SIGN in the presence of M. tuberculosis. Immunohistochemical examination of lung biopsy samples from patients with TB showed that the bacilli concentrate in pulmonary regions enriched in DC-SIGN-expressing alveolar Mφs in vivo. Ex vivo binding and inhibition of binding experiments further revealed that DC-SIGN–expressing alveolar Mφs constitute preferential target cells for M. tuberculosis, as compared to their DC-SIGN− counterparts. In contrast with what has been reported previously in MoDCs in vitro, ex vivo DC-SIGN ligation by mycobacterial products failed to induce IL-10 secretion by alveolar Mφs, and IL-10 was not detected in BALs from patients with TB. Conclusion Altogether, our results provide further evidence for an important role of DC-SIGN during TB in humans. DC-SIGN induction in alveolar Mφs may have important consequences on lung colonization by the tubercle bacillus, and on pulmonary inflammatory and immune responses in the infected host.
Prevalence of HIV Infection and Sexual Risk Behaviors Among Individuals Having Heterosexual Sex in Low Income Neighborhoods in Baltimore, MD: The BESURE Study

Data from the 2007 heterosexual wave at the Baltimore site of the National HIV Behavioral Surveillance System, a cross-sectional, venue-based sample survey targeting high-risk heterosexuals, are presented on risks associated with reporting unprotected sex with casual/exchange partners. Recruitment areas were 10 census tracts within Baltimore City categorized as being in the top 20% of tracts most affected by poverty and AIDS in the Baltimore-Towson metropolitan statistical area. Recruitment venues were not attended for the sole purpose of finding sexual partners. The study population was 301 men and women, aged 18-50, who reported sexual intercourse with a member of the opposite sex in the past 12 months. HIV prevalence was 3% overall. Factors independently associated with reporting sex with a casual or exchange partner in the past 12 months were homelessness, age, 4 or more sex partners during the past 12 months, concurrent sex partners in the past 12 months, binge drinking during the past 30 days, and history of sexually transmitted disease diagnoses. HIV testing results suggest that a generalized epidemic is occurring among the population having heterosexual sex in these areas. Furthermore, sexual risk behaviors were widespread in this population, suggesting that HIV prevention efforts in these geographic areas are needed.
Epigenetic changes play critical role in age‐associated dysfunctions of the liver

CCAAT/Enhancer Binding Proteins family proteins are important regulators of liver functions. Here, we show the critical role of C/EBPα‐mediated chromatin remodeling in the age‐associated dysfunctions of the liver and in the maintenance of physiological homeostasis. Because ph‐S193 isoform of C/EBPα is increased in livers of old mice, we have generated C/EBPα‐S193D knockin mice, which mimic the ph‐S193 isoform of C/EBPα. Analyses of these mice showed that the S193D mutation causes chromatin remodeling leading to histological appearance of ‘foci‐like’ nodules, which are also observed in livers of old mice. These ‘foci‐like’ structures contain K9 trimethylated histone H3, a marker of heterochromatin. The increase of heterochromatin regions in S193D mice correlates with the elevation of S193D‐C/EBPα‐HDAC1 complexes and with dys‐regulation of gene expression including epigenetic silencing of cyclin D1 and D2 promoters and the inhibition of liver proliferation. The elimination of C/EBPα‐HDAC1 complexes in S193D mice by inhibition of HDAC1 corrects chromatin structure and normalizes expression of cyclin D1 and D2. We found that epigenetic dys‐regulation is also associated with the elevation of C/EBPβ and with the increase of C/EBPα/β heterodimers in S193D mice. The C/EBPα/β heterodimers activate transcription of Glut4 and increase the levels of Glut4. As the result, S193D livers have accelerated uptake of glucose and accumulation of glycogen in the liver. Thus, this study demonstrates that the phosphorylation of C/EBPα at S193 leads to the appearance of heterochromatin regions, which correlates with the development of age‐related dysfunctions of the liver.
Incidence and outcomes of BK virus allograft nephropathy among ABO- and HLA-incompatible kidney transplant recipients.

BACKGROUND AND OBJECTIVES ABO-incompatible kidney transplant recipients may have a higher incidence of BK virus allograft nephropathy (BKVAN) compared with ABO-compatible recipients. It is unclear whether HLA-incompatible recipients share this risk or whether this phenomenon is unique to ABO-incompatible recipients. DESIGN, SETTING, PARTICIPATION, MEASUREMENTS: This study analyzed adult incompatible kidney transplant recipients from 1998 to 2010 (62 ABO-incompatible and 221 HLA-incompatible) and identified patients in whom BKVAN was diagnosed by biopsy (per protocol or for cause). This was a retrospective analysis of a prospectively maintained database that compared BKVAN incidence and outcomes between ABO- and HLA-incompatible recipients, respectively. BKVAN link to rejection and graft accommodation phenotype were also explored. The Johns Hopkins Institutional Review Board approved this study. RESULTS Risk for BKVAN was greater among ABO-incompatible than HLA-incompatible patients (17.7% versus 5.9%; P=0.008). Of BKVAN cases, 42% were subclinical, diagnosed by protocol biopsy. ABO-incompatibility and age were independent predictors for BKVAN on logistic regression. C4d deposition without histologic features of glomerulitis and capillaritis (graft accommodation-like phenotype) on 1-year biopsies of ABO-incompatible patients with and without BKVAN was 40% and 75.8%, respectively (P=0.04). Death-censored graft survival (91%) and serum creatinine level among surviving kidneys (1.8 mg/dl) were identical in ABO- and HLA-incompatible patients with BKVAN (median, 1399 and 1017 days after transplantation, respectively). CONCLUSIONS ABO-incompatible kidney recipients are at greater risk for BKVAN than HLA-incompatible kidney recipients. ABO-incompatible recipients not showing the typical graft accommodation-like phenotype may be at heightened risk for BKVAN, but this observation requires replication among other groups.
Multi-level clustering for clock skew optimization

Clock skew scheduling has been effectively used to reduce the clock period of sequential circuits. However, this technique may become impractical if a different skew must be applied for each memory element. This paper presents a new technique for clock skew scheduling constrained by the number of skew domains. The technique is based on a multi-level clustering approach that progressively groups flip-flops with skew affinity. This new technique has been compared with previous work, showing the efficiency in the obtained performance and computational cost. As an example, the skews for an OpenSparc with almost 16 K flip-flops and 500 K paths have been calculated in less than 5 minutes when using only 2 to 5 skew domains.
A Latent Growth Curve Analysis of Prosocial Behavior Among Rural Adolescents

The present study was designed to investigate stability and changes in prosocial behavior and the parent and peer correlates of prosocial behavior in rural adolescents. Participants were from a rural, low SES community in the Eastern United States. The participants were in 7th, 8th, and 9th grades at Time 1 and 10th, 11th, and 12th grades at Time 4, and completed measures of prosocial behavior and quality of parent and peer relationships. Latent growth curve modeling revealed that despite moderate stability in individual differences in prosocial behavior and slight increases in quality of peer and parent relationships, level of prosocial behavior declined until late high school with a slight rebound in grade 12. Furthermore, increases in the quality of peer relationships predicted decreases in prosocial behavior for girls but not boys. Discussion focuses on continuity and change in prosocial behavior and the gender-based relations between quality of parent and peer relationships and prosocial behaviors in adolescence.
INTERACTION OF SUBSTRATE AND NUTRIENT AVAILABILITY ON z . WOOD BIOFILM PROCESSES IN STREAMS

We examined the effect of decomposing leaf litter and dissolved inorganic nutrients on the heterotrophic biofilm of submerged wood in streams with and without leaves. Leaf litter was excluded from one headwater stream in August 1993 at Coweeta Hydrologic Laboratory in the southern Appalachian Mountains. We compared microbial processes on wood in the litter-excluded stream to a reference stream using microbial respiration, fungal biomass, and extracellular enzyme activity. Exclusion of leaf litter enhanced microbial respiration and extracellular enzyme activity, and fungal biomass was seven times higher than in the reference stream. Nutrient-releasing substrates placed beneath wood veneers indicated colimitation by nitrogen and phosphorus on biofilms in the reference stream. Our conclusion is that, in the absence of nutrient immobilization by leaves, nutrients are more available for other heterotrophic processes. Nutrient limitation may have been responsible for low microbial respiration, fungal biomass, and extracellular enzyme activity on wood in the reference stream containing leaves. Our results suggest that competition for nutrients may regulate heterotrophic microbial processes in these streams.
CD31 is a key coinhibitory receptor in the development of immunogenic dendritic cells

Significance Much is known about the costimulatory receptors that contribute to the full maturation of DCs, whereas the coinhibitory receptors that are involved in the control of DC maturation and the maintenance of peripheral tolerance remain largely unknown. This work reveals that CD31, a transhomophilic coreceptor constitutively expressed by resting DCs, has a key coinhibitory function. CD31 is lost by maturing DCs, and the absence of CD31 favors immunogenic maturation. In contrast, upholding CD31 signaling during maturation converts stimulated DCs into tolerogenic cells. These findings will likely have a substantial impact on immunology research, because knowledge of the immune modulation of DCs is important in immune homeostasis as well as in communicable and noncommunicable diseases, including infection, autoimmunity, and cancer. CD31 is a transhomophilic tyrosine-based inhibitory motif receptor and is expressed by both dendritic cells (DCs) and T lymphocytes. Previous studies have established that the engagement of CD31 drives immune-inhibitory signaling in T lymphocytes, but the effect exerted by CD31 signaling in DCs remains elusive. Here, we show that CD31 is a key coinhibitory receptor on stimulated DCs, favoring the development of tolerogenic functions and finally resulting in T-cell tolerance. The disruption of CD31 signaling favored the immunogenic maturation and migration of resident DCs to the draining lymph nodes. In contrast, sustaining the CD31/SHP-1 signaling during DC maturation resulted in reduced NF-κB nuclear translocation, expression of costimulatory molecules, and production of immunogenic cytokines (e.g., IL-12, IL-6), whereas the expression of TGF-β and IL-10 were increased. More importantly, CD31-conditioned DCs purified from the draining lymph nodes of ovalbumin-immunized mice favored the generation of antigen-specific regulatory T cells (CD25+ forkhead box P3+) at the expense of effector (IFN-γ+) cells upon coculture with naive ovalbumin-specific CD4+ T lymphocytes ex vivo. Finally, the adoptive transfer of CD31-conditioned myelin oligodendrocyte glycoprotein-loaded DCs carried immune tolerance against the subsequent development of MOG-induced experimental autoimmune encephalomyelitis in vivo. The key coinhibitory role exerted by CD31 on DCs highlighted by the present study may have important implications both in settings where the immunogenic function of DCs is desirable, such as infection and cancer, and in settings where tolerance-driving DCs are preferred, such as autoimmune diseases and transplantation.
Orthogonal Neighborhood Preserving Projections: A Projection-Based Dimensionality Reduction Technique

This paper considers the problem of dimensionality reduction by orthogonal projection techniques. The main feature of the proposed techniques is that they attempt to preserve both the intrinsic neighborhood geometry of the data samples and the global geometry. In particular, we propose a method, named orthogonal neighborhood preserving projections, which works by first building an "affinity" graph for the data in a way that is similar to the method of locally linear embedding (LLE). However, in contrast with the standard LLE where the mapping between the input and the reduced spaces is implicit, ONPP employs an explicit linear mapping between the two. As a result, handling new data samples becomes straightforward, as this amounts to a simple linear transformation. We show how we can define kernel variants of ONPP, as well as how we can apply the method in a supervised setting. Numerical experiments are reported to illustrate the performance of ONPP and to compare it with a few competing methods.
INTERNATIONAL CAPITAL FLOWS AND THE EMERGING MARKETS :A MENDING THE RULES OF THE GAME?

Recently, and partly as a result of the currency crises in emerging markets, a broad debate on reforming the international financial system has begun. Talk of a “new financial architecture” abounds, and academics, financiers, and politicians have offered blueprints for reforming existing institutions. Some have talked of creating a global lender of last resort, while others have argued that it is high time to abolish the International Monetary Fund (IMF). It is becoming increasingly apparent, however, that political considerations will stand in the way of true change, and it is highly likely that in the next few years we will see, at most, a modest reform of the IMF and of the other major multilateral institutions. However, we are also likely to see some important changes in exchange rate arrangements, as well as in country-specific rules governing capital mobility. Policy discussions have begun to concentrate on the following issues: (a) the conjecture that optimal exchange rate regimes are characterized by either a clean float or an institutionally rigid
ROUGE: A Package for Automatic Evaluation of Summaries

ROUGE stands for Recall-Oriented Understudy for Gisting Evaluation. It includes measures to automatically determine the quality of a summary by comparing it to other (ideal) summaries created by humans. The measures count the number of overlapping units such as n-gram, word sequences, and word pairs between the computer-generated summary to be evaluated and the ideal summaries created by humans. This paper introduces four different ROUGE measures: ROUGE-N, ROUGE-L, ROUGE-W, and ROUGE-S included in the ROUGE summarization evaluation package and their evaluations. Three of them have been used in the Document Understanding Conference (DUC) 2004, a large-scale summarization evaluation sponsored by NIST.
Validation of a Dutch translation of the fibromyalgia impact questionnaire.

OBJECTIVES To validate a Dutch translation of the fibromyalgia impact questionnaire (FIQ). MATERIALS AND METHODS Data were taken from two randomized clinical trials on Spa treatment and venlafaxine in fibromyalgia (FM). Participants completed the Dutch FIQ and a set of validated questionnaires for general health (RAND-36), depression (Beck depression inventory, BDI), pain (McGill pain questionnaire, MPQ) and fatigue (checklist individual strength, CIS). Internal consistency within the FIQ item 'physical functioning' was studied using Cronbach's alpha. Test-retest reliability was studied with intra-class-correlation (ICC) in a subsample of 76 control subjects over a 3 month period without specific intervention. Construct validity was evaluated by correlating the FIQ to other questionnaires. Sensitivity to change was studied using standardized response means (SRM). RESULTS The study sample consisted of 213 women and 11 men (mean age 47 yrs, mean disease duration 11 yrs). Cronbach's alpha for the item 'physical functioning' was 0.91, indicating high internal consistency. Test-retest reliability was acceptable, with ICC ranging from 0.45 for 'morning tiredness' to 0.71 for 'physical function'. FIQ correlated significantly with the RAND-36, with Spearman's rho ranging from -0.60 to -0.70 for items measuring the same concept. Similar patterns of correlation were seen with MPQ, BDI and CIS. Sensitivity to change was sufficient, with SRM after Spa treatment ranging from 0.3 for 'work days missed' to 0.9 for 'days felt good'. Similar SRM were found in the venlafaxine trial for patients reporting general improvement. CONCLUSION The Dutch FIQ is a valid instrument for measuring health status in FM, showing sufficient reliability, construct validity and responsiveness.
Desorption electrospray ionization mass spectrometry reveals surface-mediated antifungal chemical defense of a tropical seaweed

Organism surfaces represent signaling sites for attraction of allies and defense against enemies. However, our understanding of these signals has been impeded by methodological limitations that have precluded direct fine-scale evaluation of compounds on native surfaces. Here, we asked whether natural products from the red macroalga Callophycus serratus act in surface-mediated defense against pathogenic microbes. Bromophycolides and callophycoic acids from algal extracts inhibited growth of Lindra thalassiae, a marine fungal pathogen, and represent the largest group of algal antifungal chemical defenses reported to date. Desorption electrospray ionization mass spectrometry (DESI-MS) imaging revealed that surface-associated bromophycolides were found exclusively in association with distinct surface patches at concentrations sufficient for fungal inhibition; DESI-MS also indicated the presence of bromophycolides within internal algal tissue. This is among the first examples of natural product imaging on biological surfaces, suggesting the importance of secondary metabolites in localized ecological interactions, and illustrating the potential of DESI-MS in understanding chemically-mediated biological processes.
An Oldest Dryas glacier expansion on Mount Pelister (Former Yugoslavian Republic of Macedonia) according to 10Be cosmogenic dating

We provide a geomorphological analysis of a glacial valley on Mount Pelister, in Macedonia. Three boulders from a frontal moraine were dated with the cosmogenic nuclide isotope 10Be. The results demonstrate that the boulders have been exposed since 15.24 ± 0.85 ka. This age constrains the formation of the frontal moraine to the Oldest Dryas cold event. This age fits with that of other glacier deposits dated to the Older Dryas in the Alps, Balkans, Carpathians and Turkish mountains. The Pelister palaeoglacier has been reconstructed and its equilibrium line altitude extracted, returning a value of 2250 m a.s. l. This is in good agreement with the equilibrium line altitudes of most other reconstructed glaciers of the same age in the circum-Mediterranean mountains, demonstrating a comparable response to the Oldest Dryas event. Other palaeoenvironmental records near the Pelister mountain indicate that the Older Dryas was here characterized by a cold and remarkably dry event. The temporal relationship between Older Dryas glacier advances in the Balkan region and recorded changes in the Atlantic thermohaline circulation during the Laurentide Ice Sheet massive ice discharge (H1 event) confirms the strong climatic link between the pan-Mediterranean regions and the North Atlantic Ocean. Supplementary material: Geochemical laboratory results are available at http://doi.org/10.6084/m9.figshare. c.3830254
Study of the Quasi‐5‐Day Wave in the MLT Region by a Meteor Radar Chain

An extensive analysis of quasi 5‐day waves (5DWs) in the mesosphere and lower thermosphere and their responses to a major sudden stratospheric warming (SSW) event (January 2013) are presented. The analysis is based on data conducted from a meteor radar chain in the period from December 2008 to November 2017 and Aura Microwave Limb Sounder satellite. The radar chain includes three stations located at Mohe (MH, 53.5°N, 122.3°E), Beijing (BJ, 40.3°N, 116.2°E), and Wuhan (WH, 30.5°N, 114.6°E). The 5DWs present clear interannual and seasonal variations, which are observed by both the radar wind data and Aura‐temperature data. Interestingly, the ter‐annual oscillation is found to be as important as the commonly recognized annual oscillation and semiannual oscillation at the three stations in both neutral wind components. The 5DWs are strong mainly during the August/September in the meridional component, while they are primarily enhanced in the period of January, April/May, and late summer in the zonal component. An enhancement of 5DWs is observed during the 2013 SSW event in the mesosphere and lower thermosphere region at the three stations. The amplitudes during the SSW are more than 2 times larger than the January average. The strength of the amplification is most prominent at MH and reduces as latitude decreases. According to the results obtained from the radar wind and Aura temperature, the enhanced 5DW modes are W1 at MH, and W2 at BJ and WH. Our results indicate that the amplification of the 5DWs is very likely associated with the 2013 SSW.
Primary and secondary prophylaxis of gastric variceal bleeding

Gastric variceal bleeding is a common problem in patients with cirrhosis and is associated with increased morbidity and mortality. Management is complex and includes pharmacotherapy, endoscopic therapy, and shunt placement. Recent studies indicate that endoscopic therapy with tissue adhesives has similar hemostasis rates and outcomes in terms of mortality as shunt placement but has a lower complication rate and therefore could be considered the first line therapy for acute bleeding and secondary prophylaxis of gastric varices.