Miracle-dz/UniFAR-FTUs huggingface dataset:
Transferable Anergy: Superantigen Treatment Induces Cd4 Ϩ T Cell Tolerance That Is Reversible and Requires Cd4 Ϫ Cd8 Ϫ Cells and Interferon ␥

Bacterial superantigens induce peripheral unresponsiveness in CD4 ϩ T cell populations that express appropriate V ␤ chains. We have used V ␤ 3/V ␣ 11 T cell receptor transgenic (Tg) mice and the V ␤ 3-specific superantigen staphylococcal enterotoxin A (SEA) to further investigate the mechanisms that contribute to such unresponsiveness. As in other models, in vivo exposure to SEA rendered the Tg CD4 ϩ cells unresponsive to subsequent restimulation in vitro with an-tigen or mitogens. However, when the SEA-treated CD4 ϩ cells were completely purified away from all other contaminating cells, they regained the ability to proliferate and secrete cy-tokines. Moreover, enriched CD4 Ϫ CD8 Ϫ cells from the SEA-treated mice suppressed the responses of fresh control CD4 ϩ cells in mixed cultures indicating that the apparent " anergy " was both transferable and reversible. Further analysis demonstrated that interferon ␥ , but not the Fas receptor, played a critical role in the suppression. U nder optimum conditions, immune responses are tightly regulated to prevent prolonged inflammation and indiscriminate damage to healthy tissue. Multiple mechanisms are known to contribute to the maintenance of immune tolerance (1) including: deletion of self-reactive T cells during thymic selection (2) and in the periphery (3–5) and the induction of unresponsiveness or anergy among specific B (6) and T cell subsets (7–10). However, the relative contributions of these mechanisms to the in situ downregula-tion of specific immune responses remain unclear in most instances. Many experimental models have been developed to identify mechanisms that participate in the induction of tolerance , including injection of (11–13) and oral exposure to (14) soluble proteins. Other models use natural superanti-gens (SAg 1 ; 15), such as those encoded by the mouse mam-mary tumor virus genes (5). The fact that both bacteria and viruses have independently evolved similar strategies to subvert host immune responses suggests that SAg often play an important role in host–pathogen interactions. It is therefore important to understand the mechanisms by which SAg induce T cell anergy, both for the purpose of counteracting their effects and because similar strategies may participate in other processes that the host uses to promote self tolerance. In contrast to some other polyclonal T cell activators, SAg interact specifically with class II MHC molecules (16), stimulating T cells through V ␤-restricted T cell–APC interactions (17) in a way that closely mimics recognition of peptide–MHC complexes. Thus, it is likely that SAg …
Paraná flood basalts: Rapid extrusion hypothesis confirmed by new 40Ar/39Ar results

The duration of volcanism in the Parana continental flood basalt (CFB) province, essential information to assess models of melt generation, eruption rates, continental breakup, and volcanism-driven extinction events, remains unresolved due to conflicting sets of 40Ar/39Ar geochronology data. Some results suggest that the Parana CFB volcanism began at 134.7 ± 1 Ma and lasted <1 m.y. Another set of results reveals an extrusion interval of 11 m.y. , from ca. 140 Ma to ca. 129 Ma. To resolve this controversy, we reanalyzed three of the exact hand specimens that previously yielded the oldest and youngest ages in the protracted 11 m.y. range. Our new ages are statistically indistinguishable from each other and the previous 134.7 ± 1 Ma result and indicate a short eruption event. A rapid extrusion for the Parana CFB and the lack of a major cotemporal extinction event challenge proposed direct links between CFB volcanism and mass extinctions and refute petrological models that rely on a protracted extrusion of the Parana CFB.
Interleukin 2-mediated Induction of c-myb Gene Expression Is Dependent on T Lymphocyte Activation State

Theinteraction ofIL-2 withthe IL-2-Rplaysacentralrole in theregulation ofTlymphocyteproliferation(1). Triggering oftheTCRleadstothesynthesisofIL-2(incertainTlymphocyte subsets) andto theinduction of high affinity IL-2-Rs inantigen-activatedTlymphocytes(2-4). It is thebindingofIL-2to thehigh affinityIL-2-R (and the subsequent internalization ofthis complex) that leads to the cas-cade of events resulting in Tlymphocyte proliferation (5, 6). Whilethe role ofIL-2/IL-2-Rinteractionin drivingTlymphocytesintothecellcycle is well established, the factors that controlthemagnitude andduration ofTlymphocyteproliferation in responseto antigenareless well understood. Earlyevi-dencefavoredtheviewthatIL-2availability wasthesole regulatorofTlymphocyteproliferation(1, 4). Later studieson thekinetics ofIL-2-R expression revealedthatIL-2-Rswere onlytransientlyexpressed on activated Tlymphocytesandthat thelevel ofcell surface IL-2-Rs declined as afunction of time after activation (7, 8). Thisevidencesuggestedasecondsite ofhormonalcontrolofTlymphocyteprolifer-ation, i.e., levelofexpression ofthehormone(IL-2) receptor. Accordingly, antigenwouldthenservetotriggerTlymphocyteexpansionbyengagingtheTCRonquies-centTlymphocytesandthereby stimulateaburst ofIL-2-Rexpression. Morere-cently,athirdpossiblesitefortheregulationofTlymphocyteproliferationhasbeensuggested from ourobservations onthe timecourse ofhighaffinity IL-2-Rexpres-sion in antigen-regulatedmurineTlymphocyte clones. ThisanalysisrevealedthatTlymphocytesthathaveundergoneacycleofantigen-drivenproliferation(6-10 di-visions)were refractoryto the proliferative stimulusofIL-2 in spite ofhigh levelsofhighaffinity IL-2-Rs(9). Thehigh affinity IL-2-Rsonthesequiescent refractoryTlymphocytesarefunctionalbyseveralcriteria, e.g., internalization ofIL-2/1L-2-Rcomplexes,upregulation ofexpression ofthe IL-2-Rp55gene, andproteinexpres-sion. Engagement oftheTlymphocyte antigen receptoronthesequiescentTlym-phocytesrapidlyrenderedthecells sensitiveto theproliferative stimulus ofIL-2 (9,10). Thesefindingsimpliedthat an intracellularregulator(orfamilyofregulators)
T Cell Receptor Speciﬁcity Is Critical for the Development of Epidermal (cid:2)(cid:3) T Cells

A particular feature of (cid:2)(cid:3) T cell biology is that cells expressing T cell receptor (TCR) using specific V (cid:2) /V (cid:3) segments are localized in distinct epithelial sites, e.g., in mouse epidermis nearly all (cid:2)(cid:3) T cells express V (cid:2) 3/V (cid:3) 1. These cells, referred to as dendritic epidermal T cells (DETC) originate from fetal V (cid:2) 3 (cid:4) thymocytes. The role of (cid:2)(cid:3) TCR specificity in DETC’s migration/ localization to the skin has remained controversial. To address this issue we have generated transgenic (Tg) mice expressing a TCR (cid:3) chain (V (cid:3) 6.3-D (cid:3) 1-D (cid:3) 2-J (cid:3) 1-C (cid:3) ), which can pair with V (cid:2) 3 in fetal thymocytes but is not normally expressed by DETC. In wild-type (wt) V (cid:3) 6.3Tg mice DETC were present and virtually all of them express V (cid:3) 6.3. However, DETC were absent in TCR- (cid:3) (cid:5) / (cid:5) V (cid:3) 6.3Tg mice, despite the fact that V (cid:3) 6.3Tg (cid:2)(cid:3) T cells were present in normal numbers in other lymphoid and nonlymphoid tissues. In wt V (cid:3) 6.3Tg mice, a high proportion of in-frame V (cid:3) 1 transcripts were found in DETC, suggesting that the expression of an endogenous TCR- (cid:3) (most probably V (cid:3) 1) was required for the development of V (cid:3) 6.3 (cid:4) epidermal (cid:2)(cid:3) T cells. Collectively our data demonstrate that TCR specificity is essential for the development of (cid:2)(cid:3) T cells in the epidermis. Moreover, they show that the TCR- (cid:3) locus is not allelically excluded. We show These suggest that for Our results are in the allelic
Alternativas en el manejo del riesgo de demanda en concesiones de infraestructura vial

In road concessions – where the effort of the concessionaire cannot increase the demand for infrastructure – it is better not to allocate risk of demand into the concessionaire. Engel et. al. (1997) introduced variable term concessions in order to mitigate risk of demand allocated to the concessionaire. In this paper we introduce variable investment concessions to achieve the same target. We show that both mechanisms are equivalent in their objective of mitigate risk of demand, although the mechanism proposed is more difficult to be implemented. We compare the application of both mechanism in the case of Uruguay.
Temperature variability in the Gulf of California during the last century: A record of the recent strong El Niño

The oxygen isotopic ratio of diatom silica from a box core collected on the eastern slope of the Guaymas Basin (Gulf of California) has been analyzed. This core covers the last 90 years. The isotopic record indicates a progressive and continuous temperature increase of about 8°C from the end of the last century until 1980 with superimposed, rapid temperature fluctuations of 2 to 4°C. Although the Gulf of California is not directly under the influence of El Nino, short temperature increases may be associated with the El Nino events described by Quinn et al. (1987). The longer term changes are attributed to a decrease of upwelling intensity linked to weakening of the trade winds in the Northern Hemisphere.
Spatio-temporal patterns of hydrological processes and their responses to human activities in the Poyang Lake basin, China

Abstract Poyang Lake is the largest freshwater lake in China, and plays a major role in flood mitigation, restoration and conservation of the ecological environment in the middle Yangtze River basin. Sediment load and streamflow variations in Poyang Lake basin are important for the scouring and deposition changes of this lake. However, these hydrological processes are heavily influenced by human activities, such as construction of water reservoirs, and land-use/land cover changes. By thorough analysis of long series of sediment and streamflow obtained from five major hydrological stations, we systematically investigated the spatial and temporal patterns of these hydrological processes and the hydrological responses to human activities using the Mann-Kendall trend test, the double cumulative mass curve and the linear regression method. The results show: (1) no significant change in streamflow followed by an increasing tendency after the 1990s that turns to be decreasing about 2000; and (2) a sharp increase of sediment load during the late 1960s and 1970s triggered by extensive deforestation (during the “Cultural Revolution” in China) followed by a tendency to decrease after the early 1980s. Construction of water reservoirs has greatly reduced the sediment load of the Poyang Lake basin, and this is particularly the case in the Ganjiang River, where the sediment load changes may be attributed to the trapping effects of the Wan'an Reservoir, the largest water reservoir within the Poyang Lake basin. There is no evidence to corroborate the influence of water reservoirs on the streamflow variations. It seems that the streamflow variations are subject mainly to precipitation changes, but this requires further analysis. The current study may be of scientific and practical benefit in the conservation and restoration of Poyang Lake, as a kind of wetland, and also in flood mitigation in the middle Yangtze River basin that is under the influence of human activities. Citation Zhang, Q. , Sun, P., Jiang, T. & Chen, X. -H. (2011) Spatio-temporal patterns of hydrological processes and their hydrological responses to human activities in the Poyang Lake basin, China. Hydrol. Sci. J. 56(2), 305–318.
Differential Membrane Localization and Intermolecular Associations of ␣ -dystrobrevin Isoforms in Skeletal Muscle

␣-Dystrobrevin is both a dystrophin homo-logue and a component of the dystrophin protein complex. Alternative splicing yields five forms, of which two predominate in skeletal muscle: full-length ␣-dys-trobrevin-1 (84 kD), and COOH-terminal truncated ␣-dystrobrevin-2 (65 kD). Using isoform-specific anti-bodies, we find that ␣-dystrobrevin-2 is localized on the sarcolemma and at the neuromuscular synapse, where, like dystrophin, it is most concentrated in the depths of the postjunctional folds. ␣-Dystrobrevin-2 preferentially copurifies with dystrophin from muscle extracts. In contrast, ␣-dystrobrevin-1 is more highly restricted to the synapse, like the dystrophin homologue utro-phin, and preferentially copurifies with utrophin. In yeast two-hybrid experiments and coimmunoprecipita-tion of in vitro–translated proteins, ␣-dystrobrevin-2 binds dystrophin, whereas ␣-dystrobrevin-1 binds both dystrophin and utrophin. ␣-Dystrobrevin-2 was lost from the nonsynaptic sarcolemma of dystrophin-deficient mdx mice, but was retained on the perisynaptic sarcolemma even in mice lacking both utrophin and dystrophin. In contrast, ␣-dystrobrevin-1 remained syn-aptically localized in mdx and utrophin-negative muscle , but was absent in double mutants. Thus, the distinct distributions of ␣-dystrobrevin-1 and-2 can be partly explained by specific associations with utrophin and dystrophin, but other factors are also involved. These results show that alternative splicing confers distinct properties of association on the ␣-dystrobrevins. M utations that disrupt the expression or function of dystrophin cause Duchenne muscular dystro-phy, a myopathy that leads to muscle cell degen-eration (3, 34). Dystrophin is a large, 427-kD protein composed of an NH 2-terminal actin-binding domain (33), a series of spectrin-like repeats, and a cysteine-rich (CR) 1 region, and a COOH-terminal (CT) domain, both of which contain sites for interaction with other proteins (3). Association between dystrophin and ␤-dystroglycan, a transmembrane protein, provides a link to the extracellu-lar ␣-dystroglycan, which in turn binds laminin and agrin (for review see reference 33). Thus, one function of the dystrophin complex is to link the extracellular matrix to cortical actin. A group of four proteins, the sarcoglycans, are also part of the dystrophin complex. Although the function of the sarcoglycans are unknown, they are altered in several of the limb girdle muscular dystrophies in which dystrophin is found to be normal (40, 42). Other proteins in the complex include dystrobrevin and the syntrophins (25, 28, 29, 36). Dystrophin is expressed at highest levels in skeletal muscle, where it may serve to stabilize the sarcolemma during cycles of muscle contraction and relaxation. In addition to this structural role, however, the dystrophin complex may also be involved …
Calibration of rainfall runoff models in ungauged catchments: Regionalization relationships for a rainfall runoff model

In many regions where rainfall runoff models are required, there is a lack of streamflow data available to calibrate the model parameters. Along with streamflow data simply not being recorded, there are many reasons for a lack of a suitable data set for model calibration, such as significant modifications to catchment characteristics, or long periods of unseasonable rainfall producing unrepresentative relationships. Generally, for an ungauged catchment, it is desirable to implement a model with as few free parameters as possible, provided the conceptualization of the model is suitable for the catchment under consideration. The Australian Water Balance Model (AWBM) is a rainfall runoff model that is commonly used in Australia. Typically it has 7 parameters, however methods are available to determine the storage size and capacity parameters for the AWBM based on an estimate of the average annual runoff. This is a great advantage when applying the model to ungauged catchments. However, there are two AWBM parameters which cannot be determined by this approach, namely the baseflow index and baseflow recession constant. The aim of this paper is to develop regionalization relationships to allow these two parameters to be estimated for ungauged catchments, based on the characteristics of the catchment that can be easily identified. General Regression Neural Networks are used to identify the relationships between model parameters and catchment characteristics. The results indicate that by using only easily identifiable characteristics of an ungauged catchment, suitable estimates of the unknown AWBM parameter values can be obtained, thereby allowing reasonable rainfall-runoff models to be developed. While the relationships developed in this work are specific to Australian catchments, the methodology used can be easily adapted to develop relationships for other regions.
Activation of trace amine-associated receptor 1 (TAAR1) reduces alcohol drinking behaviors in mice

Rationale: Trace amine-associated receptor 1 (TAAR1) is an important modulator of dopaminergic neurotransmission and has been recognized as a potential therapeutic target for alcoholism treatment. The interaction of alcohol with the dopamine reward system in the brain may promote the development of alcohol abuse. Objectives: The aim of the study was to evaluate the role of TAAR1 receptor stimulation on alcohol drinking behaviors in mice. Methods: We investigated the blood-brain barrier (BBB) penetration of the RO5256390 in mice by mass spectrometry. Then, wild-type (WT) mice were housed in an automatic behavioral system, IntelliCage, and habituated to drinking alcohol. The animals were further administrated either with RO526390 (10 mg/kg, intraperitoneally) or vehicle and studied on alcohol consumption, alcohol consumption after abstinence, and motivation to drink alcohol. Results: We found that RO5256390 highly penetrated the BBB. R05256390 administration also transiently reduced alcohol consumption and alcohol consumption after abstinence in mice with a high preference for alcohol in comparison to high-drinking mice from the vehicle group. Furthermore, RO5256390 attenuated the motivation for drinking alcohol. Conclusions: Our data suggest that activation of Taar1 reduces alcohol drinking behavior in mice. The experiments were carried out on adult 8-week C57Bl/6 female mice (n=43), bred at The study used female mice to eliminate aggressive and leadership behaviors. Animals were housed in 3 IntelliCage either 15 or 13 mice per cage, in rooms with a controlled temperature of 22 o C under a 12/12 h light-dark cycle. Before caging, mice were anesthetized with isoflurane and were implanted with RFID transponders (8.5 mm in length and 1.4 mm in diameter). Mice were weighed three times during the study. After behavioral studies, mice were sacrificed by decapitation under isoflurane anesthesia. All procedures were performed following the Animal Protection Act in Poland, Directive 2010/63/EU, and were approved by the Local Ethics
The Soil Freezing Characteristic: Its Measurement and Similarity to the Soil Moisture Characteristic

A soil freezing characteristic (SFC) represents the relationship between the quantity and the energy status of liquid water in frozen soil. The SFC is the analogue to the soil moisture characteristic (SMC) and is essential to modeling the transport of water, heat, and solutes in frozen soil. This paper presents a new, automated technique to measure an SFC in situ, for which there has previously been no method. Liquid water content in frozen soil was measured with time domain reflectometry. The corresponding energy status was inferred from accurate soil temperature measurements with a generalized form of the Clapeyron equation. Since both SFC and SMC describe water retention properties in soil, their similarity was investigated. The SMC and SFC agreed to within 1% moisture content across a wide range of matric potentials. Determination of the SMC is reliable at high matric potentials but becomes increasingly inaccurate and time consuming as soil dries. By contrast, the SFC determination becomes more accurate and rapid at lower matric potentials. We thus propose that water retention properties at high matric potentials are best obtained from draining and at low matric potentials from freezing.
Survival Prediction By Baseline Systemic Immune-In�ammation Index And Its Changes During First-Line Platinum-Based Treatment In A Caucasian Population Of Patients With Metastatic Urothelial Carcinoma

Background: Systemic immune-in�ammation index (SII) predicts survival in patients with various malignancies. This study explores the prognostic value of SII in metastatic urothelial carcinoma (MUC) subjects. Methods: We evaluated 181 consecutive MUC (148 bladder, 27 upper tract) patients (135 men) treated with �rst-line platinum-based therapy. Karnofsky performance status <80% and visceral metastasis were present in 18.2% and 46.4%, respectively. SII was based on platelet x neutrophil/lymphocyte counts. Study population was dichotomized by median into high SII and low SII groups before the initiation of chemotherapy (median 1326) and at week 6 (median 705). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared with log-rank test. Results: At median follow-up of 9.6 months (range 1.7-191.1 months), 174 patients (96.1%) experienced disease progression and 173 (95.6%) died. Subjects with low SII at baseline and at week 6 had signi�cantly better PFS (HR 0.58; P = 0.0002 and HR 0.55; P < 0.0001) and OS (HR 0.54; P < 0.0001 and HR 0.54; P < 0.0001) compared to patients with high SII. Independent prognostic value of SII was con�rmed in a multivariate analysis. Patients with low SII at baseline and at week 6 had signi�cantly better PFS and OS compared to patients with high SII at both timepoints (P < 0.0001). Conclusion: High SII before chemotherapy that persists at week 6 negatively affects survival. SII at baseline can be used in strati�cation of patients within clinical trials and in clinical practice.
The healthy Nordic diet and Mediterranean diet and incidence of disability 10 years later in 1 home-dwelling old adults 2 3

47 Background/Objective: Diet has a major impact on a person’s health. However, limited 48 information exists on the long-term role of the whole diet on disability. We investigated the 49 association of the healthy Nordic diet and the Mediterranean diet with incident disability 10 years 50 later. 51 Design: Longitudinal, with a follow-up of 10 years. 52 Settings/Participants: A total of 962 home-dwelling men and women from the Helsinki Birth 53 Cohort Study, mean age 61.6 y, who were free of disability at baseline. 54 Measurements: At baseline, 2001-2004, the Nordic diet score (NDS) and modified Mediterranean 55 diet score (mMDS) were calculated using a validated 128-item food-frequency questionnaire. 56 Higher scores indicated better adherence to the diet. Participants’ incident disability was assessed 57 during 2011-2013 by a self-reported questionnaire and was based on mobility limitations and 58 difficulties to perform self-care activities. Analyses were performed using logistic regression and 59 adjusted for potential confounding factors. 60 Results: In total, 94 participants (9.8%) developed mobility limitations and 45 participants (4.7%) 61 developed difficulties in self-care activities during 10 year follow-up. The likelihood of having 62 mobility limitations (odds ratio (OR) 0.42, 95% confidence interval (CI) 0.22–0.80) and difficulties 63 in self-care activities (OR 0.38, 95% CI 0.15–0.94) were lower among those in the highest NDS 64 tertile than among those in the lowest NDS tertile. Greater mMDS was associated with a lower 65 disability incidence; however, the association was not statistically significant. 66 Conclusions/Implications: Adherence to the healthy Nordic diet predicts 10-year incidence of 67 mobility limitations and difficulties to perform self-care activities in old age and may thus be 68 protective against disability in Nordic population. 69