Miracle-dz/UniFAR-FTUs huggingface dataset:
with Human and Bovine Type II Collagen (DRB1*0401) Transgenic Mice by Immunization Induction of Autoimmune Arthritis in HLA-DR4

Although associations between the expression of particular HLA genes and the susceptibility to speciﬁc autoimmune diseases has been known for some time, the role that these HLA molecules play in the autoimmune response is unclear. Through the estab-lishment of a chimeric HLA-DR/I-E transgene, we have examined the function of the rheumatoid arthritis (RA) susceptibility allele HLA-DR4 (DRB1*0401) in presenting antigenic peptides derived from the model Ag, type II collagen (CII), and in mediating an autoimmune response. As a transgene, the chimeric DR4 molecule conferred susceptibility to an autoimmune arthritis induced by immunization with human CII or bovine CII. These mice developed an inﬂammatory, autoimmune arthritis that was similar both histologically and in severity to that previously described for the collagen-induced arthritis model. The DR4-mediated autoimmune arthritis was accompanied by T cell and B cell responses to both the immunogen and the autoantigen, murine CII. The DR4-restricted T cell response to human CII was focused on an immunodominant determinant within CII263–270 and a minor determinant within CII286–300, the same CII determinants recently identiﬁed for yet another RA susceptibility allele, HLA-DR1 (DRB1*0101). Thus these data demonstrate that, like HLA-DR1, HLA-DR4 is capable of binding peptides derived from human CII and therefore probably plays a role in the autoimmune response to human CII observed in RA patients.
Inflammation in Rats Aggravate Temporomandibular Joint Activation through Cadherin-11 To Estradiol Promotes M1-like Macrophage

Macrophages play a major role in joint inﬂammation. Estrogen is involved in rheumatoid arthritis and temporomandibular disorders. However, the underlying mechanism is still unclear. This study was done to verify and test how estrogen affects M1/M2-like macrophage polarization and then contributes to joint inﬂammation. Female rats were ovariectomized and treated with increasing doses of 17 b -estradiol for 10 d and then intra-articularly injected with CFA to induce temporomandibular joint (TMJ) inﬂammation. The polarization of macrophages and expression of cadherin-11 was evaluated at 24 h after the induction of TMJ inﬂammation and after blocking cadherin-11 or estrogen receptors. NR8383 macrophages were treated with estradiol and TNF- a , with or without blocking cadherin-11 or estrogen receptors, to evaluate the expression of the M1/M2-like macrophage-associated genes. We found that estradiol increased the inﬁltration of macrophages with a proinﬂammatory M1-like predominant proﬁle in the synovium of inﬂamed TMJ. In addition, estradiol dose-dependently upregulated the expressions of the M1-associated proinﬂammatory factor inducible NO synthase (iNOS) but repressed the expressions of the M2-associated genes IL-10 and arginase in NR8383 macrophages. Furthermore, estradiol mainly promoted cadherin-11 expression in M1-like macrophages of inﬂamed TMJ. By contrast, blockage of cadherin-11 concurrently reversed estradiol-potentiated M1-like macrophage activation and TMJ inﬂammation, as well as reversed TNF- a –induced induction of inducible NO synthase and NO in NR8383 macrophages. The blocking of estrogen receptors reversed estradiol-potentiated M1-like macrophage activation and cadherin-11 expression. These results suggested that estradiol could promote M1-like macrophage activation through cadherin-11 to aggravate the acute inﬂammation of TMJs. The Journal of Immunology , 2015, 194: 000–000.
Is admittance to specialised palliative care among cancer patients related to sex, age and cancer diagnosis? A nation-wide study from the Danish Palliative Care Database to specialised among patients A study

Background: Specialised palliative care (SPC) takes place in specialised services for patients with complex symptoms and problems. Little is known about what determines the admission of patients to SPC and whether there are differences in relation to institution type. The aims of the study were to investigate whether cancer patients ’ admittance to SPC in Denmark varied in relation to sex, age and diagnosis, and whether the patterns differed by type of institution (hospital-based palliative care team/unit, hospice, or both). Methods: This was a register-based study of adult patients living in Denmark who died from cancer in 2010 – 2012. Data sources were the Danish Palliative Care Database, Danish Register of Causes of Death and Danish Cancer Registry. The associations between the explanatory variables (sex, age, diagnosis) and admittance to SPC were investigated using logistic regression. Results: In the study population ( N = 44,548) the overall admittance proportion to SPC was 37%. Higher odds of overall admittance to SPC were found for women (OR = 1.23; 1.17 – 1.28), younger patients (<40 compared with 80+ years old) (OR = 6.44; 5.19 – 7.99) and patients with sarcoma, pancreatic and stomach cancers, whereas the lowest were for patients with haematological malignancies. The higher admission found for women was most pronounced for hospices compared to hospital-based palliative care teams/units, whereas higher admission of younger patients was more pronounced for hospital-based palliative care teams/units. Patients with brain cancer were more often admitted to hospices, whereas patients with prostate cancer were more often admitted to hospital-based palliative care teams/units. Conclusion: It is unlikely that the in to sex, and cancer diagnoses can be fully explained by differences in need. Future research should investigate whether the groups having the lowest admittance to SPC receive sufficient palliative care elsewhere.
Plant Disease Detection using Machine Learning Algorithm

: In various applications of the agricultural industry, computer methodologies have been used for automation. Timely farming decisions and disease management are taken using image analysis and machinery of learning techniques in planning and creating a method for the diagnosis of diseases. As human beings are still tracking crop disease, human visual vision is used for diagnosing plant disease. Machine learning and image processing methods are also ideally suited to this end. In this study, the processing of diseased pictures of plant leaf is taken into account. The work focuses on the identification and diagnosis of plant leaf diseases based on visual symptoms, anthracnose, and powdery mildew. Machine learning and image processing require many steps to identify and distinguish disease signs. Step one is the acquisition of images. In the second step, photographs from the UCI repository are pre-processed and segmented. After this method is segmented, the best functions dependent on mathematical data are derived further. Finally, separate classifiers are used for the full classification.
Membrane Proteases and Aminoglycoside Antibiotic Resistance (cid:1) †

We present genetic studies that help deﬁne the functional network underlying intrinsic aminoglycoside resistance in Pseudomonas aeruginosa . Our analysis shows that proteolysis, particularly that controlled by the membrane protease FtsH, is a major determinant of resistance. First, we examined the consequences of inactivating genes controlled by AmgRS, a two-component regulator required for intrinsic tobramycin resistance. Three of the gene products account for resistance: a modulator of FtsH protease (YccA), a membrane protease (HtpX), and a membrane protein of unknown function (PA5528). Second, we screened mutations inactivating 66 predicted proteases and related functions. Insertions inactivating two FtsH protease accessory factors (HﬂK and HﬂC) and a cytoplasmic protease (HslUV) increased tobramycin sensitivity. Finally, we generated an ftsH deletion mutation. The mutation dramatically increased aminoglycoside sensitivity. Many of the functions whose inactivation increased sensitivity appeared to act independently, since multiple mutations led to additive or synergistic effects. Up to 500-fold increases in tobramycin sensitivity were observed. Most of the mutations also were highly pleiotropic, increasing sensitivity to a membrane protein hybrid, several classes of antibiotics, alkaline pH, NaCl, and other compounds. We propose that the network of proteases provides robust protection from aminoglycosides and other substances through the elimination of membrane-disruptive mistranslation products. The intrinsic antibiotic of no added salt. Construction of multiple mutants. Mutants carrying multiple transposon in- sertions were generated using a technique analogous to that described previously for Francisella novicida (10). Transposon insertions (IS phoA /hah and IS lacZ / hah) were converted into 189-bp insertions by Cre recombination at loxP sequences at the ends of the transposons (2). This recombination eliminates the tetracycline resistance markers carried on the transposons and makes it possible to introduce additional mutations by recombination following transformation with chromosomal DNA. The process was used to generate double, triple, and quadruple mutants. For Cre recombination at loxP sites, a plasmid encoding Cre recombinase (pCre1) was introduced into PAO1 transposon mutants by conjugation with E. coli SM10 (cid:4) pir (2). Exconjugates were screened for the loss of the IS phoA /hah and IS lacZ /hah tetracycline resistance genes. the appropriate recombina-*
HOW TO PROMOTE COOPERA TION WITHIN CONFLICTING AND DIVIDED SOCIETIES ? Some thoughts about the transformation of industrial relations in Europe

The paper tries to explain why and how can be triggered the transition from one adversarial labour regime to a more cooperative one, since such a change does not seem self-fulfilling. First, a survey of the interpretations by game theory of the emergence of cooperation among capitalists and workers is provided, considering bath coordination games and prisoner dilemma problems. Second, a taxonomy for the various methods for overcoming the hysteresis of prevailing social norms is provided. Third, these methods are checked against the empirical evidence concerning the European countries now experiencing cooperation and a minimum trust. A major concern for future, multiple interactions and intertemporal bargaining, reciprocity more than altruism are shawn to be important and the se features often need to be embedded into a coherent set of institutions. COMMENT FAVORISER LA COOPERATION DANS DES SOCIETES CONFLICTUELLES? Quelques réflexions sur la transformation des relations professionnelles en Europe Robert BaYER
Comparison of Mentors’ and Mentees’ Perceptions of Mentees’ Research Skill Gains at The Citadel

Dr. Kathy Zanin is an Associate Professor of Immunology, Cell, and Developmental Biology. Her current research interest is exploring histone proteins in the mitochondria. She has also developed a hypothesis for a cure for HIV infection. Dr. Zanin is active in promoting stronger pre-college education in the STEM fields and is a regular participant in activities sponsored by the Center for Excellence and Innovation in Teaching. She was the 2009 recipient of The Citadel’s Clinton A. Medbery Award for Dedication in Teaching, the 2018 recipient of the School of Science and Math’s Early Career Faculty Award, and the 2018 recipient of the Citadel Faculty Excellence in Service Award. She is also the Pre-Health Advisor, the administrator of the Pre-Health Mentorship Program, and she serves on the Online Education Advisory Board.
Edinburgh Explorer Epigenetic measures of ageing predict prevalence and incidence of leading causes of death and disease burden

Background: Individuals of the same chronological age display different rates of biological ageing. A number of measures of biological age have been proposed which harness age-related changes in DNA methylation profiles. These measures include five ‘ epigenetic clocks ’ which provide an index of how much an individual ’ s biological age differs from their chronological age at the time of measurement. The five clocks encompass methylation-based predictors of chronological age (HorvathAge, HannumAge), all-cause mortality (DNAm PhenoAge, DNAm GrimAge) and telomere length (DNAm Telomere Length). A sixth epigenetic measure of ageing differs from these clocks in that it acts as a speedometer providing a single time-point measurement of the pace of an individual ’ s biological ageing. This measure of ageing is termed DunedinPoAm. In this study, we test the association between these six epigenetic measures of ageing and the prevalence and incidence of the leading causes of disease burden and mortality in high-income countries ( n ≤ 9537, Generation Scotland: Scottish Family Health Study). Results: DNAm GrimAge predicted incidence of clinically diagnosed chronic obstructive pulmonary disease (COPD), type 2 diabetes and ischemic heart disease after 13 years of follow-up (hazard ratios = 2.22, 1.52 and 1.41, respectively). DunedinPoAm predicted the incidence of COPD and lung cancer (hazard ratios = 2.02 and 1.45, respectively). DNAm PhenoAge predicted incidence of type 2 diabetes (hazard ratio = 1.54). DNAm Telomere Length associated with the incidence of ischemic heart disease (hazard ratio = 0.80). DNAm GrimAge associated with all-cause mortality, the prevalence of COPD and spirometry measures at the study baseline. These associations were present after adjusting for possible confounding risk factors including alcohol consumption, body mass index, deprivation, education and tobacco smoking and surpassed stringent Bonferroni-corrected significance thresholds. Conclusions: Our data suggest that epigenetic measures of ageing may have utility in clinical settings to complement gold-standard methods for disease assessment and management.
Magnetic Resonance Imaging Pro ﬁ le of Blood – Brain Barrier Injury in Patients With Acute Intracerebral Hemorrhage

Background- — Spontaneous intracerebral hemorrhage (ICH) is associated with blood – brain barrier (BBB) injury, which is a poorly understood factor in ICH pathogenesis, potentially contributing to edema formation and perihematomal tissue injury. We aimed to assess and quantify BBB permeability following human spontaneous ICH using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). We also investigated whether hematoma size or location affected the amount of BBB leakage. Methods and Results- — Twenty- ﬁ ve prospectively enrolled patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were examined using DCE MRI at 1 week after symptom onset. Contrast agent dynamics in the brain tissue and general tracer kinetic modeling were used to estimate the forward leakage rate (K trans ) in regions of interest (ROI) in and surrounding the hematoma and in contralateral mirror – image locations (control ROI). In all patients BBB permeability was signi ﬁ cantly increased in the brain tissue immediately adjacent to the hematoma, that is, the hematoma rim, compared to the contralateral mirror ROI ( P < 0.0001). Large hematomas ( > 30 mL) had higher K trans values than small hematomas ( P < 0.005). K trans values of lobar hemorrhages were signi ﬁ cantly higher than the K trans values of deep hemorrhages ( P < 0.005), independent of hematoma volume. Higher K trans values were associated with larger edema volumes. Conclusions- — BBB leakage in the brain tissue immediately bordering the hematoma can be measured and quanti ﬁ ed by DCE MRI in human ICH. BBB leakage at 1 week is greater in larger hematomas as well as in hematomas in lobar locations and is associated with larger edema volumes. ( J Am Heart Assoc. 2013;2:e000161 doi: 10.1161/JAHA.113.000161)
Inhibition of plasminogen activation by apolipoprotein(a): Role of carboxyl-terminal lysines and identification of inhibitory domains in apolipoprotein(a)

lipoprotein(a), exhibits sequence similarity to plasminogen and can inhibit binding of plasminogen to cell surfaces. Plasmin generated on the surface of vascular cells plays a role in cell migration and proliferation, two of the fibroproliferative inflammatory events that underlie atherosclerosis. The ability of apo(a) to inhibit pericellular plasminogen activation on vascular cells was therefore evaluated. Two isoforms of apo(a), 12K and 17K, were found to significantly decrease tPA-mediated plasminogen activation on HUVECs and THP-1 monocytes and macrophages. Lp(a) purified from human plasma decreased plasminogen activation on THP-1 monocytes and HUVECs but not on THP-1 macrophages. Removal of kringle V or the strong lysine binding site in kringle IV 10 completely abolished the inhibitory effect of apo(a). Treatment with carboxypeptidase B (CpB) to assess the roles of carboxyl-terminal lysines in cellular receptors lead in most cases to decreases in plasminogen activation as well as plasminogen and apo(a) binding; inhibition of plasminogen activation by apo(a) was unaffected, however. Our findings directly demonstrate that apo(a) inhibits pericellular plasminogen activation in all three cell types, although binding of apo(a) to cell-surface receptors containing carboxyl-terminal lysines does not appear to play a major role in the inhibition mechanism. The construction and expression in human embryonic kidney (HEK293) cells of the r-apo(a) variants utilized in this study (KIV 5-8 , 12K, 12ΔV, 17K, 17KΔLBS 10 , and 17KΔV) has been previously described (17,33,34,45-48). Variants were purified from conditioned medium, harvested from stably-expressing cell lines, using lysine-Sepharose affinity chromatography as previously described (17,33,34,45-48). Protein concentrations were determined spectrophotometrically (17,33,34,45-48) and assessed for purity by SDS-PAGE under non-reduced and reduced conditions followed by silver staining.
Staged anticonvulsant screening for chronic epilepsy The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters

Objective : Current anticonvulsant screening programs are based on seizures evoked in normal animals. One-third of epileptic patients do not respond to the anticonvulsants discovered with these models. We evaluated a tiered program based on chronic epilepsy and spontaneous seizures, with compounds advancing from high-throughput in vitro models to low-throughput in vivo models. Methods : Epileptogenesis in organotypic hippocampal slice cultures was quantiﬁed by lactate production and lactate dehydrogenase release into culture media as rapid assays for seizure-like activity and cell death, respectively. Compounds that reduced these biochemical measures were retested with in vitro electrophysiological conﬁrmation (i.e., second stage). The third stage involved crossover testing in the kainate model of chronic epilepsy, with blinded analysis of spontaneous seizures after continuous electrographic recordings. Results : We screened 407 compound-concentration combinations. The cyclooxygenase inhibitor, celecoxib, had no effect on seizures evoked in normal brain tissue but demonstrated robust antiseizure activity in all tested models of chronic epilepsy. Interpretation : The use of organotypic hippocampal cultures, where epileptogenesis occurs on a compressed time scale, and where seizure-like activity and seizure-induced cell death can be easily quantiﬁed with biomarker assays, allowed us to circumvent the throughput limitations of in vivo chronic epilepsy models. Ability to rapidly screen compounds in a chronic model of epilepsy allowed us to ﬁnd an anticonvulsant that would be missed by screening in acute models.
Modelling the Marine Microplastic Distribution from Municipal Wastewater in Saronikos Gulf (E. Mediterranean)

A three-dimensional hydrodynamic model is coupled with a Lagrangian-Individual Based Model to simulate the floating microplastics (<300μm) dispersal and transport in the Saronikos Gulf. Considering municipal wastewaters as their main source, simulations were carried out over 2011–2012. A comparison with hydrodynamic observational data has shown that the model qualitatively reproduces the main circulation structure and hydrodynamic features. To explore the fate and distribution of microplastics, model results were analyzed taking into account the seasonal variability of near-surface circulation. Simulation results gave a qualitative description of affected areas from microplastics pollution, suggesting that the most affected part of Saronikos Gulf is the coastal area that extends from Psitallia Waste water treatment plant to the east. Despite some limitations, this is a first model attempt to explore the dispersal and distribution of microplastics in the Saronikos Gulf. Abbrevations: A more quantitative validation of the simulated near-surface circulation can be obtained comparing the model simulated SSH pattern with satellite altimetry data, given that low/high SSH areas represent cyclonic/anticyclonic flows. Our results show that the model captures quite well the observed SSH pattern Figure although a model deviation from the observed values was produced. the Mediterranean basin scale SSH variability, differences between simulated and observed absolute values expected. anticyclonic
Adverse Consequences of High Sympathetic Nervous Activity in the Failing Human Heart

Objectives. In view of previous experimental evidence relating sympathetic nervous overactivity in the heart to myocardial necrosis and ventricular arrhythmias, we prospectively examined the hypothesis that heightened cardiac sympathetic nervous activity is associated with an adverse outcome in patients with moderate to severe heart failure. Background. Despite recent therapeutic advances, patients with heart failure continue to have high mortality from progressive hemodynamic decompensation and lethal ventricular arrhythmias. It is believed that initially compensatory increases in sympathetic nervous system activity may ultimately be maladaptive, potentially contributing to subsequent adverse events. Methods. Sixty patients with moderate to severe heart failure (left ventricular ejection fraction 18.9 -+ 0.9% [mean _+ SE]) were studied prospectively. In addition to the compilation of a bemodynamic, biochemical and electrocardiographic profile for each patient, whole-body and cardiac sympathetic activity were determined by isotope dilution. The relation of these variables to outcome was determined by Cox proportional hazards analysis. Results. The mean follow-up period of the study group was 7 --1 months (range 1 to 24) with a 12-month actuarial survival of 75%. Deaths (14 in all) were accounted for either by sudden death or progressive heart failure in equal numbers. The rate of release of norepinephrine from the heart was significantly higher in patients with heart failure than in healthy subjects (402 "¢37 vs. 105 -+ 19 pmol/min, p < 0.01), although the values for heart failure ranged widely from normal to 10 times normal. By univariate Cox proportional hazards analysis, pulmonary capil. lary wedge pressure (p < 0.01), mean pulmonary artery pressure (p < 0.001), serum sodium levels (p < 0.01) and cardiac norepi. nephrine spill-over rate (p < 0.001) were identified as significant prognostic markers. In a multivariate analysis, cardiac norepinephrine spillover rate was identified as the most powerful prognostic marker (p = 0.0006) of those evaluated in this study, Conclusions. These results suggest that activation of the sympathetic nervous system in patients with heart failure, specifically the cardiac sympathetic nerves, may contribute to the poor prognosis associated with severe heart failure. The data therefore provide a rationale for the use of drugs such as beta-adrenergic blocking agents in the management of patients with heart failure. (J Am Coil Cardiol 1995;26:1257-63)