Miracle-dz/UniFAR-FTUs huggingface dataset:
From TGN 1412 to TAB 08 : the return of CD 28 superagonist therapy to clinical development for the treatment of rheumatoid arthritis

1TheraMAB LLC, Würzburg, Germany, and Moscow, Russia; 2Institute for Virology and Immunobiology, University of Würzburg, Germany Dmitry Tyrsin, PhD Sergey Chuvpilo, PhD Alexey Matskevich, PhD Daniil Nemenov, MD Paula S. Römer, PhD Paula Tabares, PhD Thomas Hünig, PhD Please address correspondence to: Thomas Hünig, Institute for Virology and Immunobiology, University of Würzburg, Versbacher str. 7, 97078 Würzburg, Germany. E-mail: huenig@vim.uni-wuerzburg.de Received and accepted on June 30, 2016. Clin Exp Rheumatol 2016; 34 (Suppl. 98): S45-S48. © Copyright CliniCal and ExpErimEntal rhEumatology 2016.
Xpo7 is a broad-spectrum exportin and a nuclear import receptor

Exportins bind cargo molecules in a RanGTP-dependent manner inside nuclei and transport them through nuclear pores to the cytoplasm. CRM1/Xpo1 is the best-characterized exportin because specific inhibitors such as leptomycin B allow straightforward cargo validations in vivo. The analysis of other exportins lagged far behind, foremost because no such inhibitors had been available for them. In this study, we explored the cargo spectrum of exportin 7/Xpo7 in depth and identified not only ∼200 potential export cargoes but also, surprisingly, ∼30 nuclear import substrates. Moreover, we developed anti-Xpo7 nanobodies that acutely block Xpo7 function when transfected into cultured cells. The inhibition is pathway specific, mislocalizes export cargoes of Xpo7 to the nucleus and import substrates to the cytoplasm, and allowed validation of numerous tested cargo candidates. This establishes Xpo7 as a broad-spectrum bidirectional transporter and paves the way for a much deeper analysis of exportin and importin function in the future.
Visual processing as a potential endophenotype in youths with attention‐deficit/hyperactivity disorder: A sibling study design using the counting Stroop functional MRI

Deficits in inhibitory control and visual processing are common in youths with attention‐deficit/hyperactivity disorder (ADHD), but little is known about endophenotypes for unaffected siblings of youths with ADHD. This study aimed to investigate the potential endophenotypes of brain activation and performance in inhibitory control and visual processing among ADHD probands, their unaffected siblings, and neurotypical youths. We assessed 27 ADHD probands, 27 unaffected siblings, and 27 age‐, gender‐, and IQ‐matched neurotypical youths using the counting Stroop functional magnetic resonance imaging and two tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): rapid visual information processing (RVP) for inhibitory control and spatial span (SSP) for visual processing. ADHD probands showed greater activation than their unaffected siblings and neurotypical youths in the right inferior frontal gyrus (IFG) and anterior cingulate cortex. Increased activation in the right IFG was positively correlated with the mean latency of the RVP in ADHD probands. Moreover, ADHD probands and their unaffected siblings showed less activation in the left superior parietal lobule (SPL) than neurotypical youths. Increased activation in the left SPL was positively correlated with the spatial length of the SSP in neurotypical youths. Our findings suggest that less activation in the left SPL might be considered as a candidate imaging endophenotype for visual processing in ADHD.
The Privacy Policymaking of State Attorneys General

Accounts of privacy law have focused on legislation, federal agencies, and the self-regulation of privacy professionals. Crucial agents of regulatory change, however, have been ignored: the state attorneys general. This article is the first in-depth study of the privacy norm entrepreneurship of state attorneys general. Because so little has been written about this phenomenon, I engaged with primary sources — first interviewing state attorneys general and current and former career staff, and then examining documentary evidence received through FOIA requests submitted to AG offices around the country. Much as Justice Louis Brandeis imagined states as laboratories of the law, offices of state attorneys general have been laboratories of privacy enforcement. State attorneys general have been nimble privacy enforcement pioneers where federal agencies have been more conservative or constrained by politics. Their local knowledge, specialization, multi-state coordination, and broad legal authority have allowed them to experiment in ways that federal agencies cannot. These characteristics have enabled them to establish baseline fair information protections; expand the frontiers of privacy law to cover sexual intimacy and youth; and pursue enforcement actions that have harmonized privacy policy. Although certain systemic practices enhance AG privacy policy making, others blunt its impact, including an over reliance on informal agreements that lack law’s influence and a reluctance to issue closing letters identifying data practices that comply with the law. This article offers ways state attorneys general can function more effectively through informal and formal proceedings. It addresses concerns about the potential pile-up of enforcement activity, federal preemption, and the dormant Commerce Clause. It urges state enforcers to act more boldly in the face of certain shadowy data practices.
Genetic Patterns of Common-Bean Seed Acquisition and Early-Stage Adoption Among Farmer Groups in Western Uganda

Widespread adoption of new varieties can be valuable, especially where improved agricultural production technologies are hard to access. However, as farmers adopt new varieties, in situ population structure and genetic diversity of their seed holdings can change drastically. Consequences of adoption are still poorly understood due to a lack of crop genetic diversity assessments and detailed surveys of farmers' seed management practices. Common bean (Phaseolus vulgaris) is an excellent model for these types of studies, as it has a long history of cultivation among smallholder farmers, exhibits eco-geographic patterns of diversity (e.g., Andean vs. Mesoamerican gene-pools), and has been subjected to post-Columbian dispersal and recent introduction of improved cultivars. The Hoima district of western Uganda additionally provides an excellent social setting for evaluating consequences of adoption because access to improved varieties has varied across farmer groups in this production region. This study establishes a baseline understanding of the common bean diversity found among household producers in Uganda and compares the crop population structure, diversity and consequences of adoption of household producers with different adoption practices. Molecular diversity analysis, based on 4,955 single nucleotide polymorphism (SNP) markers, evaluated a total of 1,156 seed samples that included 196 household samples collected from household producers in the Hoima district, 19 breeder-selected varieties used in participatory breeding activities that had taken place prior to the study in the region, and a global bean germplasm collection. Households that had participated in regional participatory breeding efforts were more likely to adopt new varieties and, consequently, diversify their seed stocks than those that had not participated. Of the three farmer groups that participated in breeding efforts, households from the farmer group with the longest history of bean production were more likely to conserve “Seed Engufu”, a local “Calima”-type variety of the Andean bean gene pool, and, at the same time, introduce rare Mesoamerican gene pool varieties into household seed stocks.
Evaluation of a mixed beam therapy for postmastectomy breast cancer patients: Bolus electron conformal therapy combined with intensity modulated photon radiotherapy and volumetric modulated photon arc therapy

Purpose The purpose of this study was to assess the potential benefits and limitations of a mixed beam therapy, which combined bolus electron conformal therapy (BECT) with intensity modulated photon radiotherapy (IMRT) and volumetric modulated photon arc therapy (VMAT), for left‐sided postmastectomy breast cancer patients. Methods Mixed beam treatment plans were produced for nine postmastectomy radiotherapy (PMRT) patients previously treated at our clinic with VMAT alone. The mixed beam plans consisted of 40 Gy to the chest wall area using BECT, 40 Gy to the supraclavicular area using parallel opposed IMRT, and 10 Gy to the total planning target volume (PTV) by optimizing VMAT on top of the BECT + IMRT dose distribution. The treatment plans were created in a commercial treatment planning system (TPS), and all plans were evaluated based on PTV coverage, dose homogeneity index (DHI), conformity index (CI), dose to organs at risk (OARs), normal tissue complication probability (NTCP), and secondary cancer complication probability (SCCP). The standard VMAT alone planning technique was used as the reference for comparison. Results Both techniques produced clinically acceptable PMRT plans but with a few significant differences: VMAT showed significantly better CI (0.70 vs 0.53, P < 0.001) and DHI (0.12 vs 0.20, P < 0.001) over mixed beam therapy. For normal tissues, mixed beam therapy showed better OAR sparing and significantly reduced NTCP for cardiac mortality (0.23% vs 0.80%, P = 0.01) and SCCP for contralateral breast (1.7% vs 3.1% based on linear model, and 1.2% vs 1.9% based on linear‐exponential model, P < 0.001 in both cases), but showed significantly higher mean (50.8 Gy vs 49.3 Gy, P < 0.001) and maximum skin doses (59.7 Gy vs 53.3 Gy, P < 0.001) compared with VMAT. Patients with more tissue (minimum distance between the distal PTV surface and lung approximately > 0.5 cm and volume of tissue between the distal PTV surface and heart or lung approximately > 250 cm3) between distal PTV surface and lung may benefit the most from mixed beam therapy. Conclusion This work has demonstrated that mixed beam therapy (BECT + IMRT:VMAT = 4:1) produces clinically acceptable plans having reduced OAR doses and risks of side effects compared with VMAT. Even though VMAT alone produces more homogenous and conformal dose distributions, mixed beam therapy remains as a viable option for treating postmastectomy patients, possibly leading to reduced normal tissue complications.
Endocrine cells in pig ’ s gallbladder , ductus cysticus and ductus choledochus with special reference to ghrelin

184 Endocrine cells in pig’s gallbladder, ductus cysticus and ductus choledochus with special reference to ghrelin M.V. Gulubova , I.V. Valkova, K.V. Ivanova, I.G. Ganeva, D.K. Prangova, M.M. K. Ignatova, S.R. Vasilev, I.S. Stefanov 1 Department of General and Clinical Pathology,Medical Faculty, Trakia University,Stara Zagora, Bulgaria 2 Department of Anantomy,Medical Faculty, Trakia University,Stara Zagora, Bulgaria 3 Department of Physiology, Pathophysiology and Pharmacology,Medical Faculty, Trakia University, Stara Zagora, Bulgaria
Relationship Between Gratitude and Symptoms of Post-traumatic Stress Disorder Among Adolescents:Mediation of Social Support and Resilience

To examine the relationship between gratitude and symptoms of post-traumatic stress disorder(PTSD) and explore the mediated role of resilience and social support playing in that relation,by conducting an assessment 18 months after the disaster with a school-based sample of 1439 students who experienced the May 12th Wenchuan Earthquake.Results indicated that:(1) PTSD symptoms were significantly correlated to gratitude(r=-0.18,p0.001),social support(r=-0.17,p0.001) as well as resilience(r=-0.24,p0.001),and(2) gratitude not only had direct effect on PTSD symptoms,but also indirectly influenced PTSD symptoms.Significant partial mediation of resilience and social support on the association between gratitude and PTSD symptoms were revealed.
Application of a qPCR Assay in the Investigation of Susceptibility to Malaria Infection of the M and S Molecular Forms of An. gambiae s.s. in Cameroon

Plasmodium falciparum is the causative agent of malaria, a disease that kills almost one million persons each year, mainly in sub-Saharan Africa. P. falciparum is transmitted to the human host by the bite of an Anopheles female mosquito, and Anopheles gambiae sensus stricto is the most tremendous malaria vector in Africa, widespread throughout the afro-tropical belt. An. gambiae s.s. is subdivided into two distinct molecular forms, namely M and S forms. The two molecular forms are morphologically identical but they are distinct genetically, and differ by their distribution and their ecological preferences. The epidemiological importance of the two molecular forms in malaria transmission has been poorly investigated so far and gave distinct results in different areas. We have developed a real-time quantitative PCR (qPCR) assay, and used it to detect P. falciparum at the oocyst stage in wild An. gambiae s.s. mosquitoes experimentally infected with natural isolates of parasites. Mosquitoes were collected at immature stages in sympatric and allopatric breeding sites and further infected at the adult stage. We next measured the infection prevalence and intensity in female mosquitoes using the qPCR assay and correlated the infection success with the mosquito molecular forms. Our results revealed different prevalence of infection between the M and S molecular forms of An. gambiae s.s. in Cameroon, for both sympatric and allopatric populations of mosquitoes. However, no difference in the infection intensity was observed. Thus, the distribution of the molecular forms of An. gambiae s.s. may impact on the malaria epidemiology, and it will be important to monitor the efficiency of malaria control interventions on the two M and S forms.
High-Speed Lateral Flow Strategy for a Fast Biosensing with an Improved Selectivity and Binding Affinity

We report a high-speed lateral flow strategy for a fast biosensing with an improved selectivity and binding affinity even under harsh conditions. In this strategy, biosensors were fixed at a location away from the center of a round shape disk, and the disk was rotated to create the lateral flow of a target solution on the biosensors during the sensing measurements. Experimental results using the strategy showed high reaction speeds, high binding affinity, and low nonspecific adsorptions of target molecules to biosensors. Furthermore, binding affinity between target molecules and sensing molecules was enhanced even in harsh conditions such as low pH and low ionic strength conditions. These results show that the strategy can improve the performance of conventional biosensors by generating high-speed lateral flows on a biosensor surface. Therefore, our strategy can be utilized as a simple but powerful tool for versatile bio and medical applications.
Amino-Acid Network Clique Analysis of Protein Mutation Non-Additive Effects: A Case Study of Lysozyme

Optimizing amino-acid mutations in enzyme design has been a very challenging task in modern bio-industrial applications. It is well known that many successful designs often hinge on extensive correlations among mutations at different sites within the enzyme, however, the underpinning mechanism for these correlations is far from clear. Here, we present a topology-based model to quantitively characterize non-additive effects between mutations. The method is based on the molecular dynamic simulations and the amino-acid network clique analysis. It examines if the two mutation sites of a double-site mutation fall into to a 3-clique structure, and associates such topological property of mutational site spatial distribution with mutation additivity features. We analyzed 13 dual mutations of T4 phage lysozyme and found that the clique-based model successfully distinguishes highly correlated or non-additive double-site mutations from those additive ones whose component mutations have less correlation. We also applied the model to protein Eglin c whose structural topology is significantly different from that of T4 phage lysozyme, and found that the model can, to some extension, still identify non-additive mutations from additive ones. Our calculations showed that mutation non-additive effects may heavily depend on a structural topology relationship between mutation sites, which can be quantitatively determined using amino-acid network k-cliques. We also showed that double-site mutation correlations can be significantly altered by exerting a third mutation, indicating that more detailed physicochemical interactions should be considered along with the network clique-based model for better understanding of this elusive mutation-correlation principle.
Resveratrol attenuates myocardial injury in septic rats via inhibition of the JAK 2 / STAT 3 signaling pathway

Resveratrol (Res) is reported to exert anti-inflammatory and anti-oxidative properties. Sepsis-induced myocardial injury is tightly associated with inflammation. However, the mechanisms underlying the protective effect of Res remain unclear. The present study investigated the protective effect of Res on myocardial injury in septic rats and the role of the Janus Kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Res treatment was found to significantly inhibit the activation of JAK2 and STAT3 in myocardial tissue. It also attenuated the level of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β in the serum and myocardial tissue. In addition, Res alleviated myocardial apoptosis. In conclusion, the results indicate that Res exhibits substantial therapeutic potential for the treatment of sepsis-induced myocardial injury via JAK2/ STAT3 signaling inhibition.
OPTIMIZATION LOOP BASED ON A CFD RANS CODE .

The design of gas turbine engines is a complex and time consuming engineering task involving numerous iterative processes. Among all the devices composing an engine, the combustion chamber benefits from recent progress in High Performance Computing for Computational Fluid Dynamics (CFD) which is intensively used. Although CFD offers substantial improvements in flexibility and costs when compared to experimental approaches, the number of CFD computations still remains large and engineering intensive. A strategy to alleviate the CFD specialist involvement in reaching an optimal solution is desired to fully capitalize on the method. One solution aims at automating the optimization process performed with CFD computations. From the optimization point of view, the expensive step is the CFD run necessary to evaluate the objective function value representing the performance of a set of control parameters. The promising method developed in this work consists in performing optimization with classical techniques based on an inexpensive metamodeling [1] of the objective function. The idea is to reduce the number of CFD computations while proposing a rigorous framework to converge robustly to an optimal design. Implementation issues such as efficiency, numerical stability of the model, techniques to accelerate the optimization process, exploration / exploitation conflict and the different levels of parallelism involved in CFD optimization are addressed in this paper. Practicality of the optimization tool is here inherited from the powerful coupling device PALM [2]. Illustration of the approach when applied to a simple engine cooling system is presented: Validations steps and comparisons of the proposed surrogate approach with the very well known optimization method Simplex [3] are shown.
A multiband 2-port vector network analyzer based on Six-Port junctions for biomedical measurement applications between 6 GHz and 33 GHz

Concentration measurements of dissolved substances in fluids are of great interest for biomedical as well as industrial applications. In this work a multiband vector network analyzer is presented that is capable of determining phase variations due to changes in the concentration. A topology comprising two Six-Port networks optimized for the frequencies 6.6 GHz, 19.7 GHz and 32.4 GHz has been implemented. Measurement results show a characteristic change of the phase when increasing the glucose concentration in binary aqueous solutions.
Comparison of Levosimendan and Milrinone for ECLS Weaning in Patients After Cardiac Surgery-A Retrospective Before-and-After Study.

OBJECTIVES Pharmacodynamics suggests that levosimendan might be a valuable inotrope for weaning from extracorporeal life support (ECLS). As there is a paucity of evidence regarding the effectiveness and safety of such an approach, the aim was to report the authors' experiences in ECLS weaning before and after the implementation of levosimendan in clinical practice. DESIGN Retrospective before-and-after study. SETTING Cardiac intensive care unit of a university hospital. PARTICIPANTS A total of 64 patients under ECLS for postcardiotomy cardiac failure, who underwent an ECLS weaning trial. INTERVENTION Group comparisons between patients treated with levosimendan and patients treated with milrinone were made with the Mann-Whitney U test or the Pearson chi-squared test. Results are given as median (interquartile range) or numbers (percentages). MEASUREMENTS AND MAIN RESULTS Of 64 patients, 26 (41%) received levosimendan. Successful ECLS weaning was achieved in 24 (92%) and 30 patients (79%) in the levosimendan and milrinone group, respectively (p = 0.18). In the levosimendan group, fewer patients had an intra-aortic balloon pump for weaning (2 [7.7%] v 15 [40%], p = 0.008). The support with norepinephrine was similar in the levosimendan and milrinone groups at the time of ECLS removal (0.06 [0.01-0.11] v 0.07 [0.01-0.16] µg/kg/min, p = 0.64) and 24 hours later (0.06 [0.04-0.09] v 0.04 [0.00-0.09] µg/kg/min, p = 0.15). Twenty-eight days (9/26 (35%) v 14/35 (40%), p = 0.28) and 180 days (13/26 [50%] v 15/34 [44%], p = 0.80) mortalities after ECLS removal were similar in the levosimendan and the milrinone groups. CONCLUSION Levosimendan enabled ECLS weaning without increasing norepinephrine requirements when compared to a control group receiving milrinone.
Real-Time Traffic Signal Control with Dynamic Evolutionary Computation

Nowadays real-time traffic signal control is a crucial issue with potential benefits in the fields of traffic control, environmental pollution, and energy utilization. In the literature, few related studies have been done with dynamic evolutionary algorithms. In this paper, we proposed a strategy using Collaborative Evolutionary-Swarm Optimization (CESO), which is able to track time-varying optimal solutions effectively. We use the simulator of urban mobility (SUMO), a popular traffic simulator to generate traffic flows. A grid traffic network is designed with several scenarios to simulate changes of traffic flows captured by traffic monitors. We test different traffic changes in the network using the proposed strategy and compare its performance with a traditional evolutionary algorithm. Experimental results show that our algorithm can obtain promising configuration of traffic light cycles and reduce the average delay time of all vehicles in various scenarios.