Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional cloning of BRF1, a regulator of ARE‐dependent mRNA turnover

To identify regulators of AU‐rich element (ARE)‐dependent mRNA turnover we have followed a genetic approach using a mutagenized cell line (slowC) that fails to degrade cytokine mRNA. Accordingly, a GFP reporter construct whose mRNA is under control of the ARE from interleukin‐3 gives an increased fluorescence signal in slowC. Here we describe rescue of slowC by a retroviral cDNA library. Flow cytometry allowed us to isolate revertants with reconstituted rapid mRNA decay. The cDNA was identified as butyrate response factor‐1 (BRF1), encoding a zinc finger protein homologous to tristetraprolin. Mutant slowC carries frame‐shift mutations in both BRF1 alleles, whereas slowB with intermediate decay kinetics is heterozygous. By use of small interfering (si)RNA, independent evidence for an active role of BRF1 in mRNA degradation was obtained. In transiently transfected NIH 3T3 cells, BRF1 accelerated mRNA decay and antagonized the stabilizing effect of PI3‐kinase, while mutation of the zinc fingers abolished both function and ARE‐binding activity. This approach, which identified BRF1 as an essential regulator of ARE‐dependent mRNA decay, should also be applicable to other cis‐elements of mRNA turnover.
Striatal dopamine D2 receptor binding of risperidone in schizophrenic patients as assessed by 123I-iodobenzamide SPECT: a comparative study with olanzapine

The aim of this investigation was to compare the degree of striatal dopamine-(D2) receptor blockade by two atypical antipsychotic drugs, risperidone and olanzapine. The percentage of D2 receptor occupancy during treatment was calculated by comparing the results of 123I-iodobenzamide SPECT with those from healthy control subjects. Twenty inpatients suffering from schizophrenia or schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with clinically recommended doses of risperidone and compared with 13 inpatients treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade correlated strongly for both risperidone (Pearson r = –0.86, p = 0.0001) and olanzapine (Pearson r = –0.77, p = 0.002). There was no significant difference between the D2 receptor occupancy of the two substances when given in the clinically recommended dose range (unpaired t-test, t= –0.112, p=0.911).
Diffusion Tensor Imaging Tractography of the Facial Nerve in Patients With Cerebellopontine Angle Tumors

Objective: To demonstrate the utility of diffusion tensor imaging (DTI) fiber tractography of the facial nerve in patients with cerebellopontine angle (CPA) tumors. Study Design: Prospective. Setting: Tertiary referral center. Patients: DTI technique was established in 113 patients without tumors and in 28 patients with CPA tumors. Subsequently, DTI results were compared with intraoperative findings in 21 patients with medium and large-sized tumors, treated surgically via a translabyrinthine approach. Intervention: Three Tesla magnetic resonance (MR) was used for DTI tractography. For patients without CPA tumors, the scanning protocol was 32 directions with a 3 × 3 × 3 mm voxel size. For CPA tumor patients, scanning protocol was 32 directions with a 2 × 2 × 2 mm voxel size. DTI data were used to track the facial nerve. Main Outcome Measures: Facial nerve identification rate. Results: Facial nerve identification rate in MR-DTI was 97% and 100% in patients without tumors and in patients with tumors of the CPA of the internal auditory canal that were not treated surgically, respectively. MR-DTI identification of the facial nerve was successful in 20 patients who were treated surgically (95%). Good agreement between surgical findings and MR-DTI results was found in 19 patients (90%). Conclusion: MR DTI tractography is an effective technique in positively identifying the position of the facial nerve in patients with CPA tumors.
Twelve‐membered macrolactones: privileged scaffolds for the development of new therapeutics

Natural products commonly produced as secondary metabolites of various plants and micro‐organisms represent a diverse chemical space of compounds. The diversity of natural products makes them an attractive target for interrogation by both chemists and biologists alike. Indeed, the study of 12‐membered macrolactones has already led to the discovery of lead drug compounds and new biological targets, which has motivated the development of diverted total synthetic routes to libraries of analogs. This review explores the discovery, biological characterization, and synthesis of several 12‐membered macrolactones, exploiting examples that underscore their importance in the drug discovery field. It is our hope that this review will motivate further interest in this class of natural products, a group of molecules that we think merit the classification of ‘privileged scaffolds’ within the medicinal chemistry community, to further investigate and develop novel compounds with promising bioactivity.
Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice

Background and purpose: Elephantopus scaber L. (Asteraceae) is a traditional herbal medicine with anti‐cancer effects. We evaluated the in vitro and in vivo efficacy of a major sesquiterpene lactone constituent of E. scaber, deoxyelephantopin (DET), against mammary adenocarcinoma and the underlying molecular mechanism.
Search for Past Life on Mars: Possible Relic Biogenic Activity in Martian Meteorite ALH84001

Fresh fracture surfaces of the martian meteorite ALH84001 contain abundant polycyclic aromatic hydrocarbons (PAHs). These fresh fracture surfaces also display carbonate globules. Contamination studies suggest that the PAHs are indigenous to the meteorite. High-resolution scanning and transmission electron microscopy study of surface textures and internal structures of selected carbonate globules show that the globules contain fine-grained, secondary phases of single-domain magnetite and iron sulfides. The carbonate globules are similar in texture and size to some terrestrial bacterially induced carbonate precipitates. Although inorganic formation is possible, formation of the globules by biogenic processes could explain many of the observed features, including the PAHs. The PAHs, the carbonate globules, and their associated secondary mineral phases and textures could thus be fossil remains of a past martian biota.
Metabolic and cardiodynamic responses of isolated turtle hearts to ischemia and reperfusion.

We used 31P and 1H nuclear magnetic resonance spectroscopy to measure intracellular pH, high energy phosphates, and lactate levels in hearts of turtles (Chrysemys picta bellii) subjected to 1.5 h of global ischemia followed by reperfusion. We simultaneously monitored maximum ventricular developed pressure (Pmax), maximal rate of pressure development (dP/dtmax), rate-pressure product (RPP), cardiac output, and heart rate and also measured lactate efflux from the hearts during reperfusion. Our goal was to test the hypothesis that turtle hearts would prove tolerant of prolonged global ischemia at 20 degrees C and would recover completely on reperfusion without any indication of ischemia-or reperfusion-related injury. The 1.5 h of ischemia resulted in decreases in phosphocreatine and ATP to 31.4 +/- 2.8 and 87.3 +/- 6.3% of control, respectively, while Pi rose to 236.6 +/- 26.3%. Intracellular pH decreased during this period from 7.38 +/- 0.02 to 6.87 +/- 0.04. Most of these changes occurred during the first 30 min. Tissue lactate rose during 1.5 h of ischemia from approximately 1.5 to 22.3 mumol/g wet tissue wt. However, the rate of lactate production was much higher during the first 21 min of ischemia (0.41 mumol.g-1.min-1) than during the remaining 70 min (0.10 mumol.g-1.min-1). With the onset of ischemia, Pmax, dP/dtmax, RPP, and heart rate all decreased dramatically with roughly the same time course as the changes in high-energy phosphates and intracellular pH. On reperfusion, turtle hearts rapidly restored high-energy phosphates, intracellular pH, lactate, and cardiodynamics to control levels, usually within 15-30 min, with no evidence of reperfusion injury. (ABSTRACT TRUNCATED AT 250 WORDS)
On the role of multiples in Marchenko imaging

ABSTRACTMarchenko imaging can produce seismic reflection images in which artifacts related to multiples are suppressed. However, in state-of-the-art implementations, multiples do not contribute to the imaged reflectors. With an “event-by-event” deconvolution imaging approach, it is possible to use multiples in Marchenko imaging. We illustrate this for a 1D reflection response in which the primary reflection of a specific interface is missing.
Ultraviolet/Optical Emission of the Ionized Gas in AGN: Diagnostics of the Ionizing Source and Gas Properties

Spectroscopic studies of active galactic nuclei (AGN) are powerful means of probing the physical properties of the ionized gas within them. In particular, near future observational facilities, such as the {\itshape James Webb Space Telescope} (JWST), will allow detailed statistical studies of rest-frame ultraviolet and optical spectral features of the very distant AGN with unprecedented accuracy. In this proceedings, we discuss the various ways of exploiting new dedicated photoionization models of the narrow-line emitting regions (NLR) of AGN for the interpretation of forthcoming revolutionary datasets.
Topology-based personal selection in multi-objective Particle Swarm Optimization

Particle Swarm Optimization (PSO) is a stochastic multi-point search algorithm. It was inspired by the social behavior observed in nature, such as flocks of birds and schools of fish. In recent years, multi-objective optimization by using PSO is receiving much attention. There are two difference steps from standard single objective PSO; 1) the use of archives to reserve Pareto optimal candidates, and 2) the selection of appropriate guides for multi-objective optimization. Topology is often used for standard PSO to make appropriate balance between exploration and exploitation. However, the use of topology in multi-objective PSO is not well studied. From this viewpoint, we propose a PSO model that introduces a topology-based guide selection scheme for multi-objective optimization, in this paper. The numerical simulation results show that the proposed guide selection method is effective in multi-objective optimization benchmark problems.
Skewed X‐chromosome inactivation is not associated with premature ovarian failure in a large cohort of Italian patients

Silvia Bione, Sara Benedetti, Mara Goegan, Immacolata Menditto, Anna Marozzi, Maurizio Ferrari, and Daniela Toniolo* Institute of Molecular Genetics, CNR, Pavia, Italy DIBIT, San Raffaele Scientific Institute, Milan, Italy Clinical Molecular Biology, Diagnostics and Research San Raffaele, Milan, Italy Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy Unit for Genomics for Human Disease Diagnosis, San Raffaele Scientific Institute, Milan, Italy Vita-Salute San Raffaele University, Milan, Italy
Pulmonary Sclerosing Hemangioma Consistently Expresses Thyroid Transcription Factor-1 (TTF-1): A New Clue to Its Histogenesis

The histogenesis of pulmonary sclerosing hemangioma has remained controversial despite extensive studies by many investigators. The availability of an antibody to thyroid transcription factor-1 (TTF-1), which is expressed in type II pneumocytes and Clara cells, has prompted us to readdress this issue. Sixteen cases were immunostained with a panel of antibodies including TTF-1. The patients were predominantly women with an age range of 30 to 73 years (mean, 52 yrs). All tumors were solitary. The single male patient showed regional lymph node metastases, an unusual occurrence reported only once in the literature. All cases exhibited the classic histologic features, with variegated patterns. TTF-1 expression was observed in both the surface lining cells and the pale polygonal cells. The surface lining cells were epithelial membrane antigen (EMA)+ cytokeratin+ surfactant apoprotein A+, whereas the polygonal cells were EMA+ cytokeratin-surfactant apoprotein A-. The neuroendocrine markers synaptophysin and chromogranin were both negative. The metastatic deposits in the lymph nodes comprised only polygonal cells and exhibited an EMA+ cytokeratin-surfactant apoprotein A- TTF-1+ immunophenotype. These results suggest that pulmonary sclerosing hemangioma is an epithelial neoplasm derived from primitive respiratory epithelium or incompletely differentiated type II pneumocyte or Clara cell.
Percutaneous Reduction and Fixation of Displaced Intra-Articular Calcaneus Fractures

Objectives: The purpose of this study is to assess the initial results of percutaneously reducing and fixing calcaneus fractures compared with a concurrent control group that was openly reduced and internally fixed through an extensile lateral approach. Design: Retrospective cohort study, consecutive series. Setting: Level I trauma center. Patients/Participants: One hundred twenty patients with 125 intra-articular calcaneus fractures were selected as a consecutive series with treatment method randomized by surgeon and time of presentation. Intervention: Patients treated with open reduction and internal fixation (OR group) had an extended lateral approach and fractures were fixed with plates and screws. Patients treated with percutaneous reduction (PR group) had small incisions with indirect fragment manipulation, and the reduction achieved was secured with screws alone. Main Outcome Measurement: Clinical and radiographic assessment. Results: There were 41 patients with 42 fractures in the OR group and 79 patients with 83 fractures in the PR group. There were no significant differences in sex, age, open fractures, fracture classification, or initial Bohler's angle between the two groups. Bohler's angle was improved after surgery by an average of 22.4° in the OR group and 25.3° in the PR group (P = 0.31). The average loss of reduction at healing (minimum 4 months postoperatively) was not significantly different between the two groups. Deep infection occurred in six of 42 of the OR group and zero of 83 of the PR group (P = 0.002). The incidence of minor wound complications was nine of 42 in the OR group and five of 83 in the PR group (P = 0.03). The need for late subtalar fusions (two of 26 and three of 41 with full 2-year follow-up) and implant removal (five of 42 and 10 of 83) was not significantly different. Conclusions: The results of this study suggest that in comparison to open reduction, this method of percutaneously reducing and fixing calcaneus fractures minimizes complications and achieves and maintains extra-articular reductions as well as the standard extensile open reduction and internal fixation. Further study of this technique is warranted. This should include assessment of articular reduction and longer follow-up of a larger number of patients.
Relationship between oro and nasopharynx permeability and the direction of facial growth.

AIM Most scientific literature relates vertical growth to individuals with decreased upper airway permeability. However, we often find subjects with a long face and a normal breathing pattern, most likely caused by other aetiological factors. And, frequently, we also find decreased upper airway permeability with horizontal growth. The aim of the study was to compare the cephalometric measurements of the oro and nasopharynx permeability with the facial growth direction and to identify the most common facial growth direction in individuals with decreased upper airway permeability. MATERIALS AND METHODS Cephalometric analysis was carried out in 158 pre-adolescent patients at the Orthodontic appointment, using facial profile teleradiographs. Parameters used were Jabarak's ratio and measurement of oro-nasopharynx space. Data collected were submitted to statistical treatment. RESULTS This study points to the presence of an intermediate growth in individuals with diminished oro and nasopharynx permeability, either simultaneous or separate. The number of individuals with diminished permeability and vertical growth is close to the number of individuals with horizontal growth. CONCLUSIONS The individuals with diminished permeability of the upper airway present an intermediate growth direction, representing the most frequent type. In the less common growth directions, there is a slight tendency to horizontal facial growth verified in individuals with diminished nasopharynx permeability. Also, a light tendency to vertical facial growth is present when oropharynx permeability is reduced.
Control of Power Converters in AC Microgrids

The enabling of ac microgrids in distribution networks allows delivering distributed power and providing grid support services during regular operation of the grid, as well as powering isolated islands in case of faults and contingencies, thus increasing the performance and reliability of the electrical system. The high penetration of distributed generators, linked to the grid through highly controllable power processors based on power electronics, together with the incorporation of electrical energy storage systems, communication technologies, and controllable loads, opens new horizons to the effective expansion of microgrid applications integrated into electrical power systems. This paper carries out an overview about microgrid structures and control techniques at different hierarchical levels. At the power converter level, a detailed analysis of the main operation modes and control structures for power converters belonging to microgrids is carried out, focusing mainly on grid-forming, grid-feeding, and grid-supporting configurations. This analysis is extended as well toward the hierarchical control scheme of microgrids, which, based on the primary, secondary, and tertiary control layer division, is devoted to minimize the operation cost, coordinating support services, meanwhile maximizing the reliability and the controllability of microgrids. Finally, the main grid services that microgrids can offer to the main network, as well as the future trends in the development of their operation and control for the next future, are presented and discussed.
The Activating Immunoreceptor NKG2D and Its Ligands Are Involved in Allograft Transplant Rejection1

Although the linkage between innate and adaptive immunity in transplantation has been recognized, the mechanisms underlying this cooperation remain to be fully elucidated. In this study, we show that early “danger” signals associated with transplantation lead to rapid up-regulation of NKG2D ligands. A second wave of NKG2D ligand up-regulation is mediated by the adaptive immune response to allografts. Treatment with an Ab to NKG2D was highly effective in preventing CD28-independent rejection of cardiac allografts. Notably, NKG2D blockade did not deplete CD8+ T cells or NK1.1+ cells nor affect their migration to the allografts. These results establish a functional role of NKG2D and its ligands in the rejection of solid organ transplants.
Mutation analysis in Saudi Duchenne and Becker muscular dystrophy patients using multiplex PCR

Introduction: In Saudi Arabia, only limited work has been reported on the mutation patterns of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). This study looks at the spectrum of deletions in the 'hot spot' regions of the DMD gene in Saudi DMD/BMD patients using an enhanced multiplex PCR technique. Material and methods: Twenty-six exons of the DMD gene were analyzed, in eight unrelated DMD/BMD cases aged 4-19 years, using four different multiplex PCR sets. Each multiplex PCR set amplified a total of six or seven exons. Normal controls were included for validation. Results: Using an optimized multiplex PCR method, 5 out of 8 DMD/BMD patients showed deletions, while the remaining three had no deletions in regions analyzed. Set 1 detected no deletions in any of the patients, whereas each of sets 2, 3 and 4 detected two, four and three deletions respectively. All of these mutations were located in the distal 'hot spot' region. No deletions were detected in the proximal 'hot spot' region. The normal control samples showed no deletions in any of the 26 exons tested. Conclusions: In this study, multiplex PCR technology was utilized to demonstrate the frequency of the most commonly found deletions in a limited group of Saudi DMD/BMD patients. The overall distribution of deletion mutations in the distal 'hot spot' region was in accordance with DMD/BMD cases investigated elsewhere. The study also serves as a good starting point for further investigations into the genetic aspects of the Saudi DMD/BMD population.
How Uncertainty Avoidance Affects Innovation Resistance in Mobile Banking: The Moderating Role of Age and Gender

While Internet banking has received the attention of the masses in many developed countries, mobile banking adoption is still in its infancy. This paper explores the role of uncertainty avoidance on innovation resistance in the context of mobile banking. Hypotheses of the effect of uncertainty avoidance on five adoption barriers, namely usage, value, risk, tradition and image, were tested using a large data set consisting of 1556 effective responses from online bank customers. The results show that uncertainty avoidance has a highly significant effect on innovation resistance, the strongest influence related to image and risk barriers. Moreover, age appear not to moderate the effects while gender is found to be a highly significant moderator. The results contribute to the earlier literature by evincing that uncertainty avoidance indeed increases resistance to innovations despite the age of a consumer. However, this influence varies between genders, which partly contradicts with the earlier debate.
Evaluation of exposure to electromagnetic radiofrequency radiation in the indoor workplace accessible to the public by the use of frequency-selective exposimeters

ObjectivesThe aim of the study was to identify and assess electromagnetic radiofrequency radiation (EMRR) exposure in a workplace located in a publicly accessible environment, and represented by offices (where exposure is caused by various transmitters of local fixed indoor and outdoor wireless communication systems). Material and MethodsThe investigations were performed in 45 buildings (in urban and rural areas in various regions of Poland), using frequency-selective electric field strength (E-field) exposimeters sensitive to the EMRR with a frequency range of 88–2500 MHz, split into 12 sub-bands corresponding to the operating frequencies of typical EMRR sources. The variability of the E-field was analyzed for each frequency range and the total level of exposure by statistical parameters of recorded exposimetric profiles: minimum, maximum, median values and 25–75th — percentiles.ResultsThe main sources of exposure to EMRR are mobile phone base transceiver stations (BTS) and radio-television transmitters (RTV). The frequency composition in a particular office depends on the building’s location. The E-field recorded in buildings in urban and rural areas from the outdoor BTS did not exceed respectively: medians − 0.19 and 0.05 V/m, 75th percentiles −0.25 and 0.09 V/m. In buildings equipped with the indoor BTS antennas the E-field did not exceed: medians − 1 V/m, 75th percentiles − 1.8 V/m. Whereas in urban and rural areas, the median and 75th percentile values of the E-field recorded in buildings located near the RTV (within 1 km) did not exceed: 1.5 and 3.8 V/m or 0.4 and 0.8 V/m, for radio FM band or for TV bands, respectively.ConclusionsInvestigations confirmed the practical applicability of the exposimetric measurements technique for evaluating parameters of worker’s exposure in both frequency- and time-domain. The presented results show EMRR exposure of workers or general public in locations comparable to offices to be well below international limits.