Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylation and Activation of both Iron Regulatory Proteins 1 and 2 in HL-60 Cells (*)

Iron regulatory proteins (IRPs) are RNA-binding proteins that post-transcriptionally regulate synthesis of iron uptake (transferrin receptor) and storage (ferritin) proteins. Our previous work demonstrating that IRP1 is phosphorylated by protein kinase C supported the hypothesis that factors in addition to iron modulate IRP function. We have investigated changes in activity and expression of both IRP1 and IRP2 during phorbol 12-myristate 13-acetate (PMA)-induced differentiation of HL-60 cells. In contrast to IRP1, IRP2 was highly phosphorylated in untreated cells. PMA stimulated phosphorylation of IRP1 and IRP2 by at least 2-3-fold without affecting incorporation of [S]methionine into the proteins. IRP1 and IRP2 isolated from PMA-treated cells displayed different phosphopeptides. Phosphorylation of IRPs was associated with a 2-fold increase in high affinity RNA binding activity without altering K, and this was accompanied by a 50% increase in transferrin receptor mRNA abundance. PMA acted on a latent pool of binding activity that is present in a nonaconitase oxidized form and is largely composed of a stable but inactive species of IRP2. Desferal and hemin modulated iron-responsive element binding activity in HL-60 cells without affecting the phosphorylation state of IRP1. Hemin appeared to reduce the abundance of phosphorylated IRP2. Thus, multiple factors affect the function of both IRPs and indicate that extracellular agents may program changes in cellular iron metabolism by altering the phosphorylation state of these regulatory RNA-binding proteins.
Trimeric structure for an essential protein in L1 retrotransposition

Two proteins are encoded by the mammalian retrotransposon long interspersed nuclear element 1 (LINE-1 or L1); both are essential for retrotransposition. The function of the protein encoded by the 5′-most ORF, ORF1p, is incompletely understood, although the ORF1p from mouse L1 is known to bind single-stranded nucleic acids and function as a nucleic acid chaperone. ORF1p self-associates by means of a long coiled-coil domain in the N-terminal region of the protein, and the basic, C-terminal region (C-1/3 domain) contains the nucleic acid binding activity. The full-length and C-1/3 domains of ORF1p were purified to near homogeneity then analyzed by gel filtration chromatography and analytical ultracentrifugation. Both proteins were structurally homogeneous and asymmetric in solution, with the full-length version forming a stable trimer and the C-1/3 domain remaining a monomer. Examination of the full-length protein by atomic force microscopy revealed an asymmetric dumbbell shape, congruent with the chromatography and ultracentrifugation results. These structural features are compatible with the nucleic acid binding and chaperone activities of L1 ORF1p and offer further insight into the functions of this unique protein during LINE-1 retrotransposition.
Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, have been postulated to play important roles in health and disease for nearly half a century. Recent discoveries, which include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of an alternative mechanism by which CTS can signal through the Na+/K+-ATPase, have increased the interest in this field substantially. Although CTS were first considered important in the regulation of renal sodium transport and arterial pressure, more recent work implicates these hormones in the regulation of cell growth, differentiation, apoptosis, and fibrosis, the modulation of immunity and of carbohydrate metabolism, and the control of various central nervous functions and even behavior. This review focuses on the physiological interactions between CTS and other regulatory systems that may be important in the pathophysiology of essential hypertension, preeclampsia, end-stage renal disease, congestive heart failure, and diabetes mellitus. Based on our increasing understanding of the regulation of CTS as well as the molecular mechanisms of these hormone increases, we also discuss potential therapeutic strategies.
Imaging epileptogenic tubers in children with tuberous sclerosis complex usingα‐[11C]Methyl‐L‐tryptophan positron emission tomography

Several reports have indicated that cortical resection is effective in alleviating intractable epilepsy in children with tuberous sclerosis complex (TSC). Because of the multitude of cortical lesions, however, identifying the epileptogenic tuber(s) is difficult and often requires invaise intracranial electroencephalographic (EEG) monitoring. As increased concentrations of serotonin and serotonin‐immunoreactive processes have been reported in resected human epileptic cortex, we used α‐[11C]methyl‐L‐tryptophan ([11C]AMT) position emission tomography (PET) to test the hypothesis that serotonin synthesis is increased interictally in epileptogenic tubers in patients with TSC. Nine children with TSC and epilepsy, aged 1 to 9 years (mean, 4 years 1 month), were studied. All children underwent scalp video‐EEG monitoring, PET scans of glucose metabolism and serotonin synthesis, and EEG monitoring during both PET studies. [11C]AMT scans were coregistred with magnetic resonance imaging and with glucose metabolism scans. Whereas glucose metabolism PET showed multifocal cortical hypometabolism corresponding to the locations of tubers in all 9 children, [11C]AMT uptake was increased in one tuber (n = 3), two tubers (n = 3), three tubers (n = 1), and four tubers (n = 1) in 8 of the 9 children. All other tubers showed decreased [11C]AMT uptake. Ictal EEG data available in 8 children showed seizure onset corresponding to foci of increased [11C]AMT uptake in 4 children (including 2 with intracranial EEG recordings). In 2 children, ictal EEG was nonlocalizing, and in 1 child there was discordance between the region of increased [11C]AMT uptake and the region of ictal onset on EEG. The only child whose [11C]AMT scan showed to no regions of increased uptake had a left frontal seizure focus on EEG; however, at the time of his [11C]AMT PET scan, his seizures had come under control. [11C]AMT PET may be a powerful tool in differentiating between epileptogenic and nonepileptogenic tubers in patients with TSC.
2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis

To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6–8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.
Device Model for Ballistic CNFETs Using the First Conducting Band

This efficient approximation model for the drain-source current in a CNFET is analytic, its execution is fast, and it is suitable for simulating circuits consisting of many CNFET devices in a CAD environment. Evaluation results show that the model encounters a very modest normalized RMS error for diameter, Fermi level, and bias variations, while significantly improving simulation performance.
Electrospun Polymer Fibers for Electronic Applications

Nano- and micro- fibers of conjugated polymer semiconductors are particularly interesting both for applications and for fundamental research. They allow an investigation into how electronic properties are influenced by size confinement and chain orientation within microstructures that are not readily accessible within thin films. Moreover, they open the way to many applications in organic electronics, optoelectronics and sensing. Electro-spinning, the technique subject of this review, is a simple method to effectively form and control conjugated polymer fibers. We provide the basics of the technique and its recent advancements for the formation of highly conducting and high mobility polymer fibers towards their adoption in electronic applications.
Observer-Based Direct Adaptive Fuzzy-Neural Control for Anti-lock Braking Systems

In this paper, an observer-based direct adaptive fuzzy-neural controller (ODAFNC) for an anti-lock braking system (ABS) is developed under the constraint that only the system output, i.e., the wheel slip ratio, is measurable. The main control strategy is to force the wheel slip ratio to well track the optimal value, which may vary with the environment. The observer-based output feedback control law and update law for on-line tuning of the weighting factors of the direct adaptive fuzzy-neural controller are derived. By using the strictly-positive-real (SPR) Lyapunov theory, the stability of the closed-loop system can be guaranteed. Simulation results demonstrate the effectiveness of the proposed control scheme for ABS control.
Impact of Dietary Fatty Acids on Oocyte Quality and Development in Lactating Dairy Cows1

Abstract The purpose of this study was to examine the effects of level of rumen inert fatty acids on developmental competence of oocytes in lactating dairy cows. Estrous cycles were synchronized in 22 cows on a silage-based diet supplemented with either low (200 g/day) or high (800 g/day) fat. A total of 1051 oocytes were collected by ultrasound-guided ovum pickup (OPU) in seven sessions/cow at 3–4 day intervals. Oocytes were matured, fertilized, and cultured to the blastocyst stage in vitro. Embryo quality was assessed by differential staining of Day 8 blastocysts. The high-fat diet reduced numbers of small and medium follicles. There was no effect on the quality of oocytes (grades 1–4) or cleavage rate. However, high fat significantly improved blastocyst production from matured (P < 0.005) and cleaved (P < 0.05) oocytes. Blastocysts from the high-fat group had significantly more total, inner cell mass and trophectoderm cells than the low-fat group (P < 0.05). Regression analysis showed negative effects of milk yield (P < 0.001), dry matter intake (P < 0.001), metabolizable energy intake (P < 0.005), and starch intake (P < 0.001) on blastocyst production in the low-fat group but not in the high-fat group. Within the low-fat group, blastocyst production was negatively related to growth hormone (P < 0.05) and positively related to leptin (P < 0.05). The low-fat group had higher nonesterified fatty acids than the high-fat group (P < 0.05). In conclusion, higher milk yields were associated with reduced developmental potential of oocytes in cows given a low-fat diet. Provision of a high-fat diet buffered oocytes against these effects, resulting in significantly improved developmental potential.
A new species of Boechera (Brassicaceae) from Utah and Colorado

A new species,Boechera glareosa, is described and a key is provided to separate it from its apparent closest relative,B. gunnisoniana (Rollins) W. A. Weber. Twelve transfers are made fromArabis toBoechera to bring the nomenclature of Rocky Mountain region taxa in line with current DNA data.
Childhood Poverty and Brain Development

Childhood poverty is a major health problem worldwide. According to the Organisation for Economic Co-operation and Development (OECD), nearly 50 million children live below the national poverty level in industrial countries. The numbers would be orders of magnitude greater in developing countries. Living in poverty places children at high risk for many health conditions later in life. Perhaps the biggest problem is that a low socioeconomic status (SES) in childhood correlates with poor cognitive development, language, memory, socioemotional processing, and ultimately income and health in adulthood. But what is the connection? One clue came from a landmark study 20 years ago by Hart and Risley [1995]. Hart and Risley followed the children of 42 families of disparate demographics for 2 1 / 2 years (ages 7–9 months to 36 months) by observing the families at home each month for an hour. Their data showed that, although all of the families had good parents, there was a large discrepancy in the vocabulary of the children that was related to SES, with children from high-SES families having about twice the vocabulary as those from low-SES families. When the verbal skills of the children were measured at age 9 to 10, the SES-related difference remained and had actually grown larger. The difference in vocabulary at age 3 was related to the number of words that the children had been exposed to in the home. The authors concluded that over a year, the highSES children would have been exposed to about 11 million words and the low-SES children to about 3.2 million words. By age 4, the average lower-SES child would have been exposed to about 30 million fewer words than the upper-SES child. This is a staggering difference and clearly shows the hours of intervention that would be needed to change children’s lives. But what are the biological implications of the 30 million word deficit? Several recent noninvasive imaging studies have begun to provide answers. A study by Jamie Hanson and colleagues [Hanson, Hair, Shen, Shi, Gilmore, Wolfe, & Pollak, 2013] did repeated MRI scans on newborn to 3-year-old children demographically balanced to represent proportions defined by the US Census Bureau in terms of gender, race, ethnicity, and income distribution. The results showed that, although infants from different SES levels had similar gray matter volumes, by age 4 the lower-SES children had lower gray matter volumes in the frontal and parietal cortex than more advantaged children. Lower total gray matter volume was associated with behavioral prob-
The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus

Abstract Objectives. Active inflammatory responses play an important role in the pathogenesis of depression. We hypothesized that the rapid antidepressant effect of ketamine is associated with the down-regulation of pro-inflammatory mediators. Methods. Forty-eight rats were equally randomized into six groups (a control and five chronic unpredictable mild stress (CUMS) groups) and given either saline or 10 mg/kg ketamine, respectively. The forced swimming test was performed, and the hippocampus was subsequently harvested for the determination of levels of interleukin (IL)-1β, IL-6, tumour necrosis factor-α (TNF-α), indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), and tryptophan (TRP). Results. CUMS induced depression-like behaviours and up-regulated the hippocampal levels of IL-1β, IL-6, TNF-α, IDO, and the KYN/TRP ratio, which were attenuated by a sub-anaesthetic dose of ketamine. Conclusion. CUMS-induced depression-like behaviours are associated with a reduction in hippocampal inflammatory mediators, whereas ketamine’s antidepressant effect is associated with a down-regulation of pro-inflammatory cytokines in the rat hippocampus.
A micro energy harvester with 3D wire bonded microcoils

We developed the first micro energy harvester with optimized wire bonded microcoils. The coils were fabricated with a fully automated process on PCB. The 3D coils enable to effectively use the magnetic field and generate an output power of 0.62 µW at 1 ms−2 within a total harvester volume of 0.46 cm3. With the coil wire thickness of only 25 µm this corresponds to the high load voltage of 10.4 mV. The results evidence that this approach can help developing high performance energy harvesters with an increased output voltage.
The role of heterochromatin in centromere function

Chromatin at centromeres is distinct from the chromatin in which the remainder of the genome is assembled. Two features consistently distinguish centromeres: the presence of the histone H3 variant CENP-A and, in most organisms, the presence of heterochromatin. In fission yeast, domains of silent ‘heterochromatin’ flank the CENP-A chromatin domain that forms a platform upon which the kinetochore is assembled. Thus, fission yeast centromeres resemble their metazoan counterparts where the kinetochore is embedded in centromeric heterochromatin. The centromeric outer repeat chromatin is underacetylated on histones H3 and H4, and methylated on lysine 9 of histone H3, which provides a binding site for the chromodomain protein Swi6 (orthologue of Heterochromatin Protein 1, HP1). The remarkable demonstration that the assembly of repressive heterochromatin is dependent on the RNA interference machinery provokes many questions about the mechanisms of this process that may be tractable in fission yeast. Heterochromatin ensures that a high density of cohesin is recruited to centromeric regions, but it could have additional roles in centromere architecture and the prevention of merotely, and it might also act as a trigger for kinetochore assembly. In addition, we discuss an epigenetic model for ensuring that CENP-A is targeted and replenished at the kinetochore domain.
First case of pancreas transplant alone in a patient with diabetes and HIV infection

Chronic conditions have largely replaced opportunistic infections as the leading causes of mortality in human immunodeficiency virus (HIV) infection. Pancreas transplantation alone can be performed for people with difficult to manage diabetes associated with severe hypoglycaemic unawareness. For carefully selected patients, pancreas transplantation alone has the potential to dramatically improve quality and quantity of life. Historically, HIV was considered a contraindication to transplantation; however, today renal transplantation for people with end-stage kidney disease and HIV infection is increasingly common. We describe the use of a standard immunosuppression regimen in combination with effective antiretroviral control using a stable highly active antiretroviral therapy regimen with minimal interaction with immunosuppressants. We describe what is, to our knowledge, the first case of pancreas transplantation alone performed for this particularly challenging group, resulting in complete resolution of hypoglycaemic symptoms. We suggest that this group of patients should receive optimal diabetes management, including access to transplantation where appropriate, and demonstrate that pancreas transplantation alone is feasible for people with HIV infection.
A study for the feature selection to identify Giemsa-stained human chromosomes based on artificial neural network

Many studies in computer-based chromosome analysis have shown that it is possible to classify chromosomes into 24 subgroups. In addition, artificial neural networks (ANNs) have been adopted for the human chromosome classification. It is important to select the optimum features for training the neural network classifier. We selected some features - relative length, normalized density profile (d.p) and centromeric index - used to identify chromosomes and trained the neural network classifier by changing the number of samples which were used to get the d.p. We found the fact that the classification error was shown to be at a minimum when this number was equal to or greater than the length of the no.1 human chromosome.
An instructable, adaptive interface for discovering and monitoring information on the World-Wide Web

We are creating a customizable, intelligent interface to the World-Wide Web that assists a user in locating specific, current, and relevant information. The Wisconsin Adaptive Web Assistant (WAWA) is capable of accepting instructions regarding what type of information that users are seeking and how to go about looking for it. WAWA compiles these instructions into neural networks, which means that the system’s behavior can be modified via training examples. Users can create these training examples by rating pages retrieved by WAWA, but more importantly the system uses techniques from reinforcement learning to internally create its own examples (users can also later provide additional instructions). WAWA uses these neural networks to guide its autonomous navigation of the Web, thereby producing an interface to the Web that users periodically instruct and which in the background searches the Web for relevant information, including periodically revisiting pages that change regularly.
Genetic structure and conservation of Mountain Lions in the South-Brazilian Atlantic Rain Forest

The Brazilian Atlantic Rain Forest, one of the most endangered ecosystems worldwide, is also among the most important hotspots as regards biodiversity. Through intensive logging, the initial area has been reduced to around 12% of its original size. In this study we investigated the genetic variability and structure of the mountain lion, Puma concolor. Using 18 microsatellite loci we analyzed evidence of allele dropout, null alleles and stuttering, calculated the number of allele/locus, PIC, observed and expected heterozygosity, linkage disequilibrium, Hardy-Weinberg equilibrium, FIS, effective population size and genetic structure (MICROCHECKER, CERVUS, GENEPOP, FSTAT, ARLEQUIN, ONESAMP, LDNe, PCAGEN, GENECLASS software), we also determine whether there was evidence of a bottleneck (HYBRIDLAB, BOTTLENECK software) that might influence the future viability of the population in south Brazil. 106 alleles were identified, with the number of alleles/locus ranging from 2 to 11. Mean observed heterozygosity, mean number of alleles and polymorphism information content were 0.609, 5.89, and 0.6255, respectively. This population presented evidence of a recent bottleneck and loss of genetic variation. Persistent regional poaching constitutes an increasing in the extinction risk.
Visualizing Software Changes

A key problem in software engineering is changing the code. We present a sequence of visualizations and visual metaphors designed to help engineers understand and manage the software change process. The principal metaphors are matrix views, cityscapes, bar and pie charts, data sheets and networks. Linked by selection mechanisms, multiple views are combined to form perspectives that both enable discovery of high-level structure in software change data and allow effective access to details of those data. Use of the views and perspectives is illustrated in two important contexts: understanding software change by exploration of software change data and management of software development. Our approach complements existing visualizations of software structure and software execution.