Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of the Cellular Phosphatase DUSP1 in Vaccinia Virus Infection

Poxviruses encode a large variety of proteins that mimic, block or enhance host cell signaling pathways on their own benefit. It has been reported that mitogen-activated protein kinases (MAPKs) are specifically upregulated during vaccinia virus (VACV) infection. Here, we have evaluated the role of the MAPK negative regulator dual specificity phosphatase 1 (DUSP1) in the infection of VACV. We demonstrated that DUSP1 expression is enhanced upon infection with the replicative WR virus and with the attenuated VACV viruses MVA and NYVAC. This upregulation is dependent on early viral gene expression. In the absence of DUSP1 in cultured cells, there is an increased activation of its molecular targets JNK and ERK and an enhanced WR replication. Moreover, DUSP1 knock-out (KO) mice are more susceptible to WR infection as a result of enhanced virus replication in the lungs. Significantly, MVA, which is known to produce non-permissive infections in most mammalian cell lines, is able to grow in DUSP1 KO immortalized murine embryo fibroblasts (MEFs). By confocal and electron microscopy assays, we showed that in the absence of DUSP1 MVA morphogenesis is similar as in permissive cell lines and demonstrated that DUSP1 is involved at the stage of transition between IVN and MV in VACV morphogenesis. In addition, we have observed that the secretion of pro-inflammatory cytokines at early times post-infection in KO mice infected with MVA and NYVAC is increased and that the adaptive immune response is enhanced in comparison with WT-infected mice. Altogether, these findings reveal that DUSP1 is involved in the replication and host range of VACV and in the regulation of host immune responses through the modulation of MAPKs. Thus, in this study we demonstrate that DUSP1 is actively involved in the antiviral host defense mechanism against a poxvirus infection.
PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate.

OBJECTIVE The abuse potential of methylphenidate has been related to the drug's capacity to produce a rapid onset of blockade of the presynaptic dopamine transporter in the brain. An oral once-a-day osmotic controlled-release formulation of methylphenidate produces a more gradual rise in plasma methylphenidate concentration, compared with immediate-release methylphenidate. The authors hypothesized that osmotic-release methylphenidate would also produce a slower onset of blockade of the presynaptic dopamine transporter and would be associated with a lower risk for detection and likeability, compared to immediate-release methylphenidate. METHOD Twelve healthy adults were randomly assigned to receive single doses of immediate-release methylphenidate or osmotic-release methylphenidate. Doses predicted to produce equivalent maximum concentration (C(max)) values were selected (40 mg of immediate-release methylphenidate and 90 mg of osmotic-release methylphenidate). Plasma d-methylphenidate levels and responses to detection/likeability questionnaire items were obtained hourly for 10 hours after administration of methylphenidate on two separate occasions for each subject. Dopamine transporter receptor occupancies were measured at hours 1, 3, 5, and 7 by using a carbon-11-labeled imaging agent (Altropane) and positron emission tomography. RESULTS Despite similar C(max) values for both formulations, osmotic-release methylphenidate was associated with a longer time to maximum concentration, longer time to maximum CNS dopamine transporter occupancy, and no detection/likeability, compared with immediate-release methylphenidate. CONCLUSIONS The findings suggest that the abuse potential of oral methylphenidate is strongly influenced by the rate of delivery and not solely by the magnitude of plasma concentration or brain transporter occupancy. These results advance understanding of the underlying central effects of methylphenidate in humans and identify a potentially less abusable methylphenidate formulation.
PCA-LDA based face recognition system & results comparison by various classification techniques

Face recognition has a major impact in security measures which makes it one of the most appealing areas to explore. To perform face recognition, researchers adopt mathematical calculations to develop automatic recognition systems. As a face recognition system has to perform over wide range of database, dimension reduction techniques become a prime requirement to reduce time and increase accuracy. In this paper, face recognition is performed using Principal Component Analysis followed by Linear Discriminant Analysis based dimension reduction techniques. Sequencing of this paper is preprocessing, dimension reduction of training database set by PCA, extraction of features for class separability by LDA and finally testing by nearest mean classification techniques. The proposed method is tested over ORL face database. It is found that recognition rate on this database is 96.35% and hence showing efficiency of the proposed method than previously adopted methods of face recognition systems.
Patterns of Subject Uptake and Examination Entry 1984–1997

In 1984, the APU science survey collected information on the courses followed by Year 11 pupils. In this paper, the APU survey will be compared with recent GCSE examination level data and will describe the impact of the National Curriculum on the sexes and on pupils of differing ability. In 1984, there were considerable differences in uptake by the sexes and by ability. In 1997, pupils were taking more examinations than were pupils in 1984. Also, girls were taking more GCSEs than boys in 1997. This could be the result of changes in the provision of subjects. The subjects favoured by males, such as science and technology, tend to have been merged with other subjects. The amount of physics studied by boys has decreased with the introduction of the GCSE (from a whole subject to half a subject). Subjects stereotypically preferred by girls such as modern languages, drama and English literature have increased. In this sense, it could be said that there has been a feminisation of the curriculum, but these changes would only account for some of the differential performance between the sexes.
The Illusion of Leadership: Misattribution of Cause in Coordination Games

This paper reports the results of experiments which examine attributions of leadership quality. Subjects played an abstract coordination game which is like many organizational problems. Previous research showed that when larger groups play the game, they rarely coordinate on the Pareto-optimal (efficient) outcome, but small groups almost always coordinate on the efficient outcome. After two or three periods of playing the game, one subject who was randomly selected from among the participants to be the "leader" for the experiment was instructed to make a speech exhorting others to choose the efficient action. Based on previous studies, we predicted that small groups would succeed in achieving efficiency but that large groups would fail. Based on social psychological studies of the fundamental attribution error, we predicted that the subjects would underestimate the strength of the situational effect (group size) and attribute cause to personal traits of the leaders instead--leaders would be credited for the success of the small groups, and blamed for the failure of the large groups. This hypothesis proved true: Subjects attributed differences in outcomes between conditions to differences in the effectiveness of leaders. In a second experiment, subjects voted to replace the leaders more frequently in the large-group condition (at a small cost to themselves), showing that misattributions of leadership ability also affect actual behavior by subjects. Previous research has demonstrated a tendency to credit or blame leaders for unusual performance. The difference in our study is that subjects should be blaming a structural condition--the size of the group--but they blame the leaders instead. Thus, our experiment is the first to establish a mistaken illusion of leadership.
Real-world Experiments in Ecological Restoration

A new epoch demands a new science. As we move steadily into the ‘Anthropocene’, a period in which human activities are categorized as a major geologic force (Zalasiewicz et al., 2010), we see movements on several scholarly fronts as people contend with the inextricability of human and natural environments. Indeed, the usefulness of the term ‘natural’ is seriously challenged by a world in which the impact of the human is everywhere. The situation is confounded, moreover, by a general pall of uncertainty; even in the context of increasing awareness of our own influences on the Earth’s fundamental processes, we are also contending with our inability to manage and control that world. As Giddens (1990) and Beck (1992) laid out decades ago, our scientific and technological successes have run away from us, and now engender risks we did not foresee. And more recent scientific discoveries in fields like microbiology, cybernetics, advanced prosthetics and artificial intelligence reveal and create increasingly intertwined and hybrid nature-cultures—insisting on a re-evaluation of long-standing categories (Gandy, 2008; Hird, 2009). Despite our best attempts at modernization, as Latour (1993) would argue, we have never succeeded in separating ourselves from nature, and are, in the end, natural to the core. Thus, the boundary between nature and society, which was surely never black and white, is increasingly manifest as an ever-expanding band of grey. Science as Culture Vol. 21, No. 4, 582–586, December 2012
Animated Depth Images for Interactive Remote Visualization of Time-Varying Data Sets

Remote visualization has become both a necessity, as data set sizes have grown faster than computer network performance, and an opportunity, as laptop, tablet, and smartphone mobile computing platforms have become ubiquitous. However, the conventional remote visualization (CRV) approach of sending a new image from the server to the client for every view parameter change suffers from reduced interactivity. One problem is high latency, as the network has to be traversed twice, once to communicate the view parameters to the server and once to transmit the new image to the client. A second problem is reduced image quality due to aggressive compression or low resolution. We address these problems by constructing and transmitting enhanced images that are sufficient for quality output frame reconstruction at the client for a range of view parameter values. The client reconstructs thousands of frames locally, without any additional data from the server, which avoids latency and aggressive compression. We introduce animated depth images, which not only store a color and depth sample at every pixel, but also store the trajectory of the samples for a given time interval. Sample trajectories are stored compactly by partitioning the image into semi-rigid sample clusters and by storing one sequence of rigid body transformations per cluster. Animated depth images leverage sample trajectory coherence to achieve a good compression of animation data, with a small and user-controllable approximation error. We demonstrate animated depth images in the context of finite element analysis and SPH data sets.
The genomic context of natural killer receptor extended gene families

Summary: The two sets of inhibitory and activating natural killer (NK) receptor genes belong either to the Ig or to the C‐type lectin superfamilies. Both are extensive and diverse, comprising genes of varying degrees of relatedness, indicative of a process of iterative duplication. We have constructed gene maps to help understand how and when NK receptor genes developed and the nature of their polymorphism. A cluster of over 15 C‐type lectin genes, the natural killer complex is located on human chromosome 12p13.1, syntenic with a region in mouse that borders multiple Ly49 loci. The equivalent locus in man is occupied by a single pseudogene, LY49L. The immunoglobulin superfamily of loci, the leukocyte receptor complex (LRC), on chromosome 19q13.4, contains many polymorphic killer cell immunoglobulin‐like receptor (KIR) genes as well as multiple related sequences. These include immunoglobulin‐like transcript (ILT) (or leukocyte immunoglobulin‐like receptor genes), leukocyte‐associated inhibitory receptor genes (LAIR), NKp46, FcαR and the platelet glycoprotein receptor VI locus, which encodes a collagen‐binding molecule. KIRs are expressed mostly on NK cells and some T cells. The other LRC loci are more widely expressed. Further centromeric of the LRC are sets of additional loci with weak sequence similarity to the KIRs, including the extensive CD66(CEA) and Siglec families. The LRC‐syntenic region in mice contains no orthologues of KIRs. Some of the KIR genes are highly polymorphic in terms of sequence as well as for presence/absence of genes on different haplotypes. Some anchor loci, such as KIR2DL4, are present on most haplotypes. A few ILT loci, such as ILT5 and ILT8, are polymorphic, but only ILT6 exhibits presence/absence variation. This knowledge of the genomic organisation of the extensive NK superfamilies underpins efforts to understand the functions of the encoded NK receptor molecules. It leads to the conclusion that the functional homology of human KIR and mouse Ly49 genes arose by convergent evolution. NK receptor immunogenetics has interesting parallels with the major histocompatibility complex (MHC) in which some of the polymorphic genes are ligands for NK molecules. There are hints of an ancient genetic relationship between NK receptor genes and MHC‐paralogous regions on chromosomes 1, 9 and 19. The picture that emerges from both complexes is of eternal evolutionary restlessness, presumably in response to resistance to disease.
Receptive field characteristics of tactile units with myelinated afferents in hairy skin of human subjects.

1. Impulses in single nerve fibres from the lateral antebrachial cutaneous nerve were recorded using the microneurography technique in human subjects. 2. In a sample of fifty‐five mechanoreceptive units with fast‐conducting nerve fibres, five types were identified, i.e. SAI (slowly adapting type I, Merkel), SAII (slowly adapting type II, Ruffini), hair units, field units and Pacinian‐type units. The latter three unit types were all rapidly adapting. 3. The detailed structure of thirty‐five receptive fields of SAI, SAII, hair and field units was explored with a method which was objective and independent of the experimenter's skill and experience. A lightweight probe was used to scan the receptive field area in a series of tracks 0.23 mm apart while single‐unit activity was recorded. 4. SAI fields were small and composed of two to four well‐separated high‐sensitivity spots and often, in addition, one minor spot of lower sensitivity. SAII units typically fired spontaneously at a low and regular rate. Most fields consisted of one single spot of high sensitivity with diffuse borders. The hair units innervated ten to thirty‐three (or more) hairs, which were evenly distributed over a large area. The field units were characterized by a number of small and closely packed high‐sensitivity spots with diffuse borders. A conservative estimate indicated eleven spots per unit. 5. The findings indicate that the sheet of mechanoreceptors on the skin of the forearm is distinctly different from that on the dorsum of the hand and in the face. It seems reasonable to assume that the former is more representative for the hairy skin covering the main parts of the body.
Rituximab in the Treatment of Anti-Neutrophil Cytoplasm Antibody-Associated Vasculitis

The introduction of cyclophosphamide and high-dose glucocorticoids for anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) has allowed a reduction in 1-year mortality from 80% to 10-20%. AAV is now a chronic disease, and greater emphasis has turned to improving treatment-related toxicity, reducing relapses and providing alternative treatments for refractory disease. Rituximab, an anti-CD20 B cell-depleting therapy, has been used for over a decade in patients with AAV. Rituximab offers a significant advance in the treatment of these diseases. It has an established role for remission induction and is now being investigated as a remission maintenance agent. For remission induction, randomised trials have reported similar remission rates with rituximab and cyclophosphamide, and rituximab is now an approved alternative to cyclophosphamide in severe AAV. In clinical practice, rituximab is increasingly used for refractory and relapsing disease. Further remission induction data with rituximab for life-threatening renal and pulmonary disease may be provided by the ongoing PEXIVAS trial (NCT00987389). With standard therapies, 50% of patients with newly diagnosed AAV relapse by 5 years. Relapses are higher still in patients with known relapsing disease. For remission maintenance, treatment trials are comparing repeat rituximab dosing to azathioprine. The MAINRITSAN trial (NCT00748644) included mainly newly diagnosed AAV patients following cyclophosphamide induction therapy. The RITAZAREM trial (NCT01697267) is randomising patients with relapsing disease after rituximab induction therapy. Preliminary results with rituximab maintenance therapy are encouraging, although the optimal dosing regimen and duration has yet to be defined. Other areas for further investigation include remission maintenance therapy requirement after rituximab induction in newly diagnosed AAV, and the role of rituximab in eosinophilic granulomatosis with polyangiitis where no randomised data exists.
Effects of a high-protein, low-carbohydrate diet on degradation of sucrase-isomaltase in rat jejunoileum.

During the degradation of intestinal sucrase-isomaltase by pancreatic proteinases, degradation of sucrase-active site precedes that of the isomaltase-active site in rats. In the present paper, we demonstrate that the extent of degradation of sucrase-isomaltase is altered by dietary manipulation in vivo. Adult rats were starved for 24 h and received either a standard diet (20 cal% protein, 55% carbohydrate) or an isocaloric high-protein, low-carbohydrate diet (70 cal% protein, 5% carbohydrate). Animals were killed 15 h after the refeeding. In rats fed a high-protein, low-carbohydrate diet, luminal trypsin activity was three times higher than controls, and sucrase activity in proximal ileum was significantly lower (P less than 0.001) than controls, whereas isomaltase activity was similar in both groups. In proximal jejunum, luminal trypsin activity was remarkably lower (P less than 0.01) than in proximal ileum in both groups; sucrase and isomaltase activity was similar in both groups. Crossed immunoelectrophoresis demonstrated that a degradation product of sucrase-isomaltase, i.e., isomaltase monomer, was present in a larger amount in rats fed a high-protein, low-carbohydrate diet. In rats with bypassed pancreatic ducts, the amount of this degradation product was decreased and effect of a high-protein, low-carbohydrate diet was abolished. Experiments with a sequential isolation of epithelial cells of proximal ileum revealed that sucrase activity was decreased along the entire height of the villus in animals fed a high-protein, low-carbohydrate diet. (ABSTRACT TRUNCATED AT 250 WORDS)
Immersed in Virtual Worlds and Minds

Past research on video game effects was often limited to explaining effects of game content and mode, leaving structural and contextual game elements scarcely investigated. The present research examined the yet unclear role of narration in video games, by adapting concepts and methodology from video game research based on self-determination theory as well as past research on the effects of literary fiction. Results provided evidence for the facilitation of immersion and an immersion-mediated enhancement of autonomy and relatedness need satisfaction through in-game storytelling, suggesting a mutual enhancement of immersion and need satisfaction. Moreover, in-game storytelling enhanced affective theory of mind. Perspectives on future research, connecting in-game storytelling and game content to complement current knowledge of video game effects on various real-world outcomes, are discussed.
Combination treatment of PKD utilizing dual inhibition of EGF-receptor activity and ligand bioavailability.

BACKGROUND We have previously demonstrated an essential role for increased epidermal growth factor receptor (EGFR) activity in mediating renal cyst formation and biliary ductal ectasia (BDE) in murine models of autosomal-recessive polycystic kidney disease (ARPKD) such as the BPK mouse. The current study was designed to determine (1). if treatment with a second-generation inhibitor of EGFR tyrosine kinase activity, EKB-569, was effective in treatment of ARPKD; (2). if tyrosine kinase inhibitor therapy used in combination with pharmacologic reduction of the availability of transforming growth factor-alpha (TGF-alpha), using WTACE2, could provide improved therapeutic efficacy and/or decrease potential toxicity; and (3). if effectiveness of treatment could be monitored noninvasively in murine ARPKD models by use of serial ultrasonography. METHODS BPK litters were treated with EKB-569 by intraperitoneal injection from postnatal day 7 to postnatal day 21. EKB-569's effectiveness alone or in combination with WTACE2 was measured by reduction in kidney weight/body weight ratios, morphometric renal cystic index, and evaluation of renal function. Renal ultrasound was performed on normal and cystic animals, under different therapeutic regimens, utilizing a 15 mHz linear array transducer, and ultrasound data were compared with histology and renal functional data. RESULTS Treatment of BPK mice with EKB-569 alone resulted in a marked reduction of kidney weight/body weight ratios, dramatically reduced collecting tubule cystic index, as well as BDE, and improved renal function. The combined treatment with EKB-569 and WTACE2 permitted a 67% reduction in EKB-569 dosage necessary to achieve results equivalent to those produced with EKB-569 alone. Untreated cystic animals died of renal failure, on average, at postnatal day 24 with a collecting tubule cystic index of 4.8, significant BDE, and maximal urine osmolarity of 361 mOsm. Cystic animals treated with EKB-569 and WTACE2 to postnatal day 21 were alive and well with normal renal function, a reduced collecting tubule cystic index of 1.7 (P < 0.02), improvement in BDE, and a threefold increase in maximum urinary concentrating ability (P < 0.01). Renal ultrasound could reliably detect cystic kidneys as early as postnatal day 7 and the natural history as well as effects of therapeutic intervention were clearly delineated by ultrasound evaluation. CONCLUSION This study demonstrates that in murine ARPKD (1). EKB-569 is as effective as first-generation EGFR tyrosine kinase inhibitors in reducing cyst formation and preserving renal function; (2). combination therapy with EKB-569 and WTACE2 provides maximum efficacy in improving renal and biliary abnormalities, at lower doses, thereby minimizing potential toxicity; and (3). renal ultrasound provides a simple, reliable, noninvasive method of following natural history and effect of treatment regimens.