Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Inflammatory Bowel Disease on Pubertal Growth

Background: Puberty is thought to be commonly affected in adolescents with inflammatory bowel disease (IBD). Aims: To determine the impact of Crohn’s disease (CD) and ulcerative colitis (UC) on the pubertal growth spurt. Methods: Retrospective study of 30 boys with CD (CD-M), 11 girls with CD (CD-F), 14 boys with UC (UC-M) and 12 girls with UC (UC-F). Pubertal growth was assessed by calculating peak height velocity SDS (PHV SDS), height SDS at diagnosis (HtDiag) and height SDS at PHV (HtPHV) and age at PHV (AgePHV). Systemic markers of disease activity were also collected. Results: Altered parameters of pubertal growth were observed in the CD groups compared to the normal population: in the CD-M group, median HtDiag was –0.56 (p = 0.001) and median AgePHV was 14.45 years (p = 0.004), and in the CD-F group, median HtDiag was –1.14 (p = 0.007) and HtPHV was –0.79 (p = 0.039). Individually, 8/30 CD-M cases had one or more parameter affected: 2 boys had HtDiag <–2, 3 boys had HtPHV <–2, 2 boys had an AgePHV >2 years above population mean, and 2 boys had a PHV SDS <–2. In the whole group, AgePHV showed an association with erythrocyte sedimentation rate (r = 0.4; p = 0.005) and an inverse association with BMI (r = 0.4; p = 0.001). Conclusion: Disorders of pubertal growth are more likely to occur in CD and, particularly, in boys.
A Multi-client architecture for hybrid terrain rendering on mobile devices

Mobile devices such as Personal Digital Assistants (PDAs) or smart phones are rapidly increasing their graphics and networking capabilities. However, real-time rendering of large terrains is still a challenging task to accomplish in such limited devices. In this paper we describe the principles involved in the design and development of a scalable client-server architecture for hybrid rendering of terrains over wireless networks on mobile devices. We have developed a hybrid adaptive streaming and rendering method based on a server-client approach. The rendering workload is distributed between a server and the clients and the terrain is partitioned into the close-range geometry and the background. The close-range geometry is downloaded from the database and rendered on the mobile client, and the background is portrayed as a view-dependent panoramic impostor and rendered by the server on demand then it is sent on request to the server for display. The system architecture is organized in three levels: the main server, the panorama server and the mobile device client. This architecture provides support for efficient delivery of geometry and impostors to mobile clients according to their capabilities. As a proof of concept, we have implemented a prototype and carried out exhaustive experiments considering different network scenarios and different number of connected clients. The analysis of the server workload and response times shows that our architecture achieves a great scalability and performance even when using low-end mobile devices.
Processing and Subcellular Trafficking of ER-Tethered EIN2 Control Response to Ethylene Gas

Cleave and Leave Plants produce ethylene gas, which acts as a hormone and is essential for the ripening of fruit, the resistance of plants to pathogens, the adaptation of plants to stress conditions, and stem cell maintenance. Although many components of the ethylene gas signaling pathway have been well studied, little is known about how the ethylene receptors located in the endoplasmic reticulum (ER) membrane can transmit the signal to the nucleus. Studying Arabidopsis, Qiao et al. (p. 390, published online 30 August) found that perception of ethylene gas in the ER promotes signal transduction via cleavage and rapid ER-nucleus translocation of the cytosolic portion of the transmembrane ETHYLENE INSENSITIVE2 protein, which activates ethylene-dependent gene expression and other ethylene response phenotypes in plants. The plant hormone ethylene triggers cleavage and translocation to the nucleus of a signaling component. Ethylene gas is essential for many developmental processes and stress responses in plants. ETHYLENE INSENSITIVE2 (EIN2), an NRAMP-like integral membrane protein, plays an essential role in ethylene signaling, but its function remains enigmatic. Here we report that phosphorylation-regulated proteolytic processing of EIN2 triggers its endoplasmic reticulum (ER)–to–nucleus translocation. ER-tethered EIN2 shows CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) kinase–dependent phosphorylation. Ethylene triggers dephosphorylation at several sites and proteolytic cleavage at one of these sites, resulting in nuclear translocation of a carboxyl-terminal EIN2 fragment (EIN2-C′). Mutations that mimic EIN2 dephosphorylation, or inactivate CTR1, show constitutive cleavage and nuclear localization of EIN2-C′ and EIN3 and EIN3-LIKE1–dependent activation of ethylene responses. These findings uncover a mechanism of subcellular communication whereby ethylene stimulates phosphorylation-dependent cleavage and nuclear movement of the EIN2-C′ peptide, linking hormone perception and signaling components in the ER with nuclear-localized transcriptional regulators.
Investigation of the inhibitory effects of PGE2 and selective EP agonists on chemotaxis of human neutrophils

1 The aims of this study were to investigate the inhibitory effects of prostaglandin E2 (PGE2) on chemotaxis of N‐formyl‐methionyl‐leucine‐phenylalahine (FMLP)‐stimulated human neutrophils, and to test the hypothesis that cyclic AMP is the second messenger involved. For this purpose, the inhibitory effect of selective EP agonists, and the modulatory effects of the adenylate cyclase inhibitor, SQ 22536, the protein kinase A (PKA) inhibitors H‐89 and Rp‐cAMPS, and the type IV phosphodiesterase (PDE) inhibitors, rolipram and Ro20‐1724 have been examined. 2 Chemotaxis has been measured using blindwell chambers. When human neutrophils were stimulated with FMLP (100 nM), PGE2 inhibited chemotaxis in a concentration‐dependent manner (0.01–10 μm), with an EC50 of 90±24.5 nM, a maximum effect ranging from 45–75% and a mean inhibition of 64.5 ±2.4%. 3 The EP2‐receptor agonists, 11‐deoxy PGE1, butaprost and AH 13205 also inhibited chemotaxis. The order of potency of these agonists was PGE2 > butaprost (EC50= 106.4 ± 63 nM)> 11‐deoxy PGE1 (EC50= 140.9±64.7 nM)>AH 13205(EC50= 1.58±0.73 μm). Correlation of the ability of EP2 agonists to increase cyclic AMP and to inhibit chemotaxis was poor (r=0.38). 4 The IP agonist, cicaprost gave similar increases in cyclic AMP to those achieved with PGE2, yet produced 50% of the maximum inhibition of chemotaxis observed with PGE2. 5 Slight potentiation of the inhibitory effects of PGE2 after type IV PDE block was observed with rolipram (EC50 for PGE2=57.2 ±5.9; 35.2 ±6.8 nM) but not Ro20‐1724 (EC50 for PGE2 216.0 ±59.7; 97.8 ±50.6 nM). Type IV PDE inhibitors are themselves potent inhibitors of chemotaxis with EC50 values of 23.0 ±2.3 and 73.6 ±10.3 nM for rolipram and Ro20‐1724, respectively. 6 Inhibition of cyclic AMP production with the adenylate cyclase inhibitor SQ 22,536 (0.1 mm) failed to antagonize inhibition of chemotaxis by PGE2 (EC50S for PGE2 of 57.2 ±5.9 and 56.8 ±27.3 nM, in the absence and presence of SQ 22,536, respectively) despite a reduction in the increase in cyclic AMP induced by PGE2. 7 Inhibition of PKA with either H‐89 (10 μm) or Rp cyclic AMPS (10 μm) similarly failed to antagonize inhibition of chemotaxis by PGE2; EC50 for PGE2 of 90 ±40 and PGE2+H‐89 60 ± 17 nM; PGE2 216.0±58.7 and PGE2Rp cyclic AMP 76.9±14.7nM. 8 Of the two PKA inhibitors tested, H‐89 (10 μm) and Rp cyclic AMPS (10 /zm), the more effective inhibitor of PGE2‐induced inhibition of neutrophil superoxide anion generation was H‐89 (EC50S for PGE2 were 0.36 ±0.1 and >10 μm, respectively). We have previously shown this to be a cyclic AMP‐dependent effect of PGE2. 9 Confirmation of block of PKA by H‐89 was suggested by the finding that H‐89 blocked inhibition of superoxide anion generation observed with the type IV PDE inhibitors rolipram and Ro20‐1724; EC50S of 12.9 ±8.9 nM for rolipram alone and rolipram+H‐89 >1 μm; Ro20‐1724 alone 59.5 ±28.1 nM and Ro20‐1724+H‐89 >1μm. 10 The results suggest that inhibition of chemotaxis by PGE2 and EP2 agonists is not mediated by increased neutrophil cyclic AMP levels.
Catalytic domain of plasmid pAD1 relaxase TraX defines a group of relaxases related to restriction endonucleases

Plasmid pAD1 is a 60-kb conjugative element commonly found in clinical isolates of Enterococcus faecalis. The relaxase TraX and the primary origin of transfer oriT2 are located close to each other and have been shown to be essential for conjugation. The oriT2 site contains a large inverted repeat (where the nic site is located) adjacent to a series of short direct repeats. TraX does not show any of the typical relaxase sequence motifs but is the prototype of a unique family of relaxases (MOBC). The present study focuses on the genetic, biochemical, and structural analysis of TraX, whose 3D structure could be predicted by protein threading. The structure consists of two domains: (i) an N-terminal domain sharing the topology of the DNA binding domain of the MarR family of transcriptional regulators and (ii) a C-terminal catalytic domain related to the PD-(D/E)XK family of restriction endonucleases. Alignment of MOBC relaxase amino acid sequences pointed to several conserved polar amino acid residues (E28, D152, E170, E172, K176, R180, Y181, and Y203) that were mutated to alanine. Functional analysis of these mutants (in vivo DNA transfer and cleavage assays) revealed the importance of these residues for relaxase activity and suggests Y181 as a potential catalytic residue similarly to His-hydrophobe-His relaxases. We also show that TraX binds specifically to dsDNA containing the oriT2 direct repeat sequences, confirming their role in transfer specificity. The results provide insights into the catalytic mechanism of MOBC relaxases, which differs radically from that of His-hydrophobe-His relaxases.
A Suppressive Role of the Prolyl Isomerase Pin1 in Cellular Apoptosis Mediated by the Death-associated Protein Daxx*

The death-associated protein Daxx is a multifunctional factor that regulates a variety of cellular processes, including transcription and apoptosis. Several previous reports have indicated that Daxx is induced upon oxidative stress and is then subjected to phosphorylation-based functional modification. However, the precise molecular events underlying these phosphorylation events remain largely unknown. We report in our current study that the peptidyl-prolyl isomerase Pin1 is highly overexpressed in malignant human gliomas and inhibits Daxx-mediated cellular apoptosis. The targeted inhibition of Pin1 by small interfering RNA in A172 glioblastoma cells significantly enhances the apoptotic response induced by hydrogen peroxide or stimulatory Fas antibodies. This is in turn accompanied by the increased induction of Daxx and the activation of the apoptosis signal-regulating kinase 1/c-Jun N-terminal kinase pathway. Furthermore, Pin1 binds to the phosphorylated Ser178-Pro motif in the Daxx protein, and Pin1 overexpression results in the rapid degradation of Daxx via the ubiquitin-proteasome pathway. Moreover, a Daxx-S178A mutant, which cannot interact with Pin1, demonstrates higher proapoptotic activity and is refractory to Pin1-mediated antiapoptotic effects. We further found that the expression levels of Pin1 inversely correlate with the degree of Daxx nuclear accumulation in human glioblastoma tissues. These results together indicate that Pin1-mediated prolyl isomerization plays an important role in the negative regulation of Daxx and thereby inhibits the oxidative stress-induced cellular apoptotic response, particularly in malignant tumor cells where Pin1 is often overexpressed.
Blood pressure levels in pre‐diabetic stages are associated with worse cognitive functioning in patients with type 2 diabetes

Type 2 diabetes mellitus (T2DM) is associated with mild decrements in cognitive functioning, but the relation of these decrements to metabolic and vascular risk factors is unclear. The present study compared the vascular risk factor profile over the preceding 16 years between T2DM patients with good cognitive functioning and those with poor cognitive functioning.
Effects of Temocapril and Olmesartan on Myocardial Sympathetic Nervous Activity and Fatty Acid Metabolism in Rats with Chronic &bgr;‐Adrenergic Stimulation

Summary: We investigated the effects of an angiotensin‐converting enzyme inhibitor (temocapril) and an angiotensin II type 1 receptor blocker (olmesartan) on changes in myocardial sympathetic nervous activity, fatty acid metabolism and myocardial blood flow using 131I‐meta‐iodobenzylguanidine,125I‐&bgr;‐methyl‐iodophenyl pentadecanoic acid and 99mTc‐tetrofosmin, respectively, in rats with isoproterenol‐induced cardiac hypertrophy. Male Sprague‐Dawley rats underwent isoproterenol administration (3 mg/kg per day) for 1 week by osmotic mini‐pump. The hearts were excised and analyzed for the uptake of meta‐iodobenzylguanidine, &bgr;‐methyliodophenyl pentadecanoic acid and tetrofosmin in 11 segments in four groups; sham group (saline), isoproterenol group (isoproterenol alone), angiotensin‐converting enzyme inhibitor group (isoproterenol and temocapril), and angiotensin II type 1 receptor blocker group (isoproterenol and olmesartan). Isoproterenol significantly increased the heart weight compared with the sham group, whereas it was significantly blunted in the angiotensin‐converting enzyme inhibitor and angiotensin II type 1 receptor blocker groups. The ratio of the percent kilogram dose per gram of meta‐iodobenzylguanidine to tetrofosmin, an index of myocardial sympathetic nervous activity, was significantly decreased in the isoproterenol group (0.18 ± 0.01) compared with the sham group (0.41 ± 0.03). Importantly, these changes were significantly improved in the angiotensin‐converting enzyme inhibitor (0.28 ± 0.01) and the angiotensin II type 1 receptor blocker groups (0.32 ± 0.01). The ratio of the percent kilogram dose per gram of &bgr;‐methyliodophenyl pentadecanoic acid to tetrofosmin, an index of myocardial fatty acid metabolism, was significantly decreased in the isoproterenol group (1.30 ± 0.03) compared with the sham group (1.60 ± 0.10). In contrast, there were no significant differences in &bgr;‐methyl‐iodophenyl pentadecanoic acid to tetrofosmin ratios between the sham and angiotensin‐converting enzyme inhibitor groups, or the angiotensin II type 1 receptor blocker group. Cardiac hypertrophy induced by chronic &bgr;‐adrenergic stimulation is accompanied by impairment of sympathetic nervous activity and fatty acid metabolism. These abnormalities are effectively prevented by the angiotensin‐converting enzyme inhibitor and the angiotensin II type 1 receptor blocker.
Seasat Synthetic-Aperture Radar Data Reduction Using Parallel Programmable Array Processors

This paper presents a digital signal processing system that produces the SEASAT synthetic-aperture radar (SAR) imagery. The system consists of a SEL 32/77 host minicomputer and three AP-120B array processors. The partitioning of the SAR processing functions and the design of softwae modules is described. The rationale for selecting the parallel array processor architecture and the methodology for developing the parallel processing scheme on this system is described. This system attains a SEASAT SAR data reduction speed of 2.5 h per 25-m resolution 4-look and 100 km X 100 km image frame. A prelininary performance evaluation of this parallel processing system and potential future applications for remote sensing data reduction are described.
A PWM Current Source-Based DC Transmission System for Multiple Wind Turbine Interfacing

A pulsewidth modulation (PWM) current source wind energy conversion system based on a parallel configuration for high voltage direct current application is proposed. A comparison between the parallel and series configurations for current source-based systems is investigated, which shows the merits of the proposed system. A new control technique for the PWM current source inverter is proposed. It can effectively control the average dc-link voltage with a feed-forward loop, while independently controlling reactive power according to grid code requirements. The system simulation confirms the performance of the proposed system with no interaction between wind turbine modules and satisfying performance with grid integration. Practical implementation further verifies the proposed inverter control. Finally, a brief comparison between conventional line-commutated converter-based systems and the proposed PWM current source converter-based system is presented.
Multiple extreme climatic events strengthen selection for earlier breeding in a wild passerine

Global climate warming results in an increase in mean temperatures and in the frequency of extreme climatic events (ECEs), which could both strongly impact ecosystems and populations. Most studies assessing the impact of global warming on ecosystems have focused on warming trends while neglecting ECEs. In particular, the effects of multiple ECEs on fitness, and their consequences for selection, are still missing. Here we explored the effects of daily extreme rainfalls, as well as the occurrence of extremely hot and cold days, on clutch size and laying date in a wild blue tit population (Cyanistes caeruleus) monitored over 25 years. During the nestling phase (8–15 days old), the number of fledglings in a brood was negatively correlated with extremely hot days. The presence of extremely hot days between days 8 and 15 was also associated with an increase in the strength of selection acting on laying date, independently of mean temperature trends during the same period: when 10% of broods in the population experienced this type of ECE, selection for earlier breeding increased by 39%. Our results represent a unique quantification of the impact of multiple ECEs on the fitness landscape and emphasize their role as climatic drivers of selection. This article is part of the themed issue ‘Behavioural, ecological and evolutionary responses to extreme climatic events’.
Establishment of a rat cell line inducible for the expression of human cytomegalovirus immediate-early gene products by protein synthesis inhibition

Upon transfection of Rat-2-TK- cells with plasmid pES, containing the cloned 7.0-kilobase (kb) EcoRI-SalI fragment (0.063 to 0.089 map units) of the human cytomegalovirus genome, major immediate-early antigen expression was obtained in 1 to 2% of the nuclei of the transfected cells, as determined by immunofluorescence with the E3 monoclonal antibody. Cotransfection of pES with the cloned herpes simplex virus type 1 thymidine kinase gene resulted in the establishment of a hypoxanthine-aminopterin-thymidine-resistant cell line which expressed a major immediate-early antigen in approximately 1% of the cells at early passages, with expression gradually declining to less than 0.1% upon subculturing. Southern blot analysis of DNA extracted from this cell line revealed the presence of multiple integration events of pES DNA sequences into cellular DNA, including a head-to-tail tandem array of approximately 10 copies of pES. The integration pattern was stable for at least 80 passages. Metaphase chromosomes prepared from this cell line showed, upon in situ hybridization, a strong hybridization signal in both sister chromatids of a large submetacentric chromosome which is considered to have harbored the tandemly integrated pES molecules. Whereas in most cells of the population, immediate-early expression seemed to be repressed, this repression could be overcome by protein synthesis inhibition, resulting in a massive induction of human-cytomegalovirus-specific transcripts of 2.1 and 1.9 kb and a minor species of 2.9 kb. After release from protein synthesis inhibition, approximately 20% of the cells showed nuclear fluorescence when the E3 monoclonal antibody was used.
Low 1/f noise and DC offset RF mixer for direct conversion receiver using parasitic vertical NPN bipolar transistor in deep n-well CMOS technology

RF characteristics of the parasitic vertical NPN bipolar junction transistor (BJT) available in 0.18 /spl mu/m foundry deep n-well CMOS technology are reported for the first time. The experimental results show that the vertical NPN BJT has about 20 of current gain, 7 V of collector-emitter breakdown voltage, 20 V of collector-base breakdown voltage, 40 V of early voltage, 2.3 GHz of cutoff frequency, and 3.5 GHz of maximum oscillation frequency at room temperature. The corner frequency of flicker noise is lower than 4 kHz at 0.5 mA. Double balanced RF mixer using V-NPN shows almost free 1/f noise as well as order of magnitude smaller DC offset with other characteristics comparable with CMOS one and 12 dB flat up to the cutoff frequency, opening the possibility of high performance direct conversion receiver implementation in CMOS technology.
Lowering the risk of neuropathy, foot ulcers and amputations

Peripheral neuropathy is one of the most common long‐term complications of Type 2 diabetes. A population‐based study in the north of England showed that 42 % of Type 2 diabetic patients had clinical evidence of neuropathy. The Diabetes Control and Complications Trial (DCCT) has shown that the incidence of neuropathy in Type 1 diabetes can be reduced by over 50 % with intensive therapy and optimal glycaemic control. Hyperglycaemia is believed to be a major aetiological factor in the development of neuropathy in Type 2 diabetes. Neuropathy cannot be diagnosed through history alone; therefore, careful examination of the feet for evidence of sensory loss and an assessment of the circulation must form part of the annual review of each patient. Peripheral somatic and autonomic neuropathy, together with peripheral vascular disease, are major contributing factors to the development of foot ulcers. In addition, abnormalities of foot shape (e.g. claw toes, prominent metatarsal heads) and the presence of plantar callus are signs of foot‐ulcer risk. Effective patient education can reduce the incidence of foot ulceration and amputation by over 50 %; therefore, all patients with a high risk of foot ulcers should be informed and, if indicated, referred for regular podiatry. The team approach to diabetic foot problems is an effective method of providing treatment for active ulcers. This should be followed by appropriate education, the provision of follow up and if indicated, suitable footwear and hosiery. Key members of the team are the podiatrist, the specialist nurse and the orthotist; medical staff may include the diabetologist and a vascular or orthopaedic surgeon. Thus, the risk of foot ulceration and amputation can be reduced by careful screening and patient education, without the need for expensive equipment. Copyright © 1998 John Wiley & Sons, Ltd.