Miracle-dz/UniFAR-FTUs huggingface dataset:
Gemin5 Binds to the Survival Motor Neuron mRNA to Regulate SMN Expression*

Background: Spinal muscular atrophy (SMA), a neurodegenerative disease, is caused by low levels of expression of the survival motor neuron (SMN) protein. Results: Gemin5 binds to and regulates translation of the mature SMN mRNA. Conclusion: Gemin5 functions in the regulation of the SMN mRNA. Significance: Investigation of the regulation of SMN expression is critical for understanding SMA and developing therapeutics. Reduced expression of SMN causes spinal muscular atrophy, a severe neurodegenerative disease. Despite the importance of maintaining SMN levels, relatively little is known about the mechanisms by which SMN levels are regulated. We show here that Gemin5, the snRNA-binding protein of the SMN complex, binds directly to the SMN mRNA and regulates SMN expression. Gemin5 binds with high specificity, both in vitro and in vivo, to sequence and structural elements in the SMN mRNA 3′-untranslated region that are reminiscent of the snRNP code to which Gemin5 binds on snRNAs. Reduction of Gemin5 redistributes the SMN mRNA from heavy polysomes to lighter polysomes and monosomes, suggesting that Gemin5 functions as an activator of SMN translation. SMN protein is not stoichiometrically present on the SMN mRNA with Gemin5, but the mRNA-binding activity of Gemin5 is dependent on SMN levels, providing a feedback mechanism for SMN to regulate its own expression via Gemin5. This work both reveals a new autoregulatory pathway governing SMN expression, and identifies a new mechanism through which SMN can modulate specific mRNA expression via Gemin5.
Pollution Liability and Insurance: An Application of Economic Theory

Recently, interest has emerged in pollution liability insurance (PLI) as a response to the pollution risk. In this paper, an externalities model is used as a theoretical construct within which to analyze PLI as a mechanism for pricing pollution losses and to compare PLI with other schemes for dealing with the pollution problem. The model and analysis presented in this paper should serve to organize future research in the pollution liability insurance as well as other liability insurance areas.
Double-channel, frequency-steered acoustic transducer with 2-D imaging capabilities

A frequency-steerable acoustic transducer (FSAT) is employed for imaging of damage in plates through guided wave inspection. The FSAT is a shaped array with a spatial distribution that defines a spiral in wavenumber space. Its resulting frequency-dependent directional properties allow beam steering to be performed by a single two-channel device, which can be used for the imaging of a two-dimensional half-plane. Ad hoc signal processing algorithms are developed and applied to the localization of acoustic sources and scatterers when FSAT arrays are used as part of pitch-catch and pulse-echo configurations. Localization schemes rely on the spectrogram analysis of received signals upon dispersion compensation through frequency warping and the application of the frequency-angle map characteristic of FSAT. The effectiveness of FSAT designs and associated imaging schemes are demonstrated through numerical simulations and experiments. Preliminary experimental validation is performed by forming a discrete array through the points of the measurement grid of a scanning laser Doppler vibrometer. The presented results demonstrate the frequency-dependent directionality of the spiral FSAT and suggest its application for frequency-selective acoustic sensors, for the localization of broadband acoustic events, or for the directional generation of Lamb waves for active interrogation of structural health.
Vertical variants of PIN and p-NOI tunnel electronic devices and potential applications

Communication traffic continue to improve due to the rapid growth in broadband access in recent years, frequently based on PIN or tunnel devices. The present paper discuses two kind of tunnel devices, in a vertical configuration through the cross-section, allowing the tunnel current flow from upper anode to bottom cathode: PIN and NOI device in a planar technology (p-NOI). Recently, the NOI — Nothing On Insulator device was proposed and timely updated. It belongs to a vacuum nano-transistor class. The simulations reveal few better device parameters versus related devices from literature. The vertical p-NOI device with a dual MOS gated diode configuration, overpass the fabricated vacuum nanotransistors with SS=0.4V/dec << SS=4.1V/dec. The PIN vertical diode with three compensated drift regions offers higher breakdown voltage, keeping the forward series resistance as low as possible. Finally, the applications of the PIN and NOI devices are presented.
Efflux transporter breast cancer resistance protein dominantly expresses on the membrane of red blood cells, hinders partitioning of its substrates into the cells, and alters drug–drug interaction profiles

Abstract 1. Red blood cell (RBC) partitioning is important in determining pharmacokinetic and pharmacodynamic properties of a compound; however, active transport across RBC membranes is not well understood, particularly without transporter-related cell membrane proteomics data. 2. In this study, we quantified breast cancer resistance protein (BCRP/Bcrp) and MDR1/P-glycoprotein (P-gp) protein expression in RBCs from humans, monkeys, dogs, rats and mice using nanoLC/MS/MS, and evaluated their effect on RBC partitioning and plasma exposure of their substrates. BCRP-specific substrate Cpd-1 and MDR1-specific substrate Cpd-2 were characterized using Caco-2 Transwell® system and then administered to Bcrp or P-gp knockout mice. 3. The quantification revealed BCRP/Bcrp but not MDR1/P-gp to be highly expressed on RBC membranes. The knockout mouse study indicated BCRP/Bcrp pumps the substrate out of RBCs, lowering its partitioning and thus preventing binding to intracellular targets. This result was supported by a Cpd-1 and Bcrp inhibitor ML753286 drug–drug interaction (DDI) study in mice. Because of enhanced partitioning of Cpd-1 into RBCs after BCRP/Bcrp inhibition, Cpd-1 plasma concentration changed much less extent with genetic or chemical knockout of Bcrp albeit marked blood concentration increase, suggesting less DDI effect. 4. This finding is fundamentally meaningful to RBC partitioning, pharmacokinetics and DDI studies of BCRP-specific substrates.
I/O scheduling and performance analysis on multi‐core platforms

Multi‐core platforms are being widely used in many technology areas. These technology shifts not only provide a compute‐intensive service, but also require us to improve the I/O‐intensive service in performance. However, the existing I/O scheduling approaches lack either quantitative analysis or workload adaptability. These approaches become worse when the application scenarios have either diverse I/O tasks or heterogeneous multi‐cores. Based on the analysis of traditional software pipelining technology, we first propose a reverse interleaved pipelining scheduling strategy to decrease the total I/O execution time and balance the workloads of homogeneous processors in this paper. Theoretical analysis shows that this balancing strategy is fair. As for the heterogeneous processors' circumstance, a Self‐adaptive scheduling method is presented for selecting one of the most‐appropriate multi‐core services for the expected I/O tasks. Simulation studies show that the performance of this scheduling strategy self‐adapts to application and multi‐core diversity well. Copyright © 2009 John Wiley & Sons, Ltd.
Effects of p21Cip1/Waf1 at Both the G1/S and the G2/M Cell Cycle Transitions: pRb Is a Critical Determinant in Blocking DNA Replication and in Preventing Endoreduplication

ABSTRACT It has been proposed that the functions of the cyclin-dependent kinase inhibitors p21Cip1/Waf1 and p27Kip1 are limited to cell cycle control at the G1/S-phase transition and in the maintenance of cellular quiescence. To test the validity of this hypothesis, p21 was expressed in a diverse panel of cell lines, thus isolating the effects of p21 activity from the pleiotropic effects of upstream signaling pathways that normally induce p21 expression. The data show that at physiological levels of accumulation, p21, in addition to its role in negatively regulating the G1/S transition, contributes to regulation of the G2/M transition. Both G1- and G2-arrested cells were observed in all cell types, with different preponderances. Preponderant G1 arrest in response to p21 expression correlated with the presence of functional pRb. G2 arrest was more prominent in pRb-negative cells. The arrest distribution did not correlate with the p53 status, and proliferating-cell nuclear antigen (PCNA) binding activity of p21 did not appear to be involved, since p27, which lacks a PCNA binding domain, produced similar arrest Bs. In addition, DNA endoreduplication occurred in pRb-negative but not in pRb-positive cells, suggesting that functional pRb is necessary to prevent DNA replication in p21 G2-arrested cells. These results suggest that the primary target of the Cip/Kip family of inhibitors leading to efficient G1 arrest as well as to blockade of DNA replication from either G1 or G2 phase is the pRb regulatory system. Finally, the tendency of Rb-negative cells to undergo endoreduplication cycles when p21 is expressed may have negative implications in the therapy of Rb-negative cancers with genotoxic agents that activate the p53/p21 pathway.
A Cross-Layer Design Method for Multiple Realtime Video Streams in Multi-Hop Wireless Networks

In this paper, a novel cross-layer design method for realtime video traffics in CDMA multi-hop wireless networks is proposed. First, the performances of application, physical, MAC, and network layers are modelled by some classical models under reasonable assumptions. Then, we present a framework in which source coding, power control, ARQ control, and delay partitioning functionalities at different layers can be jointly optimized. Our studied problem is to maximize the video quality under strict end-to-end delay constraints through adjusting the source coding rate, end-to-end delay distribution, and each node's transmit power. This optimization problem is proved to be a nonlinear but log-convex one. Finally, we propose a centralized solution based on the geometric programming theory, as well as a partially distributed solution based on the Lagrangian dual decomposition technique. And both solutions are proved to converge to the global optimum of the above problem.
Biomechanics and Physiology of Gait Selection in Flying Birds*

Two wing‐beat gaits, distinguished by the presence or absence of lift production during the upstroke, are currently used to describe avian flight. Vortex‐visualization studies indicate that lift is produced only during the downstroke in the vortex‐ring gait and that lift is produced continuously in the continuous‐vortex gait. Tip‐reversal and feathered upstrokes represent different forms of vortex‐ring gait distinguished by wing kinematics. Useful aerodynamic forces may be produced during tip‐reversal upstroke in slow flight and during a feathered upstroke in fast flight, but it is probable that downstroke forces are much greater in magnitude. Uncertainty about the function of these types of upstroke may be resolved when more data are available on wake structure in different flight speeds and modes. Inferring from wing kinematics and available data on wake structure, birds with long wings or wings of high aspect ratio use a vortex‐ring gait with tip‐reversal upstroke at slow speeds, a vortex‐ring gait with a feathered upstroke at intermediate speeds, and a continuous‐vortex gait at fast speeds. Birds with short wings or wings of low aspect ratio use a vortex‐ring gait with a feathered upstroke at all speeds. Regardless of wing shape, species tend to use a vortex‐ring gait for acceleration and a continuous‐vortex gait for deceleration. Some correlations may exist between gait selection and the function of the muscular and respiratory system. However, overall variation in wing kinematics, muscle activity, and respiratory activity is continuous rather than categorical. To further our understanding of gait selection in flying birds, it is important to test whether upstroke function varies in a similar manner. Transitions between lifting and nonlifting upstrokes may be more subtle and gradual than implied by a binomial scheme of classification.
Real Macro Economic Variables and Stock Prices: Test of Proxy Hypothesis in Turkey

The aim of this study is to investigate the relationship between reel macroeconomic variables and stock prices in Turkey under "Proxy hypothesis" developed by Fama (1981). According to Proxy hypothesis of Fama, real macroeconomic variables such as consumption expenditures, economic growth, employment, fixed investment affect stock prices via inflation. In the study, consumption expenditures, industrial production index, employment level and fixed investments are used as indicators of real economic activity and consumption price index as indicator of inflation. The long-run relationship between the variables is tested by Bound testing approach developed by Paseran et al (2001). Our findings support the validity of the Proxy Hypothesis of Fama (1981) for Turkey.
pH-dependent unfolding of aspergillopepsin II studied by small-angle X-ray scattering.

Aspergillopepsin II (EC 3.4.23.6) secreted from the fungus Aspergillus niger var. macrosporus is a non-pepsin-type acid proteinase. It consists of two polypeptide chains (i.e., a heavy chain and a light chain), which are bound noncovalently to each other. The pH titration analysis using small-angle X-ray scattering (SAXS) as well as circular dichroism (CD) and gel filtration indicated that the enzyme was unfolded around a neutral pH with concomitant dissociation of the two chains. Detailed analyses showed that the midpoint pH values for the unfolding are not coincident with one another (pH 6.1 in circular dichroism and gel filtration, pH 6.4 in zero-angle intensity of SAXS, pH 6.8 in radius of gyration). The difference between these values suggested the existence of an intermediate state during the unfolding. Further analyses of the SAXS data showed that the heavy chain just after the dissociation still kept molecular compactness and that it gradually increased its dimensions as the pH was further raised. Noncoincidence of the two phenomena (i.e., chain dissociation and swelling) led to elucidation of a novel intermediate state during unfolding, which was confirmed by the subsequent singular value decomposition (SVD) analysis.
Key Considerations for Planning the European Capital of Culture - The Case of Veliko Tarnovo

This paper presents principle planning issues for one of the biggest cultural initiatives introduced by the European Commission - the ‘European Capital of Culture’ programme. Evaluating the success of past European Capitals of Culture, scholars particularly emphasise the need for a well prepared and systematic planning approach. The main objective was to scrutinize how a city can successfully prepare itself for the title year and to develop a framework that depicts key planning areas for the programme. This framework in combination with guiding questions for each of the key planning areas aims to assist future applicant cities in the planning and preparation phase of the programme. One of these applicant cities is the Bulgarian town of Veliko Tarnovo. A comprehensive literature review provided a first insight into the topic. In a second step, in-depth interviews with former European Capitals of Culture experts were conducted with the final aim to develop the aforementioned framework and guiding questions. Finally, the findings were applied to the city of Veliko Tarnovo and recommendations were given. The results indicate that during the planning phase particular attention needs to be paid to the field of organisation, marketing and communication as well as funding and infrastructure investment. Organisers ought to be precise on the aims and objectives of the programme, keeping in mind its stakeholders and the legacy they want to leave for after the title year.
Percutaneous radiofrequency ablation versus surgical radiofrequency ablation for malignant liver tumours: the long-term results.

BACKGROUND Radiofrequency ablation (RFA) has been used to treat hepatocellular carcinoma (HCC) and liver metastases for more than 10 years with promising early outcomes. Preliminary results comparing percutaneous and surgical approaches have shown no difference in short-term outcomes. In this study, the longer-term outcomes were presented. METHODS Patients with liver malignancies treated by RFA were prospectively studied from 2003 to 2011. Post-ablation assessment by computed tomography (CT) scan and serum biochemistry was performed at regular intervals. Recurrence rates and long-term survival were analysed. RESULTS A total of 233 patients with liver malignancies (75.5% HCC and 24.5% liver metastases) were analysed. Three RFA approaches were used (percutaneous 58.4%, laparoscopic 9.4% and open 32.2%). The median follow-up time was 29 months. Complete ablation was achieved in 83.7%, with no difference between the two approaches. More wound and chest complications were observed in the surgical group. Intra-hepatic recurrences were observed in 69.5%; extra-hepatic recurrences were detected in 22.3%, with no difference between the two groups. There was no statistical difference between the two approaches in overall 1-, 3- and 5-year survival. CONCLUSION An extended period of follow-up in patients with liver malignancies showed that RFA is an effective treatment. No difference was demonstrated between the percutaneous and surgical approach, in terms of recurrence and survival.
Novel transport mechanism of SiGe dot MOS tunneling diodes

The blockage of the hole transport due to the excess hole in SiGe quantum dots was observed in the metal-oxide-semiconductor (MOS) tunneling diodes for the first time. The hole tunneling current from Pt gate electrode to p-type Si dominates the inversion current at the positive gate bias and is seven order of magnitude higher than the Al gate/oxide/p-Si device. The SiGe quantum dots confine the excess holes in the valence band, and form the repulsive barrier to reduce the hole transport current from Pt to SiGe quantum dots by three order of magnitude as compared to the Pt/oxide/p-Si device. This repulsive barrier also reduces the hole tunneling current from SiGe quantum dots to Pt for the accumulation current at positive gate bias.
How retirement, health benefits and longevity affect household savings ?

This paper analyses the impact of welfare systems and longevity on savings. It develops a life-cycle model embodying social transfers (health care and pension expenditures) and changes in longevity to determine the level of household savings. We simulated an aggregate saving equation and derived a reduced-form model, together with other factors such as public deficits and the population structure. The model is estimated for a panel of 18 OECD countries. Our principal result is that both pension and health transfers may have a significant negative impact on the household saving. Therefore these interactions should be taken account when designing welfare reforms.
Inhibitory effect of emodin on fatty acid synthase, colon cancer proliferation and apoptosis

Fatty acid synthase (FASN) is a key anabolic enzyme for de novo fatty acid synthesis, which is important in the development of colon carcinoma. The high expression of FASN is considered a promising molecular target for colon cancer therapy. Emodin, a naturally occurring anthraquinone, exhibits an anticancer effect in various types of human cancer, including colon cancer; however, the molecular mechanisms remain to be fully elucidated. Cell viability was evaluated using a Cell Counting Kit-8 assay. The apoptosis rate of cells was quantified via flow cytometry following Annexin V/propidium iodide staining. FASN activity was measured by monitoring oxidation of nicotinamide adenine dinucleotide phosphate at a wavelength of 340 nm, and intracellular free fatty acid levels were detected using a Free Fatty Acid Quantification kit. Western blot analysis and reverse transcription-polymerase chain reaction were used to detect target gene and protein expression. The present study was performed to investigate whether the gene expression of FASN and its enzymatic activity are regulated by emodin in a human colon cancer cell line. Emodin markedly inhibited the proliferation of HCT116 cells and a higher protein level of FASN was expressed, compared with that in SW480, SNU-C2A or SNU-C5 cells. Emodin significantly downregulated the protein expression of FASN in HCT116 cells, which was caused by protein degradation due to elevated protein ubiquitination. Emodin also inhibited intracellular FASN enzymatic activity and reduced the levels of intracellular free fatty acids. Emodin enhanced antiproliferation and apoptosis in a dose- and time-dependent manner. The combined treatment of emodin and cerulenin, a commercial FASN inhibitor, had an additive effect on these activities. Palmitate, the final product of the FASN reaction, rescued emodin-induced viability and apoptosis. In addition, emodin altered FASN-involved signaling pathways, including phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinases/extracellular signal-regulated kinases 1/2. These results suggested that emodin-regulated cell growth and apoptosis were mediated by inhibiting FASN and provide a molecular basis for colon cancer therapy.
Identification of Enterostatin, the Pancreatic Procolipase Activation Peptide in the Intestine of Rat: Effect of CCK‐8 and High‐Fat Feeding

Enterostatin, the procolipase activation peptide, has been suggested in previous studies to act as a satiety signal for food intake, with a specificity for fat intake. In this study, by use of a competitive enzymelinked immunosorbent assay with a detection limit of 4.1 15 nmol/L and within 6% intra- and interassay variation, the immunoreactive and chromatographic characterization of enterostatin in intestinal content was undertaken in Sprague-Dawley rats. Following intravenous infusion of cholecystokinin octapeptide (CCK-8; 200 pmol/ kgh) for 60 min, the concentration of intestinal enterostatin increased from a basal level of 2.0 ± 0.7 KM to 5.64 ± 1.1 μM at time point 60 min. The enterostatin level remained at 4.24 ± 0.54 μM for 120 min after the CCK infusion had ceased. Pancreatic lipase and colipase activities in rat intestinal content also increased during the CCK-8 infusion. The enzyme activities reached the maximal level after 30 min of CCK infusion and thereafter progressively decreased to basal levels, remaining there during the following 2 h. The basal level of intestinal enterostatin in rats fed with standard pellets was found to be increased from 1.42 ± 0.14 to 3.86 ± 0.4,3.17 k 0.54, and 5.02 ± 1.6 FM on days 1, 3, and 7, respectively, after high-fat feeding. Parallel to the increase in intestinal enterostatin, there was a significant increase in pancreatic lipase and colipase activities in the intestine during the ingestion period of high-fat diet as compared with the control group. The estimated molecular mass of enterostatin immunoreactivity of intestinal content was similar to that of the synthetic pentapeptide. These results suggest that immunoreactive enterostatin (Val-Pro-Gly- Pro-Arg) is normally present in rat intestinal content, is significantly increased after stimulation with CCK-8, and is also increased after prolonged high-fat feeding.