Miracle-dz/UniFAR-FTUs huggingface dataset:
Agonist Action at D2(short) Dopamine Receptors Determined in Ligand Binding and Functional Assays

Abstract: Mechanisms of agonist action at the G protein‐coupled D2(short) dopamine receptor expressed in Chinese hamster ovary cells have been investigated. Agonist binding was assayed in the presence and absence of GTP (100 µM). Data in the absence of GTP were fitted best by a two‐site model (apomorphine, dopamine, 10,11‐dihydroxy‐N‐n‐propylnorapomorphine hydrochloride, and quinpirole) or a one‐site model [bromocriptine, dihydroergocristine, and (−)‐3‐(3‐hydroxyphenyl)‐N‐propylpiperidine hydrochloride], whereas in the presence of GTP a one‐site model was the best fit for all compounds. Agonist binding parameters were used to provide a measure of the ability of the agonist to stabilise the ternary complex of agonist/receptor/G protein. Agonist stimulation of [35S]guanosine 5′‐O‐(3‐thiotriphosphate) ([35S]‐GTPγS) binding for a range of agonist concentrations was measured and the EC50 and maximal effects determined. The initial rates of [35S]GTPγS binding induced by maximally stimulating agonist concentrations were also recorded. Simultaneous inhibition of agonist‐stimulated [35S]GTPγS binding and receptor occupancy by spiperone was determined. Agonist inhibition of forskolin‐stimulated cyclic AMP accumulation was determined for a range of agonist concentrations and the EC50 and maximal inhibition recorded. The data on the maximal agonist responses showed that it was possible to detect a spectrum of agonist efficacy (partial and full agonism) in both functional assays. The data on the apparent potencies of agonists to elicit the functional responses showed that different extents of amplification of response were seen for different agonists in both assays. The maximal activity data have been compared with the stabilisation of the agonist/receptor/G protein ternary complex as measured in binding assays.
A 3-V delay-modulated PLL synthesizer for analog FM transmitters

An analog FM modulator operating within the loop bandwidth of a frequency synthesizer is presented. Its operation is based on delay-modulating the reference frequency of the synthesizer PLL, thus causing phase modulation in the synthesized carrier. To convert delay-control to FM, modulating input is first integrated. The modulator circuit is implemented in a 1. 2µm BiCMOS process, has 2.8 V supply voltage and 1.5 mA supply current. In in-system tests, the modulator showed 7 kHz/V gain, 20 Hz(rms) residual FM and -31. -37 dB THD on audio band.
Broad-Spectrum Inhibition of Retroviral and Filoviral Particle Release by Tetherin

ABSTRACT The expression of many putative antiviral genes is upregulated when cells encounter type I interferon (IFN), but the actual mechanisms by which many IFN-induced gene products inhibit virus replication are poorly understood. A recently identified IFN-induced antiretroviral protein, termed tetherin (previously known as BST-2 or CD317), blocks the release of nascent human immunodeficiency virus type 1 (HIV-1) particles from infected cells, and an HIV-1 accessory protein, Vpu, acts as a viral antagonist of tetherin. Here, we show that tetherin is capable of blocking not only the release of HIV-1 particles but also the release of particles assembled using the major structural proteins of a variety of prototype retroviruses, including members of the alpharetrovirus, betaretrovirus, deltaretrovirus, lentivirus, and spumaretrovirus families. Moreover, we show that the release of particles assembled using filovirus matrix proteins from Marburg virus and Ebola virus is also sensitive to inhibition by tetherin. These findings indicate that tetherin is a broadly specific inhibitor of enveloped particle release, and therefore, inhibition is unlikely to require specific interactions with viral proteins. Nonetheless, tetherin colocalized with nascent virus-like particles generated by several retroviral and filoviral structural proteins, indicating that it is present at, or recruited to, sites of particle assembly. Overall, tetherin is potentially active against many enveloped viruses and likely to be an important component of the antiviral innate immune defense.
Isotype-Restricted Corepressor Recruitment: a Constitutively Closed Helix 12 Conformation in Retinoic Acid Receptors β and γ Interferes with Corepressor Recruitment and Prevents Transcriptional Repression

ABSTRACT Retinoic acid receptors (RARs) are ligand-regulated transcription factors that play multiple roles in vertebrate development and differentiation. RARs as a class are capable of both repressing and activating target gene expression. Transcriptional repression is mediated through the recruitment of corepressor proteins such as SMRT. Notably, vertebrates encode three major forms of RARs, α, β, and γ, and these distinct RAR isotypes differ in the ability to recruit a corepressor. RARα strongly interacts with SMRT and can repress target gene transcription, whereas RARβ and -γ interact with SMRT only weakly and fail to repress. We report here the use of a genetic suppressor approach, based on a yeast two-hybrid interaction assay using Saccharomyces cerevisiae, for the isolation of RARβ mutants that have gained the RARα-like corepressor phenotype, i.e., a strong interaction with SMRT and the ability to repress gene expression in vertebrate cells. Analysis of these gain-of-function mutants indicates that the different corepressor interaction properties of RARα, -β and -γ are determined by a gating mechanism through which amino acid differences in the helix 3 region of these receptors influence the position of the receptor C-terminal helix 12 domain. As a consequence, the RARβ and RARγ receptors appear to adopt a constitutively closed helix 12 conformation in the absence of hormone that may approximate the conformation of RARα when bound to hormone agonist. This closed helix 12 conformation in RARβ and RARγ blocks corepressor binding, prevents repression, and permits significant levels of target gene activation even in the absence of hormone. We refer to this phenomenon as a “gate-latch” model of corepressor regulation.
Long-Term Risk to Develop Hypertension in Women With Former Preeclampsia

Introduction: Women with former preeclampsia (exPE) develop chronic hypertension 4 times more often than healthy parous controls. Women, destined to develop remote chronic hypertension, had increased left ventricular mass index (LVMI) and diastolic blood pressure (BP) prior to the onset of hypertension as compared to those remaining normotensive. However, longitudinal data on the progress of this increased LVMI in women destined to develop hypertension are lacking. Methods: We included 20 women with exPE and 8 parous controls. At both 1- and 14-year postpartum (pp), we performed cardiac ultrasound and determined circulating levels of the metabolic syndrome variables. Of 14-year pp, 7 (35%) former patients had developed chronic hypertension. We compared these 7 former patients with both the 13 former patients who remained normotensive and the 8 parous controls using the Mann-Whitney U test and Kruskal-Wallis analysis. Results: Women with hypertensive exPE differed from their normotensive counterparts by a higher incidence of early-onset preeclampsia (PE) in their index pregnancy and a higher rate of recurrence in next pregnancies. At 1-year pp, they also had high/normal BP and higher fasting insulin levels. At 14 years pp, the relative left ventricular wall thickness was higher, and the E/A ratio was lower, in the hypertensive group relative to those remaining normotensive. Conclusion: Women with exPE are at increased risk of developing chronic hypertension, when (1) the PE in the index pregnancy had an early-onset and/or recurred in next pregnancies and (2) the 1-year pp. Blood pressure was high normal. We also noticed that at 14 years pp, the hypertensive group showed signs of concentric left ventricular remodeling along with a decreased E/A ratio.
Generic Proposal Evaluator: A Lazy Learning Strategy Toward Blind Proposal Quality Assessment

Existing detection or recognition systems typically select one state-of-the-art proposal algorithm to produce massive object-covered candidate windows, and a quality metric specifically designed for this algorithm is utilized to single out small amounts of proposals. However, in practice, the accuracies of different proposal algorithms significantly change from one image content to another one. To obtain more robust proposal results, a generic proposal evaluator (GPE) is highly desired, which could choose optimal candidate windows across multiple proposal algorithms. In this paper, we propose a lazy learning strategy to train the GPE, which aims to blindly estimate the quality of each proposal without accessing to its manual annotation. Unlike the traditional end-to-end framework that learns a universal model from all training samples, we try to build query-specific training subset for each given proposal, where only its ${k}$ -nearest-neighborhoods are collected from all labeled candidate windows. Benefits from the capability of updating the regression parameters for different visual contents, the proposed method delivers a higher quality prediction accuracy even with respect to the deep neural network learned by end-to-end method. Experimental results confirm that the proposed algorithm significantly outperforms many state-of-the-art proposal quality metrics.
Dutch Disease in Central and Eastern European Countries

Bulgaria, Croatia, Estonia, Latvia, Lithuania, Hungary, Poland, Czech Republic, Romania, Slovenia, and Slovakia have all benefited from an increase of European Union capital transfers of funds since the demand for European integration. At the same time, foreign direct investments have risen, mainly due to the liberalisation of capital movements. The effects of those funds and the reduction of financial costs can be considered as analogous to the phenomenon known as Dutch Disease. That is to say, the inflow of financial transfers is also considered a curse. In order to eliminate this curse we must take into account the two effects associated with Dutch Disease: the ‘spending effect’ and the ‘resource movement effect’. Public policies have not been appropriate and have not prevented the real exchange rate appreciation, thereby contributing to a poor performance in terms of competitiveness and economic growth. After a descriptive analysis of some variables, we estimate a set of equations that take account of the direct and indirect effects of European Union funds and financial costs on the economy where the effects on the real exchange rate play the major role.
Cloning the origin of transfer region of the resistance plasmid R1.

The insertion of a 7.7‐kb EcoRI fragment of the resistance plasmid R1 into pBR325 yielded a plasmid which is mobilizable by pDB12, a multicopy derivative of R1drd‐19 lacking most of the resistance determinants. The vector alone was not mobilizable in this system. From this observation we conclude that we have cloned the origin of transfer (oriT) of R1. After inserting a 5.3‐kb PvuII‐EcoRI fragment of the 7.7‐kb region into pUC9 the DNA was cleaved randomly with DNaseI and BamHI linkers were attached to the ends. A subsequent BamHI digestion and electrophoretic separation of the resulting DNA molecules by their size allowed us to generate an ordered series of stepwise shortened plasmids. Plasmids with a deletion of approximately 3400 bp could no longer be mobilized. Since the next larger plasmid with 284 additional base pairs could be mobilized, we are able to confine the oriT location within this extra nucleotide stretch. The DNA sequence of this region was determined. Dominant features within the DNA region are a high AT content and five inverted repeats, which might function as recognition or substrate sites for proteins of the conjugational transfer system.
Screening for lectins from basidiomycetes and isolation of Punctularia atropurpurascens lectin

Aqueous extracts of basidiomycete fungi were screened for the presence of lectins by hemagglutination (HA) assays with mouse, rabbit, and sheep red blood cells. From mycelia and/or fruiting bodies, 23 extracts were prepared; 15 extracts exhibited HA activity towards mouse erythrocytes, with specific activities ranging from 12 to 440 lectin units (LU) mg−1 protein. In HA inhibition assays, 43 carbohydrates including mono‐, di‐, tri‐, tetrasaccharides, glycoproteins, and polysaccharides were tested as haptens, to determine the saccharide‐binding specificities of the lectins. A novel lectin with specificity towards N‐acetyl‐glucosamine was purified from mycelia of Punctularia atropurpurascens using affinity chromatography on chitosan–Sepharose. The lectin has a subunit molecular mass of 67 kDa determined by SDS–PAGE and a pI of 5.0.
An Inexpensive Digital Image Analysis Technique for Liver Fibrosis Quantification in Chronic Hepatitis B Patients.

BACKGROUND AND AIM Quantitative digital imaging analysis to evaluate liver fibrosis is accurate, but its clinical use is limited by its high cost and lack of standardization. We aimed to validate an inexpensive digital imaging analysis technique for fibrosis quantification in chronic hepatitis B patients. MATERIAL AND METHODS In total, 142 chronic hepatitis B patients who underwent liver biopsy and analysis of serum fibrosis markers were included. Images of Sirius red stain sections were captured and processed using Adobe Photoshop CS3 software. The percentage of fibrosis (fibrosis index) was determined by the ratio of the fibrosis area to the total sample area, expressed in pixels, and calculated automatically. RESULTS A strong correlation between the fibrosis index and the Ishak, Metavir, and Laennec histological staging systems were observed (r = 0.83, 0.86, and 0.84, respectively; < 0.001). The cutoff value associated with cirrhosis was 7.7% with an area under the receiver operating characteristic curve (AUROC) of 0.95 (95% confidence interval [CI], 0.92-0.99, p < 0.001). Furthermore, the fibrosis index yielded a cutoff value of 8.9% (AUROC, 0.74; 95% CI, 0.66-0.86), 12% (AUROC, 0.84; 95% CI, 0.75-0.93), and 14% (AUROC, 0.97; 95% CI, 0.92-1.0) for the diagnosis of cirrhosis 4a, 4b, and 4c, respectively. No serum markers or fibrosis models were correlated with the fibrosis index in Metavir F2-F4. CONCLUSIONS The present digital imaging analysis technique is reproducible and available worldwide, allowing its use in clinical practice, and can be considered as a complementary tool to traditional histological methods.
Financial report and public accountability culture in Indonesia

Studi ini mengkaji kualitas Akuntabilitas publik di Indonesia yang representasikan oleh praktik laporan keuangan menggunakan teori legitimasi. Kami menemukan praktik akuntabilitas publik di Indonesia masih di legitimasi pragmatis. Laporan keuangan dan audit laporan ini dikembangkan hanya untuk pengguna utama laporan keuangan. Mereka tidak disiapkan untuk kepentingan masyarakat umum, DPR dan pemerintah sebagai representasi dari masyarakat belum mengembangkan budaya tata kelola laporan keuangan dan audit untuk memastikan bahwa praktek akuntabilitas di Indonesia menyajikan informasi yang benar atau adil yang diharapkan oleh masyarakat. Masyarakat membutuhkan informasi tentang seberapa efektif pemerintah dalam menggunakan dana negara untuk memenuhi janji mereka dalam kampanye pemilu serta kewajiban mereka sebagaimana diatur dalam banyak hukum yang mengatur operasi dari pemerintah. Masyarakat juga perlu informasi tentang keamanan dan tumbuh dari kekayaan mereka disimpan di sektor keuangan seperti yang dijanjikan oleh bank dan lembaga keuangan non-bank.
A jam-jar model of life expectancy and limits to life

Age at death will increasingly cluster in the 90s and the life expectancy of men and women will converge, according to a study by academics from Cass Business School in partnership with the ILC-UK. Over the coming decades, men in particular will live longer, increasing the need for the country to face the challenges of an ageing society. Based on historical mortality data from England and Wales, the researchers developed a new method for forecasting life expectancy – the results will be beneficial to individuals, government policy makers, pension providers and insurers as the new forecasts provide more certainty with which to plan. One of great success stories in the United Kingdom is that people are living longer and men’s life expectancy is catching up with women’s. Male life expectancy at birth is now almost 80 years, having advanced 14 years since 1950 thanks to reductions in smoking, a decline in hazardous occupations, better health care and higher standards of living. This success presents the country with a huge economic opportunity if these extra years are spent in prosperity and good health, but significant economic danger if they are not. Realising the full potential of older citizens of the United Kingdom will be central to the Government’s response to changing economic circumstances and the drive to build a strong, fair economy for the twenty-first century. However, the challenges posed by an ageing society come at a cost in terms of pensions, higher health and social care costs and infrastructural change. Professor Mayhew and co-author David Smith used a pioneering new mathematical technique known as decomposition - or the 'jam-jar model' - to produce contributions to life expectancy for each 10 year age band (e.g. 70 to 80). The method provides more certainty over which age groups are experiencing significant gains and more accurate information about possible limits to life expectancy. Talking about the model, Professor Mayhew said: “Each decade of retired life can be imagined as a jam-jar which if filled to the brim with life years would give a maximum of 10 years. As each jam-jar approaches the brim, extra life years are transmitted to the next decade of life in a predictable wave-like fashion until all are full. ” To illustrate this, in 1950, when male life expectancy at 60 in England and Wales was 15 years, the contribution from the decade of life between 80 and 90 was only 9.1% of the total. By 2009, when life expectancy was 22 years, this decade of life contributed 18.5%
A super compact multilayer broadband left-handed metamaterials for RF/MMIC applications

A super compact multilayer broadband left-handed metamaterial medium for RF/MMIC applications is proposed and demonstrated by the full wave simulation and equivalent circuit analysis. Here we propose to employ multilayer technology to realize left-handedness. The unit cell of the multilayer structure is a thousand times smaller than that of the microstrip structure to achieve the same series capacitance. The left handedness of the novel structure extends from 2.1GHz to 28.2GHz. performing in much wider bandwidth than those reported so far. The compactness and broad left-handed operating bandwidth make the proposed left-handed metamaterial be well incorporated with RF/MMIC applications.
Distinct regulation of mitochondrial localization and stability of two human Sirt5 isoforms

Seven human Sir2 homologues (sirtuin) have been identified to date. In this study, we clarified the mechanism of subcellular localization of two SIRT5 isoforms (i.e., SIRT5iso1 and SIRT5iso2) encoded by the human SIRT5 gene and whose C‐termini slightly differ from each other. Although both isoforms contain cleavable mitochondrial targeting signals at their N‐termini, we found that the cleaved SIRT5iso2 was localized mainly in mitochondria, whereas the cleaved SIRT5iso1 was localized in both mitochondria and cytoplasm. SIRT5ΔC, which is composed of only the common domain, showed the same mitochondrial localization as that of SIRT5iso2. These results suggest that the cytoplasmic localization of cleaved SIRT5iso1 is dependent on the SIRT5iso1‐specific C‐terminus. Further analysis showed that the C‐terminus of SIRT5iso2, which is rich in hydrophobic amino acid residues, functions as a mitochondrial membrane insertion signal. In addition, a de novo protein synthesis inhibition experiment using cycloheximide showed that the SIRT5iso1‐specific C‐terminus is necessary for maintaining the stability of SIRT5iso1. Moreover, genome sequence analysis from each organism examined indicated that SIRT5iso2 is a primate‐specific isoform. Taken together, these results indicate that human SIRT5 potentially controls various primate‐specific functions via two isoforms with different intracellular localizations or stabilities.
A survey on NB-IoT downlink scheduling: Issues and potential solutions

The NarrowBand Internet of Things (NB-IoT) is one of the most promising technologies that fits the requirements of the low-power wide area networks (LPWAN). NB-IoT targets on supporting communications for small amount of data during a relatively long period of time (i.e., delay tolerant), which is one of the key features of IoT applications. Several studies have been conducted by some standard working groups to define the standards for NB-IoT. For example, the working group 3GPP aims to provide communication protocols with low energy consumption, good coverage penetration, and so on. Compared with the existing wireless communication protocols, less spectrum is allocated for NB-IoT. Thus, how to more efficiently use the resource/spectrum (i.e., resource allocation and scheduling) is one of the key issues. In this paper, we first describe the design of the physical layer for the downlink communication, especially the scheduling process. Secondly, we discuss the issues for resource allocation in NB-IoT while the delay requirement in the physical layer is satisfied. Thirdly, we discuss the open questions and possible solutions.
NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients

Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motoneurons in the cerebral cortex, brainstem and spinal cord. Neuroinflammation plays an important role in the pathogenesis of ALS and involves the activation of microglia and astrocytes. Intracellular inflammasome complexes are part of the innate immunity as they sense and execute host inflammatory responses. The best characterized component is the NLRP3 inflammasome comprised of the NLR protein NLRP3, the adaptor ASC and pro‐caspase 1. The NLRP3 inflammasome is critical for the activation of caspase 1 and the processing and release of IL1β and IL18. In this study, we investigated the expression, activation and co‐localization of the NLRP3 inflammasome in the spinal cord of male SOD1(G93A) mice carrying a mutant human superoxide dismutase 1 (SOD1) variant and regarded as an animal model for ALS as well as in post‐mortem tissue of ALS patients. NLRP3 and its molecular components as well as IL1β were already detectable in SOD1 mice at a pre‐symptomatic stage after 9 weeks and further increased in 14 week old animals. Spinal cord astrocytes were identified as the major cell type expressing NLRP3 components. In human ALS tissue, we also found increased NLRP3, ASC, IL18 and active caspase 1 levels compared to control patients. Our findings suggest that astroglial NLRP3 inflammasome complexes are critically involved in neuroinflammation in ALS. GLIA 2015;63:2260–2273