Miracle-dz/UniFAR-FTUs huggingface dataset:
Measuring Disease Modification in Alzheimer's Disease

Abstract We appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ42 secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (active β -amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.
Dihydropyridine‐sensitive and omega‐conotoxin‐sensitive calcium channels in a mammalian neuroblastoma‐glioma cell line.

1. Pharmacological and kinetic properties of high‐voltage‐activated (HVA) Ca2+ channel currents were studied using the whole‐cell and perforated patch‐clamp methods in a mouse neuroblastoma and rat glioma hybrid cell line, NG108‐15, differentiated by dibutyryl cyclic AMP or by prostaglandin E1 and theophylline. 2. The HVA currents were separated into two components by use of two organic Ca2+ channel antagonists, omega‐conotoxin GVIA (omega CgTX) and a dihydropyridine (DHP) compound, nifedipine. One current component, IDHP, was blocked by nifedipine (Kd = 8.2 nM) and was resistant to omega CgTX. Conversely, the other component, I omega CgTX, was irreversibly blocked by omega CgTX and was resistant to DHPs. Thus, IDHP could be studied in isolation by a short application of omega CgTX, while I omega CgTX could be studied in the presence of nifedipine. 3. The voltage for half‐activation of IDHP was smaller than that of I omega CgTX by 13 mV. IDHP was activated at potentials that were subthreshold for voltage‐dependent K+ currents of the cell, whereas I omega CgTX was not. 4. Time courses of activation and deactivation of IDHP were faster than those of I omega CgTX. 5. Voltage‐dependent inactivation was small for both IDHP and I omega CgTX at any potential. 6. Ca(2+)‐dependent inactivation of IDHP was faster and more prominent than that of I omega CgTX. The time course of the Ca(2+)‐dependent inactivation of IDHP, but not I omega CgTX, was slowed as the membrane potential was made more positive between ‐20 and 30 mV, although amplitude of the current was increased. 7. Alkaline earth metal ions carried the two components of IHVA in the same order: Ba2+ greater than Sr2+ greater than Ca2+. 8. Metal ions blocked the two components of IHVA in the same order of potency: Gd3+ greater than La3+ greater than Cd2+ greater than Cu2+ greater than Mn2+ greater than Ni2+. 9. An alkylating agent, N‐ethylmaleimide (NEM, 0.1 mM), selectively augmented IDHP by 30%. 10. During the course of cellular differentiation induced by dibutyryl cyclic AMP, IDHP appeared earlier than I omega CgTX. 11. These results indicate that two classes of Ca2+ channels contribute to the HVA currents of this cell line. The DHP‐sensitive channel is more apt to generate Ca2+ spikes and Ca2+ plateau potentials than the omega CgTX‐sensitive channel.
The increasing recreational use of nitrous oxide: history revisited.

of insulin-resistant and insulin-sensitive obesity. J Clin Endocrinol Metab 2015; 100: 4082–91 24. Coutinho T, Goel K, Correa de Sa D, et al. Central obesity and survival in subjects with coronary artery disease: a systematic review of the literature and collaborative analysis with individual subject data. J Am Coll Cardiol 2011; 57: 1877–86 25. Dutton DJ, McLaren L. The usefulness of ‘corrected’ body mass index vs. self-reported body mass index: comparing the population distributions, sensitivity, specificity, and predictive utility of three correction equations using Canadian population-based data. BMC Public Health 2014; 14: 430 26. Yusuf S, Hawken S, Ounpuu S, et al. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet 2005; 366: 1640–9 27. CoutinhoT, Goel K, Correa de SaD, et al. Combining bodymass index with measures of central obesity in the assessment of mortality in subjects with coronary disease: role of ‘normal weight central obesity’. J Am Coll Cardiol 2013; 61: 553–60 28. Peixoto Mdo R, Benicio MH, Latorre Mdo R, Jardim PC. Waist circumference and body mass index as predictors of hypertension. Arq Bras Cardiol 2006; 87: 462–70 29. Tanamas SK, LeanME, Combet E, Vlassopoulos A, Zimmet PZ, Peeters A. Changing guards: time to move beyond body mass index for population monitoring of excess adiposity. QJM Advance Access published on November 1, 2015, doi: 10.1093/ qjmed/hcv201 30. Tsukada K, Miyazaki T, Kato H, et al. Body fat accumulation and postoperative complications after abdominal surgery. Am Surg 2004; 70: 347–51 31. Kartheuser AH, Leonard DF, Penninckx F, et al. Waist circumference and waist/hip ratio are better predictive risk factors for mortality and morbidity after colorectal surgery than body mass index and body surface area. Ann Surg 2013; 258: 722–30 32. Ozhan H, Alemdar R, Caglar O, et al. Performance of bioelectrical impedance analysis in the diagnosis of metabolic syndrome. J Investig Med 2012; 60: 587–91 33. Wang H, Chen YE, Eitzman DT. Imaging body fat: techniques and cardiometabolic implications. Arterioscler Thromb Vasc Biol 2014; 34: 2217–23 34. Bays H. Central obesity as a clinical marker of adiposopathy; increased visceral adiposity as a surrogate marker for global fat dysfunction. Curr Opin Endocrinol Diabetes Obes 2014; 21: 345–51 35. Pouliot MC, Despres JP, Lemieux S, et al. Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am J Cardiol 1994; 73: 460–8 36. Seidell JC, Perusse L, Despres JP, Bouchard C. Waist and hip circumferences have independent and opposite effects on cardiovascular disease risk factors: the Quebec Family Study. Am J Clin Nutr 2001; 74: 315–21
Distribution of genetic variation in the growth hormone 1 gene in Atlantic salmon (Salmo salar) populations from Europe and North America

The level and hierarchical distribution of genetic variation in complete sequences of the Atlantic salmon (Salmo salar) growth hormone (GH1) gene were investigated in populations from Europe and North America with a view to inferring the major evolutionary forces affecting genetic variation at this locus. Seventeen polymorphic sites were identified in complete sequences from nine populations, with levels of noncoding (intron and untranslated region sequences) nucleotide diversity being similar to those observed in other species. No variation, however, was observed in exonic sequences, indicating that nucleotide diversity in the Atlantic salmon GH1 gene is three and 25 times less than that estimated for human and Drosophila coding sequences, respectively. This suggests that purifying selection is the predominant contemporary force controlling the molecular evolution of GH1 coding sequences. Comparison of haplotype relationships within and between populations indicated that differentiation between populations from Europe and North America was greater than within‐continent comparisons. However, several haplotypes observed in the northernmost European populations were more similar to those observed in North American than to any other haplotypes observed in Europe. This is most likely to be a result of historical, rather than contemporary, gene flow. Neutrality test statistics, such as Tajima's D, were significantly positive in the European populations in which North American‐like haplotypes were observed. Although a positive Tajima's D is commonly interpreted as the signal of balancing selection, a more likely explanation in this case is that either historical migration or ascertainment bias, rather than within population local adaptation, has given rise to an excess of intermediate frequency alleles.
Evaluation of Bioactivity of Linalool-rich Essential Oils from Ocimum basilucum and Coriandrum sativum Varieties

Essential oils from Ocimum basilicum L. and Coriandrum sativum L. varieties originating from Turkey were investigated for their antimicrobial properties. The antimicrobial effects of the oil varieties were evaluated by the disc diffusion and minimum inhibitory concentration (MIC) methods against eight bacteria and three fungi. The compositions of the essential oils were analyzed and identified by GC and GC-MS. O. basilicum, C. sativum var. macrocarpum and var. microcarpum oils revealed the presence of linalool (54.4%), eugenol (9.6%), methyl eugenol (7.6%); linalool (78.8%), γ-terpinene (6.0%), nerol acetate (3.5%); and linalool (90.6%), and nerol acetate (3.3%) as the major components, respectively. The oils exhibited antibacterial activity ranging from 1.25 to 10 μL disc−1 against the test organisms with inhibition zones of 9.5-39.0 mm and minimal inhibitory concentrations values in the range 0.5-≥1μL/L. Linalool, eugenol, and methyl eugenol at 1.25 μL disc−1 had antimicrobial effects on all microorganisms, giving inhibition zones ranging from 7 to 19 mm.
Short-term forecasts and scaling of intense events in turbulence

Extreme events such as intense tornadoes and huge floods, though infrequent, are particularly important because of their disproportionate impact. Our ability to forecast them is poor at present. Large events occur also in intermittent features of turbulent flows. Some dynamical understanding of these features is possible because the governing equations are known and can be solved with good accuracy on a computer. Here, we study large-amplitude events of turbulent vorticity using results from direct numerical simulations of isotropic turbulence in conjunction with the vorticity evolution equation. We show that the advection is the dominant process by which an observer fixed to the laboratory frame perceives vorticity evolution on a short time scale and that the growth of squared vorticity during large excursions is quadratic in time when normalized appropriately. This result is not inconsistent with the multifractal description and is simpler for present purposes. Computational data show that the peak in the viscous term of the vorticity equation can act as a precursor for the upcoming peak of vorticity, forming a reasonable basis for forecasts on short time scales that can be estimated simply. This idea can be applied to other intermittent quantities and, possibly, more broadly to forecasting other extreme quantities, e.g. in seismology.
Denormalizing data into schema-free databases

With the proliferation of cloud service providers, the use of non-relational (NoSQL) data stores is increasing. In contrast to standard relational database schema design, which has its strong mathematical background in relational algebra and set theory, development with NoSQL data stores is largely based on empirical best practices. Furthermore, the huge variety of NoSQL variants may require different design considerations. In this paper, an algorithm is introduced to automatically derive cost and performance optimal schema in column-oriented data stores based on predefined queries and an initial relational database schema. Algorithms are given to perform database denormalization, as well as to transform the original queries to meet the newly created schemas.
Cloning and Characterization of a Novel Mouse AP-2 Transcription Factor, Ap-2δ, with Unique DNA Binding and Transactivation Properties*

AP-2 transcription factors are sequence-specific DNA-binding proteins expressed in neural crest and other tissues during mammalian development. Three mammalian genes, AP-2α,AP-2β, and AP-2γ, have been reported previously. A partial predicted AP-2 gene was identified in tandem with AP-2β on human chromosome 6p12-p21.1. The orthologous mouse gene, which we named Ap-2δ, was identified from a fetal mouse head cDNA library. Northern analysis revealed two transcripts in embryonic and newborn mouse brain, with markedly higher steady-state levels in the former. The predicted Ap-2δ protein comprised 452 amino acids and was highly similar to other AP-2 proteins across the DNA-binding and dimerization domains. Ap-2δ formed homodimers and heterodimers in vitro, bound an optimized AP-2 consensus DNA sequence, and transactivated gene expression in eukaryotic cells. Ap-2δ dimers bound poorly to an AP-2 binding sequence from the human metallothionein IIa promoter in vitro, revealing a sequence specificity not previously observed among other AP-2 proteins. The PY motif and critical residues in the transactivation domain, which are highly conserved in the AP-2 family and believed necessary for transactivation, were divergent in Ap-2δ. The unique protein sequence and functional features of Ap-2δ suggest mechanisms, besides tissue-specific AP-2 gene expression, for specific control of target gene activation.
Wide-band model for dielectric response of oil-impregnated paper insulation

To address the equivalent model of dielectric response of oil-impregnated paper insulation, the paper outlined a method to effectively determine parameters of the extended Debye model (EDM) using frequency domain spectroscopy (FDS) in wideband. Firstly, vector fitting method (VFM) was employed for rational approximation of the FDS curves. Thereafter, the capacitance and resistance in geometry and polarization branches of EDM were determined using circuit synthesis method. Further, to match clear physical essence in dielectric behaviors, passive enforcement was applied to strictly confine each component of EDM to be passive. In case study, a condenser body of an actual 126kV oil-impregnated paper condenser transformer bushing was modeled and solved using the proposed method. Comparative analysis on the reconstructed FDS, and RVM test results finally validated the effectiveness of the proposed method. The work conduces to improving the multi-parameter fitting problem of EDM parameterization using frequency response data.
Robust Energy Management System for a Microgrid Based on a Fuzzy Prediction Interval Model

Microgrids have emerged as an alternative to alleviate increasing energy demands. However, because microgrids are primarily based on nonconventional energy sources (NCES), there is high uncertainty involved in their operation. The aim of this paper is to formulate a robust energy management system (EMS) for a microgrid that uses model predictive control theory as the mathematical framework. The robust EMS (REMS) is formulated using a fuzzy prediction interval model as the prediction model. This model allows us to represent both nonlinear dynamic behavior and uncertainty in the available energy from NCES. In particular, the uncertainty in wind-based energy sources can be represented. In this way, upper and lower boundaries for the trajectories of the available energy are obtained. These boundaries are used to derive a robust formulation of the EMS. The microgrid installed in Huatacondo was used as a test bench. The results indicated that, in comparison with a nonrobust approach, the proposed formulation adequately integrated the uncertainty into the EMS, increasing the robustness of the microgrid by using the diesel generator as spinning reserve. However, the operating costs were also slightly increased due to the additional reserves. This achievement indicates that the proposed REMS is an appropriate alternative for improving the robustness, against the wind power variations, in the operation of microgrids.
23.4 An extremely low-standby-power 3.733Gb/s/pin 2Gb LPDDR4 SDRAM for wearable devices

With the growth of wearable devices, such as smart watches and smart glasses, there is an increasing demand for lower power dissipation, to achieve longer battery life with limited battery capacity. Nevertheless, memory bandwidth needs to increase to support high-resolution graphic engines. Since most wearable devices are event driven, they consume a bulk of power in standby mode. Therefore, it is crictical to reduce standby-mode power, as well as improve active-mode power efficiency. However, DRAM's periodic self-refresh, critical for data retention, imposes a lower bound on standby-mode power. This paper presents a 2Gb LPDDR4 SDRAM with 0.15mW standby mode power, which is 66% lower than the standby power for a memory of the same density. The proposed memory also achieves a bandwidth of 3.733Gb/s/pin. To extremely reduce standby mode power, an in-DRAM error-correction-code (ECC) engine is used for self-refresh current reduction. Intensive power gating in deep-power-down (DPD) mode, a temperature controlled internal power generator and an aggressively increased gate length is also used to reduce leakage current. In addition, active-mode power efficiency is improved by using a dual-page-size scheme.
Comparative study of stochastic wind speed prediction models

Global weather concerns have diverted the researchers to look out for clean and green energy sources. The wind power has been utilized since old days for applications such as pumping water, grain grinding mills, driving ships, etc. However, due to its uneven nature, wind energy has never been a choice of power engineers. With the inherent variability of wind due to fluctuating weather conditions, wind speed prediction techniques play a vital role in determining the feasibility of esteemed wind power projects. Modern weather forecasting involves a combination of analyzed data, computer models, knowledge of trends and patterns. In this paper various short-term statistical wind speed forecasting techniques have been analyzed and focused upon.
De novo transcriptome assembly and SSR marker development in apricot (Prunus armeniaca)

Apricot (Prunus armeniaca) is an important fruit crop worldwide. We have performed a de novo transcriptome assembly for 7 apricot accessions (`Stark Early Orange' (SEO), `Hacihaliloglu' (HH), `Perfection', `Igdir', `Roxana', `Esen1', and `Esen2'), which yielded a total number of transcripts ranging from 30,363 for `SEO' to 59,751 for `Igdir'. The pool of the reads produced from 7 accessions were assembled into 85,766 transcripts, with an average of 1165.69 nt. Functional annotation (Gene Ontology- GO and Kyoto Encyclopedia of Genes and Genomes- KEGG) was performed successfully for the transcripts. Simple sequence repeats (SSRs) were searched in the transcript pool and 14,722 di-, tri- tetra-, penta-, and hexanucleotide motif loci with a minimum of 5 repetitions for all motifs were identified. Primers were designed for 206 loci, and 72 of them were found to be polymorphic by amplifying diverse 24 apricot accessions, including 7 Plum Pox Virus (PPV)-resistant and 17 PPV-susceptible accessions. In order to test the amplification success of publicly available genomic SSRs (gSSRs) for diverse apricot accessions, an additional 88 published Prunus gSSRs were characterized amplifying the same 24 apricots and only 54 (62%) produced polymorphic bands. The new EST-SSRs could be a reliable source of primers for characterization and mapping studies of apricots, especially because they mostly flank easily scorable tri- and tetranucleotide repeats.
Multi-timescale optimization strategy for three-phase/single-phase multi-microgrids

With the increasing amount and type of connected microgrids in the near-term future power networks, how to optimize the operation of a multi-microgrid system efficiently and reliably has become essential for taking full advantage of the complex systems. In this paper, we propose a multi-timescale coordinated optimization strategy for hybrid three-phase/single-phase multi-microgrids. With the consideration of the economy of microgrids and three-phase unbalance constraints of multi-microgrids, a strategy of collecting-distributing fuzzy modified adaptive particle swarm economic optimization is provided. In this day-ahead strategy, the system is constructed as a bi-layer rolling optimizing structure, where the lower layer sets objectives for economic optimization, and the upper layer balances constrained tie-line power of single-phase microgrids based on the optimized results obtained from lower layer. On this basis, by taking day-ahead optimized tie-line power as baseline values, we obtain the real-time power of energy storage systems using an improved nondominated sorting genetic algorithm, which achieves distributed real-time optimization for the multi-microgrid. Simulation results verify that the proposed strategy is feasible.
Genotypic and technological characterization of enterococci isolated from artisanal Fiore Sardo cheese

A total of 118 enterococcal strains isolated from artisanal Fiore Sardo cheese were characterized technologically and genetically. The presence of potential virulence factors was also investigated. Strains were classified as Ec. faecium (84 strains), Ec. durans (24 strains) and Ec. faecalis (10 strains). RAPD-PCR analysis with two different primers (M13 and XD9) confirmed species identification and proved useful for the detection of interstrain variations, especially among Ec. faecium isolates. Most strains could hydrolyse casein and had weak acidifying activity in milk. None of the isolates produced lipolytic reactions. Gelatinase activity was observed in two strains of Ec. faecalis and one strain of Ec. durans. β-Haemolysis on horses' blood was never detected in any of the strains, independently of species. Most strains produced tyramine from tyrosine but none decarboxylated lysine, histidine or ornithine. Overall, a wide spectrum of resistance was observed. Almost all strains were resistant to the aminoglycosides, gentamycin, kanamycin, streptomycin, neomycin, and to the semisynthetic penicillin, oxacillin, but resistance to vancomycin was not widespread among our strains: only one Ec. faecium and one Ec. durans strain were found to be vancomycin resistant. Our results show a certain diversity in technological traits of the enterococcal strains isolated from artisanal Fiore Sardo, together with a low incidence of some potentially pathogenic traits of health concern.
Design and Implementation of a Triple-Band Re-Configurable Microstrip Antenna

A hybrid combination of RF MEMS and microstrip patch triple band inset-fed reconfigurable antenna is presented. A rectangular slot is placed on the antenna to obtain a dual frequency antenna. Furthermore, MEMS switches are placed on the slot to change the electrical length of the slot and obtain a third resonance frequency. Similarly, MEMS switches are used in the inset to match the antenna input impedance at different frequencies. All of the parts are manufactured and the hybrid structure will be built