Miracle-dz/UniFAR-FTUs huggingface dataset:
Haemodynamic Correlates of Early and Delayed Responses to Sublingual Administration of Isosorbide Dinitrate in Migraine Patients

In normal subjects or migraine patients, nitrates induce a non-specific early headache caused by vasodilation of intracranial arteries. In migraineurs a delayed headache response to nitrates may have a typical clinical profile of a spontaneous migraine attack. The cerebral vasomotor changes of this delayed response require further study. Isosorbide dinitrate (IDN), an exogenous nitric oxide (NO) donor, was given at a dose of 5 mg sublingually and a bilateral transcranial Doppler device was used to monitor bilateral mean velocity (Vm) changes at the middle cerebral artery (MCA) after IDN administration and until delayed headache occurred. Spontaneous migraine-like headache occurred only in migraine patients during the delayed phase after IDN and was accompanied by a prolonged arterial vasodilation compared to normal subjects. This vasomotor response was more evident on the customary side of the head pain of a spontaneous migraine attack. Our findings suggest a particular vasomotor response to nitrates in migraine patients. This response is associated with the nitrate-induced headache and it is not evident in healthy pain-free controls during the delayed phase after administration of an NO donor. Owing to the short half-life of NO, the neurotransmitter released by IDN, and because of the late onset of headache, we believe the mechanism is unlikely to be vascular in origin, but may have a neurogenic component.
Psychologic Processes in Daily Life With Chronic Whiplash: Relations of Posttraumatic Stress Symptoms and Fear-of-pain to Hourly Pain and Uptime

ObjectivesRecent models of the relationship between posttraumatic stress and whiplash pain suggest that psychological stress relating to a motor vehicle crash may influence pain perception. The mechanisms of this relationship may be through more direct, psychological pathways, or through factors proposed by the fear-avoidance models of chronic pain. This study sought to investigate the relative contribution of fear-of-pain and trauma symptomatology to daily pain and time spent in an upright posture (uptime) in chronic whiplash-associated disorder (WAD). MethodsHourly electronic-diary reports were used to explore the within-day relationship of psychological trauma symptoms and fear-of-pain to same-hour and next-hour pain reports and next-hour uptime (measured by accelerometers) in 32 individuals with a chronic WAD. Within-person effects were analyzed for 329 diary entries using multilevel modeling with fixed slopes and random intercepts. ResultsReports of trauma-related hyperarousal were associated with greater same-hour pain, and this relationship was mediated by fear-of-pain. Fear-of-pain and uptime were independently associated with reports of increased next-hour pain (controlling for first-order serial autocorrelation). Fear-of-pain was unrelated to next-hour uptime, but trauma-related avoidance symptoms were associated with reduced uptime. This study supports the relationship between psychological trauma responses and pain, suggesting behavioral (avoidance) pathways and effects on pain perception through fear-of-pain. These findings reinforce the need to evaluate traumatic stress as a factor in recovery from WAD.
Plant Sterol Feeding Induces Tumor Formation and Alters Sterol Metabolism in the Intestine of Apc MinMice

Dietary plant sterols reduce the absorption of cholesterol and therefore increase intraluminal cholesterol concentration. We examined how plant sterol esters from functional foods affect intestinal tumorigenesis in tumor-prone adenomatous polyposis coli (Apc) Minmice. Feeding plant sterols at 0.8% increased the number of intestinal adenomas, and the effect was significant in female mice. The concentration of mucosal free sitosterol increased by eightfold in plant sterol males and by threefold in plant sterol females when compared with respective controls. The concentration of mucosal free cholesterol was significantly lower in plant sterol males than in control males, and the decrease in free cholesterol was accompanied with a significant increase in nuclear sterol regulatory element binding protein-2. No difference was found in the levels of β-catenin, cyclin D1, epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, or caveolin-1 in either gender after plant sterol feeding. Among all measured parameters, higher levels of estrogen receptor β and free cholesterol in the mucosa were among the strongest predictors of increased intestinal tumorigenesis. In addition, gene expression data showed significant enrichment of up-regulated genes of cell cycle control and cholesterol biosynthesis in plant sterol females. The results indicate that high intake of plant sterols accelerates intestinal tumorigenesis in female Apc Minmice; however, the mechanism behind the adverse effect remains to be discovered.
CDKN2A but not TP53 mutations nor HPV presence predict poor outcome in metastatic squamous cell carcinoma of the skin

Genetic alterations in metastatic cutaneous squamous cell carcinoma (CSCC) which might serve as prognostic biomarkers are not well investigated. We investigated the mutation status and protein expression of the CDKN2A (INK4a‐ARF) and TP53 genes in metastatic CSCCs and correlated this with clinicopathological variables, HPV presence, and survival data. Sequence analysis was performed on formalin‐fixed and paraffin‐embedded tissue of 35 metastases and their primary tumors, and was correlated with immunohistochemical stainings for p53, p16 and p14. Beta‐PV and alpha‐PV DNA was detected using PCR‐based assays. Kaplan–Meier and Cox regression methods were used for survival assessment. CDKN2A was mutated in 31% of the metastases and their primary tumors, while the TP53 gene was mutated in 51% of the metastases. P53 protein expression was significantly associated with missense type of mutations (p = 0.002). No persistent HPV types were detected. CDKN2A mutations were significantly associated with disease‐specific death (p = 0.001). A significant difference was observed in disease‐specific survival between patients with or without a CDKN2A mutation (p = 0.010), while this was not the case for TP53. At univariate Cox's regression analysis tumor size (p = 0.010), invasion depth (p = 0.030) and CDKN2A mutations (p = 0.040) were significantly related to shorter disease‐specific survival. At multivariate Cox's regression only tumor size had an adverse effect on survival (p = 0.002). In conclusion, our study indicates that the CDKN2A mutation status might be of prognostic value in metastatic CSCCs. In most cases, CDKN2A and TP53 mutations are early genetic events in CSCC tumorigenesis. The possible role of HPV in metastatic CSCC needs further exploration.
A simple method for automated extraction of BJT thermal resistance from Early voltage measurements

We present a methodology for thermal resistance R/sub TH/ extraction from the Early voltage dependence on collector current. This method does not require pulsed, temperature, or frequency measurements and hence, can be easily automated. Results for a BJT from an SOI/DTI complementary BiCMOS process and for a SiGe HBT from a 50 GHz BiCMOS process are presented and comparison to SPICE simulations is made.
Advances in active control of machinery and device noise

Active control has been gaining an increasing role in protecting humans against excessive exposure to lowfrequency acoustic noise. They are designed as supplements to passive isolation techniques or as autonomous solutions. Rapid development of technology including smart materials, electronics, control theory and signal processing algorithms makes active noise control an attractive field for research, development and applications. The plenary lecture presents the problem of machinery and device noise control and author's contribution to this technology. Ideas behind classical and modern control structures and techniques along with guidelines for their choice are demonstrated. Emerging modeling, identification and control problems are also addressed. They are related to complex coupled physical and control phenomena. Concepts and solutions without taking unrealistic assumptions are presented. Perspectives for active control of machinery and device noise are outlined.
Code Quality: Examining the Efficacy of Automated Tools

A number of software tools have been designed to determine code quality. These automated tools can examine a computer program and provide a score based on a designed set of software metrics. In this exploratory study, we examined the quality of code written by students in an introductory Python programming course on one programming assignment. Each student submission was evaluated using an automated tool, Pylint, a code analyzer widely used by the Python community. The instructor also graded these submissions using predefined rubrics that evaluated code logic, syntax and style. We compared the two code quality scores. We found that Pylint does a good job of identifying errors, and formatting issues. But, the Pylint scores were lower than those provided manually by instructors.
Natives and non‐natives plants show different responses to elevation and disturbance on the tropical high Andes of Ecuador

Abstract The aim was to assess patterns of plant diversity in response to elevation and disturbance in a tropical mountain. The study area was located in north‐central portion of the Eastern Cordillera of the Ecuadorian Andes, on a road from 1,150 m a.s. l. (Osayacu) to 4,000 (Papallacta). Along a mountain road spanning a wide altitudinal gradient, at 20 elevations we sampled three plots: one at the roadside and two perpendicular to the roadside. The relationship between elevation and species richness was assessed using linear and quadratic regressions, the effect of disturbance on species richness was determined by ANCOVA and a t test with parameters obtained from quadratic equations. Similarity of species composition among the roadside and sites distant was evaluated with the Chao‐Jaccard and classic Jaccard similarity indices, the distribution of non‐native species according to their origin were analyzed with linear and quadratic regression. The native species showed a linearly monotonic decrease with elevation, whereas non‐natives showed a quadratic distribution. Disturbed areas had the greatest number of non‐native species and lower native species richness, showing also a high floristic similarity; less disturbed areas showed the opposite. The non‐native species of temperate origin were more numerous and showed unimodal elevational distribution, while species of tropical origin were few and decreased linearly with elevation. We conclude that in a tropical highland mountain range, native and non‐native plant species respond differently to elevation: native species exhibit a monotonically linear decrease, and non‐native species show a unimodal trend. Disturbance positively affects non‐native species showing higher richness and fewer species turnover. In addition, the non‐native species are located along of the elevational gradient in relation to their biogeographic origin.
Separating Accuracy from Forecast Certainty: A Modified Miscalibration Measure

The standard interval forecasting task is modified, asking subjects to provide point predictions for future returns and assess the likelihood of fixed length intervals around their point estimates. The difference between the subjective likelihood estimates and the realized hit rate is advanced as an improved miscalibration measure. Class and take-home studies reveal that 140 of 169 finance students and experts overestimate their hit rates, confirming the overprecision hypothesis. A comparative study additionally shows that the revised task weakly decreases the miscalibration rates from 50% to 38% (p=0.16).
Good Governance and Agricultural Efficiency

This study aims to understand the effects governance indicators on the agricultural efficiency using European countries as a tool. It focuses on the efficiency of EU countries together with Turkey. In the first stage Data Envelopment Analysis and Malmquist Index are used to derive efficiency scores and the Total Productivity Change in time for 24 countries during the study period. A panel data Tobit regression is employed in the second stage to assess the key governance indicators explaining the observed variations in the efficiency levels. Four governance indicators namely, voice and accountability control of corruption, government effectiveness and regulatory quality together with the control variables; agricultural exports, education, research and development expenditures are analyzed in this stage. Findings show that the average efficiency of EU countries was slightly increased during the study period. The impact of voice and accountability, the share of R&D in GDP and the share of food products in exports upon the agricultural efficiency are positive whereas the impacts of the share of GDP allocated to education upon agricultural efficiency is negative.
Evidence of non‐linearity in the association of glycemic control with influenza/pneumonia mortality: a study of 19 000 adults from the US general population

Diabetes is a major public health problem and thought to be a risk factor for infectious diseases, but pertinent epidemiological evidence is limited. This study aimed to analyse the associations of diabetes, disease duration and glycated haemoglobin levels (HbA1c) with infectious diseases mortality in the general population, including the investigation of potential non‐linear relationships.
Statistics and Deep Belief Network-Based Cardiovascular Risk Prediction

Objectives Cardiovascular predictions are related to patients' quality of life and health. Therefore, a risk prediction model for cardiovascular conditions is needed. Methods In this paper, we propose a cardiovascular disease prediction model using the sixth Korea National Health and Nutrition Examination Survey (KNHANES-VI) 2013 dataset to analyze cardiovascular-related health data. First, statistical analysis was performed to find variables related to cardiovascular disease using health data related to cardiovascular disease. Second, a model of cardiovascular risk prediction by learning based on the deep belief network (DBN) was developed. Results The proposed statistical DBN-based prediction model showed accuracy and an ROC curve of 83.9% and 0.790, respectively. Thus, the proposed statistical DBN performed better than other prediction algorithms. Conclusions The DBN proposed in this study appears to be effective in predicting cardiovascular risk and, in particular, is expected to be applicable to the prediction of cardiovascular disease in Koreans.
A new political system model: Semi‐parliamentary government

Semi-parliamentary government is a distinct executive-legislative system that mirrors semi-presidentialism. It exists when the legislature is divided into two equally legitimate parts, only one of which can dismiss the prime minister in a no-confidence vote. This system has distinct advantages over pure parliamentary and presidential systems: it establishes a branch-based separation of powers and can balance the ‘majoritarian’ and ‘proportional’ visions of democracy without concentrating executive power in a single individual. This article analyses bicameral versions of semi-parliamentary government in Australia and Japan, and compares empirical patterns of democracy in the Australian Commonwealth as well as New South Wales to 20 advanced parliamentary and semi-presidential systems. It discusses new semi-parliamentary designs, some of which do not require formal bicameralism, and pays special attention to semi-parliamentary options for democratising the European Union.
MMP-9 Sheds the β2 Integrin Subunit (CD18) from Macrophages*S

Activated macrophages are essential effectors of immunity and a rich source of matrix metalloproteinase-9 (MMP-9; gelatinase B). To search for cellular substrates of the enzyme, we subjected wild-type macrophages and macrophages expressing an autoactivating form of pro-MMP-9 (M9A macrophages) to proteomics analysis. Two-dimensional liquid chromatography together with tandem mass spectrometry identified 467 proteins in medium conditioned by M9A and/or wild-type macrophages. Subtractive proteomics identified 18 candidate MMP-9 substrates. Biochemical studies confirmed that two transmembrane proteins, β2 integrin subunit (CD18) and amyloid protein precursor (APP), were enriched in the medium of M9A macrophages. To identify potential cleavage sites, we synthesized an overlapping library of peptides that spanned 60 residues of the ectodomain and transmembrane domain of β2 integrin. Active MMP-9 cleaved a single peptide, ECVKGPNVAAIVGGT, at residues corresponding to Ala705 and Ile706 of the β2 integrin. Peptides corresponding to this cleavage site were detected by tandem mass spectrometric analysis only in medium from M9A macrophages, strongly supporting the proposal that β2 integrin is shed by autoactivating MMP-9. Our observations indicate that subtractive proteomics in concert with peptide substrate mapping is a powerful approach for identifying proteolytic substrates and suggest that MMP-9 plays previously unsuspected roles in the regulation and shedding of β2 integrin.
Liver Retinol Transporter and Receptor for Serum Retinol-binding Protein (RBP4)*

Background: Mechanisms by which RBP4 interacts with cells are not completely understood. Results: 1300002K09Rik (RBPR2) is identified as a Stra6-related protein expressed in liver, intestine, and obese fat that mediates RBP4 binding and retinol transport. Conclusion: RBPR2 is a novel RBP4 receptor that mediates retinol uptake. Significance: RBPR2 may be important for whole body retinol homeostasis or cellular actions of RBP4 in certain tissues. Vitamin A (retinol) is absorbed in the small intestine, stored in liver, and secreted into circulation bound to serum retinol-binding protein (RBP4). Circulating retinol may be taken up by extrahepatic tissues or recycled back to liver multiple times before it is finally metabolized or degraded. Liver exhibits high affinity binding sites for RBP4, but specific receptors have not been identified. The only known high affinity receptor for RBP4, Stra6, is not expressed in the liver. Here we report discovery of RBP4 receptor-2 (RBPR2), a novel retinol transporter expressed primarily in liver and intestine and induced in adipose tissue of obese mice. RBPR2 is structurally related to Stra6 and highly conserved in vertebrates, including humans. Expression of RBPR2 in cultured cells confers high affinity RBP4 binding and retinol transport, and RBPR2 knockdown reduces RBP4 binding/retinol transport. RBPR2 expression is suppressed by retinol and retinoic acid and correlates inversely with liver retinol stores in vivo. We conclude that RBPR2 is a novel retinol transporter that potentially regulates retinol homeostasis in liver and other tissues. In addition, expression of RBPR2 in liver and fat suggests a possible role in mediating established metabolic actions of RBP4 in those tissues.
More on decentralization and economic growth

This article casts new evidence on the effects of decentralization on economic growth. Based on the literature on the effects of institutions on the economy, such effects are assumed to accrue through total factor productivity (TFP). Five variables to capture decentralization are proposed in order to overcome the recent criticisms of the empirical approaches regarding the proper measures of variables capturing decentralization. Panel data for the regions of Spain over the 1986–2010 period are used. In general, the results show that the financial autonomy and the share of regional investment in public infrastructure seem to positively affect the economic growth of Spanish regions. However, a negative effect is found for a proxy for the number of responsibilities transferred to the regions. Moreover, empirical evidence provided for three sub‐sample periods could be suggesting that the Spanish state might be around the optimal level of decentralization. Results are fairly robust to different estimation methods and measures of TFP, regardless of the assumption of constant returns to scale. Este articulo ofrece nueva evidencia sobre los efectos de la descentralizacion en el crecimiento economico. Segun la literatura sobre los efectos de las instituciones en la economia, se asume que dichos efectos se acumulan a traves de la productividad total de los factores (PTF). Se proponen cinco variables para definir la descentralizacion, con el fin de superar las criticas recientes de los enfoques empiricos con respecto a las medidas adecuadas de identificacion de las variables que definen la descentralizacion. Se utilizaron datos de panel para las regiones de Espana durante el periodo 1986–2010. En general, los resultados muestran que la autonomia financiera y la participacion en la inversion regional en infraestructura publica parecen afectar positivamente el crecimiento economico de las regiones espanolas. Sin embargo, se encontro un efecto negativo para un indicador del numero de responsabilidades transferidas a las regiones. Ademas, la evidencia empirica proporcionada por tres periodos de submuestra podria sugerir que el estado espanol podria estar alrededor del nivel optimo de descentralizacion. Los resultados son suficientemente rigurosos respecto a diferentes metodos de estimacion y medidas de la PTF, independientemente del supuesto de rendimientos constantes a escala. 本稿では、分散化が経済成長に及ぼす効果を示す新たなエビデンスを報告する。 経済に対する制度の効果に関する文献に基づくと、その効果は全要素生産性(total factor productivity:TFP)から生じると想定される。 最近、分散化を捉える変数の適切な測定方法に関する実証的アプローチに対して批判があるが、これを克服するために分散化を捉える5つの変数を提示する。 1986年から2010年の、スペインの地方のパネルデータを使用する。 概して、結果から、地方財政の自主性と公共インフラへの地方の投資のシェアがスペインの地方の経済成長に対してプラスに作用していると考えられる。 しかし、地方に転嫁されている多くの責務のプロキシにはマイナスの作用が認められる。 さらに3つのサブサンプルの期間の条件とされる実証的エビデンスは、スペインが分散化の最適レベルの状態に近いことを示唆している可能性がある。 結果は、仮定の規模に関する収穫不変にかかわらず、様々な推定方法およびTFPの測定法に対してかなり頑健である。
The BECN1 N-terminal domain is intrinsically disordered

ABSTRACT BECN1/Beclin 1 has a critical role in the early stages of autophagosome formation. Recently, structures of its central and C-terminal domains were reported, however, little structural information is available on the N-terminal domain, comprising a third of the protein. This lack of structural information largely stems from the inability to produce this region in a purified form. Here, we describe the expression and purification of the N-terminal domain of BECN1 (residues 1 to 150) and detailed biophysical characterization, including NMR spectroscopy. Combined, our studies demonstrated at the atomic level that the BECN1 N-terminal domain is intrinsically disordered, and apart from the BH3 subdomain, remains disordered following interaction with a binding partner, BCL2L1/BCL-XL. In addition, the BH3 domain α-helix induced upon interaction with BCL2L1 reverts to a disordered state when the complex is dissociated by exposure to a competitive inhibitor. No significant interactions between N- and C-terminal domains were detected.