Miracle-dz/UniFAR-FTUs huggingface dataset:
High on treatment platelet reactivity against aspirin by non-steroidal anti-inflammatory drugs – pharmacological mechanisms and clinical relevance

Summary Inhibition of platelet function by aspirin results from irreversible inhibition of platelet cyclooxygenase (COX)-1. While sufficient inhibition is obtained at antiplatelet doses (75–325 mg/day) in most (≥95%) treated patients, the antiplatelet effect of aspirin and subsequent cardiovascular risk reduction is much less in clinical settings and disease-dependent. Several reasons for this “high on treatment platelet reactivity” are known. This paper reviews the evidence for an interaction between aspirin and other COX inhibitors, namely non-steroidal antiinflammatory drugs (NSAIDs). Numerous experimental studies demonstrated a pharmacodynamic interaction between aspirin and NSAIDs. This likely occurs within the hydrophobic substrate channel of platelet COX-1 and might be explained by molecular competition between inhibitor drugs and substrate (arachidonic acid) at overlapping binding sites. This interaction is found with some compounds, notably ibuprofen and dipyrone (metamizole), but not with others, such as diclofenac and acetaminophen (paracetamol). Hence, this interaction is not a class effect of NSAIDs and/or non-steroidal analgesics but rather due to specific structural requirements which still remain to be defined. In vivo studies on healthy subjects and patients tend to confirm this type of interaction as well as large differences between NSAIDs and non-steroidal analgesics, respectively. These interactions may be clinically relevant and may increase the cardiovascular risk in long-term treatment for primary and secondary cardiovascular prevention in patients with chronic inflammation, such as rheumatoid arthritis. These patients have an elevated risk for myocardial infarctions and may require chronic antiplatelet treatment by aspirin in addition to treatment of inflammatory pain.
Heterogenous band 3 deficiency in hereditary spherocytosis related to different band 3 gene defects

Among 80 hereditary spherocytosis (HS) kindreds studied using denaturing electrophoretic separation of solubilized eythrocyte membrane proteins, we recognized three prominent subsets: HS with isolated spectrin deficiency, HS with combined spectrin and ankyrin deficiency, and HS with band 3 deficiency. These three subsets represent more than 80% of the HS kindreds studied. In this study, eight dominant HS kindreds with band 3 deficiency were investigated for band 3 mutations. In three of these kindreds, linkage analyses confirmed the band 3 gene as the culprit gene. In an attempt to identify the responsible mutations, denaturing gradient gel electrophoresis (DGGE) was used to explore the coding exons (exons 2–20) of band 3 gene. Five different mutations were found in the eight kindreds. In five kindreds we identified substitutions of highly conserved residues, positioned at boundaries of putative transmembrane segments: a C → T substitution at codon 490 changed arginine (CGC) to cysteine (TGC) in three kindreds, a C → T substitution at codon 837 changed threonine (ACG) to methionine (ATG) in two kindreds. In the sixth kindred a G deletion was found in a stretch of five G starting at position 1475, leading to a stop codon either at position 1527 or 1565. In the seventh kindred a T deletion at position 1600 resulted in a stop codon at position 1733 and in the last kindred a T deletion was identified at position 355, leading to a stop codon at position 447. The mutant transcript was present in HS patients bearing missense mutations, whereas only the normal transcript was found in HS patients with frameshift mutations. In the latter group the mean decrease in membrane band 3 content was significantly lower, leading to speculation that missense mutations may have some sort of dominant negative effect.
Cancer Death and Antihypertensive Drug Treatment—Letter

The increasing cancer-related mortality related to rapid decreases in blood pressure from the pharmacologic treatment of hypertension as seen in the Systolic Hypertension in the Elderly Program (SHEP; [1][1]) draws interesting parallels to the PROspective Study of Pravastatin in the Elderly at Risk
Market orientation in Finnish pharmacies

Purpose of study The concept of market orientation has been studied since 1970’s. The dimensions of this concept have been described slightly differently by different researchers. Though this concept has been studied also among SMEs, even in Finland, there has not been a single-industry study focusing on Finnish pharmacies. The main objective of this study was to gain research information of market orientation within Finnish pharmacies, and whether this strategic paradigm can be related to Finnish pharmacists’ strategy work. Methodology Online survey was conducted in fall 2013 to collect the research data of this study. Invitation to this survey was sent to 584 pharmacists throughout Finland. 118 effective responses with response rate 20.2 per cent were received. Data analysis was conducted in two phases. In the first phase Exploratory factor analysis was used to identify the importance of market orientation to Finnish pharmacy owners. In the second phase t test and One-way Anova were used to test differences between demography variables sub groups among respondents. Findings One of the key findings of this study was that Finnish pharmacists did recognize dimensions of market orientation important to their strategy work. This study shows that these entrepreneurs were most active in responsiveness, while in information generation and dissemination they were slightly less active. This outcome is in line with the findings of previous research done among Finnish SMEs. Another key finding was that those pharmacists who possess PD education were less market oriented compared to those who do not have this further education. This would be somewhat unexpected result. The results of this study suggest that market orientation is relevant concept in the context of Finnish pharmacies. Such concept and related frameworks, e.g. MARKOR, could offer a guideline for entrepreneurs in this field of business as it confronts the competitive challenges of 21st century.
Novel techniques for achieving high at-speed transition fault test coverage for Motorola's microprocessors based on PowerPC/spl trade/ instruction set architecture

Scan based at-speed transition fault testing of Motorola's microprocessors based on the PowerPC/spl trade/ instruction set architecture requires broad-side transition fault test patterns that have a specific launch and capture clocking sequence. We describe the concepts we developed and incorporated in the ATPG tool to support efficient generation of such test patterns to achieve high transition fault test coverage and for analysis of undetected transition faults. Using the enhanced ATPG tool, we generated 15,000 transition fault test patterns and achieved 76% test coverage for the MPC7400 microprocessor based on the PowerPC/spl trade/ instruction set architecture that has 10.5 million transistors and runs at 540 MHz.
Detection of Chromosomal Abnormalities, an Outcome of Ultrasound Screening

Abstract: Chromosomal abnormalities were recorded from all the fetuses of women who benefited from sonographic examinations in the Eurofetus centers, excluding those for whom karyotyping was motivated by age or personal history. Among the 378 chromosomal abnormalities recorded, 210 were detected before birth (sensitivity = 55.6%). Down syndrome (trisomy 21) represented 197 cases, of which 68 were detected before birth (sensitivity = 34.5%). Eighty‐two of the cases of Down syndrome had associated structural abnormalities; the sensitivity in these cases increased to 57%. Among the 115 cases of Down syndrome without structural abnormalities, 21 (18.3%) had associated abnormal ultrasound findings that led to prenatal detection. Sensitivity of prenatal detection was 58.1% for trisomy 13 and 79% for trisomy 18. For the abnormalities detected before birth, spontaneous fetal death occurred in 27% of cases, and an early termination of pregnancy was decided in 53% of cases.
A Robust PMU Placement Method Against Spoofing Attacks ; Spoofing Detection and Data Refinement

In some recent articles, the spoofing of Phasor measurement unit (PMU) GPS receiver has been highlighted as a threat to power grid protection system. Having spoofed PMU GPS signals, one can manipulate the measurements and inject bad data to power grid protection system. The previous anti spoofing methods are all based on GPS signal analysis. The mentioned methods are just able to detect spoofing without any data refinement. Besides, some of these methods lose their certainty in noisy and harsh environments and some others need additional infrastructures which may be highly cost. In this paper, a novel anti spoofing algorithm has been proposed based on power grid infrastructures. The proposed algorithm relies on a robust PMU placement method against spoofing attacks. The algorithm is not only able to detect PMU GPS receiver spoofing, but also is able to refine manipulated data. Keywords-component; PMU; PMU placement; Spoofing attacks
Multimodal biometrics system based on face profile and ear

Face recognition from a side profile view, has recently received significant attention in the literature. Even though current face recognition systems have reached a certain level of maturity at angles up to 30 degrees, their success is still limited with side profile angles. This paper presents an efficient technique for the fusion of face profile and ear biometrics. We propose to use a Block-based Local Binary Pattern (LBP) to generate the features for recognition from face profile images and ear images. These feature distributions are then fused at the score level using simple mean rule. Experimental results show that the proposed multimodal system can achieve 97:98% recognition performance, compared to unimodal biometrics of face profile 96.76%, and unimodal biometrics of ear 96.95%, details in the Experimental Results Section. Comparisons with other multimodal systems used in the literature, like Principal Component Analysis (PCA), Full-space Linear Discriminant Analysis (FSLDA) and Kernel Fisher discriminant analysis (KFDA), are presented in the Experimental Results Section.
Aging of Competitive Athletes

Demographics of human aging are rapidly changing. As illustrated in the biomedicalization of aging, an ever increasing number of older adults is affected by a variety of clinical conditions and diseases, including vascular stiffening, sarcopenia, physical disability, and poor quality of life. One population that is situated in the opposite end of the health and functional spectrum to the sedentary frail elderly is Masters athletes. These older competitive athletes are endowed with substantial functional capacity, overall long-term health, high motivation, and psychosocial outlook. Masters athletes are combating the dogma and negative stereotypes of older adults and aging. From the scientific standpoint, examining Masters athletes can provide insight into preventive gerontology, primary prevention of age-related diseases and dysfunctions, and exercise-based medical practices. Moreover, the study on Masters athletes is simply joyous and entertaining as they often remind us what can be possible in aging.
Alternative splicing provides a proactive mechanism for the diurnal CONSTANS dynamics in Arabidopsis photoperiodic flowering

The circadian clock control of CONSTANS (CO) transcription and the light-mediated stabilization of its encoded protein coordinately adjust photoperiodic flowering by triggering rhythmic expression of the floral integrator flowering locus T (FT). Diurnal accumulation of CO is modulated sequentially by distinct E3 ubiquitin ligases, allowing peak CO to occur in the late afternoon under long days. Here we show that CO abundance is not simply targeted by E3 enzymes but is also actively self-adjusted through dynamic interactions between two CO isoforms. Alternative splicing of CO produces two protein variants, the full-size COα and the truncated COβ lacking DNA-binding affinity. Notably, COβ, which is resistant to E3 enzymes, induces the interaction of COα with CO-destabilizing E3 enzymes but inhibits the association of COα with CO-stabilizing E3 ligase. These observations demonstrate that CO plays an active role in sustaining its diurnal accumulation dynamics during Arabidopsis photoperiodic flowering.
Rod photopigment kinetics after photodisruption of the retinal pigment epithelium.

PURPOSE Advances in retinal imaging have led to the discovery of long-lasting retinal changes caused by light exposures below published safety limits, including disruption of the RPE. To investigate the functional consequences of RPE disruption, we combined adaptive optics ophthalmoscopy with retinal densitometry. METHODS A modified adaptive optics scanning light ophthalmoscope (AOSLO) measured the apparent density and regeneration rate of rhodopsin in two macaques before and after four different 568-nm retinal radiant exposures (RREs; 400-3200 J/cm(2)). Optical coherence tomography (OCT) was used to measure the optical path length through the photoreceptor outer segments before and after RPE disruption. RESULTS All tested RREs caused visible RPE disruption. Apparent rhodopsin density was significantly reduced following 1600 (P = 0.01) and 3200 J/cm(2) (P = 0.007) exposures. No significant change in apparent density was observed in response to 800 J/cm(2). Surprisingly, exposure to 400 J/cm(2) showed a significant increase in apparent density (P = 0.047). Rhodopsin recovery rate was not significantly affected by these RREs. Optical coherence tomography measurements showed a significant decrease in the optical path length through the photoreceptor outer segments for RREs above 800 J/cm(2) (P < 0.001). CONCLUSIONS At higher RREs, optical path length through the outer segments was reduced. However, the rate of photopigment regeneration was unchanged. While some ambiguity remains as to the correlation between measured reflectivity and absolute rhodopsin density; at the lowest RREs, RPE disruption appears not to be accompanied by a loss of apparent rhodopsin density, which would have been indicative of functional loss.
Larvicidal Activity of Myrtaceae Essential Oils and Their Components Against Aedes aegypti, Acute Toxicity on Daphnia magna, and Aqueous Residue

ABSTRACT The larvicidal activity of 11 Myrtaceae essential oils and their constituents was evaluated against Aedes aegypti L. Of the 11, Melaleuca linariifolia Sm. , Melaleuca dissitiflora F. Muell. , Melaleuca quinquenervia (Cav.) S. T. Blake, and Eucalyptus globulus Labill oils at 0.1 mg/ml exhibited ≥80% larval mortality. At this same concentration, the individual constituents tested, allyl isothiocyanate, &agr;-terpinene, p-cymene, (+)-limonene, (-)-limonene, &ggr;-terpinene, and (E)-nerolidol, resulted in ≥95% mortality. We also tested the acute toxicity of these four active oils earlier mentioned and their constituents against Daphnia magna Straus. M. linariifolia and allyl isothiocyanate was the most toxic to D. magna. Two days after treatment, residues of M. dissitiflora, M. linariifolia, M. quinquenervia, and E. globulus oils in water were 55.4, 46.6, 32.4, and 14.8%, respectively. Less than 10% of allyl isothiocyanate, &agr;-terpinene, p-cymene, (-) -limonene, (+) -limonene, and &ggr;-terpinene was detected in the water at 2 d after treatment. Our results indicated that oils and their constituents could easily volatilize in water within a few days after application, thus minimizing their effect on the aqueous ecosystem. Therefore, Myrtaceae essential oils and their constituents could be developed as control agents against mosquito larvae.
Regulator of G Protein Signaling 3 Protects Against Cardiac Hypertrophy in Mice

Regulator of G protein signaling 3 (RGS3) is a negative regulator of G protein‐mediated signaling. RGS3 has previously been shown to be expressed among various cell types within the mature heart. Basic and clinical studies have reported abnormal expressions of RGS3 in hypertrophic hearts and in the failing myocardium. However, the role of RGS3 in cardiac remodeling remains unclear. In this study, we investigated the effect of cardiac overexpression of human RGS3 on cardiac hypertrophy induced by aortic banding (AB) in RGS3 transgenic mice and wild‐type littermates. The extent of cardiac hypertrophy was evaluated by echocardiography as well as pathological and molecular analyses of heart samples. RGS3 overexpression in the heart markedly reduced the extent of cardiac hypertrophy, fibrosis, and left ventricular dysfunction in response to AB. These beneficial effects were associated with the inhibition of MEK‐ERK1/2 signaling. In vitro studies performed in cultured neonatal rat cardiomyocytes confirmed that RGS3 overexpression inhibits hypertrophic growth induced by angiotensin II, which was associated with the attenuation of MEK‐ERK1/2 signaling. Therefore, cardiac overexpression of RGS3 inhibits maladaptive hypertrophy and fibrosis and improves cardiac function by blocking MEK‐ERK1/2 signaling. J. Cell. Biochem. 115: 977–986, 2014. © 2013 Wiley Periodicals, Inc.
The p92 Polymerase Coding Region Contains an Internal RNA Element Required at an Early Step in Tombusvirus Genome Replication

ABSTRACT The replication of positive-strand RNA viral genomes involves various cis-acting RNA sequences. Generally, regulatory RNA sequences are present at or near genomic termini; however, internal replication elements (IREs) also exist. Here we report the structural and functional characterization of an IRE present in the readthrough portion of the p92 polymerase gene of Tomato bushy stunt virus. Analysis of this element in the context of a noncoding defective interfering RNA revealed a functional core structure composed of two noncontiguous segments of sequence that interact with each other to form an extended helical conformation. IRE activity required maintenance of several base-paired sections as well as two distinct structural features: (i) a short, highly conserved segment that can potentially form two different and mutually exclusive structures and (ii) an internal loop that contains a critical CC mismatch. The IRE was also shown to play an essential role within the context of the viral genome. In vivo analysis with novel RNA-based temperature-sensitive genomic mutants and translationally active subgenomic viral replicons revealed the following about the IRE: (i) it is active in the positive strand, (ii) it is dispensable late in the viral RNA replication process, and (iii) it is functionally inhibited by active translation over its sequence. Together, these results suggest that IRE activity is required in the cytosol at an early step in the viral replication process, such as template recruitment and/or replicase complex assembly.
Jackknife and Bootstrap Bias Correction for Single-Subject Information Transfer in Audiological Testing

Percent of information transferred (IT) is the average reduction in stimulus entropy given a subject’s response, expressed as a percent of total stimulus entropy. Miller and Nicely (1955) advocated the use of the information transfer IT statistic as a measure of the amount of speech information transmitted from a speaker to a listener. The technique was subsequently widely adopted in speech and hearing research as a tool for investigating the capacity of various hearing augmentation devices to enhance or restore the perception of particular speech features by hearing impaired individuals. Inter alia, Von Wallenberg, Hochmair and Hochmair-Desoyer (1990), Dorman, et al. (1990), Van Tasell, et al. (1992), Mckay and McDermott (1993), Summers, et al. (1994), and Cazals, et al. (1994) all report information transfer statistics. The Iowa consonant confusion test (Tyler, et al., 1983) is a typical example of the type of stimulusresponse paradigm used to estimate information transfer. This test involves 12 presentations of each of 10 consonants (p,t,k,c,b,d,v,z,n,m) in completely random order. The results of a single administration can be displayed as a confusion matrix similar to Figure 1.
Passive ripple mirror circuit and its application in pulse-width modulated DC-DC converters

In this paper, a simple modular passive ripple mirror circuit (PRMC) is adopted for eliminating the inherent high frequency current ripple of pulse-width modulated (PWM) DC-DC converters. The PRMC doesn't require any additional active switches, driver circuits or any extra control; the cost can be saved easily. Only the reflected high frequency ripples are automatically induced and processed for proper cancellation with the original ripples. It turns out that not only the output power quality can be enhanced but also the inductance of the main power conversion circuit can be reduced greatly. In this paper, both the circuit structure and operation principle of the PRMC are described. Furthermore, the PRMC technique is then integrated into a family of PWM DC-DC converters, such as buck, boost, Cuk, Zeta, and SEPIC converters. Finally, as the demonstration, experimental results of the Cuk PWM converter integrated with PRMC are provided to verify the feasibility of the principle.
The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre‐eclampsia

Objectives (1) To investigate the effects of plasma from non‐pregnant, normal pregnant and pre‐eclamptic women on myogenic tone and endothelium‐dependent relaxation; (2) To investigate the role of matrix metalloproteinases (MMPs) in these parameters of vascular function.
Enhanced matching perturbation attenuation with discrete-time implementations of sliding-mode controllers

Continuous-time Sliding Mode Control yields when embedded into Filippov's mathematical framework, closed-loop systems with a set-valued controller, represented by differential inclusions. In particular, besides finite-time convergence to the sliding surface and robustness to matched disturbances, such controllers allow an exact compensation of the disturbance on the sliding manifold. In other words, the set-valued input is the exact copy of minus the perturbation. A novel discretization methodology has been recently introduced by the authors, which is based on an implicit discretization of the Filippov's differential inclusion, which in theory totally suppresses the chattering due to the discretization (numerical chattering). In this work we propose an extension of the implicit method, enhancing the perturbation attenuation (in terms of chattering) by using previous values of the set-valued input. This allows to estimate on-line the unknown perturbation, with a time delay due to the sampling. Simulation results illustrate the effectiveness of the method.