Miracle-dz/UniFAR-FTUs huggingface dataset:
Lateralized and widespread brain activation during transient blood pressure elevation revealed by magnetic resonance imaging

The location and possible lateralization of structures mediating autonomic processing are not well‐described in the human. Functional magnetic resonance imaging procedures were used to demonstrate signal changes in multiple brain sites during blood pressure challenges. Magnetic resonance signals in brain tissue were visualized with a 1.5 Tesla scanner in 11 healthy volunteers (22–37 years), by using echo‐planar procedures. Images were collected during baseline states and three pressor challenges: cold application to the hand or forehead, and a Valsalva maneuver. Image values from experimental conditions were compared with corresponding baseline values on a voxel‐by‐voxel basis to identify brain regions responsive to physiologic activation. Probability maps (P < 0.01) of voxel changes, with Bonferroni corrections for multiple comparisons, were determined, and amplitude of signal changes associated with significance maps were pseudocolored and overlaid on anatomic images. The time courses and extent of signal alterations in defined unilateral regions were followed and compared with changes in corresponding regions on the contralateral side. Pressor challenges elicited significant regional signal intensity changes within the orbitomedial prefrontal cortex, temporal cortex, amygdala, hippocampal formation, thalamus, and hypothalamus. Cerebellar, midbrain, and pontine areas were also recruited. Signal changes, especially at forebrain sites, were often highly lateralized. The findings indicate that (1) transient, behaviorally‐coupled cardiovascular challenges elicit discrete activity changes over multiple brain sites, and (2) these activity changes, especially in specific prefrontal and temporal forebrain regions and cerebellum, are often expressed unilaterally, even to a bilateral challenge. J. Comp. Neurol. 417:195–204, 2000. ©2000 Wiley‐Liss, Inc.
Resting calcium concentrations in isolated skeletal muscle fibres of dystrophic mice.

1. Single, intact muscle fibres were dissociated enzymatically from skeletal muscles of phenotypically normal (+/? ) and dystrophic mice (129/ReJ dy/dy: Dystrophia muscularis), and resting Ca2+ levels were measured by image analysis of intracellular Fura‐2 fluorescence in distinct parts of the fibres. 2. Fura‐2 was introduced into fibres by ionophoresis with glass microelectrodes to concentrations of between 50 and 200 microM. Over this concentration range there was no apparent buffering of intracellular Ca2+ by Fura‐2. 3. Fibres isolated from the soleus, flexor digitorum brevis (FDB) and extensor digitorum longus (EDL) muscles of normal animals maintained resting [Ca2+] of 106 +/‐ 2 nM. Ca2+ distributions within individual fibres were homogeneous. 4. Fibres from dystrophic animals maintained [Ca2+] that was elevated two‐ to fourfold in comparison to normal fibres. 5. The population of skeletal fibres from dystrophic mice which displayed morphology similar to that of fibres of normal animals were found to have Ca2+ levels that averaged 189 +/‐ 2 nM. The distribution of Ca2+ within these fibres appeared uniform. 6. The population of dystrophic fibres that possessed morphological abnormalities maintained even higher Ca2+ concentrations (368 +/‐ 3 nM). Several fibres from this morphological group displayed obvious heterogeneity in Ca2+ distribution with distinct, localized areas of higher Ca2+. 7. These results support the contention that Ca2+ homeostasis is markedly impaired in dystrophic muscle. The elevated Ca2+ levels are near the threshold for contraction and, together with severe morphological fibre abnormalities, are probably centrally involved in fibre necrosis apparent in muscular dystrophy.
Highly Active Antiretroviral Therapy Interruption: Predictors and Virological and Immunologic Consequences

Objective: To characterize the magnitude and the predictors of highly active antiretroviral therapy (HAART) interruption (TI) and to investigate its immunologic and virological consequences. Methods: Using Concerted Action on Seroconversion to AIDS and Death in Europe data from 8300 persons with well-documented seroconversion dates, we identified subjects with stable first HAART (for at least 90 days) not initiated during primary infection. A TI was defined as an interruption of all antiretroviral therapy drugs for at least 14 days. Results: Of 1551 subjects starting HAART, 299 (19.3%) interrupted treatment. Median (interquartile range) duration of the TI was 189 (101-382) days. The cumulative probability (95% confidence interval) of TI at 2 years was 15.9% (14.0%-18.1%). Women were more likely to have a TI than men in the same exposure group (35.8% vs 24.2% among drug users, 22.1% vs 13.3% among heterosexuals; P < 0.05). Higher baseline viremia and poor immunologic response to HAART were associated with higher probabilities of TI. Median (interquartile range) individual CD4 cell loss during TI was 94 (1-220) cells/&mgr;L. Older age at HAART (>40 yr), lower pre-HAART nadir (<200 cells/&mgr;L), and lower CD4 at start of TI (<350 cells/&mgr;L) were significantly associated with greater relative CD4 loss during TI. Conclusions: We estimate that almost 1 in 6 subjects on HAART interrupts treatment by 2 years. Further research is needed to investigate the reasons why TI is higher in women. We have identified characteristics of subjects with the greatest risk for CD4 loss in whom TI may have greater risks.
Moral-up first, immoral-down last: the time course of moral metaphors on a vertical dimension

Many abstract bipolar concepts are usually represented by metaphors on vertical dimensions (e.g. positive-up, negative-down). However, several studies have found an asymmetry in the way in which individuals process bipolar dimensions, with +polarities being stronger than −polarities. The current research focused on moral metaphors on a vertical dimension (e.g. moral-up and immoral-down) and examined the asymmetric representation of moral and immoral concepts. The first experiment showed a distinct metaphorical association between morality and vertical space, consistent with earlier research. The second experiment showed that moral and immoral words are processed differently depending on whether they are used as metaphorically congruent or incongruent vertical cues. ‘Moral-up’ association modulated the amplitudes of the N1, P2, and late positive-going potential during the processing of moral words, whereas the ‘immoral-down’ association only modulated the amplitudes of the late positive-going potential induced during the processing of immoral words. These results suggest that asymmetry in the processing of vertically represented morality metaphors is reflected in the time course of the representation of these bipolar concepts, with the ‘moral-up’ association having an earlier effect than the ‘immoral-down’ association.
Supraorbital electrical stimulation in management of chronic type tension headache: A randomized controlled study

ABSTRACT Background and Purpose: Headache disorders are considered one of the ten most disabling conditions, for both males and females, according to the World Health Organization. Chronic type tension headache (CTTH) has a prevalence of 2–3% within the general population. The purpose of this research was to investigate the effect of stimulating noninvasively the trigeminal nerve in the supraorbital area (SOES) for treatment of CTTH. Methods: In an 8-week period of intervention, 45 patients were divided equally into three groups. Both group A “study” and group B received conventional physical therapy program three times a week. Group A received additional SOES for 20 minutes daily. Group C was on prescribed medications only. Assessments occurred pre and post intervention using Headache Impact Test (HIT), headache frequency, and visual analogue scale (VAS) for pain. Results: In between groups, comparison showed statistically significant differences between all groups (p < 0.000). Within-group comparisons showed that both groups A and B showed a significant improvement in all measured data. Improvement percent of group A was HIT = 18.4% and VAS = 63.0%, p ≤ 0.0001, and group B was HIT = 12.5% and VAS = 28.2%, p ≤ 0.0002, while group C showed no significant improvement with improvement percent HIIT = 1.2% and VAS = 8.6%, p ≤ 0.5. Patients in groups A and B reported less headache frequencies than group C. Conclusion: SOES had positive therapeutic results for treatment of CTTH.
Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia.

PURPOSE Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL). Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO. PATIENTS AND METHODS Between 1998 and 2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20 patients with relapsed APL, all previously treated with ATRA-containing chemotherapy. The primary objective was to demonstrate a significant reduction in the time necessary to obtain a complete remission (CR) in the ATO/ATRA group compared with the ATO group. Secondary objectives were safety and molecular response. RESULTS The CR rate after one ATO with or without ATRA induction cycle was 80%. Clinical and pharmacokinetic observations indicated that the main mechanism of action of ATO in vivo was the induction of APL cell differentiation. Hematologic and molecular response, time necessary to reach CR, and outcome were comparable in both treatment groups. Of 16 CR patients, three patients who reached a molecular remission after one induction cycle had all received chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients who received further additional ATO with or without ATRA cycles converted later to molecular negativity. CONCLUSION ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL. Other potential combinations, including ATO plus chemotherapy, have to be tested.
Towards Greener Software Engineering Using Software Analytics: A Systematic Mapping

Sustainability in software engineering is a relatively new and fast growing field of research. Green software engineering aims to produce sustainable software products with minimum negative impact on the environment. In order to make greener software products, software practitioners need actionable timely information, to make useful trade-offs between energy efficiency and other quality attributes, like performance, during development. Software analytics could be used to provide this support, as it combines information from different software artifacts and converts it into useful information. The objective of this paper is to provide an overview of the sub-domains, contribution types, research types, research methods, future research potentials and the role of software analytics in the field of green software engineering in 2015-16. We applied the systematic mapping method and conducted a search for studies in six online databases. Screening of papers was done according to inclusion/exclusion criteria and 50 selected studies were classified after analysis and data extraction. We found that there are many validation studies but hardly any evaluation and experience papers in the domain of green software engineering. Only 11 out of 50 papers in the green software engineering domain used software analytics techniques to foster green software engineering. Our results indicate the need to develop new/improved automated software analytics tools for software practitioners along with metrics explaining the correlation between energy usage and other quality attributes.
How to organize data with measurement errors?

Clustering analysis is an outstanding contribution to data mining and knowledge discovery from large-scale data, which has become an important research direction. Many excellent researches have been developed, whereas there is a blind point which is not addressed. How to organize data with measurement errors? What is needed for this purpose is the concept of error number- an error number which is defined as a(x)±αa(x), where a(x) is the measurement value of an object x under an attribute a, and αa(x) is the value of its measurement error. In this paper, we will explore tentatively data clustering with measurement errors through employing the framework of k-means clustering algorithm, which can be regarded as an introductory work.
Levosalbutamol for chronic obstructive pulmonary disease: a treatment evaluation

Introduction: Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder associated with considerable morbidity and mortality. β2-adrenoceptor agonists (β2-agonists) act by stimulating the β2-adrenoceptor present on smooth muscle and other cells in the airways, resulting in bronchodilatation. β2-agonists play a central role in the treatment of breathlessness in patients with COPD. Salbutamol is a chiral drug with (R)- and (S)- isomers. Almost all β2-agonists that are currently used are racemic mixtures of (R)- and (S)-salbutamol. Areas covered: (R)-salbutamol alone (Xenopex®, generically known as levosalbutamol) is now indicated for the treatment or prevention of bronchospasm with reversible obstructive airway disease. This evaluation demonstrates that (R)-salbutamol provides a beneficial β2-agonist effect at a cellular level and in experimental models of airways disease. Furthermore, we demonstrate that (S)-salbutamol opposes the desirable effects of (R)-salbutamol and can actually cause features of asthma and COPD in vitro and in experimental asthma. Expert opinion: Despite this strong body of preclinical experimental evidence, (R)-salbutamol has not shown consistent superiority over (S)- or racemic salbutamol in the treatment of patients with COPD.
Antiangiogenic agents after first line and sorafenib plus chemoembolization: a systematic review

Transarterial chemoembolization (TACE) is the standard treatment for intermediate stage, although the combination of TACE with sorafenib may theoretically benefit HCC patients in intermediate stage. Owing to the significant antiangiogenic effect of sorafenib and the limitation of TACE, it is rational to combine them. Though the strategy of combining TACE and sorafenib has been increasingly used in patients with unresectable HCC but the current evidence is controversial and its clinical role has not been determined yet. In first-line therapy, patients receiving sorafenib had increased overall survival and progression free survival. Therefore several antiangiogenic agents have entered clinical studies on HCC, many with negative results. This review discusses the current drug development for patients with HCC and role of TACE plus sorafenib.
A 5.5Gb/s 5mm contactless interface containing a 50Mb/s bidirectional sub-channel employing common-mode OOK signaling

High-volume, mm-range, contact-less interfaces between modules, which would replace existing interfaces that use wire harnesses and connectors, are expected to be employed in many applications because they would provide such features as immunity to mechanical failures due to vibration/friction, isolation from water/chemicals, and lower fabrication costs. Such conventional radio-wave techniques as UWBs or mm-waves that have been optimized for communication at distances greater than 1cm would suffer from inefficiency in power performance compared with wireline communications. This paper introduces proximity communication using a coupler-in-package that provides a wide-band channel between modules. The relatively large coupler-size in our coupler-in-package permits communication distances to be 1cm or less, while conventional techniques for communication between stacked chips [1,2] have communication distances of less than hundreds of μm. The wideband channel enables baseband communication between chips to support Gb/s-range data transfer with power efficiency comparable to that of conventional wireline transceivers.
Clustering based Transcoding for Congestion Control in Wireless Networks

Multimedia applications such as video conferencing and media streaming require service guarantees and demand strict timing requirements. Limited network resources along with heterogeneous client devices usually act as a limiting factor on the seamless global delivery of multimedia data. The key issue that needs to be addressed in adaptation and delivery of such multimedia data to diverse devices is to strike a balance between usage of network resources and the quality of delivered content. In this paper we propose a transcoding approach for video streaming to heterogeneous mobile client devices over a wireless network with limited resources and bandwidth. Our approach is based on: (a) Clustering client devices based on their capabilities to determine the format of content suitable for them; (b) Adapting content appropriate to the determined content formats by transcoding and achieving reduction in content size by removing redundant information from content in the process of transcoding; (d) Using subscriber distribution and the devices they own to optimize the number of versions of content; and (e) Using transcoding to further reduce the size of content for each device cluster while maintaining the quality of content.
Disrupted intracellular calcium regulates BACE1 gene expression via nuclear factor of activated T cells 1 (NFAT 1) signaling

Beta‐site APP‐cleaving enzyme 1 (BACE1) expression is elevated in the brains of Alzheimer's disease (AD) patients and in aged‐animal models. Because both AD and aging are associated with disrupted calcium homeostasis, we investigated the role of nuclear factor of activated T cells (NFAT) – a transcription factor regulated by the calcium‐ and calmodulin‐dependent phosphatase calcineurin – in BACE1 expression. BACE1 expression was stimulated by a calcium ionophore in primary cortical cultures, and by SH‐SY5Y neuroblastoma cells, which was both blocked by pretreatment with either cyclosporin A, an inhibitor of calcineurin, or ethyleneglycotetraacetic acid, a calcium chelator. Gel shift assays revealed direct binding of NFAT1 to specific DNA sequences within the BACE1 gene promoter region. Treatment with amyloid beta (Aβ), one of the major factors in AD pathogenesis, stimulated activation and nuclear translocation of NFAT1 following up‐regulation of BACE1 expression. In addition, primary cortical cultures from Tg2576 mouse brains generated more Aβ by ionophore stimulation, which was reversed by cyclosporin A treatment. Furthermore, NFAT1 activation was observed in Tg2576 mouse brains. These results suggest that calcium ionophore‐ or Aβ‐induced increases in intracellular calcium concentration stimulate BACE1 expression, resulting in accelerated Aβ generation, and that this process is mediated through the calcineurin‐NFAT1 signaling pathway. This process may play a significant role in the pathogenesis of AD and aging.
Promoter methylation and mRNA expression of DKK-3 and WIF-1 in hepatocellular carcinoma.

AIM To investigate the promoter methylation status and mRNA expression of DKK-3 and WIF-1 gene in hepatocellular carcinoma (HCC). METHODS DKK-3 and WIF-1 acted as Wnt-antagonists and tumor suppressors, but hypermethylation of the gene promoter and low mRNA expression activated Wnt signaling aberrantly and induced the development of HCC. Methylation status of the DKK-3 and WIF-1 gene promoter was investigated using methylation specific polymerase chain reaction (PCR) in tumor and adjacent non-cancerous tissues from 33 HCC patients and 20 normal liver tissues served as control. The expression of DKK-3 and WIF-1 mRNA was also determined by real-time quantitative reverse transcriptase PCR. The relationship between methylation, mRNA expression, and clinical data, as well as methylation and mRNA expression of the two genes were analyzed. RESULTS The methylation of DKK-3 and WIF-1 genes in HCC increased significantly compared with adjacent non-cancerous tissues and normal control tissues (chi(2) =7.79, P < 0.05; chi(2) = 4.89, P < 0.05), and no significant difference in methylation between adjacent non-cancerous tissues and normal control tissues was observed. In HCC tissues, significant differences in the DKK-3 promoter methylation were observed in age and cirrhosis, and significant differences of the WIF-1 promoter methylation were observed in HBsAg and cirrhosis. The average expression of DKK-3 mRNA in HCC and adjacent non-cancerous tissues was increased significantly compared with normal control tissues. The average expression of WIF-1 mRNA showed no significant difference among the three tissues. The mRNA expression of DKK-3 gene in HCC was decreased as the pathological grade increased. CONCLUSION The aberrant promoter methylation and decreased expression of DKK-3 and WIF-1 may be an important mechanism in HCC, and may be a far-reaching significance in early diagnosis and therapy of HCC.
How can we improve adherence to blood pressure-lowering medication in ambulatory care? Systematic review of randomized controlled trials.

BACKGROUND Lack of adherence to blood pressure-lowering medication is a major reason for poor control of hypertension worldwide. The objective of this study was to determine the effectiveness of interventions to increase adherence to blood pressure-lowering medication. METHODS We performed a systematic review of randomized controlled trials and searched for all-language publications in the Cochrane Controlled Trials Register, MEDLINE, EMBASE, and CINAHL in April 2002. RESULTS We included 38 studies testing 58 different interventions and containing data on 15 519 patients. The studies were conducted in 9 countries between 1975 and 2000. The duration of follow-up ranged from 2 to 60 months. Because of heterogeneity between studies in terms of interventions and the methods used to measure adherence, we did not pool the results. Simplifying dosing regimens increased adherence in 7 of 9 studies, with a relative increase in adherence of 8% to 19.6%. Motivational strategies were partly successful in 10 of 24 studies with generally small increases in adherence up to a maximum of 23%. Complex interventions comparing more than 1 technique increased adherence in 8 of 18 studies, ranging from 5% to a maximum of 41%. Patient education alone seemed largely unsuccessful. CONCLUSIONS Reducing the number of daily doses appears to be effective in increasing adherence to blood pressure-lowering medication and should be tried as a first-line strategy, although there is so far less evidence of an effect on blood pressure reduction. Some motivational strategies and complex interventions appear promising, but we need more evidence on their effect through carefully designed randomized controlled trials.
Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers

Friend of GATA‐1 (FOG‐1) is a zinc finger protein that has been shown to interact physically with the erythroid DNA‐binding protein GATA‐1 and modulate its transcriptional activity. Recently, two new members of the FOG family have been identified: a mammalian protein, FOG‐2, that also associates with GATA‐1 and other mammalian GATA factors; and U‐shaped, a Drosophila protein that interacts with the Drosophila GATA protein Pannier. FOG proteins contain multiple zinc fingers and it has been shown previously that the sixth finger of FOG‐1 interacts specifically with the N‐finger but not the C‐finger of GATA‐1. Here we show that fingers 1, 5 and 9 of FOG‐1 also interact with the N‐finger of GATA‐1 and that FOG‐2 and U‐shaped also contain multiple GATA‐interacting fingers. We define the key contact residues and show that these residues are highly conserved in GATA‐interacting fingers. We examine the effect of selectively mutating the four interacting fingers of FOG‐1 and show that each contributes to FOG‐1's ability to modulate GATA‐1 activity. Finally, we show that FOG‐1 can repress GATA‐1‐mediated activation and present evidence that this ability involves the recently described CtBP co‐repressor proteins that recognize all known FOG proteins.