Miracle-dz/UniFAR-FTUs huggingface dataset:
Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons

The proopiomelanocortin gene (POMC) is expressed in a group of neurons present in the arcuate nucleus of the hypothalamus. Neuron-specific POMC expression in mammals is conveyed by two distal enhancers, named nPE1 and nPE2. Previous transgenic mouse studies showed that nPE1 and nPE2 independently drive reporter gene expression to POMC neurons. Here, we investigated the evolutionary mechanisms that shaped not one but two neuron-specific POMC enhancers and tested whether nPE1 and nPE2 drive identical or complementary spatiotemporal expression patterns. Sequence comparison among representative genomes of most vertebrate classes and mammalian orders showed that nPE1 is a placental novelty. Using in silico paleogenomics we found that nPE1 originated from the exaptation of a mammalian-apparent LTR retrotransposon sometime between the metatherian/eutherian split (147 Mya) and the placental mammal radiation (≈90 Mya). Thus, the evolutionary origin of nPE1 differs, in kind and time, from that previously demonstrated for nPE2, which was exapted from a CORE-short interspersed nucleotide element (SINE) retroposon before the origin of prototherians, 166 Mya. Transgenic mice expressing the fluorescent markers tomato and EGFP driven by nPE1 or nPE2, respectively, demonstrated coexpression of both reporter genes along the entire arcuate nucleus. The onset of reporter gene expression guided by nPE1 and nPE2 was also identical and coincidental with the onset of Pomc expression in the presumptive mouse diencephalon. Thus, the independent exaptation of two unrelated retroposons into functional analogs regulating neuronal POMC expression constitutes an authentic example of convergent molecular evolution of cell-specific enhancers.
Kuroshio meanders in the East China Sea

Abstract An array of seven inverted echo sounders was moored along and across the Kuroshio in the East China Sea for more than one year. The data from this array show evidence of energetic meanders with periods of 7, 11, and 16 days. The respective phase velocities of these meanders are 28, 20, and 17 km day−1 downstream. The 7- and 16-day waves are intermittent, but the 11-day waves are present throughout the deployment. The instability responsible for these waves is investigated with a spectral numerical model applied to a background state representing the Kuroshio in this region. The fastest-growing instability from the model has e-folding growth time of 2 days, period of 12 days, and phase velocity of 18 km day−1 downstream. It appears to be a close representation of the 11-day wave seen in the observational data. Such a model has been previously used to represent meanders in the Gulf Stream at similar latitudes off the east coast of the United States. The Kuroshio meanders have approximately half the.
Characteristics of Children and Adolescents With Multiple Sclerosis

OBJECTIVES: To describe the demographic and clinical characteristics of pediatric multiple sclerosis (MS) in the United States. METHODS: This prospective observational study included children and adolescents with MS. Cases were evaluated across 9 geographically diverse sites as part of the US Network of Pediatric MS Centers. RESULTS: A total of 490 children and adolescents (324 girls, 166 boys) were enrolled; 28% developed symptoms before 12 years of age. The proportion of girls increased with age from 58% (<12 years) to 70% (≥12 years). Race and ethnicity as self-identified were: white, 67%; African American, 21%; and non-Hispanic, 70%. Most (94%) of the cases were born in the United States, and 39% had 1 or both foreign-born parents. Fifty-five percent of cases had a monofocal presentation; 31% had a prodrome (most frequently infectious), most often among those aged <12 years (P < .001). Children aged <12 years presented more commonly with encephalopathy and coordination problems (P < .001). Sensory symptoms were more frequently reported by older children (ie, those aged ≥12 years) (P < .001); 78% of girls had MS onset postmenarche. The initial Expanded Disability Status Scale score for the group was <3.0, and the annualized relapse rate was 0.647 for the first 2 years. Interval from symptom onset to diagnosis and from diagnosis to initiation of disease-modifying therapy was longer among those <12 years of age. CONCLUSIONS: Pediatric MS in the United States is characterized by racial and ethnic diversity, a high proportion of children with foreign-born parents, and differences in clinical features and timing of treatment among those <12 years of age compared with older children.
Examination of Non-Uniform Distribution of Current on Worst-Case Crosstalk Noise for Distributed RLC Interconnect

Considering circuit designs at the deep sub-micron level, the more that interconnect wires of small cross section are packed closer together, coupled with longer length of interconnect and an increase in the number of layers of interconnect may cause different parts of an interconnect line to experience a varying degree of coupling effect from other interconnects, with the consequent variation in the induced-current across the interconnect. An analytical model to examine the effect of non-uniform distribution of current on the mutual inductance and capacitance between on-chip interconnects is presented.
Systematic Review Systematic Review and Meta-Analysis of Brief Cognitive Instruments to Evaluate Suspected Dementia in Chinese-Speaking Populations

Background: Chinese is the most commonly spoken world language; however, most cognitive tests were developed and validated in the West. It is essential to ﬁnd out which tests are valid and practical in Chinese speaking people with suspected dementia. Objective: We therefore conducted a systematic review and meta-analysis of brief cognitive tests adapted for Chinese-speaking populations in people presenting for assessment of suspected dementia. Methods: Wesearchedelectronicdatabasesforstudiesreportingbrief( ≤ 20minutes)cognitivetest’ssensitivityandspeciﬁcity as part of dementia diagnosis for Chinese-speaking populations in clinical settings. We assessed quality using Centre for EvidenceBasedMedicine(CEBM)criteriaandtranslationandculturaladaptationusingtheManchesterTranslationReporting Questionnaire(MTRQ),andManchesterCulturalAdaptationReportingQuestionnaire(MCAR). Weassessedheterogeneity andcombinedsensitivityinmeta-analyses. Results: 38 studies met inclusion criteria and 22 were included in meta-analyses. None met the highest CEBM criteria. Five studies met the highest criteria of MTRQ and MCAR. In meta-analyses of studies with acceptable heterogeneity (I 2 <75%), Addenbrooke’s Cognitive Examination Revised &III (ACE-R & ACE-III) had the best sensitivity and speciﬁcity; speciﬁcally, for dementia (93.5% & 85.6%) and mild cognitive impairment (81.4% & 76.7%). Conclusions: Current evidence is that the ACE-R and ACE-III are the best brief cognitive assessments for dementia and mild cognitive impairment in Chinese-speaking populations. They may improve time taken to diagnosis, allowing people to access interventions and future planning.
Secondary Stroke Prevention in Atrial Fibrillation: Lessons From Clinical Practice

Background and Purpose Secondary prevention trials do not distinguish outcomes according to stroke cause. The purpose of the study was to determine whether trial efficacy of anticoagulation for secondary prevention could be replicated in clinical practice in strokes of different etiology. Methods A 2-year observation study was undertaken in 288 stroke patients with atrial fibrillation (mean age 76 years; 55% women) who were receiving anticoagulation therapy to maintain an international normalized ratio of 2.0 to 3.0. Comparisons were made of (1) patient characteristics, anticoagulation control, and annual stroke/hemorrhage rates with those of the European Atrial Fibrillation Trial and (2) cause of recurrent stroke by initial stroke subtype. Results Subjects were 5 years older (95% CI 3 to 7 years), and more patients had small-vessel stroke (26% versus 14%; 95% CI 3% to 17%) compared with corresponding trial data. The duration spent in the target anticoagulation range (55% versus 59%), recurrent stroke rate (5.1% versus 3.6% per year), and major (2.3% versus 2.2% per year) or minor (9.5% versus 11.8% per year) hemorrhage rates were comparable with those in patients receiving warfarin in the randomized study. Ten of 14 (71%) of embolic recurrences occurred in patients with a previous cardioembolic episode, and 8 of 11 (73%) lacunar recurrences occurred in patients with previous lacunar stroke as the qualifying event for anticoagulation (P =0.025). Only 3 of 14 cardioembolic compared with 8 of 11 lacunar recurrences occurred during adequate anticoagulation. Conclusions Anticoagulation for secondary stroke prevention in clinical practice achieves outcomes comparable with those of randomized trials. Nearly 26% of qualifying strokes and 40% of recurrences were nonembolic; stroke subtype should be considered when making treatment decisions.
Quality assurance of conventional non-CT-based internal mammary lymph node irradiation in a prospective Danish Breast Cancer Cooperative Group trial: The DBCG-IMN study

Abstract In 2003, the Danish Breast Cancer Cooperative Group (DBCG) initiated DBCG-IMN, a prospective study on the effect of adjuvant internal mammary lymph node radiotherapy (IMN-RT) in patients with early lymph node positive breast cancer (BC). In the study, standard DBCG IMN-RT was provided only to patients with right-sided BC. We provide estimates of doses to IMNs and organs at risk (OARs) in patients treated with the non-CT-based RT techniques used during the DBCG-IMN study. Material and methods. Five DBCG RT regimens were simulated on planning CT scans from 50 consecutively scanned BC patients, 10 in each group. Intended target volumes were chest wall or breast and regional lymph nodes ± IMNs. Field planning was conducted in the EclipseTM RT treatment planning system. Subsequently, IMN clinical target volumes (CTVs) and OARs were delineated. Estimates on doses to the IMN-CTV and OARs were made. Results. IMN dose coverage estimates were consistently higher in right-sided techniques where IMN treatment was intended (p < 0.0001). Estimated doses to cardiac structures were low regardless of whether IMNs were treated or not. Post-lumpectomy patients had the highest estimated lung doses. Conclusion. Overall, simulator-based treatment using the DBCG RT techniques resulted in satisfactory coverage of IMNs and acceptable levels of OAR irradiation.
Optical Image Generation and High-precision Line-of-Sight Extraction for Mars Approach Navigation

A high-precision line-of-sight extraction technique is essential for autonomous optical navigation during the Mars approach phase. To support future Mars exploration missions, an optical image simulation system is a necessary ground verification facility for Mars image generation and line-of-sight extraction algorithm tests. In this paper, an optical image generation procedure is first developed according to projection relationships, reference flight profiles and camera parameters. Next, a hybrid image processing and subpixel-level line-of-sight extraction algorithm is proposed through modification of moment-based sub-pixel edge detection and improvement of direct least-square fitting approaches. Finally, an optical image simulation system is established, and the experimental results show that the proposed procedure can effectively simulate the optical image in the field-of-view of a Mars spacecraft, and the hybrid extraction algorithm can obtain high-precision Mars centroid information.
Electromyographic analysis of hip rehabilitation exercises in a group of healthy subjects.

STUDY DESIGN Single-occasion, repeated-measures design. OBJECTIVE To determine the magnitude of hip abductor muscle activation during 6 rehabilitation exercises. BACKGROUND Many researchers have reported that hip strengthening, especially of the hip abductors, is an important component of a lower extremity rehabilitation program. Clinicians employ non-weight-bearing and weight-bearing exercise to strengthen the hip musculature; however, researchers have not examined relative differences in muscle activation during commonly used exercises. Information regarding these differences may provide clinicians with a scientific rationale needed for exercise prescription. METHODS AND MEASURES Sixteen healthy subjects (mean +/- SD age, 27 +/- 5 years; range, 18-42 years; mean +/- SD height, 1.7 +/- 0.2 m; mean +/- SD body mass, 76 +/- 15 kg) volunteered for this study. Bipolar surface electrodes were applied to the right gluteus medius muscle. We measured muscle activation as subjects performed 3 non-weight-bearing (sidelying right hip abduction and standing right hip abduction with the hip at 0 degrees and 20 degrees of flexion) and 3 weight-bearing (left-sided pelvic drop and weight-bearing left hip abduction with the hips at 0 degrees and 20 degrees of flexion) exercises. Data were expressed as a percent of maximum voluntary isometric contraction of the right gluteus medius. Differences in muscle activation across exercises were determined using a 1-way analysis of variance with repeated measures, followed by a sequentially rejective Bonferroni post hoc analysis to identify differences between exercises. RESULTS The weight-bearing exercises demonstrated significantly greater EMG amplitudes (P<.001) than all non-weight-bearing exercises except non-weight-bearing sidelying hip abduction. CONCLUSION The weight-bearing exercises and non-weight-bearing sidelying hip abduction exercise resulted in greater muscle activation because of the greater external torque applied to the hip abductor musculature. Although the non-weight-bearing standing hip abduction exercises required the least activation, they may benefit patients who cannot safely perform the weight-bearing or sidelying hip abduction exercises. Clinicians may use results from this study when designing hip rehabilitation programs.
Interleukin 15-mediated induction of cytotoxic effector cells capable of eliminating Epstein-Barr virus-transformed/immortalized lymphocytes in culture.

BACKGROUND Interleukin 15 (IL-15) activates cytotoxic lymphocytes and drives the expansion of memory T cells. Its role in immune control of virus-transformed cells and other tumor cells remains to be elucidated. We investigated the role of IL-15 in controlling Epstein-Barr virus (EBV)-transformed/immortalized lymphocytes in culture. EBV is a highly potent lymphocyte-transforming and opportunistic oncogenic herpesvirus associated with several human tumors. METHODS Peripheral blood mononuclear cells (PBMCs) from healthy donors were infected with EBV and cultured with either IL-15 or IL-15 plus anti-IL-15 antibodies for 3-4 weeks. We monitored EBV-induced transformation by assessing the clearly visible cell clusters by microscopy and analyzing the expression of EBV-encoded latent membrane oncoprotein-1 (LMP-1) and the EBV nuclear antigen (EBNA) complex by immunoblotting and immunofluorescence techniques, respectively. We depleted EBV-infected cultures of PBMCs of specific effector cell populations to investigate the effector cells involved in mediating IL-15 effect. RESULTS The presence of IL-15 resulted in the complete elimination of EBV-transformed cells in PBMC cultures. Western blot and immunofluorescence analyses performed 3-4 weeks after infection showed no detectable levels of LMP-1 and EBNA in IL-15-treated EBV-infected cultures, whereas IL-15-untreated EBV-infected cultures and IL-15/anti-IL-15-treated cultures expressed both proteins. IL-15 mediated its anti-EBV effect through early and late response mechanisms, i.e., by first activating natural killer (NK) cells and subsequently inducing cytolytic NK-T cells. The presence of anti-IL-15 neutralizing antibodies abrogated IL-15's effect on both mechanisms. CONCLUSION In vitro, IL-15 mediated complete elimination of EBV-infected/transformed lymphocytes via successive activation of NK and NK-T cytotoxic effectors. If these in vitro findings reflect in vivo mechanisms, then IL-15 might be considered for cytokine-based immunotherapy in patients with EBV-associated lymphoproliferative disorders/malignancies.
Bortezomib induces schedule-dependent modulation of gemcitabine pharmacokinetics and pharmacodynamics in non-small cell lung cancer and blood mononuclear cells

Bortezomib combination with gemcitabine/cisplatin in patients with advanced tumors, predominantly non-small cell lung cancer (NSCLC), showed an unexpected transient drop in the deoxycytidine plasma levels, a marker for gemcitabine activity. This study investigates the pharmacokinetic/pharmacodynamic effect of bortezomib on gemcitabine in NSCLC and peripheral blood mononuclear cells (PBMC). Gemcitabine metabolites, including difluoro-dCTP (dFdCTP), were studied in PBMCs from bortezomib/gemcitabine/cisplatin-treated patients and from volunteers and NSCLC cells (H460 and SW1573) exposed to 4 h simultaneous or sequential treatments of gemcitabine (50 μmol/L, 4 h) and bortezomib (100 nmol/L, 2 h). Gemcitabine total phosphate levels measured by liquid chromatography-tandem mass spectrometry in PBMCs from bortezomib/gemcitabine/cisplatin-treated patients were strongly reduced after 90 min (−82.2%) up to 4 h post-gemcitabine infusion compared with gemcitabine/cisplatin-treated patients. Accordingly, bortezomib/gemcitabine combinations reduced dFdCTP in PBMCs treated ex vivo. Surprisingly, differential effects were observed in NSCLC cells. dFdCTP decreased after 4 h following gemcitabine removal in H460 but continued to increase for 24 h in SW1573. However, dFdCTP significantly increased (2-fold) in both cell lines in the bortezomib→gemcitabine exposure, coinciding with a major reduction in cell growth compared with single drugs, and the highest increase of deoxycytidine kinase expression, possibly mediated via E2F-1. Bortezomib affects differently gemcitabine pharmacokinetics/pharmacodynamics in PBMCs and NSCLC cells, suggesting that PBMCs are not adequate to evaluate the anticancer activity of bortezomib/gemcitabine combinations. The bortezomib→gemcitabine/cisplatin schedule appeared a safe and active combination for the treatment of advanced NSCLC and the bortezomib→gemcitabine was the most cytotoxic combination in NSCLC cells. The increase of deoxycytidine kinase and dFdCTP might contribute to this synergistic interaction and supports its further clinical investigation. [Mol Cancer Ther 2009;8(5):1026–36]
Riding the Lexical Speedway: A Critical Review on the Time Course of Lexical Selection in Speech Production

Speech requires time. How much time often depends on the amount of labor the brain has to perform in order to retrieve the linguistic information related to the ideas we want to express. Although most psycholinguistic research in the field of language production has focused on the net result of time required to utter words in various experimental conditions, over the last years more and more researchers pursued the objective to flesh out the time course of particular stages implicated in language production. Here we critically review these studies, with particular interest for the time course of lexical selection. First, we evaluate the data underlying the estimates of an influential temporal meta-analysis on language production (Indefrey and Levelt, 2004). We conclude that those data alone are not sufficient to provide a reliable time frame of lexical selection. Next, we discuss recent neurophysiological evidence which we argue to offer more explicit insights into the time course of lexical selection. Based on this evidence we suggest that, despite the absence of a clear time frame of how long lexical selection takes, there is sufficient direct evidence to conclude that the brain initiates lexical access within 200 ms after stimulus presentation, hereby confirming Indefrey and Levelt’s estimate. In a final section, we briefly review the proposed mechanisms which could lead to this rapid onset of lexical access, namely automatic spreading activation versus specific concept selection, and discuss novel data which support the notion of spreading activation, but indicate that the speed with which this principle takes effect is driven by a top-down signal in function of the intention to engage in a speech act.
White matter microstructural impairments and genetic liability to familial bipolar I disorder

Background Subtle abnormalities in frontal white matter have been reported in bipolar disorder. Aims To assess whether impaired integrity of white matter tracts is associated with bipolar disorder and genetic liability for the disorder. Method A total of 19 patients with psychotic bipolar I disorder from multiply affected families, 21 unaffected first-degree relatives and 18 comparison individuals (controls) underwent diffusion tensor imaging. Whole brain voxel-based analyses compared fractional anisotropy between patients and relatives with controls, and its relationship with a quantitative measure of genetic liability. Results Patients had decreased fractional anisotropy compared with controls in the genu of the corpus callosum, right inferior longitudinal fasciculus and left superior longitudinal fasciculus. Increased genetic liability for bipolar disorder was associated with reduced fractional anisotropy across distributed regions of white matter in patients and their unaffected relatives. Conclusions Disturbed structural integrity within key intra- and interhemispheric tracts characterises both bipolar disorder and genetic liability for this illness.
Cultural Expectations and Perceptions of Politeness: The “Rude Chinese”?

As globalization steams ahead, China continues to open its borders and interact with the rest of the world. Along with the obvious industrial and economical exchange in ideas, the cultural impact of this phenomenon is also becoming apparent. Unfortunately, Chinese are often seen as impolite or even rude by individuals of other cultures. This paper studies cultural and linguistic expectations, along with how perceptions of politeness are formed, and attempts to find the source of these “cultural clashes”. Participants in this study are also asked to explain, from their own point of view, what they perceive as the root of the problem. Lastly, a remedy to this problem is suggested.