Miracle-dz/UniFAR-FTUs huggingface dataset:
Position-effect protection and enhancer blocking by the chicken β-globin insulator are separable activities

The 1.2-kb DNA sequence element (5′HS4) at the 5′ end of the chicken β-globin locus has the two defining properties of an insulator: it prevents an “external” enhancer from acting on a promoter when placed between them (“enhancer blocking”) and acts as a barrier to chromosomal position effect (CPE) when it surrounds a stably integrated reporter. We previously reported that a single CTCF-binding site in 5′HS4 is necessary and sufficient for enhancer blocking. We show here that a 250-bp “core” element from within 5′HS4 is sufficient to confer protection against silencing of transgenes caused by CPE. Further dissection of the core reveals that 5′HS4 is a compound element in which it is possible to separate enhancer blocking and barrier activities. We demonstrate that full protection against CPE is conferred by mutant 5′HS4 sequences from which the CTCF-binding site has been deleted. In contrast, mutations of four other protein binding sites within 5′HS4 result in varying reductions in the ability to protect against CPE. We find that binding sites for CTCF are neither necessary nor sufficient for protection against CPE. Comparison of the properties of 5′HS4 with those of other CTCF-binding enhancer-blocking elements suggests that CPE protection is associated with maintenance of a high level of histone acetylation near the insulator, conferred by insulator binding-proteins other than CTCF.
Transplantation for hepatocellular carcinoma and cirrhosis: Sensitivity of magnetic resonance imaging

The sensitivity of magnetic resonance imaging (MRI) in patients who undergo transplantation for hepatocellular carcinoma (HCC) and cirrhosis is not known. We prospectively evaluated 24 patients with known HCC who underwent MRI and subsequent transplantation within 60 days (mean, 20 days). Using a phased‐array coil at 1.5T, breath‐hold turbo STIR and T2‐weighted MR images were performed. Dynamic gadolinium‐enhanced MRI was performed using a two‐ or three‐dimensional gradient echo pulse sequence with images obtained in the hepatic arterial, portal venous, and equilibrium phases. The prospective interpretation of the MR study was directly compared with thin‐section pathology evaluation of the explanted livers. All 24 patients had at least one HCC, and MR diagnosed tumor in 21 (88%) of these patients. On a lesion‐by‐lesion basis, MRI depicted 39 of 118 HCC for an overall sensitivity of 33%. MRI detected five (100%) of five lesions >5 cm, 20 (100%) of 20 lesions >2 cm but not exceeding 5 cm, 11 (52%) of 21 lesions between 1 and 2 cm, and three (4%) of 72 lesions <1 cm. Of the nine patients with carcinomatosis (innumerable lesions less than 1 cm), MR detected three lesions in one patient. Of the 15 dysplastic nodules found at pathology, MRI depicted a single 1.8‐cm high‐grade lesion, for a sensitivity of 7%. In conclusion, MRI is sensitive for the detection of HCC measuring at least 2 cm in diameter but is insensitive for the diagnosis of small HCC (<2 cm) and carcinomatosis.
VARIATION IN ASEXUAL LINEAGE AGE IN POTAMOPYRGUS ANTIPODARUM, A NEW ZEALAND SNAIL

Abstract Asexual lineages are thought to be subject to rapid extinction because they cannot generate recombinant offspring. Accordingly, extant asexual lineages are expected to be of recent derivation from sexual individuals. We examined this prediction by using mitochondrial DNA sequence data to estimate asexual lineage age in populations of a freshwater snail (Potamopyrgus antipodarum) native to New Zealand and characterized by varying frequency of sexual and asexual individuals. We found considerable variation in the amount of genetic divergence of asexual lineages from sexual relatives, pointing to a wide range of asexual lineage ages. Most asexual lineages had close genetic ties (∼0.1% sequence divergence) to haplotypes found in sexual representatives, indicating a recent origin from sexual progenitors. There were, however, two asexual clades that were quite genetically distinct (>1.2% sequence divergence) from sexual lineages and may have diverged from sexual progenitors more than 500,000 years ago. These two clades were found in lakes that had a significantly lower frequency of sexual individuals than lakes without the old clades, suggesting that the conditions that favor sex might select against ancient asexuality. Our results also emphasize the need for large sample sizes and spatially representative sampling when hypotheses for the age of asexual lineages are tested to adequately deal with potential biases in age estimates.
Coronary stent length predicts PCI-induced cardiac myonecrosis

BackgroundMyocardial necrosis complicates one-third of percutaneous coronary intervention (PCI, MI4a) and may adversely affect the outcome. We assessed the angiographic variables associated with MI4a that may help to identify those at highest risk. Methods and resultsCardiac troponin-I (cTnI) was measured after PCI in 243 patients undergoing elective PCI. Patients were grouped according to post-procedure cTnI result: minor or no elevation (<0.1 ng/ml), PCI-related MI4a (0.1 to <0.78 ng/ml) and WHO defined MI by the Troponin-I Ultra method (≥0.78 ng/ml). Angiographic variables were analyzed in blinded manner and correlated with cTnI rise. Minor or no cTnI elevation after PCI occurred in 116 of 243 (48%) patients, MI4a in 65 of 243 (27%) and WHO defined MI in 62 of 243 (25%). Independent predictors of MI4a included stent length [odds ratio (OR) 1.04 per mm; P=0.0015], X-ray screening time (OR 1.05 per minute; P=0.016) and procedural chest pain requiring opiates (OR 7.92; P=0.00066). The stenting of proximal vessel segments with fewer collaterals (large myocardial area at risk), diminished myocardial perfusion (P=0.0065) and side branch compromise were associated with cTnI elevation. Clinical events were more frequent following MI4a (9.4 vs. 3.4%, P=0.07). ConclusionThese data show that cTnI release after elective PCI is predominantly related to stent length. Minimizing the stent length deployed may reduce the cTnI release and improve prognosis.
Throughput–Power Tradeoff Association for User Equipment in WLAN/Cellular Integrated Networks

To meet the dramatic growth in mobile traffic, wireless local area networks (WLANs) have been integrated with cellular networks. We investigate the user equipment (UE) association problem in WLAN/cellular integrated networks from game-theoretic perspective by taking into account throughput and power consumption. In the case of WLAN offloading, random uplink traffic from UEs inevitably brings contention and collisions into WLANs; thus, the capacity of a WLAN system is decreased. To eliminate this side effect, UEs are encouraged to deliver uplink traffic over contention-free cellular networks. However, UEs will consume much more power when their uplink traffic is delivered over cellular networks instead of WLANs. Observing the above contradiction between throughput and power consumption, we define a utility function to reconcile the contradiction and formulate the UE association problem as a game. An incentive mechanism is involved to encourage UEs with enough energy to redirect their uplink traffic over cellular networks. We prove that this game is an exact potential game with at least one pure-strategy Nash equilibrium. Then, a distributed algorithm is proposed for each UE to determine its uplink association. Finally, extensive numerical simulations validate the feasibility and effectiveness of the proposed association strategy.
4‐Aminopyridine and low Ca2+ differentiate presynaptic inhibition mediated by neuropeptide Y, baclofen and 2‐chloroadenosine in rat hippocampal CA1 in vitro

1 Presynaptic inhibition is mediated by several receptors at the stratum radiatum‐CA1 synapse of rat hippocampus. We tested whether the same mechanism is activated by neuropeptide Y (NPY), baclofen and 2‐chloroadenosine (2‐CA), reasoning that if the receptors all activated the same process, then they should all respond to indirect manipulations of transmitter release in the same manner. 2 The effects on presynaptic inhibition by the potassium channel blocker, 4‐aminopyridine (4‐AP) and low extracellular concentrations of Ca2+ in the presence of 4‐AP were compared using evoked population excitatory postsynaptic potentials (p.e.p.s.p.) responses in the rat hippocampal slice in vitro. 3 Log concentration‐effect relationships for the inhibition of excitatory transmission were constructed for all 3 drugs in normal saline, and in the presence of 30 and 100 μm 4‐AP. 4‐AP reduced the inhibition mediated by all three substances, 100 μm 4‐AP was only slightly more effective than 30 μm. 4 Lowering extracellular Ca2+ from 1.5 to 0.75 mm in the presence of 30 μm 4‐AP restored the presynaptic inhibition caused by all effective concentrations of NPY and baclofen. By contrast, inhibition caused by 2‐CA was not restored by lowering Ca2+, except at concentrations of 2‐CA greater than 10 μm. 5 The results are consistent with the hypothesis that presynaptic NPY Y2 and GABAB receptors both inhibit transmitter release by the inhibition of voltage‐dependent Ca2+ influx, but that the A1 adenosine receptor may activate a different presynaptic mechanism.
Analyzing Radiation-Induced Complex Chromosome Rearrangements by Combinatorial Painting1

Abstract Cornforth, M. N. Analyzing Radiation-Induced Complex Chromosome Rearrangements by Combinatorial Painting. Radiat. Res. 155, 643–659 (2001). Prior to the advent of whole-chromosome painting, it was universally assumed that virtually all radiation-induced exchanges represented a simple rejoining between pairs of chromosome breaks. It is now known that a substantial proportion of such exchanges are actually complex, meaning that they involve the interaction of three (or more) breaks distributed among two (or more) chromosomes. The purpose of this review is to discuss some of the implications of aberration analysis using whole-chromosome painting, with emphasis given to newer combinatorial painting schemes that allow for the unambiguous identification of all homologous chromosome pairs. Such analysis requires reconsideration of how resulting information is to be handled for the purposes of tabulating and communicating raw data, quantifying aberration yields, and presenting experimental results in a cogent manner. Facilitating these objectives requires the introduction of certain concepts and terminologies that have no counterpart in conventional cytogenetic analyses.
Photoperiodic Effects on Tumor Development and Immune Function

Seasonal changes in adaptations associated with winter coping strategies have been frequently studied. Central among the suite of energy-saving, winter-coping strategies is the suspension of reproductive activities. The inhibition of reproduction by nontropical rodents is mediated by daylength changes. Although balanced annual energy budgets are critical, survival and subsequent reproductive success also require avoiding predators, illness, and early death. Because the stressors of winter could lead to suppressed immune function, we hypothesized that animals should have evolved survival strategies involving immunoenhancement. Short daylengths provide a predictive cue to individuals that could be used to enhance immune function in advance of stress-induced immunosuppression. In Experiment 1, adult female deer mice (Peromyscus maniculatus) were housed in either long (LD 16:8) or short (LD 8:16) days for 8 weeks, then injected with the chemical carcinogen 9,10-dimethyl-1,2-benzanthracene (DMBA) dissolved in dimethyl sulfoxide (DMSO) or with the DMSO vehicle alone. Animals were evaluated weekly for 8 weeks after injection. None of the animals treated with DMSO developed tumors in any of the experiments. Nearly 90% of the long-day deer mice injected with DMBA developed squamous cell carcinoma. None of the short-day deer mice injected with DMBA developed tumors. Small lesions developed at the site of injection; short-day females had less severe lesions and healed faster than long-day females. Immunoglobulin G (IgG) response to i.p. injection of sheep red blood cells (SRBC) did not differ between photoperiodic conditions. The role of estrogens in the photoperiodic responses was evaluated in Experiment 2: Ovariectomized or sham-ovariectomized deer mice received estradiol benzoate replacement therapy or a control procedure in long daylengths for 8 weeks prior to injection of DMBA or DMSO, then were monitored for 8 additional weeks. Females treated with DMBA developed tumors at the same rate, regardless of estrogen manipulation. Estrogen did not affect healing rates. In Experiment 3, female deer mice were injected with a slurry of microspheres that either contained bromocriptine or were empty. Suppression of prolactin with bromocryptine resulted in a decrease of tumor incidence from 55.6% to 24% in long-day females 8 weeks after injection with DMBA. Healing rates were not affected by prolactin manipulations. Silastic capsules that were filled with either melatonin or cholesterol were implanted into long-day female deer mice in Experiment 4; 8 weeks later, females received an injection of either DMBA or DMSO, then were monitored for 8 weeks. Approximately 66% of females implanted with cholesterol and injected with DMSO developed histologically verified tumors. None of the melatonin-implanted mice developed tumors. Melatonin did not affect healing rates. Taken together, these results indicate that photoperiod can exert a functionally significant effect on immune processes and clinical disease.
Tumor necrosis factor alpha stimulates NMDA receptor activity in mouse cortical neurons resulting in ERK‐dependent death

Multiple cytokines are secreted in the brain during pro‐inflammatory conditions and likely affect neuron survival. Previously, we demonstrated that glutamate and tumor necrosis factor alpha (TNFα) kill neurons via activation of the N‐methyl‐d‐aspartate (NMDA) and TNFα receptors, respectively. This report continues characterizing the signaling cross‐talk pathway initiated during this inflammation‐related mechanism of death. Stimulation of mouse cortical neuron cultures with TNFα results in a transient increase in NMDA receptor‐dependent calcium influx that is additive with NMDA stimulation and inhibited by pre‐treatment with the NMDA receptor antagonist, dl‐2‐amino‐5‐phosphonovaleric acid, or the α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate/kainate receptor antagonist, 6,7‐dinitroquinoxaline‐2,3‐dione. Pre‐treatment with N‐type calcium channel antagonist, ω‐conotoxin, or the voltage‐gated sodium channel antagonist, tetrodotoxin, also prevents the TNFα‐stimulated calcium influx. Combined TNFα and NMDA stimulation results in a transient increase in activity of extracellular signal‐regulated kinases (ERKs) and c‐Jun N‐terminal kinases (JNKs). Specific inhibition of ERKs but not JNKs is protective against TNFα and NMDA‐dependent death. Death is mediated via the low‐affinity TNFα receptor, TNFRII, as agonist antibodies for TNFRII but not TNFRI stimulate NMDA receptor‐dependent calcium influx and death. These data demonstrate how microglial pro‐inflammatory secretions including TNFα can acutely facilitate glutamate‐dependent neuron death.
Evaluation of the educational utility of patient follow-up.

OBJECTIVES To date, no studies in emergency medicine (EM) have addressed the educational value of the Residency Review Committee for Emergency Medicine's (RRC-EM) requirement for patient follow-up (FU). The authors examined whether performance of patient FU improved EM resident education. METHODS All EM resident FU encounters from September 25, 2001, through September 24, 2002, were documented and analyzed. All EM residents at a regional tertiary referral emergency department (ED) initiated patient FU encounters by entering information regarding patients' initial ED presentations into a Web-based follow-up system (WBFUS), subsequently entered FU information, and indicated whether they thought that the specific FU encounters improved their education (yes/no). Supervising faculty members then reviewed the residents' completed FU entries. Blinded to residents' responses regarding educational utility, faculty members evaluated whether they thought the specific FU encounters were educational for the residents (yes/no). Data entered into the WBFUS were then summarized as percentages. RESULTS Eight hundred forty-seven FU encounters were completed by 18 EM residents and 29 EM faculty. Ninety-three percent of the FU entries were deemed by at least one evaluator (resident or faculty) to have educational value. Residents found the act of performing FU educational in 81.3% of cases, whereas faculty thought 80.4% were educational for the resident. Although the residents and faculty agreed on the educational value in 75.4% of cases, the overall strength of the agreement was slight to fair (kappa statistic = 0.21). CONCLUSIONS This study indicates that EM residents and faculty believe that the act of performing patient FU has educational value for EM residents; however, the interobserver agreement between residents and faculty was low.
Multiattribute Selection of Acute Stroke Imaging Software Platform for Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) Clinical Trial

Background The appropriateness of a software platform for rapid MRI assessment of the amount of salvageable brain tissue after stroke is critical for both the validity of the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) Clinical Trial of stroke thrombolysis beyond 4.5 hours and for stroke patient care outcomes. Aims The objective of this research is to develop and implement a methodology for selecting the acute stroke imaging software platform most appropriate for the setting of a multi-centre clinical trial. Methods A multi-disciplinary decision making panel formulated the set of preferentially independent evaluation attributes. Alternative Multi-Attribute Value Measurement methods were used to identify the best imaging software platform followed by sensitivity analysis to ensure the validity and robustness of the proposed solution. Results Four alternative imaging software platforms were identified. RApid processing of Perfusion and Diffusion (RAPID) software was selected as the most appropriate for the needs of the EXTEND trial. A theoretically grounded generic multi-attribute selection methodology for imaging software was developed and implemented. Conclusions The developed methodology assured both a high quality decision outcome and a rational and transparent decision process. This development contributes to stroke literature in the area of comprehensive evaluation of MRI clinical software. At the time of evaluation, RAPID software presented the most appropriate imaging software platform for use in the EXTEND clinical trial. The proposed multi-attribute imaging software evaluation methodology is based on sound theoretical foundations of multiple criteria decision analysis and can be successfully used for choosing the most appropriate imaging software while ensuring both robust decision process and outcomes.
Immunosuppressive effect of cyclosporine in the hyperlipidemic rat model

The immunosuppressive effects of 2·5 (n = 6) and 5 mg kg−1 day−1 (n = 7) of cyclosporine (CSA) given intravenously for 9 days to the immunized, hyperlipidemic Zucker rat model were compared with drug‐free animals (n = 6) and lean litter‐mates given 0 (n = 6), 5 (n = 6), and 10 mg kg−1 day−1 (n = 8) of CSA. Thus, based on body weights, both obese rats and lean litter‐mates received total doses of 0, 1, and 2 mg of CSA. No significant differences in percent change in baseline body weight were found; in contrast, spleen weights were markedly greater in treated animals compared with controls. Serum cholesterol, triglycerides, and lipoprotein levels of obese rats were significantly greater than values found in lean litter‐mates. CSA concentrations in whole blood, serum, and the lipoprotein fractions obtained 4h after the final dose were greater in obese rats compared with lean litter‐mates. Immunosuppressive activity, as assessed by ex vivo T‐lymphocyte proliferation assay, was equivocal between all rats given CSA, independent of dose and obesity, and significantly greater than control animals. Whereas serum CSA levels were correlated to cholesterol levels (r = 0·95, p ± 0·0001), there were no significant correlations with immunosuppressive activity. The present data suggest that increased binding of CSA to lipoproteins in the vascular compartment does not significantly impact on its immunosuppressive activity.
Unaltered Drug Metabolizing Enzyme Systems in Type II Diabetes Mellitus Before and During Glyburide Therapy

Diabetes mellitus is associated with alterations in hepatic drug metabolizing enzyme activities in experimental animals. To determine whether Type II diabetes or glyburide affect hepatic drug metabolism, the authors used 13C‐labeled aminopyrine and caffeine breath tests as in vivo probes of the hepatic cytochrome P450 and P1450 enzyme activities respectively in six subjects with Type II diabetes (4 women, 2 men). These subjects had been treated previously with diet, had an age range of 41–63 years, had a body mass index range of 24.1–43.3 kg/m2 and had a mean fasting plasma glucose of 14.6 ± 1.2 mM and a mean hemoglobin A1c of 12.2 ± 0.7%. These subjects did not drink alcohol or take drugs known to affect hepatic drug metabolism. The caffeine and aminopyrine breath tests (CBT, ABT) were performed sequentially while fasting before the start of glyburide treatment (5 mg daily) and at weekly intervals for 4 weeks. ABT and CBT values are expressed as cumulative percentage of dose exhaled through 2 hours. Before beginning glyburide, the mean ABT and CBT results were 10.2 ± 0.7% and 4.2 ± 0.7% respectively, well within the normal ranges for these tests (ABT 6.5–15%; CBT 2.5–10%). The ABT and CBT values remained unaltered during 4 weeks of glyburide therapy. However, FBS decreased to 10.2 ± 1.1 mM and HbA1C to 10.1 ± 0.8% by the end of drug treatment.
[Post-operative progress of patients with Rasmussen's encephalitis who have undergone hemispherotomy surgery].

INTRODUCTION Rasmussen's encephalitis (RE) is a progressive pathology affecting the brain that causes unilateral hemispheric atrophy, neurological dysfunction and refractory epilepsy. Hemispherotomy is considered the most effective treatment today, but some cases present certain peculiarities that can seriously affect the decision to go ahead with this procedure. AIMS To evaluate the post-operative progress made by children with RE who have undergone hemispherotomy surgery, and who, in the pre-operative assessment, presented certain characteristics that complicated the decision to perform surgery. PATIENTS AND METHODS The sample selected for study consisted of the cases of RE attended in the Hospital Sao Paulo between 2003 and 2012 who, in the pre-surgery evaluation, presented clinical, electroencephalographic or neuroimaging evidence of involvement of both brain hemispheres, compromise of the dominant brain hemisphere, absence of severe neurological deficit and absence of criteria for refractory epilepsy and atypical crises. The post-operative assessment of the epileptic seizures was evaluated using the Engel scale; motor function was analysed with the Gross Motor Function Classification System and Manual Ability Classification System scales, and language was evaluated clinically. RESULTS Six cases were selected (four girls), with a mean age at clinical onset of 3.3 ± 1.2 years (range: 2-7 years) and a mean age at hemispherotomy of 6.7 years (range: 2.3-16.5 years). The mean post-surgery follow-up time was three years (range: 0.5-7.2 years). In the post-surgery evaluation of the epileptic seizures, four cases were classified as Engel class I (66%); there was some improvement in motor functioning in five of them, and language improved in all cases. CONCLUSIONS Hemispherotomy must be considered an efficient option for treatment in children with RE.