Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoxia Induces c-fos Transcription via a Mitogen-activated Protein Kinase-dependent Pathway*

Hypoxia is a pathophysiological condition that occurs during injury, ischemia, and stroke. It is characterized by a decrease of reactive oxygen intermediates and a change of the intracellular redox level. In tumors hypoxia is regarded as a trigger for enhanced growth and metastasis. Here we report that in HeLa cells, hypoxic conditions induce the transcriptional activation of c-fos transcription via the serum response element. Mutations in the binding site for the ternary complex factor Elk-1 and the serum response factor abolished this induction, indicating that a ternary complex at the serum response element is necessary for the induction of the c-fos gene under hypoxia. The transcription factor Elk-1 was covalently modified by phosphorylation in response to hypoxia. Furthermore this hyperphosphorylation of Elk-1, the activation of mitogen-activated protein kinase (MAPK), and the induction of c-fos transcripts were blocked by PD98059, a specific inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase kinase 1. Anin vitro kinase assay with Elk-1 as substrate showed that MAPK is activated under hypoxia. The activation of MAPK corresponds temporally with the phosphorylation and activation of Elk-1. Thus, a decrease of the intracellular reactive oxygen intermediate level by hypoxia induces c-fos via the MAPK pathway. These results suggest that the intracellular redox levels may be directly coupled to tumor growth, invasion, and metastasis via Elk-1-dependent induction of c-Fos controlled genes.
Hirschsprung's Disease in Neonates with Special Reference to Calretinin Immunohistochemistry.

BACKGROUND Hirschsprung's disease is a classic example of a complex genetic disease, characterized by the lack of enteric ganglia in the submucosal and myenteric plexuses, along variable portions of the distal gut. The diagnosis of Hirschsprung's disease is based on a combination of clinical features, radiological appearance of the bowel and histological features in Haematoxylin & Eosin stained sections of intestinal biopsies. Calretinin Immunohistochemistry is emerging to be one of the newer methods. AIMS AND OBJECTIVES This study was undertaken to ascertain 1) clinical profile; 2) mode of presentation; 3) to evaluate the role of Calretinin immunostain in the diagnosis of Hirschsprung's Disease. MATERIALS AND METHODS This prospective and observational study was conducted in the Department of Pathology IPGME&R from July 2013 to September 2014. Eighty nine patients, clinically and radiologically diagnosed with Hirschsprung's disease underwent surgery and were included in the study. The data of every patient including age, sex and presenting symptoms were recorded. Eventually, histopathological examination & immunohistochemistry were done. RESULTS Total number of cases studied was 89 which aged between 0 days to 28 days. Overall sensitivity in our study to diagnose presence or absence of ganglion cells by calretinin immunohistochemistry was 100% and the specificity is 97.44% with positive and negative predictive value of 84.62 % and 100 % respectively. CONCLUSION Calretinin immunohistochemistry holds several advantages, and it's simple and not doubtful; and it is either positive or negative.
Radiotherapy-induced secondary cancer risk for breast cancer: 3D conformal therapy versus IMRT versus VMAT

This study evaluated the secondary cancer risk to various organs due to radiation treatment for breast cancer. Organ doses to an anthropomorphic phantom were measured using a photoluminescent dosimeter (PLD) for breast cancer treatment with 3D conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). Cancer risk based on the measured dose was calculated using the BEIR (Biological Effects of Ionizing Radiation) VII models. The secondary dose per treatment dose (50.4 Gy) to various organs ranged from 0.02 to 0.36 Gy for 3D-CRT, but from 0.07 to 8.48 Gy for IMRT and VMAT, indicating that the latter methods are associated with higher secondary radiation doses than 3D-CRT. The result of the homogeneity index in the breast target shows that the dose homogeneity of 3D-CRT was worse than those of IMRT and VMAT. The organ specific lifetime attributable risks (LARs) to the thyroid, contralateral breast and ipsilateral lung per 100 000 population were 0.02, 19.71, and 0.76 respectively for 3D-CRT, much lower than the 0.11, 463.56, and 10.59 respectively for IMRT and the 0.12, 290.32, and 12.28 respectively for VMAT. The overall estimation of LAR indicated that the radiation-induced cancer risk due to breast radiation therapy was lower with 3D-CRT than with IMRT or VMAT.
Spiny neurons lacking choline acetyltransferase immunoreactivity are major targets of cholinergic and catecholaminergic terminals in rat striatum

The ultrastructural substrate for functional interactions between intrinsic cholinergic neurons and catecholaminergic afferents to the caudate‐putamen nucleus and nucleus accumbens septi (NAS) was investigated immunocytochemically. Single sections of glutaraldehyde‐fixed rat brain were processed (1) for the immunoperoxidase labeling of a rat monoclonal antibody against the acetylcholine‐synthesizing enzyme choline acetyltransferase (CAT) and (2) for the immunoautoradiographic localization localization of a rabbit polyclonal antiserum against the catecholamine‐synthesizing enzyme tyrosine hydroxylase (TH). The ultrastructural morphology and cellular associations did not significantly differ in the caudate‐putamen versus NAS. Immunoperoxidase reaction for CAT was seen in perikarya, dendrites, and terminals, whereas immunoautoradiography for TH was in terminals. The perikarya and dendrites immunolabeled for CAT were large, sparsely spiny, and postsynaptic mainly to unlabeled axon terminals. Only 2–3% of the CAT‐labeled terminals (n = 136) and less than 1% of the TH‐labeled terminals (n = 86) were apposed to, or formed synapses with, perikarya or dendrites immunoreactive for CAT. Most unlabeled and all labeled terminals formed symmetric synapses. In the same sample, 18% of the CAT and 16% of the TH‐labeled terminals were directly apposed to each other. Unlabeled dendritic shafts received the major (40% for CAT versus 23% for TH) synaptic input from cholinergic terminals, while unlabeled spines received the major (47% for TH versus 23% for CAT) synaptic input from catecholaminergic terminals. Neither the unlabeled dendrites or spines received detectable convergent input from CAT and TH‐labeled terminals. Thirteen percent of the CAT‐labeled and 14% of TH‐labeled terminals were in apposition to unlabeled terminals forming asymmetric, presumably excitatory, synapses with unlabeled dendritic spines. We conclude that in both the caudateputamen and NAS cholinergic and catecholaminergic terminals (1) form symmetric, most likely inhibitory, synapses primarily with non‐cholinergic neurons, (2) differentially synapse on shafts or spines of separate dendrites, and (3) have axonal appositions suggesting the possibility of presynaptic physiological interactions. These results support the hypothesis that the cholinergic‐dopaminergic balance in striatal function may be mediated through inhibition of separate sets of spiny projection neurons with opposing excitatory and inhibitory functions.
Comparative dose‐dependence study of FK506 on transected mouse sciatic nerve repaired by allograft or xenograft

Abstract We evaluated the effects of FK506, at doses of 0.2, 2, and 5 mg/kg/day, on the response to nerve grafts implanted in outbred mice. A 6 mm long segment of the sciatic nerve was transected and repaired by autograft (the same segment resected), allograft (from another mouse), or xenograft (from a rat nerve). The regenerating nerves were harvested after 3 weeks and studied under light and electron microscope. Allografts of animals treated with the 5 mg/kg/day dose of FK506 appeared similar to those from autografts, demonstrating an equivalent number of myelinated fibers. In mice treated with the 2 mg/kg/day dose, regeneration was slightly hindered, as indicated by the reduced number of myelinated fibers. In contrast, in mice given a 0.2 mg/kg/day dose of FK506, allografts were not different from untreated allografts; both groups showed a marked rejection response with only few unmyelinated axons and no myelinated fibers. Xenografts showed a more severe rejection than allografts, with a marked inflammatory cell reaction throughout the graft. In contrast, in mice treated with the 5 mg/kg/day dose, xenografts exhibited a mild cell reaction and a greater number of regenerated myelinated fibers. In conclusion, effective axonal regeneration is achieved with FK506 administration at doses of 5 mg/kg/day through allografts and, partially, through xenografts.
Insect Population Control by Homing Endonuclease-Based Gene Drive: An Evaluation in Drosophila melanogaster

Insects play a major role as vectors of human disease as well as causing significant agricultural losses. Harnessing the activity of customized homing endonuclease genes (HEGs) has been proposed as a method for spreading deleterious mutations through populations with a view to controlling disease vectors. Here, we demonstrate the feasibility of this method in Drosophila melanogaster, utilizing the well-characterized HEG, I-SceI. In particular, we show that high rates of homing can be achieved within spermatogonia and in the female germline. We show that homed constructs continue to exhibit HEG activity in the subsequent generation and that the ectopic homing events required for initiating the strategy occur at an acceptable rate. We conclude that the requirements for successful deployment of a HEG-based gene drive strategy can be satisfied in a model dipteran and that there is a reasonable prospect of the method working in other dipterans. In characterizing the system we measured repair outcomes at the spermatogonial, spermatocyte, and spermatid stages of spermatogenesis. We show that homologous recombination is restricted to spermatogonia and that it immediately ceases when they become primary spermatocytes, indicating that the choice of DNA repair pathway in the Drosophila testis can switch abruptly during differentiation.
Self, Memory, and the Self-Reference Effect

The author argues that the self is a multifaceted entity that does not easily submit to clear and precise description. The aspect of self studied by most investigators is actually a subset of the cognitive and neural underpinnings of “self” and not the “self” of first-person subjectivity. The author then looks at the dominant theoretical treatment of human long-term memory—the systems approach—and examines how the construct of “self” is situated in this framework. Finally, he reviews the best-known paradigm for exploring the role of self in memory—the self-reference effect (SRE) manipulation. He argues that there is not one SRE but rather a family of related SREs that are influenced by a variety of variables and contexts. Accordingly, researchers must exercise caution when attempting to draw conclusions about the self from the results of SRE memory performance.
Potassium-Channel Openers KMUP-1 and Pinacidil Prevent Subarachnoid Hemorrhage–Induced Vasospasm by Restoring the BKCa-Channel Activity

Alterations in the activity of vascular K+ channels are commonly associated with abnormalities in cerebral vascular function after subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage–induced vasospasm remains incompletely understood; nevertheless, activation of K+ channels may be of benefit in relieving spastic constriction. This study was to examine whether the vasodilators KMUP-1 and pinacidil, a KATP-channel opener, have the ability to prevent SAH-induced vasospasm via the large-conductance Ca2+-activated K+ (BKCa) channels in cerebral arteries. Rats were divided into four groups including sham-operated, SAH, KMUP-1 treated, and pinacidil treated. Subarachnoid hemorrhage rats were induced by injecting autologous blood into cisterna magna, and then KMUP-1 or pinacidil (1 mg/kg) was injected intraperitoneally 1 and 24 h after SAH. Behavioral tests were assessed on day 2 after SAH before the rats were killed. Cerebral myocytes were enzymatically isolated from rat basilar arteries and used to monitor BKCa-channel activities. In isolated basilar arteries, KMUP-1–treated and pinacidil-treated rats showed normalized vascular reactivity. In whole-cell recordings, BKCa currents were attenuated in SAH rats compared with sham-operated rats. In inside-out patches, the conductance and voltage sensitivity of single BKCa-channels were unchanged among the four groups. In contrast, SAH rats showed markedly decreased BKCa-channel activity and &bgr;1-subunit expression associated Ca2+ sensitivity that was further confirmed by immunofluorescence staining and Western blotting. Subarachnoid hemorrhage–induced deficits in motor function and BKCa-channel inhibition were improved by KMUP-1–treated and pinacidil-treated rats. In addition, SAH appears to modify BKCa-channel calcium sensitivity. KMUP-1 and pinacidil prevent SAH-induced vasospasm at least in part by the restoration of BKCa-channel activities. ABBREVIATIONS BKCa channels—large-conductance Ca2+-activated K+ channels IbTX—iberitoxin NPo—channel activity SAH—subarachnoid hemorrhage
Tat is required for efficient HIV‐1 reverse transcription

The ability of human immunodeficiency virus‐1 (HIV‐1) to undergo efficient reverse transcription is dependent on a number of parameters. These include the binding of the tRNA3Lys to the HIV‐1 primer binding site and the subsequent interaction with the heterodimeric reverse transcriptase. Recently, we demonstrated that TAR RNA was also necessary for efficient HIV‐1 reverse transcription. Given the fact that the Tat protein is involved in the activation of HIV‐1 gene expression in conjunction with TAR, we wished to determine whether Tat might also be involved in the control of HIV‐1 reverse transcription. HIV‐1 virions deleted in the tat gene were unable to initiate reverse transcription efficiently upon infection of peripheral blood mononuclear cells (PBMCs). This defect was not due to decreased amounts of genomic RNA, reverse transcriptase or other HIV‐1 proteins which were incorporated into the virion. Following transfection of wild‐type but not mutant tat genes into cell lines producing HIV‐1 lacking tat, the virions produced could be complemented for defects in reverse transcription upon subsequent infection of PBMCs. In contrast, the defect in reverse transcription seen with HIV‐1 lacking the tat gene could not be complemented when the target cells rather than the producer cells contained tat. Viruses lacking tat were also defective in endogenous assays of reverse transcription, although these viruses contained similar levels of reverse transcriptase. These results indicate that the Tat protein, in addition to regulating the level of gene expression, is also important for efficient HIV‐1 reverse transcription.
A trial of flunarizine in the treatment of duchenne muscular dystrophy

Twenty‐seven boys with Duchenne muscular dystrophy (DMD) entered a double‐blind controlled trial of treatment with the calcium antagonist flunarizine. They were matched for age and disability. At monthly intervals, muscle power, functional ability, locomotor score, contractures, and forced vital capacity were measured by a team not involved in clinical care. Over a period of 1 year, flunarizine in a dose of up to 0.25 mg/kg/day had no effect on the clinical course of the disease.
Low genomic diversity in tropical oceanic N2-fixing cyanobacteria

High levels of genomic and allelic microvariation have been found in major marine planktonic microbial species, including the ubiquitous open ocean cyanobacterium, Prochlorococcus marinus. Crocosphaera watsonii is a unicellular cyanobacterium that has recently been shown to be important in oceanic N2 fixation and has been reported from the Atlantic and Pacific oceans in both hemispheres, and the Arabian Sea. In direct contrast to the current observations of genomic variability in marine non-N2-fixing planktonic cyanobacteria, which can range up to >15% nucleotide sequence divergence, we discovered that the marine planktonic nitrogen-fixing cyanobacterial genus Crocosphaera has remarkably low genomic diversity, with <1% nucleotide sequence divergence in several genes among widely distributed populations and strains. The cultivated C. watsonii WH8501 genome sequence was virtually identical to DNA sequences of large metagenomic fragments cloned from the subtropical North Pacific Ocean with <1% sequence divergence even in intergenic regions. Thus, there appears to be multiple strategies for evolution, adaptation, and diversification in oceanic microbial populations. The C. watsonii genome contains multiple copies of several families of transposases that may be involved in maintaining genetic diversity through genome rearrangements. Although genomic diversity seems to be the rule in many, if not most, marine microbial lineages, different forces may control the evolution and diversification in low abundance microorganisms, such as the nitrogen-fixing cyanobacteria.
A comparison of four frequency-doubled Nd:YAG (532 nm) laser systems for treatment of facial telangiectases.

BACKGROUND Telangiectases are cosmetically concerning for millions of individuals who develop them on the face as they mature. The causative factors are numerous. Lasers have recently become the focus for treating small facial telangiectases because of their ability to selectively target vessels. OBJECTIVE The purpose of this study was to compare the efficacy of four different frequency-doubled neodymium:yttrium-aluminum-garnet (FD Nd:YAG) laser (532 nm) systems for the treatment of facial arteriolar telangiectases. METHODS Forty adult subjects with Fitzpatrick skin phenotypes I and II were randomly assigned to four treatment groups. Each group, consisting of 10 subjects, had telangiectases less than 1000 microm in diameter treated with one of four different FD Nd:YAG laser systems with a wavelength of 532 nm. Patients were treated once and clinical improvement and potential adverse effects were assessed at 1 and 8 weeks after treatment. RESULTS All treated patients showed improvement after one laser session. No patients were seen to have scarring or pigmentary changes. There was no significant difference in the clinical response following treatment with each laser. CONCLUSION The four different FD Nd:YAG lasers performed equally well in treating facial telangiectases. With a wavelength of 532 nm and pulse durations in the millisecond range, vessels can be selectively targeted with a minimal incidence of post-operative complications.
A Meta-Analytic Investigation of the Relationship of State and Trait Anxiety to Performance on Figural and Verbal Creative Tasks

Extensive research suggests when and how anxiety has debilitating or facilitating effects on routine cognitive tasks or motor tasks. However, research examining anxiety’s relation to performance on creative tasks such as divergent thinking and artistic tasks is less conclusive despite a rather substantial literature. The authors’ meta-analytic investigation of 59 independent samples finds that anxiety is significantly and negatively related to creative performance. In addition, the findings provide insights into factors such as task complexity, type of task (i.e., figural or verbal), and type of anxiety (i.e., state or trait) that moderate the relationship between anxiety and creativity—all of which are consistent with the idea that anxiety and creativity present competing cognitive demands. In addition to identifying gaps in the literature such as the need for research using a two-component model of anxiety in relation to creativity, the authors’ results have practical implications for those seeking to increase individual creativity.
Are Children More Exposed to Radio Frequency Energy From Mobile Phones Than Adults?

There has been long-standing controversy, both among scientists and in the public, about whether children absorb more radio frequency (RF) energy in their heads than adults when using a mobile telephone. This review summarizes the current understanding of this issue, and some of the complexities in comparing the absorption of RF energy in different individuals from use of mobile phones. The discussion is limited to dosimetric issues, i.e., possible age-related differences in absorption of RF energy in the heads of mobile phone users. For most metrics of exposure, in particular those relevant to assessing the compliance of handsets with regulatory limits, there is no clear evidence for age-related differences in exposure. For two metrics of exposure, there is a clear evidence that age can play a factor: 1) the local specific absorption rate (SAR), in particular anatomically defined locations within the brain, will vary with head size and hence with age and 2) the SAR, in particular tissues, (e.g., bone marrow in the skull) can vary with age due to age-related differences in the dielectric properties of tissue. However, these differences involve SAR levels that are below the 1-g or 10-g peak spatial SAR (psSAR averaged over 1 or 10 g of tissue) and have no significance for compliance assessment. Age-related differences observed in worst case simulations such as presently considered are difficult to generalize to human populations under real-world exposure conditions due to many variables that determine SAR during realistic usages.
Line Edge Roughness of Metal Lines and Time-Dependent Dielectric Breakdown Characteristics of Low-k Interconnect Dielectrics

We present both experimentally and numerically the effect of the line edge roughness (LER) of metal lines on breakdown characteristics of low-k interconnect dielectrics. Experimental results show that the LER-induced metal-to-metal space variation significantly affects the Weibull slope, field acceleration parameter and hence the time-dependent dielectric breakdown (TDDB) reliability lifetime of sub-100 nm metal-to-metal spacing interconnects. For detailed quantitative explanation of the effect, we have developed a Monte Carlo simulation model, calibrated to experimental results, and performed a number of Monte Carlo simulations under various conditions. Both experimental and numerical simulation results support that lithography and dry etch processes affecting LER are of great importance to ensure robust low-k TDDB reliability of aggressively scaled interconnects.
Effect of Battery Degradation on Multi-Service Portfolios of Energy Storage

In an electricity market environment, energy storage plant owners are remunerated for the provision of services to multiple electricity sectors. Some of these services, however, may accelerate battery aging and degradation and hence this needs to be properly balanced against associated services remunerations. In this framework, we propose a combined economic-degradation model to quantify effects of operational policies (mainly focused on constraining State of Charge -SOC- to prescribed levels in order to reduce effects of aging) on gross revenue, multi-service portfolios, degradation and lifespan of distributed energy storage plants that can provide multiple services to energy and balancing market participants and Distribution Network Operators. Through various case studies based on the Great Britain system, we demonstrate that although operational policies focused on battery damage reduction will lead to a revenue loss in the short-term, such loss can be more than compensated by long-term revenues due to a lengthier battery lifespan. We also demonstrate that operational policies to reduce battery degradation mainly affect services related to the energy (rather than balancing) market, which represents a smaller proportion of the overall revenue streams of a distributed storage plant. The model is also used to study effects of ambient temperature fluctuations.