Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcription termination in the Escherichia coli dnaA gene is not mediated by the internal DnaA box

DnaA protein is a DNA-binding protein which recognizes a 9-bp consensus sequence called the DnaA box. By binding to DnaA boxes, DnaA protein regulates initiation of chromosomal replication and transcription of several genes. The dnaA gene contains two DnaA boxes, one located in the regulatory region and one within the structural gene. In this paper, we explore the role of the internal DnaA box in dnaA expression because it has been proposed that the DnaA box-DnaA protein complex can block transcribing RNA polymerase. Firstly, we analyzed the degree of derepression of the dnaA gene, measured as beta-galactosidase activity of a dnaA-lacZ fusion inserted onto the bacterial chromosome, produced by an extra copy number of the dnaA DnaA boxes carried by multicopy plasmids. Secondly, we analyzed repression produced by elevated levels of DnaA protein on single-copy dnaA-lacZ fusions containing or not containing the internal DnaA box. Our results indicate that the internal DnaA box does not play a regulatory role in dnaA expression.
SUNYAEV–ZEL'DOVICH-MEASURED PRESSURE PROFILES FROM THE BOLOCAM X-RAY/SZ GALAXY CLUSTER SAMPLE

We describe Sunyaev–Zel'dovich (SZ) effect measurements and analysis of the intracluster medium (ICM) pressure profiles of a set of 45 massive galaxy clusters imaged using Bolocam at the Caltech Submillimeter Observatory. We deproject the average pressure profile of our sample into 13 logarithmically spaced radial bins between 0.07R500 and 3.5R500, and we find that a generalized Navarro, Frenk, and White (gNFW) profile describes our data with sufficient goodness-of-fit and best-fit parameters (C500, α, β, γ, P0 = 1.18, 0.86, 3.67, 0.67, 4.29). We use X-ray data to define cool-core and disturbed subsamples of clusters, and we constrain the average pressure profiles of each of these subsamples. We find that, given the precision of our data, the average pressure profiles of disturbed and cool-core clusters are consistent with one another at R ≳ 0.15R500, with cool-core systems showing indications of higher pressure at R ≲ 0.15R500. In addition, for the first time, we place simultaneous constraints on the mass scaling of cluster pressure profiles, their ensemble mean profile, and their radius-dependent intrinsic scatter between 0.1R500 and 2.0R500. The scatter among profiles is minimized at radii between ≃ 0.2R500 and ≃ 0.5R500, with a value of ≃ 20%. These results for the intrinsic scatter are largely consistent with previous analyses, most of which have relied heavily on X-ray derived pressures of clusters at significantly lower masses and redshifts compared to our sample. Therefore, our data provide further evidence that cluster pressure profiles are largely universal with scatter of ≃ 20%–40% about the universal profile over a wide range of masses and redshifts.
The diverse role of miR‐31 in regulating cancer associated phenotypes

In the past 10 years research on miRNAs has demonstrated their central role in regulating gene expression both in normal and diseased tissue. The expression of miRNAs is widely altered in cancer, leading to abnormal expression of the genes regulated by these miRNAs, and subsequently alterations in entire molecular networks and pathways. One especially interesting cancer‐related miRNA is miR‐31 which is frequently altered in a large variety of cancers. The functional role of miR‐31 is extremely complex and miR‐31 can hold both tumor suppressive and oncogenic roles in different tumor types. The phenotype caused by aberrant miR‐31 expression seems to be strongly dependent on the endogenous expression levels. For example, in breast cancer loss of miR‐31 expression is associated with high risk of metastases, whereas in colorectal cancer high miR‐31 expression correlates with advanced disease stage. This review summarizes the complex expression patterns of miR‐31 in human cancers, describes the variable phenotypes caused by altered miR‐31 expression, and highlights the current knowledge on the genes targeted by miR‐31. © 2013 Wiley Periodicals, Inc.
Airway Responses During Desflurane Versus Sevoflurane Administration via a Laryngeal Mask Airway in Smokers

Cigarette smokers have a greater risk of respiratory complications during anesthesia compared with nonsmokers. It is not known whether the relative pungency of an inhaled anesthetic further contributes to the smokers’ increased rate of such complications. In the present study, we tested whether the use of a more pungent anesthetic (desflurane) would result in a higher rate of coughing, breath holding, laryngospasm, or desaturation among patients who smoke. We randomly assigned 110 smokers to anesthesia with desflurane (n = 55) or sevoflurane (n = 55), administered via a laryngeal mask airway. Five patients (9%) receiving desflurane and nine patients (16%) receiving sevoflurane coughed (P = 0.39). Most coughing occurred during induction (33%) or emergence (56%), in the setting of airway manipulation and low anesthetic concentration. The rate of breath holding, laryngospasm, and desaturation was similar between those receiving desflurane versus sevoflurane. A retrospective comparison of this cohort of 110 smokers to a previous group consisting of 100 nonsmokers and 27 smokers receiving an identical anesthetic regimen indicates that cigarette smoking, but not choice of anesthetic, places patients at increased risk of respiratory complications.
Indices of Language Outcome 11 Years After Intrathecal Chemotherapy for Acute Lymphoblastic Leukemia: A Sibling Case-Control Study

Studies are emerging that suggest that major language indices do not differentiate children treated for acute lymphoblastic leukemia (ALL) with risk-adapted intrathecal chemotherapy (ITC) from control children matched on age, gender, and educational level. No study to date has controlled for cognitive environment, an important variable influencing language achievement and outcome. This case-control study applies the deconfounding principle by using a sibling as a control to investigate language outcomes in a male child 11 years after administration of ITC for ALL at the age of 2 years 3 months. A comprehensive behavioral language test battery failed to differentiate the siblings on current language performance when descriptively compared, but neurophysiological assessment revealed that the ITC-treated child required more time and elicited a smaller N400 component compared to his sibling during picture-word matching. The findings suggest that in the absence of pretreatment performance indices, comparison with sibling achievement may supplement what is known on posttreatment language skill development drawn from comparative studies using children matched on age, sex, and educational level drawn from the community. The study's findings offer pilot data of language outcomes following ITC beyond the early stage of survivorship. The benefits and limitations of using siblings in research where the cognitive environment is known to make an important contribution to skill development are discussed.
Intracellular Localization of Ornithine Decarboxylase and Its Regulatory Protein, Antizyme-1

The enzyme ornithine decarboxylase (ODC) and its regulatory protein antizyme-1 (AZ1) are key regulators in the homeostasis of polyamines. To gain more insight into the exact intracellular distribution of ODC and AZ1, we performed immunocytochemical and Green Fluorescent Protein-fluorocytochemical studies in cultured human cervix carcinoma and human prostatic carcinoma (PC-346C) cells. ODC localization patterns varied from predominantly cytoplasmic to both cytoplasmic and nuclear staining, whereas AZ1 was mostly found in the nucleus. In cells that were synchronized in the mitotic phase, localization of both ODC and AZ1 changed from perinuclear at the beginning of mitosis into nucleoplasmic at close proximity to the chromosomes during meta-, ana- and telophase. Upon completion of mitosis, localization of ODC and AZ1 was reverted back to the cytoplasm, i.e., predominantly perinuclear immediately after cytokinesis. When PC-346C cells were treated with polyamines to induce AZ1-regulated ODC degradation, ODC was predominantly found in the nucleus and colocalized with immunoreactive AZ1. A comparable accumulation of ODC and AZ1 in the nucleus was found in PC-346C cells treated with the polyamine analog SL-11093. The present study suggests that AZ1 is involved in nucleocyto-plasmic shuttling of ODC, which may be a prerequisite for ODC regulation and/or function.
MYCN Is the only highly expressed gene from the core amplified domain in human neuroblastomas

MYCN amplification in neuroblastomas is strongly associated with advanced stages of disease and a poor prognosis. We have recently defined a 130 kb core region of the MYCN amplicon that is consistently amplified in neuroblastomas. However, it has been argued that other expressed sequences were coamplified with MYCN and, as a result, might contribute to the aggressive phenotype of MYCN‐amplified neuroblastomas. Therefore, we have screened cosmids representing the core MYCN‐amplified domain and surrounding DNA by using a differential hybridization approach to detect other amplified, highly expressed genes from this region. Our results suggest that MYCN is the only highly expressed gene consistently amplified in human neuroblastomas, and that the MYCN gene is likely to be the only selective marker for genomic amplification in these tumors. Genes Chromosomes Cancer 23:134–140, 1998. © 1998 Wiley‐Liss, Inc.
Shoulder Injuries in English Community Rugby Union

Abstract The aim of this study was to describe the incidence, severity and type of shoulder injuries resulting from match play in adult community rugby union between 2009–2013. A total of 254 time-loss shoulder injuries were reported, an overall incidence of 2.2 per 1 000 h (95% CI: 1.9 to 2.4), and a mean injury severity of 9.5 weeks missed (95% CI: 8.2 to 10.8). The semi-professional group had an incidence of 2.8 injuries per 1 000 h (95% CI: 2.2 to 3.5), which was higher than the recreational group at 1.8 injuries per 1 000 h (95% CI: 1.4 to 2.2, p=0.004). The incidence of acromioclavicular joint injury for semi-professional players was 1.2 per 1 000 h (95% CI: 0.8 to 1.6); which was significantly higher than the incidence of this injury type in recreational players (0.5 per 1 000 h 95% CI: 0.3 to 0.7, p=0.002). Overall, back row players sustained the highest incidence of all shoulder injuries for a given playing position, 2.9 injuries per 1 000 h (95% CI: 2.2 to 3.6). The tackle was the main event associated with injury. Injury prevention programs and coaching strategies that consider tackle technique and physical conditioning of the shoulder region are therefore considered important.
Brain biometals and Alzheimer's disease – boon or bane?

Alzheimer's disease (AD) is the most common form of dementia. Several hypotheses have been put forward to explain the basis of disease onset and progression. A complicated array of molecular events has been implicated in the pathogenesis of AD. It is attributed to a variety of pathological conditions that share similar critical processes, such as oxidative stress, proteinaceous aggregations, mitochondrial dysfunctions and energy failure. There is increasing evidence suggesting that metal homeostasis is dysregulated in the pathology of AD. Biometals play an important role in the normal body functioning but AD may be mediated or triggered by disproportion of metal ions leading to changes in critical biological systems and initiating a cascade of events finally leading to neurodegeneration and cell death. The link is multifactorial, and although the source of the shift in oxidative homeostasis is still unclear, current evidence points to changes in the balance of redox transition metals, especially iron, copper (Cu) and other trace metals. Their levels in the brain are found to be elevated in AD. In other neurodegenerative disorders, Cu, zinc, aluminum and manganese are involved. This paper is a review of recent advances of the role of metals in the pathogenesis and pathophysiology of AD and related neurodegenerative diseases.
BINDING OF CARDIOGLOBULIN-C-CA45 TO CARDIAC MUSCLE AND RELEASE BY CARDIOGLOBULIN-A.

The cardiotonic action of cardioglobulin on the frog heart is a result of the interaction of three globulins, cardioglobulin-A, -B, and -C. Cardioglobulin-B binds to the heart. It has been shown that cardioglobulin-C binds to a cardioglobulin-B heart, but not to a heart without cardioglobulin-B. Cardioglobulin-C binding has been demonstrated both by biological activity and by persistence of cardioglobulin-C-Ca45 counts on the heart. The addition of cardioglobulin-A to a cardioglobulin-B-C heart causes the characteristic cardiotonic action of the system. Addition of cardioglobulin-A is associated with release of tracer from bound cardioglobulin-C-Ca45, measured as a decrease in heart radioactivity. The correlations between biological activity and localization of Ca45 of labeled cardioglobulin-C are consistent with the hypothesis that cardioglobulin action is associated with the release of cardioglobulin-C calcium into the cell. The amount of calcium involved has been estimated to be of the order of 10–4 µm for an 80-mg frog heart.
Management of intracranial fungal infections in patients with haematological malignancies

The incidence of, and mortality associated with, invasive fungal infections remains far higher than hoped. As a consequence of the overall increase in the incidence of such infections over time, the incidence of central nervous system (CNS) fungal infections is also increasing and, despite improvements in diagnostic techniques and the introduction of novel antifungal agents, therapy for CNS infections is still associated with discouragingly poor results. In patients with haematological malignancies, opportunistic infections with Candida or Aspergillus remain the most common infections affecting the CNS; however, opportunistic infections with less well‐known fungi are becoming more common and must be considered in the differential diagnosis. New techniques for the early diagnosis of invasive fungal infections are emerging. Pharmacologic options for treating invasive fungal infections have also improved during the past few years, with new drugs becoming available that have broader antifungal spectra and better safety profiles. Other novel treatment approaches, such as combination therapy, are also being explored. Early investigations have produced encouraging results; however, large, prospective studies involving many patients are necessary to validate the widespread use of these approaches. This review analyses the existing guidelines for treatment of CNS fungal infections and the literature available on the use of new drugs to generate sets of recommendations for treatment of these life‐threatening infections in patients with haematological malignancies.
Expression of urinary miRNAs targeting NLRs inflammasomes in bladder cancer

Aim of the study Inflammasome, a large complex of NOD-like receptors (NLRs), drives tumor growth and progression. The present study aimed at exploring the alteration in expression of urinary inflammasome-related microRNAs (miRNAs) in bladder cancer (BC). Our previous report demonstrated the up-regulation of NLRs genes (NLRP3, NLRP4, NLRP9 and NAIP) in urine sediments of patients harboring BC. The expression levels of miRNAs targeting these NLRs (miR-146a-5p, miR-106a-5p, miR-17-5p, miR-223-3p, miR-141-3p, miR-19a-3p, miR-145-5p, miR-185-5p) were assayed in the same patient cohort. Materials and methods Forty-six subjects affected by BC, 28 healthy controls (CTR0) and 31 subjects with histologically confirmed bladder inflammation (CTR1) were recruited. Total RNA was extracted from urine sediment and resulting cDNA was used for amplification by real-time polymerase chain reaction. MiRNA expression levels were evaluated and compared among selected groups. Patients were further stratified according to tumor stage, grade and risk of recurrence and progression. Moreover, non-muscle invasive low-grade and high-grade (HG) BC patients were compared. Results MiR 141-3p and miR-19a-3p expression decreased in CTR1 with respect to both BC and CTR0. In contrast, miR-146a-5p was up-regulated in BC compared with CTR0. MiR106a-5p, miR17-5p and miR19a-5p were significantly up-regulated in HG, high-risk (HR) and non-muscle invasive HG BC patients, while miR-185-5p was significantly higher in muscle invasive tumors, according to T stage stratification. Conclusion The increased expression of miRNAs targeting NLRs in HG and HR BC patients is in accordance with the decrease in NLR mRNAs observed in our previous report. These data corroborate the direct role of NLR genes and respective regulatory miRNAs in BC making these inflammasome-related molecules a reliable non-invasive tool for BC diagnosis.
Design of small hand‐launched solar‐powered UAVs: From concept study to a multi‐day world endurance record flight

We present the development process behind AtlantikSolar, a small 6.9 kg hand‐launchable low‐altitude solar‐powered unmanned aerial vehicle (UAV) that recently completed an 81‐hour continuous flight and thereby established a new flight endurance world record for all aircraft below 50 kg mass. The goal of our work is to increase the usability of such solar‐powered robotic aircraft by maximizing their perpetual flight robustness to meteorological deteriorations such as clouds or winds. We present energetic system models and a design methodology, implement them in our publicly available conceptual design framework for perpetual flight‐capable solar‐powered UAVs, and finally apply the framework to the AtlantikSolar UAV. We present the detailed AtlantikSolar characteristics as a practical design example. Airframe, avionics, hardware, state estimation, and control method development for autonomous flight operations are described. Flight data are used to validate the conceptual design framework. Flight results from the continuous 81‐hour and 2,338 km covered ground distance flight show that AtlantikSolar achieves 39% minimum state‐of‐charge, 6.8 h excess time and 6.2 h charge margin. These performance metrics are a significant improvement over previous solar‐powered UAVs. A performance outlook shows that AtlantikSolar allows perpetual flight in a 6‐month window around June 21 at mid‐European latitudes, and that multi‐day flights with small optical‐ or infrared‐camera payloads are possible for the first time. The demonstrated performance represents the current state‐of‐the‐art in solar‐powered low‐altitude perpetual flight performance. We conclude with lessons learned from the three‐year AtlantikSolar UAV development process and with a sensitivity analysis that identifies the most promising technological areas for future solar‐powered UAV performance improvements.
A Perceptually Based Method for Enhancing Pulmonary Nodule Recognition

RATIONALE AND OBJECTIVES.Feedback of chest areas receiving prolonged gaze durations significantly increases nodule detection performance. Why feedback circling enhances performance when other cueing methods produce equivocal results was assessed. METHODS.Chest and noise images with nodule targets were used to determine: what type of cue is most effective; whether circling influences the way the eye samples the target; whether circling limits processing of distracting information outside its boundary. RESULTS.Circling improves performance more than cues with less complete boundaries and increases the accuracy and frequency with which nodules are fixated. Outside distractors were detected less often with than without the circle present. CONCLUSIONS.Circling isolates the abnormal region from the rest of the image, making disembedding and integration of nodule features more likely and insulates this region from distractors. The facilitative effects of circling are generalizable to other images in which low contrast targets are embedded in noisy backgrounds.
A comparison of sugammadex and neostigmine for reversal of rocuronium‐induced neuromuscular blockade in children

Sugammadex is designed to be a reversal agent for steroidal muscle relaxants. The current trial was aimed to compare between sugammadex and neostigmine concerning the recovery time from neuromuscular blockade. We hypothesised that sugammadex might have shorter recovery time than neostigmine.
Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma: a Pediatric Oncology Group study.

PURPOSE Children less than 1 year of age with metastatic neuroblastoma NB are at high risk of death. The need to identify new and effective chemotherapy agents is clear. A study was conducted by the Pediatric Oncology Group (POG) to determine the efficacy and safety of administering two courses of a single phase II agent before conventional treatment as a means to evaluate new agents in this setting. PATIENTS AND METHODS One hundred seventy-three eligible patients more than 1 year of age with disseminated neuroblastoma received two courses of one of the following: ifosfamide (IFOS) 2 g/m2/d for 4 days intravenously (IV) plus mesna; carboplatin (CARB) 560 mg/m2 i.v. over 1 hour; iproplatin (CHIP) 325 mg/m2 IV over 2 hours; or epirubicin (EPIR) 90 mg/m2 i.v. push. Following evaluation for response and toxicity, eligible patients were randomized to receive either cisplatin 90 mg/m2 i.v. on day 1, etoposide 200 mg/m2 i.v. on day 3, cyclophosphamide 150 mg/m2/d orally on days 7 to 13, doxorubicin 35 mg/m2 i.v. on day 14 (CECA), or cisplatin 40 mg/m2 IV on days 1 to 5 and etoposide 200 mg/m2 i.v. on days 2 to 4 alternating at 3-week intervals with cyclophosphamide 150 mg/m2/d orally on days 1 to 7 and doxorubicin 35 mg/m2 IV on day 8 (HDP/VP/CA). An additional 86 patients were randomized to receive either CECA or HDP/VP/CA without initial phase II therapy. RESULTS After phase II therapy, only 20% of patients experienced grade 3/4 hematopoietic toxicity. No toxic deaths occurred. Objective response rates (partial responses [PRs] plus minor responses [MRs]) following IFOS, CARB, CHIP, and EPIR were 70%, 77%, 67%, and 26%, respectively. Following phase III treatment, there was no statistically significant difference in rates of complete response (CR)/PR or progressive disease (PD), or in time to PD of patients who participated in the phase II window versus those who received only CECA or HDP/VP/CA. CONCLUSION IFOS, CARB, and CHIP are efficacious in neuroblastoma, are well tolerated, and should be incorporated into primary treatment regimens. Combination regimens using these agents may be possible, since most repeat courses were given within 2 weeks. Administering phase II therapy to untreated patients with high-risk tumors provides a unique and sensitive method to assess new agents without compromising patient outcome.