Miracle-dz/UniFAR-FTUs huggingface dataset:
Escherichia coli endonuclease VIII: cloning, sequencing, and overexpression of the nei structural gene and characterization of nei and nei nth mutants

Escherichia coli possesses two DNA glycosylase/apurinic lyase activities with overlapping substrate specificities, endonuclease III and endonuclease VIII, that recognize and remove oxidized pyrimidines from DNA. Endonuclease III is encoded by the nth gene. Endonuclease VIII has now been purified to apparent homogeneity, and the gene, nei, has been cloned by using reverse genetics. The gene nei is located at 16 min on the E. coli chromosome and encodes a 263-amino-acid protein which shows significant homology in the N-terminal and C-terminal regions to five bacterial Fpg proteins. A nei partial deletion replacement mutant was constructed, and deletion of nei was confirmed by genomic PCR, activity analysis, and Western blot analysis. nth nei double mutants were hypersensitive to ionizing radiation and hydrogen peroxide but not as sensitive as mutants devoid of base excision repair (xth nfo). Single nth mutants exhibited wild-type sensitivity to X rays, while nei mutants were consistently slightly more sensitive than the wild type. Double mutants lacking both endonucleases III and VIII exhibited a strong spontaneous mutator phenotype (about 20-fold) as determined by a rifampin forward mutation assay. In contrast to nth mutants, which showed a weak mutator phenotype, nei single mutants behaved as the wild type.
HIF-1, An Oxygen and Metal Responsive Transcription Factor

Normal development and function of metazoan organisms depend on oxygen availability. The level of oxygen can be sensed by individual cells, which respond to reduced oxygenation (hypoxia) largely through activation of hypoxia-inducible factor-1 (HIF-1). At the organism level the response to hypoxia involves an increase in red blood cell production. Within tissues, HIF activation increases the blood supply and blood vessel growth. At the individual cell level it is manifested as an increase in anaerobic metabolism in order to sustain basic cellular functions. Iron is central to the oxygen sensing mechanism, and sensitivity to other metals, namely cobalt and nickel, is a distinctive feature of the HIF system; in fact, this is often used as an initial way of implicating HIF-1 in a biological response. Historically, the fact that nickel or cobalt mimicked hypoxia provided an important clue as to the nature of the oxygen sensing mechanism. It also raises the possibility that nickel or cobalt exposure may have important toxic and pathological effects mediated by HIF activation. Here we review the implications of the metal sensitivity of the HIF-1 system, and examine the hypothesis that HIF-1 activation may play an important role in metal induced carcinogenesis.
The CCCH tandem zinc-finger protein Zfp36l2 is crucial for female fertility and early embryonic development

The CCCH tandem zinc finger protein, Zfp36l2, like its better-known relative tristetraprolin (TTP), can decrease the stability of AU-rich element-containing transcripts in cell transfection studies; however, its physiological importance is unknown. We disrupted Zfp36l2 in mice, resulting in decreased expression of a truncated protein in which the N-terminal 29 amino acids had been deleted (ΔN-Zfp36l2). Mice derived from different clones of ES cells exhibited complete female infertility, despite evidence from embryo and ovary transplantation experiments that they could gestate and rear wild-type young. ΔN-Zfp36l2 females apparently cycled and ovulated normally, and their ova could be fertilized; however, the embryos did not progress beyond the two-cell stage of development. These mice represent a specific model of disruption of the earliest stages of embryogenesis, implicating Zfp36l2, a probable mRNA-binding and destabilizing protein, in the physiological control of female fertility at the level of early embryonic development. This newly identified biological role for Zfp36l2 may have implications for maternal mRNA turnover in normal embryogenesis, and conceivably could be involved in some cases of unexplained human female infertility.
Reflex sympathetic dystrophy--a complex regional pain syndrome

Reflex sympathetic dystrophy (RSD) is a complex and poorly-understood condition characterized by: (a) pain and altered sensation; (b) motor disturbance and soft tissue change; (c) vasomotor and autonomic changes; and (d) psychosocial disturbance. Neurological symptoms typically do not conform to any particular pattern of nerve damage. Many different names have been ascribed to this condition and most recently the term 'complex regional pain syndrome' has been coined to emphasize the complex interaction of somatic, psychological and behavioural factors. Diagnostic criteria have been proposed by the International Association for the Study of Pain, but are still subject to debate. This review article describes the clinical features which may present as part of the condition, and the patho-physiology and pre-disposing factors so far identified. The evidence for effectiveness of different interventions is presented and a treatment approach outlined for inter-disciplinary management. While RSD is traditionally associated with pain in the extremities, the possibility is raised that the same process may underlie chronic pain syndromes affecting more central structures, such as testicular or pelvic pain.
PD-L1 expression in non-small cell lung cancer: Correlations with genetic alterations

ABSTRACT Inhibition of the PD-1/PD-L1 pathway may induce anticancer immune responses in non-small cell lung cancer (NSCLC). Two PD-L1 immunohistochemistry (IHC) assays have been approved as companion diagnostic tests for therapeutic anti-PD-1 antibodies. However, many aspects of PD-L1 prevalence and association with genetically defined subtypes have not been addressed systematically. Here, we analyzed PD-L1 expression in 436 genetically annotated NSCLC specimens enriched for early stages using PD-L1 antibody 5H1. Expression of PD-L1 was detected in the tumor cells (TC) (34% of cases) and in associated immune cells (IC) (49%) across all stages of NSCLC, either alone or in combination. PD-L1 IHC-positive TC, but not IC showed significantly higher PD-L1 RNA expression levels. Expression in TC was associated with TP53, KRAS and STK11 mutational status in adenocarcinomas (AD) and with NFE2L2 mutations in squamous cell carcinomas (SQ). No correlations with histological subtype, clinical characteristics and overall survival were found. The presence of PD-L1-positive IC was significantly associated with patients' smoking status in AD. The findings are in agreement with the emerging concept that tumors with high mutational burden are more likely to benefit from immunotherapy, since TP53 and KRAS mutations are linked to smoking, increased numbers of somatic mutations and expression of neoantigens. Current clinical studies focus on stage IIIB and IV NSCLC; however, PD-L1 expression occurs in earlier stages and might be a predictive biomarker in clinical trials testing (neo-) adjuvant strategies.
Indocyanine Green Angiography (ICGA) is Essential for the Early Diagnosis of Birdshot Chorioretinopathy

Abstract Background: Birdshot chorioretinitis (BC) is a rare disease involving the retina and the choroid independently. The hallmark for BC is the presence of depigmented oval lesion of the choroid, the so called “birdshot lesions”, however in the early phase of disease these lesions are often not visible. Methods: A retrospective analysis of BC patients that were investigated in Centre for Ophthalmic Specialised Care, Lausanne, Switzerland between 1995 and 2010 was performed. Patients seen in the initial phase of BC disease devoid of a specific diagnosis when referred were included. Clinical investigations along with fluorescein angiography (FA), indocyanine green angiography (ICGA) and visual field testing (VF) were analysed. Results: Three out of 7 patients (43 %) seen in the initial phase of the disease devoid of a diagnosis at presentation were analysed. These patients presented with no “birdshot” lesions whatsoever. All three patients were HLA-A29 positive, presented with vitreitis and retinal vasculitis on FA. On ICGA, all 3 patients presented bilateral evenly distributed choroidal hypofluorescent dark dots (HDD) representing choroidal granulomas. Conclusions: ICGA, by providing occult information on the choroid, is an essential tool for early diagnosis of BC. Because ICGA is still not universally practiced in uveitis centres early disease is often missed, its diagnosis delayed and proper treatment started late.
Neurodevelopmental and body composition outcomes in children with congenital hypothyroidism treated with high-dose initial replacement and close monitoring.

BACKGROUND Despite newborn screening and early levothyroxine replacement, there are continued reports of mild neurocognitive impairment in children with congenital hypothyroidism (CHT). In Auckland, New Zealand, cases are identified by a neonatal screening program with rapid institution of high-dose levothyroxine replacement (10-15 μg/kg·d), producing prompt normalization of thyroid function. Subsequently, frequent monitoring and dose alterations are performed for 2 years. We aimed to assess whether the Auckland treatment strategy prevents impairment of intellectual and motor development. METHODS This study encompassed all children with CHT born in 1993-2006 in Auckland and their siblings. Neurocognitive assessments included the following: 1) intelligence quotient via Weschler Preschool and Primary Scale of Intelligence III or Weschler Intelligence Scale for Children IV; 2) Movement Assessment Battery for Children; and 3) Beery Developmental Test of Visual-Motor Integration. Body composition was assessed by dual-energy x-ray absorptiometry. RESULTS Forty-four CHT cases and 53 sibling controls aged 9.6 ± 3.9 years were studied. Overall intelligence quotient was similar among CHT cases and controls (95.2 vs 98.6; P = .20), and there were also no differences in motor function. Severity of CHT did not influence outcome, but greater time to normalize free T4 was associated with worse motor balance. There were no differences in anthropometry or body composition between groups. CONCLUSIONS These findings suggest that a strategy of rapidly identifying and treating infants with CHT using high-dose levothyroxine replacement is associated with normal intellectual and motor development. The subtle negative impact on motor function associated with time to normalize free T4 levels is consistent with benefit from rapid initial correction.
A longitudinal study of racing thoroughbreds: performance during the first years of racing.

OBJECTIVES To develop a profile of the racing careers of Thoroughbred horses in south-eastern Queensland, and to examine factors that affect racing during the first years of racing. DESIGN AND PROCEDURE A longitudinal study using the racing records of a defined cohort of Thoroughbred horses that were born on or within 12 months following 1 August 1991. Data collection commenced in 1996 and will continue until all horses cease racing. In this paper two measures of performance were examined: race earnings during the first year of racing and cumulative proportion of horses still racing up to 2 years after their first start. Univariable and multivariable methods were used to describe and identify factors associated with the performance of these horses. RESULTS By 31 July 1997, 1804 horses were enrolled in the study including 916, 701, 152 and 35 horses that first raced at 2, 3, 4 and 5 years of age, respectively. During their first year of racing, half the horses earned no more than A$450 from race earnings, and 710 (39.4%) horses earned no money at all. In comparison to poorly performing horses, well-performing horses were more likely to be male, to have started as 2-year-olds and to have had more starts during this year. Of the horses that first started as 2 and 3-year-olds, only 71 and 46% continued racing for at least 1 and 2 years after their first start, respectively. Length of racing life was associated with performance during the first year of racing (number of starts and average earnings per race), and with sex, date of birth and age at first start. CONCLUSIONS The study confirmed a high wastage among racing Thoroughbreds. As expected, premature retirement from racing was linked to poor performance. During the first year of racing, the race earnings of an estimated 1567 (86.9%) horses were insufficient to cover training costs. The 2-year-old racing cohort outperformed the older racing cohorts in each of the performance measures under investigation. Interpretation of this result, and the long-term effects of 2-year-old racing, was limited by the problem of confounding.
Complications following peripheral angioplasty.

BACKGROUND Peripheral angioplasty is increasingly the first choice intervention in patients with peripheral vascular disease. The aim of the current study was to audit prospectively all major complications, especially the requirement for emergency surgical intervention. PATIENTS AND METHODS A prospective audit of outcome after peripheral angioplasty in 988 patients undergoing 1377 interventional procedures between 1 October 1995 and 30 September 1998 at which 1619 vessel segments were angioplastied. RESULTS Major medical morbidity (bronchopneumonia, stroke, renal failure, myocardial infarction) complicated 33/1377 procedures (2.4%). Emergency surgical intervention was required after 31/1377 procedures (2.3%) with the commonest aetiologies being acute limb ischaemia and haemorrhagic complications. The amputation rate following angioplasty was 0.6% and no patient presenting with claudication or graft complications underwent amputation. The amputation rate following angioplasty for critical limb ischaemia was 2.2%. Overall, the risk of death and/or major medical complication and/or requiring emergency surgical intervention was 3.5%. The rate of complications was no different for subintimal as opposed to transluminal angioplasties. CONCLUSIONS Peripheral angioplasty is associated with a low risk of major medical and surgical complications.
TFIID and Spt-Ada-Gcn5-Acetyltransferase Functions Probed by Genome-wide Synthetic Genetic Array Analysis Using a Saccharomyces cerevisiae taf9-ts Allele

TAF9 is a TATA-binding protein associated factor (TAF) conserved from yeast to humans and shared by two transcription coactivator complexes, TFIID and SAGA. The essentiality of the TAFs has made it difficult to ascertain their roles in TFIID and SAGA function. Here we performed a genomic synthetic genetic array analysis using a temperature-sensitive allele of TAF9 as a query. Results from this experiment showed that TAF9 interacts genetically with: (1) genes for multiple transcription factor complexes predominantly involving Mediator, chromatin modification/remodeling complexes, and regulators of transcription elongation; (2) virtually all nonessential genes encoding subunits of the SWR-C chromatin-remodeling complex and both TAF9 and SWR-C required for expressing the essential housekeeping gene RPS5; and (3) key genes for cell cycle control at the G1/S transition, as well as genes involved in cell polarity, cell integrity, and protein synthesis, suggesting a link between TAF9 function and cell growth control. We also showed that disruption of SAGA by deletion of SPT20 alters histone-DNA contacts and phosphorylated forms of RNA polymerase II at coding sequences. Our results raise the possibility of an unappreciated role for TAF9 in transcription elongation, perhaps in the context of SAGA, and provide further support for TAF9 involvement in cell cycle progression and growth control.
Recent Developments of the High Temperature Superconducting Maglev at ASCLab

This year marks the tenth anniversary of the first man-loading high temperature superconducting (HTS) maglev test vehicle “Century” in the world. This report summarizes development advances of major topics related to the HTS maglev vehicle at the Applied Superconductivity Laboratory (ASCLab) at Southwest Jiaotong University (SWJTU). The HTS Maglev measurement systems are described, including the HTS maglev dynamic test system capable of speeds up to 300 km/h. Through these measurement systems, many problems related to the HTS maglev have been studied such as system optimization, stability control, influence from ramp angles, influence from AC field, and investigation of the system's properties at temperatures lower than 77 K. Apart from experimental studies, the 3-D model of the HTS maglev was constructed via two different methods to simulate the Maglev's behavior.
Effects of the Novel Antiepileptic Drug Levetiracetam on Spontaneous Recurrent Seizures in the Rat Pilocarpine Model of Temporal Lobe Epilepsy

Summary: Purpose: Animal models in which seizures are elicited by chemical or electrical means are commonly used for identification and preclinical testing of novel antiepileptic drugs (AEDs). Such models have been successful in discovering all the new AEDs. However, despite the high efficacy of AEDs against elicited seizures in rodent models, a significant proportion of epilepsy patients with spontaneous recurrent seizures is resistant to these drugs. It is not known whether drug testing in rodent models with spontaneous recurrent seizures would yield a more predictive result with respect to AED efficacy in the clinic. This led us to test one of the novel AEDs, levetiracetam (LEV), in a rat model of temporal lobe epilepsy (TLE) with spontaneous recurrent seizures.
Piecewise Linear Modulation Technique for Spread Spectrum Clock Generation

We propose a novel modulation profile for a spread spectrum clock generator (SSCG). The proposed piecewise linear (PWL) modulation profile significantly reduces electromagnetic interference with a simple implementation. Two SSCGs with two- and three-slope-PWL modulation profiles are used. Both SSCGs consist of the proposed spread spectrum control profile generator and a phase-locked loop that includes a high-resolution fractional divider to reduce quantization noise from a delta-sigma modulator. The SSCG with the two-slope-PWL modulation profile was fabricated in a 0.18 μm 1P4M CMOS technology. The measured peak power reduction level of the two-slope-PWL modulation profile is 14.2 dB with 5000 ppm down spreading at 1.5 GHz. The SSCG occupies an active area of 0.49 mm2 and consumes 40 mW of power at 1.5 GHz. The SSCG with the three-slope-PWL modulation profile was fabricated in a 0.13 μm 1P6M CMOS technology. The measured peak power reduction level of the three-slope-PWL modulation profile is 10.3 and 10.52 dB with 5000 ppm down spreading at 162 and 270 MHz, respectively. The SSCG occupies an active area of 0.096 mm2 and dissipates 1 mW of power at 270 MHz.
Medications, youth therapeutic cultures and performance consumptions: A sociological approach

This article analyses performance consumptions among young people. The theme is explored along two main axes. The first concerns the social heterogeneity in this field, considered on two levels: the different purposes for those investments – cognitive/mental and physical performance; and the different social contexts – university and work – where performance practices and dispositions may be fostered. The second axis explores the roles of pharmacological and natural consumptions, and their interrelationship, in the dissemination of these practices. The empirical data for this analysis were drawn from an ongoing research project on performance consumptions among young people (aged 18−29 years) in Portugal, including both university students and young workers without university education. The results correspond to the stage of extensive research, for which a questionnaire was organised at a national level, using non-proportional quota sampling. On the one hand, they show that (a) there is a hierarchy of acceptance of consumptions according to their purposes, with cognitive/mental performance showing higher acceptance and (b) both pharmaceuticals and natural products are consumed for every type of performance investment. On the other, the comparison between students and workers introduces a certain heterogeneity in this general backdrop, both in terms of the purposes for their consumptions and their opting for natural or pharmacological resources. These threads of heterogeneity will prompt a discussion of the dynamics of pharmaceuticalisation within the field of performance, in particular how therapeutic cultures may be changing in terms of the way individuals relate to medications, expanding their uses in social life.
Neurobehavioral functions in operating theatre personnel exposed to anesthetic gases.

Neurobehavioral functions in paramedical operating theatre personnel were assessed in a cross-sectional survey. Sixty-two subjects (40 males and 22 females) occupationally exposed to anesthetic gases were examined and compared to 46 unexposed hospital workers (18 males and 28 females). The Simple Reaction Time (SRT) test was selected from the MANS battery (Milan Automated Neurobehavioural System). In order to evaluate acute and subacute types of effects on performance, the test was administered before and after the work shift, at the beginning and at the end of the working week. In addition, the complete battery was administered during one working day without exposure to anesthetic gases. On the last day of the working week, atmospheric nitrous oxide (N2Oa) ranged from 7 to 553 ppm (geometric mean 62.6), atmospheric ethrane (ETHa) ranged from 0.1 to 18.8 ppm (geometric mean 1.3), and urinary N2O (N2Ou) ranged from 4 to 297 micrograms/l (geometric mean 26.8). An impairment of performance on the SRT test was observed at the end of the working week in subjects exposed to anesthetic gases compared to controls. This alteration was observed also considering only the subjects exposed to less than 55 micrograms/l (which is the Italian exposure limit for N2Ou, equivalent to 100 ppm for N2Oa). No significant differences were observed for the other psychometric tests. No dose-effect relationships where found between SRT test score and the indicators of exposure (N2Oa, ETHa, N2Ou). (ABSTRACT TRUNCATED AT 250 WORDS)
Awareness of hepatitis B virus among undergraduate medical and non-medical students.

OBJECTIVE To investigate the awareness of Omani medical and non-medical students of hepatitis-B virus (HBV) infection. METHODS A structured questionnaire of 31 different statements concerning basic knowledge of HBV, its modes of transmission, diagnosis, risk behaviors, prevention, treatment, beliefs as well as attitudes towards patients with HBV infection were distributed to 280 students (154 females and 126 males). Of these 138 were pre-clinical medical students and 142 were non-medical students. The study was conducted at Sultan Qaboos University, Muscat, Sultanate of Oman during the period of 2001 to 2003. RESULTS The majority of the students (75%) were aware that HBV is a common cause of hepatitis and 50.7% of them think that HBV infection is preventable. Availability of vaccine is a fact appreciated more by medical (65.2%) than by non-medical (35.2%) students (p<0.05). Approximately 70% of the cohort believed that screening blood for HBV renders blood safe for transfusion. Hepatitis B virus infected student or colleague in the same classroom or working place was accepted by 58% of medical and 46.5% of non-medical students. However, the majority of students (63.2%) hesitate to take care of a HBV infected patient. CONCLUSION The majority of students showed some knowledge regarding HBV transmission, risk behaviors and prevention. However, there are still misconceptions regarding the attitudes, which reflect a false perception of the disease among students. This calls for well-structured health education programs stressing on such misconceptions.