Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of Vertebrate Polκ in Rad18-independent Postreplication Repair of UV Damage* 210

DNA damage, which is left unrepaired by excision repair pathways, often blocks replication, leading to lesions such as breaks and gaps on the sister chromatids. These lesions may be processed by either homologous recombination (HR) repair or translesion DNA synthesis (TLS). Vertebrate Polκ belongs to the DNA polymerase Y family, as do most TLS polymerases. However, the role for Polκ in vertebrate cells is unclear because of the lack of reverse genetic studies. Here, we generated cells deficient in Polκ (polκ cells) from the chicken B lymphocyte line DT40. Although purified Polκ is unable to bypass ultraviolet (UV) damage,polκ cells exhibited increased UV sensitivity, and the phenotype was suppressed by expression of human and chicken Polκ, suggesting that Polκ is involved in TLS of UV photoproduct. Defects in both Polκ and Rad18, which regulates TLS in yeast, in DT40 showed an additive effect on UV sensitivity. Interestingly, the level of sister chromatid exchange, which reflects HR-mediated repair, was elevated in normally cycling polκ cells. This implies functional redundancy between HR and Polκ in maintaining chromosomal DNA. In conclusion, vertebrate Polκ is involved in Rad18-independent TLS of UV damage and plays a role in maintaining genomic stability.
Personalization of dexamethasone therapy in childhood acute lymphoblastic leukaemia

Dexamethasone is a key component in the treatment of childhood acute lymphoblastic leukaemia (ALL). Despite playing a key role in the improved survival of ALL over several decades, intensification of dexamethasone therapy has also contributed to the increased toxicity associated with treatment, which is now seen to be at unacceptable levels given the favourable disease prognosis. Therefore the focus for treatment is now shifting towards reducing toxicity whilst maintaining current survival rates. As approximately 50% of patients were successfully treated on less intensive protocols of the 1980s, it has been questioned whether therapy intensification is necessary in all patients. Furthermore, there remains a subset of children who are still not cured of their disease. New strategies are therefore needed to identify patients who could benefit from dose reduction or intensification. However, adjusting a potentially life threatening therapy is a challenging task, particularly given the heterogeneous nature of ALL. This review focuses on the potential for patient stratification based on our current knowledge of dexamethasone pharmacokinetics, pharmacogenetics and the action of dexamethasone at the cellular level. A carefully designed, combined approach is needed if we are to achieve the aim of improved personalization of dexamethasone therapy for future patients.
Treatment of rheumatoid arthritis by extracorporeal photochemotherapy. A pilot study.

In a 6-month pilot study of 7 patients with rheumatoid arthritis, we tested a treatment involving the extracorporeal photoactivation of biologically inert methoxsalen (8-methoxypsoralen) by ultraviolet A energy to a form that covalently cross-links lymphocyte DNA; the injured cells are reinfused into the patient. Prior experimental studies had indicated that this regimen produces an immune reaction against antigens on treated T cells, and a clinical trial in patients with cutaneous T cell lymphoma had been successful. The current study patients were treated monthly, on 2 successive days (or biweekly, later on). Between 12 and 16 weeks of therapy, there appeared to be a breakpoint, after which the joint counts and joint scores of 4 of the patients began to improve. In 3 of the 4 patients, these measures eventually diminished by a mean of 71% and 80% of baseline values, respectively, and there was variable improvement in less direct indicators of clinical response. The joint counts and scores of the fourth patient improved modestly (by 33% and 59% of baselines, respectively) but he required alternative therapy, and those of the remaining 3 study patients did not improve. Mean slopes for the joint counts were significantly different from zero after the apparent breakpoint (but not before), whether one examined the 4 apparent responders (P = 0.01) or the entire group of 7 patients (P = 0.01). After completion of therapy, there was also a delay, of 2-3 months, in the clinical deterioration of those patients who had improved. There was only 1 mechanical adverse effect--a single episode of transient hypotension in 102 treatment sessions--and no toxic effects. (ABSTRACT TRUNCATED AT 250 WORDS)
Effect of ethacrynic acid on aqueous outflow dynamics in monkeys.

PURPOSE To determine the long-term effect of ethacrynic acid (ECA) on aqueous outflow dynamics in ocular normotensive monkeys. METHODS (1) Twelve cynomolgus monkeys received 10 microliters of 2.5 mM (= 7.5 micrograms) ECA intracamerally in one eye, vehicle in the other; outflow facility (perfusion) was determined at 1 hour, 24 hours, or 1 week, and intraocular pressure (IOP; applanation) at 24 hours, 1 week, and 6 to 7 weeks later. Six other cynomolgi received 10 microliters of 0.13 or 1.3 mM phalloidin in one eye 45 minutes before receiving ECA OU; facility was measured 1 hour after ECA. (2) Groups of five rhesus monkeys underwent intracameral injection of 2.5, 5.0, or 10 micrograms ECA in one eye, vehicle in the other, with IOP measured hours to weeks thereafter. (3) Five rhesus monkeys received 540 micrograms of ECA unilaterally as a 30-microliter topical drop once daily for 4 days. On the first and fourth treatment days, baseline IOP, pupil diameter, and refraction were measured immediately before and again at 2, 4, and 7 hours after topical treatment. RESULTS (1) ECA divided by vehicle facility averaged 1.83 +/- 0.23 (SEM) (P < 0.02, n = 6), 1.50 +/- 0.27 (P < 0.11, n = 7), and 1.05 +/- 0.10 (n = 7) at 1 hour, 24 hours, and 1 week, respectively. IOP was 1 to 2 mm Hg lower in ECA eyes 24 hours (P < 0.05, n = 5) and 6 to 7 weeks (P < 0.05, n = 7) after treatment. Phalloidin did not diminish the 1-hour ECA facility effect. (2) Five (but not 2.5 or 10) micrograms of ECA lowered IOP 1 to 3 mm Hg, starting at 2 hours and lasting up to 48 hours. The maximum ECA effect (-2.6 +/- 0.25 mm Hg; P < 0.001, n = 5) occurred at 4 hours. IOP, corneal thickness and endothelial cell count, and anterior chamber depth were not significantly different 8 weeks after 5 micrograms ECA or vehicle. (3) Once-daily unilateral topical application of 540 micrograms of ECA induced no change in IOP, refraction, or pupil diameter compared to contralateral vehicle-treated control eyes. There were no significant ECA-related ocular bio-microscopic abnormalities. CONCLUSIONS ECA may lower IOP and increase outflow facility longer than previously thought, but not by affecting meshwork actin filaments.
Expression of a xanthine permease and phosphate transporter in cultures and field populations of the harmful alga Aureococcus anophagefferens: tracking nutritional deficiency during brown tides.

Targeted gene expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed to track patterns in the expression of genes indicative of nitrogen or phosphorus deficiency in the brown tide-forming alga Aureococcus anophagefferens. During culture experiments, a xanthine/uracil/vitamin C permease (XUV) was upregulated ∼20-fold under nitrogen-deficient conditions relative to a nitrogen-replete control and rapidly returned to nitrogen-replete levels after nitrogen-deficient cells were resupplied with nitrate or ammonium. It was not responsive to phosphorus deficiency. Expression of an inorganic phosphate transporter (PTA3) was enriched ∼10-fold under phosphorus-deficient conditions relative to a phosphorus-replete control, and this signal was rapidly lost upon phosphate resupply. PTA3 was not upregulated by nitrogen deficiency. Natural A. anophagefferens populations from a dense brown tide that occurred in Long Island, NY, in 2009 were assayed for XUV and PTA3 expression and compared with nutrient concentrations over the peak of a bloom. Patterns in XUV expression were consistent with nitrogen-replete growth, never reaching the values observed in N-deficient cultures. PTA3 expression was highest prior to peak bloom stages, reaching expression levels within the range of P-deficient cultures. These data highlight the value of molecular-level assessments of nutrient deficiency and suggest that phosphorus deficiency could play a role in the dynamics of destructive A. anophagefferens blooms.
Protocol biopsy of the stable renal transplant: a multicenter study of methods and complication rates

Background. Clinical trials in renal transplantation must use surrogate markers of long-term graft survival if conclusions are to be drawn at acceptable speed and cost. Morphologic changes in transplant biopsies provide the earliest available evidence of damage, and “protocol” biopsies from stable grafts can be used to reduce the number of patients needed in clinical trials. This approach has been inhibited by concerns over safety, but the risk of biopsy of a stable kidney, with no active inflammation or acute functional impairment, has never been formally estimated. Methods. In accordance with a predefined set of questions, a retrospective audit of a sequential series of protocol biopsies was performed in four major transplant centers. Results. A total of 2,127 biopsy events were assessed for major complications, and 1,486 were assessed for minor ones. There were no deaths. One graft was lost, under circumstances indicating that the loss should have been prevented. Three episodes of hemorrhage required direct intervention. Three further patients required transfusion. There were two episodes of peritonitis, but one was arguably an unrelated event. All serious complications presented within 4 hr of biopsy. Conclusions. The incidence of clinically significant complications after protocol biopsy of a stable renal transplant is low. Direct benefits to the patients concerned (irrespective of the benefit that may accrue in clinical trials) were not formally assessed but seem likely to outweigh the risk of the procedure. We believe that it is ethically justifiable to ask renal transplant recipients to undergo protocol biopsies in clinical trials and routine care.
Acute Pancreatic Pseudocysts: Incidence and Implications

OF 92 patients with moderately severe acute pancreatitis initially studied within three weeks of onset by ultrasonic tomography, 52 developed an acute fluid collection in the lesser sac. Documentation of the ultrasound prediction of pseudocyst was achieved by surgery or autopsy in 26 cases. Spontaneous resolution of the acute pseudocyst was demonstrated by serial ultrasonography and radiography in another 10 patients. Exploration exposed 3 false positive predictions of pseudocyst. Eleven other patients with a cystic configuration either refused surgery or were lost to followup. Acute pseudocyst formation is a relatively common phenomenon in the early phases of moderately severe pancreatitis. While spontaneous resolution of acute pseudocysts is frequent, in approximately 50% of cases acute pseudocysts progress to chronic pseudocysts. A distinction between acute and chronic pseudocyst is necessary since specific surgical management depends upon the phase of pseudocyst development. Unless regional sepsis supervenes, acute pseudocyts of less than three weeks duration may be followed by serial ultrasonography in the hope of spontaneous resolution. When a pseudocyst has achieved chronic status, spontaneous resolution is rare. Persistent conservative management under these conditions invites the excessive mortality and morbidity of spontaneous rupture.
Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development

The formation of complex bacterial communities known as biofilms begins with the interaction of planktonic cells with a surface in response to appropriate environmental signals. We report the isolation and characterization of mutants of Pseudomonas aeruginosa PA14 defective in the initiation of biofilm formation on an abiotic surface, polyvinylchloride (PVC) plastic. These mutants are designated surface attachment defective (sad ). Two classes of sad mutants were analysed: (i) mutants defective in flagellar‐mediated motility and (ii) mutants defective in biogenesis of the polar‐localized type IV pili. We followed the development of the biofilm formed by the wild type over 8 h using phase‐contrast microscopy. The wild‐type strain first formed a monolayer of cells on the abiotic surface, followed by the appearance of microcolonies that were dispersed throughout the monolayer of cells. Using time‐lapse microscopy, we present evidence that microcolonies form by aggregation of cells present in the monolayer. As observed with the wild type, strains with mutations in genes required for the synthesis of type IV pili formed a monolayer of cells on the PVC plastic. However, in contrast to the wild‐type strain, the type IV pili mutants did not develop microcolonies over the course of the experiments, suggesting that these structures play an important role in microcolony formation. Very few cells of a non‐motile strain (carrying a mutation in flgK ) attached to PVC even after 8 h of incubation, suggesting a role for flagella and/or motility in the initial cell‐to‐surface interactions. The phenotype of these mutants thus allows us to initiate the dissection of the developmental pathway leading to biofilm formation.
Interest group framing in Denmark and the UK: membership representation or public appeal?

ABSTRACT Appearing in the news media is crucial for interest groups. When making a media presence, groups carefully frame their messages to push political processes in their preferred direction and to maintain organisational support. This article provides a cross-country comparison of the frames used by interest groups appearing in the news media. The article addresses the extent to which groups portray their demands as intended to further the interests of group members or other societal groups or to appeal to benefits to the economy or to the public at large. The analysis uses a dataset registering interest group appearances in the news media in Denmark and the UK. It includes 1,958 group appearances in two major UK newspapers and 3,284 appearances in two comparable Danish newspapers. Differences in frame use are demonstrated across the two countries; between different policy areas as well as between different types of interest groups.
Repeated-Sprint Performance, Locomotor Profile and Muscle Oxygen Uptake Recovery: Effect of Training Background

Abstract The aim of the present study was to examine the respective importance of locomotor profile and muscle oxygen uptake (mV˙ O2) recovery on repeated-sprint ability (RSA) and overall repeated-sprint performance. 11 sprint- (STR) and 10 middle-distance-trained (MDTR) athletes (20.8±4.0 yr) performed an incremental test and a 40-to-50-m sprint to estimate their maximal aerobic (MAS) and sprinting (MSS) speeds. They also performed 6×30-m sprints, departing every 30 s, where mean (RSmean) sprint time was calculated. Muscle oxygenation (Near-infrared spectroscopy, NIRS, [Hbdiff]) was measured for ~ 4 min post test. The mean response time of [Hbdiff]−mV˙ O 2 recovery (monoexponential curve fitting, MRT[Hbdiff]−mV˙ O 2) was calculated. Compared with MDTR, STR presented faster MSS (+11.4±6.7%, with 99% chances to observe a substantially greater value) and RSmean (−3.7±5.4%, 78%), but slower MAS (−15.8±8.0%, 100%) and MRT[Hbdiff]−mV˙ O 2 (+46.2±31.7%, 96%). RSmean was largely correlated with MSS [r=−0.83 (90%CL, −0.92;−0.67)], but neither with MAS [r=−0.12 (−0.47;0.25)] nor MRT[Hbdiff]−mV˙ O 2 [r=−0.27(−0.58;0.11)]. RSmean adjusted for MSS (which indirectly reflects RSA) was largely correlated with both MAS [r=0.51(0.18;0.74)] and MRT[Hbdiff]−mV˙ O 2 [r=0.53(0.20;0.75)]. While a fast mV˙ O 2 recovery is associated with an improved RSA, MSS remains of primary importance for overall repeated-sprint performance (i.e., RSmean).
Up‐regulation of Fas ligand at early stages and down‐regulation of Fas at progressed stages of intrahepatic cholangiocarcinoma reflect evasion from immune surveillance

We examined immunohistochemically the possible participation of the Fas/Fas ligand (FasL) system in intrahepatic cholangiocarcinoma (ICC) during the escape from immune surveillance, using 68 cases of ICC, 29 cases of normal intrahepatic large bile ducts, and 18 cases of biliary dysplasia. Apoptosis of tumor‐infiltrating lymphocytes (TIL) was examined by terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL). Fas was weakly expressed in normal intrahepatic bile ducts. Almost all biliary dysplasia and well‐differentiated ICCs showed moderate to marked expression of Fas, while Fas expression was variable in moderately and poorly differentiated ICCs. Down‐regulation of Fas expression was significantly correlated with histologic de‐differentiation, vascular invasion, the size of ICCs, and short survival of ICC patients. By in situ hybridization, FasL mRNA were frequently and strongly expressed in biliary dysplasia compared with non‐neoplastic intrahepatic bile duct. In well‐differentiated ICCs, FasL mRNA expression was frequent and intense. But, the expression gradually decreased in moderately and poorly differentiated ICCs. Down‐regulation of FasL mRNA expression in ICCs was correlated with perineural invasion and tumor size (over 4 cm) (P < .05). Apoptotic TIL were more frequent in ICC foci than in non‐neoplastic foci remote from ICC foci. These findings suggest that a tumor evasion mechanism involving Fas/FasL exists in ICC; frequent and intense expression of FasL mRNA in well‐differentiated ICCs enable them to escape immune surveillance by counterattacking Fas‐bearing TIL. This counterattack becomes insensitive in poorly differentiated ICCs, in which the down‐regulation of Fas gives them a resistance against the FasL‐expressing TIL. These mechanisms may be involved in the tumor progression.
Anthropometric approximation of body weight in unresponsive stroke patients

Background and purpose: Thrombolysis of acute ischaemic stroke is based strictly on body weight to ensure efficacy and to prevent bleeding complications. Many candidate stroke patients are unable to communicate their body weight, and there is often neither the means nor the time to weigh the patient. Instead, weight is estimated visually by the attending physician, but this is known to be inaccurate. Methods: Based on a large general population sample of nearly 7000 subjects, we constructed approximation formulae for estimating body weight from simple anthropometric measurements (body height, and waist and hip circumference). These formulae were validated in a sample of 178 consecutive inpatients admitted to our stroke unit, and their accuracy was compared with the best visual estimation of two experienced physicians. Results: The simplest formula gave the most accurate approximation (mean absolute difference 3.1 (2.6) kg), which was considerably better than the best visual estimation (physician 1: 6.5 (5.2) kg; physician 2: 7.4 (5.7) kg). It reduced the proportion of weight approximations mismatched by >10% from 31.5% and 40.4% (physicians 1 and 2, respectively) to 6.2% (anthropometric approximation). Only the patient’s own estimation was more accurate (mean absolute difference 2.7 (2.4) kg). Conclusions: By using an approximation formula based on simple anthropometric measurements (body height, and waist and hip circumference), it is possible to obtain a quick and accurate approximation of body weight. In situations where the exact weight of unresponsive patients cannot be ascertained quickly, we recommend using this approximation method rather than visual estimation.
Psychosocial characteristics of young Norwegian women interested in liposuction, breast augmentation, rhinoplasty, and abdominoplasty: a population-based study.

BACKGROUND The present study investigated various psychosocial factors expected to predict an interest in liposuction, breast augmentation, rhinoplasty, and abdominoplasty. METHODS Questionnaire data were obtained from 1862 participants who responded to a survey distributed to a representative sample of 3500 women from northern Norway aged 18 to 35 years. RESULTS Liposuction was the most popular procedure (25 percent), followed by breast augmentation (15 percent), rhinoplasty (7.0 percent), and abdominoplasty (5.6 percent). Most of the women interested in rhinoplasty and breast augmentation reported interest in more than one procedure, whereas the vast majority of women interested in abdominoplasty were not interested in any other procedure. Multiple regression analyses showed that a low level of education, indicators of social acceptance of cosmetic surgery, and negative appearance evaluation were predictors of an interest in all procedures. Body dysmorphic disorder-like symptoms, appearance orientation, and teasing history were predictors of an interest in all procedures except for abdominoplasty, whereas having children was a predictor of all procedures except for rhinoplasty. Divorce rate and eating disorder were predictors of an interest in liposuction only. Univariate regression analyses showed that the Big-Five personality traits were associated with all procedures except abdominoplasty. CONCLUSIONS It appears that women interested in abdominoplasty may be motivated by a desire to repair the bodily changes occurring after childbirth, whereas women interested in liposuction, breast augmentation, and rhinoplasty may have more complex psychological factors associated with their interest in cosmetic surgery. The findings of this study provide increased knowledge about psychosocial factors characterizing women interested in liposuction, breast augmentation, rhinoplasty, and abdominoplasty.
The Relationship between a Country’s Level of Tourism and Environmental Performance

The tourism industry has come under scrutiny as a human activity that contributes to the increase in greenhouse gas (GHG) emissions. While tourism certainly contributes to GHG emissions, it would be interesting to know if the level of tourism has an effect on environmental performance. The purpose of this paper is to examine the impact of the level of tourism on GHG emissions on a global level using WDI panel data from 1995 to 2016. The findings indicate that the level of tourism does have an impact on GHG emissions. There is evidence that countries that rely more heavily on tourism as a percentage of GDP, have more tourism arrivals, and have higher tourism density actually have lower amounts of GHG emissions and better environmental performance.