Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiproliferative potencies of interferons on melanoma cell lines and xenografts: higher efficacy of interferon beta.

BACKGROUND Human melanomas have shown only limited responsiveness to clinical therapy with interferon (IFN). PURPOSE Our aim was to determine the most effective class of IFN for inhibiting growth of melanoma cells and to establish whether variation exists in response of various cell lines to different IFNs. METHODS We compared the direct antiproliferative effects of the type I IFN alpha-2b, IFN alpha-4a, and IFN-beta and the type II IFN-gamma on eight melanoma cell lines grown in vitro. We did this comparison by determining the concentration of each IFN that resulted in 50% growth inhibition, using the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium tetrazolium bromide] dye uptake method. We also tested IFN alpha-2a and IFN-beta for their ability to inhibit the growth of xenografts of the LiBr melanoma cell line in vivo in nude mice. Receptor binding was determined using [35S]methionine-labeled IFN alpha-4a, in competition with unlabeled IFN alpha-2b, IFN alpha-4a, and IFN-beta. RESULTS The melanoma cell lines differed markedly in their sensitivity to the IFNs tested: Five were sensitive to low concentrations (less than 30 pM) of IFN-beta, only one was sensitive to similar concentrations of IFN alpha-2b, and none were sensitive to IFN alpha-4a at concentrations up to 920 pM. For all cell lines, the antiproliferative potency of the type I IFNs was IFN-beta greater than IFN alpha-2b greater than IFN alpha-4a. IFN-gamma was less active than IFN-beta on all except one of the cell lines. Similarly, IFN-beta was more potent than IFN alpha-2a in inhibiting the growth of the LiBr xenograft in nude mice. Labeled IFN alpha-4a bound with high specificity in all four melanoma lines tested, and competitive binding experiments showed that the order of binding affinity (IFN-beta greater than IFN alpha-2b greater than IFN alpha-4a) correlated with the order of antiproliferative potency. CONCLUSION The finding that melanoma cell lines differ intrinsically in their sensitivity to IFNs may explain differences in clinical response. Our results suggest that IFN-beta may be the most effective IFN in the treatment of melanoma, although confirmation will require clinical trials involving large numbers of patients.
Stepwise proteolysis liberates tau fragments that nucleate the Alzheimer-like aggregation of full-length tau in a neuronal cell model

Tau is a highly soluble protein, yet it aggregates abnormally in Alzheimer's disease. Here, we address the question of proteolytic processing of tau and the nucleation of aggregates by tau fragments. We show in neuronal cell models that fragments of the repeat domain of tau containing mutations of FTDP17 (frontotemporal dementia with parkinsonism linked to chromosome 17), produced by endogenous proteases, can induce the aggregation of full-length tau. Fragments are generated by successive cleavages, first N-terminally between K257 and S258, then C-terminally around residues 353–364; conversely, when the N-terminal cleavage is inhibited, no fragmentation and aggregation takes place. The C-terminal truncation and the coaggregation of fragments with full-length tau depends on the propensity for β-structure. The aggregation is modulated by phosphorylation but does not depend on it. Aggregation but not fragmentation as such is toxic to cells; conversely, toxicity can be prevented by inhibiting either aggregation or proteolysis. The results reveal a novel pathway of abnormal tau aggregation in neuronal cells.
Carboxyhaemoglobin concentration, smoking habit, and mortality in 25 years in the Renfrew/Paisley prospective cohort study

Objective: To investigate how carboxyhaemoglobin concentration is related to smoking habit and to assess whether carboxyhaemoglobin concentration is related to mortality. Design: Prospective cohort study. Setting: Residents of the towns of Renfrew and Paisley in Scotland. Participants: The whole Renfrew/Paisley study, conducted between 1972 and 1976, consisted of 7048 men and 8354 women aged 45–64 years. This study was based on 3372 men and 4192 women who were screened after the measurement of carboxyhaemoglobin concentration was introduced about halfway through the study. Main outcome measures: Deaths from coronary heart disease (CHD), stroke, chronic obstructive pulmonary disease (COPD), lung cancer, and all causes in 25 years after screening. Results: Carboxyhaemoglobin concentration was related to self reported smoking and for each smoking category was higher in participants who reported inhaling than in those who reported not inhaling. Carboxyhaemoglobin concentration was positively related to all causes of mortality analysed (relative rates associated with a 1 SD (2.93) increase in carboxyhaemoglobin for all causes, CHD, stroke, COPD, and lung cancer were 1.26 (95% confidence interval (CI) 1.19 to 1.34), 1.19 (95% CI 1.13 to 1.26), 1.19 (95% CI 1.13 to 1.26), 1.64 (95% CI 1.47 to 1.84), and 1.69 (95% CI 1.60 to 1.79), respectively). Adjustment for self reported cigarette smoking attenuated the associations but they remained relatively strong. Conclusions: Self reported smoking data were validated by the objective measure of carboxyhaemoglobin concentration. Since carboxyhaemoglobin concentration remained associated with mortality after adjustment for smoking, carboxyhaemoglobin seems to capture more of the risk associated with smoking tobacco than does self reported tobacco consumption alone. Analysing mortality by self reported cigarette smoking underestimates the strength of association between smoking and mortality.
Effect of a Sustained Program of Resistance Training on the Acute Growth Hormone Response to Resistance Exercise in Older Adults

We have previously shown that an episode of resistance exercise provokes an acute rise in circulating growth hormone (GH), and that this rise is severely blunted in older men and women. To determine whether this impairment simply reflects the decreased physical fitness of older people, we studied the effects of long-term resistance training on circulating levels of GH and insulin-like growth factor I (IGF-I) and on the acute GH response to exercise in 5 men and 9 women, aged 69.6 +/- 1.1 yrs (SEM). Subjects were randomly assigned to either an exercise program, consisting of 12 weight-lifting exercises (3 sets of 8 repetitions, 3 times each week) or to a control group. After testing maximum baseline strength by the 1 RM method, subjects returned to the laboratory for assessment of basal GH and IGF-I levels and the GH response to exercise. Venous blood was drawn at baseline, after each of 12 exercises (3 sets of 8 repetitions at 85% 1 RM), and every 2 minutes into the first 10 minutes of recovery. The exercise circuit with blood sampling was repeated at 15, 30 and 52 weeks for both groups. Basal GH and IGF-I values did not change in either group throughout the training period nor did the GH secretory response to exercise. Three exercisers had a peak GH concentration greater than 8 micrograms/l after 30 weeks of training, although only one of these showed a significant increase (29 micrograms/l) after 52 weeks. (ABSTRACT TRUNCATED AT 250 WORDS)
Corporate saving and dissaving decisions in different cash-flow regimes

Saving and dissaving decisions are fundamental to empirical research in corporate finance. We propose an augmented model of cash holding behavior with major sources and uses of cash funds, intertemporal saving, and initial stocks of assets and liabilities. We show that (dis)saving is sensitive to the sign of cash flow regime. Firms save modestly in a positive cash-flow regime because they use their cash flows to exploit growth opportunities and invest in non-cash productive assets. Firms dissave more aggressively to counteract the effects of a negative cash-flow regime. Our evidence is robust to mismeasured Tobin’s q and inconsistent cash-flow estimates. JEL Classification Number: G31, G32.
Classic cases revisited – Oxygen in court and the problem of therapeutic illusion

Medical science attempts to inform clinical practice. Law is concerned with causality. Intersection of law and medicine at times highlights the shortcomings in the medical approach to causality. Evidence-based medicine is only as good as the process of gathering evidence and this is inherently imperfect as suggested by philosophers. There is a risk of attributing a causal relationship when there is none, which can result in a false belief about an intervention. False beliefs can become entrenched forming a dogma. An application of treatment and a subsequent observation of clinical improvement may create a therapeutic illusion of benefit. It is possible that oxygen is used in this way. We cannot safely infer based on harm associated with its deprivation that supplementation of oxygen is beneficial in all patients. Evidence of benefit of oxygen therapy versus harm is not overwhelmingly convincing. The case of oxygen serves to illustrate a potential for a wider problem in science and medicine where potentially harmful treatments are administered based on beliefs rather than evidence and on the extrapolations from population-wide observations and without considering particulars of each case. Current application of oxygen is possibly inappropriate and efforts should be made to reappraise its use.
Aflatoxin M1 in processed milk and infant formulae and corresponding exposure of adult population in Serbia in 2013–2014

Aflatoxin M1 (AFM1) occurrence was analysed in 80 samples of milk and 21 samples of infant formulae on the Serbian market, using high-performance liquid chromatography with fluorescence detection. All milk samples collected in 2013 showed AFM1 contamination in the range 0.02–0.32 μg kg−1, with a mean level of 0.13 μg kg−1. The EU maximum level for AFM1 in milk (0.05 μg kg−1) was exceeded in 75% of the samples. In 2014, AFM1 was found in 83%, 70%, 80% and 58% of the samples collected in April, July, September and December, respectively, exceeding the limit in 5% of the samples taken in July. The additional number of liver cancer cases per year associated with exposure to AFM1 was estimated to be 0.004 in the adult population. Regarding infant formulae, AFM1 was found in only one sample.
Seasonal incidence of cleft lip and palate in Czech regions.

Experimental teratology and experimental genetics have considerably advanced our knowledge concerning the origin of cleft lip and palate in animals. In humans the matter is much more complicated and less is known about it. Many environmental factors are involved, including possibly the influence of the seasons of the year. The latter relationship has been discussed for many diseases since ancient times. In recent years many attempts have been made to find out whether there is seasonal variation in cancer, prematurity, mental deficiency, and various congenital malformations. Several authors have searched for seasonal incidence of cleft lip and palate. Edwards (1, 4) has found the seasonal dependence in cleft lip very marked in a series of 113 probands. On the contrary, Woolf and associates (5) and Knox and Braithwaite (3) found no significant differences in seasonal birth rate of any type of clefts in Utah and England. We tried to approach this problem on the basis of the great number of cleft patients treated in the Prague Clinic of Plastic Surgery, Charles University.
A physical map of the Salmonella typhimurium LT2 genome made by using XbaI analysis

XbaI digestion and pulsed-field gel electrophoresis of the genome of Salmonella typhimurium LT2 yields 24 fragments: 23 fragments (total size, 4,807 kb) are from the chromosome, and one fragment (90 kb) is from the virulence plasmid pSLT. Some of the 23 fragments from the chromosome were located on the linkage map by the use of cloned genes as probes and by analysis of strains which gain an XbaI site from the insertion of Tn10. Twenty-one of the fragments were arranged as a circular physical map by the use of linking probes from a set of 41 lysogens in which Mud-P22 was stably inserted at different sites of the chromosome; fragment W (6.6 kb) and fragment X (6.4 kb) were not located on the physical map. XbaI digestion of strains with Tn10 insertions allowed the physical locations of specific genes along the chromosome to be determined on the basis of analysis of new-fragment sizes. There is good agreement between the order of genes on the linkage map, which is based primarily on P22 joint transduction and F-mediated conjugation, and the physical map, but there are frequently differences in the length of the interval from the two methods. These analyses allowed the measurement of the amount of DNA packaged in phage P22 heads by Mud-P22 lysogens following induction; this varies from ca. 100 kb (2 min) to 240 kb (5 min) in different parts of the chromosome.
[Insulin resistance indices in population-based study and their predictive value in defining metabolic syndrome].

UNLABELLED In clinical studies insulin resistance, the main factor of the Metabolic Syndrome (MS), is determined directly by metabolic clamp technique, while in epidemiological studies is estimated on the basis of indices calculated from oral glucose tolerance test glycemia and insulinemia. The aim of the study was to find out which insulin resistance indicator best predicts the risk of the MS. MATERIAL AND METHODS The study population consisted of 2673 inhabitants of Kraków, aged 35-75 years, who participated in the "Polish Multicenter Study on Diabetes Epidemiology". Fasting insulin, HOMA-IR, QUICKI and Matsuda's index were determined for all subjects. Insulin resistance was defined as the cutoff values for the population with normal glucose tolerance and with BMI < 25 kg/m2. RESULTS All insulin resistance indices were closely correlated (r=0.78-0.98), and the frequency of insulin resistance in the general population was similar (47%-54%), however the highest prevalence of insulin resistance was observed when Matsuda index was used. The risk of insulin resistance, increased with the category of glucose tolerance, and was the highest when Matsuda index was used. The MSWHO was observed in 42% to 45% of the studied population and the predictive value of insulin resistance indices were similar when using WHO criteria. The highest sensitivity in the MSNCEP identification was observed when Matsuda index was used. Matsuda index had also the highest sensitivity to diagnose MSNCEP as compared with the remaining insulin resistance indices. CONCLUSIONS The study insulin resistance indices have a similar value in predicting the MSWHO while Matsuda index predicts best the MSNCEP. Matsuda index as well predicts best the risk of insulin resistance. This argues in favor of using oral glucose tolerance test to estimate risk for diabetes mellitus and cardiovascular disease.
GaInAsSb-AlGaAsSb tapered lasers emitting at 2 mu m

Tapered oscillators fabricated from GaInAsSb-AlGaAsSb quantum-well structure are reported for the first time. The quantum-well laser structure, grown by molecular beam epitaxy, has broad-stripe pulsed threshold current densities as low as 330 A/cm/sup 2/ at room temperature. One tapered laser emitting at 2.02 mu m has exhibited continuous wave (CW) output power up to 750 mW, with power in the near-diffraction-limited central lobe as high as 200 mW. <<ETX>>
Cytogenetic damage in female Pakistani agricultural workers exposed to pesticides

Bhawalpur is a major cotton‐growing area in Pakistan. Cotton picking in Pakistan is carried out by females and as a result of the intensive use of pesticides during the growing season these females are exposed to pesticide residues in the picking season. In the present study, peripheral blood was obtained from 69 cotton pickers and 69 unexposed females and used to assess the effect of pesticide exposure on genetic damage as well as on hepatic enzymes and serum cholinesterase. The subjects were of similar average age in workers and control groups (37.55 ± 12.75 vs. 37.52 ± 13.47, P > 0.05). Average exposure time of the picker females was 10.26 ± 6.14 years. Subjects from the exposed group did not use any protective measures during their work activities. Levels of serum cholinesterase were lower, and levels of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were higher in the exposed workers as compared with the control group (P < 0.001). The exposed group exhibited significantly increased frequencies of binucleated cells with micronuclei (12.72 ± 3.48 vs. 4.35 ± 2.44, P < 0.001) and total number of micronuclei in binucleated lymphocytes (16.51 ± 4.27 vs. 5.86 ± 3.09, P < 0.001) in comparison with subjects of the control group. The binucleated cells with micronuclei frequency also seemed to increase with age in both the groups, however, the magnitude of increase was greater in exposed group than the control. Results from the present study indicate that occupational exposure to pesticide mixtures results in cytogenetic damage in exposed females. Environ. Mol. Mutagen. , 2008. © 2008 Wiley‐Liss, Inc.
All-Optical Canonical Logic Units-Based Programmable Logic Array (CLUs-PLA) Using Semiconductor Optical Amplifiers

All-optical programmable logic arrays (PLAs) based on canonical logic units (CLUs), i.e., minterms and maxterms, are presented. We experimentally demonstrated the full set of two-input and three-input minterms as well as maxterms using the cross-gain modulation in semiconductor optical amplifiers (SOAs). Maxterms can be easily obtained based on minterms. The reconfigurability and scalability of the system are largely enhanced compared to our previous work. Correct and clear temporal waveforms are achieved for all the canonical logic units. The measured extinction ratios of two-input and three-input CLUs are ~ 15 dB and ~ 11 dB, respectively. Based on the CLUs, both sum-of-products and product-of-sums typed PLAs are exhibited. Six important logic functions, including full-adder, full-subtractor, multiplier, multiplexer, demultiplexer and decoder, are presented as examples to show that the canonical logic units-based programmable logic array (CLUs-PLA) can be reconfigured to perform different logic functions. The features of simple architectures, integration ability of SOA and programmable filter enable the great integration potential for CLUs-PLA.
Rare Loss-of-Function Variants in NPC1 Predispose to Human Obesity

Some Shanghai Clinical Center f a role of Niemann-Pick type C1 (NPC1) for obesity traits. However, whether the loss-of-function mutations in NPC1 cause adiposity in humans remains unknown. We recruited 25 probands with rare autosomal-recessive Niemann-Pick type C (NP-C) disease and their parents in assessment of the effect of heterozygous NPC1 mutations on adiposity. We found that male NPC1+/− carriers had a significantly higher BMI than matched control subjects or the whole population-based control subjects. Consistently, male NPC1+/− mice had increased fat storage while eating a high-fat diet. We further conducted an in-depth assessment of rare variants in the NPC1 gene in young, severely obese subjects and lean control subjects and identified 17 rare nonsynonymous/frameshift variants in NPC1 (minor allele frequency <1%) that were significantly associated with an increased risk of obesity (3.40% vs. 0.73%, respectively, in obese patients and control subjects, P = 0.0008, odds ratio = 4.8, 95% CI 1.7–13.2), indicating that rare NPC1 variants were enriched in young, morbidly obese Chinese subjects. Importantly, participants carrying rare variants with severely damaged cholesterol-transporting ability had more fat accumulation than those with mild/no damage rare variants. In summary, rare loss-of-function NPC1 mutations were identified as being associated with human adiposity with a high penetrance, providing potential therapeutic interventions for obesity in addition to the role of NPC1 in the familial NP-C disease.
Study of Accelerated Aging of Supercapacitors for Transport Applications

One important part of the electrical transportation systems is the energy-storage system. This can be based, for example, on supercapacitors. In this paper, we propose to study its behavior under constraints similar to their uses in power and railway-traction systems. We define an adequate measurement protocol for accelerated aging which is applied to supercapacitors according to two accelerated factors: effective current and temperature. We model the supercapacitors for different states of health. The modeling gives a good estimation of the variation of electrical parameters of the supercapacitor at different states. We reveal general indicators of the supercapacitor's aging, and we discuss about its life cycle.
Engaging with children as co-researchers: challenges,counter-challenges and solutions

Participatory approaches have become de rigueur in social research involving children. A growing trend is research by children where researchers engage (or employ) children as co-researchers or primary researchers. In this paper, we critique the ethical, methodological and practical issues associated with this participatory approach. The discussion is framed around six challenges: (1) Children lack research competence; (2) A comprehensive training programme is required; (3) Insider/outsider perspectives are difficult to balance; (4) Remuneration is complex; (5) Power differentials need to be overcome; and (6) Children need to be protected. For each challenge we propose a counter-challenge. Additionally, we offer pragmatic solutions to the issues raised, so that the paper holds practical utility to social researchers who utilise this type of participatory approach. Overall we argue that despite the approach’s inherent challenges, children as researchers are a powerful conduit for other children’s voices.
Folate Transport in Mouse Cumulus-Oocyte Complexes and Preimplantation Embryos1

ABSTRACT Endogenous folate stores are required in preimplantation embryos of several species, but how folates are accumulated and whether they can be replenished has not been determined. Folates are generally taken up into cells by specific transporters, mainly the reduced folate carrier RFC1 (SLC19A1 protein) and the high-affinity folate receptors FOLR1 and FOLR2. Quantitative RT-PCR showed that Slc19a1 mRNA was expressed in mouse cumulus-oocyte complexes (COCs) and oocytes, whereas Folr1 showed expression only in preimplantation embryos, increasing from the 2-cell stage onward. The mRNAs encoding Folr2 and the intestinal folate transporter Slc46a1 were not detected. Methotrexate (MTX), an antifolate often used as a model substrate for folate transport, exhibited saturable transport in COCs and in preimplantation embryos starting at the 2-cell stage. However, folate transport characteristics differed between COCs and embryos. In COCs, transport of MTX and the reduced folate leucovorin was inhibited by the anion transport inhibitor SITS that blocks RFC1 but was insensitive to dynasore, a specific dynamin inhibitor that instead inhibits folate receptor-receptor mediated endocytosis, whereas the opposite was found in 2-cell embryos and blastocysts. The inhibitor profile and transport properties of MTX and leucovorin in COCs correspond to established transport characteristics of RFC1 (SLC19A1), whereas those in 2-cell embryos and blastocysts correspond with those of FOLR1, consistent with the mRNA expression patterns. Considerable folate was accumulated in COCs via RFC1, but the presence of cumulus cells did not enhance folate accumulation in the enclosed oocyte, indicating a lack of transfer from cumulus to oocyte.