Miracle-dz/UniFAR-FTUs huggingface dataset:
Embryotoxicity of artesunate in animal species related to drug tissue distribution and toxicokinetic profiles.

BACKGROUND Injectable artesunate (AS) can cause fetal death and teratogenic effects in animals at levels below the human therapeutic dose. Similar toxicity has also been found for oral artemisinins in various animal species, but has not been found in humans. METHODS Studies on tissue distribution (5 mg/kg) and toxicokinetics (TK, 30 mg/kg x 3) were conducted in pregnant (GD11-13) and non-pregnant rats. RESULTS TK profiles of AS showed that the two groups of rats were similar after a single AS dose but were significantly different after multiple doses. Following a daily dose for 3 days, no change in AS concentration was found in the pregnant animals, but a significant concentration decline was seen in the non-pregnant rats on day 3. In addition, a higher conversion rate of AS to dihydroartemisinin (DHA) was detected in the pregnant rats after either single or multiple doses compared to non-pregnant controls. The ratios of AUC(DHA)/AUC(AS) were 0.99-1.02 for the pregnant rats and 0.42-0.48 for non-pregnant animals, resulting in a total AUC(DHA D1-3) that was about 3.7-fold higher in pregnant rats (15,049 ng.h/ml) than in non-pregnant rats (4,015 ng.h/ml). Furthermore, the tissue/blood partition coefficients demonstrated that the level of radiolabeled AS that was distributed into uterus, placenta, and ovary was 2-4-fold higher than in blood. CONCLUSIONS TK data showed that unchanged AS and DHA in the blood of pregnant rats were 1.53- and 3.74-fold, respectively, higher than those of non-pregnant animals, which all likely relate to the severe embryotoxicity of AS, even with a low-dosage regimen in pregnant animals.
Intralesional Injection of Adenovirus Encoding CC Chemokine Ligand 16 Inhibits Mammary Tumor Growth and Prevents Metastatic-Induced Death after Surgical Removal of the Treated Primary Tumor1

The CC chemokine ligand (CCL)16 exerts chemotactic activity on human monocytes and lymphocytes. Although no murine homologous has been defined, the TSA mouse adenocarcinoma cells engineered to express human CCL16 are rapidly rejected by syngenic mice. An adenovirus encoding CCL16 (AdCCL16) was generated using a Cre-Lox-based system and was used to determine whether this chemokine might also block pre-existing tumors. Both recombinant and viral CCL16 showed in vitro chemotactic activity for murine CD4+ and CD8+ lymphocytes and dendritic cells (DC). AdCCL16, but not the control empty vector, when injected in established nodules significantly delayed tumor growth. Immunohistochemistry revealed accumulation of CD4+ and CD8+ T cells and DC in the treated tumors as well as in draining lymph nodes. DC from such lymph nodes stimulated IFN-γ by a T cell clone specific for the known TSA tumor-associated Ag (TAA), suggesting the tumor origin of these cells. Lymphocytes from the same nodes showed specific CTL activity against TSA tumor cells and their immunodominant TAA peptide. Antitumor activity required CD4, CD8, and IFN-γ production, as shown using subset-depleted and knockout mice. Despite the robust and rapid immune response triggered by intratumoral injection of AdCCL16, the lesions were not completely rejected; however, the same treatment given before surgical excision of primary lesions prevented metastatic spread and cured 63% of mice bearing the 4T1 mammary adenocarcinoma, which is perhaps the most compelling model of spontaneous metastasis.
Repetitive Elements in Genomes of Parasitic Protozoa

SUMMARY Repetitive DNA elements have been a part of the genomic fauna of eukaryotes perhaps since their very beginnings. Millions of years of coevolution have given repeats central roles in chromosome maintenance and genetic modulation. Here we review the genomes of parasitic protozoa in the context of the current understanding of repetitive elements. Particular reference is made to repeats in five medically important species with ongoing or completed genome sequencing projects: Plasmodium falciparum, Leishmania major, Trypanosoma brucei, Trypanosoma cruzi, and Giardia lamblia. These organisms are used to illustrate five thematic classes of repeats with different structures and genomic locations. We discuss how these repeat classes may interact with parasitic life-style and also how they can be used as experimental tools. The story which emerges is one of opportunism and upheaval which have been employed to add genetic diversity and genomic flexibility.
Head and Shoulders Above the Rest? The Performance of Institutional Portfolio Managers Who Use Technical Analysis

This study takes a novel approach to testing the efficacy of technical analysis. Rather than testing specific trading rules as is typically done in the literature, we rely on institutional portfolio managers’ statements about whether and how intensely they use technical analysis, irrespective of the form in which they implement it. In our sample of more than 10,000 portfolios, about one-third of actively managed equity and balanced funds use technical analysis. We compare the investment performance of funds that use technical analysis versus those that do not using five metrics. Mean and median (3 and 4-factor) alpha values are generally slightly higher for a cross section of funds using technical analysis, but performance volatility is also higher. Benchmark-adjusted returns are also higher, particularly when market prices are declining. The most remarkable finding is that portfolios with greater reliance on technical analysis have elevated skewness and kurtosis levels relative to portfolios that do not use technical analysis. Funds using technical analysis appear to have provided a meaningful advantage to their investors, albeit in an unexpected way.
Patterns of mineral lick visitation by spider monkeys and howler monkeys in Amazonia: are licks perceived as risky areas?

Mineral licks—also known as “salados,” “saladeros,” or “collpas”—are specific sites in tropical and temperate ecosystems where a large diversity of mammals and birds come regularly to feed on soil. Although the reasons for vertebrate geophagy are not completely understood, animals are argued to obtain a variety of nutritional and health benefits from the ingestion of soil at mineral licks. We studied the temporal patterns of mineral lick use by white‐bellied spider monkey (Ateles belzebuth) and red howler monkey (Alouatta seniculus) in a lowland rain forest in Amazonian Ecuador. Using camera and video traps at four different mineral licks, combined with behavioral follows of one group of spider monkeys, we documented rates of mineral lick visitation by both primate species and the relative frequency and intensity of mineral lick use by spider monkeys. On the basis of 1,612 days and 888 nights of mineral lick monitoring, we found that A. belzebuth and A. seniculus both visit mineral licks frequently throughout the year (on average ∼14% of days for both species), and mineral lick visitation was influenced by short‐term environmental conditions (e.g. sunny and dry weather). For spider monkeys, the area surrounding the lick was also the most frequently and most intensively used region within the group's home range. The fact that spider monkeys spent long periods at the lick area before coming to the ground to obtain soil, and the fact that both species visited the lick preferentially during dry sunny conditions (when predator detectability is presumed to be relatively high) and visited simultaneously more often than expected by chance, together suggest that licks are indeed perceived as risky areas by these primates. We suggest that howler and spider monkeys employ behavioral strategies aimed at minimizing the probability of predation while visiting the forest floor at risky mineral lick sites. Am. J. Primatol. 73:386–396, 2011. © 2010 Wiley‐Liss, Inc.
Polyclonal B-cell activator with esterolytic activity and polyclonal gammopathy induced by allogeneic cells in rabbits.

A factor associated with α-macroglobulin (αM) which behaves in an Ig-turnover assay as any T-independent antigen or polyclonal B-cell activator (PBA) can be induced in vivo by inoculating rabbits with allogeneic lymph node cells (A1-LNC) or with sheep red blood cells (SRBC). Before inoculation and 3 days after inoculation, the PBA activity was not detected in the serum. PBA appeared and reached a maximum on day 4, decreased gradually after 1 week, and became undetectable at 6 to 7 weeks. The PBA titre for rabbits inoculated with A1-LNC was 100 to 1000 times higher than for rabbits inoculated with SRBC. The PBA activity was associated entirely with the αM fraction. The αM separated from normal rabbit serum had no PBA activity but when normal αM was complexed with trypsin, a high PBA titre was obtained. Trypsin had PBA, proteolytic and esterolytic activity but when it was bound to αM, it lost its proteolytic activity and maintained its esterolytic and PBA activity. The PBA activity of the normal αM-trypsin complex and of the αM from A1-LNC injected rabbits were inhibited by serine protease inhibitors of low molecular weight, such as aprotinin and phenylmethylsulphonyl fluoride, but not by an inhibitor of high molecular weight such as soybean trypsin inhibitor. The inhibition of PBA activity correlated with the loss of esterolytic activity. For the rabbits inoculated with A1-LNC, the IgG concentration increased in the serum to a four-fold maximum at 3–5 week. We concluded that the PBA induced in vivo by allogeneic stimulation is an αM-serine protease complex which appears in the serum and that this is followed by a transitory polyclonal gammopathy.
Women's Unemployment During Transition: Evidence from the Czech and Slovak Micro-Data

We analyse women's weekly probabilities of leaving unemployment in the Czech and Slovak Republics (CR and SR) in order to investigate three questions: 1) Why are unemployment rates much lower in the CR than the SR? ; 2) Does the unemployment compensation scheme (UCS) substantially lengthen unemploment spells? ; and 3) Why are women's unemployment rates higher than men's? We find that differences in the behaviour of the individuals, employers and institutions in the SR and CR (as measured by differences in coefficients) play a larger role in determining the CR's shorter female unemployment spells than do differences in measured demand and demographic variables. The UCS has only a moderate effect on duration and its impact is greater in the CR. The differences between men's and women's spells (in each republic) are explained more by differences in coefficients than by differences in observed characteristics.
Relationship of serum fibroblast growth factor 21 with abnormal glucose metabolism and insulin resistance: the Baltimore Longitudinal Study of Aging.

CONTEXT The relationship of fibroblast growth factor 21 (FGF21) with glucose metabolism and insulin resistance has not been well characterized in community-dwelling adults. OBJECTIVE The objective of the study was to examine the relationship of FGF21 with glucose metabolism and insulin resistance. DESIGN Serum FGF21, fasting plasma glucose (FPG), glucose tolerance, and insulin resistance were measured in a cross-sectional study, 2002-2007. SETTING The study was the Baltimore Longitudinal Study of Aging, a natural history cohort study of aging in community-dwelling men and women. PARTICIPANTS Seven hundred adults, mean age 63.3 yr, participated in the study. MAIN OUTCOME MEASURES FPG, 2-h plasma glucose, homeostasis model of insulin resistance, whole-body insulin sensitivity (Matsuda index), glucose area under the curve (AUC), and insulin AUC were measured. RESULTS Overall, the median (25th and 75th percentiles) FGF21 concentration was 225 (126, 370) pg/ml. The proportion of adults with normal, impaired, and diabetic FPG was 77.0, 21.4, and 1.6%, and those with normal, impaired, and diabetic 2-h plasma glucose was 76.7, 19.1, and 4.1%, respectively. Log serum FGF21 (picograms per milliliter), per 1 sd increase, was associated with an FPG (odds ratio 1.43, 95% confidence interval 1.15, 1.77, P = 0.001) and with 2-h plasma glucose (odds ratio 1.39, 95% confidence interval 1.12, 1.73, P = 0.003), in respective multivariate, ordered logistic regression models, adjusted for potential confounders. Serum FGF21 (picograms per milliliter) was associated with the homeostasis model of insulin resistance, the Matsuda index, glucose AUC, and insulin AUC (all P < 0.0001) in respective multivariable linear regression models adjusted for potential confounders. CONCLUSIONS Higher serum FGF21 concentrations were associated with abnormal glucose metabolism and insulin resistance in community-dwelling adults.
Effects of intravenous anaesthetic agents on fast inhibitory oscillations in the rat hippocampus in vitro

1 General anaesthetic agents prevent awareness of sensory input and subsequent recall of sensory events after administration. The mechanisms involved in higher sensory processing, including awareness and recall, are not fully elucidated. However, fast oscillations in neuronal activity in the 20–80 Hz (gamma) range have been strongly implicated. Here we have investigated the effects of two anaesthetic agents and a sedative/hypnotic drug on these oscillations. 2 Trains of fast oscillations, shown previously to be shaped by γ‐aminobutyric acid (GABAA) receptor activation, were evoked by pressure ejection of L‐glutamate (10 mM) onto the perisomatic region of hippocampal area CA1 in the presence of 3‐((R)‐2‐carboxypiperazin‐4‐yl)‐propyl‐1‐phosphonic acid (R‐CPP), 50 μm, 6‐nitro‐7‐sulphamoylbenzo[f]quinoxaline‐2,3‐dione (NBQX), 50 μm and 2‐hydroxysaclofen, 0.2 mM. 3 Thiopentone (10–200 μm) and propofol (0.5–10 μm) dose‐dependently decreased both the maximum oscillation frequency, by approx. 90%, and the incidence of evoked rhythmic oscillations by approx. 60%. Diazepam (0.05‐1 μm) decreased maximum oscillation frequency by about 40% but did not affect the incidence of evoked oscillations. 4 The similar effects of thiopentone and propofol were mediated by both a large (about 600%) increase in the decay constant (τD) of GABAA receptor‐mediated inhibitory postsynaptic currents (i.p.s.cs) and a bicuculline‐sensitive leak current. The two drugs had differing effects on i.p.s.c. amplitude. Diazepam caused a small increase in τD (about 170%) and did not alter leak currents at the doses used. 5 Effects of the anaesthetic agents were seen on the above measurements at similar concentrations to those estimated in the CNS during clinical and veterinary anaesthesia. We suggest that the effects on fast oscillations associated with cognition may contribute to the mechanism by which these agents produce general anaesthesia.
Peripheral Nerve Injury and Repair

&NA; Peripheral nerve injuries are common, and there is no easily available formula for successful treatment. Incomplete injuries are most frequent. Seddon classified nerve injuries into three categories: neurapraxia, axonotmesis, and neu-rotmesis. After complete axonal transection, the neuron undergoes a number of degenerative processes, followed by attempts at regeneration. A distal growth cone seeks out connections with the degenerated distal fiber. The current surgical standard is epineurial repair with nylon suture. To span gaps that primary repair cannot bridge without excessive tension, nerve-cable interfascicular autografts are employed. Unfortunately, results of nerve repair to date have been no better than fair, with only 50% of patients regaining useful function. There is much ongoing research regarding pharmacologic agents, immune system modulators, enhancing factors, and entubulation chambers. Clinically applicable developments from these investigations will continue to improve the results of treatment of nerve injuries.
Innovations, patent races and endogenous growth

This paper presents a model of innovations and endogenous economic growth with two main assumptions: first, the cost of searching for innovations differs across innovations, and second, innovations take time to find. The paper shows that given these two assumptions together, competition leads to patent races and to duplication of innovative activity. The paper then shows that duplication significantly reduces the effect of scale on growth. It also shows that competitive R&D creates too much research on easy innovations, and too little research on the difficult ones. Finally, the paper shows that risk sharing might increase duplication and reduce growth.
Stock Repurchase Announcements and Stock Prices Evidence from Taiwan

This paper uses an event study methodology to examine the stock price behavior surrounding announcements of stock repurchases made by Taiwan firms from 2000 to 2008. Our analysis shows that stock prices go up in response to stock repurchase announcements. We also find the announcement effects between various industries to be significantly different; the announcement effect is greatest in the financial industry and least in the electronics industry. Finally, firms which fully executed stock repurchases were confirmed to have experienced a relatively large stock price decline in the pre-announcement period compared with those which executed less than 10% stock repurchases; however, there is no significant difference in their announcement effects.
Bank earnings management through loan loss provisions

We investigate whether banks use of loan loss provisions (LLPs) to manage the level and volatility of their earnings and examine the implications for bank risk. We find that banks use LLPs to manage the level and volatility of earnings downward when they are abnormally high and when expected dividends are lower than current earnings. Moreover, banks adjust LLPs to avoid fluctuations in their risk-weighted assets. Our findings highlight an important trade- off in the provisioning for expected and unexpected losses that affects bank risk and profitability.
The Architecture of Global Banking: From International to Multinational?

The financial crisis has led to a reconsideration of banks' global business models. This special feature draws on the BIS banking statistics to distinguish between "international" and "multinational" banks and the implied geographical funding patterns, and to consider how the crisis put these funding models to the test. We find that local positions proved to be more stable, especially in emerging markets.
Financing on-site sanitation for the poor : a six country comparative review and analysis

The present study offers evidence on alternative financing approaches for on-site household sanitation from case studies in six countries: Bangladesh, Ecuador, India, Mozambique, Senegal, and Vietnam. This evidence can help identify the best-performing approaches and the relevant factors and issues to consider in designing a sanitation financing strategy. The study systematically compares alternative financing approaches based on a set of common indicators, including in terms of the effectiveness in the use of public funds and targeting. The team chose to focus on those projects recognized as successes to obtain a reasonable representation of the better practices in sanitation programs. The study identified a number of useful examples and tentative lessons about finance which should help to advance the design of sanitation finance at the outset of a project. Replicating such experiences will require a better understanding of what drives household investment and what the key constraints limiting such investment are, in both financial and non-financial terms. The sanitation challenge continues to grow with population, as does the cost of failing to meet it. This study is a worthwhile contribution to addressing the challenge of how to pay for sanitation.
OBSERVATIONS ON THE ORIGIN OF AMNIOTIC FLUID ENZYMES

An enquiry has been made into the origins of a group of amniotic fluid enzymes which have complex specific activity patterns during gestation. Between 13 and 18 weeks of gestation, the specific activities of hexosaminidase, α‐l, 4‐glucosidase, and the placental and heat‐labile alkaline phosphatases in amniotic fluid were in excess of those expected on the hypothesis of a serum origin. In contrast, a significant fraction of the acid phosphatase activity during this period could be attributed to its influx from maternal serum. In amniotic fluid at term, hexosaminidase, heat‐labile alkaline phosphatase and acid phosphatase appeared to originate from the surrounding tissues, although fetal urine was found to be an additional source of acid phosphatase. The placental alkaline phosphatase in amniotic fluid at term had a mean specific activity which was the closest to that expected on the hypothesis of a serum origin. It is probable that tissue protein is released into the amniotic fluid at term, and possibly also between 13 and 18 weeks of gestation. The methods used to draw these conclusions may be of general use for examining the origins of individual proteins in amniotic fluid.
IDEA MANAGEMENT IN THE INNOVATION PROCESS

The employees of a company often want to make themselves useful and to make life easier at work by providing potentially useful ideas, aimed at eliminating problems or to exploit the opportunities. Without the ability to obtain new ideas, an organization stagnates, declines and eventually is eliminated by the competitors who have new ideas. To materialize the idea into an innovative product, it is desirable that it corresponds to the company's goals to be achieved with the existing technology and resources in order to reduce the investments. Thus, it appeared the need for an idea management to bring order in the set of ideas and to create a transparent and effective mode in attracting and management of these ideas. This paper proposes, starting from a number of scientific approaches in the literature, to address to the idea management as a complex model and to identify which are those dedicated IT solutions that could help going over various phases and sub-phases of such a complex model, particularly useful for the management of a company.
Reduced side lobe level of sparse linear antenna array by optimized spacing and excitation amplitude using particle swarm optimization

Sparse antenna array has many advantages like low mutual coupling, directive beam and cost effective because of less number of elements as compare to equally spaced antenna array. While the main limitation in this array is of high side lobe levels because of different inter element spacing. In this paper optimized values of elements spacing and excitation amplitude for sparse linear antenna array are achieved to minimize the peak side lobe level using particle swarm optimization (PSO) with better convergence rate. Random values of spacing are considered in half and one wave length range. And maintained the main beam direction.