Miracle-dz/UniFAR-FTUs huggingface dataset:
Alignment and structure prediction of divergent protein families: periplasmic and outer membrane proteins of bacterial efflux pumps.

Broad-specificity efflux pumps have been implicated in multidrug-resistant strains of Pseudomonas aeruginosa and other Gram-negative bacteria. Most Gram-negative pumps of clinical relevance have three components, an inner membrane transporter, an outer membrane channel protein, and a periplasmic protein, which together coordinate efflux from the cytoplasmic membrane across the outer membrane through an unknown mechanism. The periplasmic efflux proteins (PEPs) and outer membrane efflux proteins (OEPs) are not obviously related to proteins of known structure, and understanding the structure and function of these proteins has been hindered by the difficulty of obtaining reasonable multiple alignments. We present a general strategy for the alignment and structure prediction of protein families with low mutual sequence similarity using the PEP and OEP families as detailed examples. Gibbs sampling, hidden Markov models, and other analysis techniques were used to locate motifs, generate multiple alignments, and assign PEP or OEP function to hypothetical proteins in several species. We also developed an automated procedure which combines multiple alignments with structure prediction algorithms in order to identify conserved structural features in protein families. This process was used to identify a probable alpha-helical hairpin in the PEP family and was applied to the detection of transmembrane beta-strands in OEPs. We also show that all OEPs contain a large tandem duplication, and demonstrate that the OEP family is unlikely to adopt a porin fold, in contrast to previous predictions.
Isoform-Specific Regulation of Cytochromes P450 Expression by Estradiol and Progesterone

Results from clinical studies suggest that pregnancy alters hepatic drug metabolism in a cytochrome P450 (P450) isoform-specific manner, and rising concentrations of female hormones are potentially responsible for the changes. The objective of this study was to comprehensively characterize the effects of estrogen and progesterone on the expression and activity of major drug-metabolizing P450s. To this end, primary human hepatocytes were treated with estradiol and progesterone, and mRNA expression and activity levels of 10 different P450 isoforms were determined. The results showed that estradiol enhances CYP2A6, CYP2B6, and CYP3A4 expression, whereas progesterone induces CYP2A6, CYP2B6, CYP2C8, CYP3A4, and CYP3A5 expression. The induction was mainly observed when the average hormone concentrations were at the levels reached during pregnancy, suggesting that these effects are likely pregnancy-specific. Estradiol also increased enzyme activities of CYP2C9 and CYP2E1 without affecting the mRNA expression levels by unknown mechanisms. Taken together, our results show differential effects of estrogen and progesterone on P450 expression, suggesting involvement of different regulatory mechanisms in female hormone-mediated P450 regulation. Our findings potentially provide a basis in mechanistic understanding for altered drug metabolism during pregnancy.
THE ROLE OF L. METHIONINE, L. CARNITINE, CHOLINE AND/OR SILYMARIN IN HEPATOPROTECTION AGAINST PARACETAMOL INTOXICATION AND OXIDATIVE STRESS IN BROILERS

Paracetamol (Acetaminophen) was used for long time in poultry as an antipyretic drug and as a growth stimulator. However, high doses of paracetamol cause unpleasant side effects such as hepatorenal toxicity as mirrored by depletion of glutathione reserve, increase lipid peroxidation and increase liver enzymes or even sudden death with lethal doses. Therefore, this study was designated to evaluate the ameliorative effect of L. methionine, L. carnitine, choline and/or silymarin on the hepatotoxic effect induced by high doses of paracetamol. The study was applied on 80 chicks (from 1 till 33 days old) in special cages divided into 8 groups each one contained 10 chicks. The 1 st group was used as a control, while the next 2-5 groups were supplemented with L. methionine, L. carnitine, choline and silymarin, respectively with doses as recommended by NRC, the 5 th group was supplemented with silymarin (1 g/kg diet), the 6 th group was supplemented with a mixture of the 4 supplements, the 7 th group (hepatic intoxicated group) was given paracetamol (650 mg/kg diet for 7 days), and the 8 th Â group was administrated paracetamol with a mixture of the 4 supplements. Serum samples were collected to determine levels of lipid profile [triglycerides (TG) and total cholesterol (TC)], liver damage enzymes [alanine transaminase (ALT), aspartate transferase (AST)], lipid peroxidation marker malondialdehyde (MDA), and activity of antioxidant enzymes [glutathione reductase (GR), superoxide dismutase (SOD)]. The obtained results revealed that there was a significant improvement in all measured serum biochemical parameters and final body weight gain in the combined group (4 supplements + paracetamol) as compared to the paracetamol group. These data conclude that supplementation of poultry diets with L. methionine, L. carnitine, choline and silymarin can improve the negative effect of paracetamol through increasing the body weight gain and antioxidant activity of glutathione and superoxide dismutase and decreasing malondialdehyde, liver enzymes, cholesterol and triglycerides. Key words: L. methionine; choline; L. carnitine; silymarin; hepatoprotection; broilers
Decoding Inside Information

Using a simple empirical strategy, we decode the information in insider trades. Exploiting the fact that insiders trade for a variety of reasons, we show that there is predictable, identifiable "routine" insider trading that is not informative for the future of firms. Stripping away these routine trades, which comprise over half the entire universe of insider trades, leaves a set of information-rich "opportunistic" trades that contains all the predictive power in the insider trading universe. A portfolio strategy that focuses solely on opportunistic insider trades yields value-weight abnormal returns of 82 basis points per month, while the abnormal returns associated with routine traders are essentially zero. Further, opportunistic trades predict future news and events at a firm level, while routine trades do not.
DryadeParent, An Efficient and Robust Closed Attribute Tree Mining Algorithm

In this paper, we present a new tree mining algorithm, DryadeParent, based on the hooking principle first introduced in DRYADE. In the experiments, we demonstrate that the branching factor and depth of the frequent patterns to find are key factors of complexity for tree mining algorithms, even if often overlooked in previous work. We show that DryadeParent outperforms the current fastest algorithm, CMTreeMiner, by orders of magnitude on data sets where the frequent tree patterns have a high branching factor.
In vitro replication of mouse hepatitis virus strain A59

An in vitro replication system for mouse hepatitis virus (MHV) strain A59 was developed using lysolecithin to produce cell extracts. In extracts of MHV-infected cells, radiolabeled UMP was incorporated at a linear rate for up to 1 h into RNA, which hybridized to MHV-specific cDNA probes and migrated in denaturing formaldehyde-agarose gels to the same position as MHV genomic RNA. The incorporation of [32P]UMP into genome-sized RNA in vitro correlated with the observed increase of [3H]uridine incorporation in MHV-infected cells labeled in vivo. Incorporation of [32P]UMP into genome-sized RNA was inhibited when extracts were incubated with puromycin. The addition to the assay of antiserum to the MHV-A59 nucleocapsid protein N inhibited synthesis of genome-sized RNA by 90% compared with the addition of preimmune serum. In contrast, antiserum to the E1 or E2 glycoproteins did not significantly inhibit RNA replication. In vitro-synthesized RNA banded in cesium chloride gradients as a ribonucleoprotein complex with the characteristic density of MHV nucleocapsids isolated from virions. These experiments suggest that ongoing protein synthesis is necessary for replication of MHV genomic RNA and indicate that the N protein plays an important role in MHV replication.
Probabilistic forecasting, linearity and nonlinearity hypothesis tests with bootstrapped linear and nonlinear artificial neural network

ABSTRACT Time series can contain both linear and nonlinear components, and linear and nonlinear artificial neural networks (L&NL-ANNs) have been proposed to forecast them. Although L&NL-ANNs can produce well forecasting results, these neural networks have a handicap in point of view statistical science like other neural networks. The forecasts obtained from L&NL-ANNs may change depending on the time series samples, but this variation is neglected in the literature. The objective of this study has overcome this handicap and producing a method which can give point forecasts, confidence intervals and some weights significance hypothesis tests besides the proposed method performs linearity and nonlinearity hypothesis tests. The proposed method is compared with other conventional methods using a Monte Carlo simulation study and real-world time series data which are Nikkei 225, Dow Jones and Istanbul Stock Exchange time series datasets as well as Australian beer consumption time series. The performance of the proposed method is evaluated using the application and simulation results and found to perform well overall with respect to other methods. It is shown that bootstrapped L&NL-ANN produced the smallest mean and variance of forecast errors for results obtained from different random initial parameters.
Tolerance of Sponge Assemblages to Temperature Anomalies: Resilience and Proliferation of Sponges following the 1997–8 El-Niño Southern Oscillation

Coral reefs across the world are under threat from a range of stressors, and while there has been considerable focus on the impacts of these stressors on corals, far less is known about their effect on other reef organisms. The 1997–8 El-Niño Southern Oscillation (ENSO) had notable and severe impacts on coral reefs worldwide, but not all reef organisms were negatively impacted by this large-scale event. Here we describe how the sponge fauna at Bahia, Brazil was influenced by the 1997–8 ENSO event. Sponge assemblages from three contrasting reef habitats (reef tops, walls and shallow banks) at four sites were assessed annually from 1995 to 2011. The within-habitat sponge diversity did not vary significantly across the study period; however, there was a significant increase in density in all habitats. Multivariate analyses revealed no significant difference in sponge assemblage composition (ANOSIM) between pre- and post-ENSO years for any of the habitats, suggesting that neither the 1997–8 nor any subsequent smaller ENSO events have had any measurable impact on the reef sponge assemblage. Importantly, this is in marked contrast to the results previously reported for a suite of other taxa (including corals, echinoderms, bryozoans, and ascidians), which all suffered mass mortalities as a result of the ENSO event. Our results suggest that of all reef taxa, sponges have the potential to be resilient to large-scale thermal stress events and we hypothesize that sponges might be less affected by projected increases in sea surface temperature compared to other major groups of reef organisms.
Overall survival and PD‐L1 expression in metastasized malignant melanoma

Cancers are known to elude the immune system, for example, by MHC loss, FAS up‐regulation, or increased secretion of TGF‐beta. Recently, ligands of coinhibitory receptors like programmed cell death ligand–1 (PD‐L1, B7‐H1) have come to attention for their role in tumor immune escape. Various tumors have been tested for PD‐L1 expression, and conflicting results were obtained regarding its correlative impact on patient survival. This study aimed to determine the prognostic relevance of PD‐L1 expression for the survival of melanoma patients.
Preoperative versus postoperative chemoradiotherapy for rectal cancer.

BACKGROUND Postoperative chemoradiotherapy is the recommended standard therapy for patients with locally advanced rectal cancer. In recent years, encouraging results with preoperative radiotherapy have been reported. We compared preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally advanced rectal cancer. METHODS We randomly assigned patients with clinical stage T3 or T4 or node-positive disease to receive either preoperative or postoperative chemoradiotherapy. The preoperative treatment consisted of 5040 cGy delivered in fractions of 180 cGy per day, five days per week, and fluorouracil, given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per square meter of body-surface area per day during the first and fifth weeks of radiotherapy. Surgery was performed six weeks after the completion of chemoradiotherapy. One month after surgery, four five-day cycles of fluorouracil (500 mg per square meter per day) were given. Chemoradiotherapy was identical in the postoperative-treatment group, except for the delivery of a boost of 540 cGy. The primary end point was overall survival. RESULTS Four hundred twenty-one patients were randomly assigned to receive preoperative chemoradiotherapy and 402 patients to receive postoperative chemoradiotherapy. The overall five-year survival rates were 76 percent and 74 percent, respectively (P=0.80). The five-year cumulative incidence of local relapse was 6 percent for patients assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-treatment group (P=0.006). Grade 3 or 4 acute toxic effects occurred in 27 percent of the patients in the preoperative-treatment group, as compared with 40 percent of the patients in the postoperative-treatment group (P=0.001); the corresponding rates of long-term toxic effects were 14 percent and 24 percent, respectively (P=0.01). CONCLUSIONS Preoperative chemoradiotherapy, as compared with postoperative chemoradiotherapy, improved local control and was associated with reduced toxicity but did not improve overall survival.
Stability of ferrous-iron-rich bridgmanite under reducing midmantle conditions

Significance This paper reports an unexpected change in the oxidation state of Fe in bridgmanite, the most dominant mineral in the lower mantle. The oxidation state change resolves the discrepancy between laboratory and seismic studies on the chemical composition of the lower mantle, showing that the lower mantle has major element chemistry similar to the upper mantle. The oxidation state change will also lead to a lower Fe content in bridgmanite in the midmantle, whereas the total Fe content remains the same. Such a change can lead to an increase in viscosity at 1,100- to 1,700-km depths, providing a viable mineralogical explanation on possible viscosity elevation suggested by geophysical studies at the same depth range. Our current understanding of the electronic state of iron in lower-mantle minerals leads to a considerable disagreement in bulk sound speed with seismic measurements if the lower mantle has the same composition as the upper mantle (pyrolite). In the modeling studies, the content and oxidation state of Fe in the minerals have been assumed to be constant throughout the lower mantle. Here, we report high-pressure experimental results in which Fe becomes dominantly Fe2+ in bridgmanite synthesized at 40–70 GPa and 2,000 K, while it is in mixed oxidation state (Fe3+/∑Fe = 60%) in the samples synthesized below and above the pressure range. Little Fe3+ in bridgmanite combined with the strong partitioning of Fe2+ into ferropericlase will alter the Fe content for these minerals at 1,100- to 1,700-km depths. Our calculations show that the change in iron content harmonizes the bulk sound speed of pyrolite with the seismic values in this region. Our experiments support no significant changes in bulk composition for most of the mantle, but possible changes in physical properties and processes (such as viscosity and mantle flow patterns) in the midmantle.
Lack of orientation due to a congenital brain malformation: A case study

Topographical disorientation is usually described in patients who have lost the ability to orient themselves as a consequence of acquired focal brain damage. Here, we describe the case of a 20-year-old woman with a congenital brain malformation who has never been able to orient herself within the environment. We addressed in detail her ability to orient and navigate within the environment by administering a number of tasks in both ecological and experimental surroundings. The results indicate a complete inability to use any kind of strategy useful for orientation.
Emerging anti-inflammatory agents for allergic rhinitis

Allergic rhinitis (AR) is a high-prevalence disease, affecting 10 – 15% of the general population. AR is sustained by an IgE-mediated reaction, and by a complex inflammatory network of cells, mediators and cytokines that becomes chronic when exposure to allergen persists. A T helper 2 (TH2)-biased immune response is the basis for the allergic inflammation. The current therapeutic strategy is mainly based on drugs (antihistamines, nasal corticosteroids, cromones, decongestants) and allergen immunotherapy. Drugs are overall effective in controlling symptoms, but do not modify the immune background that leads to allergic inflammation, and safety concerns may be present especially for prolonged treatments. Immunotherapy can modify the allergic response, but there is still space for improvement. Nowadays, several approaches are under investigation to optimise the management of AR. On one hand, new drugs and antimediators are being developed; on the other hand, attempts are made to selectively block relevant signal pathways of allergic reaction. Finally, one of the major goals is to modify the TH2-biased immune response by improving the characteristics and modes of action of allergen immunotherapy.
Personality and Body Composition in Monozygotic Twins with an Affective Disorder

In recent years, studies on patients suffering from manic-depressive and depressive illness have shown that these patients have certain psychological and biochemical characteristics and also abnormalities in body-build and body-composition. Some of these characteristics are clearly concomitants of the illness itself, as they revert to normal after clinical recovery. However, some remain abnormal even after recovery, and the question arises: are these constitutional characteristics perhaps genetically determined, or are they the persisting result of the illness itself?
In a Vietnamese population, MSX1 variants contribute to cleft lip and palate

Purpose: To identify causes of nonsyndromic cleft lip and palate in a Vietnamese population.Methods: In this study, 175 families with at least one case of cleft lip and/or palate were studied using the candidate genes TGFA, MSX1, and TGFB3.Results: Transmission distortion for alleles of MSX1 were demonstrated for the whole population and two missense mutations were identified, including one (P147Q) that is found in approximately 2% of the population. The P147Q appears to arise from a founder individual based on shared haplotypes in unrelated families.Conclusions: MSX1 contributes to nonsyndromic clefting in a Vietnamese population, and consistent with other studies, identifiable mutations in this gene cause about 2% of cases of nonsyndromic clefting.
Phenology of Early-Season and Mid-Season Grasshoppers Shows Contrasted Responses Toward Climatic Variations in an Arid Area

: The response of grasshoppers to climatic changes is rarely documented in arid areas. Here we address this subject in terms of phenology, i.e. the peaks of larva and adult abundance, according to species through bimonthly samplings in 2012 and 2013. The study was conducted in the Belezma National Park (northern Algeria) at Djerma (1021 m). The arid character is assessed by annual rainfalls around 330 mm. 2365 grasshoppers from 15 species were collected. Two assemblages were found, separated by the date of adult peaks, a spring one composed of 6 species (Pamphagidae and Pyrgomorphidae) and a summer one composed of 9 species (mainly Acrididae, Oedipodinae). Temperatures recorded in situ in 2102 were regularly higher than in 2013, almost from mid-May, whereas there was a humidity in spring 2012, and in summer 2013. In response to temperature and rainfall variations between these two years, the species of spring assemblage are in advance in 2012, and the contrary for those of summer assemblage. The phenology advance of spring assemblage species corresponds to a greater accumulation of degree-days during spring 2012. As regard summer assemblage, the 17 days-delay of nymphs observed in 2012 is reduced by 9 days in adults, in relation with the highest temperatures of summer 2012. Here it is hypothesized the major role of winter humidity that may have slowed down the hatching time of eggs and/or development of the first instars of summer assemblage species, surpassing the effect of temperatures. This winter humidity does not seem to affect the species of spring assemblage, mainly sensitive to warming.
The impact of processing methods on chemical composition, mineral bioavailability and functional properties of Nigerian-grown cashew flour

In this study, the effect of processing methods on the nutritional quality and functional properties of cashew ( Anacardium occidentale Linn) kernels were investigated. The kernels were soaked, autoclaved, roasted or germinated at varying time duration; raw kernel served as control. The samples were analysed for chemical, mineral bioavailability and functional properties. Data was subjected to analysis of variance and means were separated by the Duncan multiple range test. The result of chemical composition analyses revealed that raw cashew kernels contained 3.55±0.08% moisture, 21.3±0.05% protein, 45.0±0.15% fat, 2.53±0.02% fibre, 1.59±0.02% ash, 26.1±0.01% carbohydrate, 521.75 Kcal/g energy, 2210.09±0.02mg/kg calcium, 1712.54±0.03mg/kg magnesium, 60.04±0.01 mg/kg iron and 36.74±0.02mg/kg zinc. Tannin, phytate and oxalate concentrations in the raw cashew kernel were 10.14±0.03 mg/kg, 99.30±0.02mg/kg and 11.03±0.03mg/kg respectively. Increased fat, ash and fibre levels were noted for treated samples compared to raw kernels. Mineral concentrations were increased significantly by various treatments compared to raw kernel; however, germination resulted in the highest increase of mineral content. A reduction trend was observed in phytate, oxalate and tannin concentrations in the treated samples with respect to increased processing time. Consequently, various treatments influenced the bioavailability of mineral elements. Treated samples exhibited significant differences in loose and packed bulk densities, water and oil absorption capacities when compared to raw kernels. Germination shows potential to generate not only much needed nutrients in cashew for human development, but also improved bioavailability of nutrients and functionality compared to other processing methods. This approach can used in Community Nutrition and Emergency Feeding Programmes, in developing countries, where the consequence of anti-nutritional factors may worsen the incidence of malnutrition and disease.