Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling the Efficacy of Natalizumab in Multiple Sclerosis Patients Who Switch From Every‐4‐Week Dosing to Extended‐Interval Dosing

Natalizumab is approved for multiple sclerosis treatment at a dose of 300 mg every 4 weeks. Extended‐interval dosing of natalizumab has been proposed as a strategy to mitigate the risk of progressive multifocal leukoencephalopathy, but the efficacy of extended‐interval dosing is not established. Previous models suggesting lower efficacy when initiating natalizumab treatment with extended‐interval dosing rather than every‐4‐week dosing are inconsistent with reports from clinical observations and real‐world studies conducted in patient populations switching to extended‐interval dosing after a period of receiving natalizumab every 4 weeks. Here, the efficacy of natalizumab extended‐interval dosing was modeled specifically in patients switching from every‐4‐week dosing to extended‐interval dosing. Published population pharmacokinetic/pharmacodynamic models were used to simulate the distribution of alpha‐4 integrin saturations for different body weight categories and dosing intervals (every 5, 6, 7, 8, 10, or 12 weeks). Generalized estimating equations relating alpha‐4 integrin saturation to probability of multiple sclerosis lesion or relapse were derived from RESTORE trial data, which included patients (n = 175) who discontinued natalizumab after being treated every 4 weeks for ≥1 year and had no relapses in the year before discontinuation. The model‐based simulations described indicate that every‐5‐week or every‐6‐week dosing is likely to maintain the efficacy of natalizumab, particularly at body weights <80 kg, in patients who switch after a period of stability on every‐4‐week dosing. The efficacy of natalizumab decreases as dosing intervals and body weight increase. Partial model validation was achieved in that observed outcomes in an independent clinical study were similar to those predicted by the models.
The H3K4me3/2 histone demethylase RBR-2 controls axon guidance by repressing the actin-remodeling gene wsp-1

The dynamic regulation of histone modifications is important for modulating transcriptional programs during development. Aberrant H3K4 methylation is associated with neurological disorders, but how the levels and the recognition of this modification affect specific neuronal processes is unclear. Here, we show that RBR-2, the sole homolog of the KDM5 family of H3K4me3/2 demethylases in Caenorhabditis elegans, ensures correct axon guidance by controlling the expression of the actin regulator wsp-1. Loss of rbr-2 results in increased levels of H3K4me3 at the transcriptional start site of wsp-1, with concomitant higher wsp-1 expression responsible for defective axon guidance. In agreement, overexpression of WSP-1 mimics rbr-2 loss, and its depletion restores normal axon guidance in rbr-2 mutants. NURF-1, an H3K4me3-binding protein and member of the chromatin-remodeling complex NURF, is required for promoting aberrant wsp-1 transcription in rbr-2 mutants and its ablation restores wild-type expression of wsp-1 and axon guidance. Thus, our results establish a precise role for epigenetic regulation in neuronal development by demonstrating a functional link between RBR-2 activity, H3K4me3 levels, the NURF complex and the expression of WSP-1. Summary: In C. elegans, depletion of the histone demethylase rbr-2 leads to axon guidance defects that can be attributed to NURF-mediated ectopic expression of the actin regulator wsp-1.
A composite filter for low FDR of protein-protein interactions detected by in vivo cross-linking

In vivo chemical cross-linking combined with LCMSMS of digested extracts (in vivo CX-MS) can reveal stable and dynamic protein-protein interactions at a proteome wide-scale and at the peptide level. In vivo CX-MS requires a membrane permeable and cleavable cross-linker that enables isolation of target peptides and a fast and sensitive search engine to identify the linked peptides. Here we explore the use of the search engine pLink 2 for analysis of a previously obtained LCMSMS dataset from exponentially growing Bacillus subtilis treated in culture with the cross-linker bis(succinimidyl)-3-azidomethyl-glutarate (BAMG). Cross-linked peptide pairs were identified by pLink 2 in very short time at an overall FDR of < 5%. To also obtain a FDR < 5% for inter-protein cross-linked peptide pairs additional thresholds values were applied for matched fragment intensity and for the numbers of unambiguous y and b ions to be assigned for both composite peptides. Threshold values were based on a set of decoy sequences from yeast and human sequence databases. Also the mass- and charge-dependent retention times of target peptides purified by diagonal strong cation exchange chromatography were used as a criterion to distinguish true from false positives. After this filtering, pLink 2 identified more than 80% of previously reported protein-protein interactions. In addition the use of pLink 2 revealed interesting new inter-protein cross-linked peptide pairs, among others showing interactions between the global transcriptional repressor AbrB and elongation factor Tu and between the essential protein YlaN of unknown function and the ferric uptake repressor Fur. Highlights Improved protocol for identification of PPIs at low FDR by in vivo cross-linking with BAMG The use of all intra-protein cross-linked peptide pairs as true positives The cytosolic aminopeptidase (AMPA_BACSU) interacts with the 50S ribosomal protein L17 The transition state regulator AbrB interacts with elongation factor Tu The essential protein YlaN of unknown function interacts with the iron uptake repressor Fur Significance Important for reliable identification of PPIs by chemical cross-linking in vivo is a low FDR of non-redundant inter-protein peptide pairs. Here we describe how to recognize the presence of spurious interactions in a dataset of cross-linked peptide pairs enriched by 2D strong cation exchange chromatography and identified by LCMSMS by taking into account chromatographic behavior of cross-linked peptide pairs and protein abundance of corresponding peptides. Based on these criteria we assessed that the FDR of the fraction of non-redundant inter-protein cross-linked peptide pairs was approx. 20-25% by interrogating an entire species specific database at an overall FDR of 5% or 0.1% with a search engine that otherwise scores best in sensitivity among other search engines. We have defined a composite filter to decrease this high FDR of inter-protein cross-linked peptide pairs to only about 2%.
Protein variation in the malaria parasite Plasmodium falciparum

Proteins of the asexual, erythrocytic stages of the human malaria parasite Plasmodium falciparum have been analysed by two-dimensional gel electrophoresis (2DGE). Metabolic labelling of in vitro cultures was combined with double label autoradiography in order to compare the proteins of a range of parasite isolates. Nineteen out of one hundred proteins analysed varied electrophoretically in some isolates and thirteen of these proteins were selected as a basis for typing parasite isolates. Sixteen different combinations of variants of these proteins were observed among twenty-one isolates analysed. Fourteen isolates from Thailand and one from the Gambia all had unique protein profiles. Six Papua New Guinea isolates appeared identical to each other but were distinct from the others. The extent and pattern of this intraspecific variation has been considered in relation to the population structure of P. falciparum and to the geographical origin of the isolates. Seven isolates which apparently had more than-one electrophoretic variant of certain proteins were provisionally classed as being mixtures of different parasite types. This has been confirmed for one of these isolates (T9). Analysis of several cloned lines derived from T9 identified two types of clone, each possessing only one variant of each protein. The parasite proteins resolved on 2D gels were also characterised in terms of their molecular weight (MW), iso electric point, stage-specificity, glycosylation and antigenicity with the aim of compiling a bank of data about the major parasite proteins. The stage-specific synthesis of proteins during the development of the ring, trophozoite and schizont stages of the erythrocytic cycle was investigated in synchronous cultures. 30 out of 107 proteins analysed exhibited some degree of stage-specificity with the majority of these being synthesised specifically by trophozoites and/or schizonts. Metabolic labelling with 3H-glucosamine identified five intensely labelled glycoproteins, one of which was a high MW basic protein previously shown to vary between isolates. Immune serum was used to identify parasite antigens on 1D and 2D gels. These antigens included a number of strainand stage-specific proteins. The high MW glycoprotein described above was the major protein recognised by one sample of Thai human serum and was also the target antigen of two monoclonal antibodies analysed. The results presented in this thesis have been discussed in relation to the relative merits of 2DGE, enzyme electrophoresis and antigen typing for strain differentiation in P. falciparum and in relation to the results of Similar ZD gel studies of other organisms. The identity of some of the parasite proteins resolved on 2D gels and the potential value of 2DGE in malaria research have also been considered.
Diversity and genetic lineages of environmental staphylococci: a surface waters overview.

Antimicrobial resistance in the environmental dimension is one the greatest challenges and emerging threats. The presence of resistant bacteria and resistance genes in the environment, especially in aquatic systems, has been a matter of growing concern in the past decade. Monitoring the presence of antimicrobial resistance species, in this particular case, Staphylococcus spp. , in natural water environments could lead to a better understanding of the epidemiology of staphylococci infections. Thus, the investigation of natural waters as a potential reservoir and vehicle for transmission of these bacteria is imperative. Only a few studies have investigated the prevalence, antimicrobial resistance and genetic lineages of staphylococci in natural waters. Those studies reported a high diversity of staphylococci species and lineages in surface waters. Methicillin-resistant S. aureus (MRSA) were relatively prevalent in surface waters and, as expected, often presenting a multidrug-resistant profile. There was a high diversity of S. aureus lineages in surface waters. The presence of S. aureus CC8 and CC5 suggests a human origin. Among the coagulase-negative staphylococci, the most frequently found in natural waters was S. warneri and S. epidermidis. These studies are extremely important to estimate the contribution of the aquatic environment in the spread of pathogenic bacteria.
Postremission therapy with repeated courses of high‐dose cytarabine, idarubicin, and limited autologous stem cell support achieves a very good long‐term outcome in European leukemia net favorable and intermediate‐risk acute myeloid leukemia

Consolidation treatment in acute myeloid leukemia (AML) patients achieving complete remission (CR) is warranted. High‐dose cytarabine (HDAC) is considered first choice in favorable risk and an option in intermediate‐risk AML. However, its optimal dose and schedule, as well as the benefit of additional chemotherapy agents remain controversial. Herein, we report on the long‐term outcome of consecutive unselected AML patients treated with repeated courses of HDAC, with the addition of idarubicin, followed by autologous peripheral blood stem cell (PBSC) support, in order to limit toxicity, according to Northern Italy Leukemia Group (NILG) AML‐01/00 study (EUDRACT number 00400673). Among 338 patients consecutively diagnosed from 2001 to 2017 at our center, 148 with high‐risk AML (adverse cytogenetic, isolated FLT3‐internal tandem duplication mutation, refractory to first induction) were addressed to allogeneic stem cell transplant. All other cases, 186 patients (55%), median age 53 (range 19–75), were considered standard‐risk and received the NILG AML‐01/00 program. After achieving CR, patients were mobilized with cytarabine 8 g/sqm to collect autologous CD34+‐PBSC and received three consolidation cycles with HDAC (20 g/sqm) plus idarubicin (20 mg/sqm) per cycle, followed by reinfusion of limited doses of CD34+ PBSC (1‐2x106/kg). The program was completed by 160 (86%) patients. Toxicity was acceptable. Neutrophils recovered a median of 10 days. Treatment‐related mortality was 3/160 (1.8%). After a median follow‐up of 66.4 months, overall survival (OS) and relapse‐free survival (RFS) at 5‐years were 61.4% and 52.4%, respectively. Twenty‐eight selected patients aged >65 had similar outcomes. According to European leukemia net‐2010 classification, the OS and RFS at 5‐years were 76.4% and 65% in favorable risk, without differences between molecular subgroups, 52.3% and 47.2% in Intermediate‐I, 45.2% and 36.5% in Intermediate‐II risk patients, respectively. In conclusion, consolidation including repeated courses of high dose cytarabine and idarubicin, with limited PBSC support, proved feasible and very effective in nonhigh risk patients. The incorporation of novel agents in its backbone may be tested to further improve patient's prognosis.
Effect of enhanced chromium in Groundnut (Arachis hypogaea L.) and its treatment

Chromium is one of the major environmental stresses that affect plant growth and their toxic level in soils are result of heavy traffic, mining, industrials and agricultural activity. Chromium first accumulates in soil to reach the plant through roots. The chromium present at trace level in fertilizers may accumulate in agricultural soils and pose a hazard to plant growth and yield. In this way present study aimed at the effects of chromium accumulation in groundnut with special reference to various morphological and biochemical analysis done. Pot culture experiment were conducted with groundnut crop, growth in the soil mixed various amount of chromium concentrations of chromium, namely 50, 100, 150, 200 and 250 mg kg. The inner surface of pots were lined with a polythene sheets. Each pot contained 5kg of ash dried soils. Uniform irrigation was done once in a week for the entire period of experiment. The soil without chromium is treated as control. The morphological parameters like shoot length, root length, fresh and dry weight, total leaf area and biochemical content such as starch, proline, sugar and protin of groundnut plant were analyzed on various sampling days (30,60and 90 days). The biochemical content (except 50mg kg) decreased with increase of concentrations of chromium. The present investigation it was concluded that the 50mg kg level of chromium in the soil was beneficial for the growth of G. hypogea plants.
Stocking for a trophy bass fishery: searching for size differences among largemouth bass and hybrids in southern Arkansas reservoirs

ABSTRACT Lamothe KA, Allen RM, Winningham K, Dennis C, Johnson RL. 2016. Stocking for a trophy bass fishery: searching for size differences among largemouth bass and hybrids in southern Arkansas reservoirs. Lake Reserve Manage. 32:194–207. Within the southern United States, game and fish agencies have introduced nonnative Florida bass (FB), Micropterus floridanus (Lesueur 1822), as an alternative to native northern largemouth bass (NLMB), M. salmoides (Lacèpéde 1802), for decades because of suspected maximum size differences between the 2 species. The goal of this study was to determine if bass with differing levels of FB alleles demonstrated differential size structure within 6 southern Arkansas reservoirs stocked with FB. Despite millions of FB being introduced into these reservoirs over the last decade, FB made up <2% of the sampled bass for 5 of 6 reservoirs. Most sampled populations consisted primarily of one species and hybrids genetically similar to that species. In Lake Monticello, where FB numbers were relatively high, FB had significantly greater mean lengths and weights than FB × NLMB hybrids. By contrast, other reservoir bass populations showed no significant pairwise differences among species or their hybrids. From a fisheries management perspective, introducing FB outside its native range remains a controversial issue, and long-term controlled studies are needed in Arkansas to better resolve size differences observed among FB, NLMB, and their hybrids.
Defective Infection and Nodulation of Clovers by Exopolysaccharide Mutants of Rhizobium leguminosarum bv. trifolii

The biological and symbiotic properties of two types of exopolysaccharide deficient (Exo- phenotype) mutants of Rhizobium leguminosarum were investigated. One mutant, a pss1 derivative (ANU437) of R. l. bv. trifolii, produces very low levels of acidic exopolysaccharide (EPS) and of the acidic oligosaccharide (AOS) repeating unit lacking its O-acetyl substituent. The second strain, originally a R. I. bv. viciae derivative, but containing a clover pSym plasmid (Exo-1 mutant ANU54(pBRIAN)), did not produce any EPS polymer or detectable oligosaccharide repeating unit. The Exo- mutants formed no capsules and their growth in laboratory media was comparable to their parent strains but was inhibited by the addition of the phytoalexins medicarpin and kievitone, but not by the phytoalexin pisatin. Both Exo- mutants were slow to induce clover root hair curling (Hac+), and formed growing infection threads (Inf-) only on white clovers. However, the extent of these early symbiotic defects depended on the plant growth conditions used. Both mutants induced small non-nitrogen-fixing (Fix-) nodules on white and subterranean clovers. Within the white clover nodules induced by mutant ANU437, bacteria were released into plant cells. On white clovers at elevated light and temperature conditions, the Exo-1 mutant ANU54(pBRIAN) usually failed to initiate infection threads and thus formed empty nodules which do not contain any bacteria. In addition, this mutant formed only empty nodules without infection threads on subterranean clovers under all growth conditions tested. The outermost layers of plant cells in these empty nodules had thickened cell walls and deposited materials. These experiments show that EPS synthesis is essential for the induction of rapid root hair curling, proper infection thread formation and the ability to sustain the growth of induced nodules on various clovers.
Studies on genetic variability, heritability and genetic advance in French marigold (Tagetes patula)

The eleven genotypes of French marigold (Tagetes patula) numbered as var. Dainty Marietta, Boy-OBoy, Gulzafri Orange, Gulzafri Yellow, Bolero Red, Queen Sophia, Pusa Arpita, Orange Winner, Red Brocade, F/R-8 and F/R-2, were evaluated to determine genetic variability, heritability, genetic gain for twenty three contributing characters. In present study, the magnitude of PCV was higher than the GCV for all the twenty three characters under study. Heritability was high for all the growth and flowering parameters which ranged from 86.57 % to 99.34 %. Highest heritability was observed for fresh weight per flower (99.34%) followed by flower yield per plant (99.24%). High genetic advance and genetic advance as per cent of mean was observed highest in flower yield per plant (464.27) followed by number of flowers per plant (93.66). The estimates of genotypic and phenotypic coefficient of variations were ranged from 12.32 % to 63.15% and 12.65% to 63.39%, respectively. The characters like weight of flowers per plant, weight of flowers per plants, number of disc florets per flower and number of flowers per plant could be exploited for improvement through crop breeding programme.
Predicting payment migration in Canada

Des demarches sont en cours pour remplacer les deux systemes de paiement de base du Canada par trois nouveaux systemes. Nous utilisons un modele de choix discrets pour predire quels systemes les utilisateurs finaux et institutions financieres choisiront d’utiliser apres la transition, puis analysons les implications pour le cadre reglementaire.
Spectrum Sensing for Cognitive Radio Systems Using Modulation Classiﬁcation: A Review

: Spectrum sensing is the most important procedure for the operation of cognitive radio systems. To overcome the shortcomings of the conventional spectrum sensing techniques, considerable attention has been recently focused on the use of Modulation Classiﬁcation (MC) for spectrum sensing. It relies on the fact that all primary users employ one modulation scheme or another for the transmission over the wireless channel; therefore, detecting any modulation scheme would be enough to conﬁrm the presence of the primary user’s signal in the wireless channel. This paper discusses the spectrum sensing for cognitive radio systems using modulation classiﬁcation and provides a critical review of the existing methods; where gaps in the knowledge base are highlighted and directions for future research are suggested
Primary phytochemical investigation of Sphagneticola trilobata (L.) Puruski

Sphagneticola trilobata (L.) Pruski. , commonly referred as Wdelia trilobata has been used as traditional folk medicinal plant for the treatment of various ailments. A study is designed to explore the preliminary phytochemical analysis of Sphagneticola trilobata (L.) Pruski. , which is responsible for its pharmacological properties. Qualitative phytochemical screening of Sphagneticola trilobata (L.) Pruski. , was studied. Four solvents viz; ethanol, petroleum ether, chloroform and distilled water were used to obtain extracts from powdered leaves, stem and roots. The extracts were subjected to qualitative phytochemical screening using standard procedures. From the results, it was observed that of the thirteen phytochemicals screened, ten were found present in various solvent extracts. They are alkaloids, flavonoids, saponins, terpenoids, steroids, glycosides, tannins, proteins, aminoacids and carbohydrates. In all, more phytochemicals were found present in extract prepared with ethanol. Remarkably, quinones, phlobatannins and oxalates were absent in all extracts from different parts of the plant. Phytochemicals found present in the Sphagneticola trilobata (L) Puruski. indicates its ability as a source of principles that may supply novel medicines.
A Self-Weakening Mechanism for Tropical Cyclones: Self-weakening of Tropical Cyclones

A mechanism leading to the self-weakening of tropical cyclones is proposed using the Weather and Research and Forecasting model. A comparison between an experiment with variable Coriolis parameter f and one on an f -plane shows that after the initial intensification the former is characterized by a smaller intensity. As opposed to the tropical cyclone on the f -plane, the one with variable f weakens significantly after reaching maturity. Analyses of the 3-D circulation show that the main reason for the weakening is dry intrusion in the mid-upper troposphere from the west. Once the dry intrusion reaches the inner vortex, strong downdrafts reduce the high equivalent potential temperature in the boundary layer inflow. The subsequent updrafts in the eyewall, characterized by lower equivalent potential temperature, are considerably reduced and, consequently, the secondary circulation weakens. Back-trajectories are used to determine the origin of the dry intrusion. It is found that the air parcels expelled from the storm deep convection into the outflow layer recirculate anticyclonically back into the vortex, causing a self-weakening of the tropical cyclone. A time span for the recirculation of at least 48 h allows the air parcels to sink substantially before reaching the vortex circulation. Some implications of the intrinsic nature of this process are briefly discussed.