Miracle-dz/UniFAR-FTUs huggingface dataset:
Negative Correlations Between Resistance to Three Organophosphate Insecticides and Productivity Within a Natural Population of Drosophila melanogaster (Diptera: Drosophilidae)

Abstract To investigate the relationship between resistance to organophosphate insecticides and fitness components, we first measured resistance to three organophosphates, malathion, prothiophos, and fenitrothion, and productivity, a measure of fitness components, for each of the isofemale lines from the same natural population of Drosophila melanogaster (Meigen). Pearson correlation coefficients indicated that positive correlations among resistance to the organophosphates and negative correlations between resistance to each of the organophosphates and the productivity existed within the natural population. We further investigated the genetic basis of the correlations among resistance to the organophosphates and the productivity, by using chromosome-substituted lines between a resistant and a susceptible inbred line established from the same natural population. Chromosomal analyses indicated that the third chromosome from the resistant line exhibited not only significant, positive effects on resistance to all of the organophosphates tested but also a significant negative effect on the productivity, suggesting positive genetic correlations between resistance to each organophosphate and negative genetic correlations between resistance to each organophosphate and the productivity. In addition, a significant negative effect on the productivity was also detected from the second chromosome, which did not exhibit significant major effects on resistance to the organophosphates. This suggests that fitness components of resistant lines could be also affected by factors independent of insecticide resistance. The dynamics of genetic variation in resistance to the organophosphates within the natural population of D. melanogaster are discussed from the standpoint of negative genetic correlations between resistance to the organophosphates and the productivity.
Pharmacokinetics, Metabolism, and Excretion of the Intestinal Peptide Transporter 1 (SLC15A1)-Targeted Prodrug (1S,2S,5R,6S)-2-[(2′S)-(2-Amino)propionyl]aminobicyclo[3.1.0.]hexen-2,6-dicarboxylic acid (LY544344) in Rats and Dogs: Assessment of First-Pass Bioactivation and Dose Linearity

The peptidyl prodrug (1S,2S,5R,6S)-2-[(2′S)-(2-Amino)propionyl]a-minobicyclo[3.1. 0. ]hexen-2,6-dicarboxylic acid, also known as LY544344, was discovered to improve the oral bioavailability of the parent drug (+)-2-aminobicyclo[3.1. 0]hexane-2,6-dicarboxylic acid (LY354740), a potent group II metabotropic glutamate receptor agonist. This prodrug has been shown to deliver high plasma concentrations of the active drug via intestinal peptide transporter 1 (SLC15A1) (PepT1)-mediated intestinal transport and presystemic hydrolysis in preclinical species. The current data describe the pharmacokinetic behavior of LY544344 and LY354740, with a specific focus on the first-pass activation processes and dose linearity in rats and dogs. The PepT1 transporter makes an attractive prodrug target because of its high capacity and relatively broad substrate specificity. This was demonstrated by the wide dose proportionality observed in both species (up to 1000 mg/kg in rats and 140 mg/kg in dogs). After oral administration of LY544344, absorption and bioactivation were extensive and rapid, with greater than 97% of prodrug hydrolysis occurring before its appearance in the hepatic portal vein. Systemic activation was likewise extensive, with 100% conversion of a 7-mg/kg intravenous dose in dogs. Radiolabeled studies confirmed that hydrolysis to LY354740 was the only metabolic pathway and that the excretion pattern of the active drug was not altered by administration of the prodrug. These results demonstrate the nearly ideal prodrug properties of LY544344 and further validate the utility of the peptide transporter-directed approach to prodrug design.
ARNT controls the expression of epidermal differentiation genes through HDAC- and EGFR-dependent pathways

Summary Previously we showed that spatial and developmental modulation of ARNT (HIF1&bgr;) expression in mouse epidermis is essential for maintenance of keratinocyte differentiation, proper formation of the barrier and normal desquamation. Here, using lentiviral suppression or induction of ARNT in TERT-immortalized (N-TERT) and HaCaT cells we assessed the nature and mechanisms of ARNT involvement in control of differentiation in human epidermal keratinocytes. ARNT depletion did not affect the levels of basal keratins K5 and K14, but significantly induced expression of several key differentiation markers (an effect abolished by EGF supplementation). Furthermore, ARNT deficiency resulted in the downregulation of amphiregulin (AREG) – the most highly expressed EGFR ligand in human keratinocytes – whereas upregulation of ARNT showed the opposite. In ARNT-deficient monolayer cultures and 3D epidermal equivalents, the downregulation of AREG was concurrent with a decline of EGFR and ERK1/2 phosphorylation. TSA, a potent suppressor of HDAC activity, abolished the effects of ARNT deficiency, implying a role for HDACs in ARNT-dependent modulation of the AREG–EGFR pathway and downstream epidermal genes. Total HDAC activity was significantly increased in ARNT-depleted cells and decreased with ARNT overexpression. ARNT-dependent shifts in HDAC activity were specifically attributed to significant changes in the levels of HDAC1, HDAC2 and HDAC3 proteins (but not mRNA) in both monolayer and 3D cultures. Collectively, our results suggest that ARNT controls AREG expression and the downstream EGFR–ERK pathway in keratinocytes, at least in part, by modulating HDAC activity. This novel regulatory pathway targeting advanced stages of epidermal differentiation might have important implications for skin pathology such as psoriasis, atopic dermatitis and cancer.
RNA-Seq Reveals Enhanced Sugar Metabolism in Streptococcus mutans Co-cultured with Candida albicans within Mixed-Species Biofilms

Early childhood caries (ECC), which can lead to rampant tooth-decay that is painful and costly to treat, is one of the most prevalent infectious diseases affecting children worldwide. Previous studies support that interactions between Streptococcus mutans and Candida albicans are associated with the pathogenesis of ECC. The presence of Candida enhances S. mutans growth, fitness and accumulation within biofilms in vitro, although the molecular basis for these behaviors is undefined. Using an established co-cultivation biofilm model and RNA-Seq, we investigated how C. albicans influences the transcriptome of S. mutans. The presence of C. albicans dramatically altered gene expression in S. mutans in the dual-species biofilm, resulting in 393 genes differentially expressed, compared to mono-species biofilms of S. mutans. By Gene Ontology analysis, the majority of up-regulated genes were related to carbohydrate transport and metabolic/catabolic processes. KEGG pathway impact analysis showed elevated pyruvate and galactose metabolism, suggesting that co-cultivation with C. albicans influences carbohydrate utilization by S. mutans. Analysis of metabolites confirmed the increases in carbohydrate metabolism, with elevated amounts of formate in the culture medium of co-cultured biofilms. Moreover, co-cultivation with C. albicans altered transcription of S. mutans signal transduction (comC and ciaRH) genes associated with fitness and virulence. Interestingly, the expression of genes for mutacins (bacteriocins) and CRISPR were down-regulated. Collectively, the data provide a comprehensive insight into S. mutans transcriptomic changes induced by C. albicans, and offer novel insights into how bacterial–fungal interactions may enhance the severity of dental caries.
Learning Multi-Relational Semantics Using Neural-Embedding Models

In this paper we present a unified framework for modeling multi-relational representations, scoring, and learning, and conduct an empirical study of several recent multi-relational embedding models under the framework. We investigate the different choices of relation operators based on linear and bilinear transformations, and also the effects of entity representations by incorporating unsupervised vectors pre-trained on extra textual resources. Our results show several interesting findings, enabling the design of a simple embedding model that achieves the new state-of-the-art performance on a popular knowledge base completion task evaluated on Freebase.
The Fiscal Multiplier

We measure the size of the fiscal multiplier using a heterogeneous-agent model with incomplete markets, capital and rigid prices and wages. The environment encompasses the essential elements necessary for a quantitative analysis of fiscal policy. First, output is partially demand-determined due to pricing frictions in product and labor markets, so that a fiscal stimulus increases aggregate demand. Second, incomplete markets deliver a realistic distribution of dynamic consumption and investment responses to stimulus policies across the population. These elements give rise to the standard textbook Keynesian-cross logic which, and unlike conventional wisdom would suggest, is significantly reinforced in our dynamic forward looking model. We find that market incompleteness is key to determining the size of the fiscal multiplier, which is uniquely determined in our model for any combination of fiscal and monetary policies of interest. The multiplier is 1.34 if deficit-financed and 0.61 if contemporaneously tax-financed for a pegged nominal interest rate, with similar values in a liquidity trap. If monetary policy follows a Taylor rule, the numbers drop to 0.66 and 0.54, respectively. We elucidate the importance of market incompleteness for our results and contrast them to models featuring complete markets or hand-to-mouth consumers.
Circularization of the HIV-1 RNA genome

Genomic RNA circularization has been proposed for several RNA viruses. In this study, we examined if the 5′ and 3′ ends of the 9-kb HIV-1 RNA genome can interact. In vitro assays demonstrated a specific interaction between transcripts encompassing the 5′ and 3′ terminal 1 kb, suggesting that the HIV-1 RNA genome can circularize. Truncation of the transcripts indicated that the 5′–3′ interaction is formed by 600–700 nt in the gag open reading frame and the terminal 123 nt of the genomic RNA. Detailed RNA structure probing indicates that sequences flanking the 3′ TAR hairpin interact with complementary sequences in the gag gene. Phylogenetic analysis indicates that all HIV-1 subtypes can form the 5′/3′ interaction despite considerable sequence divergence, suggesting an important role of RNA circularization in the HIV-1 replication cycle.
Delay tolerant information dissemination via coded cooperative data exchange

In this paper, we introduce a system and a set of algorithms for disseminating popular content to a large group of wireless clients spread over a wide area. This area is partitioned into multiple cells and there is a base station in each cell which is able to broadcast to the clients within its radio coverage. Dissemination of information in the proposed system is hybrid in nature: Each base station broadcasts a fraction of information in the form of random linear combinations of data blocks. Then the clients cooperate by exchanging packets to obtain their desired messages while they are moving arbitrarily over the area. In this paper, fundamental trade-offs between the average information delivery completion time at the clients and different parameters of the system such as bandwidth usage by the base stations, average energy consumption by the clients and the popularity of the spread information are studied. Moreover different heuristic algorithms are proposed to control and maintain a balance over these trade-offs. Also, the more complicated case of multiple sessions where each client is interested in an arbitrary subset of sessions is considered and two variants of the basic dissemination algorithm are proposed. The performance of all the proposed algorithms is evaluated via extensive numerical experiments.
Implantation of human pedunculopontine nucleus: a safe and clinically relevant target in Parkinson's disease

The peduncolopontine nucleus modulates locomotor activity and dysfunction in this nucleus may be responsible for the gait and postural impairments seen in Parkinson's disease and other movement disorders. We report the first surgical exploration and implantation of deep brain stimulating electrodes of the peduncolopontine nucleus area in two Parkinson's disease patients to examine the safety and the potential benefit of chronic electrical stimulation at this site. Under local anesthesia, the peduncolopontine nucleus was approached from a coronal burr hole using a trajectory that was 78–80° and 62–64° on the coronal and sagittal planes. Microrecordings helped to identify neurons in peduncolopontine nucleus and the adjacent substantia nigra pars reticulata. Chronic deep brain stimulating electrodes were implanted within the peduncolopontine nucleus in a manner similar to that practiced with deep brain stimulating surgery at other targets. Peduncolopontine nucleus neurons were characterized by small and broad multiunits (230 μV, 2.5 ms, 14.6 Hz). Caudal to this area, neurons firing at higher frequency, approximately 70 Hz, characteristic of nigral neuronal discharges, were encountered, followed by 2 mm of cells similar to those recorded in the dorsal peduncolopontine nucleus area. After deep brain stimulating electrodes implantation, acute intraoperative stimulation (up to 3 V) was performed with two stimulation frequencies in each session. Stimulation at 80 Hz has little discernable effect. On the other hand, stimulation at 10 Hz fostered a subjective feeling of ‘well-being’ and a time-locked amelioration of the clinical scores. These findings demonstrate that the stereotactic approach of peduncolopontine nucleus is safe. The target may reliably be identified by microrecordings. Low-frequency stimulation may produce acute improvements in motor function.
Automated Mapping of Explosives Particles in Composition C‐4 Fingerprints *†‡

Abstract: A method is described to perform automated mapping of hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine (RDX) particles in C‐4 fingerprints. The method employs polarized light microscopy and image analysis to map the entire fingerprint and the distribution of RDX particles. This method can be used to evaluate a large number of fingerprints to aid in the development of threat libraries that can be used to determine performance requirements of explosive trace detectors. A series of 50 C‐4 fingerprints were characterized, and results show that the number of particles varies significantly from print to print, and within a print. The particle size distributions can be used to estimate the mass of RDX in the fingerprint. These estimates were found to be within ±26% relative of the results obtained from dissolution gas chromatography/μ‐electron capture detection for four of six prints, which is quite encouraging for a particle counting approach. By evaluating the average mass and frequency of particles with respect to size for this series of fingerprints, we conclude that particles 10–20 μm in diameter could be targeted to improve detection of traces of C‐4 explosives.
Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension.

BACKGROUND Endothelium regulates vascular tone by influencing the contractile activity of vascular smooth muscle. This regulatory effect of the endothelium on blood vessels has been shown to be impaired in atherosclerotic arteries in humans and animals and in animal models of hypertension. METHODS To determine whether patients with essential hypertension have an endothelium-dependent abnormality in vascular relaxation, we studied the response of the forearm vasculature to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct dilator of smooth muscle) in 18 hypertensive patients (mean age [+/- SD], 50.7 +/- 10 years; 10 men and 8 women) two weeks after the withdrawal of antihypertensive medications and in 18 normal controls (mean age, 49.9 +/- 9; 9 men and 9 women). The drugs were infused at increasing concentrations into the brachial artery, and the response in forearm blood flow was measured by strain-gauge plethysmography. RESULTS The basal forearm blood flow was similar in the patients and controls (mean +/- SD, 3.4 +/- 1.3 and 3.7 +/- 0.8 ml per minute per 100 ml of forearm tissue, respectively; P not significant). The responses of blood flow and vascular resistance to acetylcholine were significantly reduced in the hypertensive patients (P less than 0.0001); maximal forearm flow was 9.1 +/- 5 ml per minute per 100 ml in the patients and 20.0 +/- 8 ml per minute per 100 ml in the controls (P less than 0.0002). However, there were no significant differences between groups in the responses of blood flow and vascular resistance to sodium nitroprusside. Because the vasodilator effect of acetylcholine might also be due to presynaptic inhibition of the release of norepinephrine by adrenergic nerve terminals, the effect of acetylcholine was assessed during phentolamine-induced alpha-adrenergic blockade. Under these conditions, it was also evident that the responses to acetylcholine were significantly blunted in the hypertensive patients (P less than 0.03). CONCLUSIONS Endothelium-mediated vasodilation is impaired in patients with essential hypertension. This defect may play an important part in the functional abnormalities of resistance vessels that are observed in hypertensive patients.
The Relapse of Single and Mixed Infections of Trypanosoma congolense and Trypanosoma brucei in Red Sokoto Bucks after Treatment with Isometamidium Chloride

Field reports by Veterinarians indicate that Isometamidium Chloride used in the treatment of trypanosomosis is not efficacious. This study was designed to determine the efficacy of 2% of this drug in the treatment of single and mixed infections of T. Congoense and T. brucei in Red Sokoto Bucks. Twenty four (24) Red Sokoto Bucks, 8 months 1 year old were randomly selected and divided into four groups viz (I, II, III, and IV) of six each. These were used to investigate the relapse of infections of single and mixed trypanosome parasites. Group 1 served as un-infected control; Group II and III were inoculated with 2 ml of 1 x 10 6 Trypanosoma brucei and T. congolense respectively while Group IV were inoculated with 2 ml of 1x10 6 parasites each of T. congolense and T. brucei . Animals in the infected groups were treated on day 14 post patency with Isometamidium Chloride at the dose rate of 0.5 mg/kg IM. The Bucks were monitored pre-infection, post-infection and post treatment daily for rectal temperature, weekly body weight, PCV, WBC, total proteins and clinical signs. There was aparasitaemia 12hours after treatment. Relapse of the parasites were observed in all infected and treated group of Bucks two weeks post treatment. A buck died in Group II, three goats died in Group III while all goats died in Group IV. Isometamidium Chloride was observed to be efficacious against T. brucei and T. congolense 12 hours after treatment and this was maintained for two weeks when there was a relapse of the parasite. The need for further studies to determine the reason for the relapse is imperative and may necessitate a repeat of treatment two weeks later.
Turkish preservice mathematics teachers' mathematical values: Positivist and constructivist values

The present study aimed to investigate preservice mathematics teachers' values toward their mathematics teaching with regard to their grade level, gender and departments. In the study, the positivist and constructivist values were used as value variables. Data were collected from 231 preservice primary and secondary mathematics teachers using a Likert-type questionnaire. Descriptive statistics were used to describe the demographic characteristics of the participants. Then, multivariate analysis was performed to determine the effects of department, gender and grade level on subdimensions of mathematics values. The results revealed that preservice primary and secondary mathematics teachers tend to adopt constructivist values rather than positivist values in the mathematics teaching. Teacher candidates’ other values regarding mathematics are also presented.
Sick-Leave due to Psychiatric Disorder: Higher Incidence among Women and Longer Duration for Men

Background Women take sick-leave more often than men, both in general and because of psychiatric disorders. The aim of the present study was to introduce the new dimension of sick-leave duration in the analysis of gender differences in minor psychiatric disorders. Method A population-based register was used which included all sick-leave spells exceeding seven consecutive days, 1985–1987, in a Swedish county. Results Sick-leave duration was longer for men. The greatest gender differences were found in the youngest and oldest age-groups. Women had higher incidence also in the longest spells. An increase in duration over the three years was found among women, leading to decreased gender differences. Conclusions Contrary to other studies on minor psychiatric disorders, small gender differences were found. It is suggested that sick-leave duration can be used as a quantitative measure of health-related working capacity.
93% Power Reduction by Automatic Self Power Gating (ASPG) and Multistage Inverter for Negative Resistance (MINR) in 0.7V, 9.2uW, 39MHz Crystal Oscillator

Introduction Fig. 1 shows a target application of a proposed crystal oscillator (XO). XO must be always powered ON not only in an active mode but also in a stand-by mode. The power reduction of XO is important, because XO dominates the power in the stand-by mode. In the active mode, a low phase noise of XO is required for RF blocks, while the low phase noise is not required in the stand-by mode, because the RF blocks are powered OFF. Therefore, in this paper, a new low power mode of XO with an automatic self power gating (ASPG) is proposed. A multistage inverter for a negative resistance (MINR) is also proposed to reduce the power.
Optical Crosstalk in InGaAs/InP SPAD Array: Analysis and Reduction With FIB-Etched Trenches

This letter describes the reduction of optical crosstalk by means of focused ion beam-etched trenches in InGaAs/InP single-photon avalanche diode arrays. Platinum-filled trenches have been fabricated in a linear array in order to limit the direct optical crosstalk between neighboring pixels. Experimental measurements prove that optical crosstalk has been reduced by ~60% thanks to a strong suppression of direct optical paths. An optical model is introduced in order to describe the main contributions to crosstalk and to validate measurements.