Miracle-dz/UniFAR-FTUs huggingface dataset:
ESI-MS/MS stability-indicating bioanalytical method development and validation for simultaneous estimation of donepezil, 5-desmethyl donepezil and 6-desmethyl donepezil in human plasma.

A bioanalytical method was developed and validated to estimate donepezil, 6-desmethyl donepezil and 5-desmethyl donepezil simultaneously in human plasma using galantamine as an internal standard (IS). The chromatographic separation was achieved on a reverse-phase XTerra RP (150 × 4.6 mm, 5 µm) column without affecting recovery (mean recovery > 60% with CV < 10%) for all analytes. ESI-MS/MS multiple reaction monitoring in positive polarity was used to detect mass pairs for donepezil (m/z 380.3 → 91.3), 6-desmethyl donepezil (m/z 366.4 → 91.3), 5-desmethyl donepezil (m/z 366.4 → 91.3) and galantamine m/z (288.1 → 213.0). The linearity was established over a dynamic range of 0.339-51.870, 0.100-15.380 and 0.103-15.763 ng/mL for donepezil, 6-desmethyl donepezil and 5-desmethyl donepezil, respectively. The current method shows that minimal conversion of labile metabolites to parent donepezil in plasma as stability was successfully achieved for 211 days at -15 °C storage temperature. The method was successfully applied to a clinical study after administration of 10 mg donepezil tablets to healthy male Indian volunteers.
Complete and directed complete Omega-categories

Let Ω be a commutative, unital quantale. Complete and directed complete Ω -categories are the core objects in Quantitative Domain Theory. This paper, based on the theory of Φ-completeness for enriched categories, presents a systematic investigation of completeness and directed completeness of Ω -categories. c © 2007 Elsevier B.V. All rights reserved.
Item and Test Analysis to Identify Quality Multiple Choice Questions (MCQs) from an Assessment of Medical Students of Ahmedabad, Gujarat

Background: Multiple choice questions (MCQs) are frequently used to assess students in different educational streams for their objectivity and wide reach of coverage in less time. However, the MCQs to be used must be of quality which depends upon its difficulty index (DIF I), discrimination index (DI) and distracter efficiency (DE). Objective: To evaluate MCQs or items and develop a pool of valid items by assessing with DIF I, DI and DE and also to revise/ store or discard items based on obtained results. Settings: Study was conducted in a medical school of Ahmedabad. Materials and Methods: An internal examination in Community Medicine was conducted after 40 hours teaching during 1st MBBS which was attended by 148 out of 150 students. Total 50 MCQs or items and 150 distractors were analyzed. Statistical Analysis: Data was entered and analyzed in MS Excel 2007 and simple proportions, mean, standard deviations, coefficient of variation were calculated and unpaired t test was applied. Results: Out of 50 items, 24 had “good to excellent” DIF I (31 - 60%) and 15 had “good to excellent” DI (> 0.25). Mean DE was 88.6% considered as ideal/ acceptable and non functional distractors (NFD) were only 11.4%. Mean DI was 0.14. Poor DI (< 0.15) with negative DI in 10 items indicates poor preparedness of students and some issues with framing of at least some of the MCQs. Increased proportion of NFDs (incorrect alternatives selected by < 5% students) in an item decrease DE and makes it easier. There were 15 items with 17 NFDs, while rest items did not have any NFD with mean DE of 100%. Conclusion: Study emphasizes the selection of quality MCQs which truly assess the knowledge and are able to differentiate the students of different abilities in correct manner.
Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition

Non-small cell lung cancers with activating mutations in the epidermal growth factor receptor (EGFR) are highly responsive to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. Such cancers are “addicted” to EGFR, and treatment with a TKI invariably leads to down-regulation of the PI3K-AKT-mTOR and MEK-ERK signaling pathways, resulting in apoptosis. Using a dual PI3K-mTOR inhibitor, NVP-BEZ235, we evaluated whether PI3K-mTOR inhibition alone induced apoptosis in these cancers. In contrast to HER2-amplified breast cancers, we found that PI3K-mTOR inhibition did not promote substantial apoptosis in the EGFR mutant lung cancers. However, blocking both PI3K-mTOR and MEK simultaneously led to apoptosis to similar levels as the EGFR TKIs, suggesting that down-regulation of these pathways may account for much of the apoptosis promoted by EGFR inhibition. In EGFR mutant lung cancers, down-regulation of both intracellular pathways converged on the BH3 family of proteins regulating apoptosis. PI3K inhibition led to down-regulation of Mcl-1, and MEK inhibition led to up-regulation of BIM. In fact, down-regulation of Mcl-1 by siRNA was sufficient to sensitize these cancers to single-agent MEK inhibitors. Surprisingly, an AKT inhibitor did not decrease Mcl-1 levels, and when combined with MEK inhibitors, failed to induce apoptosis. Importantly, we observed that the combination of PI3K-mTOR and MEK inhibitors effectively shrunk tumors in a transgenic and xenograft model of EGFR T790M-L858R cancers. These data indicate simultaneous inhibition of PI3K-mTOR and MEK signaling is an effective strategy for treating EGFR mutant lung cancers, including those with acquired resistance to EGFR TKIs.
Maternal–foetal genomic conflict and speciation: no evidence for hybrid placental dysplasia in crosses between two house mouse subspecies

Interspecific hybridization between closely related mammalian species, including various species of the genus Mus, is commonly associated with abnormal growth of the placenta and hybrid foetuses, a phenomenon known as hybrid placental dysplasia (HPD). The role of HPD in speciation is anticipated but still poorly understood. Here, we studied placental and foetal growth in F1 crosses between four inbred mouse strains derived from two house mouse subspecies, Mus musculus musculus and Mus musculus domesticus. These subspecies are in the early stage of speciation and still hybridize in nature. In accordance with the maternal–foetal genomic conflict hypothesis, we found different parental influences on placental and foetal development, with placental weight most affected by the father's body weight and foetal weight by the mother's body weight. After removing the effects of parents’ body weight, we did not find any significant differences in foetal or placental weights between intra‐subspecific and inter‐subspecific F1 crosses. Nevertheless, we found that the variability in placental weight in inter‐subspecific crosses is linked to the X chromosome, similarly as for HPD in interspecific mouse crosses. Our results suggest that maternal–foetal genomic conflict occurs in the house mouse system, but has not yet diverged sufficiently to cause abnormalities in placental and foetal growth in inter‐subspecific crosses. HPD is thus unlikely to contribute to speciation in the house mouse system. However, we cannot rule out that it might have contributed to other speciation events in the genus Mus, where differences in the levels of polyandry exist between the species.
The changing dynamics of US inflation persistence: a quantile regression approach

Abstract We examine both the degree and the structural stability of inflation persistence at different quantiles of the conditional inflation distribution. Previous research focused exclusively on persistence at the conditional mean of the inflation rate. As economic theory provides reasons for inflation persistence to differ across conditional quantiles, this is a potentially severe constraint. Conventional studies of inflation persistence cannot identify changes in persistence at selected quantiles that leave persistence at the mean of the distribution unchanged. Based on post-war US data we indeed find robust evidence for a structural break in persistence at all quantiles of the inflation process in the early 1980s. While prior to the 1980s inflation was not mean reverting, quantile autoregression based unit root tests suggest that since the end of the Volcker disinflation the unit root can be rejected at every quantile of the conditional inflation distribution.
Very low rate and light smokers: smoking patterns and cessation-related behaviour in England, 2006-11.

AIMS There is a growing interest in very low rate [fewer than one cigarette per day (CPD)] and light (one to nine CPD) smokers and in some parts of the world their numbers appear to be increasing. This paper examined changes in prevalence over the past 5 years, cessation patterns, and smoking and demographic characteristics of very low rate, light and moderate-to-heavy (10+ CPD) smokers in England. DESIGN Cross-sectional and longitudinal data from aggregated monthly waves of a household survey: the Smoking Toolkit Study. SETTING England. PARTICIPANTS A total of 23,245 smokers interviewed between November 2006 and May 2011 and 4147 who provided data at 6-month follow-up. MEASUREMENTS We compared the demographic and smoking characteristics between the three groups of smokers at baseline, and the rate of attempts to quit, use of aids to cessation and success of quit attempts at follow-up. FINDINGS Very low rate smoking remained extremely rare (1.9% of smokers in 2006 to 2.8% in 2011), but light smoking became increasingly common (23.9-32.8%). Compared with moderate-to-heavy smokers, very low rate and light smokers were younger, more often female and from a higher socio-economic background. They were more motivated to quit and enjoyed smoking less. During the 6-month follow-up period, light smokers, but not very low rate smokers, were more likely to attempt to quit than moderate-to-heavy smokers. When they tried to quit, very low rate and light smokers used aids to cessation less than moderate-to-heavy smokers but still used them to a substantial degree: 18%, 31% and 44% used over-the-counter nicotine replacement therapy in their most recent quit attempt for the three types of smoker, respectively. Even very low rate smokers had a substantial failure rate: 65% failed in their most recent quit attempt within 6 months. CONCLUSIONS Very low rate (fewer than one cigarette per day) and light (one to nine cigarettes per day) smokers in England are at least as motivated to quit as heavier smokers. Although they use cessation medication less than heavier smokers and are more likely to succeed, they still use such medication and fail in quit attempts to a substantial degree.
The induction of behavioural sensitization is associated with cocaine‐induced structural plasticity in the core (but not shell) of the nucleus accumbens

Repeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (Acb) and pyramidal cells in the medial prefrontal cortex (mPFC). To determine if this is associated with the development of psychomotor sensitization, rats were given daily i.p. injections of 15 mg/kg of cocaine (or saline) for 8 days, either in their home cage (which failed to induce significant psychomotor sensitization) or in a distinct and relatively novel test cage (which induced robust psychomotor sensitization). Their brains were obtained 2 weeks after the last injection and processed for Golgi–Cox staining. In the Acb core (AcbC) cocaine treatment increased spine density only in the group that developed psychomotor sensitization (i.e. in the Novel but not Home group), and there was a significant positive correlation between the degree of psychomotor sensitization and spine density. In the Acb shell (AcbS) cocaine increased spine density to the same extent in both groups; i.e. independent of psychomotor sensitization. In the mPFC cocaine increased spine density in both groups, but to a significantly greater extent in the Novel group. Furthermore, when rats were treated at Home with a higher dose of cocaine (30 mg/kg), cocaine now induced psychomotor sensitization in this context, and also increased spine density in the AcbC. Thus, the context in which cocaine is experienced influences its ability to reorganize patterns of synaptic connectivity in the Acb and mPFC, and the induction of psychomotor sensitization is associated with structural plasticity in the AcbC and mPFC, but not the AcbS.
Capacity Limits and Multiplexing Gains of MIMO Channels with Transceiver Impairments

The capacity of ideal MIMO channels has a high-SNR slope that equals the minimum of the number of transmit and receive antennas. This letter analyzes if this result holds when there are distortions from physical transceiver impairments. We prove analytically that such physical MIMO channels have a finite upper capacity limit, for any channel distribution and SNR. The high-SNR slope thus collapses to zero. This appears discouraging, but we prove the encouraging result that the relative capacity gain of employing MIMO is at least as large as with ideal transceivers.
A spectral 2-D Wold decomposition algorithm for homogeneous random fields

The theory of the 2-D Wold decomposition of homogeneous random fields is effective in image and video analysis, synthesis, and modeling. However, a robust and computationally efficient decomposition algorithm is needed for use of the theory in practical applications. This paper presents a spectral 3-D Wold decomposition algorithm for homogeneous and near homogeneous random fields. The algorithm relies on the intrinsic fundamental-harmonic relationship among Fourier spectral peaks to identify harmonic frequencies, and uses a Hough transformation to detect spectral evanescent components. A local variance based procedure is developed to determine the spectral peak support. Compared to the two other existing methods for Wold decompositions, global thresholding and maximum-likelihood parameter estimation, this algorithm is more robust and flexible for the large variety of natural images, as well as computationally more efficient than the maximum-likelihood method.
Hormone‐induced repression of genes requires BRG1‐mediated H1.2 deposition at target promoters

Eukaryotic gene regulation is associated with changes in chromatin compaction that modulate access to DNA regulatory sequences relevant for transcriptional activation or repression. Although much is known about the mechanism of chromatin remodeling in hormonal gene activation, how repression is accomplished is much less understood. Here we report that in breast cancer cells, ligand‐activated progesterone receptor (PR) is directly recruited to transcriptionally repressed genes involved in cell proliferation along with the kinases ERK1/2 and MSK1. PR recruits BRG1 associated with the HP1γ‐LSD1 complex repressor complex, which is further anchored via binding of HP1γ to the H3K9me3 signal deposited by SUV39H2. In contrast to what is observed during gene activation, only BRG1 and not the BAF complex is recruited to repressed promoters, likely due to local enrichment of the pioneer factor FOXA1. BRG1 participates in gene repression by interacting with H1.2, facilitating its deposition and stabilizing nucleosome positioning around the transcription start site. Our results uncover a mechanism of hormone‐dependent transcriptional repression and a novel role for BRG1 in progestin regulation of breast cancer cell growth.
Arrhythmogenic Risk Assessment Following Four-Week Pretreatment With Nicotine and Black Tea in Rat

Background: There is the controversy concerning the main component of tobacco, which is responsible for its arrhythmogenesis. In addition, there is the lack of adequate information about the influence of combination of black tea and nicotine on heart rhythm. Objectives: This study aimed to examine whether pretreatment with black tea and nicotine could modulate the susceptibility to lethal ventricular arrhythmias. Materials and Methods: Animals were randomized to control, black tea, nicotine, and black tea plus nicotine groups. Test groups were treated with black tea brewed (orally) and nicotine (2 mg/kg, subcutaneous), alone and in combination for four weeks. On day 29, aconitine was infused intravenously for induction of cardiac arrhythmia. Results: In comparison with the control group, each of tea and nicotine significantly decreased the duration of the ventricular tachycardia (VT) plus ventricular fibrillation (VF) and the score of arrhythmia severity (P < 0.05 and P < 0.01, respectively,). The latency for the first VT event was significantly longer in the all test groups, but VF latency was significant only in tea and nicotine groups compared with control group (P < 0.05 and P < 0.01, respectively). Threshold dose of aconitine for inducing VT and VF increased in all test groups, but only VT showed a significant difference in comparison to the control group (P < 0.001). Conclusions: The findings suggest that sub-chronic consumption of nicotine or black tea alone with appropriate doses could potentially be antiarrhythmic and its combination regimen does not increase the risk of fatal ventricular arrhythmias during four-week consumption period in rats.
Description of Trichuris travassosi n. sp. (Nematoda: Trichurinae) from a Brazilian rodent, by light and scanning electron microscopy.

A new species of a trichurid nematode Trichuris travassosi n. sp. , recovered from a wild rodent in the State of Rio Grande do Sul, Brazil, is described and compared to T. myocastoris (Enigk, 1933) and their differentiation was on the basis of a detailed morphometrical study. Oryzomys nigripes (Olfers, 1818) is a new host record for the genus. The denomination spicular prepuce is proposed to designate the structure previously named spicular sheath and, conversely, spicular sheath to indicate the cuticle that covers the spicule.
Network-timing-dependent plasticity

Bursts of activity in networks of neurons are thought to convey salient information and drive synaptic plasticity. Here we report that network bursts also exert a profound effect on Spike-Timing-Dependent Plasticity (STDP). In acute slices of juvenile rat somatosensory cortex we paired a network burst, which alone induced long-term depression (LTD), with STDP-induced long-term potentiation (LTP) and LTD. We observed that STDP-induced LTP was either unaffected, blocked or flipped into LTD by the network burst, and that STDP-induced LTD was either saturated or flipped into LTP, depending on the relative timing of the network burst with respect to spike coincidences of the STDP event. We hypothesized that network bursts flip STDP-induced LTP to LTD by depleting resources needed for LTP and therefore developed a resource-dependent STDP learning rule. In a model neural network under the influence of the proposed resource-dependent STDP rule, we found that excitatory synaptic coupling was homeostatically regulated to produce power law distributed burst amplitudes reflecting self-organized criticality, a state that ensures optimal information coding.
Bacterial toxin YafQ is an endoribonuclease that associates with the ribosome and blocks translation elongation through sequence‐specific and frame‐dependent mRNA cleavage

Toxin–antitoxin (TA) systems on the chromosomes of free‐living bacteria appear to facilitate cell survival during intervals of stress by inducing a state of reversible growth arrest. However, upon prolonged stress, TA toxin action leads to cell death. They have been implicated in several clinically important phenomena – bacterial persistence during antibiotic treatment, biofilm formation and bacterial pathogenesis – and serve as attractive new antibiotic targets for pathogens. We determined the mode of action of the YafQ toxin of the DinJ–YafQ TA system. YafQ expression resulted in inhibition of translation, but not transcription or replication. Purified YafQ exhibited robust ribonuclease activity in vitro that was specifically blocked by the addition of DinJ. However, YafQ associated with ribosomes in vivo and facilitated rapid mRNA degradation near the 5′ end via cleavage at AAA lysine codons followed by a G or A. YafQ(H87Q) mutants lost toxicity and cleavage activity but retained ribosome association. Finally, LexA bound to the dinJ–yafQ palindrome and triggered module transcription after DNA damage. YafQ function is distinct from other TA toxins: it associates with the ribosome through the 50S subunit and mediates sequence‐specific and frame‐dependent mRNA cleavage at 5′AAA – G/A3′ sequences leading to rapid decay possibly facilitated by the mRNA degradosome.
EFFECT OF MOBILE PHONE FREQUENCY RADIATION ON EARLY DEVELOPMENT OF CHICK EMBRYO

The countless increase in towers and mobile phones has increased the amount of non-ionizing radio waves in surroundings during last two decades. Several reports have revealed non-desirable after effects of mobile phone frequency electromagnetic field radiations at cellular level. Thus, the present study was designed to evaluate the effect of cell- phone frequency electromagnetic field (EMF) radiations on early development of chick embryos. To carry out the studies, zero hour incubated fertilized eggs were divided into four groups including normal control and rest three EMF treated groups, exposed to 900 MHz EMF for different durations and at different power levels. During the study, higher mortality and somite development alteration in exposed groups has been observed as compared to normal control group. Hence, the study concludes that EMF exposure induces detrimental effects on development of chick embryo during early incubation period.
Caries InhibitionWith aCO 2 9 . 3 m mLaser : An InVitro Study

Peter Rechmann, DMD, PhD, Beate M.T. Rechmann, William H. Groves Jr., Charles Q. Le, Marcia L. Rapozo-Hilo, Richard Kinsel, DDS, and John D.B. Featherstone, MSc, PhD Department of Preventive and Restorative Dental Sciences, University of California at San Francisco, School of Dentistry, 707 Parnassus Avenue, San Francisco, California 94143 Convergent Dental, Inc., 2 Vision Drive, Natick, Massachusetts 01760