Overexpression of the type 1 adenylyl cyclase in the forebrain leads to deficits of behavioral inhibition

The type 1 adenylyl cyclase (AC1) is an activity-dependent, calcium-stimulated adenylyl cyclase expressed in the nervous system that is implicated in memory formation. We examined the locomotor activity, and impulsive and social behaviors of AC1+ mice, a transgenic mouse strain overexpressing AC1 in the forebrain. Here we report that AC1+ mice exhibit hyperactive behaviors and demonstrate increased impulsivity and reduced sociability. In contrast, AC1 and AC8 double knock-out mice are hypoactive, and exhibit increased sociability and reduced impulsivity. Interestingly, the hyperactivity of AC1+ mice can be corrected by valproate, a mood-stabilizing drug. These data indicate that increased expression of AC1 in the forebrain leads to deficits in behavioral inhibition

Evaluation of novel attitude estimation algorithm for high performance fighter aircraft

This paper discusses the evaluation of a novel attitude estimation algorithm (Kamali et al.(2013)) for a high performance fighter aircraft. This algorithm employs a new modelling approach in the Extended Kalman Filtering (EKF) framework to estimate aircraft attitude information without using forward acceleration sensor, Global Positioning System (GPS) sensors or magnetometer. Evaluation of the algorithm is conducted using flight data from a high performance fighter aircraft and using flight simulation data. Estimation results during various manoeuvres such as full rolls, inverted loops, split-S manoeuvres, steep climbs, and dives, are studied. Effect of different wind perturbations (gust, shear,turbulence, etc.), on estimation results, is also studied. Results using flight data are compared with those obtained from a GPS-assisted Inertial Navigation System (INS), whereas for results using simulation data, the simulation itself provides true values. Conclusions are drawn for the performance of the algorithm based on simulation and flight data

Genetic repression of the antioxidant enzymes reduces the lifespan in Drosophila melanogaster

Aging is a biological process associated with gradual loss of function caused by cellular and molecular damages ultimately leading to mortality. Free radicals are implicated in oxidative damage which affects the longevity of organisms. Natural cellular defenses involving antioxidant enzymes delay or prevent oxidative damage and, therefore, influence the aging process and longevity has been shown in many species including Drosophila. We and others have shown that oxidative resistance is an important mechanism in the aging process in Drosophila. Therefore, we hypothesized that repressing endogenous antioxidant defenses shortens longevity in Drosophila. To study the influence of natural defense mechanisms against oxidative stress in aging, we have investigated the effect of genetic repression of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), on longevity in Drosophila using transgenic RNAi flies and in vivo inhibition of the enzymes with chemical inhibitors. RNAi lines of Drosophila viz., UAS-sod1-IR and UAS-cat-IR, are driven ubiquitously using Act5C-Gal4 and Tubulin-Gal4 to achieve the suppression of SOD1 and CAT activities, respectively. We show that genetic repression of SOD1 and CAT by RNAi in transgenic flies led to drastically reduced longevity (SOD1, 77%; CAT, 83%), presenting the evidence for the role of endogenous antioxidant defenses in lifespan extension in Drosophila. Further, our study shows that the enzyme inhibitors, diethyldithiocarbamate and 3-amino-1,2,4-triazole, although lower the enzyme activities in vivo in flies, but did not affect longevity, which could be attributed to the factors such as bioavailability and metabolism of the inhibitors and adaptive mechanisms involving de novo synthesis of the enzymes. Our study of genetic repression using transgenic RNAi provides experimental evidence that extended longevity is associated with endogenous antioxidant defenses and aging is correlated with oxidative stress resistance

Impaired endogenous fibrinolysis at high shear using a point-of-care test in STEMI is associated with alterations in clot architecture

© The Author(s) 2019Impaired endogenous fibrinolysis is an adverse prognostic biomarker in acute coronary syndrome (ACS). Abnormally dense in vitro fibrin thrombi have been demonstrated in ACS patients and related to hypofibrinolysis using cumbersome, laboratory-based methods. We aimed to assess endogenous fibrinolysis using a point-of-care technique and relate this to clot architecture. From patients with ST-segment elevation myocardial infarction (STEMI), venous blood was drawn immediately on arrival to assess thrombotic status. Blood was assessed using the point-of-care Global Thrombosis Test which measures occlusive thrombus formation under high shear and subsequently endogenous fibrinolysis (lysis time, LT). Two samples per patient were run in parallel. In one channel, the measurement was allowed to proceed as normal. In the other, after occlusion, thrombus was extracted, washed, fixed in glutaraldehyde, dried, sputter-coated, and assessed using scanning electron microscope. Endogenous fibrinolysis was strongly associated fibrin fibre thickness (p = 0.0001). As LT increased (less efficient fibrinolysis), the fibrin network of the thrombus was significantly more compact and dense, with thinner fibrin fibres and smaller gaps. Fibrin fibre thickness correlated inversely with LT (r = - 0.89, p = 0.001). Adverse clot architecture in vitro is directly related to impaired endogenous fibrinolysis using a relatively new point-of-care technique in patients with STEMI. This may transform the relevance of fibrin clot architecture from an off-line laboratory association to being directly relevant to endogenous fibrinolysis at the patient bedside, which could be used as a near-patient test to guide prognosis and assess the effect of treatment.Peer reviewedFinal Published versio

Development of spectrophotometric fingerprinting method for Talisadi Churna

Selective and efficient analytical methods are required not only for quality assurance but also for authentication of herbal formulations. A simple, rapid and validated fingerprint method has developed for estimation of piperine in ‘Talisadi churna’, a well known herbal formulation in India. The estimation was carried out in two laboratory batches and three marketed formulation by an ultraviolet spectrophotometric method at 342.8 nm. Keywords: Talisadi churna, PiperinEast and Central African Journal of Pharmaceutical Sciences Vol. 12 (2009) 52-5

Granular discharge and clogging for tilted hoppers

We measure the flux of spherical glass beads through a hole as a systematic function of both tilt angle and hole diameter, for two different size beads. The discharge increases with hole diameter in accord with the Beverloo relation for both horizontal and vertical holes, but in the latter case with a larger small-hole cutoff. For large holes the flux decreases linearly in cosine of the tilt angle, vanishing smoothly somewhat below the angle of repose. For small holes it vanishes abruptly at a smaller angle. The conditions for zero flux are discussed in the context of a {\it clogging phase diagram} of flow state vs tilt angle and ratio of hole to grain size

TLC densitometric fingerprint development and validation of 6-gingerol as marker in poly-herbal ayurvedic formulations

The poly herbal formulations containing ginger are widely used for different medicinal properties. The present paper deals with the development of densitometric method for fingerprint of ginger mainly using 6-gingerol in the form of densitogram following charring of the chromatographic as internal standard that could be useful for marker-based quality assurance of the poly herbal products containing Zingiber officinale. The fast rapid and reproducible method was developed. The accuracy of method was validated by analysis of spiked blank and standard addition samples and precision by performing replicate analyses on a single day and on different days. Recoveries from spiked blank and standard addition sample were 98.03-99.47 %. Repeatability for sample, each of which was analyzed six times on a single plate, was 0.001903 % relative standard deviation. The intra and inter precision was 0.001242 and 0.010676 % relative standard deviation for a sample analyzed in duplicate once per plate on same day and the different days over a seven-day period. The content of 6-Gingerol was found to be 0.698 ± 0.000577, 0.689 ± 0.002, 0.687 ± 0.001528 mg/g in lab formulations. The method was shown to be simple, precise and accurate suitable for routine analysis of 6-Gingerol at different levels from raw material to finished formulations.Colegio de Farmacéuticos de la Provincia de Buenos Aire

TLC densitometric fingerprint development and validation of 6-gingerol as marker in poly-herbal ayurvedic formulations

The poly herbal formulations containing ginger are widely used for different medicinal properties. The present paper deals with the development of densitometric method for fingerprint of ginger mainly using 6-gingerol in the form of densitogram following charring of the chromatographic as internal standard that could be useful for marker-based quality assurance of the poly herbal products containing Zingiber officinale. The fast rapid and reproducible method was developed. The accuracy of method was validated by analysis of spiked blank and standard addition samples and precision by performing replicate analyses on a single day and on different days. Recoveries from spiked blank and standard addition sample were 98.03-99.47 %. Repeatability for sample, each of which was analyzed six times on a single plate, was 0.001903 % relative standard deviation. The intra and inter precision was 0.001242 and 0.010676 % relative standard deviation for a sample analyzed in duplicate once per plate on same day and the different days over a seven-day period. The content of 6-Gingerol was found to be 0.698 ± 0.000577, 0.689 ± 0.002, 0.687 ± 0.001528 mg/g in lab formulations. The method was shown to be simple, precise and accurate suitable for routine analysis of 6-Gingerol at different levels from raw material to finished formulations.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects

In gravitational-wave detection, special emphasis is put onto searches that focus on cosmic events detected by other types of astrophysical observatories. The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical telescopes and neutrino observatories, provide a trigger time for analyzing gravitational wave data coincident with the event. In certain cases the expected frequency range, source energetics, directional and progenitor information is also available. Beyond allowing the recognition of gravitational waveforms with amplitudes closer to the noise floor of the detector, these triggered searches should also lead to rich science results even before the onset of Advanced LIGO. In this paper we provide a broad review of LIGO's astrophysically triggered searches and the sources they target