Predicting Axonal Response to Molecular Gradients with a Computational Model of Filopodial Dynamics

Axons are often guided to their targets in the developing nervous system by attractive or repulsive molecular concentration gradients. We propose a computational model for gradient sensing and directed movement of the growth cone mediated by filopodia. We show that relatively simple mechanisms are sufficient to generate realistic rajectories for both the short-term response of axons to steep gradients and the long-term response of axons to shallow gradients. The model makes testable predictions for axonal response to attractive and repulsive gradients of different concentrations and steepness, the size of the intracellular amplification of the gradient signal, and the differences in intracellular signaling required for repulsive versus attractive turning

Submillimeter-wave emission of three Galactic red novae: cool molecular outflows produced by stellar mergers

Red novae are optical transients erupting at luminosities typically higher than those of classical novae. Their outbursts are believed to be caused by stellar mergers. We present millimeter/submillimeter-wave observations with ALMA and SMA of the three best known Galactic red novae, V4332 Sgr, V1309 Sco, and V838 Mon. The observations were taken 22, 8, and 14 yr after their respective eruptions and reveal the presence of molecular gas at excitation temperatures of 35-200 K. The gas displays molecular emission in rotational transitions with very broad lines (full width $\sim$400 km\s). We found emission of CO, SiO, SO, SO$_2$ (in all three red novae), H$_2$S (covered only in V838 Mon) and AlO (present in V4332 Sgr and V1309 Sco). No anomalies were found in the isotopic composition of the molecular material and the chemical (molecular) compositions of the three red novae appear similar to those of oxygen-rich envelopes of classical evolved stars (RSGs, AGBs, post-AGBs). The minimum masses of the molecular material that most likely was dispersed in the red-nova eruptions are 0.1, 0.01, and 10$^{-4}$ M$_{\odot}$ for V838 Mon, V4332 Sgr, and V1309 Sco, respectively. The molecular outflows in V4332 Sgr and V1309 Sco are spatially resolved and appear bipolar. The kinematic distances to V1309 Sco and V4332 Sgr are 2.1 and 4.2 kpc, respectively. The kinetic energy stored in the ejecta of the two older red-nova remnants of V838 Mon and V4332 Sgr is of order $10^{46}$ erg, similar to values found for some post-AGB (pre-PN) objects whose bipolar ejecta were also formed in a short-duration eruption. Our observations strengthen the link between these post-AGB objects and red novae and support the hypothesis that some of the post-AGB objects were formed in a common-envelope ejection event or its most catastrophic outcome, a merger.Comment: 19 pages, 13 figures, accepted to A&

FORMULATION AND PROCESS OPTIMIZATION OF GASTRO-RETENTIVE FLOATING TABLET OF ONDANSETRON HCL

Ondansetron HCl is a potent, highly selective 5-HT3receptor-antagonist used to prevent nausea andvomiting, mainly in patients undergoing chemotherapyand radiation treatments. The aim of present work wasto formulate, evaluate and optimize gastro-retentivetablet of Ondansetron HCl which would beadvantageous, that can provide prolong gastricretention and increase efficacy of the dosage form. Informulation optimization, different formulation ofHPMC polymer, NaCMC and NaHCO3 were studiedwith help of 32 full factorial designs. It was found thatHPMC K4M with concentration 40%, NaCMC 5%and NaHCO3 with 17% concentrations showed goodsustained and floating ability and it releases 94.51%drug within 24 hrs. During study of effect of processparameters, it was concluded that release of drugdecreases with decreasing granular size. The dryingtime (10 and 20 min) and drying temperature (40° and50°C), does not have any significant effect on therelease profile of drug

Box-Behnkenov eksperimentalni dizajn u izradi pektin-kompritol ATO 888 obloženih tableta za ciljanu isporuku mesalamina u kolon

The aim of this study was to investigate the combined influence of 3 independent variables in the compression coated tablet of mesalamine for ulcerative colitis. A 3-factor, 3-level Box-Behnken design was used to derive a second order polynomial equation and construct contour plots to predict responses. The independent variables selected were: percentage of polymers (pectin and compritol ATO 888) in compression coating (X1), coating mass (X2) and coating force (X3). Fifteen batches were prepared and evaluated for percent of drug released in 5 h (Y5), time required for 50 % mesalamine to disolve (t50) with rat cecal (RC) content and without rat cecal content (t50), percent of drug released in 24 h in the presence of rat cecal content (Y24 with RC). Transformed values of independent and dependent variables were subjected to multiple regressions to establish a full-model second-order polynomial equation. F was calculated to confirm the omission of insignificant terms from the full-model equation. The computer optimization process and contour plots predicted the levels of independent variables X1, X2, and X3 (0, 0.2 and –0.15 respectively) for colon targeting and total percent of drug released up to 24 h.Cilj rada bio je ispitati utjecaj tri nezavisne varijable u obloženim tabletama mesalamina za ulcerativni kolitis. 3-faktorijalni, Box-Behnkenov dizajn na 3 nivoa upotrijebljen je za dobivanje polinomske jednadžbe drugog reda i konstruiranje konturnih krivulja za predviđanje odgovora. Izabrane nezavisne varijable bile su: udio polimera (pektin i kompritol ATO 888) u oblaganju kompresijom (X1), masa tvari za oblaganje (X2) i sila za oblaganje (X3). Izrađeno je petnaest pripravaka kojima su ispitani sljedeći parametri: udio lijeka oslobođenog nakon 5 h (Y5), vrijeme potrebno za otapanje 50 % mesalamina (t50) uz i bez prisutnosti crijevnog sadržaja štakora (RC), postotak oslobođenog lijeka tijekom 24 h u prisutnosti crijevnog sadržaja (Y24 uz RC). Transformirane vrijednosti nezavisnih i zavisnih varijabla podvrgnute su višestrukoj regresijskoj analizi da se odredi polinomska jednadžba drugog reda potpunog modela. F vrijednost izračunata je da se potvrdi izostavljanje neznačajnih članova iz jednadžbe potpunog modela. Kompjutorski optimizirani proces i krivulje predviđaju nezavisne varijable X1, X2 i X3 (0, 0,2, odnosno –0,15) za ciljanu isporuku u kolon i ukupni postotak lijeka oslobođenog tijekom 24 h

Hot Core, Outflows and Magnetic Fields in W43-MM1 (G30.79 FIR 10)

We present submillimeter spectral line and dust continuum polarization observations of a remarkable hot core and multiple outflows in the high-mass star-forming region W43-MM1 (G30.79 FIR 10), obtained using the Submillimeter Array (SMA). A temperature of $\sim$ 400 K is estimated for the hot-core using CH$_3$CN (J=19-18) lines, with detections of 11 K-ladder components. The high temperature and the mass estimates for the outflows indicate high-mass star-formation. The continuum polarization pattern shows an ordered distribution, and its orientation over the main outflow appears aligned to the outflow. The derived magnetic field indicates slightly super-critical conditions. While the magnetic and outflow energies are comparable, the B-field orientation appears to have changed from parsec scales to $\sim$ 0.1 pc scales during the core/star-formation process.Comment: accepted, ApJ Letter

A Case Report on Metformin-Associated Lactic Acidosis.

Metformin is the first-line therapy for patients with type 2 diabetes, and its most common adverse effects are gastrointestinal. Lactic acidosis associated with metformin use is rare. Here, we report the case of a 77-year-old man with a medical history of diabetes (treated with metformin), hypertension, chronic alcohol abuse, and prostate and bladder cancer, who presented with abdominal pain, nausea, vomiting, and diarrhea for five days. He was admitted with severe metabolic acidosis due to metformin toxicity (metformin-associated lactic acidosis) with metformin level 23 mcg/mL (therapeutic range approximately 1-2 mcg/mL) in the setting of acute kidney failure due to acute pancreatitis and sepsis secondary to aspiration pneumonia. He was intubated, required pressor support, and received daily hemodialysis. Despite aggressive management, his hospital course became complicated with acute respiratory distress syndrome, myocardial infarction, acute hepatic failure, and ischemic and metabolic encephalopathy. In the end, the family decided to withdraw care and the patient was terminally extubated

Pre-implantation genetic testing: a retrospective observational study of 13 cases of various genetic diseases successfully detected and managed at an IVF centre

Pre-implantation genetic testing (PGT) is an advanced form of prenatal genetic testing that is done as a part of ART cycles. The purpose of PGT is to identify genetically normal embryos in a given cohort, in order to select the most desirable embryos for implantation. With the gaining popularity of day 5 trophectoderms biopsy over day 3 blastomere biopsy, the role of PGT has become more clinically significant. To report the data of 13 couples, with diagnosed genetic condition and having risk of transmitting this condition to their offspring’s, who underwent Pre-implantation genetic diagnostics (PGT M/SR). PGT was performed in 13 couples with various rare chromosomal conditions like Hereditary Inclusion body myopathy, Col4a1 gene mutation etc at our Infertility Centre from January 2016 to January 2020. The clinical data of all these patients was reviewed and is reported in our study. A total of 193 oocytes were retrieved and 158 oocytes were fertilized by ICSI. 62 blastocysts were obtained and 55 blastocysts were biopsied for analysis. Among the 35 normal embryos, 17 embryos were transferred. 11 clinical pregnancies were established resulting in 8, disease free, live births. PGT (M/SR) is an effective molecular diagnostic test, that is a ray of hope for many genetically affected couples, as its prevents the transmission of their unwanted genetic condition to their offspring’s